J.Peter VanDorsten

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.).

Predicting success of external cephalic version.

OBJECTIVE Many authors have identified prognostic factors for external cephalic version success, but there has not been an attempt to integrate these factors into a simple, quantitative scoring system for predicting version success. Nor have any prognostic factors been prospectively tested. STUDY DESIGN We examined the clinical characteristics of 108 consecutive breech versions performed between 1984 and 1986. These characteristics were evaluated by stepwise linear regression and discriminate analysis to identify those factors associated with success. Five factors explained the majority of the variability in outcome (parity, placental location, dilation, station, and estimated fetal weight). A model was developed to incorporate the trends identified among these five variables to create a scoring system similar to that of Bishop. This scoring system was then applied to 286 women undergoing external cephalic version since October 1986. RESULTS There was a positive relationship between a rising version score and the likelihood of successful breech version. No versions were successful with a score < or = 2, and all breech versions were successful with a score of 9 or 10. The results of the version score may have significantly altered physician recommendations in more than one third of cases. CONCLUSION We believe that this simple, quantifiable scoring system is a refinement in our ability to predict the likelihood of external cephalic version success.

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.

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.)

Fetal anomaly detection by second-trimester ultrasonography in a tertiary center

OBJECTIVE Our purpose was to determine the relative accuracy of indicated versus screening second-trimester ultrasonography for detection of fetal anomalies and to assess the cost effectiveness of anomaly screening. STUDY DESIGN The study population consisted of 2031 pregnant women with singleton gestations who prospectively underwent ultrasonographic scanning between 15 and 22 weeks and received complete obstetric care at the Medical University of South Carolina between July 1, 1993, and June 30, 1996. Patients were divided into two groups: (1) indicated and (2) screening. The cost of screening ultrasonography was compared with the cost of newborn care for selected anomalous fetuses. RESULTS Forty-seven fetuses (2.3%) were diagnosed by ultrasonography as having a major anomaly: 8.6% in the indicated group and 0.68% in the screening group (p=0.001). The sensitivity for detecting the anomalous fetus was 75.0% overall: 89.7% in the indicated group and 47.6% in the screening group (p=0.001). Of the 47 patients diagnosed with fetal anomalies, 11 (23.4%) chose pregnancy termination; of the 35 (74.5%) live-born anomalous infants, 29 (82.9%) were discharged alive. Projected newborn cost savings offset the cost of routine midtrimester screening. CONCLUSIONS Detection of anomalous fetuses was significantly better in the indicated compared with the screening group. Nevertheless, routine ultrasonographic screening appeared cost-effective in our population.

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

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.

Route of delivery for the breech presentation: A conundrum☆

OBJECTIVE Our purpose was to determine the feasibility of resolving the controversy regarding route of delivery for breech presentation in a randomized, prospective fashion. STUDY DESIGN The National Institute of Child Health and Human Development-sponsored Maternal-Fetal Medicine Units Network, which is composed of 11 perinatal centers, was surveyed to determine the feasibility of a randomized clinical trial of cesarean section versus trial of labor for breech presentation. A review of the literature was performed to determine the experience of other investigators with designing and conducting an adequate prospective, randomized trial. RESULTS Principal investigators and faculty from seven of 11 centers within the Maternal-Fetal Medicine Units Network agreed to participate adn felt that they could adequately recruit patients for a trial in very-low-birth-weight infants. This would provide approximately 200 very-low-birth-weight fetuses in a breech presentation per year. Sample size calculations indicated that 1700 infants would be required. Investigators also had strong reservations about performing a trial of vaginal breech delivery for other gestational ages. A review of the literature indicates that other authors have encountered difficulty in attempting randomized clinical trials of this nature. CONCLUSIONS The Maternal-Fetal Medicine Units Network with its pool of 60,000 deliveries per year agreed that a randomized, controlled delivery route of labor in the 24- to 28-week breech presentation was not feasible in a reasonable period of time. A randomized clinical trial of larger fetuses in a breech presentation was also considered extremely difficult. These findings are similar to those of other authors who have attempted or proposed randomized clinical trials to determine the safety of planned vaginal delivery of the breech presentation at various gestational ages.

Glucometer analysis of one-hour glucose challenge samples

OBJECTIVE Our purpose was to explore a cost-saving measure for diabetes screening by using glucometer testing on venous whole blood obtained after a 1-hour glucose challenge test. Glucometer results falling above an upper threshold would predict abnormal plasma values and mandate a glucose tolerance test; results below the lower threshold would predict normal plasma values and avoid further testing. Results between the thresholds would require traditional plasma analysis. STUDY DESIGN We performed a prospective cohort study on 222 consecutive pregnant women. A standard 50 gm glucose screen was performed with venous blood drawn at 1 hour. We immediately removed a drop of whole blood from the venous sample and analyzed it on a portable glucometer, Accu-Chek III. The remaining sample was submitted immediately for routine plasma analysis. All values were obtained on the same glucometer, which was calibrated daily in our clinic laboratory. Regression analysis was performed on 129 samples to select the two thresholds. The selected thresholds were then applied prospectively to the next 93 consecutive samples for validation. RESULTS Excellent correlation (r = 0.9045) exists between the glucometer and laboratory values. Glucometer threshold values of 110 mg/dl and 155 mg/dl were selected because they predicted plasma values < 135 mg/dl or > 135 mg/dl with 95% certainty, respectively. Prospectively, the thresholds were completely accurate in classifying the values. CONCLUSION Venous whole blood assayed by glucometer can reliably predict an elevated or normal automated plasma glucose value. By applying thresholds, three fourths of all patients can immediately receive reassuring information, whereas the patients with poorest glucose tolerance are immediately identified and diagnostic testing is scheduled. Additionally, our model reduces the number of automated laboratory studies by 80% and reduces the cost of diabetic screening.

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.