Katherine L. Grantz

Racial/ethnic standards for fetal growth: The NICHD Fetal Growth Studies

OBJECTIVE Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. STUDY DESIGN We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. RESULTS EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). CONCLUSION Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus

BACKGROUND Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. METHODS Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5μm (PM2.5) and PM2.5 constituents, PM ≤ 10μm (PM10), nitrogen oxides (NOx), carbon monoxide, sulfur dioxide (SO2) and ozone (O3) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1-24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. RESULTS Preconception maternal exposure to NOX (RR=1.09, 95% CI: 1.04, 1.13) and SO2 (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O3 was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. CONCLUSION Maternal exposures to NOx and SO2 preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O3 appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation.

Obstetric and Neonatal Risks Among Obese Women Without Chronic Disease.

OBJECTIVE: To investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease. METHODS: Singleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race–ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site. RESULTS: Obstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose–response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86–2.13], 2.94 [2.73–3.18], 3.97 [3.61–4.36], and 5.47 [4.96–6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose–response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45–1.58), 1.74 (1.65–1.83), 1.93 (1.79–2.07), and 2.32 (2.14–2.52) as BMI category increased. CONCLUSION: Prepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases.

Adverse Maternal and Neonatal Outcomes in Adolescent Pregnancy.

STUDY OBJECTIVE To investigate the outcomes of adolescent pregnancy. DESIGN Retrospective cohort study from the Consortium on Safe Labor between 2002 and 2008. SETTING Twelve clinical centers with 19 hospitals in the United States. PARTICIPANTS Nulliparous women (n = 43,537) younger than 25 years of age, including 1189 younger adolescents (age ≤ 15.9 years), 14,703 older adolescents (age 16-19.9 years), and 27,645 young adults (age 20-24.9 years). INTERVENTIONS Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated, controlling for maternal characteristics and pregnancy complications (young adults as a reference group). MAIN OUTCOME MEASURES Maternal, neonatal outcomes, cesarean indications, and length of labor. RESULTS Younger adolescents had an increased risk of maternal anemia (aOR = 1.25; 95% CI, 1.07-1.45), preterm delivery at less than 37 weeks of gestation (aOR = 1.36; 95% CI, 1.14-1.62), postpartum hemorrhage (aOR = 1.46; 95% CI, 1.10-1.95), preeclampsia or hemolysis, increased liver enzyme levels, and low platelet syndrome (aOR = 1.44; 95% CI, 1.17-1.77) but had a decreased risk of cesarean delivery (aOR = 0.49; 95% CI, 0.42-0.59), chorioamnionitis (aOR = 0.63; 95% CI, 0.47-0.84), and neonatal intensive care unit admission (aOR = 0.80; 95% CI, 0.65-0.98). Older adolescents had an increased risk of maternal anemia (aOR = 1.15; 95% CI, 1.09-1.22), preterm delivery at less than 37 weeks of gestation (aOR = 1.16; 95% CI, 1.08-1.25), and blood transfusion (aOR = 1.21; 95% CI, 1.02-1.43), but had a decreased risk of cesarean delivery (aOR = 0.75; 95% CI, 0.71-0.79), chorioamnionitis (aOR = 0.83; 95% CI, 0.75-0.91), major perineal laceration (aOR = 0.82; 95% CI, 0.71-0.95), and neonatal intensive care unit admission (aOR = 0.89; 95% CI, 0.83-0.96). Older adolescents were less likely to have a cesarean delivery for failure to progress or cephalopelvic disproportion (aOR = 0.89; 95% CI, 0.81-0.98). For adolescents who entered spontaneous labor, the second stage of labor was shorter (P < .01). CONCLUSION Adolescents were less likely to have a cesarean delivery. Failure to progress or cephalopelvic disproportion occurred less frequently in older adolescents. Adolescents who entered spontaneous labor had a shorter second stage of labor.

Previous prelabor or intrapartum cesarean delivery and risk of placenta previa

OBJECTIVE The purpose of this study was to examine the association between previous cesarean delivery and subsequent placenta previa while distinguishing cesarean delivery before the onset of labor from intrapartum cesarean delivery. STUDY DESIGN We conducted a retrospective cohort study of electronic medical records from 20 Utah hospitals (2002-2010) with restriction to the first 2 singleton deliveries of nulliparous women at study entry (n=26,987). First pregnancy delivery mode was classified as (1) vaginal (reference), (2) cesarean delivery before labor onset (prelabor), or (3) cesarean delivery after labor onset (intrapartum). Risk of second delivery previa was estimated by previous delivery mode with the use of logistic regression and was adjusted for maternal age, insurance, smoking, comorbidities, previous pregnancy loss, and history of previa. RESULTS Most first deliveries were vaginal (82%; n=22,142), followed by intrapartum cesarean delivery (14.6%; n=3931), or prelabor cesarean delivery (3.4%; n=914). Incidence of second delivery previa was 0.29% (n=78) and differed by previous delivery mode: vaginal, 0.24%; prelabor cesarean delivery, 0.98%; intrapartum cesarean delivery, 0.38% (P<.001). Relative to vaginal delivery, previous prelabor cesarean delivery was associated with an increased risk of second delivery previa (adjusted odds ratio, 2.62; 95% confidence interval, 1.24-5.56). There was no significant association between previous intrapartum cesarean delivery and previa (adjusted odds ratio, 1.22; 95% confidence interval, 0.68-2.19). CONCLUSION Previous prelabor cesarean delivery was associated with a >2-fold significantly increased risk of previa in the second delivery, although the approximately 20% increased risk of previa that was associated with previous intrapartum cesarean delivery was not significant. Although rare, the increased risk of placenta previa after previous prelabor cesarean delivery may be important when considering nonmedically indicated prelabor cesarean delivery.

Joint Effects of Structural Racism and Income Inequality on Small-for-Gestational-Age Birth

OBJECTIVES We examined potential synergistic effects of racial and socioeconomic inequality associated with small-for-gestational-age (SGA) birth. METHODS Electronic medical records from singleton births to White and Black women in 10 US states and the District of Columbia (n = 121 758) were linked to state-level indicators of structural racism, including the ratios of Blacks to Whites who were employed, were incarcerated, and had a bachelors or higher degree. We used state-level Gini coefficients to assess income inequality. Generalized estimating equations models were used to quantify the adjusted odds of SGA birth associated with each indicator and the joint effects of structural racism and income inequality. RESULTS Structural racism indicators were associated with higher odds of SGA birth, and similar effects were observed for both races. The joint effects of racial and income inequality were significantly associated with SGA birth only when levels of both were high; in areas with high inequality levels, adjusted odds ratios ranged from 1.81 to 2.11 for the 3 structural racism indicators. CONCLUSIONS High levels of racial inequality and socioeconomic inequality appear to increase the risk of SGA birth, particularly when they co-occur.

Racial/ethnic differences in preterm perinatal outcomes.

Background: Racial disparities in preterm birth and infant death have been well documented. Less is known about racial disparities in neonatal morbidities among infants who are born at <37 weeks of gestation. Objective: The purpose of this study was to determine whether the risk for morbidity and death among infants who are born preterm differs by maternal race. Study Design: A retrospective cohort design included medical records from preterm deliveries of 19,325 black, Hispanic, and white women in the Consortium on Safe Labor. Sequentially adjusted Poisson models with generalized estimating equations estimated racial differences in the risk for neonatal morbidities and death, controlling for maternal demographics, health behaviors, and medical history. Sex differences between and within race were examined. Results: Black preterm infants had an elevated risk for perinatal death, but there was no difference in risk for neonatal death across racial groups. Relative to white infants, black infants were significantly more likely to experience sepsis (9.1% vs 13.6%), peri‐ or intraventricular hemorrhage (2.6% vs 3.3%), intracranial hemorrhage (0.6% vs 1.8%), and retinopathy of prematurity (1.0% vs 2.6%). Hispanic and white preterm neonates had similar risk profiles. In general, female infants had lower risk relative to male infants, with white female infants having the lowest prevalence of a composite indicator of perinatal death or any morbidity across all races (30.9%). Differences in maternal demographics, health behaviors, and medical history did little to influence these associations, which were robust to sensitivity analyses of pregnancy complications as potential underlying mechanisms. Conclusion: Preterm infants were at similar risk for neonatal death, regardless of race; however, there were notable racial disparities and sex differences in rare, but serious, adverse neonatal morbidities.

Maternal and Neonatal Outcomes by Attempted Mode of Operative Delivery From a Low Station in the Second Stage of Labor.

OBJECTIVE: To evaluate maternal and neonatal outcomes by attempted mode of operative delivery from a low station in the second stage of labor. METHODS: Retrospective study of 2,518 women carrying singleton fetuses at 37 weeks of gestation or greater who underwent attempted forceps-assisted delivery, attempted vacuum-assisted vaginal delivery, or cesarean delivery from a low station in the second stage of labor. Primary outcomes were stratified by parity and included a maternal adverse outcome composite (postpartum hemorrhage, transfusion, endometritis, peripartum hysterectomy, or intensive care unit admission) and a neonatal adverse outcome composite (5-minute Apgar score less than 4, respiratory morbidity, neonatal intensive care unit admission, shoulder dystocia, birth trauma, or sepsis). RESULTS: In nulliparous patients, the maternal adverse composite was not significantly different between women who underwent attempted forceps (12.1% compared with 10.8%, adjusted odds ratio [OR] 0.77, 95% confidence interval [CI] 0.40–1.34) or vacuum (8.3% compared with 10.8%, adjusted OR 0.68, 95% CI 0.40–1.16) delivery compared with cesarean delivery. Among parous women, the maternal adverse composite was not significantly different with attempted forceps (10.7% compared with 12.5%, adjusted OR 0.40, 95% CI 0.09–1.71) or vacuum (11.3% compared with 12.5%, adjusted OR 0.44, 95% CI 0.11–1.72) compared with cesarean delivery. Compared with neonates delivered by cesarean, the neonatal adverse composite was significantly lower among neonates born to nulliparous women who underwent attempted forceps (9.4% compared with 16.7%, adjusted OR 0.44, 95% CI 0.27–0.72) but not among those who underwent vacuum delivery (11.9% compared with 16.7%, adjusted OR 0.68, 95% CI 0.44–1.04). Among parous women, the neonatal adverse composite was not significantly different after attempted forceps (4.1% compared with 12.5%, adjusted OR 0.28, 95% CI 0.06–1.35) or vacuum (12.5% compared with 12.5%, adjusted OR 1.03, 95% CI 0.28–3.87) compared with cesarean delivery. CONCLUSION: A trial of forceps delivery from a low station compared with cesarean delivery was associated with decreased neonatal morbidity among neonates born to nulliparous women. LEVEL OF EVIDENCE: II

Persistent organic pollutants and pregnancy complications.

We sought to investigate the relationship between maternal preconception exposures to persistent organic pollutants (POPs) and pregnancy complications, gestational diabetes (GDM) and gestational hypertension. Data from 258 (51%) women with human chorionic gonadotropin (hCG) confirmed pregnancies reaching ≥24weeks gestation, from a prospective cohort of 501 couples who discontinued contraception to attempt pregnancy, were analyzed. Preconception concentrations of 9 organochlorine pesticides (OCPs) and 10 polybrominated diphenyl ethers (PBDEs) were quantified in serum. In separate multiple logistic regression models of self-reported physician diagnosed outcomes: GDM (11%) and gestational hypertension (10%), chemicals were natural log-transformed and rescaled by their standard deviation (SD). Models were adjusted for serum lipids, and then adjusted for age, body mass index, race, and smoking. Models were additionally adjusted for the sum of the remaining POPs in each chemical class. Womens serum concentration of PBDE congener 153 (PBDE-153) was positively associated with an increased odds of GDM per SD increase in log-transformed concentration, for unadjusted (OR=1.36, 95%CI: 1.02-1.81), a priori adjusted (OR=1.38, 95% CI: 1.03-1.86) and with the sum of remaining PBDEs (OR=1.79, 95% CI: 1.18, 2.74) models. Our findings suggest that at environmentally relevant concentrations, maternal exposure to POPs prior to conception may contribute to increased chance of developing GDM.

Air pollution exposure and preeclampsia among US women with and without asthma

Maternal asthma and air pollutants have been independently associated with preeclampsia but rarely studied together. Our objective was to comprehensively evaluate preeclampsia risk based on the interaction of maternal asthma and air pollutants. Preeclampsia and asthma diagnoses, demographic and clinical data came from electronic medical records for 210,508 singleton deliveries. Modified Community Multiscale Air Quality models estimated preconception, first and second trimester and whole pregnancy exposure to: particulate matter (PM)<2.5 and <10µm, ozone, nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO); PM2.5 constituents; volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Asthma-pollutant interaction adjusted relative risks (RR) and 95% confidence intervals (CI) for preeclampsia were calculated by interquartile range for criteria pollutants and high exposure (≥75th percentile) for PAHs and VOCs. Asthmatics had higher risk associated with first trimester NOx and SO2 and whole pregnancy elemental carbon (EC) exposure than non-asthmatics, but only EC significantly increased risk (RR=1.11, CI:1.03-1.21). Asthmatics also had a 10% increased risk associated with second trimester CO. Significant interactions were observed for nearly all VOCs and asthmatics had higher risk during all time windows for benzene, ethylbenzene, m-xylene, o-xylene, p-xylene and toluene while most PAHs did not increase risk.