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/m2 ; 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.
Background Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. ...This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. This study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. Methods Brain development and affective problems were evaluated in 54 children (56% female), aged 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. Results Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). More than 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Furthermore, children with more affective problems had a thinner left rACC. Conclusions Fetal exposure to synthetic glucocorticoids has neurologic consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raise the possibility that glucocorticoid-associated neurologic changes increase vulnerability to mental health problems.
To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM).
In this ...prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models.
Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM.
There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.
Background Inadequate or excessive total gestational weight gain is associated with increased risks of small- and large-for-gestational-age births, respectively, but evidence is sparse regarding ...overall and trimester-specific patterns of gestational weight gain in relation to these risks. Characterizing the interrelationship between patterns of gestational weight gain across trimesters can reveal whether the trajectory of gestational weight gain in the first trimester sets the path for gestational weight gain in subsequent trimesters, thereby serving as an early marker for at-risk pregnancies. Objective We sought to describe overall trajectories of gestational weight gain across gestation and assess the risk of adverse birthweight outcomes associated with the overall trajectory and whether the timing of gestational weight gain (first vs second/third trimester) is differentially associated with adverse outcomes. Study Design We conducted a secondary analysis of a prospective cohort of 2802 singleton pregnancies from 12 US prenatal centers (2009 through 2013). Small and large for gestational age were calculated using sex-specific birthweight references <5th, <10th, or ≥90th percentiles, respectively. At each of the research visits, women’s weight was measured following a standardized anthropometric protocol. Maternal weight at antenatal clinical visits was also abstracted from the prenatal records. Semiparametric, group-based, latent class, trajectory models estimated overall gestational weight gain and separate first- and second-/third-trimester trajectories to assess tracking. Robust Poisson regression was used to estimate the relative risk of small- and large-for-gestational-age outcomes by the probability of trajectory membership. We tested whether relationships were modified by prepregnancy body mass index. Results There were 2779 women with a mean of 15 (SD 5) weights measured across gestation. Four distinct gestational weight gain trajectories were identified based on the lowest Bayesian information criterion value, classifying 10.0%, 41.8%, 39.2%, and 9.0% of the population from lowest to highest weight gain trajectories, with an inflection at 14 weeks. The average rate in each trajectory group from lowest to highest for 0-<14 weeks was –0.20, 0.04, 0.21, and 0.52 kg/wk and for 14-39 weeks was 0.29, 0.48, 0.63, and 0.79 kg/wk, respectively; the second lowest gaining trajectory resembled the Institute of Medicine recommendations and was designated as the reference with the other trajectories classified as low, moderate-high, or high. Accuracy of assignment was assessed and found to be high (median posterior probability 0.99, interquartile range 0.99-1.00). Compared with the referent trajectory, a low overall trajectory, but not other trajectories, was associated with a 1.55-fold (95% confidence interval, 1.06–2.25) and 1.58-fold (95% confidence interval, 0.88–2.82) increased risk of small-for-gestational-age <10th and <5th, respectively, while a moderate-high and high trajectory were associated with a 1.78-fold (95% confidence interval, 1.31–2.41) and 2.45-fold (95% confidence interval, 1.66–3.61) increased risk of large for gestational age, respectively. In a separate analysis investigating whether early (<14 weeks) gestational weight gain tracked with later (≥14 weeks) gestational weight gain, only 49% (n = 127) of women in the low first-trimester trajectory group continued as low in the second/third trimester, and had a 1.59-fold increased risk of small for gestational age; for the other 51% (n = 129) of women without a subsequently low second-/third-trimester gestational weight gain trajectory, there was no increased risk of small for gestational age (RR, 0.75; 95% confidence interval, 0.47–1.38). Prepregnancy body mass index did not modify the association between gestational weight gain trajectory and small for gestational age ( P = 0.52) or large for gestational age ( P = .69). Conclusion Our findings are reassuring for women who experience weight loss or excessive weight gain in the first trimester; however, the risk of small or large for gestational age is significantly increased if women gain weight below or above the reference trajectory in the second/third trimester.
Background Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation that are performed in controlled clinical settings. Currently, there ...are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated with the use of the same benchmarks as singleton growth. Objectives Our objective was to define the trajectory of fetal growth in dichorionic twins empirically using longitudinal 2-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard that was developed by our group for singletons. Study Design A prospective cohort of 171 women with twin gestations was recruited from 8 US sites from 2012–2013. After an initial sonogram at 11 weeks 0 days–13 weeks 6 days of gestation during which dichorionicity was confirmed, women were assigned randomly to 1 of 2 serial ultrasonography schedules. Growth curves and percentiles were estimated with the use of linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education, and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories with the use of likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements in which there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests that were computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, which was defined as <10th percentile that would be introduced if fetal growth estimation for twins was based on an unweighted singleton standard. Results Women underwent a median of 5 ultrasound scans. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks of gestation; biparietal diameter in twins was smaller from 34–36 weeks of gestation. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks of gestation, which indicated a comparatively asymmetric growth pattern. At 35 weeks of gestation, the average gestational age at delivery for twins, the estimated fetal weights for the 10th, 50th, and 90th percentiles were 1960, 2376, and 2879 g for dichorionic twins, respectively, and 2180, 2567, and 3022 g for the singletons, respectively. At 32 weeks of gestation, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age with the use of a singleton, non-Hispanic white standard. By 35 weeks of gestation, 38% of twins would be classified as small for gestational age. Conclusion The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks of gestation, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard.
Adherence to alternate Healthy Eating Index (AHEI), alternate Mediterranean diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) has been linked to lower risks of chronic diseases. ...However, their associations with common pregnancy complications are unclear.
This study investigates the associations of AHEI, AMED, and DASH during periconception and pregnancy with common pregnancy complication risks.
The study included 1887 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons. Women responded to an FFQ at 8–13 gestational weeks, and they performed a 24-h dietary recall at 16–22 and 24–29 wk. Gestational diabetes (GDM), gestational hypertension, preeclampsia, and preterm delivery were ascertained using medical records.
Healthier diet indicated by higher AHEI, AMED, and DASH scores was generally related to lower risks of pregnancy complications. Significant inverse associations were observed between AHEI score reported at 16–22 wk and GDM risk adjusted RR (95% CI), highest (Q4) vs. lowest quartile (Q1): 0.32 (0.16, 0.66), P-trend = 0.002; DASH score reported at both 8–13 adjusted RR (95% CI), Q4 vs. Q1: 0.45 (0.17, 1.17), P-trend = 0.04 and 16–22 wk adjusted RR (95% CI), Q4 vs. Q1: 0.19 (0.05, 0.65), P-trend = 0.01 and gestational hypertension risk; AHEI score reported at 24–29 wk and preeclampsia risk adjusted RR (95% CI), Q4 vs. Q1: 0.31 (0.11, 0.87), P-trend = 0.03; AMED score reported at 8–13 wk adjusted RR (95% CI), Q4 vs. Q1: 0.50 (0.25, 1.01), P-trend = 0.03 and DASH score reported at 24–29 wk adjusted RR (95% CI), Q4 vs. Q1: 0.50, (0.26, 0.96), P-trend = 0.03 and preterm delivery risk.
Adherence to AHEI, AMED, or DASH during periconception and pregnancy was related to lower risks of GDM, gestational hypertension, preeclampsia, and preterm delivery.
This study was registered at ClinicalTrials.gov as NCT00912132.
Abstract Background Experimental and epidemiologic data suggest that among non-pregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly ...complain of poor sleep, few studies have objectively evaluated the quality of sleep in pregnancy or have explored the relationship between sleep disturbances and maternal and perinatal outcomes. Objectives Our objective was to examine the relationship between objectively assessed sleep duration, timing and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. Study Design This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks’ gestation. They were asked to wear a wrist actigraphy monitor and to complete a daily sleep log for a seven consecutive-day period. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (< 7 hours/night), late sleep midpoint (midpoint between sleep onset and sleep offset > 5 AM), and top quartile of minutes of wake time after sleep onset (WASO) and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes (GDM). Chi-square tests were used to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and GDM. For associations that were significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. Results Nine-hundred and one eligible women consented to participate. Of these women 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of GDM (OR 2.24, 95% CI 1.11, 4.53; OR 2.58, 95% CI 1.24, 5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with GDM remained significant (aOR 2.06, 95% CI 1.01, 4.19; aOR 2.37, 95% CI 1.13, 4.97, respectively). Additionally, after adjusting separately for age, BMI and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with GDM. No associations were demonstrated between the sleep quality measures (WASO, sleep fragmentation) and hypertensive disorders or GDM. Conclusions Our results demonstrate a relationship between short sleep duration and later sleep midpoint with GDM. Our data suggest independent contributions of these two sleep characteristics to the risk for GDM in nulliparous women.
To assess the relationships between self-reported psychosocial stress and preterm birth, hypertensive disease of pregnancy, and small-for-gestational-age (SGA) birth and to assess the extent to which ...these relationships account for racial and ethnic disparities in these adverse outcomes.
Self-reported measures of psychosocial stress (perceived stress, depression, racism, anxiety, resilience, and social support) were collected during pregnancy among a racially and ethnically diverse cohort of women enrolled in a prospective observational study of nulliparous women with singleton pregnancies, from eight clinical sites across the United States, between October 2010 and May 2014. The associations of preterm birth, hypertensive disease of pregnancy, and SGA birth with the self-reported measures of psychosocial stress as well as with race and ethnicity were evaluated.
The study included 9,470 women (60.4% non-Hispanic white, 13.8% non-Hispanic black, 16.7% Hispanic, 4.0% Asian, and 5.0% other). Non-Hispanic black women were significantly more likely to experience any preterm birth, hypertensive disease of pregnancy, and SGA birth than were non-Hispanic white women (12.2% vs 8.0%, 16.7% vs 13.4%, and 17.2% vs 8.6%, respectively; P<.05 for all). After adjusting for potentially confounding factors, including the six different psychosocial factors singly and in combination, non-Hispanic black women continued to be at greater risk of any preterm birth and SGA birth compared with non-Hispanic white women.
Among a large and geographically diverse cohort of nulliparous women with singleton gestations, non-Hispanic black women are most likely to experience preterm birth, hypertensive disease of pregnancy, and SGA birth. These disparities were not materially altered for preterm birth or SGA birth by adjustment for demographic differences and did not appear to be explained by differences in self-reported psychosocial factors.
Objective The primary aim of the “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, ...and environmental factors that predict adverse pregnancy outcomes. Study Design Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks’ gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. Results We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. Conclusion The “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” cohort study methods and procedures can help investigators when they plan future projects.
To examine the association between ischemic-hypoxic conditions (IHCs) and attention-deficit/hyperactivity disorder (ADHD) by gestational age and race/ethnicity.
Nested case-control study using the ...Kaiser Permanente Southern California (KPSC) medical records. The study cohort included children aged 5 to 11 years who were delivered and cared for in the KPSC between 1995 and 2010 (N = 308,634). Case children had a diagnosis of ADHD and received ≥ 2 prescriptions specific to ADHD during the follow-up period. For each case, 5 control children were matched by age at diagnosis. Exposures were defined by using International Classification of Diseases, Ninth Revision codes. A conditional regression model was used to estimate adjusted odds ratios (ORs).
Among eligible children, 13,613 (4.3%) had a diagnosis of ADHD. Compared with control children, case children were more likely to be male and of white or African American race/ethnicity. Case children were more likely to be exposed to IHCs (OR = 1.16, 95% confidence interval CI 1.11-1.21). When stratified by gestational age, cases born at 28 to 33, 34 to 36, and 37 to 42 weeks of gestation, were more likely to be exposed to IHCs (ORs, 1.6 95% CI 1.2-2.1, 1.2 95% CI 1.1-1.3, and 1.1 95% CI 1.0-1.2, respectively) compared with controls. IHC was associated with increased odds of ADHD across all race/ethnicity groups.
These findings suggest that IHCs, especially birth asphyxia, respiratory distress syndrome, and preeclampsia, are independently associated with ADHD. This association was strongest in preterm births.
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