Obstetrics

In a move that narrowly avoids a government shutdown, Congress has passed a long-awaited bill that keeps the government afloat and provides $1.1 billion in funding to combat the Zika virus.

The House cleared H.R. 5325 late Sept. 28 by a 342-85 tally, following a 72-26 vote by the Senate earlier in the day. The final package, which keeps the government operating through Dec. 9, also includes $37 million for opioid addiction and $500 million for flooding in Louisiana. The White House has indicated that President Obama will sign the bill into law.

The American Congress of Obstetricians and Gynecologists praised Congress for passing the long-delayed comprehensive Zika funding package.

“Congress has finally treated Zika like the emergency it is and shown the American people that it is capable of rising above partisanship for the health of its citizens,” Thomas Gellhaus, MD, ACOG president, said in a statement. “ACOG stands with peer organizations and government agencies in the fight to prevent and respond to the Zika virus and support the care and treatment of all people affected by it. ... The fight against the spread of Zika cannot be won without the resources to support responsive and proactive solutions. This comprehensive funding package is essential to our success and the health of women and babies.”

The bill’s passage caps months of fiery debate within Congress over what to include in the measure. The bill stalled earlier this week largely over whether to direct funds to Flint, Mich., to deal with the crisis over lead-tainted water. Leaders agreed to provide aid to Flint residents in a separate water projects bill. Legislators will address final approval of the Flint measure in December.

Of the $1.1 billion included in the final package to fight Zika, $15 million would go to Florida and $60 million to the territory of Puerto Rico to respond to Zika outbreaks in those areas. The remainder of the funding would be used to prevent, prepare for, and respond to Zika; health conditions related to such virus; and other vector-borne diseases, domestically and internationally.

If signed by the President, the money would also go toward developing necessary countermeasures and vaccines, including the development and purchase of vaccines, therapeutics, diagnostics, and necessary medical supplies. Additionally, the funding would aid research on the virology, natural history, and pathogenesis of the Zika virus infection and preclinical and clinical development of vaccines and other medical countermeasures for the Zika virus.

The American Medical Association expressed relief that Congress had finally taken action to provide resources for fighting Zika.

“It has been clear over the past several months that the U.S. has needed additional resources to combat the Zika virus,” AMA president Andrew W. Gurman, MD, said in a statement. “With the threat of the virus continuing to loom, this funding will help protect more people – particularly pregnant women and their children – from the virus’s lasting negative health effects.”

[email protected]

On Twitter @legal_med

In a move that narrowly avoids a government shutdown, Congress has passed a long-awaited bill that keeps the government afloat and provides $1.1 billion in funding to combat the Zika virus.

The House cleared H.R. 5325 late Sept. 28 by a 342-85 tally, following a 72-26 vote by the Senate earlier in the day. The final package, which keeps the government operating through Dec. 9, also includes $37 million for opioid addiction and $500 million for flooding in Louisiana. The White House has indicated that President Obama will sign the bill into law.

The American Congress of Obstetricians and Gynecologists praised Congress for passing the long-delayed comprehensive Zika funding package.

“Congress has finally treated Zika like the emergency it is and shown the American people that it is capable of rising above partisanship for the health of its citizens,” Thomas Gellhaus, MD, ACOG president, said in a statement. “ACOG stands with peer organizations and government agencies in the fight to prevent and respond to the Zika virus and support the care and treatment of all people affected by it. ... The fight against the spread of Zika cannot be won without the resources to support responsive and proactive solutions. This comprehensive funding package is essential to our success and the health of women and babies.”

The bill’s passage caps months of fiery debate within Congress over what to include in the measure. The bill stalled earlier this week largely over whether to direct funds to Flint, Mich., to deal with the crisis over lead-tainted water. Leaders agreed to provide aid to Flint residents in a separate water projects bill. Legislators will address final approval of the Flint measure in December.

Of the $1.1 billion included in the final package to fight Zika, $15 million would go to Florida and $60 million to the territory of Puerto Rico to respond to Zika outbreaks in those areas. The remainder of the funding would be used to prevent, prepare for, and respond to Zika; health conditions related to such virus; and other vector-borne diseases, domestically and internationally.

If signed by the President, the money would also go toward developing necessary countermeasures and vaccines, including the development and purchase of vaccines, therapeutics, diagnostics, and necessary medical supplies. Additionally, the funding would aid research on the virology, natural history, and pathogenesis of the Zika virus infection and preclinical and clinical development of vaccines and other medical countermeasures for the Zika virus.

The American Medical Association expressed relief that Congress had finally taken action to provide resources for fighting Zika.

“It has been clear over the past several months that the U.S. has needed additional resources to combat the Zika virus,” AMA president Andrew W. Gurman, MD, said in a statement. “With the threat of the virus continuing to loom, this funding will help protect more people – particularly pregnant women and their children – from the virus’s lasting negative health effects.”

[email protected]

On Twitter @legal_med

In a move that narrowly avoids a government shutdown, Congress has passed a long-awaited bill that keeps the government afloat and provides $1.1 billion in funding to combat the Zika virus.

The House cleared H.R. 5325 late Sept. 28 by a 342-85 tally, following a 72-26 vote by the Senate earlier in the day. The final package, which keeps the government operating through Dec. 9, also includes $37 million for opioid addiction and $500 million for flooding in Louisiana. The White House has indicated that President Obama will sign the bill into law.

The American Congress of Obstetricians and Gynecologists praised Congress for passing the long-delayed comprehensive Zika funding package.

“Congress has finally treated Zika like the emergency it is and shown the American people that it is capable of rising above partisanship for the health of its citizens,” Thomas Gellhaus, MD, ACOG president, said in a statement. “ACOG stands with peer organizations and government agencies in the fight to prevent and respond to the Zika virus and support the care and treatment of all people affected by it. ... The fight against the spread of Zika cannot be won without the resources to support responsive and proactive solutions. This comprehensive funding package is essential to our success and the health of women and babies.”

The bill’s passage caps months of fiery debate within Congress over what to include in the measure. The bill stalled earlier this week largely over whether to direct funds to Flint, Mich., to deal with the crisis over lead-tainted water. Leaders agreed to provide aid to Flint residents in a separate water projects bill. Legislators will address final approval of the Flint measure in December.

Of the $1.1 billion included in the final package to fight Zika, $15 million would go to Florida and $60 million to the territory of Puerto Rico to respond to Zika outbreaks in those areas. The remainder of the funding would be used to prevent, prepare for, and respond to Zika; health conditions related to such virus; and other vector-borne diseases, domestically and internationally.

If signed by the President, the money would also go toward developing necessary countermeasures and vaccines, including the development and purchase of vaccines, therapeutics, diagnostics, and necessary medical supplies. Additionally, the funding would aid research on the virology, natural history, and pathogenesis of the Zika virus infection and preclinical and clinical development of vaccines and other medical countermeasures for the Zika virus.

The American Medical Association expressed relief that Congress had finally taken action to provide resources for fighting Zika.

“It has been clear over the past several months that the U.S. has needed additional resources to combat the Zika virus,” AMA president Andrew W. Gurman, MD, said in a statement. “With the threat of the virus continuing to loom, this funding will help protect more people – particularly pregnant women and their children – from the virus’s lasting negative health effects.”

[email protected]

On Twitter @legal_med

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

EXPERT COMMENTARY

Cheong-See and colleagues conducted a comprehensive review and analysis of 32 studies of uncomplicated dichorionic and monochorionic twin pregnancies to determine the risks of stillbirth and neonatal complications by gestational age.

Details of the study

The authors searched major databases for studies on twin pregnancies that reported rates of stillbirth as well as neonatal outcomes (neonatal mortality was defined as death up to 28 days after delivery). A total of 32 studies were included in the analysis, with 29,685 dichorionic and 5,486 monochorionic pregnancies in 35,171 women. The authors estimated the gestational-age specific differences in risk for stillbirths and neonatal deaths after 34 weeks’ gestation.

In dichorionic pregnancies, the prospective weekly pooled risk of stillbirths from expectant management and the risk of neonatal mortality from delivery were balanced at 37 weeks of gestation (risk difference, 1.2/1,000, 95% CI, −1.3 to 3.6; I² = 0%). In monochorionic pregnancies, after 36 weeks there was a trend toward an increase in stillbirths compared with neonatal deaths, with a pooled risk difference of 2.5/1,000 (95% CI, −12.4 to 17.4; I² = 0%). Neonatal morbidity rates were consistently reduced with increasing gestational age in both monochorionic and dichorionic pregnancies.

The researchers’ recommendations

The authors recommended that dichorionic pregnancies be delivered at 37 weeks and that the evidence for delivery of monochorionic twins prior to 36 weeks is lacking. While the analysis is comprehensive and well done, it cannot escape the limitations that afflict all systematic reviews and meta-analyses, and these limitations are well addressed by the authors. Several factors, however, warrant caution regarding the adoption of the authors’ recommendations.

Cautions. First, determination of chorionicity may not have been accurate in all of the studies reviewed. Additionally, we have no data on how these pregnancies were managed with respect to antepartum fetal surveillance, ultrasound surveillance for growth and discordancy, and management of labor and delivery. There are no data on the quality of the ultrasound examinations being performed at each of the centers.

Also, the factors that may increase the risk of stillbirth are not necessarily the same factors that may influence the neonatal death rate, and this review moves between the use of these terms (stillbirth rate, neonatal mortality rate, and perinatal mortality rate) fairly frequently. For example, an improperly managed labor, an unanticipated difficult breech extraction, or the need for emergent cesarean delivery of the second twin might contribute to the neonatal death rate irrespective of gestational age at delivery. The authors acknowledge that outcomes may have been influenced by differences in obstetric and neonatal management of twin pregnancies that were observed between centers. Another concern is the authors’ use of unpublished aggregate and individual patient data.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Cheong-See and colleagues conducted a comprehensive review and analysis of 32 studies of uncomplicated dichorionic and monochorionic twin pregnancies to determine the risks of stillbirth and neonatal complications by gestational age.

Details of the study

The authors searched major databases for studies on twin pregnancies that reported rates of stillbirth as well as neonatal outcomes (neonatal mortality was defined as death up to 28 days after delivery). A total of 32 studies were included in the analysis, with 29,685 dichorionic and 5,486 monochorionic pregnancies in 35,171 women. The authors estimated the gestational-age specific differences in risk for stillbirths and neonatal deaths after 34 weeks’ gestation.

In dichorionic pregnancies, the prospective weekly pooled risk of stillbirths from expectant management and the risk of neonatal mortality from delivery were balanced at 37 weeks of gestation (risk difference, 1.2/1,000, 95% CI, −1.3 to 3.6; I² = 0%). In monochorionic pregnancies, after 36 weeks there was a trend toward an increase in stillbirths compared with neonatal deaths, with a pooled risk difference of 2.5/1,000 (95% CI, −12.4 to 17.4; I² = 0%). Neonatal morbidity rates were consistently reduced with increasing gestational age in both monochorionic and dichorionic pregnancies.

The researchers’ recommendations

The authors recommended that dichorionic pregnancies be delivered at 37 weeks and that the evidence for delivery of monochorionic twins prior to 36 weeks is lacking. While the analysis is comprehensive and well done, it cannot escape the limitations that afflict all systematic reviews and meta-analyses, and these limitations are well addressed by the authors. Several factors, however, warrant caution regarding the adoption of the authors’ recommendations.

Cautions. First, determination of chorionicity may not have been accurate in all of the studies reviewed. Additionally, we have no data on how these pregnancies were managed with respect to antepartum fetal surveillance, ultrasound surveillance for growth and discordancy, and management of labor and delivery. There are no data on the quality of the ultrasound examinations being performed at each of the centers.

Also, the factors that may increase the risk of stillbirth are not necessarily the same factors that may influence the neonatal death rate, and this review moves between the use of these terms (stillbirth rate, neonatal mortality rate, and perinatal mortality rate) fairly frequently. For example, an improperly managed labor, an unanticipated difficult breech extraction, or the need for emergent cesarean delivery of the second twin might contribute to the neonatal death rate irrespective of gestational age at delivery. The authors acknowledge that outcomes may have been influenced by differences in obstetric and neonatal management of twin pregnancies that were observed between centers. Another concern is the authors’ use of unpublished aggregate and individual patient data.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Cheong-See and colleagues conducted a comprehensive review and analysis of 32 studies of uncomplicated dichorionic and monochorionic twin pregnancies to determine the risks of stillbirth and neonatal complications by gestational age.

Details of the study

The authors searched major databases for studies on twin pregnancies that reported rates of stillbirth as well as neonatal outcomes (neonatal mortality was defined as death up to 28 days after delivery). A total of 32 studies were included in the analysis, with 29,685 dichorionic and 5,486 monochorionic pregnancies in 35,171 women. The authors estimated the gestational-age specific differences in risk for stillbirths and neonatal deaths after 34 weeks’ gestation.

In dichorionic pregnancies, the prospective weekly pooled risk of stillbirths from expectant management and the risk of neonatal mortality from delivery were balanced at 37 weeks of gestation (risk difference, 1.2/1,000, 95% CI, −1.3 to 3.6; I² = 0%). In monochorionic pregnancies, after 36 weeks there was a trend toward an increase in stillbirths compared with neonatal deaths, with a pooled risk difference of 2.5/1,000 (95% CI, −12.4 to 17.4; I² = 0%). Neonatal morbidity rates were consistently reduced with increasing gestational age in both monochorionic and dichorionic pregnancies.

The researchers’ recommendations

The authors recommended that dichorionic pregnancies be delivered at 37 weeks and that the evidence for delivery of monochorionic twins prior to 36 weeks is lacking. While the analysis is comprehensive and well done, it cannot escape the limitations that afflict all systematic reviews and meta-analyses, and these limitations are well addressed by the authors. Several factors, however, warrant caution regarding the adoption of the authors’ recommendations.

Cautions. First, determination of chorionicity may not have been accurate in all of the studies reviewed. Additionally, we have no data on how these pregnancies were managed with respect to antepartum fetal surveillance, ultrasound surveillance for growth and discordancy, and management of labor and delivery. There are no data on the quality of the ultrasound examinations being performed at each of the centers.

Also, the factors that may increase the risk of stillbirth are not necessarily the same factors that may influence the neonatal death rate, and this review moves between the use of these terms (stillbirth rate, neonatal mortality rate, and perinatal mortality rate) fairly frequently. For example, an improperly managed labor, an unanticipated difficult breech extraction, or the need for emergent cesarean delivery of the second twin might contribute to the neonatal death rate irrespective of gestational age at delivery. The authors acknowledge that outcomes may have been influenced by differences in obstetric and neonatal management of twin pregnancies that were observed between centers. Another concern is the authors’ use of unpublished aggregate and individual patient data.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Lactate measurement is widely used in emergency departments (EDs) and intensive care units (ICUs) to facilitate the early diagnosis and management of sepsis, severe trauma, ischemic bowel, and necrotizing fasciitis. Measuring lactate levels is much less commonly utilized in the practice of obstetrics and gynecology; increasing measurement in our practices may improve our early recognition and treatment of women with severe sepsis and other serious diseases.

Lactate physiology

The metabolism of glucose in the Embden-Meyerhof pathway results in the production of pyruvate and the high-energy compounds ATP and NADH. Pyruvate can enter 3 alternative metabolic pathways: 1) the mitochondrial Krebs cycle, 2) conversion to lactate in the cell cytosol, or 3) conversion back to glucose in the process of gluconeogenesis.

Under aerobic conditions, most pyruvate enters the Krebs cycle and little is converted to lactate. Molecular oxygen is an absolute requirement for Krebs cycle activity. Under anaerobic conditions, pyruvate cannot enter the Krebs cycle and is preferentially converted to lactate.¹

An elevated lactate level is a sensitive marker for tissue hypoxia caused by a variety of diseases, including sepsis, trauma, ischemic bowel, and necrotizing fasciitis. With sepsis, additional mechanisms also contribute to the increase in lactate, including increased glycolysis, impaired lactate clearance, and activation of inflammatory cells that shift cellular metabolism toward lactate production.^2,3

The normal range for venous plasma lactate in adults is 0.5 to 2.2 mM, although the normal range may vary because of differences in local laboratory methods. Arterial, capillary, and venous lactate are all highly positively correlated.⁴ Venous lactate concentrations between 2.3 and 3.9 mM are suggestive of mild physiologic dysfunction, and values ≥4.0 mM are consistent with severe physiologic dysfunction. In hospitalized patients, sepsis is one of the most common causes of a lactate level ≥4 mM.⁵

In many patients with an elevated lactate concentration the anion gap is also increased—but this is not always the case. In fact, in one large observational study, among patients with sepsis and a lactate concentration ≥4 mM, approximately 25% had a normal bicarbonate level and normal anion gap.⁶

Elevated lactate levels applied in obstetric and gynecologic practice

CASE 1. Obstetric practice: Hernia identified during labor

A 30-year-old woman (G1P0) presents in early labor at 37 weeks’ gestation. Two years prior to the pregnancy she had a Roux-en-Y gastric bypass and lost more than 100 lb. In addition to reporting lower abdominal pain occurring during contractions, she reports the new onset of mid-epigastric pain. A surgical consult is requested. The initial white blood cell count is 6,290 per uL, and the lactate level is 1.0 mM.

The surgeon consulted orders a computed tomography (CT) scan with oral contrast, but the patient has difficulty retaining the oral contrast due to her nausea, delaying the performance of the CT scan. Three hours following admission a follow-up lactate measurement is 3.3 mM, and an emergency CT scan is performed.

The CT scan shows an internal hernia with swirling of the mesenteric vessels and twisting of the small bowel mesentery. An urgent cesarean delivery and repair of the internal hernia is performed.

The patient and her newborn do well postoperatively. The postoperative lactate level is 0.8 mM.

In pregnant women with a past history of a Roux-en-Y gastric bypass and abdominal discomfort who are in labor it is challenging to rapidly diagnose internal hernias and other bowel problems.⁷⁻⁹ In this case, the increased lactate level from 1.0 mM to 3.3 mM raised concern for ischemic bowel and triggered the emergency CT and urgent exploratory laparotomy and cesarean delivery.

Up to 14% of maternal deaths in the United States are due to infection.¹⁰ In many of these cases, there is a delay in sepsis recognition because previously healthy pregnant women with sepsis may not manifest classic signs such as fever, hypotension, or mental status changes until late in the disease course. Measurement of lactate can facilitate the early recognition of severe sepsis in pregnant women, thereby accelerating and focusing their treatment.¹¹

To reduce mortality due to sepsis, aggressive intervention needs to occur within the first 6 hours following the onset of the infection.

CASE 2. Gynecologic practice: Bacterial infection identified in the presence of abdominal pain and vomiting

A 40-year-old woman presents to the ED 5 days following a myomectomy, with nausea, vomiting, and abdominal pain. Her vital signs reveal: temperature, 98.4°F (36.9°C); heart rate, 122 bpm; blood pressure, 115/70 mm Hg; and white blood cell count, 6,270 per uL. Her lactate level is 4.0 mM. She is admitted to the ICU with a presumptive diagnosis of severe sepsis and treatment with broad-spectrum antibiotics is initiated. Twenty-four hours following admission, gram-negative rods are identified in blood cultures that are later identified to be Bacteroides fragilis.

For the past 2 decades there has been a concerted national effort to reduce mortality caused by sepsis through early diagnosis and aggressive treatment of sepsis in an ICU setting. Observational studies have reported that an elevated lactate level is an excellent early biomarker for sepsis and may be observed prior to the onset of fever, elevated white blood cell count, or hypotension.⁶ For example, in one large study of patients with sepsis and a lactate measurement ≥4 mM, only 50% of patients had a systolic blood pressure <90 mm Hg.

Elevated lactate levels also are associated with an increased risk of death. Among 13,932 consecutive patients admitted to an ICU in Alberta, Canada, the mortality rate among patients with a venous or arterial lactate >2 mM was 20%, compared with a mortality rate of 5% for patients with a lactate level ≤2 mM.¹² In a study of 1,278 patients with infection admitted to the hospital from the ED, mortality increased as baseline lactate concentration rose. For lactate concentrations of 0 to 2.4, 2.5 to 3.9, and ≥4.0 mM, mortality rates were 5%, 9%, and 28%, respectively.¹³

In patients with sepsis, serial measurement of lactate can help to guide treatment. In a randomized trial, 348 patients admitted to an ICU with a lactate ≥3 mM were randomly assigned to standard treatment, in which the clinicians had no knowledge of patients’ lactate levels, or to an experimental group, in which the clinicians were provided lactate measurement results every 2 hours. Compared with clinicians in the control group, the clinicians with access to frequent lactate measurements administered more fluids and vasodilators to their patients. Compared with patients in the control group, the hospital mortality rate was lower when the clinicians had access to frequent lactate measurements (34% vs 44%, respectively; adjusted hazard ratio, 0.61; 95% confidence interval, 0.43−0.87; P = .0006).¹⁴

Elevated lactate levels in the fetus and newborn

The physiologic status of the newborn is routinely assessed with the Apgar score. Umbilical artery and venous blood gases, including measurement of pH, are often used as a corroborating biomarker. Most studies report that umbilical artery or vein lactate measurement is as useful as a pH measurement in assessing newborn physiologic status. The normal range of lactate in fetuses and newborns is not precisely defined, with values between 3.5 and 7 mM being cited as the upper limit of normal.¹⁵⁻¹⁸

In many countries (but not the United States), in utero fetal status during labor is assessed by fetal scalp sampling of blood and measurement of either pH or lactate. Fetal scalp sampling is difficult and often very little blood is obtained, making it difficult to measure pH. A Cochrane review reported that in 2 randomized trials, fetal scalp sampling produced a successful measurement of lactate in 99% of attempts, while a pH result could only be obtained in 79% of cases due to an inadequate volume of blood or clotted blood.¹⁹

Increased lactate measurement can help our patients

Measuring lactate in order to rapidly identify patients with major physiologic derangements is practiced widely in EDs and ICUs. There is significant opportunity to increase the use of lactate measurement in obstetrics and gynecology. Increasing this use will help to rapidly identify women with severe sepsis and other diseases, leading to more rapid intervention and improved outcomes.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Lactate measurement is widely used in emergency departments (EDs) and intensive care units (ICUs) to facilitate the early diagnosis and management of sepsis, severe trauma, ischemic bowel, and necrotizing fasciitis. Measuring lactate levels is much less commonly utilized in the practice of obstetrics and gynecology; increasing measurement in our practices may improve our early recognition and treatment of women with severe sepsis and other serious diseases.

Lactate physiology

The metabolism of glucose in the Embden-Meyerhof pathway results in the production of pyruvate and the high-energy compounds ATP and NADH. Pyruvate can enter 3 alternative metabolic pathways: 1) the mitochondrial Krebs cycle, 2) conversion to lactate in the cell cytosol, or 3) conversion back to glucose in the process of gluconeogenesis.

Under aerobic conditions, most pyruvate enters the Krebs cycle and little is converted to lactate. Molecular oxygen is an absolute requirement for Krebs cycle activity. Under anaerobic conditions, pyruvate cannot enter the Krebs cycle and is preferentially converted to lactate.¹

An elevated lactate level is a sensitive marker for tissue hypoxia caused by a variety of diseases, including sepsis, trauma, ischemic bowel, and necrotizing fasciitis. With sepsis, additional mechanisms also contribute to the increase in lactate, including increased glycolysis, impaired lactate clearance, and activation of inflammatory cells that shift cellular metabolism toward lactate production.^2,3

The normal range for venous plasma lactate in adults is 0.5 to 2.2 mM, although the normal range may vary because of differences in local laboratory methods. Arterial, capillary, and venous lactate are all highly positively correlated.⁴ Venous lactate concentrations between 2.3 and 3.9 mM are suggestive of mild physiologic dysfunction, and values ≥4.0 mM are consistent with severe physiologic dysfunction. In hospitalized patients, sepsis is one of the most common causes of a lactate level ≥4 mM.⁵

In many patients with an elevated lactate concentration the anion gap is also increased—but this is not always the case. In fact, in one large observational study, among patients with sepsis and a lactate concentration ≥4 mM, approximately 25% had a normal bicarbonate level and normal anion gap.⁶

Elevated lactate levels applied in obstetric and gynecologic practice

CASE 1. Obstetric practice: Hernia identified during labor

A 30-year-old woman (G1P0) presents in early labor at 37 weeks’ gestation. Two years prior to the pregnancy she had a Roux-en-Y gastric bypass and lost more than 100 lb. In addition to reporting lower abdominal pain occurring during contractions, she reports the new onset of mid-epigastric pain. A surgical consult is requested. The initial white blood cell count is 6,290 per uL, and the lactate level is 1.0 mM.

The surgeon consulted orders a computed tomography (CT) scan with oral contrast, but the patient has difficulty retaining the oral contrast due to her nausea, delaying the performance of the CT scan. Three hours following admission a follow-up lactate measurement is 3.3 mM, and an emergency CT scan is performed.

The CT scan shows an internal hernia with swirling of the mesenteric vessels and twisting of the small bowel mesentery. An urgent cesarean delivery and repair of the internal hernia is performed.

The patient and her newborn do well postoperatively. The postoperative lactate level is 0.8 mM.

In pregnant women with a past history of a Roux-en-Y gastric bypass and abdominal discomfort who are in labor it is challenging to rapidly diagnose internal hernias and other bowel problems.⁷⁻⁹ In this case, the increased lactate level from 1.0 mM to 3.3 mM raised concern for ischemic bowel and triggered the emergency CT and urgent exploratory laparotomy and cesarean delivery.

Up to 14% of maternal deaths in the United States are due to infection.¹⁰ In many of these cases, there is a delay in sepsis recognition because previously healthy pregnant women with sepsis may not manifest classic signs such as fever, hypotension, or mental status changes until late in the disease course. Measurement of lactate can facilitate the early recognition of severe sepsis in pregnant women, thereby accelerating and focusing their treatment.¹¹

To reduce mortality due to sepsis, aggressive intervention needs to occur within the first 6 hours following the onset of the infection.

CASE 2. Gynecologic practice: Bacterial infection identified in the presence of abdominal pain and vomiting

A 40-year-old woman presents to the ED 5 days following a myomectomy, with nausea, vomiting, and abdominal pain. Her vital signs reveal: temperature, 98.4°F (36.9°C); heart rate, 122 bpm; blood pressure, 115/70 mm Hg; and white blood cell count, 6,270 per uL. Her lactate level is 4.0 mM. She is admitted to the ICU with a presumptive diagnosis of severe sepsis and treatment with broad-spectrum antibiotics is initiated. Twenty-four hours following admission, gram-negative rods are identified in blood cultures that are later identified to be Bacteroides fragilis.

For the past 2 decades there has been a concerted national effort to reduce mortality caused by sepsis through early diagnosis and aggressive treatment of sepsis in an ICU setting. Observational studies have reported that an elevated lactate level is an excellent early biomarker for sepsis and may be observed prior to the onset of fever, elevated white blood cell count, or hypotension.⁶ For example, in one large study of patients with sepsis and a lactate measurement ≥4 mM, only 50% of patients had a systolic blood pressure <90 mm Hg.

Elevated lactate levels also are associated with an increased risk of death. Among 13,932 consecutive patients admitted to an ICU in Alberta, Canada, the mortality rate among patients with a venous or arterial lactate >2 mM was 20%, compared with a mortality rate of 5% for patients with a lactate level ≤2 mM.¹² In a study of 1,278 patients with infection admitted to the hospital from the ED, mortality increased as baseline lactate concentration rose. For lactate concentrations of 0 to 2.4, 2.5 to 3.9, and ≥4.0 mM, mortality rates were 5%, 9%, and 28%, respectively.¹³

In patients with sepsis, serial measurement of lactate can help to guide treatment. In a randomized trial, 348 patients admitted to an ICU with a lactate ≥3 mM were randomly assigned to standard treatment, in which the clinicians had no knowledge of patients’ lactate levels, or to an experimental group, in which the clinicians were provided lactate measurement results every 2 hours. Compared with clinicians in the control group, the clinicians with access to frequent lactate measurements administered more fluids and vasodilators to their patients. Compared with patients in the control group, the hospital mortality rate was lower when the clinicians had access to frequent lactate measurements (34% vs 44%, respectively; adjusted hazard ratio, 0.61; 95% confidence interval, 0.43−0.87; P = .0006).¹⁴

Elevated lactate levels in the fetus and newborn

The physiologic status of the newborn is routinely assessed with the Apgar score. Umbilical artery and venous blood gases, including measurement of pH, are often used as a corroborating biomarker. Most studies report that umbilical artery or vein lactate measurement is as useful as a pH measurement in assessing newborn physiologic status. The normal range of lactate in fetuses and newborns is not precisely defined, with values between 3.5 and 7 mM being cited as the upper limit of normal.¹⁵⁻¹⁸

In many countries (but not the United States), in utero fetal status during labor is assessed by fetal scalp sampling of blood and measurement of either pH or lactate. Fetal scalp sampling is difficult and often very little blood is obtained, making it difficult to measure pH. A Cochrane review reported that in 2 randomized trials, fetal scalp sampling produced a successful measurement of lactate in 99% of attempts, while a pH result could only be obtained in 79% of cases due to an inadequate volume of blood or clotted blood.¹⁹

Increased lactate measurement can help our patients

Measuring lactate in order to rapidly identify patients with major physiologic derangements is practiced widely in EDs and ICUs. There is significant opportunity to increase the use of lactate measurement in obstetrics and gynecology. Increasing this use will help to rapidly identify women with severe sepsis and other diseases, leading to more rapid intervention and improved outcomes.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Lactate measurement is widely used in emergency departments (EDs) and intensive care units (ICUs) to facilitate the early diagnosis and management of sepsis, severe trauma, ischemic bowel, and necrotizing fasciitis. Measuring lactate levels is much less commonly utilized in the practice of obstetrics and gynecology; increasing measurement in our practices may improve our early recognition and treatment of women with severe sepsis and other serious diseases.

Lactate physiology

The metabolism of glucose in the Embden-Meyerhof pathway results in the production of pyruvate and the high-energy compounds ATP and NADH. Pyruvate can enter 3 alternative metabolic pathways: 1) the mitochondrial Krebs cycle, 2) conversion to lactate in the cell cytosol, or 3) conversion back to glucose in the process of gluconeogenesis.

Under aerobic conditions, most pyruvate enters the Krebs cycle and little is converted to lactate. Molecular oxygen is an absolute requirement for Krebs cycle activity. Under anaerobic conditions, pyruvate cannot enter the Krebs cycle and is preferentially converted to lactate.¹

An elevated lactate level is a sensitive marker for tissue hypoxia caused by a variety of diseases, including sepsis, trauma, ischemic bowel, and necrotizing fasciitis. With sepsis, additional mechanisms also contribute to the increase in lactate, including increased glycolysis, impaired lactate clearance, and activation of inflammatory cells that shift cellular metabolism toward lactate production.^2,3

The normal range for venous plasma lactate in adults is 0.5 to 2.2 mM, although the normal range may vary because of differences in local laboratory methods. Arterial, capillary, and venous lactate are all highly positively correlated.⁴ Venous lactate concentrations between 2.3 and 3.9 mM are suggestive of mild physiologic dysfunction, and values ≥4.0 mM are consistent with severe physiologic dysfunction. In hospitalized patients, sepsis is one of the most common causes of a lactate level ≥4 mM.⁵

In many patients with an elevated lactate concentration the anion gap is also increased—but this is not always the case. In fact, in one large observational study, among patients with sepsis and a lactate concentration ≥4 mM, approximately 25% had a normal bicarbonate level and normal anion gap.⁶

Elevated lactate levels applied in obstetric and gynecologic practice

CASE 1. Obstetric practice: Hernia identified during labor

A 30-year-old woman (G1P0) presents in early labor at 37 weeks’ gestation. Two years prior to the pregnancy she had a Roux-en-Y gastric bypass and lost more than 100 lb. In addition to reporting lower abdominal pain occurring during contractions, she reports the new onset of mid-epigastric pain. A surgical consult is requested. The initial white blood cell count is 6,290 per uL, and the lactate level is 1.0 mM.

The surgeon consulted orders a computed tomography (CT) scan with oral contrast, but the patient has difficulty retaining the oral contrast due to her nausea, delaying the performance of the CT scan. Three hours following admission a follow-up lactate measurement is 3.3 mM, and an emergency CT scan is performed.

The CT scan shows an internal hernia with swirling of the mesenteric vessels and twisting of the small bowel mesentery. An urgent cesarean delivery and repair of the internal hernia is performed.

The patient and her newborn do well postoperatively. The postoperative lactate level is 0.8 mM.

In pregnant women with a past history of a Roux-en-Y gastric bypass and abdominal discomfort who are in labor it is challenging to rapidly diagnose internal hernias and other bowel problems.⁷⁻⁹ In this case, the increased lactate level from 1.0 mM to 3.3 mM raised concern for ischemic bowel and triggered the emergency CT and urgent exploratory laparotomy and cesarean delivery.

Up to 14% of maternal deaths in the United States are due to infection.¹⁰ In many of these cases, there is a delay in sepsis recognition because previously healthy pregnant women with sepsis may not manifest classic signs such as fever, hypotension, or mental status changes until late in the disease course. Measurement of lactate can facilitate the early recognition of severe sepsis in pregnant women, thereby accelerating and focusing their treatment.¹¹

To reduce mortality due to sepsis, aggressive intervention needs to occur within the first 6 hours following the onset of the infection.

CASE 2. Gynecologic practice: Bacterial infection identified in the presence of abdominal pain and vomiting

A 40-year-old woman presents to the ED 5 days following a myomectomy, with nausea, vomiting, and abdominal pain. Her vital signs reveal: temperature, 98.4°F (36.9°C); heart rate, 122 bpm; blood pressure, 115/70 mm Hg; and white blood cell count, 6,270 per uL. Her lactate level is 4.0 mM. She is admitted to the ICU with a presumptive diagnosis of severe sepsis and treatment with broad-spectrum antibiotics is initiated. Twenty-four hours following admission, gram-negative rods are identified in blood cultures that are later identified to be Bacteroides fragilis.

For the past 2 decades there has been a concerted national effort to reduce mortality caused by sepsis through early diagnosis and aggressive treatment of sepsis in an ICU setting. Observational studies have reported that an elevated lactate level is an excellent early biomarker for sepsis and may be observed prior to the onset of fever, elevated white blood cell count, or hypotension.⁶ For example, in one large study of patients with sepsis and a lactate measurement ≥4 mM, only 50% of patients had a systolic blood pressure <90 mm Hg.

Elevated lactate levels also are associated with an increased risk of death. Among 13,932 consecutive patients admitted to an ICU in Alberta, Canada, the mortality rate among patients with a venous or arterial lactate >2 mM was 20%, compared with a mortality rate of 5% for patients with a lactate level ≤2 mM.¹² In a study of 1,278 patients with infection admitted to the hospital from the ED, mortality increased as baseline lactate concentration rose. For lactate concentrations of 0 to 2.4, 2.5 to 3.9, and ≥4.0 mM, mortality rates were 5%, 9%, and 28%, respectively.¹³

In patients with sepsis, serial measurement of lactate can help to guide treatment. In a randomized trial, 348 patients admitted to an ICU with a lactate ≥3 mM were randomly assigned to standard treatment, in which the clinicians had no knowledge of patients’ lactate levels, or to an experimental group, in which the clinicians were provided lactate measurement results every 2 hours. Compared with clinicians in the control group, the clinicians with access to frequent lactate measurements administered more fluids and vasodilators to their patients. Compared with patients in the control group, the hospital mortality rate was lower when the clinicians had access to frequent lactate measurements (34% vs 44%, respectively; adjusted hazard ratio, 0.61; 95% confidence interval, 0.43−0.87; P = .0006).¹⁴

Elevated lactate levels in the fetus and newborn

The physiologic status of the newborn is routinely assessed with the Apgar score. Umbilical artery and venous blood gases, including measurement of pH, are often used as a corroborating biomarker. Most studies report that umbilical artery or vein lactate measurement is as useful as a pH measurement in assessing newborn physiologic status. The normal range of lactate in fetuses and newborns is not precisely defined, with values between 3.5 and 7 mM being cited as the upper limit of normal.¹⁵⁻¹⁸

In many countries (but not the United States), in utero fetal status during labor is assessed by fetal scalp sampling of blood and measurement of either pH or lactate. Fetal scalp sampling is difficult and often very little blood is obtained, making it difficult to measure pH. A Cochrane review reported that in 2 randomized trials, fetal scalp sampling produced a successful measurement of lactate in 99% of attempts, while a pH result could only be obtained in 79% of cases due to an inadequate volume of blood or clotted blood.¹⁹

Increased lactate measurement can help our patients

Measuring lactate in order to rapidly identify patients with major physiologic derangements is practiced widely in EDs and ICUs. There is significant opportunity to increase the use of lactate measurement in obstetrics and gynecology. Increasing this use will help to rapidly identify women with severe sepsis and other diseases, leading to more rapid intervention and improved outcomes.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“PROTECTING THE NEWBORN BRAIN—THE FINAL FRONTIER IN OBSTETRIC AND NEONATAL CARE”

ROBERT L. BARBIERI, MD (AUGUST 2016)

Therapeutic hypothermia

I practice in a small community hospital without a neonatal intensive care unit (NICU). We have always paid attention to warming neonates. Although we cannot start neonatal therapeutic hypothermia, as Dr. Barbieri discusses in his August Editorial, would there be any benefit to avoiding purposefully warming infants who are depressed at birth? NICU care requires a pediatric transport team, which takes at least an hour to arrive.

Jane Dawson, MD
Maryville, Missouri

Dr. Barbieri responds

I thank Dr. Dawson for her observations and query. I agree that at a hospital without a NICU, pending the arrival of a pediatric transport team, clinicians should strive to prevent hyperthermia in a newborn with encephalopathy because hyperthermia might exacerbate the ischemic injury. It may make sense to avoid aggressive warming of the newborn to permit the core temperature to decrease in order to begin the hypothermia process.

“PROTECTING THE NEWBORN BRAIN—THE FINAL FRONTIER IN OBSTETRIC AND NEONATAL CARE”

ROBERT L. BARBIERI, MD (AUGUST 2016)

Therapeutic hypothermia

I practice in a small community hospital without a neonatal intensive care unit (NICU). We have always paid attention to warming neonates. Although we cannot start neonatal therapeutic hypothermia, as Dr. Barbieri discusses in his August Editorial, would there be any benefit to avoiding purposefully warming infants who are depressed at birth? NICU care requires a pediatric transport team, which takes at least an hour to arrive.

Jane Dawson, MD
Maryville, Missouri

Dr. Barbieri responds

I thank Dr. Dawson for her observations and query. I agree that at a hospital without a NICU, pending the arrival of a pediatric transport team, clinicians should strive to prevent hyperthermia in a newborn with encephalopathy because hyperthermia might exacerbate the ischemic injury. It may make sense to avoid aggressive warming of the newborn to permit the core temperature to decrease in order to begin the hypothermia process.

“PROTECTING THE NEWBORN BRAIN—THE FINAL FRONTIER IN OBSTETRIC AND NEONATAL CARE”

ROBERT L. BARBIERI, MD (AUGUST 2016)

Therapeutic hypothermia

I practice in a small community hospital without a neonatal intensive care unit (NICU). We have always paid attention to warming neonates. Although we cannot start neonatal therapeutic hypothermia, as Dr. Barbieri discusses in his August Editorial, would there be any benefit to avoiding purposefully warming infants who are depressed at birth? NICU care requires a pediatric transport team, which takes at least an hour to arrive.

Jane Dawson, MD
Maryville, Missouri

Dr. Barbieri responds

I thank Dr. Dawson for her observations and query. I agree that at a hospital without a NICU, pending the arrival of a pediatric transport team, clinicians should strive to prevent hyperthermia in a newborn with encephalopathy because hyperthermia might exacerbate the ischemic injury. It may make sense to avoid aggressive warming of the newborn to permit the core temperature to decrease in order to begin the hypothermia process.

“STOP USING INSTRUMENTS TO ASSIST WITH DELIVERY OF THE HEAD AT CESAREAN; START DISENGAGING THE HEAD PRIOR TO SURGERY”

ERROL R. NORWITZ, MD, PHD, MBA (AUGUST 2016)

Patient positioning helps in managing impacted fetal head

As a general practice ObGyn, I have seen an increasing incidence of difficult cesareans as a result of prolonged second stage of labor. Dr. Norwitz cites this increase in his article. I have found that trying to elevate the fetal head prior to the start of surgery has been remarkably ineffective. In my practice, I place all my patients with second-stage arrest in low lithotomy stirrups (“blue fins”); this allows the nurses easier access to the vagina to elevate the head at surgery while I am reaching down from above. Usually, this facilitates delivery. It also allows better assessment of blood loss through the vagina as the cesarean progresses, and it makes placement of a Bakri balloon easier if necessary. If stirrups are not available, the patient can be placed in frog leg positioning so that my assistant can reach down and elevate the head if necessary. I find that in a patient with a very small pelvis, it is hard to get my hand down to the baby’s head. I have not yet done a breech extraction, but I know it is possible. I would probably try nitroglycerin first.

I think that difficult cesarean delivery is much more common than difficult shoulder dystocia, and we should develop standard procedures for addressing the issue and use simulation models to practice. In my time-out prior to surgery, I discuss my concerns so that everyone is ready for it, including the anesthesiologist/CRNA, and we have nitroglycerin available to relax the uterus if necessary. I hope that the American College of Obstetricians and Gynecologists (ACOG) will develop a committee opinion about this very important issue.

Marguerite P. Cohen, MD
Portland, Oregon

Assistant is key in disengaging fetal head

Disengaging the head by an assistant during a cesarean delivery is probably the most successful and useful method for managing an impacted fetal head at cesarean. The disengagement of the head prior to cesarean is practiced routinely in Europe, where forceps delivery is frequently performed. However, the disengagement should be done in the operating room (OR) just prior to or during the cesarean. To perform this in the delivery room, as suggested in Dr. Norwitz’s article, risks the associated fetal bradycardia due to head compression that might compromise an already compromised fetus. In addition, there is a risk of cord prolapse or release of excessive amniotic fluid resulting in cord compression. Also, in many hospitals in the United States, there is some delay to perform the cesarean because the OR is on a different floor from the labor and delivery room and the OR staff come from home.

Vacuum extraction can be safely used for the extraction of the head if it is not possible to deliver it manually. However, the head should be manually disimpacted and rotated to occiput anterior prior to application of the vacuum. But the presence of caput might pose some difficulty with proper application and traction.

It is important to remember that the risk factors for an impacted fetal head are also risk factors for postoperative infection. Therefore, vaginal preparation with antiseptic solution should be considered prior to cesarean delivery for all patients in labor.¹

Raymond Michael, MD
Marshall, Minnesota

Reference

1. Haas DM, Morgan Al Darei S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Syst Rev. 2010;3:CD007892.

“STOP USING INSTRUMENTS TO ASSIST WITH DELIVERY OF THE HEAD AT CESAREAN; START DISENGAGING THE HEAD PRIOR TO SURGERY”

ERROL R. NORWITZ, MD, PHD, MBA (AUGUST 2016)

Patient positioning helps in managing impacted fetal head

As a general practice ObGyn, I have seen an increasing incidence of difficult cesareans as a result of prolonged second stage of labor. Dr. Norwitz cites this increase in his article. I have found that trying to elevate the fetal head prior to the start of surgery has been remarkably ineffective. In my practice, I place all my patients with second-stage arrest in low lithotomy stirrups (“blue fins”); this allows the nurses easier access to the vagina to elevate the head at surgery while I am reaching down from above. Usually, this facilitates delivery. It also allows better assessment of blood loss through the vagina as the cesarean progresses, and it makes placement of a Bakri balloon easier if necessary. If stirrups are not available, the patient can be placed in frog leg positioning so that my assistant can reach down and elevate the head if necessary. I find that in a patient with a very small pelvis, it is hard to get my hand down to the baby’s head. I have not yet done a breech extraction, but I know it is possible. I would probably try nitroglycerin first.

I think that difficult cesarean delivery is much more common than difficult shoulder dystocia, and we should develop standard procedures for addressing the issue and use simulation models to practice. In my time-out prior to surgery, I discuss my concerns so that everyone is ready for it, including the anesthesiologist/CRNA, and we have nitroglycerin available to relax the uterus if necessary. I hope that the American College of Obstetricians and Gynecologists (ACOG) will develop a committee opinion about this very important issue.

Marguerite P. Cohen, MD
Portland, Oregon

Assistant is key in disengaging fetal head

Disengaging the head by an assistant during a cesarean delivery is probably the most successful and useful method for managing an impacted fetal head at cesarean. The disengagement of the head prior to cesarean is practiced routinely in Europe, where forceps delivery is frequently performed. However, the disengagement should be done in the operating room (OR) just prior to or during the cesarean. To perform this in the delivery room, as suggested in Dr. Norwitz’s article, risks the associated fetal bradycardia due to head compression that might compromise an already compromised fetus. In addition, there is a risk of cord prolapse or release of excessive amniotic fluid resulting in cord compression. Also, in many hospitals in the United States, there is some delay to perform the cesarean because the OR is on a different floor from the labor and delivery room and the OR staff come from home.

Vacuum extraction can be safely used for the extraction of the head if it is not possible to deliver it manually. However, the head should be manually disimpacted and rotated to occiput anterior prior to application of the vacuum. But the presence of caput might pose some difficulty with proper application and traction.

It is important to remember that the risk factors for an impacted fetal head are also risk factors for postoperative infection. Therefore, vaginal preparation with antiseptic solution should be considered prior to cesarean delivery for all patients in labor.¹

Raymond Michael, MD
Marshall, Minnesota

Reference

1. Haas DM, Morgan Al Darei S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Syst Rev. 2010;3:CD007892.

“STOP USING INSTRUMENTS TO ASSIST WITH DELIVERY OF THE HEAD AT CESAREAN; START DISENGAGING THE HEAD PRIOR TO SURGERY”

ERROL R. NORWITZ, MD, PHD, MBA (AUGUST 2016)

Patient positioning helps in managing impacted fetal head

As a general practice ObGyn, I have seen an increasing incidence of difficult cesareans as a result of prolonged second stage of labor. Dr. Norwitz cites this increase in his article. I have found that trying to elevate the fetal head prior to the start of surgery has been remarkably ineffective. In my practice, I place all my patients with second-stage arrest in low lithotomy stirrups (“blue fins”); this allows the nurses easier access to the vagina to elevate the head at surgery while I am reaching down from above. Usually, this facilitates delivery. It also allows better assessment of blood loss through the vagina as the cesarean progresses, and it makes placement of a Bakri balloon easier if necessary. If stirrups are not available, the patient can be placed in frog leg positioning so that my assistant can reach down and elevate the head if necessary. I find that in a patient with a very small pelvis, it is hard to get my hand down to the baby’s head. I have not yet done a breech extraction, but I know it is possible. I would probably try nitroglycerin first.

I think that difficult cesarean delivery is much more common than difficult shoulder dystocia, and we should develop standard procedures for addressing the issue and use simulation models to practice. In my time-out prior to surgery, I discuss my concerns so that everyone is ready for it, including the anesthesiologist/CRNA, and we have nitroglycerin available to relax the uterus if necessary. I hope that the American College of Obstetricians and Gynecologists (ACOG) will develop a committee opinion about this very important issue.

Marguerite P. Cohen, MD
Portland, Oregon

Assistant is key in disengaging fetal head

Disengaging the head by an assistant during a cesarean delivery is probably the most successful and useful method for managing an impacted fetal head at cesarean. The disengagement of the head prior to cesarean is practiced routinely in Europe, where forceps delivery is frequently performed. However, the disengagement should be done in the operating room (OR) just prior to or during the cesarean. To perform this in the delivery room, as suggested in Dr. Norwitz’s article, risks the associated fetal bradycardia due to head compression that might compromise an already compromised fetus. In addition, there is a risk of cord prolapse or release of excessive amniotic fluid resulting in cord compression. Also, in many hospitals in the United States, there is some delay to perform the cesarean because the OR is on a different floor from the labor and delivery room and the OR staff come from home.

Vacuum extraction can be safely used for the extraction of the head if it is not possible to deliver it manually. However, the head should be manually disimpacted and rotated to occiput anterior prior to application of the vacuum. But the presence of caput might pose some difficulty with proper application and traction.

It is important to remember that the risk factors for an impacted fetal head are also risk factors for postoperative infection. Therefore, vaginal preparation with antiseptic solution should be considered prior to cesarean delivery for all patients in labor.¹

Raymond Michael, MD
Marshall, Minnesota

Reference

1. Haas DM, Morgan Al Darei S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Syst Rev. 2010;3:CD007892.

Diagnostic testing needed to confirm cfDNA results for aneuploidy and microdeletions, finds retrospective study

Researchers at the David Geffen School of Medicine at the University of California-Los Angeles, found a 73.5% positive predictive value (95% CI, 63%-82%) for cfDNA screening for autosomal aneuploidy, a lower-than-reported rate. The positive predictive value for microdeletion testing was found to be 0%.

This was a retrospective cohort study published in June in the American Journal of Obstetrics and Gynecology. It included 105 patients with abnormal or nonreportable cfDNA results for trisomies 21, 18, or 13, and 26 patients with positive or nonreportable microdeletions. Of the 105 patients with abnormal results for the trisomies, 92 results (87.6%) were positive for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%) and positive for >1 parameter (3, 3.3%). An additional 13 results (12.4%) were nonreportable.

Abnormal cfDNA results were associated with positive serum screening (by group: trisomy 21 [17/48]; trisomy 18 [7/22]; trisomy 13 [3/17]; nonreportable [2/13]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45]; trisomy 18 [13/20]; trisomy 13 [6/14]; nonreportable [1/13]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories included in the study (P = .018).

In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives.

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When is NIPT appropriate for use as a diagnostic tool? Large-scale systematic review evaluates the answer.

Many systematic reviews and meta-analyses evaluating the accuracy of cell-free fetal (cf) DNA−based testing have been published. This May 2016 study in the British Journal of Obstetrics and Gynecology was the most comprehensive of singleton pregnancies to date, say researchers, who aimed to reduce analysis bias by including only cohort studies (117 analyzed), undertaking bivariate meta-analysis when possible, and including all indications for antenatal use, which allowed for a uniform comparison of NIPT use in actual clinical practice.

The researchers concluded that cell-free fetal (cf) DNA−based NIPT is diagnostic for fetal sex and rhesus D (RHD) status. For trisomies 21, 18, and 13, however, they concluded that the lower sensitivities and specificities found and disease prevalence, combined with the biological influence of confined placental mosaicism, designates NIPT as a screening test (with invasive testing required to confirm a positive test result). They advised that these factors be considered not only when clinicians are counseling patients but also in the overall assessment of the cost of introducing NIPT into routine care.

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2016 update on NIPT from the American College of Medical Genetics and Genomics

The American College of Medical Genetics and Genomics (ACMG) has published an updated position statement in Genetics in Medicine in July 2016 that replaces its 2013 statement. Among its recommendations, the ACMG advocates:

• providing up-to-date, balanced, and accurate information early in gestation to optimize patient decision making, independent of the screening approach used
• that laboratories work with public health officials, policymakers, and private payers to make NIPT, including the pretest and posttest education and counseling, accessible to all pregnant women
• informing all pregnant women that diagnostic testing (chorionic villus sampling or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant copy-number variants.

ACMG also recommends:

• informing all pregnant women that noninvasive prenatal screening (NIPS) is the most sensitive screening option for traditionally screened aneuploidies
• referring patients to a trained genetics professional when an increased risk of aneuploidy is reported after NIPS
• offering diagnostic testing when a positive screening test result is reported after NIPS
• laboratories provide readily visible and clearly stated detection rate (DR), clinical specificity (SPEC), and positive predictive values (PPV), and negative predictive values (NPVs) for conditions being screened
• laboratories not offer screening for Patau, Edwards, and Down syndromes if they cannot report DR, SPEC, and PPV values for these conditions.

ACMG does not recommend:

• NIPS to screen for autosomal aneuploidies other than those involving chromosomes 13, 18, and 21.

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Public health perspective: Long-term study concludes implementing cfDNA in high-risk women could be cost-effective

Researchers in Italy retrospectively analyzed the performance of first-trimester screening (FTS) test in a general obstetrics population, including a cost-benefit analysis of a hypothetical model that implemented universal FTS testing using cfDNA. A 2-step strategy based on nuchal translucency, serum screening, and ultrasound assessment of the nasal bone was applied when analyzing the FTS results of 6,679 women. The researchers identified 3 groups: high-risk: >1:250; intermediate-risk: 1:251-1:999; and low-risk group: <1:1000. Women at intermediate-risk underwent NB assessment and recalculation of individual risk. All women at high-risk were offered fetal karyotyping.

The investigators concluded that the Italian public health system would not be able to sustain the cost of universal cfDNA testing in women undergoing FTS. However, a possible scenario based on use of cfDNA FTS in women at high-risk would result in a 6-fold reduction in the number of invasive procedures. It would also avoid 2 false-negative results (trisomy 21) diagnosed in women with intermediate-risk using the current screening strategy of combined invasive and noninvasive testing.

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Diagnostic testing needed to confirm cfDNA results for aneuploidy and microdeletions, finds retrospective study

Researchers at the David Geffen School of Medicine at the University of California-Los Angeles, found a 73.5% positive predictive value (95% CI, 63%-82%) for cfDNA screening for autosomal aneuploidy, a lower-than-reported rate. The positive predictive value for microdeletion testing was found to be 0%.

This was a retrospective cohort study published in June in the American Journal of Obstetrics and Gynecology. It included 105 patients with abnormal or nonreportable cfDNA results for trisomies 21, 18, or 13, and 26 patients with positive or nonreportable microdeletions. Of the 105 patients with abnormal results for the trisomies, 92 results (87.6%) were positive for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%) and positive for >1 parameter (3, 3.3%). An additional 13 results (12.4%) were nonreportable.

Abnormal cfDNA results were associated with positive serum screening (by group: trisomy 21 [17/48]; trisomy 18 [7/22]; trisomy 13 [3/17]; nonreportable [2/13]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45]; trisomy 18 [13/20]; trisomy 13 [6/14]; nonreportable [1/13]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories included in the study (P = .018).

In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives.

Access study in AJOG

When is NIPT appropriate for use as a diagnostic tool? Large-scale systematic review evaluates the answer.

Many systematic reviews and meta-analyses evaluating the accuracy of cell-free fetal (cf) DNA−based testing have been published. This May 2016 study in the British Journal of Obstetrics and Gynecology was the most comprehensive of singleton pregnancies to date, say researchers, who aimed to reduce analysis bias by including only cohort studies (117 analyzed), undertaking bivariate meta-analysis when possible, and including all indications for antenatal use, which allowed for a uniform comparison of NIPT use in actual clinical practice.

The researchers concluded that cell-free fetal (cf) DNA−based NIPT is diagnostic for fetal sex and rhesus D (RHD) status. For trisomies 21, 18, and 13, however, they concluded that the lower sensitivities and specificities found and disease prevalence, combined with the biological influence of confined placental mosaicism, designates NIPT as a screening test (with invasive testing required to confirm a positive test result). They advised that these factors be considered not only when clinicians are counseling patients but also in the overall assessment of the cost of introducing NIPT into routine care.

Visit BJOG study

2016 update on NIPT from the American College of Medical Genetics and Genomics

The American College of Medical Genetics and Genomics (ACMG) has published an updated position statement in Genetics in Medicine in July 2016 that replaces its 2013 statement. Among its recommendations, the ACMG advocates:

• providing up-to-date, balanced, and accurate information early in gestation to optimize patient decision making, independent of the screening approach used
• that laboratories work with public health officials, policymakers, and private payers to make NIPT, including the pretest and posttest education and counseling, accessible to all pregnant women
• informing all pregnant women that diagnostic testing (chorionic villus sampling or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant copy-number variants.

ACMG also recommends:

• informing all pregnant women that noninvasive prenatal screening (NIPS) is the most sensitive screening option for traditionally screened aneuploidies
• referring patients to a trained genetics professional when an increased risk of aneuploidy is reported after NIPS
• offering diagnostic testing when a positive screening test result is reported after NIPS
• laboratories provide readily visible and clearly stated detection rate (DR), clinical specificity (SPEC), and positive predictive values (PPV), and negative predictive values (NPVs) for conditions being screened
• laboratories not offer screening for Patau, Edwards, and Down syndromes if they cannot report DR, SPEC, and PPV values for these conditions.

ACMG does not recommend:

• NIPS to screen for autosomal aneuploidies other than those involving chromosomes 13, 18, and 21.

Visit full recommendations

Public health perspective: Long-term study concludes implementing cfDNA in high-risk women could be cost-effective

Researchers in Italy retrospectively analyzed the performance of first-trimester screening (FTS) test in a general obstetrics population, including a cost-benefit analysis of a hypothetical model that implemented universal FTS testing using cfDNA. A 2-step strategy based on nuchal translucency, serum screening, and ultrasound assessment of the nasal bone was applied when analyzing the FTS results of 6,679 women. The researchers identified 3 groups: high-risk: >1:250; intermediate-risk: 1:251-1:999; and low-risk group: <1:1000. Women at intermediate-risk underwent NB assessment and recalculation of individual risk. All women at high-risk were offered fetal karyotyping.

The investigators concluded that the Italian public health system would not be able to sustain the cost of universal cfDNA testing in women undergoing FTS. However, a possible scenario based on use of cfDNA FTS in women at high-risk would result in a 6-fold reduction in the number of invasive procedures. It would also avoid 2 false-negative results (trisomy 21) diagnosed in women with intermediate-risk using the current screening strategy of combined invasive and noninvasive testing.

Access JECP study

Diagnostic testing needed to confirm cfDNA results for aneuploidy and microdeletions, finds retrospective study

Researchers at the David Geffen School of Medicine at the University of California-Los Angeles, found a 73.5% positive predictive value (95% CI, 63%-82%) for cfDNA screening for autosomal aneuploidy, a lower-than-reported rate. The positive predictive value for microdeletion testing was found to be 0%.

This was a retrospective cohort study published in June in the American Journal of Obstetrics and Gynecology. It included 105 patients with abnormal or nonreportable cfDNA results for trisomies 21, 18, or 13, and 26 patients with positive or nonreportable microdeletions. Of the 105 patients with abnormal results for the trisomies, 92 results (87.6%) were positive for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%) and positive for >1 parameter (3, 3.3%). An additional 13 results (12.4%) were nonreportable.

Abnormal cfDNA results were associated with positive serum screening (by group: trisomy 21 [17/48]; trisomy 18 [7/22]; trisomy 13 [3/17]; nonreportable [2/13]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45]; trisomy 18 [13/20]; trisomy 13 [6/14]; nonreportable [1/13]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories included in the study (P = .018).

In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives.

Access study in AJOG

When is NIPT appropriate for use as a diagnostic tool? Large-scale systematic review evaluates the answer.

Many systematic reviews and meta-analyses evaluating the accuracy of cell-free fetal (cf) DNA−based testing have been published. This May 2016 study in the British Journal of Obstetrics and Gynecology was the most comprehensive of singleton pregnancies to date, say researchers, who aimed to reduce analysis bias by including only cohort studies (117 analyzed), undertaking bivariate meta-analysis when possible, and including all indications for antenatal use, which allowed for a uniform comparison of NIPT use in actual clinical practice.

The researchers concluded that cell-free fetal (cf) DNA−based NIPT is diagnostic for fetal sex and rhesus D (RHD) status. For trisomies 21, 18, and 13, however, they concluded that the lower sensitivities and specificities found and disease prevalence, combined with the biological influence of confined placental mosaicism, designates NIPT as a screening test (with invasive testing required to confirm a positive test result). They advised that these factors be considered not only when clinicians are counseling patients but also in the overall assessment of the cost of introducing NIPT into routine care.

Visit BJOG study

2016 update on NIPT from the American College of Medical Genetics and Genomics

The American College of Medical Genetics and Genomics (ACMG) has published an updated position statement in Genetics in Medicine in July 2016 that replaces its 2013 statement. Among its recommendations, the ACMG advocates:

• providing up-to-date, balanced, and accurate information early in gestation to optimize patient decision making, independent of the screening approach used
• that laboratories work with public health officials, policymakers, and private payers to make NIPT, including the pretest and posttest education and counseling, accessible to all pregnant women
• informing all pregnant women that diagnostic testing (chorionic villus sampling or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant copy-number variants.

ACMG also recommends:

• informing all pregnant women that noninvasive prenatal screening (NIPS) is the most sensitive screening option for traditionally screened aneuploidies
• referring patients to a trained genetics professional when an increased risk of aneuploidy is reported after NIPS
• offering diagnostic testing when a positive screening test result is reported after NIPS
• laboratories provide readily visible and clearly stated detection rate (DR), clinical specificity (SPEC), and positive predictive values (PPV), and negative predictive values (NPVs) for conditions being screened
• laboratories not offer screening for Patau, Edwards, and Down syndromes if they cannot report DR, SPEC, and PPV values for these conditions.

ACMG does not recommend:

• NIPS to screen for autosomal aneuploidies other than those involving chromosomes 13, 18, and 21.

Visit full recommendations

Public health perspective: Long-term study concludes implementing cfDNA in high-risk women could be cost-effective

Researchers in Italy retrospectively analyzed the performance of first-trimester screening (FTS) test in a general obstetrics population, including a cost-benefit analysis of a hypothetical model that implemented universal FTS testing using cfDNA. A 2-step strategy based on nuchal translucency, serum screening, and ultrasound assessment of the nasal bone was applied when analyzing the FTS results of 6,679 women. The researchers identified 3 groups: high-risk: >1:250; intermediate-risk: 1:251-1:999; and low-risk group: <1:1000. Women at intermediate-risk underwent NB assessment and recalculation of individual risk. All women at high-risk were offered fetal karyotyping.

The investigators concluded that the Italian public health system would not be able to sustain the cost of universal cfDNA testing in women undergoing FTS. However, a possible scenario based on use of cfDNA FTS in women at high-risk would result in a 6-fold reduction in the number of invasive procedures. It would also avoid 2 false-negative results (trisomy 21) diagnosed in women with intermediate-risk using the current screening strategy of combined invasive and noninvasive testing.

Access JECP study

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

Most pregnant women with a history of immune thrombocytopenia purpura need no treatment. Of those who do, neonatal outcomes were comparable for mothers who received treatment with intravenous immunoglobulin and for those who received corticosteroids, results of an observational study indicate.

Though limited by its retrospective design and low event rates that limit inferences about treatment effects, this observational study – the first to compare the effectiveness of treatment with IVIg to treatment with corticosteroids for immune thrombocytopenia purpura (ITP) in pregnancy – shows that outcomes did not significantly differ with the two regimens. The findings also highlight the need for ongoing neonatal platelet count monitoring throughout the first week of life, regardless of the maternal platelet count, the investigators said.

©iStock

A review of medical records at two tertiary care centers identified 235 pregnancies in 195 women with a history of ITP. No treatment was required in 137 pregnancies. Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated initially with intravenous immunoglobulin (IVIg) and 51 were treated initially with corticosteroids, reported Dongmei Sun, MD, of University of Western Ontario, London, and colleagues (Blood. 2016;128[10]:1329-35).

The two treatment groups had similar mean maternal platelet counts at birth (68.7 x 10⁹/L and 77.3 x 10⁹/L for IVIg and corticosteroids, respectively). The proportion of mothers who achieved a platelet count response did not significantly differ (38% vs. 39%), the researchers reported.

“The sole difference between treatments was a higher maternal composite outcome noted in the IVIg group,” they wrote, referring to a secondary composite outcome of postpartum hemorrhage, predelivery platelet transfusion, peripartum transfusion of any blood product, or postpartum reduction in the hemoglobin concentration of 30 g/L or more. That composite outcome occurred in 46.8% of pregnancies in the IVIg group and 23.5% in the corticosteroid group.

Adverse events were reported in 13% of cases in each group, and included hemolytic anemia, headache, and “other” in those treated with IVIg, and hyperglycemia requiring treatment, hyperglycemia with neonatal hypoglycemia, infection, and “other” in those receiving corticosteroids.

No severe or fatal maternal, fetal, or neonatal hemorrhages occurred, but two newborns did experience intracranial hemorrhage. No maternal or neonatal deaths occurred, the investigators said.

In 203 neonates for whom platelet counts were available, 56 (28%) had a count of less than 150 x 10⁹/L and 18 (9%) had a count of less than 50 x 10⁹/L.

Nadir platelet counts occurred at birth for 30% of neonates. In two cases, the nadir occurred as late as day 6 postnatally. Of note, a drop in platelets to below 150 x 10⁹/L was found in 9 (11%) of 129 neonates who had a normal cord platelet count and had a repeat count.

ITP occurs in 1 to 10 of every 10,000 pregnancies, and about one-third of cases require intervention. IVIg and corticosteroids are acceptable treatments, but most data on their effectiveness are extrapolated from nonpregnant patients and the treatments have not been adequately assessed in pregnancy, the investigators said. The current study was designed to compare the efficacy of the two treatments for maternal ITP.

Study subjects were women with singleton pregnancies with an ITP diagnosis either before or during pregnancy.

At less than 40% in both groups, the response to ITP therapies was lower than has been reported for nonpregnant patients, the investigators noted.

“Our observation of a relative resistance to ITP treatment during pregnancy requires further validation in prospective studies. We speculate that increased potency of antiplatelet antibodies during pregnancy, pregnancy-associated changes in platelet turnover, or altered drug metabolism may contribute to the lower response rates we observed,” they wrote.

With respect to corticosteroids, this “may warrant consideration of starting therapy earlier in the third trimester to maximize the likelihood of reaching target platelet counts in time for delivery and raises the possibility that lower corticosteroid doses are ineffective in this setting,” they added.

“Also of significance is the finding that 9 neonates (11%) with normal cord platelet counts were found to have a reduction in their platelet count on repeat measurement. These findings highlight the need for determination of cord platelet counts in all neonates born to mothers with active or previous ITP and the need for continued monitoring of the neonatal platelet count during the first week of life, despite normal cord platelet counts,” they wrote.

“Prospective studies are needed to better characterize the safety of these regimens, to determine the optimal dose of corticosteroids, to identify risk factors for neonatal thrombocytopenia, and to explore new therapeutic options,” they concluded.

Among the options worth exploring are rituximab, a monoclonal antibody against B-cell surface antigen CD20, for which “pregnancy data are accumulating,” and romiplostim, a thrombopoietin receptor agonist, which has been used in a few cases without reported fetal complications, they noted.

This study was supported by Canadian Blood Services Small Projects Fund and Canadian Institute of Health Research/Canadian Blood Services New Investigator Award. Individual authors reported receiving support from the Canadian Institutes of Health Research and McMaster University. The authors reported having no other disclosures.

[email protected]

Most pregnant women with a history of immune thrombocytopenia purpura need no treatment. Of those who do, neonatal outcomes were comparable for mothers who received treatment with intravenous immunoglobulin and for those who received corticosteroids, results of an observational study indicate.

Though limited by its retrospective design and low event rates that limit inferences about treatment effects, this observational study – the first to compare the effectiveness of treatment with IVIg to treatment with corticosteroids for immune thrombocytopenia purpura (ITP) in pregnancy – shows that outcomes did not significantly differ with the two regimens. The findings also highlight the need for ongoing neonatal platelet count monitoring throughout the first week of life, regardless of the maternal platelet count, the investigators said.

©iStock

A review of medical records at two tertiary care centers identified 235 pregnancies in 195 women with a history of ITP. No treatment was required in 137 pregnancies. Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated initially with intravenous immunoglobulin (IVIg) and 51 were treated initially with corticosteroids, reported Dongmei Sun, MD, of University of Western Ontario, London, and colleagues (Blood. 2016;128[10]:1329-35).

The two treatment groups had similar mean maternal platelet counts at birth (68.7 x 10⁹/L and 77.3 x 10⁹/L for IVIg and corticosteroids, respectively). The proportion of mothers who achieved a platelet count response did not significantly differ (38% vs. 39%), the researchers reported.

“The sole difference between treatments was a higher maternal composite outcome noted in the IVIg group,” they wrote, referring to a secondary composite outcome of postpartum hemorrhage, predelivery platelet transfusion, peripartum transfusion of any blood product, or postpartum reduction in the hemoglobin concentration of 30 g/L or more. That composite outcome occurred in 46.8% of pregnancies in the IVIg group and 23.5% in the corticosteroid group.

Adverse events were reported in 13% of cases in each group, and included hemolytic anemia, headache, and “other” in those treated with IVIg, and hyperglycemia requiring treatment, hyperglycemia with neonatal hypoglycemia, infection, and “other” in those receiving corticosteroids.

No severe or fatal maternal, fetal, or neonatal hemorrhages occurred, but two newborns did experience intracranial hemorrhage. No maternal or neonatal deaths occurred, the investigators said.

In 203 neonates for whom platelet counts were available, 56 (28%) had a count of less than 150 x 10⁹/L and 18 (9%) had a count of less than 50 x 10⁹/L.

Nadir platelet counts occurred at birth for 30% of neonates. In two cases, the nadir occurred as late as day 6 postnatally. Of note, a drop in platelets to below 150 x 10⁹/L was found in 9 (11%) of 129 neonates who had a normal cord platelet count and had a repeat count.

ITP occurs in 1 to 10 of every 10,000 pregnancies, and about one-third of cases require intervention. IVIg and corticosteroids are acceptable treatments, but most data on their effectiveness are extrapolated from nonpregnant patients and the treatments have not been adequately assessed in pregnancy, the investigators said. The current study was designed to compare the efficacy of the two treatments for maternal ITP.

Study subjects were women with singleton pregnancies with an ITP diagnosis either before or during pregnancy.

At less than 40% in both groups, the response to ITP therapies was lower than has been reported for nonpregnant patients, the investigators noted.

“Our observation of a relative resistance to ITP treatment during pregnancy requires further validation in prospective studies. We speculate that increased potency of antiplatelet antibodies during pregnancy, pregnancy-associated changes in platelet turnover, or altered drug metabolism may contribute to the lower response rates we observed,” they wrote.

With respect to corticosteroids, this “may warrant consideration of starting therapy earlier in the third trimester to maximize the likelihood of reaching target platelet counts in time for delivery and raises the possibility that lower corticosteroid doses are ineffective in this setting,” they added.

“Also of significance is the finding that 9 neonates (11%) with normal cord platelet counts were found to have a reduction in their platelet count on repeat measurement. These findings highlight the need for determination of cord platelet counts in all neonates born to mothers with active or previous ITP and the need for continued monitoring of the neonatal platelet count during the first week of life, despite normal cord platelet counts,” they wrote.

“Prospective studies are needed to better characterize the safety of these regimens, to determine the optimal dose of corticosteroids, to identify risk factors for neonatal thrombocytopenia, and to explore new therapeutic options,” they concluded.

Among the options worth exploring are rituximab, a monoclonal antibody against B-cell surface antigen CD20, for which “pregnancy data are accumulating,” and romiplostim, a thrombopoietin receptor agonist, which has been used in a few cases without reported fetal complications, they noted.

This study was supported by Canadian Blood Services Small Projects Fund and Canadian Institute of Health Research/Canadian Blood Services New Investigator Award. Individual authors reported receiving support from the Canadian Institutes of Health Research and McMaster University. The authors reported having no other disclosures.

[email protected]

Most pregnant women with a history of immune thrombocytopenia purpura need no treatment. Of those who do, neonatal outcomes were comparable for mothers who received treatment with intravenous immunoglobulin and for those who received corticosteroids, results of an observational study indicate.

Though limited by its retrospective design and low event rates that limit inferences about treatment effects, this observational study – the first to compare the effectiveness of treatment with IVIg to treatment with corticosteroids for immune thrombocytopenia purpura (ITP) in pregnancy – shows that outcomes did not significantly differ with the two regimens. The findings also highlight the need for ongoing neonatal platelet count monitoring throughout the first week of life, regardless of the maternal platelet count, the investigators said.

©iStock

A review of medical records at two tertiary care centers identified 235 pregnancies in 195 women with a history of ITP. No treatment was required in 137 pregnancies. Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated initially with intravenous immunoglobulin (IVIg) and 51 were treated initially with corticosteroids, reported Dongmei Sun, MD, of University of Western Ontario, London, and colleagues (Blood. 2016;128[10]:1329-35).

The two treatment groups had similar mean maternal platelet counts at birth (68.7 x 10⁹/L and 77.3 x 10⁹/L for IVIg and corticosteroids, respectively). The proportion of mothers who achieved a platelet count response did not significantly differ (38% vs. 39%), the researchers reported.

“The sole difference between treatments was a higher maternal composite outcome noted in the IVIg group,” they wrote, referring to a secondary composite outcome of postpartum hemorrhage, predelivery platelet transfusion, peripartum transfusion of any blood product, or postpartum reduction in the hemoglobin concentration of 30 g/L or more. That composite outcome occurred in 46.8% of pregnancies in the IVIg group and 23.5% in the corticosteroid group.

Adverse events were reported in 13% of cases in each group, and included hemolytic anemia, headache, and “other” in those treated with IVIg, and hyperglycemia requiring treatment, hyperglycemia with neonatal hypoglycemia, infection, and “other” in those receiving corticosteroids.

No severe or fatal maternal, fetal, or neonatal hemorrhages occurred, but two newborns did experience intracranial hemorrhage. No maternal or neonatal deaths occurred, the investigators said.

In 203 neonates for whom platelet counts were available, 56 (28%) had a count of less than 150 x 10⁹/L and 18 (9%) had a count of less than 50 x 10⁹/L.

Nadir platelet counts occurred at birth for 30% of neonates. In two cases, the nadir occurred as late as day 6 postnatally. Of note, a drop in platelets to below 150 x 10⁹/L was found in 9 (11%) of 129 neonates who had a normal cord platelet count and had a repeat count.

ITP occurs in 1 to 10 of every 10,000 pregnancies, and about one-third of cases require intervention. IVIg and corticosteroids are acceptable treatments, but most data on their effectiveness are extrapolated from nonpregnant patients and the treatments have not been adequately assessed in pregnancy, the investigators said. The current study was designed to compare the efficacy of the two treatments for maternal ITP.

Study subjects were women with singleton pregnancies with an ITP diagnosis either before or during pregnancy.

At less than 40% in both groups, the response to ITP therapies was lower than has been reported for nonpregnant patients, the investigators noted.

“Our observation of a relative resistance to ITP treatment during pregnancy requires further validation in prospective studies. We speculate that increased potency of antiplatelet antibodies during pregnancy, pregnancy-associated changes in platelet turnover, or altered drug metabolism may contribute to the lower response rates we observed,” they wrote.

With respect to corticosteroids, this “may warrant consideration of starting therapy earlier in the third trimester to maximize the likelihood of reaching target platelet counts in time for delivery and raises the possibility that lower corticosteroid doses are ineffective in this setting,” they added.

“Also of significance is the finding that 9 neonates (11%) with normal cord platelet counts were found to have a reduction in their platelet count on repeat measurement. These findings highlight the need for determination of cord platelet counts in all neonates born to mothers with active or previous ITP and the need for continued monitoring of the neonatal platelet count during the first week of life, despite normal cord platelet counts,” they wrote.

“Prospective studies are needed to better characterize the safety of these regimens, to determine the optimal dose of corticosteroids, to identify risk factors for neonatal thrombocytopenia, and to explore new therapeutic options,” they concluded.

Among the options worth exploring are rituximab, a monoclonal antibody against B-cell surface antigen CD20, for which “pregnancy data are accumulating,” and romiplostim, a thrombopoietin receptor agonist, which has been used in a few cases without reported fetal complications, they noted.

This study was supported by Canadian Blood Services Small Projects Fund and Canadian Institute of Health Research/Canadian Blood Services New Investigator Award. Individual authors reported receiving support from the Canadian Institutes of Health Research and McMaster University. The authors reported having no other disclosures.

[email protected]

Nausea and vomiting in early pregnancy were associated with a substantially reduced risk of pregnancy loss in a prospective preconception cohort of almost 800 pregnant women.

Although there has long been the suggestion that nausea is a sign of a healthy pregnancy, the evidence supporting this idea has been limited.

“Much of the published literature reports on studies that enrolled women after a clinically recognized pregnancy, thereby failing to include women with early pregnancy losses or relying on participant recall of nausea and/or loss,” wrote Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and her colleagues.

©monkeybusinessimages/thinkstockphotos.com

In this study, the researchers examined data from 797 women with one or two prior pregnancy losses and a current pregnancy confirmed by an HCG pregnancy test. They all were enrolled in a randomized clinical trial on the effects of aspirin on gestation and reproduction (JAMA Intern Med. 2016 Sep 26. doi: 10.1001/jamainternmed.2016.5641).

Participants kept a daily record of nausea and vomiting symptoms for gestational weeks 2-8 and then monthly after that. At week 12, 86% of the women reported nausea and 35% reported nausea with vomiting at least once a week in the previous 4 weeks.

Overall, women with nausea and vomiting in any given week had a 75% lower risk of pregnancy loss during that week (hazard ratio, 0.25), while those with only nausea had a 50% reduction in pregnancy loss (HR, 0.50), compared with women with neither symptom.

For women who had a peri-implantation pregnancy loss, the researchers found a similar association but it did not reach statistical significance. The hazard ratio was 0.59 for women who had nausea only and 0.51 for women who experienced nausea with vomiting.

Among women who did not experience a peri-implantation pregnancy loss, nausea only and nausea with vomiting were associated with a 66% (HR, 0.44) and 80% (HR, 0.20) reduction in risk for pregnancy loss, respectively, compared with women with neither symptom. These reductions in risk were similar when the analysis was limited to first-trimester pregnancy loss and persisted even after accounting for lifestyle and fetal factors, such as number of prior pregnancy losses, body-mass index, fetal karyotype, and multiple fetal gestations.

“These findings overcome prior analytic and design limitations and represent the most definitive data available, to our knowledge, indicating the protective association of nausea and vomiting in early pregnancy on the risk for pregnancy loss and thus may provide reassurance to women experiencing these difficult symptoms in pregnancy,” researchers wrote.

The study was supported by the National Institutes of Health. The researchers reported having no financial disclosures.

Nausea and vomiting in early pregnancy were associated with a substantially reduced risk of pregnancy loss in a prospective preconception cohort of almost 800 pregnant women.

Although there has long been the suggestion that nausea is a sign of a healthy pregnancy, the evidence supporting this idea has been limited.

“Much of the published literature reports on studies that enrolled women after a clinically recognized pregnancy, thereby failing to include women with early pregnancy losses or relying on participant recall of nausea and/or loss,” wrote Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and her colleagues.

©monkeybusinessimages/thinkstockphotos.com

In this study, the researchers examined data from 797 women with one or two prior pregnancy losses and a current pregnancy confirmed by an HCG pregnancy test. They all were enrolled in a randomized clinical trial on the effects of aspirin on gestation and reproduction (JAMA Intern Med. 2016 Sep 26. doi: 10.1001/jamainternmed.2016.5641).

Participants kept a daily record of nausea and vomiting symptoms for gestational weeks 2-8 and then monthly after that. At week 12, 86% of the women reported nausea and 35% reported nausea with vomiting at least once a week in the previous 4 weeks.

Overall, women with nausea and vomiting in any given week had a 75% lower risk of pregnancy loss during that week (hazard ratio, 0.25), while those with only nausea had a 50% reduction in pregnancy loss (HR, 0.50), compared with women with neither symptom.

For women who had a peri-implantation pregnancy loss, the researchers found a similar association but it did not reach statistical significance. The hazard ratio was 0.59 for women who had nausea only and 0.51 for women who experienced nausea with vomiting.

Among women who did not experience a peri-implantation pregnancy loss, nausea only and nausea with vomiting were associated with a 66% (HR, 0.44) and 80% (HR, 0.20) reduction in risk for pregnancy loss, respectively, compared with women with neither symptom. These reductions in risk were similar when the analysis was limited to first-trimester pregnancy loss and persisted even after accounting for lifestyle and fetal factors, such as number of prior pregnancy losses, body-mass index, fetal karyotype, and multiple fetal gestations.

“These findings overcome prior analytic and design limitations and represent the most definitive data available, to our knowledge, indicating the protective association of nausea and vomiting in early pregnancy on the risk for pregnancy loss and thus may provide reassurance to women experiencing these difficult symptoms in pregnancy,” researchers wrote.

The study was supported by the National Institutes of Health. The researchers reported having no financial disclosures.

Nausea and vomiting in early pregnancy were associated with a substantially reduced risk of pregnancy loss in a prospective preconception cohort of almost 800 pregnant women.

Although there has long been the suggestion that nausea is a sign of a healthy pregnancy, the evidence supporting this idea has been limited.

“Much of the published literature reports on studies that enrolled women after a clinically recognized pregnancy, thereby failing to include women with early pregnancy losses or relying on participant recall of nausea and/or loss,” wrote Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and her colleagues.

©monkeybusinessimages/thinkstockphotos.com

In this study, the researchers examined data from 797 women with one or two prior pregnancy losses and a current pregnancy confirmed by an HCG pregnancy test. They all were enrolled in a randomized clinical trial on the effects of aspirin on gestation and reproduction (JAMA Intern Med. 2016 Sep 26. doi: 10.1001/jamainternmed.2016.5641).

Participants kept a daily record of nausea and vomiting symptoms for gestational weeks 2-8 and then monthly after that. At week 12, 86% of the women reported nausea and 35% reported nausea with vomiting at least once a week in the previous 4 weeks.

Overall, women with nausea and vomiting in any given week had a 75% lower risk of pregnancy loss during that week (hazard ratio, 0.25), while those with only nausea had a 50% reduction in pregnancy loss (HR, 0.50), compared with women with neither symptom.

For women who had a peri-implantation pregnancy loss, the researchers found a similar association but it did not reach statistical significance. The hazard ratio was 0.59 for women who had nausea only and 0.51 for women who experienced nausea with vomiting.

Among women who did not experience a peri-implantation pregnancy loss, nausea only and nausea with vomiting were associated with a 66% (HR, 0.44) and 80% (HR, 0.20) reduction in risk for pregnancy loss, respectively, compared with women with neither symptom. These reductions in risk were similar when the analysis was limited to first-trimester pregnancy loss and persisted even after accounting for lifestyle and fetal factors, such as number of prior pregnancy losses, body-mass index, fetal karyotype, and multiple fetal gestations.

“These findings overcome prior analytic and design limitations and represent the most definitive data available, to our knowledge, indicating the protective association of nausea and vomiting in early pregnancy on the risk for pregnancy loss and thus may provide reassurance to women experiencing these difficult symptoms in pregnancy,” researchers wrote.

The study was supported by the National Institutes of Health. The researchers reported having no financial disclosures.