Jagteshwar Grewal

Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies

BACKGROUND This study examined the association between maternal smoking and alcohol use (including binge drinking) during the periconceptional period (i.e., 2 months before through 2 months after conception) and the risk of orofacial clefts, NTDs, and conotruncal heart defects in offspring. METHODS Data were drawn from a population-based case-control study of fetuses and live-born infants among a cohort of California births between July 1999 and June 2003. The 1,355 cases comprised of 701 orofacial clefts, 337 NTDs, and 323 conotruncal heart defects. Information on smoking and alcohol consumption was obtained via telephone interviews with mothers of 1,355 (80% of eligibles) cases and 700 (77% of eligibles) nonmalformed, live-born controls. RESULTS Maternal smoking of five cigarettes or less per day was associated with reduced risks of NTDs (OR 0.7; 95% CI: 0.3, 1.4), whereas the risk associated with higher cigarette consumption was lower for conotruncal heart defects (OR 0.5; 95% CI: 0.2, 1.2). Maternal intake of alcohol less than 1 day per week was associated with a 1.6- to 2.1-fold higher risk of NTDs (95% CI: 0.9, 2.6), d-transposition of the great arteries (95% CI: 1.1, 3.2), and multiple cleft lip with or without cleft palate (CLP) (95% CI: 0.8, 4.5). Risks associated with more frequent alcohol intake were 2.1 for NTDs (95% CI: 1.1, 4.0) and 2.6 for multiple CLP (95% CI: 1.1, 6.1). CONCLUSIONS This study observed that maternal alcohol intake increased the risk for d-transposition of the great arteries, NTDs, and multiple CLP in infants. By contrast, smoking was associated with a lower risk of NTDs and conotruncal heart defects.

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.

Thyroid Diseases and Adverse Pregnancy Outcomes in a Contemporary US Cohort

CONTEXT Thyroid diseases are inconsistently reported to increase risk for pregnancy complications. OBJECTIVE The objective of this study was to study pregnancy complications associated with common and uncommon thyroid diseases. DESIGN, SETTING, AND PARTICIPANTS We analyzed singleton pregnancies (N = 223 512) from a retrospective US cohort, the Consortium on Safe Labor (2002-2008). Thyroid diseases and outcomes were derived from electronic medical records. Multivariable logistic regression with generalized estimating equations estimated adjusted odds ratios (ORs) with 99% confidence intervals (99% CI). MAIN OUTCOME MEASURES Hypertensive diseases, diabetes, preterm birth, cesarean sections, inductions, and intensive care unit (ICU) admissions were analyzed. RESULTS Primary hypothyroidism was associated with increased odds of preeclampsia (OR = 1.47, 99% CI = 1.20-1.81), superimposed preeclampsia (OR = 2.25, 99% CI = 1.53-3.29), gestational diabetes (OR = 1.57, 99% CI = 1.33-1.86), preterm birth (OR = 1.34, 99% CI = 1.17-1.53), induction (OR = 1.15, 99% CI = 1.04-1.28), cesarean section (prelabor, OR = 1.31, 99% CI = 1.11-1.54; after spontaneous labor OR = 1.38, 99% CI = 1.14-1.66), and ICU admission (OR = 2.08, 99% CI = 1.04-4.15). Iatrogenic hypothyroidism was associated with increased odds of placental abruption (OR = 2.89, 99% CI = 1.14-7.36), breech presentation (OR = 2.09, 99% CI = 1.07-4.07), and cesarean section after spontaneous labor (OR = 2.05, 99% CI = 1.01-4.16). Hyperthyroidism was associated with increased odds of preeclampsia (OR = 1.78, 99% CI = 1.08-2.94), superimposed preeclampsia (OR = 3.64, 99% CI = 1.82-7.29), preterm birth (OR = 1.81, 99% CI = 1.32-2.49), induction (OR = 1.40, 99% CI = 1.06-1.86), and ICU admission (OR = 3.70, 99% CI = 1.16-11.80). CONCLUSIONS Thyroid diseases were associated with obstetrical, labor, and delivery complications. Although we lacked information on treatment during pregnancy, these nationwide data suggest either that there is a need for better thyroid disease management during pregnancy or that there may be an intrinsic aspect of thyroid disease that causes poor pregnancy outcomes.

Induction of Labor in a Contemporary Obstetric Cohort

OBJECTIVE We sought to describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. STUDY DESIGN This was a retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002 through 2008. RESULTS Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe vs unripe cervix, particularly for multiparas (86.6-100%). CONCLUSION Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate.

Primary Cesarean Delivery Among Parous Women in the United States, 1990 – 2003

OBJECTIVE: To explore trends in primary cesarean delivery rates among parous women with singleton pregnancies in the United States between 1990 and 2003. METHODS: The analysis used data from national birth files based on U.S. birth certificates between 1990 and 2003. The primary cesarean delivery rate was defined as the number of primary cesarean deliveries per 100 deliveries among parous women with singleton pregnancies who have not had a previous cesarean delivery. A stratified analysis was employed to investigate whether trends varied by maternal age, gestational age, race/ethnicity, or region. RESULTS: In the United States, the primary cesarean delivery rate among parous women decreased modestly from 7.1% in 1990 to 6.6% in 1996 but increased progressively to 9.3% in 2003. The increase in cesarean rates from 1996 to 2003 varied substantially by race/ethnicity: Hispanic and non-Hispanic white women exhibited lower and similar rates, whereas rates for non-Hispanic black women were consistently higher and rose by a far greater extent across the years. There were substantial differences in cesarean delivery trends across geographic divisions, with greatest increases observed in the mid-Atlantic, South Central, and South Atlantic areas of the United States. Primary cesarean rates also declined considerably with increasing gestational age. CONCLUSION: Similar to the overall cesarean delivery rate, primary cesarean rates among parous women with singleton pregnancies have increased substantially in the United States since 1996. LEVEL OF EVIDENCE: III

Effects of Interpregnancy Interval on Blood Pressure in Consecutive Pregnancies

The lower risk of preeclampsia observed in parous women has prompted a hypothesis that cardiovascular adaptation from a first pregnancy has ongoing benefits which contribute to a reduced risk of preeclampsia in the second pregnancy. However, how the interpregnancy interval affects mean arterial pressure (MAP) as an indicator of cardiovascular adaptation in subsequent pregnancies has not been well studied. The authors examined the effect of interpregnancy interval on MAP in consecutive pregnancies using data from the Collaborative Perinatal Project (1959-1965) and a semiparametric random-effects regression model. Prenatal MAP measurements were available for 533 women with both first and second births. MAP was lower in the second pregnancy (by approximately 2 mmHg) for very short interpregnancy intervals. However, this difference diminished when the interval increased, and it totally disappeared for intervals longer than 2 years. The authors conclude that although MAP is lower in the second pregnancy than in the first pregnancy, the effect persists for only a short time. It is therefore unlikely that mechanisms involving MAP as an indicator of cardiovascular adaptation contribute appreciably to the reduced risk of preeclampsia in subsequent pregnancies. However, it does not rule out the possibility that other mechanisms of cardiovascular adaptation persist longer.

Ultrasound Quality Assurance for Singletons in the National Institute of Child Health and Human Development Fetal Growth Studies.

To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability.

Predicting Large Fetuses at Birth: Do multiple ultrasound examinations and longitudinal statistical modelling improve prediction?

Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant size was classified as large-for-gestational age (LGA, >90th centile) and macrosomia (>4000 g) or not. We used a longitudinal random effects model with quadratic fixed and random effects to predict term LGA and macrosomia at birth. Receiver-operator curves and mean-squared error were used to measure accuracy of the prediction. Ultrasound examination around 37 weeks had the best accuracy in predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations at earlier gestations did not improve the accuracy. Adjusting for maternal characteristics had limited impact on the accuracy of prediction. Thus, a single ultrasound examination at late gestation close to birth is the simplest method currently available to predict LGA and macrosomia.

Association of maternal obesity with longitudinal ultrasonographic measures of fetal growth: Findings from the nichd fetal growth studies-singletons

Importance Despite the increasing prevalence of pregravid obesity, systematic evaluation of the association of maternal obesity with fetal growth trajectories is lacking. Objective To characterize differences in fetal growth trajectories between obese and nonobese pregnant women, and to identify the timing of any observed differences. Design, Setting, and Participants The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons study enrolled cohorts of pregnant women at 12 US health care institutions. Obese women (with prepregnancy body mass index > 30) and nonobese women (prepregnancy body mass indexes, 19-29.9) without major chronic diseases were recruited between 8 weeks and 0 days’ gestation and 13 weeks and 6 days’ gestation. A mixed longitudinal randomization scheme randomized participants into 1 of 4 schedules for 2-dimensional and 3-dimensional ultrasonograms to capture weekly fetal growth data throughout the remainder of their pregnancies. Main Outcomes and Measures On each ultrasonogram, fetal humerus length, femur length, biparietal diameter, head circumference, and abdominal circumference were measured. Fetal growth curves were estimated using linear mixed models with cubic splines. Median differences in the fetal measures at each gestational week of the obese and nonobese participants were examined using the likelihood ratio and Wald tests after adjustment for maternal characteristics. Results The study enrolled 468 obese and 2334 nonobese women between 8 weeks and 0 days’ gestation and 13 weeks and 6 days’ gestation. After a priori exclusion criteria, 443 obese and 2320 nonobese women composed the final cohort. Commencing at 21 weeks’ gestation, femur length and humerus length were significantly longer for fetuses of obese woman than those of nonobese women. Differences persisted in obese and nonobese groups through 38 weeks’ gestation (median femur length, 71.0 vs 70.2 mm; P = .01; median humerus length, 62.2 vs 61.6 mm; P = .03). Averaged across gestation, head circumference was significantly larger in fetuses of obese women than those of nonobese women (P = .02). Fetal abdominal circumference was not greater in the obese cohort than in the nonobese cohort but was significantly larger than in fetuses of normal-weight women (with body mass indexes between 19.0-24.9) commencing at 32 weeks (median, 282.1 vs 280.2 mm; P = .04). Starting from 30 weeks’ gestation, estimated fetal weight was significantly larger for the fetuses of obese women (median, 1512 g [95% CI, 1494-1530 g] vs 1492 g [95% CI, 1484-1499 g]) and the difference grew as gestational age increased. Birth weight was higher by almost 100 g in neonates born to obese women than to nonobese women (mean, 3373.2 vs 3279.5 g). Conclusions and Relevance As early as 32 weeks’ gestation, fetuses of obese women had higher weights than fetuses of nonobese women. The mechanisms and long-term health implications of these findings are not yet established.

Clarification of estimating fetal weight between 10-14 weeks gestation, NICHD fetal growth studies

TO THE EDITORS: We recently discovered an aspect of our paper entitled “Racial/ethnic differences in fetal growth, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies” that we want to bring to readers’ attention but one that does not change the results or interpretation of the work in any way. For researchers wanting to replicate our methods, we want to point out that our published paper does not clearly state how we modeled estimated fetal weight (EFW) between 10 and 14 weeks’ gestation. Given the clinical uncertainty associated with EFW before 15 weeks, our original intent was to not report EFW based on the actual measurements taken by sonographers between 10 and 14 weeks but to extrapolate data from the measurements taken at 15 weeks. Because the data used for all other fetal growth parameters (eg, biparietal diameter, head circumference, abdominal