Clinical Review

Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.¹

If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.

90% of lupus cases are in reproductive-age women

SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).

Counsel the patient, gauge the risks

The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).²

As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study³ proposed the acronym PATH to help identify high-risk patients:

Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension

TABLE 1

Factors that increase the likelihood of a good outcome

Disease quiescence is not an infallible sign

One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.

Renal disease and hypertension

Nephritis

Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.⁴ Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.

Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.

Hypertension

When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.

Diagnosis of antiphospholipid syndrome

Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.

Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.

Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.

Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.

Does pregnancy bring on lupus flare?

Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.⁵ Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.

Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.⁶ This variability is due in part to differences in disease activity of the patients when they entered the studies.

One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.

The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs

Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years

Potential adverse outcomes

Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.

Diagnosis and initial management

Preventive treatments

Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.

Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.

The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.

The differential diagnosis

It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.

TABLE 2

Clinical features of preeclampsia vs lupus flare*

Is it lupus flare or preeclampsia?

The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.

A few easy tests can help (TABLE 3), but the most important are:

• positive ANA screen,
  
• active urinary sediment,
  
• hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
  
• high titers of anti-ds-DNA.
  

TABLE 3

Tests that help tell lupus flare from preeclampsia

Aggressive drug therapy is imperative

Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.

The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.

Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.

The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.

Refractory flares: Focus on damage control

In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.

Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.

The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.⁸

Early delivery: When and how

In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.

Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.

Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.

Cesarean section may be reserved for accepted obstetric indications.

Cytotoxic therapy

Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.

Cyclophosphamide

This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.⁹ Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.

Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.

Azathioprine

An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.

The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.

Methotrexate

Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.

Thrombosis requires swift anticoagulation

In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.¹⁰)

Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.¹

If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.

90% of lupus cases are in reproductive-age women

SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).

Counsel the patient, gauge the risks

The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).²

As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study³ proposed the acronym PATH to help identify high-risk patients:

Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension

TABLE 1

Factors that increase the likelihood of a good outcome

Disease quiescence is not an infallible sign

One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.

Renal disease and hypertension

Nephritis

Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.⁴ Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.

Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.

Hypertension

When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.

Diagnosis of antiphospholipid syndrome

Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.

Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.

Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.

Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.

Does pregnancy bring on lupus flare?

Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.⁵ Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.

Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.⁶ This variability is due in part to differences in disease activity of the patients when they entered the studies.

One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.

The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs

Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years

Potential adverse outcomes

Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.

Diagnosis and initial management

Preventive treatments

Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.

Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.

The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.

The differential diagnosis

It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.

TABLE 2

Clinical features of preeclampsia vs lupus flare*

Is it lupus flare or preeclampsia?

The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.

A few easy tests can help (TABLE 3), but the most important are:

• positive ANA screen,
  
• active urinary sediment,
  
• hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
  
• high titers of anti-ds-DNA.
  

TABLE 3

Tests that help tell lupus flare from preeclampsia

Aggressive drug therapy is imperative

Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.

The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.

Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.

The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.

Refractory flares: Focus on damage control

In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.

Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.

The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.⁸

Early delivery: When and how

In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.

Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.

Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.

Cesarean section may be reserved for accepted obstetric indications.

Cytotoxic therapy

Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.

Cyclophosphamide

This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.⁹ Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.

Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.

Azathioprine

An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.

The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.

Methotrexate

Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.

Thrombosis requires swift anticoagulation

In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.¹⁰)

Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.¹

If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.

90% of lupus cases are in reproductive-age women

SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).

Counsel the patient, gauge the risks

The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).²

As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study³ proposed the acronym PATH to help identify high-risk patients:

Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension

TABLE 1

Factors that increase the likelihood of a good outcome

Disease quiescence is not an infallible sign

One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.

Renal disease and hypertension

Nephritis

Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.⁴ Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.

Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.

Hypertension

When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.

Diagnosis of antiphospholipid syndrome

Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.

Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.

Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.

Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.

Does pregnancy bring on lupus flare?

Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.⁵ Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.

Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.⁶ This variability is due in part to differences in disease activity of the patients when they entered the studies.

One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.

The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs

Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years

Potential adverse outcomes

Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.

Diagnosis and initial management

Preventive treatments

Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.

Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.

The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.

The differential diagnosis

It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.

TABLE 2

Clinical features of preeclampsia vs lupus flare*

Is it lupus flare or preeclampsia?

The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.

A few easy tests can help (TABLE 3), but the most important are:

• positive ANA screen,
  
• active urinary sediment,
  
• hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
  
• high titers of anti-ds-DNA.
  

TABLE 3

Tests that help tell lupus flare from preeclampsia

Aggressive drug therapy is imperative

Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.

The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.

Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.

The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.

Refractory flares: Focus on damage control

In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.

Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.

The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.⁸

Early delivery: When and how

In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.

Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.

Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.

Cesarean section may be reserved for accepted obstetric indications.

Cytotoxic therapy

Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.

Cyclophosphamide

This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.⁹ Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.

Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.

Azathioprine

An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.

The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.

Methotrexate

Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.

Thrombosis requires swift anticoagulation

In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.¹⁰)

Hypoactive sexual desire disorder (HSDD) should be recognized as an important quality-of-life issue, particularly for those at increased risk, this report concluded. WISHeS is the first study to report the prevalence of HSDD in US women using well-validated questionnaires, and to assess sexual, relationship, and quality-of-life correlates. Psychosocial distress and significant decrements in general health status, including aspects of mental and physical health, were linked to HSDD.

TABLE

Hypoactive sexual desire disorder rates in US women

What makes hypoactive sexual desire a disorder?

HSDD is diminished desire for sexual activity, including sexual fantasies. It is considered a disorder only if it causes marked distress for the patient or serious interpersonal relationship problems.

HSDD is associated with these problems:

• greater emotional and psychological distress,
  
• lowered sexual and partner satisfaction, and
  
• diminished general health, both mental and physical.
  

Details of the study

The findings were derived from a cross-sectional, randomized convenience survey mailed to US women in 2000, as part of the larger Women’s International Study of Health and Sexuality. Respondents were 952 women (most were married and Caucasian) who comprised 28% of the total identified as potential participants. The response rate was 77%.

Results from hysterectomized (without oophorectomy) and perimenopausal women were not included in this analysis, but will be reported elsewhere. No socioeconomic data were given.

Although the study was funded by Procter&Gamble, it was conducted by an independent, survey-based research group.

3 types of questionnaires were used:

• Overall health status was measured by Short Form-36
  
• Profile of Female Sexual Function
  
• Personal Distress Scale
  

Expert Commentary

The finding that HSDD is substantially higher in young, surgically menopausal women (26%) than in premenopausal women the same age (14%) makes this an important study. Previously, estimates put the prevalence at 20% in the general population. Although it occurs in both sexes, the disorder is more common in women.

Contributing factors include medical problems such as heart disease or any disabling illness. Antihypertensives, antidepressants, and oral contraceptives also may lower sexual desire.

Role of testosterone. Endogenous testosterone levels and sexual function are not clearly linked, but exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause.^1,2

Nonmedical contributors. HSDD may be associated with communication issues or power struggles between sex partners. A lack of affection, poor emotional intimacy, or inadequate time alone together may precipitate HSDD, as can a very restrictive upbringing concerning sex, or negative or traumatic sexual experiences.

Depression, fatigue, or excessive stress may also inhibit sexual interest.

Experimental treatments

Treatment depends in part on the duration of the problem and its causes. No drug therapy has been approved for HSDD in women, although testosterone and other therapies are being studied. Psychotherapy is reported to be mildly effective.

Continuous transdermal testosterone (300-μg patch) improved sexual desire, arousal, and orgasm frequency in women after oophorectomy, with no significant side effects.³

A 24-week study⁴ determined that surgically menopausal women (n=283) who receive transdermal testosterone 300 μg daily along with estrogen experienced 1 additional episode of satisfying sexual activity every 4 weeks, as well as decreased distress and improved desire. Studies are underway to determine whether the findings are clinically significant and to establish longer-term safety and efficacy. The testosterone patch lacks FDA approval.

Don’t forget about prevention

Women who have not undergone premature surgical menopause can help prevent HSDD using these measures:

• Reserving time for nonsexual intimacy such as weekly dating to maintain a closer relationship
  
• “Separating” affection and sex so that affection is not interpreted as an invitation to proceed to intercourse
  
• Increasing communication through books, classes, or reading or watching materials with romantic or sexual content
  
• Reserving time for both talking and sexual intimacy earlier in the evening before exhaustion sets in, to encourage closeness and sexual desire.
  

Hypoactive sexual desire disorder (HSDD) should be recognized as an important quality-of-life issue, particularly for those at increased risk, this report concluded. WISHeS is the first study to report the prevalence of HSDD in US women using well-validated questionnaires, and to assess sexual, relationship, and quality-of-life correlates. Psychosocial distress and significant decrements in general health status, including aspects of mental and physical health, were linked to HSDD.

TABLE

Hypoactive sexual desire disorder rates in US women

What makes hypoactive sexual desire a disorder?

HSDD is diminished desire for sexual activity, including sexual fantasies. It is considered a disorder only if it causes marked distress for the patient or serious interpersonal relationship problems.

HSDD is associated with these problems:

• greater emotional and psychological distress,
  
• lowered sexual and partner satisfaction, and
  
• diminished general health, both mental and physical.
  

Details of the study

The findings were derived from a cross-sectional, randomized convenience survey mailed to US women in 2000, as part of the larger Women’s International Study of Health and Sexuality. Respondents were 952 women (most were married and Caucasian) who comprised 28% of the total identified as potential participants. The response rate was 77%.

Results from hysterectomized (without oophorectomy) and perimenopausal women were not included in this analysis, but will be reported elsewhere. No socioeconomic data were given.

Although the study was funded by Procter&Gamble, it was conducted by an independent, survey-based research group.

3 types of questionnaires were used:

• Overall health status was measured by Short Form-36
  
• Profile of Female Sexual Function
  
• Personal Distress Scale
  

Expert Commentary

The finding that HSDD is substantially higher in young, surgically menopausal women (26%) than in premenopausal women the same age (14%) makes this an important study. Previously, estimates put the prevalence at 20% in the general population. Although it occurs in both sexes, the disorder is more common in women.

Contributing factors include medical problems such as heart disease or any disabling illness. Antihypertensives, antidepressants, and oral contraceptives also may lower sexual desire.

Role of testosterone. Endogenous testosterone levels and sexual function are not clearly linked, but exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause.^1,2

Nonmedical contributors. HSDD may be associated with communication issues or power struggles between sex partners. A lack of affection, poor emotional intimacy, or inadequate time alone together may precipitate HSDD, as can a very restrictive upbringing concerning sex, or negative or traumatic sexual experiences.

Depression, fatigue, or excessive stress may also inhibit sexual interest.

Experimental treatments

Treatment depends in part on the duration of the problem and its causes. No drug therapy has been approved for HSDD in women, although testosterone and other therapies are being studied. Psychotherapy is reported to be mildly effective.

Continuous transdermal testosterone (300-μg patch) improved sexual desire, arousal, and orgasm frequency in women after oophorectomy, with no significant side effects.³

A 24-week study⁴ determined that surgically menopausal women (n=283) who receive transdermal testosterone 300 μg daily along with estrogen experienced 1 additional episode of satisfying sexual activity every 4 weeks, as well as decreased distress and improved desire. Studies are underway to determine whether the findings are clinically significant and to establish longer-term safety and efficacy. The testosterone patch lacks FDA approval.

Don’t forget about prevention

Women who have not undergone premature surgical menopause can help prevent HSDD using these measures:

• Reserving time for nonsexual intimacy such as weekly dating to maintain a closer relationship
  
• “Separating” affection and sex so that affection is not interpreted as an invitation to proceed to intercourse
  
• Increasing communication through books, classes, or reading or watching materials with romantic or sexual content
  
• Reserving time for both talking and sexual intimacy earlier in the evening before exhaustion sets in, to encourage closeness and sexual desire.
  

Hypoactive sexual desire disorder (HSDD) should be recognized as an important quality-of-life issue, particularly for those at increased risk, this report concluded. WISHeS is the first study to report the prevalence of HSDD in US women using well-validated questionnaires, and to assess sexual, relationship, and quality-of-life correlates. Psychosocial distress and significant decrements in general health status, including aspects of mental and physical health, were linked to HSDD.

TABLE

Hypoactive sexual desire disorder rates in US women

What makes hypoactive sexual desire a disorder?

HSDD is diminished desire for sexual activity, including sexual fantasies. It is considered a disorder only if it causes marked distress for the patient or serious interpersonal relationship problems.

HSDD is associated with these problems:

• greater emotional and psychological distress,
  
• lowered sexual and partner satisfaction, and
  
• diminished general health, both mental and physical.
  

Details of the study

The findings were derived from a cross-sectional, randomized convenience survey mailed to US women in 2000, as part of the larger Women’s International Study of Health and Sexuality. Respondents were 952 women (most were married and Caucasian) who comprised 28% of the total identified as potential participants. The response rate was 77%.

Results from hysterectomized (without oophorectomy) and perimenopausal women were not included in this analysis, but will be reported elsewhere. No socioeconomic data were given.

Although the study was funded by Procter&Gamble, it was conducted by an independent, survey-based research group.

3 types of questionnaires were used:

• Overall health status was measured by Short Form-36
  
• Profile of Female Sexual Function
  
• Personal Distress Scale
  

Expert Commentary

The finding that HSDD is substantially higher in young, surgically menopausal women (26%) than in premenopausal women the same age (14%) makes this an important study. Previously, estimates put the prevalence at 20% in the general population. Although it occurs in both sexes, the disorder is more common in women.

Contributing factors include medical problems such as heart disease or any disabling illness. Antihypertensives, antidepressants, and oral contraceptives also may lower sexual desire.

Role of testosterone. Endogenous testosterone levels and sexual function are not clearly linked, but exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause.^1,2

Nonmedical contributors. HSDD may be associated with communication issues or power struggles between sex partners. A lack of affection, poor emotional intimacy, or inadequate time alone together may precipitate HSDD, as can a very restrictive upbringing concerning sex, or negative or traumatic sexual experiences.

Depression, fatigue, or excessive stress may also inhibit sexual interest.

Experimental treatments

Treatment depends in part on the duration of the problem and its causes. No drug therapy has been approved for HSDD in women, although testosterone and other therapies are being studied. Psychotherapy is reported to be mildly effective.

Continuous transdermal testosterone (300-μg patch) improved sexual desire, arousal, and orgasm frequency in women after oophorectomy, with no significant side effects.³

A 24-week study⁴ determined that surgically menopausal women (n=283) who receive transdermal testosterone 300 μg daily along with estrogen experienced 1 additional episode of satisfying sexual activity every 4 weeks, as well as decreased distress and improved desire. Studies are underway to determine whether the findings are clinically significant and to establish longer-term safety and efficacy. The testosterone patch lacks FDA approval.

Don’t forget about prevention

Women who have not undergone premature surgical menopause can help prevent HSDD using these measures:

• Reserving time for nonsexual intimacy such as weekly dating to maintain a closer relationship
  
• “Separating” affection and sex so that affection is not interpreted as an invitation to proceed to intercourse
  
• Increasing communication through books, classes, or reading or watching materials with romantic or sexual content
  
• Reserving time for both talking and sexual intimacy earlier in the evening before exhaustion sets in, to encourage closeness and sexual desire.
  

CASE Is her request reasonable?

A 40-year-old primigravid woman presents for her first prenatal visit and asks for cesarean delivery. She explains that she has “waited all her life” for this baby and does not want to risk any harm to the infant during childbirth. She also admits that she is uncomfortable with the unpredictability of childbirth.

CASE Don’t try to dissuade her

The best way to handle this 40-year-old woman’s concerns is to avoid trying to change her mind. Instead, try to understand her view, which no doubt influences her experience of pregnancy, and do your best to remain unbiased as you gather information about her beliefs and constructs. Don’t fall into the trap of merely dispensing facts without her input, or the discussion will be unproductive.

When she reveals that other women have told her about their experiences with long labors and emergency cesarean delivery, you have an opening for discussion. Return to her concerns periodically during the course of antenatal care, telling her what to expect during pregnancy and delivery, and lay out the pros and cons of cesarean vs vaginal delivery. Other helpful resources are a second opinion, birthing classes, and prenatal yoga and expectant mothers’ groups. The next choice is up to you. Once she understands the fetal and maternal risks of cesarean delivery and still prefers an elective cesarean, the next choice is up to you. If you are morally opposed to the idea, refer the patient to another physician who would be willing to perform the cesarean delivery.

The patient should also consider how she will want to proceed if she presents in active labor before her scheduled cesarean section.

The request may be reasonable, but it is impossible to know without an extended discussion and an individualized decision.^1-11

Requests for cesarean delivery are becoming more common as the cesarean delivery rate hits all-time highs and the media focuses greater attention on the risks inherent in labor and vaginal delivery. One indicator of the increasing incidence of maternal requests for elective cesarean is the recent State of the Science Conference on the subject, convened by the National Institutes of Health, March 27–29, 2006. (See for more on this conference.)

This article describes what considerations should go into the discussion of cesarean delivery on maternal request, including ways of predicting whether vaginal delivery will be successful, the importance of knowing the number of children desired, the need to observe key ethical principles, and the balancing act necessary between physician and patient autonomy.

Gauging the likelihood of safe vaginal delivery

Cesarean on demand, without a clinical indication, may be reasonable in some circumstances, although we lack data to prove that cesarean delivery is globally superior to vaginal delivery in terms of maternal and fetal morbidity and mortality.

Scoring systems may help. For example, maternal obesity is a leading risk factor for cesarean delivery, as are short height, advanced maternal age, large pregnancy weight gain, large birth weight, and increasing gestational age.¹²

Using scoring systems that assign values to these risk factors, one can reasonably predict a patient’s likelihood of undergoing cesarean delivery after attempted vaginal delivery.^13,14

Fetal distress remains wild card

Unfortunately, these scoring tools cannot account for the unpredictability of “fetal distress,” which remains, along with shoulder dystocia, one of the main reasons for performing cesarean delivery in labor.^15,16

Ethical concerns

The principles that guide medical decision-making and counseling are:

• Respect for autonomy. The patient has a right to refuse or choose recommended treatments.
• Beneficence. The physician is obligated to promote maternal and fetal well-being, and the patient is obligated to promote the well-being of her fetus.
• Nonmaleficence centers on the goal of avoiding harm and complements the principle of beneficence.
• Justice refers to fairness to the individual and physician and the impact on society.^4-7

Consider both short- and long-term consequences

Epidemiologically, physicians bear responsibility for the short- and long-term impacts of their actions. For example, injudicious prescribing of antibiotics has led to drug resistance, and many patients now believe they have the right to request antibiotics for likely viral illness. In obstetrics, the lack of emphasis or counseling on breastfeeding created a cascade effect, which started with affluent women who rejected breastfeeding and eventually reached all socioeconomic groups.

TABLE

Maternal and fetal morbidity and mortality rates for planned vaginal and elective cesarean deliveries

Will poorer women have equal access?

Women in lower socioeconomic groups should not receive substandard care; however, the inverse care “law” describes a disturbing reality: The availability of good medical care is inversely related to the need of the population served.^17,18 Thus, the concept of justice, or taking into consideration the greater good for society, is relevant to the elective cesarean debate.

Costs and complications

Cost analysis has shown that expenditures are minimally increased by elective cesarean delivery at 39 weeks’ gestation, which also involves more efficient and predictable use of staffing resources.¹⁹

Parallel placenta accreta rate

The risk of morbidity and mortality associated with pregnancies exceeding 39 weeks’ gestation may be reduced.¹ However, the 10-fold increase in placenta accreta over the past 50 years parallels the rise in cesarean deliveries.²⁰

Fundamentals of patient counseling

Lay out benefits and risks

A detailed comparison of the relative benefits and risks of cesarean delivery (elective, intrapartum, and emergent) versus vaginal delivery (spontaneous, operative, and failed operative) is warranted, along with exploration of the patient’s fears and pressures.^1-10,16

Unfortunately, trials comparing all these modes of delivery and all possible adverse outcomes are lacking. (A brief summary of adverse fetal and maternal outcomes is given in TABLE.) Operative vaginal delivery and intrapartum cesarean delivery generally do increase the risk of injury to maternal pelvic structures, as well as the risk of shoulder dystocia and fetal intracranial hemorrhage.

It is important to remain as unbiased as possible when counseling a patient, and to try to balance the conflict between your own autonomy and hers. Acting as a fiduciary for the patient should not involve suppressing your own sound medical judgment. Nor does it remove the patient’s responsibility to remain involved in her care.^1-8

Although the patient’s right to refuse treatment is usually considered absolute, she can be prevented from demanding intervention when such intervention is not medically supported.^2,4-6,21

Don’t forget future risks

Patients desiring elective cesarean delivery should be apprised of the complications that can arise in subsequent pregnancies.

Some women choose elective cesarean delivery to avoid the hazards of a trial of labor, but may not realize additional hazards, such as placenta accreta, can arise in pregnancies after a cesarean.

Although most women choosing to have only 2 children may experience no complications from elective primary and elective repeat cesarean delivery, some run the risk of placenta previa and possible accreta during the second gestation. These women may experience severe bleeding and require preterm repeat cesarean delivery with hysterectomy. Thus, it is vital to take the patient’s reproductive goals into consideration.

Fear of urinary and rectal incontinence is another reason women often give for desiring cesarean rather than vaginal delivery. However, Rortveit and colleagues²² demonstrated that incontinence affects most elderly women regardless of parity. In addition, it is possible that pregnancy itself contributes to pelvic organ prolapse.^10,23,24

Be open to a second opinion

After counseling the patient about risks and benefits of elective cesarean delivery, raise the issue of a second opinion, and offer the appropriate referrals if one is desired.^4-8,25

Will the cesarean surge subside?

The cesarean delivery rate in the US reached an acme in 2004 at 29.1% of all deliveries. Both the total cesarean rate and the primary cesarean rate have increased each year since 1996. Primary cesarean delivery accounted for 20.6% of all deliveries in 2004—a 40% rise over a decade.^12,26

More cesareans, fewer VBACs

Vaginal birth after cesarean has declined from 28.3% to 9.2% since 1996.²⁶ In 2004, 91% of women with 1 cesarean delivery were likely to have repeat cesarean in subsequent deliveries.²⁷

Trend is up in other countries, too

Most developed countries are also seeing increasing cesarean delivery rates. For example, in the United Kingdom, the overall cesarean delivery rate was 23% in 2003–2004, up from 17% in 1996–1997.²⁸ In New South Wales, Australia, the overall cesarean delivery rate was 23.5% in 2001, up from 17.6% in 1996.²⁹ Data from other countries are older, but typically show increases.

Older “no-risk” gravidas—44% more c-sections For age 35 and older, primiparous women with “no indicated risk” had the greatest frequency of cesarean, according to 1991–2001 US birth certificate data³⁰: 44.2% in 2001—a 44% rise in 10 years.

US trend in cesarean rates per 100 live births

Data for 2003–2004 are preliminary. Due to changes in data collection from implementation of the 2003 revision of the US Standard Certificate of Live Birth, there may be small discontinuities in primary cesarean delivery and VBAC rates in 2003–2004.

SOURCE: Agency for Health Care Research and Quality²⁷

For all ages, primiparous women with no indicated risk had a cesarean delivery rate of 5.5%—a 68% increase in 10 years.

A study from Scotland did report the cesarean delivery rate specifically for “maternal request”: 7.7% in the late 1990s.³¹

CASE Is her request reasonable?

A 40-year-old primigravid woman presents for her first prenatal visit and asks for cesarean delivery. She explains that she has “waited all her life” for this baby and does not want to risk any harm to the infant during childbirth. She also admits that she is uncomfortable with the unpredictability of childbirth.

CASE Don’t try to dissuade her

The best way to handle this 40-year-old woman’s concerns is to avoid trying to change her mind. Instead, try to understand her view, which no doubt influences her experience of pregnancy, and do your best to remain unbiased as you gather information about her beliefs and constructs. Don’t fall into the trap of merely dispensing facts without her input, or the discussion will be unproductive.

When she reveals that other women have told her about their experiences with long labors and emergency cesarean delivery, you have an opening for discussion. Return to her concerns periodically during the course of antenatal care, telling her what to expect during pregnancy and delivery, and lay out the pros and cons of cesarean vs vaginal delivery. Other helpful resources are a second opinion, birthing classes, and prenatal yoga and expectant mothers’ groups. The next choice is up to you. Once she understands the fetal and maternal risks of cesarean delivery and still prefers an elective cesarean, the next choice is up to you. If you are morally opposed to the idea, refer the patient to another physician who would be willing to perform the cesarean delivery.

The patient should also consider how she will want to proceed if she presents in active labor before her scheduled cesarean section.

The request may be reasonable, but it is impossible to know without an extended discussion and an individualized decision.^1-11

Requests for cesarean delivery are becoming more common as the cesarean delivery rate hits all-time highs and the media focuses greater attention on the risks inherent in labor and vaginal delivery. One indicator of the increasing incidence of maternal requests for elective cesarean is the recent State of the Science Conference on the subject, convened by the National Institutes of Health, March 27–29, 2006. (See for more on this conference.)

This article describes what considerations should go into the discussion of cesarean delivery on maternal request, including ways of predicting whether vaginal delivery will be successful, the importance of knowing the number of children desired, the need to observe key ethical principles, and the balancing act necessary between physician and patient autonomy.

Gauging the likelihood of safe vaginal delivery

Cesarean on demand, without a clinical indication, may be reasonable in some circumstances, although we lack data to prove that cesarean delivery is globally superior to vaginal delivery in terms of maternal and fetal morbidity and mortality.

Scoring systems may help. For example, maternal obesity is a leading risk factor for cesarean delivery, as are short height, advanced maternal age, large pregnancy weight gain, large birth weight, and increasing gestational age.¹²

Using scoring systems that assign values to these risk factors, one can reasonably predict a patient’s likelihood of undergoing cesarean delivery after attempted vaginal delivery.^13,14

Fetal distress remains wild card

Unfortunately, these scoring tools cannot account for the unpredictability of “fetal distress,” which remains, along with shoulder dystocia, one of the main reasons for performing cesarean delivery in labor.^15,16

Ethical concerns

The principles that guide medical decision-making and counseling are:

• Respect for autonomy. The patient has a right to refuse or choose recommended treatments.
• Beneficence. The physician is obligated to promote maternal and fetal well-being, and the patient is obligated to promote the well-being of her fetus.
• Nonmaleficence centers on the goal of avoiding harm and complements the principle of beneficence.
• Justice refers to fairness to the individual and physician and the impact on society.^4-7

Consider both short- and long-term consequences

Epidemiologically, physicians bear responsibility for the short- and long-term impacts of their actions. For example, injudicious prescribing of antibiotics has led to drug resistance, and many patients now believe they have the right to request antibiotics for likely viral illness. In obstetrics, the lack of emphasis or counseling on breastfeeding created a cascade effect, which started with affluent women who rejected breastfeeding and eventually reached all socioeconomic groups.

TABLE

Maternal and fetal morbidity and mortality rates for planned vaginal and elective cesarean deliveries

Will poorer women have equal access?

Women in lower socioeconomic groups should not receive substandard care; however, the inverse care “law” describes a disturbing reality: The availability of good medical care is inversely related to the need of the population served.^17,18 Thus, the concept of justice, or taking into consideration the greater good for society, is relevant to the elective cesarean debate.

Costs and complications

Cost analysis has shown that expenditures are minimally increased by elective cesarean delivery at 39 weeks’ gestation, which also involves more efficient and predictable use of staffing resources.¹⁹

Parallel placenta accreta rate

The risk of morbidity and mortality associated with pregnancies exceeding 39 weeks’ gestation may be reduced.¹ However, the 10-fold increase in placenta accreta over the past 50 years parallels the rise in cesarean deliveries.²⁰

Fundamentals of patient counseling

Lay out benefits and risks

A detailed comparison of the relative benefits and risks of cesarean delivery (elective, intrapartum, and emergent) versus vaginal delivery (spontaneous, operative, and failed operative) is warranted, along with exploration of the patient’s fears and pressures.^1-10,16

Unfortunately, trials comparing all these modes of delivery and all possible adverse outcomes are lacking. (A brief summary of adverse fetal and maternal outcomes is given in TABLE.) Operative vaginal delivery and intrapartum cesarean delivery generally do increase the risk of injury to maternal pelvic structures, as well as the risk of shoulder dystocia and fetal intracranial hemorrhage.

It is important to remain as unbiased as possible when counseling a patient, and to try to balance the conflict between your own autonomy and hers. Acting as a fiduciary for the patient should not involve suppressing your own sound medical judgment. Nor does it remove the patient’s responsibility to remain involved in her care.^1-8

Although the patient’s right to refuse treatment is usually considered absolute, she can be prevented from demanding intervention when such intervention is not medically supported.^2,4-6,21

Don’t forget future risks

Patients desiring elective cesarean delivery should be apprised of the complications that can arise in subsequent pregnancies.

Some women choose elective cesarean delivery to avoid the hazards of a trial of labor, but may not realize additional hazards, such as placenta accreta, can arise in pregnancies after a cesarean.

Although most women choosing to have only 2 children may experience no complications from elective primary and elective repeat cesarean delivery, some run the risk of placenta previa and possible accreta during the second gestation. These women may experience severe bleeding and require preterm repeat cesarean delivery with hysterectomy. Thus, it is vital to take the patient’s reproductive goals into consideration.

Fear of urinary and rectal incontinence is another reason women often give for desiring cesarean rather than vaginal delivery. However, Rortveit and colleagues²² demonstrated that incontinence affects most elderly women regardless of parity. In addition, it is possible that pregnancy itself contributes to pelvic organ prolapse.^10,23,24

Be open to a second opinion

After counseling the patient about risks and benefits of elective cesarean delivery, raise the issue of a second opinion, and offer the appropriate referrals if one is desired.^4-8,25

Will the cesarean surge subside?

The cesarean delivery rate in the US reached an acme in 2004 at 29.1% of all deliveries. Both the total cesarean rate and the primary cesarean rate have increased each year since 1996. Primary cesarean delivery accounted for 20.6% of all deliveries in 2004—a 40% rise over a decade.^12,26

More cesareans, fewer VBACs

Vaginal birth after cesarean has declined from 28.3% to 9.2% since 1996.²⁶ In 2004, 91% of women with 1 cesarean delivery were likely to have repeat cesarean in subsequent deliveries.²⁷

Trend is up in other countries, too

Most developed countries are also seeing increasing cesarean delivery rates. For example, in the United Kingdom, the overall cesarean delivery rate was 23% in 2003–2004, up from 17% in 1996–1997.²⁸ In New South Wales, Australia, the overall cesarean delivery rate was 23.5% in 2001, up from 17.6% in 1996.²⁹ Data from other countries are older, but typically show increases.

Older “no-risk” gravidas—44% more c-sections For age 35 and older, primiparous women with “no indicated risk” had the greatest frequency of cesarean, according to 1991–2001 US birth certificate data³⁰: 44.2% in 2001—a 44% rise in 10 years.

US trend in cesarean rates per 100 live births

Data for 2003–2004 are preliminary. Due to changes in data collection from implementation of the 2003 revision of the US Standard Certificate of Live Birth, there may be small discontinuities in primary cesarean delivery and VBAC rates in 2003–2004.

SOURCE: Agency for Health Care Research and Quality²⁷

For all ages, primiparous women with no indicated risk had a cesarean delivery rate of 5.5%—a 68% increase in 10 years.

A study from Scotland did report the cesarean delivery rate specifically for “maternal request”: 7.7% in the late 1990s.³¹

CASE Is her request reasonable?

A 40-year-old primigravid woman presents for her first prenatal visit and asks for cesarean delivery. She explains that she has “waited all her life” for this baby and does not want to risk any harm to the infant during childbirth. She also admits that she is uncomfortable with the unpredictability of childbirth.

CASE Don’t try to dissuade her

The best way to handle this 40-year-old woman’s concerns is to avoid trying to change her mind. Instead, try to understand her view, which no doubt influences her experience of pregnancy, and do your best to remain unbiased as you gather information about her beliefs and constructs. Don’t fall into the trap of merely dispensing facts without her input, or the discussion will be unproductive.

When she reveals that other women have told her about their experiences with long labors and emergency cesarean delivery, you have an opening for discussion. Return to her concerns periodically during the course of antenatal care, telling her what to expect during pregnancy and delivery, and lay out the pros and cons of cesarean vs vaginal delivery. Other helpful resources are a second opinion, birthing classes, and prenatal yoga and expectant mothers’ groups. The next choice is up to you. Once she understands the fetal and maternal risks of cesarean delivery and still prefers an elective cesarean, the next choice is up to you. If you are morally opposed to the idea, refer the patient to another physician who would be willing to perform the cesarean delivery.

The patient should also consider how she will want to proceed if she presents in active labor before her scheduled cesarean section.

The request may be reasonable, but it is impossible to know without an extended discussion and an individualized decision.^1-11

Requests for cesarean delivery are becoming more common as the cesarean delivery rate hits all-time highs and the media focuses greater attention on the risks inherent in labor and vaginal delivery. One indicator of the increasing incidence of maternal requests for elective cesarean is the recent State of the Science Conference on the subject, convened by the National Institutes of Health, March 27–29, 2006. (See for more on this conference.)

This article describes what considerations should go into the discussion of cesarean delivery on maternal request, including ways of predicting whether vaginal delivery will be successful, the importance of knowing the number of children desired, the need to observe key ethical principles, and the balancing act necessary between physician and patient autonomy.

Gauging the likelihood of safe vaginal delivery

Cesarean on demand, without a clinical indication, may be reasonable in some circumstances, although we lack data to prove that cesarean delivery is globally superior to vaginal delivery in terms of maternal and fetal morbidity and mortality.

Scoring systems may help. For example, maternal obesity is a leading risk factor for cesarean delivery, as are short height, advanced maternal age, large pregnancy weight gain, large birth weight, and increasing gestational age.¹²

Using scoring systems that assign values to these risk factors, one can reasonably predict a patient’s likelihood of undergoing cesarean delivery after attempted vaginal delivery.^13,14

Fetal distress remains wild card

Unfortunately, these scoring tools cannot account for the unpredictability of “fetal distress,” which remains, along with shoulder dystocia, one of the main reasons for performing cesarean delivery in labor.^15,16

Ethical concerns

The principles that guide medical decision-making and counseling are:

• Respect for autonomy. The patient has a right to refuse or choose recommended treatments.
• Beneficence. The physician is obligated to promote maternal and fetal well-being, and the patient is obligated to promote the well-being of her fetus.
• Nonmaleficence centers on the goal of avoiding harm and complements the principle of beneficence.
• Justice refers to fairness to the individual and physician and the impact on society.^4-7

Consider both short- and long-term consequences

Epidemiologically, physicians bear responsibility for the short- and long-term impacts of their actions. For example, injudicious prescribing of antibiotics has led to drug resistance, and many patients now believe they have the right to request antibiotics for likely viral illness. In obstetrics, the lack of emphasis or counseling on breastfeeding created a cascade effect, which started with affluent women who rejected breastfeeding and eventually reached all socioeconomic groups.

TABLE

Maternal and fetal morbidity and mortality rates for planned vaginal and elective cesarean deliveries

Will poorer women have equal access?

Women in lower socioeconomic groups should not receive substandard care; however, the inverse care “law” describes a disturbing reality: The availability of good medical care is inversely related to the need of the population served.^17,18 Thus, the concept of justice, or taking into consideration the greater good for society, is relevant to the elective cesarean debate.

Costs and complications

Cost analysis has shown that expenditures are minimally increased by elective cesarean delivery at 39 weeks’ gestation, which also involves more efficient and predictable use of staffing resources.¹⁹

Parallel placenta accreta rate

The risk of morbidity and mortality associated with pregnancies exceeding 39 weeks’ gestation may be reduced.¹ However, the 10-fold increase in placenta accreta over the past 50 years parallels the rise in cesarean deliveries.²⁰

Fundamentals of patient counseling

Lay out benefits and risks

A detailed comparison of the relative benefits and risks of cesarean delivery (elective, intrapartum, and emergent) versus vaginal delivery (spontaneous, operative, and failed operative) is warranted, along with exploration of the patient’s fears and pressures.^1-10,16

Unfortunately, trials comparing all these modes of delivery and all possible adverse outcomes are lacking. (A brief summary of adverse fetal and maternal outcomes is given in TABLE.) Operative vaginal delivery and intrapartum cesarean delivery generally do increase the risk of injury to maternal pelvic structures, as well as the risk of shoulder dystocia and fetal intracranial hemorrhage.

It is important to remain as unbiased as possible when counseling a patient, and to try to balance the conflict between your own autonomy and hers. Acting as a fiduciary for the patient should not involve suppressing your own sound medical judgment. Nor does it remove the patient’s responsibility to remain involved in her care.^1-8

Although the patient’s right to refuse treatment is usually considered absolute, she can be prevented from demanding intervention when such intervention is not medically supported.^2,4-6,21

Don’t forget future risks

Patients desiring elective cesarean delivery should be apprised of the complications that can arise in subsequent pregnancies.

Some women choose elective cesarean delivery to avoid the hazards of a trial of labor, but may not realize additional hazards, such as placenta accreta, can arise in pregnancies after a cesarean.

Although most women choosing to have only 2 children may experience no complications from elective primary and elective repeat cesarean delivery, some run the risk of placenta previa and possible accreta during the second gestation. These women may experience severe bleeding and require preterm repeat cesarean delivery with hysterectomy. Thus, it is vital to take the patient’s reproductive goals into consideration.

Fear of urinary and rectal incontinence is another reason women often give for desiring cesarean rather than vaginal delivery. However, Rortveit and colleagues²² demonstrated that incontinence affects most elderly women regardless of parity. In addition, it is possible that pregnancy itself contributes to pelvic organ prolapse.^10,23,24

Be open to a second opinion

After counseling the patient about risks and benefits of elective cesarean delivery, raise the issue of a second opinion, and offer the appropriate referrals if one is desired.^4-8,25

Will the cesarean surge subside?

The cesarean delivery rate in the US reached an acme in 2004 at 29.1% of all deliveries. Both the total cesarean rate and the primary cesarean rate have increased each year since 1996. Primary cesarean delivery accounted for 20.6% of all deliveries in 2004—a 40% rise over a decade.^12,26

More cesareans, fewer VBACs

Vaginal birth after cesarean has declined from 28.3% to 9.2% since 1996.²⁶ In 2004, 91% of women with 1 cesarean delivery were likely to have repeat cesarean in subsequent deliveries.²⁷

Trend is up in other countries, too

Most developed countries are also seeing increasing cesarean delivery rates. For example, in the United Kingdom, the overall cesarean delivery rate was 23% in 2003–2004, up from 17% in 1996–1997.²⁸ In New South Wales, Australia, the overall cesarean delivery rate was 23.5% in 2001, up from 17.6% in 1996.²⁹ Data from other countries are older, but typically show increases.

Older “no-risk” gravidas—44% more c-sections For age 35 and older, primiparous women with “no indicated risk” had the greatest frequency of cesarean, according to 1991–2001 US birth certificate data³⁰: 44.2% in 2001—a 44% rise in 10 years.

US trend in cesarean rates per 100 live births

Data for 2003–2004 are preliminary. Due to changes in data collection from implementation of the 2003 revision of the US Standard Certificate of Live Birth, there may be small discontinuities in primary cesarean delivery and VBAC rates in 2003–2004.

SOURCE: Agency for Health Care Research and Quality²⁷

For all ages, primiparous women with no indicated risk had a cesarean delivery rate of 5.5%—a 68% increase in 10 years.

A study from Scotland did report the cesarean delivery rate specifically for “maternal request”: 7.7% in the late 1990s.³¹

Surgery may not be the best option for diagnosis and treatment of endometriosis, one of the most common causes of chronic pelvic pain. Although laparoscopy has been the traditional approach, new findings show surgery may cause more adhesions than it removes.

Recent research has also focused on endometriosis in adolescents—and the lack of consensus on what treatment is best. Finally, aromatase inhibitors, a new class of hormone-based therapy, look promising for treatment of pain due to endometriosis.

Even adhesion-reducing surgery causes (and may worsen) adhesions

• Surgery avoidance may be the best strategy for evading adhesions

Parker JD, Sinaii N, Segars JH, Godoy H, Winkel C, Stratton P. Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions. Fertil Steril. 2005;84:1457–1461.

We have known for decades that surgery causes adhesions. The importance of this study is that it demonstrated that careful and thorough surgery designed to remove adhesions and endometriotic implants appears to make no difference in the presence of adhesions 2 years later, and might even worsen adhesions.

This NIH study evaluated 38 women with chronic pelvic pain attributed to endometriosis. At the time of an initial laparoscopy, the locations of endometriosis lesions and adhesions were recorded. All lesions and adhesions were excised using a neodymium-YAG laser, with meticulous hemostasis and careful tissue handling. Ovaries were wrapped in an adhesion barrier (Interceed) after removal of endometriomas; adhesion barriers were otherwise not used. Second-look laparoscopy was performed 2 years later to assess the presence of adhesions.

At the initial surgery, 74% of the 38 patients had adhesions, and at the second-look operation, 82% of the patients had adhesions. Most of the adhesions found at the second operation were not at the original adhesion sites—they were at sites where endometriosis had been excised.

Eighteen endometriomas were excised at the first operation. Although ovaries had been wrapped in an adhesion barrier after excision of the endometriomas, operative site adhesions occurred at 15 of the 18 excision sites. Despite this apparent failure of a barrier to prevent ovarian adhesions, the authors speculated that use of an adhesion barrier after adhesiolysis and after resection of superficial lesions might have prevented some of the adhesions they saw at second-look surgery.

Do adhesions cause pain?

A question not addressed is the role of adhesions in pain; this study did not report pain results. Although the researchers stated that they assumed that adhesions can cause pain, randomized trials have not confirmed this belief.^1,2 Even if adhesions do cause pelvic pain, surgery does not appear to be an effective way to reduce adhesions in the long run.

REFERENCES

1. Peters AAW, Trimbos-Kemper GCM, Admiral C, Trimbos JB. A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain. Br J Obstet Gynaecol. 1992;99:59-62.

2. Swank DJ, Swank-Bordewijk SC, Hop WC, et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomized controlled multi-centre trial. Lancet. 2003;361:1247-1251.

Adolescents get endometriosis, too Should they have laparoscopy?

• Given the propensity of surgery to cause adhesive disease, the fertility of young women may be at risk

Song AH, Advicula AP. Adolescent chronic pelvic pain. J Pediatr Adolesc Gynecol. 2005;18:371–377.

Stavroulis AI, Saridogan E, Creighton SM, Cutner AS. Laparoscopic treatment of endometriosis in teenagers. Eur J Obstet Gynecol Reprod Biol. 2006; in press.

ACOG Committee on Adolescent Health Care. Endometriosis in adolescents. ACOG Committee Opinion No. 310. Obstet Gynecol 2005;105:921–927.

Evaluation and treatment of adolescents with chronic pelvic pain can be more challenging than the care of adults with this complaint. Song and Advicula encourage clinicians to consider endometriosis even in the very young adolescent, and they stress attention to the privacy of the adolescent and the importance of letting her decide whether an accompanying parent should be present during an examination.

It is unfortunate that laparoscopy early in the work-up is encouraged, without evidence of the effectiveness of surgery. Oral contraceptives and nonsteroidal anti-inflammatory drugs are recommended as empiric therapy, but progestins and gonadotropin-releasing hormone (GnRH) analogs are discouraged, although there is no evidence that progestins and GnRH analogs are less safe than oral contraceptives in this age group.

A number of conditions that cause chronic pelvic pain in adolescents are described, but missing are discussions of psychiatric disorders and fibromyalgia, which are important causes of chronic pain.

Stavroulis et al is the latest of anecdotal reports claiming that laparoscopic treatment of endometriosis in teenagers is safe and effective. In this retrospective review of case records of 31 girls younger than 21 years who underwent laparoscopy for chronic pelvic pain, no abnormalities were found in 36% and endometriosis was found in another 36%. The remainder had other findings, including some (ovarian cysts) that are not generally associated with chronic pain, and others (obstructed uterine horn) suggesting that endometriosis may have been missed. Six girls with severe endometriosis had surgical excision, and 5 of the 6 were described as improved after 19 to 112 months of follow-up.

As in most of the literature advocating surgical management of endometriosis, this study had no control group treated with placebo surgery or other therapies. In addition, all the young women who underwent surgery were treated postoperatively with hormonal therapy for an unspecified length of time, making it unclear how much of the pain relief was due to surgery.

What’s wrong with these recommendations?

The ACOG Committee Opinion calls attention to the importance of considering endometriosis as a cause of pain in adolescents. The Opinion offers empiric therapy as an option for the management of young women with chronic pain believed to be due to endometriosis, but does a disservice in promoting laparoscopy as a superior method of diagnosis and treatment. The empiric therapy recommendation is marred by the statement that GnRH analogs should not be used in patients younger than 18 years, with surgery as the only option in this age group. The Committee goes on to recommend that if endometriosis is not visualized at surgery, the patient should be referred for gastrointestinal or urologic evaluation and for pain management services.

Withholding GnRH analogs in women under age 18 is arbitrary and without scientific foundation. The Committee expresses the concern that these agents might interfere with mineralization during this time of maximal bone accretion, and points to the lack of studies of GnRH analog therapy in this age group; however, it is acknowledged that add-back hormone therapy prevents bone mineral loss in the general population of women treated with GnRH analogs.^1,2

Although the Committee is reluctant to recommend therapy because data from this age group are inadequate, it recommends laparoscopy despite the lack of data in this age group on either safety or effectiveness of surgery. The one study cited in support of the effectiveness of surgery³ was performed in adults, and compared laparoscopic excision to diagnostic laparoscopy, not to medical therapy. Finally, the Committee ignores danazol, a medication that continues to be useful for some patients.

Does surgery have more adverse consequences in adolescents than in adults? We don’t know. Given the propensity of surgery to cause adhesive disease, however, the fertility of these young women may be at risk. It is particularly disappointing to see the Committee recommending evaluation for gastrointestinal and urologic disease after failed surgery.

The correct approach is the evaluation and treatment of the patient before, and preferably instead of surgery.⁴

REFERENCES

1. Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol. 1998;91:16-24.

2. Surrey ES, Hornstein MD. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol. 2002;99:709-719.

3. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril. 2004;82:878-884.

4. Peters AAW, van Dorst E, Jellis B, van Zuuren E, Hermans J, Trimbos JB. A randomized trial to compare 2 different approaches to women with chronic pelvic pain. Obstet Gynecol. 1991;77:740-744.

Medical treatment: Aromatase inhibitors for endometriosis

• It is time for a controlled trial on the question of whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis

Hefler LA, Grimm C, van Trotsenburg M, Nagele F. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril. 2005;84:1033–1036.

Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE. Anastrozole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005;84:300–304.

It has been widely accepted for decades that endometriosis is estrogen-dependent. More recently, it has been suspected that ectopic endometrium contains aromatase enzyme, which can produce estrogens locally from circulating androgens. This possibility has led to the use of aromatase inhibitors for the treatment of endometriosis.

Two new studies report on the use of the aromatase inhibitor anastrozole, which is marketed for the treatment of breast cancer:

• Dose too low? Hefler and colleagues treated 10 patients with rectovaginal endometriosis, using a low dose (0.25 mg/day) of vaginal anastrozole, without much improvement in symptoms. They suggested that the dose may have been too low.
• Higher dose improved pain. Amsterdam and colleagues reported that pain improved in 15 of 18 patients who used anastrozole at a dosage of 1 mg/day by mouth. An oral contraceptive was given for hot flash control and prevention of bone mineral loss.

These results, along with other reports in the literature, are encouraging. It is now time for a controlled trial to investigate whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis.

The author has been a consultant for TAP Pharmaceuticals.

Surgery may not be the best option for diagnosis and treatment of endometriosis, one of the most common causes of chronic pelvic pain. Although laparoscopy has been the traditional approach, new findings show surgery may cause more adhesions than it removes.

Recent research has also focused on endometriosis in adolescents—and the lack of consensus on what treatment is best. Finally, aromatase inhibitors, a new class of hormone-based therapy, look promising for treatment of pain due to endometriosis.

Even adhesion-reducing surgery causes (and may worsen) adhesions

• Surgery avoidance may be the best strategy for evading adhesions

Parker JD, Sinaii N, Segars JH, Godoy H, Winkel C, Stratton P. Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions. Fertil Steril. 2005;84:1457–1461.

We have known for decades that surgery causes adhesions. The importance of this study is that it demonstrated that careful and thorough surgery designed to remove adhesions and endometriotic implants appears to make no difference in the presence of adhesions 2 years later, and might even worsen adhesions.

This NIH study evaluated 38 women with chronic pelvic pain attributed to endometriosis. At the time of an initial laparoscopy, the locations of endometriosis lesions and adhesions were recorded. All lesions and adhesions were excised using a neodymium-YAG laser, with meticulous hemostasis and careful tissue handling. Ovaries were wrapped in an adhesion barrier (Interceed) after removal of endometriomas; adhesion barriers were otherwise not used. Second-look laparoscopy was performed 2 years later to assess the presence of adhesions.

At the initial surgery, 74% of the 38 patients had adhesions, and at the second-look operation, 82% of the patients had adhesions. Most of the adhesions found at the second operation were not at the original adhesion sites—they were at sites where endometriosis had been excised.

Eighteen endometriomas were excised at the first operation. Although ovaries had been wrapped in an adhesion barrier after excision of the endometriomas, operative site adhesions occurred at 15 of the 18 excision sites. Despite this apparent failure of a barrier to prevent ovarian adhesions, the authors speculated that use of an adhesion barrier after adhesiolysis and after resection of superficial lesions might have prevented some of the adhesions they saw at second-look surgery.

Do adhesions cause pain?

A question not addressed is the role of adhesions in pain; this study did not report pain results. Although the researchers stated that they assumed that adhesions can cause pain, randomized trials have not confirmed this belief.^1,2 Even if adhesions do cause pelvic pain, surgery does not appear to be an effective way to reduce adhesions in the long run.

REFERENCES

1. Peters AAW, Trimbos-Kemper GCM, Admiral C, Trimbos JB. A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain. Br J Obstet Gynaecol. 1992;99:59-62.

2. Swank DJ, Swank-Bordewijk SC, Hop WC, et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomized controlled multi-centre trial. Lancet. 2003;361:1247-1251.

Adolescents get endometriosis, too Should they have laparoscopy?

• Given the propensity of surgery to cause adhesive disease, the fertility of young women may be at risk

Song AH, Advicula AP. Adolescent chronic pelvic pain. J Pediatr Adolesc Gynecol. 2005;18:371–377.

Stavroulis AI, Saridogan E, Creighton SM, Cutner AS. Laparoscopic treatment of endometriosis in teenagers. Eur J Obstet Gynecol Reprod Biol. 2006; in press.

ACOG Committee on Adolescent Health Care. Endometriosis in adolescents. ACOG Committee Opinion No. 310. Obstet Gynecol 2005;105:921–927.

Evaluation and treatment of adolescents with chronic pelvic pain can be more challenging than the care of adults with this complaint. Song and Advicula encourage clinicians to consider endometriosis even in the very young adolescent, and they stress attention to the privacy of the adolescent and the importance of letting her decide whether an accompanying parent should be present during an examination.

It is unfortunate that laparoscopy early in the work-up is encouraged, without evidence of the effectiveness of surgery. Oral contraceptives and nonsteroidal anti-inflammatory drugs are recommended as empiric therapy, but progestins and gonadotropin-releasing hormone (GnRH) analogs are discouraged, although there is no evidence that progestins and GnRH analogs are less safe than oral contraceptives in this age group.

A number of conditions that cause chronic pelvic pain in adolescents are described, but missing are discussions of psychiatric disorders and fibromyalgia, which are important causes of chronic pain.

Stavroulis et al is the latest of anecdotal reports claiming that laparoscopic treatment of endometriosis in teenagers is safe and effective. In this retrospective review of case records of 31 girls younger than 21 years who underwent laparoscopy for chronic pelvic pain, no abnormalities were found in 36% and endometriosis was found in another 36%. The remainder had other findings, including some (ovarian cysts) that are not generally associated with chronic pain, and others (obstructed uterine horn) suggesting that endometriosis may have been missed. Six girls with severe endometriosis had surgical excision, and 5 of the 6 were described as improved after 19 to 112 months of follow-up.

As in most of the literature advocating surgical management of endometriosis, this study had no control group treated with placebo surgery or other therapies. In addition, all the young women who underwent surgery were treated postoperatively with hormonal therapy for an unspecified length of time, making it unclear how much of the pain relief was due to surgery.

What’s wrong with these recommendations?

The ACOG Committee Opinion calls attention to the importance of considering endometriosis as a cause of pain in adolescents. The Opinion offers empiric therapy as an option for the management of young women with chronic pain believed to be due to endometriosis, but does a disservice in promoting laparoscopy as a superior method of diagnosis and treatment. The empiric therapy recommendation is marred by the statement that GnRH analogs should not be used in patients younger than 18 years, with surgery as the only option in this age group. The Committee goes on to recommend that if endometriosis is not visualized at surgery, the patient should be referred for gastrointestinal or urologic evaluation and for pain management services.

Withholding GnRH analogs in women under age 18 is arbitrary and without scientific foundation. The Committee expresses the concern that these agents might interfere with mineralization during this time of maximal bone accretion, and points to the lack of studies of GnRH analog therapy in this age group; however, it is acknowledged that add-back hormone therapy prevents bone mineral loss in the general population of women treated with GnRH analogs.^1,2

Although the Committee is reluctant to recommend therapy because data from this age group are inadequate, it recommends laparoscopy despite the lack of data in this age group on either safety or effectiveness of surgery. The one study cited in support of the effectiveness of surgery³ was performed in adults, and compared laparoscopic excision to diagnostic laparoscopy, not to medical therapy. Finally, the Committee ignores danazol, a medication that continues to be useful for some patients.

Does surgery have more adverse consequences in adolescents than in adults? We don’t know. Given the propensity of surgery to cause adhesive disease, however, the fertility of these young women may be at risk. It is particularly disappointing to see the Committee recommending evaluation for gastrointestinal and urologic disease after failed surgery.

The correct approach is the evaluation and treatment of the patient before, and preferably instead of surgery.⁴

REFERENCES

1. Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol. 1998;91:16-24.

2. Surrey ES, Hornstein MD. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol. 2002;99:709-719.

3. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril. 2004;82:878-884.

4. Peters AAW, van Dorst E, Jellis B, van Zuuren E, Hermans J, Trimbos JB. A randomized trial to compare 2 different approaches to women with chronic pelvic pain. Obstet Gynecol. 1991;77:740-744.

Medical treatment: Aromatase inhibitors for endometriosis

• It is time for a controlled trial on the question of whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis

Hefler LA, Grimm C, van Trotsenburg M, Nagele F. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril. 2005;84:1033–1036.

Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE. Anastrozole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005;84:300–304.

It has been widely accepted for decades that endometriosis is estrogen-dependent. More recently, it has been suspected that ectopic endometrium contains aromatase enzyme, which can produce estrogens locally from circulating androgens. This possibility has led to the use of aromatase inhibitors for the treatment of endometriosis.

Two new studies report on the use of the aromatase inhibitor anastrozole, which is marketed for the treatment of breast cancer:

• Dose too low? Hefler and colleagues treated 10 patients with rectovaginal endometriosis, using a low dose (0.25 mg/day) of vaginal anastrozole, without much improvement in symptoms. They suggested that the dose may have been too low.
• Higher dose improved pain. Amsterdam and colleagues reported that pain improved in 15 of 18 patients who used anastrozole at a dosage of 1 mg/day by mouth. An oral contraceptive was given for hot flash control and prevention of bone mineral loss.

These results, along with other reports in the literature, are encouraging. It is now time for a controlled trial to investigate whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis.

The author has been a consultant for TAP Pharmaceuticals.

Surgery may not be the best option for diagnosis and treatment of endometriosis, one of the most common causes of chronic pelvic pain. Although laparoscopy has been the traditional approach, new findings show surgery may cause more adhesions than it removes.

Recent research has also focused on endometriosis in adolescents—and the lack of consensus on what treatment is best. Finally, aromatase inhibitors, a new class of hormone-based therapy, look promising for treatment of pain due to endometriosis.

Even adhesion-reducing surgery causes (and may worsen) adhesions

• Surgery avoidance may be the best strategy for evading adhesions

Parker JD, Sinaii N, Segars JH, Godoy H, Winkel C, Stratton P. Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions. Fertil Steril. 2005;84:1457–1461.

We have known for decades that surgery causes adhesions. The importance of this study is that it demonstrated that careful and thorough surgery designed to remove adhesions and endometriotic implants appears to make no difference in the presence of adhesions 2 years later, and might even worsen adhesions.

This NIH study evaluated 38 women with chronic pelvic pain attributed to endometriosis. At the time of an initial laparoscopy, the locations of endometriosis lesions and adhesions were recorded. All lesions and adhesions were excised using a neodymium-YAG laser, with meticulous hemostasis and careful tissue handling. Ovaries were wrapped in an adhesion barrier (Interceed) after removal of endometriomas; adhesion barriers were otherwise not used. Second-look laparoscopy was performed 2 years later to assess the presence of adhesions.

At the initial surgery, 74% of the 38 patients had adhesions, and at the second-look operation, 82% of the patients had adhesions. Most of the adhesions found at the second operation were not at the original adhesion sites—they were at sites where endometriosis had been excised.

Eighteen endometriomas were excised at the first operation. Although ovaries had been wrapped in an adhesion barrier after excision of the endometriomas, operative site adhesions occurred at 15 of the 18 excision sites. Despite this apparent failure of a barrier to prevent ovarian adhesions, the authors speculated that use of an adhesion barrier after adhesiolysis and after resection of superficial lesions might have prevented some of the adhesions they saw at second-look surgery.

Do adhesions cause pain?

A question not addressed is the role of adhesions in pain; this study did not report pain results. Although the researchers stated that they assumed that adhesions can cause pain, randomized trials have not confirmed this belief.^1,2 Even if adhesions do cause pelvic pain, surgery does not appear to be an effective way to reduce adhesions in the long run.

REFERENCES

1. Peters AAW, Trimbos-Kemper GCM, Admiral C, Trimbos JB. A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain. Br J Obstet Gynaecol. 1992;99:59-62.

2. Swank DJ, Swank-Bordewijk SC, Hop WC, et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomized controlled multi-centre trial. Lancet. 2003;361:1247-1251.

Adolescents get endometriosis, too Should they have laparoscopy?

• Given the propensity of surgery to cause adhesive disease, the fertility of young women may be at risk

Song AH, Advicula AP. Adolescent chronic pelvic pain. J Pediatr Adolesc Gynecol. 2005;18:371–377.

Stavroulis AI, Saridogan E, Creighton SM, Cutner AS. Laparoscopic treatment of endometriosis in teenagers. Eur J Obstet Gynecol Reprod Biol. 2006; in press.

ACOG Committee on Adolescent Health Care. Endometriosis in adolescents. ACOG Committee Opinion No. 310. Obstet Gynecol 2005;105:921–927.

Evaluation and treatment of adolescents with chronic pelvic pain can be more challenging than the care of adults with this complaint. Song and Advicula encourage clinicians to consider endometriosis even in the very young adolescent, and they stress attention to the privacy of the adolescent and the importance of letting her decide whether an accompanying parent should be present during an examination.

It is unfortunate that laparoscopy early in the work-up is encouraged, without evidence of the effectiveness of surgery. Oral contraceptives and nonsteroidal anti-inflammatory drugs are recommended as empiric therapy, but progestins and gonadotropin-releasing hormone (GnRH) analogs are discouraged, although there is no evidence that progestins and GnRH analogs are less safe than oral contraceptives in this age group.

A number of conditions that cause chronic pelvic pain in adolescents are described, but missing are discussions of psychiatric disorders and fibromyalgia, which are important causes of chronic pain.

Stavroulis et al is the latest of anecdotal reports claiming that laparoscopic treatment of endometriosis in teenagers is safe and effective. In this retrospective review of case records of 31 girls younger than 21 years who underwent laparoscopy for chronic pelvic pain, no abnormalities were found in 36% and endometriosis was found in another 36%. The remainder had other findings, including some (ovarian cysts) that are not generally associated with chronic pain, and others (obstructed uterine horn) suggesting that endometriosis may have been missed. Six girls with severe endometriosis had surgical excision, and 5 of the 6 were described as improved after 19 to 112 months of follow-up.

As in most of the literature advocating surgical management of endometriosis, this study had no control group treated with placebo surgery or other therapies. In addition, all the young women who underwent surgery were treated postoperatively with hormonal therapy for an unspecified length of time, making it unclear how much of the pain relief was due to surgery.

What’s wrong with these recommendations?

The ACOG Committee Opinion calls attention to the importance of considering endometriosis as a cause of pain in adolescents. The Opinion offers empiric therapy as an option for the management of young women with chronic pain believed to be due to endometriosis, but does a disservice in promoting laparoscopy as a superior method of diagnosis and treatment. The empiric therapy recommendation is marred by the statement that GnRH analogs should not be used in patients younger than 18 years, with surgery as the only option in this age group. The Committee goes on to recommend that if endometriosis is not visualized at surgery, the patient should be referred for gastrointestinal or urologic evaluation and for pain management services.

Withholding GnRH analogs in women under age 18 is arbitrary and without scientific foundation. The Committee expresses the concern that these agents might interfere with mineralization during this time of maximal bone accretion, and points to the lack of studies of GnRH analog therapy in this age group; however, it is acknowledged that add-back hormone therapy prevents bone mineral loss in the general population of women treated with GnRH analogs.^1,2

Although the Committee is reluctant to recommend therapy because data from this age group are inadequate, it recommends laparoscopy despite the lack of data in this age group on either safety or effectiveness of surgery. The one study cited in support of the effectiveness of surgery³ was performed in adults, and compared laparoscopic excision to diagnostic laparoscopy, not to medical therapy. Finally, the Committee ignores danazol, a medication that continues to be useful for some patients.

Does surgery have more adverse consequences in adolescents than in adults? We don’t know. Given the propensity of surgery to cause adhesive disease, however, the fertility of these young women may be at risk. It is particularly disappointing to see the Committee recommending evaluation for gastrointestinal and urologic disease after failed surgery.

The correct approach is the evaluation and treatment of the patient before, and preferably instead of surgery.⁴

REFERENCES

1. Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol. 1998;91:16-24.

2. Surrey ES, Hornstein MD. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol. 2002;99:709-719.

3. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril. 2004;82:878-884.

4. Peters AAW, van Dorst E, Jellis B, van Zuuren E, Hermans J, Trimbos JB. A randomized trial to compare 2 different approaches to women with chronic pelvic pain. Obstet Gynecol. 1991;77:740-744.

Medical treatment: Aromatase inhibitors for endometriosis

• It is time for a controlled trial on the question of whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis

Hefler LA, Grimm C, van Trotsenburg M, Nagele F. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril. 2005;84:1033–1036.

Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE. Anastrozole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005;84:300–304.

It has been widely accepted for decades that endometriosis is estrogen-dependent. More recently, it has been suspected that ectopic endometrium contains aromatase enzyme, which can produce estrogens locally from circulating androgens. This possibility has led to the use of aromatase inhibitors for the treatment of endometriosis.

Two new studies report on the use of the aromatase inhibitor anastrozole, which is marketed for the treatment of breast cancer:

• Dose too low? Hefler and colleagues treated 10 patients with rectovaginal endometriosis, using a low dose (0.25 mg/day) of vaginal anastrozole, without much improvement in symptoms. They suggested that the dose may have been too low.
• Higher dose improved pain. Amsterdam and colleagues reported that pain improved in 15 of 18 patients who used anastrozole at a dosage of 1 mg/day by mouth. An oral contraceptive was given for hot flash control and prevention of bone mineral loss.

These results, along with other reports in the literature, are encouraging. It is now time for a controlled trial to investigate whether aromatase inhibitors are superior to placebo or other medical treatments for endometriosis.

The author has been a consultant for TAP Pharmaceuticals.

CASE Could fetal loss have been prevented?

“L.S.” is a 23-year-old gravida at 16 weeks’ gestation who is experiencing severe asthma. Prior to pregnancy, her asthma was moderate and persistent, but was well-controlled on a low-dose inhaled corticosteroid accompanied by monthly use of a short-acting beta-2 adrenergic inhaler and weekly allergy injections. When she learned she was pregnant, L.S. stopped all treatment except for the beta-2 adrenergic inhaler, which she now uses daily.

After stopping treatment, she remained stable until a viral infection developed, causing shortness of breath and wheezing that are affecting her sleep and daytime activity.

A physical examination reveals audible wheezing with nasal flaring and some retraction at the sternal notch. L.S. is treated with nebulized albuterol and ipratropium in the office, but refuses an injection of corticosteroid.

She is told to start oral steroids and advised that failure to do so will put her at increased risk for pregnancy complications, including fetal loss.

She calls later the same day from the hospital to report vaginal bleeding and continued wheezing. She is admitted and treated with intravenous steroids, nebulized beta-2 adrenergics, and oxygen, but suffers spontaneous abortion.

Many women assume “less is more” when it comes to asthma medications in pregnancy. When L.S. stopped her inhaled corticosteroid therapy, she mistakenly believed she was protecting her fetus. In actuality, it destabilized her condition and led to the pregnancy loss.

With few exceptions, the medications needed to control asthma will diminish maternal and fetal complications, and are safer—for both mother and fetus—than uncontrolled asthma.

The biggest barrier to good control of asthma during pregnancy is the fear—on the part of both physician and patient—that asthma medication may harm the fetus.^1,2

This article reviews current understanding of:

• Asthma control before and during gestation
• How to prevent acute asthma in the first place
• Safe treatment of acute asthma in pregnancy

Asthma is the most common chronic disease in pregnancy

Asthma in pregnancy is not an isolated occurrence but the most common chronic disease in pregnancy. It affects almost 7% of women. About one third of gravidas with asthma experience an exacerbation during pregnancy.

If the asthma is well controlled, however, it need not increase pregnancy risks. Asthma control means:

• Minimal or no chronic symptoms day or night
• Minimal or no exacerbations
• No limitations on activities
• Maintenance of near-normal pulmonary function
• Minimal use of short-acting inhaled beta-2 agonist
• Minimal or no adverse drug effects

For best results, continue asthma treatment throughout pregnancy, and closely monitor women with severe asthma, especially around 26 weeks’ gestation, as they are more likely to experience disease exacerbation. Treatment for acute asthma is similar to therapy in nonpregnant women.

Manage asthma exacerbations aggressively. When exacerbations do occur during pregnancy despite our best efforts, aggressive management—whether at home or in the hospital—is recommended by the National Asthma Education and Prevention Program (TABLE 1).

TABLE 1

What to do if asthma worsens

How pregnancy affects asthma

Pre-pregnancy severity is key

Asthma improves in approximately one third of women, remains the same in one third, and worsens in one third. The severity of asthma prior to pregnancy correlates with the response of asthma to the pregnancy. The more severe the asthma before pregnancy, the more likely severity will increase during pregnancy.³

In rare cases, asthma presents for the first time during pregnancy.

Subsequent pregnancies are similarly affected. The changes in severity that occur in 1 pregnancy tend to recur in subsequent pregnancies.⁴

Some gestational ages are more problematic. The first trimester is generally well tolerated by women with asthma, with rare exacerbations. When symptoms increase, it tends to be near the start of the second trimester until about 36 weeks. Acute exacerbations are most frequent at 26 weeks.

Asthma problems are fewer and less severe during the last 4 weeks of pregnancy, even among women whose disease has worsened over the pregnancy.

Symptoms during labor and delivery are usually mild and easily controlled

Only 10% of women with well-controlled asthma experience increased symptoms during labor and delivery, and these symptoms are usually mild and easily managed. In a study of 360 patients,⁴ 37 women were symptomatic during labor and delivery. Of these, 54% required no treatment, 15% used inhaled bronchodilators, and 5% were given intravenous (IV) aminophylline.

An 18-fold increased risk of asthma exacerbation during delivery by cesarean section was reported in another study, compared with vaginal delivery.⁵

Quick return to pre-pregnancy function. After delivery, most women promptly return to pre-pregnancy pulmonary function.

How asthma affects pregnancy

Prospective and retrospective studies confirm that severe or uncontrolled disease during pregnancy may result in adverse maternal and fetal outcomes. Maternal complications include preeclampsia (risk increases 2- to 3-fold⁶), gestational diabetes, preterm labor, vaginal hemorrhage, placenta previa, toxemia, and cesarean delivery.^7-9 A study of 24,115 women with no history of chronic hypertension found a significant association between asthma (needing treatment) and pregnancy-induced hypertension (P<.001).⁷ A direct correlation was noted between severity of asthma during pregnancy and severity of maternal hypertension.

3 elements of an asthma attack

Asthma is characterized by airway obstruction and epithelial remodeling, caused by airway muscular spasm, excess mucus production, and inflammation. Bronchospasm is the hallmark of acute exacerbations, which manifest clinically as wheezing, shortness of breath, and nonproductive cough.

Greater risk of hemorrhage, drugs or no drugs

The risk of antepartum and postpartum hemorrhage increases in women with uncontrolled asthma, independent of drug usage.⁸ In fact, the increase in postpartum hemorrhage was most pronounced in women who did not take medication. The increased risk of hemorrhage may be related to hemostatic alterations in atopic patients, including deficient platelet aggregation, decreased platelet life span, and altered arachidonic acid metabolism.

Asthma drugs are well tolerated, but save oral steroids for acute disease

In a cohort of 817 women with asthma and 13,709 without, the only significant difference in neonatal outcome was an increased risk of hyperbilirubinemia in the infants of women taking oral steroids.¹⁰

A large multicenter study⁹ of perinatal outcomes in 2,123 women with asthma showed no adverse outcomes related to the use of inhaled beta-agonists, inhaled steroids, or theophylline. However, oral corticosteroid use was significantly associated with an increase in preterm births (<37 weeks) (P=.010) caused by premature rupture of membranes, preterm labor, or for indicated reasons such as fetal distress, intrauterine growth restriction (IUGR), or preeclampsia.⁹ Oral corticosteroid use also was associated with low birth weight (<2,500 g) (P=.008). In addition, there was an increased cesarean delivery rate in the moderate-to-severe asthmatic group.¹¹

No increase in congenital malformations was seen in gravidas with asthma taking a variety of medications, according to a 20-year study in Sweden.^10,12 Recently, using data from the Swedish national birth registry, researchers conducted a subgroup analysis of 2,534 gravidas with first-trimester exposure to the inhaled corticosteroid budesonide, and found no increase in the rate of congenital anomalies.^10,12 Based on this finding, the US Food and Drug Administration (FDA) changed budesonide from pregnancy category C to category B. Although other inhaled corticosteroids may be as safe, they are still classified as category C owing to a lack of clinical data. The FDA classification of several other frequently used asthma drugs is shown in TABLE 2.

Because of the increased risk of prematurity associated with oral steroids, asthma should be carefully controlled to avoid their use if at all possible. However, for severe exacerbations triggered by viral infection or other factors, oral steroids are indicated to reduce the likelihood of other, more significant risks, including death.

It is unclear whether fetal complications associated with oral steroids are a direct result of the drugs or if increased use of oral steroids is just a marker for more severe underlying asthma or exacerbation of asthma. Nevertheless, women who require oral corticosteroids should be educated about the signs and symptoms of threatened preterm delivery.

TABLE 2

Some asthma “controller” medications are safer than others

Fetal surveillance and monitoring

Fetal distress can be caused by acute or chronic maternal hypoxia from severe chronic asthma or acute exacerbations. IUGR may also be related to hypoxia, or it may be a direct result of treatment with oral steroids.¹³

Surveillance with nonstress testing and serial ultrasound, as well as fetal monitoring, may be necessary to check for IUGR, especially in women with severe asthma, because any hypoxemia can affect the fetus. During a severe asthma attack, continuous fetal monitoring (depending on gestational age) may be necessary.

How to control asthma

“Controller” and “reliever” drugs

Daily “controller” drugs are needed to manage inflammation in the lung; they include inhaled corticosteroids and leukotriene inhibitors.

“Reliever” medications such as beta-adrenergic inhalers act rapidly to calm exacerbations, and should be kept readily available.

Individualize allergen avoidance

Environmental allergens or lung irritants can exacerbate asthma. As many as 85% of patients with asthma also have allergies to 1 or more substances such as animals, pollens, molds, and dust mites, which can worsen symptoms. Lung irritants such as smoke, chemical fumes, and environmental pollutants can also be problematic. Finally, some drugs such as aspirin and beta-blockers can trigger acute symptoms.

An important part of treatment for these patients is identification and avoidance of asthma and allergy triggers.

Strategies include keeping pets out of the bedroom, sealing old pillows and mattresses in special encasings, removing drapes, using special filter vacuum bags while cleaning, closing the windows between 5 AM and 10 AM when pollen is highest, and limiting exposure to smoke.

Preconception immunotherapy may help

Immunotherapy is a cornerstone of maintenance therapy for asthma that cannot be controlled via avoidance strategies or medication. Identification of allergy triggers requires skin testing (scratch, patch, or intradermal). Starting with minute amounts of allergen extracts, regular injections with increasing doses are given to stimulate a protective, specific immune response.

Because it takes several months for the treatments to take full effect, and because there is a greater risk of adverse reactions with increasing doses, this therapy should not be initiated during pregnancy. However, it can be carefully continued during pregnancy in women who are already benefiting from it and not experiencing adverse reactions.

If a woman is in the “build-up” phase of immunotherapy when she conceives, continue treatment without increasing the allergen dose.¹⁴

Treatment recommendations

Treatment guidelines generally categorize asthma according to severity (TABLE 3).¹⁵ While these guidelines assist in decision-making, each patient should receive an individualized treatment plan. Severity of the disease is based on clinical signs and symptoms as well as pulmonary function, as measured by FEV1 (forced expiratory volume in the first second of a pulmonary function test). This classification system is helpful in deciding how well asthma is controlled and also in following response to treatment.

Choice of the appropriate medications to control asthma during pregnancy is critical for the best maternal and fetal outcomes (TABLE 3).

No daily medication is needed in women with mild asthma.

Women with mild asthma whose day-time symptoms occur less than daily and whose nighttime symptoms occur less than weekly, often have fewer symptoms during pregnancy.

The tipping point. If the patient is using an entire canister of short-acting inhaled beta-agonist in a month, her disease control is inadequate. This is the point at which therapy should be increased to include long-term control medications, such as daily inhaled corticosteroids or leukotriene inhibitors (TABLE 3).

The most severe asthma, characterized by frequent daytime and nighttime symptoms, is more likely to become exacerbated during pregnancy. These women require careful monitoring to ensure that their medications are prescribed at adequate levels.

TABLE 3

How to determine severity—and treat accordingly

Back off as asthma is controlled

Review treatment every 1 to 3 months; gradual stepwise reduction in treatment may be possible. The goal is to use the least medication necessary to maintain good control of symptoms.

General principles

• Maintain pulmonary function to adequately oxygenate the fetus.
• Prevent acute exacerbation.
• Intervene promptly when treating acute exacerbation and associated conditions such as rhinitis, sinusitis, and gastroesophageal reflux (TABLE 1).
• Prescribe daily anti-inflammatory therapy for persistent asthma.

Recommendations from ACOG and ACAAI

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology also offer specific recommendations,¹⁶ which include:

• Avoid zileuton (Zyflo), which causes adverse fetal effects in animals and lacks human data
• Give the leukotriene modifiers montelukast (Singulair) or zafirlukast (Accolate) if the patient had a good pre-pregnancy response to these drugs
• Budesonide (Rhinocort) is a good choice for high-dose inhaled corticosteroid and is now classified as a category B drug
• Drugs to be avoided: alpha-adrenergic medications (except pseudoephedrine), iodides, tetracyclines, sulfonamides, and epinephrine (except for a life-threatening event)

In addition, we make sure:

• Every woman with asthma of any severity has a beta-adrenergic short-acting (bronchodilator) inhaler as a “rescue” treatment and knows when and how to use it.
• Women with persistent asthma have an action plan, and, in some cases, a peak-flow meter at home.
• Every patient with asthma has oral prednisone at home, with instructions to start it immediately in the event of an exacerbation unresponsive to bronchodilators and other measures in the action plan.
• Finally, we reassure gravidas that their asthma drugs will provide more benefit than harm to the fetus, compared with uncontrolled asthma.

Overcoming reluctance to treat

The reluctance to treat gravidas with asthma can be difficult to overcome, even with the proper assurance and education. Effective management requires a team effort, with communication between the allergist, obstetrician, and patient. Compliance will improve if women of childbearing age are treated with asthma drugs that can be safely continued during pregnancy.

At the first prenatal visit, reassure the patient that, in most cases, it is safer for her and her baby to control the asthma than to discontinue therapy. Every visit should include assessment of maternal asthma, and there should be a consultation with the allergist/pulmonologist whenever needed. Overall, helping a pregnant woman maintain control of her asthma and improve obstetric outcomes is easy—a matter of paying attention to the right details.

CASE Could fetal loss have been prevented?

“L.S.” is a 23-year-old gravida at 16 weeks’ gestation who is experiencing severe asthma. Prior to pregnancy, her asthma was moderate and persistent, but was well-controlled on a low-dose inhaled corticosteroid accompanied by monthly use of a short-acting beta-2 adrenergic inhaler and weekly allergy injections. When she learned she was pregnant, L.S. stopped all treatment except for the beta-2 adrenergic inhaler, which she now uses daily.

After stopping treatment, she remained stable until a viral infection developed, causing shortness of breath and wheezing that are affecting her sleep and daytime activity.

A physical examination reveals audible wheezing with nasal flaring and some retraction at the sternal notch. L.S. is treated with nebulized albuterol and ipratropium in the office, but refuses an injection of corticosteroid.

She is told to start oral steroids and advised that failure to do so will put her at increased risk for pregnancy complications, including fetal loss.

She calls later the same day from the hospital to report vaginal bleeding and continued wheezing. She is admitted and treated with intravenous steroids, nebulized beta-2 adrenergics, and oxygen, but suffers spontaneous abortion.

Many women assume “less is more” when it comes to asthma medications in pregnancy. When L.S. stopped her inhaled corticosteroid therapy, she mistakenly believed she was protecting her fetus. In actuality, it destabilized her condition and led to the pregnancy loss.

With few exceptions, the medications needed to control asthma will diminish maternal and fetal complications, and are safer—for both mother and fetus—than uncontrolled asthma.

The biggest barrier to good control of asthma during pregnancy is the fear—on the part of both physician and patient—that asthma medication may harm the fetus.^1,2

This article reviews current understanding of:

• Asthma control before and during gestation
• How to prevent acute asthma in the first place
• Safe treatment of acute asthma in pregnancy

Asthma is the most common chronic disease in pregnancy

Asthma in pregnancy is not an isolated occurrence but the most common chronic disease in pregnancy. It affects almost 7% of women. About one third of gravidas with asthma experience an exacerbation during pregnancy.

If the asthma is well controlled, however, it need not increase pregnancy risks. Asthma control means:

• Minimal or no chronic symptoms day or night
• Minimal or no exacerbations
• No limitations on activities
• Maintenance of near-normal pulmonary function
• Minimal use of short-acting inhaled beta-2 agonist
• Minimal or no adverse drug effects

For best results, continue asthma treatment throughout pregnancy, and closely monitor women with severe asthma, especially around 26 weeks’ gestation, as they are more likely to experience disease exacerbation. Treatment for acute asthma is similar to therapy in nonpregnant women.

Manage asthma exacerbations aggressively. When exacerbations do occur during pregnancy despite our best efforts, aggressive management—whether at home or in the hospital—is recommended by the National Asthma Education and Prevention Program (TABLE 1).

TABLE 1

What to do if asthma worsens

How pregnancy affects asthma

Pre-pregnancy severity is key

Asthma improves in approximately one third of women, remains the same in one third, and worsens in one third. The severity of asthma prior to pregnancy correlates with the response of asthma to the pregnancy. The more severe the asthma before pregnancy, the more likely severity will increase during pregnancy.³

In rare cases, asthma presents for the first time during pregnancy.

Subsequent pregnancies are similarly affected. The changes in severity that occur in 1 pregnancy tend to recur in subsequent pregnancies.⁴

Some gestational ages are more problematic. The first trimester is generally well tolerated by women with asthma, with rare exacerbations. When symptoms increase, it tends to be near the start of the second trimester until about 36 weeks. Acute exacerbations are most frequent at 26 weeks.

Asthma problems are fewer and less severe during the last 4 weeks of pregnancy, even among women whose disease has worsened over the pregnancy.

Symptoms during labor and delivery are usually mild and easily controlled

Only 10% of women with well-controlled asthma experience increased symptoms during labor and delivery, and these symptoms are usually mild and easily managed. In a study of 360 patients,⁴ 37 women were symptomatic during labor and delivery. Of these, 54% required no treatment, 15% used inhaled bronchodilators, and 5% were given intravenous (IV) aminophylline.

An 18-fold increased risk of asthma exacerbation during delivery by cesarean section was reported in another study, compared with vaginal delivery.⁵

Quick return to pre-pregnancy function. After delivery, most women promptly return to pre-pregnancy pulmonary function.

How asthma affects pregnancy

Prospective and retrospective studies confirm that severe or uncontrolled disease during pregnancy may result in adverse maternal and fetal outcomes. Maternal complications include preeclampsia (risk increases 2- to 3-fold⁶), gestational diabetes, preterm labor, vaginal hemorrhage, placenta previa, toxemia, and cesarean delivery.^7-9 A study of 24,115 women with no history of chronic hypertension found a significant association between asthma (needing treatment) and pregnancy-induced hypertension (P<.001).⁷ A direct correlation was noted between severity of asthma during pregnancy and severity of maternal hypertension.

3 elements of an asthma attack

Asthma is characterized by airway obstruction and epithelial remodeling, caused by airway muscular spasm, excess mucus production, and inflammation. Bronchospasm is the hallmark of acute exacerbations, which manifest clinically as wheezing, shortness of breath, and nonproductive cough.

Greater risk of hemorrhage, drugs or no drugs

The risk of antepartum and postpartum hemorrhage increases in women with uncontrolled asthma, independent of drug usage.⁸ In fact, the increase in postpartum hemorrhage was most pronounced in women who did not take medication. The increased risk of hemorrhage may be related to hemostatic alterations in atopic patients, including deficient platelet aggregation, decreased platelet life span, and altered arachidonic acid metabolism.

Asthma drugs are well tolerated, but save oral steroids for acute disease

In a cohort of 817 women with asthma and 13,709 without, the only significant difference in neonatal outcome was an increased risk of hyperbilirubinemia in the infants of women taking oral steroids.¹⁰

A large multicenter study⁹ of perinatal outcomes in 2,123 women with asthma showed no adverse outcomes related to the use of inhaled beta-agonists, inhaled steroids, or theophylline. However, oral corticosteroid use was significantly associated with an increase in preterm births (<37 weeks) (P=.010) caused by premature rupture of membranes, preterm labor, or for indicated reasons such as fetal distress, intrauterine growth restriction (IUGR), or preeclampsia.⁹ Oral corticosteroid use also was associated with low birth weight (<2,500 g) (P=.008). In addition, there was an increased cesarean delivery rate in the moderate-to-severe asthmatic group.¹¹

No increase in congenital malformations was seen in gravidas with asthma taking a variety of medications, according to a 20-year study in Sweden.^10,12 Recently, using data from the Swedish national birth registry, researchers conducted a subgroup analysis of 2,534 gravidas with first-trimester exposure to the inhaled corticosteroid budesonide, and found no increase in the rate of congenital anomalies.^10,12 Based on this finding, the US Food and Drug Administration (FDA) changed budesonide from pregnancy category C to category B. Although other inhaled corticosteroids may be as safe, they are still classified as category C owing to a lack of clinical data. The FDA classification of several other frequently used asthma drugs is shown in TABLE 2.

Because of the increased risk of prematurity associated with oral steroids, asthma should be carefully controlled to avoid their use if at all possible. However, for severe exacerbations triggered by viral infection or other factors, oral steroids are indicated to reduce the likelihood of other, more significant risks, including death.

It is unclear whether fetal complications associated with oral steroids are a direct result of the drugs or if increased use of oral steroids is just a marker for more severe underlying asthma or exacerbation of asthma. Nevertheless, women who require oral corticosteroids should be educated about the signs and symptoms of threatened preterm delivery.

TABLE 2

Some asthma “controller” medications are safer than others

Fetal surveillance and monitoring

Fetal distress can be caused by acute or chronic maternal hypoxia from severe chronic asthma or acute exacerbations. IUGR may also be related to hypoxia, or it may be a direct result of treatment with oral steroids.¹³

Surveillance with nonstress testing and serial ultrasound, as well as fetal monitoring, may be necessary to check for IUGR, especially in women with severe asthma, because any hypoxemia can affect the fetus. During a severe asthma attack, continuous fetal monitoring (depending on gestational age) may be necessary.

How to control asthma

“Controller” and “reliever” drugs

Daily “controller” drugs are needed to manage inflammation in the lung; they include inhaled corticosteroids and leukotriene inhibitors.

“Reliever” medications such as beta-adrenergic inhalers act rapidly to calm exacerbations, and should be kept readily available.

Individualize allergen avoidance

Environmental allergens or lung irritants can exacerbate asthma. As many as 85% of patients with asthma also have allergies to 1 or more substances such as animals, pollens, molds, and dust mites, which can worsen symptoms. Lung irritants such as smoke, chemical fumes, and environmental pollutants can also be problematic. Finally, some drugs such as aspirin and beta-blockers can trigger acute symptoms.

An important part of treatment for these patients is identification and avoidance of asthma and allergy triggers.

Strategies include keeping pets out of the bedroom, sealing old pillows and mattresses in special encasings, removing drapes, using special filter vacuum bags while cleaning, closing the windows between 5 AM and 10 AM when pollen is highest, and limiting exposure to smoke.

Preconception immunotherapy may help

Immunotherapy is a cornerstone of maintenance therapy for asthma that cannot be controlled via avoidance strategies or medication. Identification of allergy triggers requires skin testing (scratch, patch, or intradermal). Starting with minute amounts of allergen extracts, regular injections with increasing doses are given to stimulate a protective, specific immune response.

Because it takes several months for the treatments to take full effect, and because there is a greater risk of adverse reactions with increasing doses, this therapy should not be initiated during pregnancy. However, it can be carefully continued during pregnancy in women who are already benefiting from it and not experiencing adverse reactions.

If a woman is in the “build-up” phase of immunotherapy when she conceives, continue treatment without increasing the allergen dose.¹⁴

Treatment recommendations

Treatment guidelines generally categorize asthma according to severity (TABLE 3).¹⁵ While these guidelines assist in decision-making, each patient should receive an individualized treatment plan. Severity of the disease is based on clinical signs and symptoms as well as pulmonary function, as measured by FEV1 (forced expiratory volume in the first second of a pulmonary function test). This classification system is helpful in deciding how well asthma is controlled and also in following response to treatment.

Choice of the appropriate medications to control asthma during pregnancy is critical for the best maternal and fetal outcomes (TABLE 3).

No daily medication is needed in women with mild asthma.

Women with mild asthma whose day-time symptoms occur less than daily and whose nighttime symptoms occur less than weekly, often have fewer symptoms during pregnancy.

The tipping point. If the patient is using an entire canister of short-acting inhaled beta-agonist in a month, her disease control is inadequate. This is the point at which therapy should be increased to include long-term control medications, such as daily inhaled corticosteroids or leukotriene inhibitors (TABLE 3).

The most severe asthma, characterized by frequent daytime and nighttime symptoms, is more likely to become exacerbated during pregnancy. These women require careful monitoring to ensure that their medications are prescribed at adequate levels.

TABLE 3

How to determine severity—and treat accordingly

Back off as asthma is controlled

Review treatment every 1 to 3 months; gradual stepwise reduction in treatment may be possible. The goal is to use the least medication necessary to maintain good control of symptoms.

General principles

• Maintain pulmonary function to adequately oxygenate the fetus.
• Prevent acute exacerbation.
• Intervene promptly when treating acute exacerbation and associated conditions such as rhinitis, sinusitis, and gastroesophageal reflux (TABLE 1).
• Prescribe daily anti-inflammatory therapy for persistent asthma.

Recommendations from ACOG and ACAAI

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology also offer specific recommendations,¹⁶ which include:

• Avoid zileuton (Zyflo), which causes adverse fetal effects in animals and lacks human data
• Give the leukotriene modifiers montelukast (Singulair) or zafirlukast (Accolate) if the patient had a good pre-pregnancy response to these drugs
• Budesonide (Rhinocort) is a good choice for high-dose inhaled corticosteroid and is now classified as a category B drug
• Drugs to be avoided: alpha-adrenergic medications (except pseudoephedrine), iodides, tetracyclines, sulfonamides, and epinephrine (except for a life-threatening event)

In addition, we make sure:

• Every woman with asthma of any severity has a beta-adrenergic short-acting (bronchodilator) inhaler as a “rescue” treatment and knows when and how to use it.
• Women with persistent asthma have an action plan, and, in some cases, a peak-flow meter at home.
• Every patient with asthma has oral prednisone at home, with instructions to start it immediately in the event of an exacerbation unresponsive to bronchodilators and other measures in the action plan.
• Finally, we reassure gravidas that their asthma drugs will provide more benefit than harm to the fetus, compared with uncontrolled asthma.

Overcoming reluctance to treat

The reluctance to treat gravidas with asthma can be difficult to overcome, even with the proper assurance and education. Effective management requires a team effort, with communication between the allergist, obstetrician, and patient. Compliance will improve if women of childbearing age are treated with asthma drugs that can be safely continued during pregnancy.

At the first prenatal visit, reassure the patient that, in most cases, it is safer for her and her baby to control the asthma than to discontinue therapy. Every visit should include assessment of maternal asthma, and there should be a consultation with the allergist/pulmonologist whenever needed. Overall, helping a pregnant woman maintain control of her asthma and improve obstetric outcomes is easy—a matter of paying attention to the right details.

CASE Could fetal loss have been prevented?

“L.S.” is a 23-year-old gravida at 16 weeks’ gestation who is experiencing severe asthma. Prior to pregnancy, her asthma was moderate and persistent, but was well-controlled on a low-dose inhaled corticosteroid accompanied by monthly use of a short-acting beta-2 adrenergic inhaler and weekly allergy injections. When she learned she was pregnant, L.S. stopped all treatment except for the beta-2 adrenergic inhaler, which she now uses daily.

After stopping treatment, she remained stable until a viral infection developed, causing shortness of breath and wheezing that are affecting her sleep and daytime activity.

A physical examination reveals audible wheezing with nasal flaring and some retraction at the sternal notch. L.S. is treated with nebulized albuterol and ipratropium in the office, but refuses an injection of corticosteroid.

She is told to start oral steroids and advised that failure to do so will put her at increased risk for pregnancy complications, including fetal loss.

She calls later the same day from the hospital to report vaginal bleeding and continued wheezing. She is admitted and treated with intravenous steroids, nebulized beta-2 adrenergics, and oxygen, but suffers spontaneous abortion.

Many women assume “less is more” when it comes to asthma medications in pregnancy. When L.S. stopped her inhaled corticosteroid therapy, she mistakenly believed she was protecting her fetus. In actuality, it destabilized her condition and led to the pregnancy loss.

With few exceptions, the medications needed to control asthma will diminish maternal and fetal complications, and are safer—for both mother and fetus—than uncontrolled asthma.

The biggest barrier to good control of asthma during pregnancy is the fear—on the part of both physician and patient—that asthma medication may harm the fetus.^1,2

This article reviews current understanding of:

• Asthma control before and during gestation
• How to prevent acute asthma in the first place
• Safe treatment of acute asthma in pregnancy

Asthma is the most common chronic disease in pregnancy

Asthma in pregnancy is not an isolated occurrence but the most common chronic disease in pregnancy. It affects almost 7% of women. About one third of gravidas with asthma experience an exacerbation during pregnancy.

If the asthma is well controlled, however, it need not increase pregnancy risks. Asthma control means:

• Minimal or no chronic symptoms day or night
• Minimal or no exacerbations
• No limitations on activities
• Maintenance of near-normal pulmonary function
• Minimal use of short-acting inhaled beta-2 agonist
• Minimal or no adverse drug effects

For best results, continue asthma treatment throughout pregnancy, and closely monitor women with severe asthma, especially around 26 weeks’ gestation, as they are more likely to experience disease exacerbation. Treatment for acute asthma is similar to therapy in nonpregnant women.

Manage asthma exacerbations aggressively. When exacerbations do occur during pregnancy despite our best efforts, aggressive management—whether at home or in the hospital—is recommended by the National Asthma Education and Prevention Program (TABLE 1).

TABLE 1

What to do if asthma worsens

How pregnancy affects asthma

Pre-pregnancy severity is key

Asthma improves in approximately one third of women, remains the same in one third, and worsens in one third. The severity of asthma prior to pregnancy correlates with the response of asthma to the pregnancy. The more severe the asthma before pregnancy, the more likely severity will increase during pregnancy.³

In rare cases, asthma presents for the first time during pregnancy.

Subsequent pregnancies are similarly affected. The changes in severity that occur in 1 pregnancy tend to recur in subsequent pregnancies.⁴

Some gestational ages are more problematic. The first trimester is generally well tolerated by women with asthma, with rare exacerbations. When symptoms increase, it tends to be near the start of the second trimester until about 36 weeks. Acute exacerbations are most frequent at 26 weeks.

Asthma problems are fewer and less severe during the last 4 weeks of pregnancy, even among women whose disease has worsened over the pregnancy.

Symptoms during labor and delivery are usually mild and easily controlled

Only 10% of women with well-controlled asthma experience increased symptoms during labor and delivery, and these symptoms are usually mild and easily managed. In a study of 360 patients,⁴ 37 women were symptomatic during labor and delivery. Of these, 54% required no treatment, 15% used inhaled bronchodilators, and 5% were given intravenous (IV) aminophylline.

An 18-fold increased risk of asthma exacerbation during delivery by cesarean section was reported in another study, compared with vaginal delivery.⁵

Quick return to pre-pregnancy function. After delivery, most women promptly return to pre-pregnancy pulmonary function.

How asthma affects pregnancy

Prospective and retrospective studies confirm that severe or uncontrolled disease during pregnancy may result in adverse maternal and fetal outcomes. Maternal complications include preeclampsia (risk increases 2- to 3-fold⁶), gestational diabetes, preterm labor, vaginal hemorrhage, placenta previa, toxemia, and cesarean delivery.^7-9 A study of 24,115 women with no history of chronic hypertension found a significant association between asthma (needing treatment) and pregnancy-induced hypertension (P<.001).⁷ A direct correlation was noted between severity of asthma during pregnancy and severity of maternal hypertension.

3 elements of an asthma attack

Asthma is characterized by airway obstruction and epithelial remodeling, caused by airway muscular spasm, excess mucus production, and inflammation. Bronchospasm is the hallmark of acute exacerbations, which manifest clinically as wheezing, shortness of breath, and nonproductive cough.

Greater risk of hemorrhage, drugs or no drugs

The risk of antepartum and postpartum hemorrhage increases in women with uncontrolled asthma, independent of drug usage.⁸ In fact, the increase in postpartum hemorrhage was most pronounced in women who did not take medication. The increased risk of hemorrhage may be related to hemostatic alterations in atopic patients, including deficient platelet aggregation, decreased platelet life span, and altered arachidonic acid metabolism.

Asthma drugs are well tolerated, but save oral steroids for acute disease

In a cohort of 817 women with asthma and 13,709 without, the only significant difference in neonatal outcome was an increased risk of hyperbilirubinemia in the infants of women taking oral steroids.¹⁰

A large multicenter study⁹ of perinatal outcomes in 2,123 women with asthma showed no adverse outcomes related to the use of inhaled beta-agonists, inhaled steroids, or theophylline. However, oral corticosteroid use was significantly associated with an increase in preterm births (<37 weeks) (P=.010) caused by premature rupture of membranes, preterm labor, or for indicated reasons such as fetal distress, intrauterine growth restriction (IUGR), or preeclampsia.⁹ Oral corticosteroid use also was associated with low birth weight (<2,500 g) (P=.008). In addition, there was an increased cesarean delivery rate in the moderate-to-severe asthmatic group.¹¹

No increase in congenital malformations was seen in gravidas with asthma taking a variety of medications, according to a 20-year study in Sweden.^10,12 Recently, using data from the Swedish national birth registry, researchers conducted a subgroup analysis of 2,534 gravidas with first-trimester exposure to the inhaled corticosteroid budesonide, and found no increase in the rate of congenital anomalies.^10,12 Based on this finding, the US Food and Drug Administration (FDA) changed budesonide from pregnancy category C to category B. Although other inhaled corticosteroids may be as safe, they are still classified as category C owing to a lack of clinical data. The FDA classification of several other frequently used asthma drugs is shown in TABLE 2.

Because of the increased risk of prematurity associated with oral steroids, asthma should be carefully controlled to avoid their use if at all possible. However, for severe exacerbations triggered by viral infection or other factors, oral steroids are indicated to reduce the likelihood of other, more significant risks, including death.

It is unclear whether fetal complications associated with oral steroids are a direct result of the drugs or if increased use of oral steroids is just a marker for more severe underlying asthma or exacerbation of asthma. Nevertheless, women who require oral corticosteroids should be educated about the signs and symptoms of threatened preterm delivery.

TABLE 2

Some asthma “controller” medications are safer than others

Fetal surveillance and monitoring

Fetal distress can be caused by acute or chronic maternal hypoxia from severe chronic asthma or acute exacerbations. IUGR may also be related to hypoxia, or it may be a direct result of treatment with oral steroids.¹³

Surveillance with nonstress testing and serial ultrasound, as well as fetal monitoring, may be necessary to check for IUGR, especially in women with severe asthma, because any hypoxemia can affect the fetus. During a severe asthma attack, continuous fetal monitoring (depending on gestational age) may be necessary.

How to control asthma

“Controller” and “reliever” drugs

Daily “controller” drugs are needed to manage inflammation in the lung; they include inhaled corticosteroids and leukotriene inhibitors.

“Reliever” medications such as beta-adrenergic inhalers act rapidly to calm exacerbations, and should be kept readily available.

Individualize allergen avoidance

Environmental allergens or lung irritants can exacerbate asthma. As many as 85% of patients with asthma also have allergies to 1 or more substances such as animals, pollens, molds, and dust mites, which can worsen symptoms. Lung irritants such as smoke, chemical fumes, and environmental pollutants can also be problematic. Finally, some drugs such as aspirin and beta-blockers can trigger acute symptoms.

An important part of treatment for these patients is identification and avoidance of asthma and allergy triggers.

Strategies include keeping pets out of the bedroom, sealing old pillows and mattresses in special encasings, removing drapes, using special filter vacuum bags while cleaning, closing the windows between 5 AM and 10 AM when pollen is highest, and limiting exposure to smoke.

Preconception immunotherapy may help

Immunotherapy is a cornerstone of maintenance therapy for asthma that cannot be controlled via avoidance strategies or medication. Identification of allergy triggers requires skin testing (scratch, patch, or intradermal). Starting with minute amounts of allergen extracts, regular injections with increasing doses are given to stimulate a protective, specific immune response.

Because it takes several months for the treatments to take full effect, and because there is a greater risk of adverse reactions with increasing doses, this therapy should not be initiated during pregnancy. However, it can be carefully continued during pregnancy in women who are already benefiting from it and not experiencing adverse reactions.

If a woman is in the “build-up” phase of immunotherapy when she conceives, continue treatment without increasing the allergen dose.¹⁴

Treatment recommendations

Treatment guidelines generally categorize asthma according to severity (TABLE 3).¹⁵ While these guidelines assist in decision-making, each patient should receive an individualized treatment plan. Severity of the disease is based on clinical signs and symptoms as well as pulmonary function, as measured by FEV1 (forced expiratory volume in the first second of a pulmonary function test). This classification system is helpful in deciding how well asthma is controlled and also in following response to treatment.

Choice of the appropriate medications to control asthma during pregnancy is critical for the best maternal and fetal outcomes (TABLE 3).

No daily medication is needed in women with mild asthma.

Women with mild asthma whose day-time symptoms occur less than daily and whose nighttime symptoms occur less than weekly, often have fewer symptoms during pregnancy.

The tipping point. If the patient is using an entire canister of short-acting inhaled beta-agonist in a month, her disease control is inadequate. This is the point at which therapy should be increased to include long-term control medications, such as daily inhaled corticosteroids or leukotriene inhibitors (TABLE 3).

The most severe asthma, characterized by frequent daytime and nighttime symptoms, is more likely to become exacerbated during pregnancy. These women require careful monitoring to ensure that their medications are prescribed at adequate levels.

TABLE 3

How to determine severity—and treat accordingly

Back off as asthma is controlled

Review treatment every 1 to 3 months; gradual stepwise reduction in treatment may be possible. The goal is to use the least medication necessary to maintain good control of symptoms.

General principles

• Maintain pulmonary function to adequately oxygenate the fetus.
• Prevent acute exacerbation.
• Intervene promptly when treating acute exacerbation and associated conditions such as rhinitis, sinusitis, and gastroesophageal reflux (TABLE 1).
• Prescribe daily anti-inflammatory therapy for persistent asthma.

Recommendations from ACOG and ACAAI

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology also offer specific recommendations,¹⁶ which include:

• Avoid zileuton (Zyflo), which causes adverse fetal effects in animals and lacks human data
• Give the leukotriene modifiers montelukast (Singulair) or zafirlukast (Accolate) if the patient had a good pre-pregnancy response to these drugs
• Budesonide (Rhinocort) is a good choice for high-dose inhaled corticosteroid and is now classified as a category B drug
• Drugs to be avoided: alpha-adrenergic medications (except pseudoephedrine), iodides, tetracyclines, sulfonamides, and epinephrine (except for a life-threatening event)

In addition, we make sure:

• Every woman with asthma of any severity has a beta-adrenergic short-acting (bronchodilator) inhaler as a “rescue” treatment and knows when and how to use it.
• Women with persistent asthma have an action plan, and, in some cases, a peak-flow meter at home.
• Every patient with asthma has oral prednisone at home, with instructions to start it immediately in the event of an exacerbation unresponsive to bronchodilators and other measures in the action plan.
• Finally, we reassure gravidas that their asthma drugs will provide more benefit than harm to the fetus, compared with uncontrolled asthma.

Overcoming reluctance to treat

The reluctance to treat gravidas with asthma can be difficult to overcome, even with the proper assurance and education. Effective management requires a team effort, with communication between the allergist, obstetrician, and patient. Compliance will improve if women of childbearing age are treated with asthma drugs that can be safely continued during pregnancy.

At the first prenatal visit, reassure the patient that, in most cases, it is safer for her and her baby to control the asthma than to discontinue therapy. Every visit should include assessment of maternal asthma, and there should be a consultation with the allergist/pulmonologist whenever needed. Overall, helping a pregnant woman maintain control of her asthma and improve obstetric outcomes is easy—a matter of paying attention to the right details.

4 reasons claims are denied

1 The payer includes it in a global package

2 Lack of preauthorization

3 Payer assumes the claim is a duplicate

4 Registration process involved an error

It’s the end of another long day, and your billing manager is in tears. For the third time this month, she is frustrated about the overwhelming amount of work in the billing office. “The staff simply can’t keep up!” she exclaims.

She wants to hire another biller. But you have spent considerable time the past few months brushing up on your coding expertise and renegotiating contracts with your key payers. So why has the billing workload increased so much? Why is your staff overwhelmed?

The problem isn’t limited to your practice. All types of medical practices face increased workloads in their billing offices. Quite often, the added work is from a single source—claim denials. If your billing office always seems overwhelmed, check the volume and types of denied claims. Many of the problems are preventable.

The solution to denials is not always to hire more staff. Too often, the billing staff focuses on managing denials after they happen, but that’s a losing game. Your first line of defense is to fix the problems that cause denials. Then identify strategies to prevent the denials and manage them when they do occur.

1Don’t accept bundling of stand-alone services

Many codes encompass a predetermined period before, during, and after the service you provide. ObGyns are most familiar with the coding for deliveries. For example, a claim for a service coded 59510 includes all routine obstetric care, be it antepartum, postpartum, or the cesarean delivery itself.

If this seems cut and dried, think again. What if the patient returns a week after discharge with a minor infection in the wound site? You’d document your service and bill for an appropriate-level office visit. Despite its merit, that claim might be denied and returned, marked with words such as “inclusive,” “global period,” or “bundled.” Regardless of the exact language, the payer is saying that payment for the service was included in another payment it made.

Train staff to question denials

In many practices, staffers simply accept denials. They write off the charge as a contractual adjustment for that payer, and the money is gone—even though you deserved it! Although many services you provide during a pregnancy can be legitimately included with other procedure codes, this one—and perhaps others you bill—is not one of those bundled services.

Two terms are important: global period and bundling of multiple services.

Global period is the time (0, 10, or 90 days, for example) during which any services you provide are included in the payment for the service. For obstetric services, that period includes antepartum, delivery, and postpartum care. For gynecologic surgeries, the period varies by the surgery. These periods of time—often called “globals”—are established by the Centers for Medicare and Medicaid Services (CMS) and are published annually in the Resource-based Relative Value Scale.

Bundling means that 1 service is identified as the primary service, and any additional services during the same session are included in the payment. That is, you get paid for the primary service only. CMS publishes a list of primary procedures and the procedures secondary to them in its Correct Coding Initiative, which is updated quarterly. However, many payers establish their own bundling rules.

Note when the global period begins. Let’s return to the example of the global obstetric package. Services rendered during this period are often bundled. Often, even if it is coded appropriately (ie, separately), the first encounter is included in the package payment. ACOG attempted to clarify this situation last October, when it observed, “If a patient presents with signs or symptoms of pregnancy and the patient is there to confirm pregnancy, this visit may be reported with the appropriate level of E/M services code. However, if the OB record is initiated at this visit, then the visit becomes part of the global OB package and is not billed separately.” In fact, the visit becomes part of the global OB package whenever the OB record is started at this time, even if the physician is confirming a pregnancy diagnosed by another source.

Services that are often billed separately but considered inclusive by many payers:

• annual preventive exams, which may include a related problem-focused visit and/or related lab tests; and
• global obstetric packages, which may include ultrasounds, nonstress tests, and routine Pap smears.

ACTION PLAN

To manage denials for inclusion, require each payer to outline its rules about bundling for the services you commonly bill. For example, ask the payer to list the services included in the global obstetric package, and get it in writing. Then train yourself and your staff on what’s included—and what’s not.

Have your staff flag denials that can be appealed, and offer to dictate a letter, if necessary, explaining when services you performed were coded and billed appropriately as 2 (or more) distinct services.

2Make preauthorization top priority

Some payers require preauthorization for specific services. A common example is amniocentesis. Ask your billing staff to alert you to any claim denied for lack of preauthorization, precertification, or referral approval. Although appeals of these denials after the fact are often unsuccessful, you should usually make the attempt anyway. For example, if your patient did not provide accurate information about her coverage, you may have unknowingly failed to obtain the necessary authorization or billed the wrong insurance company. Even though it is too late to obtain the authorization after the service is rendered, write an appeal letter for this type of denial. Explain to the payer that the patient failed to disclose the correct insurance coverage; thus, you were not able to follow its rules.

ACTION PLAN

For services you commonly render, make a list of the payers that require authorizations. When the service is ordered, check that list to determine whether preauthorization is necessary. Better yet, summarize those common services and the patient’s benefit coverage in the patient’s paper or electronic chart. If services are denied, consider appealing the decision.

3Stop “duplicate billing” denials

Some claims are denied because the payer concludes it is a duplicate. This may happen if you mistakenly send a claim more than once; at other times, the patient actually had similar services performed, but the payer mistakes them for a single service.

For example, a patient presents with a urinary tract infection (UTI) twice in the same week. You appropriately code your level of service for the encounters, which may be code 99213 in both cases, and attach a diagnosis of UTI. The payer may not spot the different date for the second service, and mistakenly assumes the second is a duplicate.

ACTION PLAN

Put your staff on alert for inappropriate denials based on duplication. Appeal these denials for payment and point out in the appeal that the services were rendered and accurately coded and billed.

Your staff could be a cause of high denial rates. Perhaps they simply resubmit claims without considering the situation, or fail to attach new information to the resubmitted denial to help the payer understand that it is not a duplicate claim. Unfortunately, it is common for unproductive or unknowledgeable staff to simply rebill claims as they work open or denied claims.

Before you rebill a claim, it is important to evaluate the account carefully. Determine the status of an open claim before resubmitting it.

For a denied claim, fix the problem or attach an explanation—instead of making the same mistake twice. If that’s the case, you’ll just get a denial for a duplicate claim, no payment, and more work to do.

4Get the registration right

Many ObGyn practices are plagued by registration-related errors that translate into claim denials. If the registration process is inaccurate, even by a single keystroke, the claim will be denied. Common registration-related denials include: “subscriber not eligible on the date of service” and “subscriber not identified.”

ACTION PLAN

Be a stickler. Track down staffers who make mistakes and show them what they are doing wrong; otherwise, they’ll just keep making errors. At each patient encounter, or at least every 3 months, verify insurance and eligibility—with both patient and the payer. Use payers’ Web sites to confirm coverage.

4 reasons claims are denied

1 The payer includes it in a global package

2 Lack of preauthorization

3 Payer assumes the claim is a duplicate

4 Registration process involved an error

It’s the end of another long day, and your billing manager is in tears. For the third time this month, she is frustrated about the overwhelming amount of work in the billing office. “The staff simply can’t keep up!” she exclaims.

She wants to hire another biller. But you have spent considerable time the past few months brushing up on your coding expertise and renegotiating contracts with your key payers. So why has the billing workload increased so much? Why is your staff overwhelmed?

The problem isn’t limited to your practice. All types of medical practices face increased workloads in their billing offices. Quite often, the added work is from a single source—claim denials. If your billing office always seems overwhelmed, check the volume and types of denied claims. Many of the problems are preventable.

The solution to denials is not always to hire more staff. Too often, the billing staff focuses on managing denials after they happen, but that’s a losing game. Your first line of defense is to fix the problems that cause denials. Then identify strategies to prevent the denials and manage them when they do occur.

1Don’t accept bundling of stand-alone services

Many codes encompass a predetermined period before, during, and after the service you provide. ObGyns are most familiar with the coding for deliveries. For example, a claim for a service coded 59510 includes all routine obstetric care, be it antepartum, postpartum, or the cesarean delivery itself.

If this seems cut and dried, think again. What if the patient returns a week after discharge with a minor infection in the wound site? You’d document your service and bill for an appropriate-level office visit. Despite its merit, that claim might be denied and returned, marked with words such as “inclusive,” “global period,” or “bundled.” Regardless of the exact language, the payer is saying that payment for the service was included in another payment it made.

Train staff to question denials

In many practices, staffers simply accept denials. They write off the charge as a contractual adjustment for that payer, and the money is gone—even though you deserved it! Although many services you provide during a pregnancy can be legitimately included with other procedure codes, this one—and perhaps others you bill—is not one of those bundled services.

Two terms are important: global period and bundling of multiple services.

Global period is the time (0, 10, or 90 days, for example) during which any services you provide are included in the payment for the service. For obstetric services, that period includes antepartum, delivery, and postpartum care. For gynecologic surgeries, the period varies by the surgery. These periods of time—often called “globals”—are established by the Centers for Medicare and Medicaid Services (CMS) and are published annually in the Resource-based Relative Value Scale.

Bundling means that 1 service is identified as the primary service, and any additional services during the same session are included in the payment. That is, you get paid for the primary service only. CMS publishes a list of primary procedures and the procedures secondary to them in its Correct Coding Initiative, which is updated quarterly. However, many payers establish their own bundling rules.

Note when the global period begins. Let’s return to the example of the global obstetric package. Services rendered during this period are often bundled. Often, even if it is coded appropriately (ie, separately), the first encounter is included in the package payment. ACOG attempted to clarify this situation last October, when it observed, “If a patient presents with signs or symptoms of pregnancy and the patient is there to confirm pregnancy, this visit may be reported with the appropriate level of E/M services code. However, if the OB record is initiated at this visit, then the visit becomes part of the global OB package and is not billed separately.” In fact, the visit becomes part of the global OB package whenever the OB record is started at this time, even if the physician is confirming a pregnancy diagnosed by another source.

Services that are often billed separately but considered inclusive by many payers:

• annual preventive exams, which may include a related problem-focused visit and/or related lab tests; and
• global obstetric packages, which may include ultrasounds, nonstress tests, and routine Pap smears.

ACTION PLAN

To manage denials for inclusion, require each payer to outline its rules about bundling for the services you commonly bill. For example, ask the payer to list the services included in the global obstetric package, and get it in writing. Then train yourself and your staff on what’s included—and what’s not.

Have your staff flag denials that can be appealed, and offer to dictate a letter, if necessary, explaining when services you performed were coded and billed appropriately as 2 (or more) distinct services.

2Make preauthorization top priority

Some payers require preauthorization for specific services. A common example is amniocentesis. Ask your billing staff to alert you to any claim denied for lack of preauthorization, precertification, or referral approval. Although appeals of these denials after the fact are often unsuccessful, you should usually make the attempt anyway. For example, if your patient did not provide accurate information about her coverage, you may have unknowingly failed to obtain the necessary authorization or billed the wrong insurance company. Even though it is too late to obtain the authorization after the service is rendered, write an appeal letter for this type of denial. Explain to the payer that the patient failed to disclose the correct insurance coverage; thus, you were not able to follow its rules.

ACTION PLAN

For services you commonly render, make a list of the payers that require authorizations. When the service is ordered, check that list to determine whether preauthorization is necessary. Better yet, summarize those common services and the patient’s benefit coverage in the patient’s paper or electronic chart. If services are denied, consider appealing the decision.

3Stop “duplicate billing” denials

Some claims are denied because the payer concludes it is a duplicate. This may happen if you mistakenly send a claim more than once; at other times, the patient actually had similar services performed, but the payer mistakes them for a single service.

For example, a patient presents with a urinary tract infection (UTI) twice in the same week. You appropriately code your level of service for the encounters, which may be code 99213 in both cases, and attach a diagnosis of UTI. The payer may not spot the different date for the second service, and mistakenly assumes the second is a duplicate.

ACTION PLAN

Put your staff on alert for inappropriate denials based on duplication. Appeal these denials for payment and point out in the appeal that the services were rendered and accurately coded and billed.

Your staff could be a cause of high denial rates. Perhaps they simply resubmit claims without considering the situation, or fail to attach new information to the resubmitted denial to help the payer understand that it is not a duplicate claim. Unfortunately, it is common for unproductive or unknowledgeable staff to simply rebill claims as they work open or denied claims.

Before you rebill a claim, it is important to evaluate the account carefully. Determine the status of an open claim before resubmitting it.

For a denied claim, fix the problem or attach an explanation—instead of making the same mistake twice. If that’s the case, you’ll just get a denial for a duplicate claim, no payment, and more work to do.

4Get the registration right

Many ObGyn practices are plagued by registration-related errors that translate into claim denials. If the registration process is inaccurate, even by a single keystroke, the claim will be denied. Common registration-related denials include: “subscriber not eligible on the date of service” and “subscriber not identified.”

ACTION PLAN

Be a stickler. Track down staffers who make mistakes and show them what they are doing wrong; otherwise, they’ll just keep making errors. At each patient encounter, or at least every 3 months, verify insurance and eligibility—with both patient and the payer. Use payers’ Web sites to confirm coverage.

4 reasons claims are denied

1 The payer includes it in a global package

2 Lack of preauthorization

3 Payer assumes the claim is a duplicate

4 Registration process involved an error

It’s the end of another long day, and your billing manager is in tears. For the third time this month, she is frustrated about the overwhelming amount of work in the billing office. “The staff simply can’t keep up!” she exclaims.

She wants to hire another biller. But you have spent considerable time the past few months brushing up on your coding expertise and renegotiating contracts with your key payers. So why has the billing workload increased so much? Why is your staff overwhelmed?

The problem isn’t limited to your practice. All types of medical practices face increased workloads in their billing offices. Quite often, the added work is from a single source—claim denials. If your billing office always seems overwhelmed, check the volume and types of denied claims. Many of the problems are preventable.

The solution to denials is not always to hire more staff. Too often, the billing staff focuses on managing denials after they happen, but that’s a losing game. Your first line of defense is to fix the problems that cause denials. Then identify strategies to prevent the denials and manage them when they do occur.

1Don’t accept bundling of stand-alone services

Many codes encompass a predetermined period before, during, and after the service you provide. ObGyns are most familiar with the coding for deliveries. For example, a claim for a service coded 59510 includes all routine obstetric care, be it antepartum, postpartum, or the cesarean delivery itself.

If this seems cut and dried, think again. What if the patient returns a week after discharge with a minor infection in the wound site? You’d document your service and bill for an appropriate-level office visit. Despite its merit, that claim might be denied and returned, marked with words such as “inclusive,” “global period,” or “bundled.” Regardless of the exact language, the payer is saying that payment for the service was included in another payment it made.

Train staff to question denials

In many practices, staffers simply accept denials. They write off the charge as a contractual adjustment for that payer, and the money is gone—even though you deserved it! Although many services you provide during a pregnancy can be legitimately included with other procedure codes, this one—and perhaps others you bill—is not one of those bundled services.

Two terms are important: global period and bundling of multiple services.

Global period is the time (0, 10, or 90 days, for example) during which any services you provide are included in the payment for the service. For obstetric services, that period includes antepartum, delivery, and postpartum care. For gynecologic surgeries, the period varies by the surgery. These periods of time—often called “globals”—are established by the Centers for Medicare and Medicaid Services (CMS) and are published annually in the Resource-based Relative Value Scale.

Bundling means that 1 service is identified as the primary service, and any additional services during the same session are included in the payment. That is, you get paid for the primary service only. CMS publishes a list of primary procedures and the procedures secondary to them in its Correct Coding Initiative, which is updated quarterly. However, many payers establish their own bundling rules.

Note when the global period begins. Let’s return to the example of the global obstetric package. Services rendered during this period are often bundled. Often, even if it is coded appropriately (ie, separately), the first encounter is included in the package payment. ACOG attempted to clarify this situation last October, when it observed, “If a patient presents with signs or symptoms of pregnancy and the patient is there to confirm pregnancy, this visit may be reported with the appropriate level of E/M services code. However, if the OB record is initiated at this visit, then the visit becomes part of the global OB package and is not billed separately.” In fact, the visit becomes part of the global OB package whenever the OB record is started at this time, even if the physician is confirming a pregnancy diagnosed by another source.

Services that are often billed separately but considered inclusive by many payers:

• annual preventive exams, which may include a related problem-focused visit and/or related lab tests; and
• global obstetric packages, which may include ultrasounds, nonstress tests, and routine Pap smears.

ACTION PLAN

To manage denials for inclusion, require each payer to outline its rules about bundling for the services you commonly bill. For example, ask the payer to list the services included in the global obstetric package, and get it in writing. Then train yourself and your staff on what’s included—and what’s not.

Have your staff flag denials that can be appealed, and offer to dictate a letter, if necessary, explaining when services you performed were coded and billed appropriately as 2 (or more) distinct services.

2Make preauthorization top priority

Some payers require preauthorization for specific services. A common example is amniocentesis. Ask your billing staff to alert you to any claim denied for lack of preauthorization, precertification, or referral approval. Although appeals of these denials after the fact are often unsuccessful, you should usually make the attempt anyway. For example, if your patient did not provide accurate information about her coverage, you may have unknowingly failed to obtain the necessary authorization or billed the wrong insurance company. Even though it is too late to obtain the authorization after the service is rendered, write an appeal letter for this type of denial. Explain to the payer that the patient failed to disclose the correct insurance coverage; thus, you were not able to follow its rules.

ACTION PLAN

For services you commonly render, make a list of the payers that require authorizations. When the service is ordered, check that list to determine whether preauthorization is necessary. Better yet, summarize those common services and the patient’s benefit coverage in the patient’s paper or electronic chart. If services are denied, consider appealing the decision.

3Stop “duplicate billing” denials

Some claims are denied because the payer concludes it is a duplicate. This may happen if you mistakenly send a claim more than once; at other times, the patient actually had similar services performed, but the payer mistakes them for a single service.

For example, a patient presents with a urinary tract infection (UTI) twice in the same week. You appropriately code your level of service for the encounters, which may be code 99213 in both cases, and attach a diagnosis of UTI. The payer may not spot the different date for the second service, and mistakenly assumes the second is a duplicate.

ACTION PLAN

Put your staff on alert for inappropriate denials based on duplication. Appeal these denials for payment and point out in the appeal that the services were rendered and accurately coded and billed.

Your staff could be a cause of high denial rates. Perhaps they simply resubmit claims without considering the situation, or fail to attach new information to the resubmitted denial to help the payer understand that it is not a duplicate claim. Unfortunately, it is common for unproductive or unknowledgeable staff to simply rebill claims as they work open or denied claims.

Before you rebill a claim, it is important to evaluate the account carefully. Determine the status of an open claim before resubmitting it.

For a denied claim, fix the problem or attach an explanation—instead of making the same mistake twice. If that’s the case, you’ll just get a denial for a duplicate claim, no payment, and more work to do.

4Get the registration right

Many ObGyn practices are plagued by registration-related errors that translate into claim denials. If the registration process is inaccurate, even by a single keystroke, the claim will be denied. Common registration-related denials include: “subscriber not eligible on the date of service” and “subscriber not identified.”

ACTION PLAN

Be a stickler. Track down staffers who make mistakes and show them what they are doing wrong; otherwise, they’ll just keep making errors. At each patient encounter, or at least every 3 months, verify insurance and eligibility—with both patient and the payer. Use payers’ Web sites to confirm coverage.