Erika F. Werner, MD

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.