Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study.

OBJECTIVE: In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. STUDY DESIGN: Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. RESULTS: Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). CONCLUSION: In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. KEY POINTS: · Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..

Effect of Thyroxine Therapy on Depressive Symptoms Among Women With Subclinical Hypothyroidism.

OBJECTIVE: To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms. METHODS: We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression. RESULTS: Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results. CONCLUSIONS: This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

The relationship of maternal glycemia to childhood obesity and metabolic dysfunction‡.

Objective: To determine the association of maternal glycemia with childhood obesity and metabolic dysfunction.Study design: Secondary analysis of follow-up data 5-10 years after a mild gestational diabetes mellitus (GDM) treatment trial. The relationship between maternal oral glucose tolerance testing (OGTT) at 24-31-week gestation and body mass index (BMI), fasting glucose, insulin, and anthropometric measurements (sum of skinfolds, subscapular/triceps ratio, and waist circumference) in the offspring of untreated mild GDM and non-GDM (abnormal 50-g screen/normal OGTT) women was assessed. Multivariable regression modeling controlling for maternal and neonatal characteristics was employed.Results: A cohort of 236 untreated mild GDM and 480 non-GDM offspring were analyzed. In the combined cohort, significant correlations existed between fasting, 1, 2, and 3 h maternal glucose and subscapular/triceps ratio (all p < .04) and in all OGTT values other than the 2-hour value for homeostatic model assessment-estimated insulin resistance (HOMA-IR) (all p < .04) and sum of skinfold measurements (all p < .03). No correlation was found between OGTT values and childhood BMI Z-score. Multivariable regression modeling showed that OGTT values were associated with only sum of skinfolds and subscapular/triceps ratio and not with childhood BMI Z-score. Hispanic ethnicity and prepregnancy maternal BMI were most consistently related to childhood BMI Z-score and HOMA-IR, and Hispanic ethnicity with fasting glucose.Conclusions: Among women with untreated mild GDM and those without GDM, maternal glycemia is associated with childhood anthropometric measures of obesity but not childhood BMI, fasting glucose, or insulin resistance. Hispanic ethnicity, maternal BMI, and gestational weight gain were consistently related to childhood BMI.

Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known. Objective: To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery. Design, Setting, and Participants: This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017. Exposures: Betamethasone treatment. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681 ($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P = .02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity decreased by 2.9% (95% CI, -0.5% to -5.4%). Thus, the cost-effectiveness ratio was -$23 986 per case of respiratory morbidity averted. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions. Conclusions and Relevance: The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy.

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.

BACKGROUND: Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS: We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS: A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS: Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

Pregnancies After the Diagnosis of Mild Gestational Diabetes Mellitus and Risk of Cardiometabolic Disorders.

OBJECTIVE: To assess the association of subsequent pregnancy with subsequent metabolic syndrome and type II diabetes mellitus after a pregnancy complicated by mild gestational diabetes mellitus (GDM). METHODS: We conducted a prospective observational follow-up study of women with mild GDM randomized from 2002 to 2007 to usual care or dietary intervention and glucose self-monitoring. Women were evaluated 5-10 years after the parent study. Participants were grouped according to the number of subsequent pregnancies (group A, none [reference]; group B, one; group C, two or greater). Serum triglycerides, glucose tolerance, high-density lipoprotein cholesterol, blood pressure, and waist circumference were assessed. Metabolic syndrome was diagnosed by American Heart Association and National Heart Lung and Blood Institute criteria. Multivariable regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 905 eligible women from the original trial, 483 agreed to participate, 426 of whom were included in this analysis. Groups A, B, and C consisted of 212, 143, and 71 women, respectively. Of women with subsequent pregnancies, 32% (69/214) had another pregnancy complicated with GDM. No difference between groups was observed for metabolic syndrome (group A, 34%; group B, 33%; group C, 30%). Subsequent pregnancies were associated with diabetes mellitus outside of pregnancy (group A, 5.2%; group B, 10.5%, RR 2.62, 95% CI 1.16-5.91; group C, 11.3%, RR 2.83, 95% CI 1.06-7.59), and if complicated with GDM (no subsequent GDM pregnancy, RR 1.99, 95% CI 0.82-4.84; subsequent GDM pregnancy, RR 3.75, 95% CI 1.60-8.82). CONCLUSION: In women with prior mild GDM, subsequent pregnancies did not increase the frequency of metabolic syndrome, but subsequent pregnancies with GDM increased the risk of diabetes mellitus outside of pregnancy.

Pregnancy-Associated Hypertension in Glucose-Intolerant Pregnancy and Subsequent Metabolic Syndrome.

OBJECTIVE: To evaluate whether pregnancy-associated hypertension (preeclampsia or gestational hypertension) among women with varying degrees of glucose intolerance during pregnancy is associated with maternal metabolic syndrome 5-10 years later. METHODS: This was an observational cohort study of women previously enrolled in a treatment trial of mild gestational diabetes mellitus or an observational study of lesser degrees of glucose intolerance evaluated 5-10 years after their index pregnancy. At follow-up, women underwent anthropometric and blood pressure measurements and analysis of fasting glucose and serum lipids. RESULTS: A total of 825 women (47% of eligible women from the original study) were included in this analysis and evaluated at a median 7 years after their index pregnancy at a median age of 35 years. Overall, 239 (29%) had subsequent metabolic syndrome. The frequency of metabolic syndrome and its components was highest in the women who had pregnancy-associated hypertension and delivered preterm. After adjusting for confounding factors, pregnancy-associated hypertension in women who delivered preterm was associated with subsequent hypertension (130/85 mm Hg or greater; relative risk 3.06, 95% confidence interval [CI] 1.95-4.80, P<.001), high triglycerides (150 mg/dL or greater; relative risk 1.82, 95% CI 1.06-3.14, P=.03), and metabolic syndrome (per the American Heart Association and National Heart Lung and Blood Institute Scientific Statement; relative risk 1.78, 95% CI 1.14-2.78, P=.01) compared with women who remained normotensive throughout their index pregnancy and were delivered at term. CONCLUSION: Women with varying degrees of glucose intolerance who experienced pregnancy-associated hypertension and then delivered preterm had a higher frequency of subsequent hypertension, high triglycerides, and metabolic syndrome 5-10 years later.

Antenatal Betamethasone for Women at Risk for Late Preterm Delivery.

BACKGROUND: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities. METHODS: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery. RESULTS: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001). CONCLUSIONS: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).

A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis.

BACKGROUND: It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes. METHODS: We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor. The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected. The primary outcome was a composite of intrapartum fetal death, neonatal death, an Apgar score of 3 or less at 5 minutes, neonatal seizure, an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more, intubation for ventilation at delivery, or neonatal encephalopathy. RESULTS: A total of 11,108 patients underwent randomization; 5532 were assigned to the open group, and 5576 to the masked group. The primary outcome occurred in 52 fetuses or neonates of women in the open group (0.9%) and 40 fetuses or neonates of women in the masked group (0.7%) (relative risk, 1.31; 95% confidence interval, 0.87 to 1.98; P=0.20). Among the individual components of the primary outcome, only the frequency of a 5-minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group (0.3% vs. 0.1%, P=0.02). There were no significant between-group differences in the rate of cesarean delivery (16.9% and 16.2%, respectively; P=0.30) or any operative delivery (22.8% and 22.0%, respectively; P=0.31). Adverse events were rare and occurred with similar frequency in the two groups. CONCLUSIONS: Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical; ClinicalTrials.gov number, NCT01131260.).

Racial and ethnic disparities in maternal morbidity and obstetric care.

OBJECTIVE: To evaluate whether racial and ethnic disparities exist in obstetric care and adverse outcomes. METHODS: We analyzed data from a cohort of women who delivered at 25 hospitals across the United States over a 3-year period. Race and ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, or Asian. Associations between race and ethnicity and severe postpartum hemorrhage, peripartum infection, and severe perineal laceration at spontaneous vaginal delivery as well as between race and ethnicity and obstetric care (eg, episiotomy) relevant to the adverse outcomes were estimated by univariable analysis and multivariable logistic regression. RESULTS: Of 115,502 studied women, 95% were classified by one of the race and ethnicity categories. Non-Hispanic white women were significantly less likely to experience severe postpartum hemorrhage (1.6% non-Hispanic white compared with 3.0% non-Hispanic black compared with 3.1% Hispanic compared with 2.2% Asian) and peripartum infection (4.1% non-Hispanic white compared with 4.9% non-Hispanic black compared with 6.4% Hispanic compared with 6.2% Asian) than others (P<.001 for both). Severe perineal laceration at spontaneous vaginal delivery was significantly more likely in Asian women (2.5% non-Hispanic white compared with 1.2% non-Hispanic black compared with 1.5% Hispanic compared with 5.5% Asian; P<.001). These disparities persisted in multivariable analysis. Many types of obstetric care examined also were significantly different according to race and ethnicity in both univariable and multivariable analysis. There were no significant interactions between race and ethnicity and hospital of delivery. CONCLUSION: Racial and ethnic disparities exist for multiple adverse obstetric outcomes and types of obstetric care and do not appear to be explained by differences in patient characteristics or by delivery hospital. LEVEL OF EVIDENCE: II.

Mild gestational diabetes mellitus and long-term child health.

OBJECTIVE: To evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity. RESEARCH DESIGN AND METHODS: Follow-up study of children (ages 5-10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured. RESULTS: Five hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5-6 and 7-10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels. CONCLUSIONS: Although treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose.

Nonmedically indicated induction vs expectant treatment in term nulliparous women.

OBJECTIVE: The purpose of this study was to compare maternal and neonatal outcomes in nulliparous women with nonmedically indicated inductions at term vs those expectantly treated. STUDY DESIGN: Data were obtained from maternal and neonatal charts for all deliveries on randomly selected days across 25 US hospitals over a 3-year period. A low-risk subset of nulliparous women with vertex nonanomalous singleton gestations who delivered 38 0/7 to 41 6/7 weeks were selected. Maternal and neonatal outcomes for nonmedically indicated induction within each week were compared with women who did not undergo nonmedically indicated induction during that week. Multivariable analysis was used to adjust for hospital, maternal age, race/ethnicity, body mass index, cigarette use, and insurance status. RESULTS: We found 31,169 women who met our criteria. Neonatal complications were either less frequent with nonmedically indicated induction or no different between groups. Nonmedically indicated induction was associated with less frequent peripartum infections (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16-0.98) at 38 weeks of gestation and less frequent third- and fourth-degree lacerations (OR, 0.60; 95% CI, 0.42-0.86) and less frequent peripartum infections (OR, 0.66; 95% CI, 0.49-0.90) at 39 weeks of gestation. Nonmedically indicated induction was associated with a longer admission-to-delivery time by approximately 3-4 hours and increased odds of cesarean delivery at 38 (OR, 1.50; 95% CI, 1.08-2.08) and 40 weeks (OR, 1.30; 95% CI, 1.15-1.46) of gestation. CONCLUSION: At 39 weeks of gestation, nonmedically indicated induction is associated with lower maternal and neonatal morbidity than women who are expectantly treated.

Latency and infectious complications after preterm premature rupture of membranes: impact of body mass index.

OBJECTIVE: Obesity has been associated with chronic inflammation. We hypothesized that body mass index may be inversely related to latency and directly related to infectious complications after preterm premature rupture of membranes. STUDY DESIGN: This secondary analysis of a randomized trial of antibiotics for preterm premature rupture of membranes had information available for 562 subjects. We analyzed the association between body mass index and latency, the occurrence of chorioamnionitis, endometritis, and maternal infectious morbidity after controlling for gestational age at rupture and treatment group. Survival analysis, regression, and test of proportions were used as appropriate. RESULTS: When evaluated as a categorical or continuous variable, body mass index did not reveal any significant associations. Latency to delivery was affected by gestational age at rupture of membrane and antibiotic therapy but not by body mass index group. CONCLUSION: Body mass index was not associated with latency or the occurrence of maternal infectious complications during conservative management of premature rupture of membranes before 32 weeks' gestation.

The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy.

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious morbidity: a randomized, controlled trial.

OBJECTIVE: The objective of the study was to determine whether the administration of cefazolin prior to skin incision was superior to administration at the time of umbilical cord clamping for the prevention of postcesarean infectious morbidity. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled trial. Study subjects received cefazolin 15-60 minutes prior to incision and controls received cefazolin at the time of cord clamping. The occurrence of endomyometritis, wound infection, total infectious morbidity, and neonatal complications were compared. RESULTS: There were 357 subjects enrolled. No demographic differences were observed between groups. There were decreased total infectious morbidity in the study group (relative risk [RR] = 0.4, 95% confidence interval [CI] 0.18 to 0.87), decreased endometritis (RR = 0.2, 95% CI 0.15 to 0.94). No increase in neonatal sepsis (P = .99), sepsis workups (P = .96), or length of stay (P = .17) was observed. CONCLUSION: Administration of prophylactic cefazolin prior to skin incision resulted in a decrease in both endomyometritis and total postcesarean infectious morbidity, compared with administration at the time of cord clamping. This dosing did not result in increased neonatal septic workups or complications.

Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation?

OBJECTIVE: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women. STUDY DESIGN: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation. RESULTS: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10. CONCLUSION: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.

Serum homocysteine levels after preterm premature rupture of the membranes.

OBJECTIVE: Preterm premature rupture of the membranes (PPROM) is believed to be caused, in part, by abnormalities of collagen and increased levels of oxidative stress. Elevated homocysteine levels have been shown to induce these same pathophysiologic changes. We tested the hypothesis that serum homocysteine levels would be higher in women with PPROM when compared with matched control women. STUDY DESIGN: A secondary analysis derived from 2 previously completed studies performed in the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. We identified 99 study cases with PPROM (24 to 32 weeks' gestation) and matched them with 99 asymptomatic control women from an observational study of preterm birth prediction. Cases and control women were matched for race, gestational age at sampling, and MFMU Network center. Serum homocysteine levels were determined by immunoassay in batch fashion by personnel masked to study arm and clinical outcomes. Serum homocysteine levels were compared between groups, as were the baseline characteristics of maternal age, cigarette smoking, nulliparity, infections during pregnancy, and body mass index (BMI) <19.8 kg/m 2. Serum homocysteine levels were dichotomized as >75th, 90th, and 95th %ile of control women, and the likelihood of elevated homocysteine levels was determined in women who smoked, had a BMI <19.8 kg/m 2, or who had PPROM. Statistical analyses included the Wilcoxon rank sum, chi-square, and Pearson correlation coefficient, where appropriate. Baseline characteristics were controlled with a logistic regression model. RESULTS: Serum homocysteine levels measured in patients with PPROM were not significantly different from matched control women: median and (25th to 75th %ile): 4.9 (3.5-6.2) vs 4.8 (3.9-6.2 micromol/L), P =.73. In our population, neither the number of cigarettes smoked ( r = -0.08, P =.57), nor BMI ( r = -0.08, P =.24) correlated with serum homocysteine levels. The strongest association was seen in women with PPROM having serum homocysteine levels >95th %ile of control women (odds ratio [OR] 2.7, P =.10). After adjusting for baseline characteristics, no correlation between serum homocysteine level and the presence of PPROM was seen, OR 1.0 (.9-1.1); P =.99. CONCLUSION: Women presenting with PPROM did not have significantly increased serum homocysteine levels when compared with control women.

Time course of the regression of asymptomatic bacterial vaginosis in pregnancy with and without treatment.

OBJECTIVE: The purpose of this study was to determine the effectiveness of treatment over time for bacterial vaginosis in pregnancy and the probability of spontaneous resolution with placebo. STUDY DESIGN: Women with asymptomatic bacterial vaginosis on Gram stain were assigned randomly at 16 to 23 weeks of gestation to receive two 2-g doses of metronidazole or placebo 48 hours apart and were re-evaluated for changes in Gram stain score on one occasion > or =2 weeks later. RESULTS: Of 658 women who underwent metronidazole therapy, treatment was successful (score, <7) in 78% of those women who were seen at 2 to 3.9 weeks of gestation, which was similar to women seen > or =10 weeks after treatment. In 683 women who underwent placebo therapy, spontaneous resolution increased significantly from 13% at 2 to 3.9 weeks of gestation to 36% at > or =10 weeks of gestation. Spontaneous resolution was more common with lower vaginal pH or lactobacilli on Gram stain at the time of random assignment. CONCLUSION: The effectiveness of metronidazole therapy of bacterial vaginosis persists for > or =10 weeks. Women who underwent placebo therapy had significant remission of bacterial vaginosis over > or =10 weeks. Remission was more common when the initial vaginal microbiologic disturbances were less severe.

Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas.

OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at <37 and <35 weeks of gestation, small-for-gestational-age infant, abruptio placentae, and perinatal death. Data were compared by using chi-square analysis and Wilcoxon rank sum test. RESULTS: The rates of preeclampsia and of severe preeclampsia were significantly higher in the previous preeclamptic group as compared to the nulliparous group (17.9% vs 5.3%, P <.0001, and 7.5% vs. 2.4%, P <.0001, respectively). Women who had recurrent preeclampsia experienced more preterm deliveries before 37 and 35 weeks of gestation than nulliparous women who developed preeclampsia. In addition, among women who developed severe preeclampsia, those with recurrent preeclampsia had higher rates of preterm delivery both before 37 weeks (67% vs 33%, P =.0004) and before 35 weeks of gestation (36% vs 19%, P =.041), and higher rates of abruptio placentae (6.7% vs 1.5%) and fetal death (6.7% vs 1.4%) than did nulliparous women. CONCLUSION: Compared to nulliparous women, women with preeclampsia in a previous pregnancy had significantly higher rates of preeclampsia and adverse perinatal outcomes associated with preterm delivery as a result of preeclampsia.