Kenneth J. Leveno

A revised birth weight reference for the United States

OBJECTIVE: To generate birth weight curves based on the obstetric estimate of gestational age as specified in the revised 2003 U.S. birth certificate. METHODS: Using National Center for Health Statistics data from 2011, we constructed birth weight curves for neonates between 24 and 42 weeks of gestation. Curves were developed using the obstetric estimate of gestational age that is included in the revised 2003 U.S. birth certificate, which, when available, incorporates ultrasound dating information. Live-born singleton neonates between 500 and 6,000 g without malformations were included. These curves were compared with curves we generated using 1991 data on which the current national reference of Alexander and colleagues is based, a reference that used only last menstrual period to establish gestational age. RESULTS: The 1991 curves were based on 3,684,778 U.S. live births and the 2011 on 3,252,011 births. Birth weight percentile values were greater from 28 to 36 weeks of gestation in the 1991 data set. That is, the birth weights for preterm neonates were overestimated when 1991 reference curves were used compared with the proposed 2011 reference. For example, in 1991, a birth weight of 2,000 g was at the 50th percentile between 31 and 32 weeks of gestation, whereas in 2011, a birth weight of 2,000 g now corresponds to the 50th percentile between 33 and 34 weeks of gestation. CONCLUSIONS: Our revised reference curve for the United States provides an updated national reference for birth weight. LEVEL OF EVIDENCE: II

Morbidly Adherent Placenta Treatments and Outcomes

OBJECTIVE: To describe recent maternal and neonatal delivery outcomes among women with a morbidly adherent placenta in major centers across the United States. METHODS: This study reviewed a cohort of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011 from the Assessment of Perinatal EXcellence data set. All cases of morbidly adherent placenta were identified. Maternal demographics, procedures undertaken, and maternal and neonatal outcomes were analyzed. RESULTS: There were 158 women with a morbidly adherent placenta (1/731 births, 95% confidence interval 1/632–866). Eighteen percent of women with a morbidly adherent placenta were nulliparous and 37% had no prior cesarean delivery. Only 53% (84/158) were suspected to have a morbidly adherent placenta before delivery. Women with a prenatally suspected morbidly adherent placenta experienced large blood loss (33%), hysterectomy (92%), and intensive care unit admission (39%) compared with 19%, 45%, and 22%, respectively, in those not suspected prenatally to have a morbidly adherent placenta (P<.05 for all). CONCLUSION: Eighteen percent of women with a morbidly adherent placenta were nulliparous. Half of the morbidly adherent placenta cases were suspected before delivery and outcomes were poorer in this group, probably because the more clinically significant morbidly adherent placentas are more likely to be suspected before delivery. LEVEL OF EVIDENCE: II

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

A Randomized Trial of the Effects of Antibiotic Prophylaxis on Epidural-Related Fever in Labor

BACKGROUND:It has been suggested that the development of maternal fever during epidural analgesia could be due to intrapartum infection. We investigated whether antibiotic prophylaxis before epidural placement decreases the rate of epidural-related fever. METHODS:In this double-blind, placebo-controlled trial, 400 healthy nulliparous women requesting epidural analgesia were randomly assigned to receive either cefoxitin 2 g or placebo immediately preceding initiation of epidural labor analgesia. Maternal tympanic temperature was measured hourly, and intrapartum fever was defined as a maternal temperature of ≥38°C. Neonates born to women with fever were evaluated for possible sepsis, and available placentas were evaluated for the presence of neutrophilic inflammation. The primary outcome was maternal fever during epidural analgesia. RESULTS:Thirty-eight percent of women in the cefoxitin group and 40% of women in the placebo group developed fever (P = 0.68). The risk difference (95% confidence interval) for fever ≥38°C during labor (antibiotic versus placebo) was −2.0% (−11.5 to 7.5), and for fever >39°C during labor was −1.5% (−4.7 to 1.7). Approximately half of each study group had placental neutrophilic inflammation, but administration of cefoxitin had no significant effect on any grade of neutrophilic inflammation. Fever developed significantly more often in the women with placental neutrophilic inflammation compared with those without such inflammation (73/158 vs 33/144, P < 0.001; risk difference 23% [95% confidence interval, 13.0–34.0]). There were no significant differences in any neonatal outcomes between the antibiotic and placebo study groups. Sepsis was not diagnosed in any of the infants. There were no neonatal deaths. CONCLUSION:Fever during labor epidural analgesia is associated with placental inflammation, but fever and placental inflammation were not reduced with antibiotic prophylaxis. This finding suggests that infection is unlikely to be the cause in its development.

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.

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

OBJECTIVE The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.

Glyburide in Women with Mild Gestational Diabetes: A Randomized Controlled Trial

OBJECTIVE: To evaluate whether the addition of glyburide to diet therapy modifies pregnancy outcomes in women with mild gestational diabetes. METHODS: Women with at least two abnormal values on a 3-hour, 100-g oral glucose tolerance test according to National Diabetes Data Group criteria and fasting values less than 105 mg/dL between 24 and 30 weeks of gestation were randomized to blinded glyburide or placebo study drug. All women were placed on a 35-kcal/kg diet and recorded four times daily capillary glucose measurements. The study drug was titrated based on weekly maternal capillary glucose values with targets of less than 95 mg/dL (5.3 mmol/L) and 120 mg/dL (6.7 mmol/L) for fasting and 2-hour postprandial glucose measurements, respectively. The primary study outcome was a 200-g birth weight decrement in neonates of women treated with glyburide. The sample size estimate for this outcome was 334 total randomized women with a one-to-one allocation. RESULTS: A total of 395 women were enrolled at a single center between September 2008 and October 2012. Women treated with glyburide had a significantly greater decline in fasting glucose values over the course of therapy. However, there was no difference in the primary study outcome. Specifically, the mean birth weight was 33 g lower in the group treated with glyburide (P=.52). Although not powered to examine all outcomes associated with gestational diabetes, treatment with glyburide did not affect need for operative delivery, shoulder dystocia, clavicular fracture, Erbs palsy, or neonatal hypoglycemia. Four women in each group required insulin. CONCLUSION: The addition of glyburide to diet therapy significantly improved maternal glycemic control over time when compared with placebo. However, adding glyburide to diet did not decrease birth weight or improve maternal or neonatal outcomes in women with mild gestational diabetes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00744965. LEVEL OF EVIDENCE: I

17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study

BACKGROUND: 17‐alpha Hydroxyprogesterone caproate for prevention of recurrent preterm birth is recommended for use in the United States. OBJECTIVE: We sought to assess the clinical effectiveness of 17‐alpha hydroxyprogesterone caproate to prevent recurrent preterm birth ≤35 weeks compared to similar births in our obstetric population prior to the implementation of 17‐alpha hydroxyprogesterone caproate. STUDY DESIGN: This was a prospective cohort study of 17‐alpha hydroxyprogesterone caproate in our obstetric population. The primary outcome was the recurrence of birth ≤35 weeks for the entire study cohort compared to a historical referent rate of 16.8% of recurrent preterm birth in our population. There were 3 secondary outcomes. First, did 17‐alpha hydroxyprogesterone caproate modify a womans history of preterm birth when taking into account her prior number and sequence of preterm and term births? Second, was recurrence of preterm birth related to 17‐alpha hydroxyprogesterone caproate plasma concentration? Third, was duration of pregnancy modified by 17‐alpha hydroxyprogesterone caproate treatment compared to a prior preterm birth? RESULTS: From January 2012 through March 2016, 430 consecutive women with prior births ≤35 weeks were treated with 17‐alpha hydroxyprogesterone caproate. Nearly two thirds of the women (N = 267) began injections ≤18 weeks and 394 (92%) received a scheduled weekly injection within 10 days of reaching 35 weeks or delivery. The overall rate of recurrent preterm birth was 25% (N = 106) for the entire cohort compared to the 16.8% expected rate (P = 1.0). The 3 secondary outcomes were also negative. First, 17‐alpha hydroxyprogesterone caproate did not significantly reduce the rates of recurrence regardless of prior preterm birth number or sequence. Second, plasma concentrations of 17‐alpha hydroxyprogesterone caproate were not different (P = .17 at 24 weeks; P = .38 at 32 weeks) between women delivered ≤35 weeks and those delivered later in pregnancy. Third, the mean (±SD) interval in weeks of recurrent preterm birth before 17‐alpha hydroxyprogesterone caproate use was 0.4 ± 5.3 weeks and the interval of recurrent preterm birth after 17‐alpha hydroxyprogesterone caproate treatment was 0.1 ± 4.7 weeks (P = .63). A side effect of weekly 17‐alpha hydroxyprogesterone caproate injections was an increase in gestational diabetes. Specifically, the rate of gestational diabetes was 13.4% in 17‐alpha hydroxyprogesterone caproate–treated women compared to 8% in case‐matched controls (P = .001). CONCLUSION: 17‐alpha Hydroxyprogesterone caproate was ineffective for prevention of recurrent preterm birth and was associated with an increased rate of gestational diabetes.

Prenatal Vitamin C and e supplementation in smokers is associated with reduced placental abruption and preterm birth: A secondary analysis

Smoking and pre‐eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self‐reported smoking status focusing on outcomes known to be impacted by maternal smoking.

Does the presence of a condition-specific obstetric protocol lead to detectable improvements in pregnancy outcomes?

OBJECTIVE We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes. STUDY DESIGN This was a cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery. RESULTS Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18-0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77-0.96). CONCLUSION The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful.