Transcervical Foley Balloon Plus Vaginal Misoprostol versus Vaginal Misoprostol Alone for Cervical Ripening in Nulliparous Obese Women: A Multicenter, Randomized, Comparative-Effectiveness Trial.

OBJECTIVE: Nulliparous obese women are at increased risk of labor induction and cesarean delivery (CD). We sought to determine whether the combination of a transvaginal Foley balloon plus misoprostol prostaglandin E1 (PGE1) is superior to misoprostol alone in reducing the risk for CD. STUDY DESIGN: We undertook a multicenter, open-label, comparative-effectiveness randomized clinical trial of nulliparous obese women with unfavorable cervix (Bishop's score ≤ 6) undergoing labor induction from January 2016 to June 2018 at three tertiary centers. Those at <32 weeks' gestation, premature rupture of membranes, stillbirth, and major fetal anomalies were excluded. Women were randomized 1:1 to either a combination of Foley balloon and misoprostol or misoprostol alone. Once Bishop's score was >6, further management was deferred to treating physicians. Primary outcome was the rate of CD. Secondary maternal outcomes included duration of induction-to-delivery interval, occurrence of tachysystole, clinical chorioamnionitis, need for operative vaginal delivery, as well as a composite of maternal morbidity (postpartum endometritis, surgical-site infection, venous thromboembolism, need for transfusion, intensive care unit admission, and maternal death). Secondary neonatal outcomes included need for neonatal intensive care unit admission, transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, culture-proven sepsis, neonatal seizures, and a composite of neonatal morbidity (Apgar's score ≤7 at 5 minutes, umbilical artery cord pH ≤7.10, birth injury, perinatal death). With the rate of CD rate being 53% at Children's Memorial Herman Hospital among nulliparous obese women who underwent induction of labor at ≥32 weeks and met our inclusion criteria; 250 women (125 women per group) were required to answer the study question. All analyses were by intention to treat. RESULTS: Of the 236 women randomized, 113 (48%) were allocated to group 1 (combined Foley and PGE1) and 123 (52%) to group 2 (PGE1 alone). The rate of CD was similar between the groups (45 vs. 43%, p = 0.84, relative risk [RR]: 1.03, 95% CI: 0.75-1.42). There was no difference in the occurrence of tachysystole that resulted in fetal heart rate abnormalities between the groups (8.8 vs. 16.2%, p = 0.09, RR: 0.54, 95% CI: 0.27-1.11). The total duration of the induction-to-delivery interval was also similar between the groups (24.8 ± 13.8 vs. 24.5 ± 14.0 hours, p = 0.87) regardless of the mode of delivery. No differences were seen in the indications for CD and secondary maternal or neonatal outcomes. CONCLUSION: In this trial of nulliparous obese women undergoing labor induction, cervical ripening with combined Foley balloon and PGE1 resulted in similar CD rates than ripening with vaginal PGE1 alone. KEY POINTS: · Nulliparous obese women are at increased risk for cesarean delivery.. · Combined intravaginal misoprostol-Foley balloon versus misoprostol alone resulted in similar rates of cesarean delivery.. · Further research is warranted to determine the optimal cervical ripening strategy in this population..

Composite neonatal and maternal morbidities with small- versus appropriate- for gestational age among uncomplicated obese women undergoing repeat cesarean delivery.

PURPOSE: Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10-89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD). STUDY DESIGN: This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, > 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus <30 kg/m2. CNM included respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, seizure, or death; CMM included transfusion, hysterectomy, operative injury, coagulopathy, thromboembolism, pulmonary edema, or death. Multivariate logistic regression was used to control for confounding factors. RESULTS: Of 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p < .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19-3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02-0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03-4.59). CONCLUSIONS: SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials.

Challenges and Limitations of Clinical Trials on Labor Induction: A Review of the Literature.

Induction of labor is a common obstetric procedure performed in nearly a quarter of all deliveries in the United States. Pharmacological (prostaglandins, oxytocin) and/or mechanical methods (balloon catheters) are commonly used for labor induction; however, there is ongoing debate as to which method is the safest and most effective. This narrative review discusses key limitations of published trials on labor induction, including the lack of well-designed randomized controlled trials directly comparing specific methods of induction, heterogeneous trial populations, and wide variation in the protocols used and outcomes reported. Furthermore, the majority of published trials were underpowered to detect significant differences in the most clinically relevant efficacy and safety outcomes (e.g., cesarean delivery, neonatal mortality). By identifying the limitations of labor induction trials, we hope to highlight the importance of quality published data to better inform guidelines and drive evidence-based treatment decisions.

Torsemide for Prevention of Persistent Postpartum Hypertension in Women With Preeclampsia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether torsemide reduces the rate of persistent postpartum hypertension in women with preeclampsia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of women with preeclampsia at a tertiary center from August 2016 to September 2017. Those with gestational hypertension or renal or cardiopulmonary failure were excluded. Within 24 hours of delivery, women were randomized one to one to oral torsemide, 20 mg/d, or placebo, for 5 days. Our primary outcome was blood pressure greater than or equal to 150 mm Hg systolic or 100 mm Hg diastolic (or both) on two occasions at least 4 hours apart by postpartum day 5 or by the time of hospital discharge. Assuming a 50% rate of persistent hypertension in women with preeclampsia, 118 participants were required to detect a 50% rate reduction. Analyses were by intention to treat. RESULTS: From August 2016 to September 2017, 118 women were randomized: 59 were allocated to torsemide and 59 to placebo. Overall, 43 (73%) women in the torsemide and 45 (76%) in the placebo group had either preeclampsia with severe features or preeclampsia superimposed on chronic hypertension. The rate of persistent postpartum hypertension was 44% in the torsemide and 58% in the placebo group (relative risk 0.76, 95% CI 0.5-1.1). No differences were seen in rate of hypertension 7-10 days or 6 weeks postpartum, severe hypertension, length of postpartum hospital stay, readmission for hypertension, or adverse events. There were no cases of severe composite morbidity or deaths. CONCLUSION: In this trial of women with preeclampsia, a 5-day course of postpartum torsemide did not have a significant effect on the rate of postpartum hypertension. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02813551.

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

OBJECTIVE: To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception. STUDY DESIGN: Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death. RESULTS: There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) (p = 0.009) with a lower birth weight (p < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar. CONCLUSION: Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets.

Potential of Metformin to Improve Cardiac Risk in Postpartum Women with Gestational Diabetes.

OBJECTIVE: Pregnancy is associated with an increase in total cholesterol, high density lipoproteins (HDL), and low-density lipoproteins (LDL). Postpartum, HDL and LDL decrease over the first 12 weeks postpartum. Oxidized LDL (ox-LDL) is a marker of oxidative stress-related inflammation, which is associated with obesity and also with development of cardiovascular disease. Cardiovascular protection and weight loss are benefits from metformin, especially in women with diabetes. The objective of this study was to compare changes in lipid profiles and biomarkers for obesity during the initial 6 weeks postpartum between women with gestational diabetes mellitus (GDM) treated with metformin versus placebo. METHODS: This was a planned ancillary study of a randomized controlled trial compares metformin versus placebo in women with GDM for postpartum weight loss. Two 3 mL blood samples were collected within 24 h of delivery and 6 weeks postpartum immediately processed after collection then stored at -20°C until completion of clinical trial prior to analysis. Change in the median plasma concentrations of total cholesterol, HDL, ox-LDL, glucose, insulin, leptin, and unacylated ghrelin were compared between study groups. RESULTS: Of the 77 postpartum women were included, 35 received metformin and 42 received placebo. There was less of a reduction in HDL in the metformin group compared to placebo (-2.3 versus -7.5 mg/dL, p = 0.019). In addition, there was a greater reduction in ox-LDL in those receiving metformin (-12.2 versus -3.8 mg/dL, p = 0.038). No other differences were observed in the selected biomarkers evaluated. CONCLUSION: Biomarker levels of HDL and ox-LDL were positively affected during the initial 6 weeks postpartum in GDM women treated with metformin. Additional studies with a longer duration of metformin treatment in the postpartum period are warranted to evaluate long-term potential benefits.

Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features.

OBJECTIVE: To estimate whether nonsteroidal antiinflammatory drugs (NSAIDs) are associated with persistent postpartum hypertension in a cohort of women with preeclampsia and severe features. METHODS: We conducted a retrospective cohort study at a single, tertiary center from January 2013 to December 2015. All women diagnosed with severe preeclampsia who remained hypertensive for greater than 24 hours after delivery were included. The primary outcome was the rate of persistent postpartum hypertension, defined as systolic blood pressure 150 mm Hg or greater or diastolic 100 mm Hg or greater (or both), on two occasions, at least 4 hours apart. Secondary outcomes included severe maternal morbidity: pulmonary edema, renal dysfunction, stroke, eclampsia, and intensive care unit admission. Additional outcomes included length of postpartum hospital stay, receipt of narcotics, and hospital readmission. Multivariable logistic regression was performed to adjust for confounders. Adjusted odds ratios (ORs) are reported for applicable study outcomes. RESULTS: Of the 399 women with severe preeclampsia, 324 (81%) remained hypertensive 24 hours after delivery. Two hundred forty-three (75%) received NSAIDs (either ibuprofen or ketorolac) and 81 (25%) did not. After multivariable logistic regression, the likelihood of reaching a blood pressure of 150 mm Hg systolic or 100 mm Hg diastolic (or both), on two occasions, at least 4 hours apart, was similar between those who received NSAIDs compared with those who did not (70% compared with 73%; adjusted OR 1.1, 95% CI 0.6-2.0). Similarly, puerperal occurrence of pulmonary edema (3% compared with 10%; OR 4.4, 95% CI 1.5-13.1), renal dysfunction (5% compared with 8%; OR 1.7, 95% CI 0.6-4.8), eclampsia (1% compared with 0%; P=.34), or intensive care unit admission (3% compared with 8%; OR 2.4, 95% CI 0.8-7.1) was similar between the groups. There were no differences in the rate of narcotic use (89% compared with 75%; adjusted OR 0.6 95% CI 0.18-1.70). CONCLUSION: In this cohort of women with preeclampsia and severe features before delivery, NSAIDs were not associated with increased rates of persistent postpartum hypertension.

Can 3-dimensional power Doppler indices improve the prenatal diagnosis of a potentially morbidly adherent placenta in patients with placenta previa?

BACKGROUND: Traditionally, 2-dimensional ultrasound parameters have been used for the diagnosis of a suspected morbidly adherent placenta previa. More objective techniques have not been well studied yet. OBJECTIVE: The objective of the study was to determine the ability of prenatal 3-dimensional power Doppler analysis of flow and vascular indices to predict the morbidly adherent placenta objectively. STUDY DESIGN: A prospective cohort study was performed in women between 28 and 32 gestational weeks with known placenta previa. Patients underwent a two-dimensional gray-scale ultrasound that determined management decisions. 3-Dimensional power Doppler volumes were obtained during the same examination and vascular, flow, and vascular flow indices were calculated after manual tracing of the viewed placenta in the sweep; data were blinded to obstetricians. Morbidly adherent placenta was confirmed by histology. Severe morbidly adherent placenta was defined as increta/percreta on histology, blood loss >2000 mL, and >2 units of PRBC transfused. Sensitivities, specificities, predictive values, and likelihood ratios were calculated. Student t and χ2 tests, logistic regression, receiver-operating characteristic curves, and intra- and interrater agreements using Kappa statistics were performed. RESULTS: The following results were found: (1) 50 women were studied: 23 had morbidly adherent placenta, of which 12 (52.2%) were severe morbidly adherent placenta; (2) 2-dimensional parameters diagnosed morbidly adherent placenta with a sensitivity of 82.6% (95% confidence interval, 60.4-94.2), a specificity of 88.9% (95% confidence interval, 69.7-97.1), a positive predictive value of 86.3% (95% confidence interval, 64.0-96.4), a negative predictive value of 85.7% (95% confidence interval, 66.4-95.3), a positive likelihood ratio of 7.4 (95% confidence interval, 2.5-21.9), and a negative likelihood ratio of 0.2 (95% confidence interval, 0.08-0.48); (3) mean values of the vascular index (32.8 ± 7.4) and the vascular flow index (14.2 ± 3.8) were higher in morbidly adherent placenta (P < .001); (4) area under the receiver-operating characteristic curve for the vascular and vascular flow indices were 0.99 and 0.97, respectively; (5) the vascular index ≥21 predicted morbidly adherent placenta with a sensitivity and a specificity of 95% (95% confidence interval, 88.2-96.9) and 91%, respectively (95% confidence interval, 87.5-92.4), 92% positive predictive value (95% confidence interval, 85.5-94.3), 90% negative predictive value (95% confidence interval, 79.9-95.3), positive likelihood ratio of 10.55 (95% confidence interval, 7.06-12.75), and negative likelihood ratio of 0.05 (95% confidence interval, 0.03-0.13); and (6) for the severe morbidly adherent placenta, 2-dimensional ultrasound had a sensitivity of 33.3% (95% confidence interval, 11.3-64.6), a specificity of 81.8% (95% confidence interval, 47.8-96.8), a positive predictive value of 66.7% (95% confidence interval, 24.1-94.1), a negative predictive value of 52.9% (95% confidence interval, 28.5-76.1), a positive likelihood ratio of 1.83 (95% confidence interval, 0.41-8.11), and a negative likelihood ratio of 0.81 (95% confidence interval, 0.52-1.26). A vascular index ≥31 predicted the diagnosis of a severe morbidly adherent placenta with a 100% sensitivity (95% confidence interval, 72-100), a 90% specificity (95% confidence interval, 81.7-93.8), an 88% positive predictive value (95% confidence interval, 55.0-91.3), a 100% negative predictive value (95% confidence interval, 90.9-100), a positive likelihood ratio of 10.0 (95% confidence interval, 3.93-16.13), and a negative likelihood ratio of 0 (95% confidence interval, 0-0.34). Intrarater and interrater agreements were 94% (P < .001) and 93% (P < .001), respectively. CONCLUSION: The vascular index accurately predicts the morbidly adherent placenta in patients with placenta previa. In addition, 3-dimensional power Doppler vascular and vascular flow indices were more predictive of severe cases of morbidly adherent placenta compared with 2-dimensional ultrasound. This objective technique may limit the variations in diagnosing morbidly adherent placenta because of the subjectivity of 2-dimensional ultrasound interpretations.

Antenatal Corticosteroids for the Prevention of Respiratory Distress Syndrome in Premature Twins.

OBJECTIVE: To estimate whether antenatal corticosteroids before 34 weeks of gestation are associated with reduced incidence of respiratory distress syndrome (RDS) and composite neonatal morbidity in preterm twins. METHODS: This was a secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. All liveborn, nonanomalous twins delivered between 24 0/7 and 36 6/7 weeks of gestation were included. Neonatal outcomes were compared between women who received antenatal corticosteroids and those who did not. The primary outcome was the incidence of RDS. The secondary outcome was the incidence of serious composite neonatal morbidity. Multivariable log Poisson regression with correlation adjustment between twins born to the same mother was performed for confounder control. Adjusted relative risks (RRs) are reported for study outcomes. Based on a post hoc power analysis, this study was powered to detect an RR less than 0.63 for RDS and greater than 1.43 for composite neonatal morbidity outcomes. RESULTS: A total of 432 women (850 neonates) were included. Only 300 (35%) neonates were born to women receiving antenatal corticosteroids. After multivariable regression, antenatal corticosteroids were not associated with a reduced incidence of RDS (81 [27%] compared with 92 [17%] neonates, adjusted RR 1.28, 95% confidence interval [CI] 0.97-1.71) or composite neonatal morbidity (87 [29%] compared with 108 [20%] neonates, adjusted RR 1.21, 95% CI 0.93-1.56). However, antenatal corticosteroids were associated with increased rates of neonatal intensive care unit admissions (235 [78%] compared with 322 [59%] neonates, adjusted RR 1.22, 95% CI 1.09-1.36) and mechanical ventilation (70 [23%] compared with 66 [12%] neonates, adjusted RR 1.52, 95% CI 1.12-2.09). Focusing analysis to newborns delivered before 34 weeks of gestation (n=311), 161 (52%) received antenatal corticosteroids. Similarly, no differences in the rate of RDS (66 [41%] compared with 68 [45%] neonates, adjusted RR 1.01, 95% CI 0.76-1.34) or composite neonatal morbidity (72 [45%] compared with 81 [54%] neonates, adjusted RR 0.95, 95% CI 0.74-1.22) were noted. CONCLUSION: In this cohort of preterm twins, antenatal corticosteroid administration was not associated with a reduced incidence of RDS and composite neonatal morbidity.

Timing of Medically Indicated Delivery in Diabetic Pregnancies: A Perspective on Current Evidence-Based Recommendations.

Diabetes complicates 6 to 7% of all pregnancies in the United States. Poor glycemic control is associated with multiple immediate and long-term adverse effects on both the mother and fetus. Although uniformity exists in the antenatal management of this disease, there is a paucity of evidence-based studies upon which to dictate the optimal time of delivery among affected women. The potential risks of delayed neonatal pulmonary maturation including respiratory distress syndrome and transient tachypnea of the newborn associated with early delivery must be balanced with the increased incidence of fetal demise, overgrowth, and birth injury related to diabetes in late gestations. Even among diabetic women with optimal glycemic control, the risk of stillbirth in the third trimester is considerably higher than their normal counterparts. The current paradigm of delaying delivery to 39 weeks in women with controlled and uncomplicated diabetes has been challenged by recent evidence advocating delivery by 38 weeks to improve perinatal outcomes. However, additional well-designed and adequately powered prospective studies are needed to better understand the short- and long-term implications of the optimal timing of delivery in this high-risk population. This article reviews the most current literature regarding the optimal timing of delivery in pregnancies complicated by diabetes mellitus and gestational diabetes mellitus.

Relationship between Self-Reported Maternal Substance Abuse and Adverse Outcomes in the Premature Newborn.

OBJECTIVE: This study aims to compare neonatal and long-term outcomes among preterm newborns from women with reported versus those who did not report substance abuse. STUDY DESIGN: Secondary analysis of a trial of magnesium sulfate for cerebral palsy prevention. Cases were pregnant women who reported substance abuse, controls were those who denied it. Study outcomes included (1) composite neonatal morbidity, defined as any of the following: Apgar score ≤ 3 at 5 minutes, seizures, culture-proven sepsis, necrotizing enterocolitis grades 2 or 3, intraventricular hemorrhage grades 3 or 4, and/or death before discharge; (2) infant and childhood morbidity, defined as stillbirth or death by 1 year, or moderate/severe cerebral palsy by age of 2. RESULTS: Among 1,972 women meeting the inclusion criteria, 197 (10%) reported substance abuse. Composite neonatal, infant, and childhood morbidity rates were similar between cases and controls. However, women reporting substance abuse who delivered between 32(0/7) and 36(6/7) weeks had a higher frequency of composite infant and childhood morbidity (6.5 vs. 1.0%; adjusted odds ratio, 6.5; 95% confidence interval, 1.14-36.99). CONCLUSIONS: Preterm birth was associated with similar composite neonatal morbidity between cases and controls. After 32 weeks, self-reported substance abuse was associated with a sevenfold increase in the rates of stillbirth and long-term infant morbidity.

A Rapidly Growing Abdominal Mass: Desmoid Tumor in Pregnancy.

Background Desmoid tumors are benign soft tissue tumors that locally invade adjacent tissue. There is a paucity of reports describing the rapid growth of these tumors during pregnancy. Case A giant desmoid tumor arising from the left abdominal wall of a young female patient with rapid growth during pregnancy is described. Preoperative evaluation included ultrasonography and magnetic resonance imaging. Decision made by a multidisciplinary team was not to intervene before birth, and abdominal delivery at term was accomplished. Conclusion Desmoid tumors should be part of the differential diagnosis in an abdominal wall tumor of rapid growth during pregnancy. Future studies are needed for better understanding of the pathogenesis, diagnosis, and treatment of desmoid tumors in pregnant women.

Fetal anomalies and long-term effects associated with substance abuse in pregnancy: a literature review.

OBJECTIVES: Substance abuse in pregnancy remains a major public health problem. Fetal teratogenicity results from the effect of these substances during fetal development, particularly when used in combination. This review will focus on and attempt to clarify the existing literature regarding the association of substance abuse on the development of congenital anomalies and the long-term implications in exposed offspring. METHODS: Systematic review of available English literature using the PubMed database of all peer-reviewed articles on the subject. RESULTS: A total of 128 articles were included in this review. Alcohol was the most common substance associated with fetal anomalies, particularly facial dysmorphisms and alterations in the central nervous system development. Adverse maternal environments associated with risky behaviors and lack of adequate prenatal care precludes the timely detection of fetal anomalies, confounding most studies linking causality. In addition, although methodological differences and limited availability of well-designed trials exist, substance abuse in pregnancy has been associated with adverse long-term outcomes in infant growth, behavior, cognition, language and achievement. CONCLUSION: The literature summarized in this review suggests that drug exposure during pregnancy may increase the risk of congenital anomalies and long-term adverse effects in exposed children and adolescents. These conclusions must be tempered by the many confounders associated with drug use. A multidisciplinary approach is paramount for appropriate counseling regarding the known immediate and long-term risks of substance abuse in pregnancy.

The effects of metformin on weight loss in women with gestational diabetes: a pilot randomized, placebo-controlled trial.

OBJECTIVE: We sought to compare weight loss in the first 6 weeks postpartum among women with gestational diabetes mellitus (GDM) treated with metformin or placebo, a promising therapy to reduce later risk of progression to diabetes mellitus. STUDY DESIGN: We conducted a pilot, randomized trial of metformin vs placebo in postpartum women with GDM. Women with pre-GDM, unable to tolerate metformin, resumed on insulin or oral hypoglycemic agent, delivered <34 weeks' gestation, or with a body mass index <20 kg/m(2) were excluded. Women were randomized to either metformin 850 mg daily for 7 days, then metformin 850 mg twice a day for the next 5 weeks or placebo prescribed in a similar frequency. The subject, health care provider, and research staff were blinded to the treatment. The primary outcome was weight change from delivery to 6 weeks postpartum. Secondary outcomes included the percentage of women achieving their self-reported prepregnancy weight, reported medication adherence, adverse effects, and satisfaction. Differences in weight change between groups were determined by Wilcoxon rank sum test and in achieving prepregnancy weight by χ(2) test. RESULTS: Of 114 women randomized, 79 (69.3%) completed the 6 weeks; 36 (45.6%) were randomized to metformin and 43 (54.4%) to placebo. Metformin and placebo groups were similar in median weight loss (6.3 kg [range, -0.3 to 19.8] vs 6.5 kg [range, -0.3 to 12.1], P = .988) and percentage of women achieving reported prepregnancy weight (41.7 vs 37.2%, P = .69). Self-reported adherence in taking >50% of medication was 75% at 3 weeks and 97% at 6 weeks. Nausea, diarrhea, and hypoglycemia were reported in approximately 11-17% of women and 56-63% reported dissatisfaction with the medication. CONCLUSION: Women with GDM lost approximately 6 kg by 6 weeks' postpartum. This was similar in both groups and resulted in <50% of women achieving their prepregnancy weight. Although the reported adherence and satisfaction with the medication was high, adverse effects were reported with nearly 1 in 5 women including nausea, diarrhea, and hypoglycemia. Contrary to expectation, we found no evidence of benefit from metformin. However, longer treatment periods and larger studies with minimal attrition may be warranted.

Neonatal and infant outcomes in twin gestations with preterm premature rupture of membranes at 24-31 weeks of gestation.

OBJECTIVE: To describe the perinatal and infant and early childhood morbidity associated with preterm premature rupture of membranes (PROM) in a cohort of twin pregnancies evaluated prospectively with neonatal follow-up to 2 years of age. METHODS: This was a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Inclusion criteria were twin gestation with preterm PROM diagnosed between 24 0/7 and 31 6/7 weeks of gestation and planned expectant management. Latency (time from membrane rupture to delivery) and perinatal outcomes were evaluated by gestational age at membrane rupture. Long-term neonatal outcomes were also analyzed. RESULTS: Among 151 women who met inclusion criteria, the median gestational age at preterm PROM was 28.1 weeks (range 24.1-31.6 weeks). Approximately one-third of women achieved a latency of at least 1 week. Gestational age at preterm PROM (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.63-0.90 for each week after 24 weeks of gestation) and cervical dilation at admission (OR 0.66, 95% CI 0.49-0.90 for each centimeter of dilation) were inversely associated with a latency period of at least 1 week. There were no stillbirths (95% CI 0-1%), but the rate of neonatal mortality was 90 per 1,000 newborns (95% CI 57-112) with a 7.3% cerebral palsy rate among survivors (95% CI 4.4-10.3%). CONCLUSION: In twin pregnancies, preterm PROM from 24 to 31 weeks of gestation is associated with a neonatal mortality rate of 9.0% and an overall cerebral palsy rate of 7.3%. A longer latency period is associated with less advanced cervical dilation and later gestational age at PROM. LEVEL OF EVIEDENCE: II.

Diabetic ketoacidosis in pregnancy.

Pregnancies complicated by diabetic ketoacidosis are associated with increased rates of perinatal morbidity and mortality. A high index of suspicion is required, because diabetic ketoacidosis onset in pregnancy can be insidious, usually at lower glucose levels, and often progresses more rapidly as compared with nonpregnancy. Morbidity and mortality can be reduced with early detection of precipitating factors (ie, infection, intractable vomiting, inadequate insulin management or inappropriate insulin cessation, ß-sympathomimetic use, steroid administration for fetal lung maturation), prompt hospitalization, and targeted therapy with intensive monitoring. A multidisciplinary approach including a maternal-fetal medicine physician, medical endocrinology specialists familiar with the physiologic changes in pregnancy, an obstetric anesthesiologist, and skilled nursing is paramount. Management principles include aggressive volume replacement, initiation of intravenous insulin therapy, correction of acidosis, correction of electrolyte abnormalities and management of precipitating factors, as well as monitoring of maternal-fetal response to treatment. When diabetic ketoacidosis occurs after 24 weeks of gestation, fetal status should be continuously monitored given associated fetal hypoxemia and acidosis. The decision for delivery can be challenging and must be based on gestational age as well as maternal-fetal responses to therapy. The natural inclination is to proceed with emergent delivery for nonreassuring fetal status that is frequently present during the acute episode, but it is imperative to correct the maternal metabolic abnormalities first, because both maternal and fetal conditions will likewise improve. Prevention strategies should include education of diabetic pregnant women about the risks of diabetic ketoacidosis, precipitating factors, and the importance of reporting signs and symptoms in a timely fashion.