Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial.

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7-206/7 weeks' gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67-0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58-0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term (the BEGIN trial): a randomized controlled trial.

BACKGROUND: Combining pharmacologic agents with mechanical ripening achieves the shortest time to labor; however, there is no clear evidence on route of drug administration. Buccal administration of misoprostol has shown greater patient acceptance but remains understudied. OBJECTIVE: This study aimed to evaluate the difference in time to delivery between buccal and vaginal administration of misoprostol along with a Foley catheter for induction of labor. STUDY DESIGN: The BEGIN trial (buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term) was an institutional review board-approved, randomized clinical trial conducted from June 2019 to January 2020 comparing identical doses (25 µg) of buccal misoprostol and vaginal misoprostol along with a Foley catheter for induction of labor. Randomization was stratified by parity. Labor management was standardized among participants. Individuals undergoing induction of labor at ≥37 weeks with a singleton gestation and needing cervical ripening were included. Our primary outcome was time to delivery. Kruskal-Wallis, Pearson chi-squared, and Cox survival analyses with intent-to-treat principles were performed. A sample size of 216 was planned to detect a 4-hour reduction in delivery time. RESULTS: A total of 215 women (108 in the buccal drug administration group and 107 in the vaginal drug administration group) were randomized. The vaginal route of drug administration achieved a faster median time to delivery than the buccal route of drug administration (19.7 hours in the vaginal route vs 24.1 hours in the buccal route; P<.001). A greater percentage of women in the vaginal drug administration group delivered within 24 hours compared with the buccal drug administration group (65% vs 49%; P=.02). There was no difference in the cesarean delivery rate between the 2 groups (17% in the vaginal drug administration group vs 21% in the buccal drug administration group; P=.6). Individuals who received vaginal misoprostol with Foley catheter delivered 2 times faster than women who received buccal misoprostol with Foley catheter after censoring for cesarean delivery and adjusting for parity (hazard ratio, 2.13; 95% confidence interval, 1.44-3.17). There was no significant difference in maternal and neonatal outcomes. CONCLUSION: We found that vaginal administration of misoprostol was superior to buccal administration of misoprostol along with a Foley catheter for induction of labor. Furthermore, vaginal administration of misoprostol resulted in twice the chance of delivering earlier compared with buccal administration of misoprostol with no difference in cesarean delivery rates. Therefore, the vaginal route of administration of misoprostol should be preferred among individuals undergoing a combined pharmacologic and mechanical induction.

Accuracy of Routine Prenatal Genetic Screening in Patients Referred for Genetic Counseling.

OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) guidelines recommend routine prenatal screening for genetic diseases that could affect the pregnancy. We sought to determine the rate of missed genetic information in the general obstetrician's routine prenatal genetic screening process. STUDY DESIGN: This is a sequential case series of women referred for genetic counseling between March and August of 2015. Once identified, all women completed a personalized genetic history/exposure intake form (GHEF) created by our certified genetic counselors, followed by an in-person genetic counseling session with pedigree generation. The corresponding prenatal record was reviewed for genetic history obtained by the referring provider, most often utilizing the standardized ACOG prenatal intake form's genetic and family history sections. This information was then compared with that discovered in the GHEF and through the in-person genetic counseling session. Missed genetic information was defined as information discovered on the GHEF or during the in-person genetic counseling session which was not noted on the prenatal genetic screening document from the obstetric provider. Missing genetic information that lead to a change in clinical care, either through additional laboratory screening tests, fetal imaging or prenatal diagnostic testing through chorionic villus sampling, or amniocentesis was considered significant. We also assessed the study population as to maternal race, parity, and referral source. Statistical significance was assessed using Chi-squared testing with p < 0.05 identifying significance. RESULTS: A total of 299 patients underwent genetic counseling. Of them, 57.5% patients were referred from private providers, 28.1% from academic faculty practice, and 14.4% from a federally funded clinic. Missed genetic information was discovered in 171/299 (57.2%) of patients in the genetic counseling process. Of these 171 patients, 28.7% were identified via the GHEF and 52.6% during the in-person genetic counseling session. Of the 171 patients who had new genetic information discovered, 73 (42.7%) findings were significant. There was no statistical difference in patient race or referring office setting in the occurrence of new information found. CONCLUSION: In our population, genetic history obtained in the general obstetrician's office, regardless of practice type, missed genetic information in over half of cases with approximately 40% of that information leading to a subsequent change in clinical care. Developing a genetic intake form similar to our pregenetic counseling form, or modification/clarification of the "Family History and Genetic Screening" section within the standardized ACOG prenatal genetic history form, used at most practices in our region may decrease missed genetic information in the general obstetrician's office.

Obesity and the association with maternal mental health symptoms.

OBJECTIVE: To evaluate the association between maternal obesity and mood disorders including depression, anxiety, stress, and pregnancy-specific stress during pregnancy. STUDY DESIGN: This was a planned secondary analysis of a prospective cohort study investigating factors associated with preterm delivery. The cohort included women who initiated prenatal care before 20 weeks with a singleton pregnancy. Maternal mental health was assessed using four standard psychosocial behavioral measures to screen for depression, pregnancy-specific stress, anxiety, and stress. Screen positive scores for each tool were established based on previously published "high" scores. RESULTS: Of the 1010 women included in the cohort, 355 (35.1%) were obese. There was no significant difference in the number of obese women with stress (64.2% versus 68.4%, p = 0.18), pregnancy-specific stress (26.2% versus 22.1%, p = 0.15), or anxiety (38.6% versus 41.2%, p = 0.42); however, a greater number of obese women did report symptoms consistent with major depression when compared to women with BMIs <30 (30.4% versus 21.2%, p < 0.01). CONCLUSION: Obese women had higher rates of depression in early pregnancy compared to nonobese women. As many of the health behavior interventions for obese women during pregnancy have proven ineffective, incorporating depression screening and treatment into prenatal care may improve perinatal outcomes.

The Effect of Early Excessive Weight Gain on the Development of Hypertension in Pregnancy.

Background Previous studies have shown an association between total excessive gestational weight gain and hypertension in pregnancy. However, this may be a reflection of excessive water retention associated with the pathophysiology of hypertensive disorders of pregnancy. Early excessive weight gain, prior to the third trimester, results in greater maternal fat deposition and inflammation, which has also been associated with the development of hypertension. By focusing on early excessive weight gain, the association between maternal weight gain and the future development of hypertension can be examined. Objective To evaluate the association between early excessive maternal weight gain and the development of hypertension during pregnancy. Study Design This was a secondary analysis of a longitudinal cohort study of 1,441 women without chronic hypertension who were enrolled in a prospective study evaluating maternal angiogenic factors and the prediction of preeclampsia. Initial body mass index (BMI) was calculated by weight and height at the first study visit. Early excessive maternal weight gain was defined as weight gain by 28 weeks that exceeded the Institute of Medicine (IOM) guidelines and was calculated utilizing the maximum amount of weight gain per week recommended by the IOM based on the patient's starting BMI (normal: 0.45 kg; overweight: 0.32 kg; obese: 0.27 kg). Hypertension was defined as a sustained systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg. Logistic regression was used to determine the association between early excessive weight gain, initial BMI, and the development of hypertension, including gestational hypertension and preeclampsia, during pregnancy. Results Of 1,441 women, 767 (53.2%) had weight gain that exceeded the IOM guidelines in the first 28 weeks and 154 (10.8%) developed hypertension during pregnancy. Women whose weight gain exceeded the IOM guidelines were more likely to develop hypertension even after adjusting for relevant confounders (12.5 vs. 8.6%; p = 0.02; adjusted odds ratio [OR] = 1.70; 95% confidence interval [CI]: 1.18-2.44; p < 0.01). Obese women had a 2.4-fold increased risk of developing hypertension, even after controlling for excessive weight gain (adjusted OR = 2.44; 95% CI: 1.66-3.59; p < 0.01) Conclusions Early excessive maternal weight gain and initial BMI are independently associated with the diagnosis of a hypertensive disorder of pregnancy. Women should be counseled regarding the benefits of achieving a normal BMI prior to pregnancy and appropriate weight gain during pregnancy, as well as the potential harms of excessive weight gain related to perinatal outcomes.

Induction of labor in the obese patient.

Obese women are at an increased risk of antepartum pregnancy complications and are therefore more likely to require an induction of labor than normal weight women. They also have an increased rate of failing an induction of labor, a rate that rises significantly with increasing body mass index, and subsequent surgical and neonatal complications of an intrapartum cesarean delivery. This increase in induction failure may be due to differences in the myometrium of obese women resulting in decreased contraction strength. There have been only a few studies comparing the efficacy of the various cervical ripening agents in obese women and at this point no recommendation can be made as to what method may result in the greatest chance of a successful induction.

Foley catheter vs prostaglandin as ripening agent in pregnant women with premature rupture of membranes.

CONTEXT: Although studies support the efficacy of the Foley catheter (FC) as a cervical ripening agent in pregnant women at term with intact membranes, its efficacy has not been well studied in women with premature rupture of membranes (PROM). OBJECTIVE: To compare the interval to delivery in women with PROM who underwent induction of labor and cervical ripening with mechanical (FC) vs nonmechanical (prostaglandin [PG]) cervical ripening agents. DESIGN: Retrospective medical record review at 2 hospitals of pregnant women who delivered between January 2009 and April 2011. SETTING: Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, and Christiana Care Health System in Newark, Delaware. PATIENTS: Pregnant women with singleton gestations 36 weeks or greater who presented with PROM. INTERVENTIONS: Cervical ripening with FC or PG. MAIN OUTCOME MEASURES: The primary outcome was time from induction until delivery. Secondary outcomes included epidural use, maximum temperature during labor, number of vaginal examinations, occurrence of tachysystole, oxytocin dose, delivery mode, chorioamnionitis, and neonatal Apgar score. RESULTS: Of 155 medical records of patients who met the inclusion criteria, 33 women underwent cervical ripening with PG (ie, misoprostol) and 122 with FC. The interval to delivery was almost halved in women who underwent cervical ripening with FC compared with misoprostol (736 vs 1354 minutes; P<.01). Compared with the women in the misoprostol group, those in the FC group received a statistically significant higher dose of oxytocin (P<.01). There were no statistically significant differences between the groups with respect to the remaining secondary outcomes. Of note, all of the women who received FC were from Christiana Care Health System, and all women who received misoprostol were from Thomas Jefferson University Hospital. CONCLUSION: Foley catheters may help shorten the interval to delivery in women who are candidates for cervical ripening after PROM at or near term. There does not appear to be an increased risk for cesarean delivery or chorioamnionitis in those treated with FC.

The timing of adverse events with Foley catheter preinduction cervical ripening; implications for outpatient use.

OBJECTIVE: We sought to determine the rate and timing of adverse events that occur during preinduction cervical ripening using the Foley catheter before extrusion of the balloon and institution of oxytocin. STUDY DESIGN: Using electronic medical records, we identified all women who presented for preinduction cervical ripening using a Foley catheter with a term (≥37 weeks) singleton vertex live fetus from January 1, 2006, to June 14, 2009. Women were excluded if they had had a previous cesarean delivery, gestational hypertension or preeclampsia, pregestational diabetes, rupture of membranes before induction, fetal anomaly, or antepartum stillbirth. Outcomes were cesarean delivery for nonreassuring fetal tracing, vaginal bleeding, placental abruption, or intrapartum stillbirth occurring between 2 hours after Foley catheter placement and 6 am. RESULTS: Among 2,514 women, 1,905 met the inclusion criteria. No adverse outcomes were noted among term, singleton uncomplicated pregnancies receiving a Foley catheter for preinduction cervical ripening who met inclusion criteria (relative risk, 0.0; 95% confidence interval, 0.0-0.002). CONCLUSIONS: In a low-risk population, the use of the Foley catheter for preinduction cervical ripening was associated with no adverse outcomes. It appears to be a safe mechanism for cervical ripening and has the potential for use in the outpatient setting in a selected subset of women.