Comparing Fetal Ultrasound Biometric Measurements to Neonatal Anthropometry at the Extremes of Birthweight.

OBJECTIVE: Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. STUDY DESIGN: We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th-90th), and large-for-gestational age (LGA, >90th) newborns. RESULTS: Average differences between EFW and birthweight for SGA neonates were: -40.2 g (confidence interval [CI]: -82.1, 1.6) at 14 days versus 13.6 g (CI: -52.4, 79.7) at 7 days; for AGA, -122.4 g (-139.6, -105.1) at 14 days versus -27.2 g (-50.4, -4.0) at 7 days; and for LGA, -242.8 g (-306.5, -179.1) at 14 days versus -72.1 g (-152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. CONCLUSION: Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. KEY POINTS: · Ultrasound measurements may be inadequate to predict neonatal size at birth.. · Birthweight estimation error is higher for neonates >90th percentile.. · There is higher error in AC closer to birth..

Longitudinal changes in maternal anthropometry in relation to neonatal anthropometry.

OBJECTIVE: To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition. DESIGN: In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15-28 weeks) and third trimester (28-39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes. SETTING: Women were recruited from twelve US sites (2009-2013).ParticipantsNon-obese women with singleton pregnancies (n 2334). RESULTS: A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (-0·57 to -0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (-0·05 to 0·06 mm per week). CONCLUSIONS: The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.

Fetal growth velocity: the NICHD fetal growth studies.

BACKGROUND: Accurately identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses. OBJECTIVE: We sought to complement fetal size standards with fetal growth velocity, develop a model to compute fetal growth velocity percentiles for any given set of gestational week intervals, and determine association between fetal growth velocity and birthweight. STUDY DESIGN: This was a prospective cohort study with data collected at 12 US sites (2009 through 2013) from 1733 nonobese, low-risk pregnancies included in the singleton standard. Following a standardized sonogram at 10w0d-13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16-22, 24-29, 30-33, 34-37, and 38-41 weeks). Study visits could occur ± 1 week from the targeted GA. Ultrasound biometric measurements included biparietal diameter, head circumference, abdominal circumference, and femur length, and estimated fetal weight was calculated. We used linear mixed models with cubic splines for the fixed effects and random effects to flexibly model ultrasound trajectories. We computed velocity percentiles in 2 ways: (1) difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) difference between any 2 ultrasounds at a clinically reasonable difference between 2 gestational ages (ie, velocity calculator). We compared correlation between fetal growth velocity percentiles and estimated fetal weight percentiles at 4-week intervals, with 32 (±1) weeks' gestation for illustration. Growth velocity was computed as estimated fetal growth rate (g/wk) between ultrasound at that gestational age and from prior visit [ie, for 28-32 weeks' gestational age: velocity = (estimated fetal weight 32-28)/(gestational age 32-28)]. We examined differences in birthweight by whether or not estimated fetal weight and estimated fetal weight velocity were <5th or ≥5th percentiles using χ2. RESULTS: Fetal growth velocity was nonmonotonic, with acceleration early in pregnancy, peaking at 13, 14, 15, and 16 weeks for biparietal diameter, head circumference, femur length, and abdominal circumference, respectively. Biparietal diameter, head circumference, and abdominal circumference had a second acceleration at 19-22, 19-21, and 27-31 weeks, respectively. Estimated fetal weight velocity peaked around 35 weeks. Fetal growth velocity varied slightly by race/ethnicity although comparisons reflected differences for parameters at various gestational ages. Estimated fetal weight velocity percentiles were not highly correlated with fetal size percentiles (Pearson r = 0.40-0.41, P < .001), suggesting that these measurements reflect different aspects of fetal growth and velocity may add additional information to a single measure of estimated fetal weight. At 32 (SD ± 1) weeks, if both estimated fetal weight velocity and size were <5th percentile, mean birthweight was 2550 g; however, even when size remained <5th percentile but velocity was ≥5th percentile, birthweight increased to 2867 g, reflecting the important contribution of higher growth velocities. For estimated fetal weight ≥5th percentile, but growth velocity <5th, birthweight was smaller (3208 vs 3357 g, respectively, P < .001). CONCLUSION: We provide fetal growth velocity data to complement our previous work on fetal growth size standards, and have developed a calculator to compute fetal growth velocity. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study.

Three recently completed longitudinal cohort studies have developed intrauterine fetal growth charts, one in the United States and two international. This expert review compares and contrasts the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies, INTERGROWTH-21st and World Health Organization Multicentre Growth Reference Study conclusions in light of differences in aims, sampling frames, and analytical approaches. An area of controversy is whether a single growth reference is representative of growth, regardless of ethnic or country origin. The INTERGROWTH and World Health Organization Fetal studies used a similar approach as the World Health Organization Multicentre Growth Reference Study for infants and children, the aim of which was to create a single international reference for the best physiological growth for children aged 0-5 years. INTERGROWTH made the same assumption (ie, that there would be no differences internationally among countries or racial/ethnic groups in fetal growth when conditions were optimal). INTERGROWTH found differences in crown-rump length and head circumference among countries but interpreted the differences as not meaningful and presented a pooled standard. The World Health Organization Multicentre Growth Reference Study was designed to create a pooled reference, although they evaluated for and presented country differences, along with discussion of the implications. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Study was designed to assess whether racial/ethnic-specific fetal growth standards were needed, in recognition of the fact that fetal size is commonly estimated from dimensions (head circumference, abdominal circumference, and femur length) in which there are known differences in children and adults of differing racial/ethnic groups. A pooled standard would be derived if no racial/ethnic differences were found. Highly statistically significant racial/ethnic differences in fetal growth were found resulting in the publication of racial/ethnic-specific derived standards. Despite all 3 studies including low-risk status women, the percentiles for fetal dimensions and estimated fetal weight varied among the studies. Specifically, at 39 weeks, the 50th percentile for estimated fetal weight was 3502 g for whites, 3330 g for Hispanics, 3263 g for Asians, and 3256 for blacks in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study, compared with 3186 g for INTERGROWTH and 3403 g for World Health Organization Multicentre Growth Reference Study. When applying these standards to a clinical population, it is important to be aware that different percentages of small- and large-for-gestational-age fetuses will be identified. Also, it may be necessary to use more restrictive cut points, such as the 2.5th or 97.5th, for small-for-gestational-age or large-for-gestational-age fetuses, respectively. Ideally, a comparison of diagnostic accuracy, or misclassification rates, of small-for-gestational-age and large-for-gestational-age fetuses in relation to morbidity and mortality using different criteria is necessary to make recommendations and remains an important data gap. Identification of the appropriate percentile cutoffs in relation to neonatal morbidity and mortality is needed in local populations, depending on which fetal growth chart is used. On a final point, assessment of fetal growth with a one-time measurement remains standard clinical practice, despite recognition that a single measurement can indicate only size. Ultimately, it is knowledge about fetal growth in addition to other factors and clinical judgment that should trigger intervention.

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.

Maternal weight gain and associations with longitudinal fetal growth in dichorionic twin pregnancies: a prospective cohort study.

Background: Maternal metabolic demands are much greater with twin gestations; however, there are no accepted recommendations for maternal weight gain in twin pregnancies.Objective: We assessed the association of maternal weight gain and fetal growth in dichorionic twins throughout pregnancy.Design: This was a prospective US cohort study (n = 143, 2012-2013) of dichorionic twin pregnancies with known birth outcomes followed from enrollment (11-13 wk) and for ≤6 research visits throughout gestation. Maternal prepregnancy weight was self-reported, and current weight was measured at each research visit and abstracted from prenatal records. Fetal biometry was assessed by ultrasound at each research visit. Maternal weight and twin-pair fetal size trajectories across gestation were modeled. The adjusted associations between maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk and fetal growth at the subsequent week (i.e., 14, 21, 28, and 35 wk, respectively) were estimated with the use of linear regression.Results: The mean ± SD maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk was 2.8 ± 3.0 kg, 3.9 ± 1.2 kg, 3.8 ± 1.4 kg, and 4.4 ± 2.2 kg, respectively, with a total gain of 17.7 ± 7.4 kg. Maternal weight gain from 0 to 13 wk (first trimester) was not associated with fetal size at 14 wk. Maternal weight gain from 14 to 20 and 21 to 27 wk (second trimester) was significantly associated with increased fetal weight at 21 wk [increase of 10.5 g/kg maternal weight gain (95% CI: 1.2, 19.8 g)] and 28 wk [increase of 21.3 g/kg maternal weight gain (95% CI: 0.6, 42.0 g)]. Maternal weight gain from 14 to 20 wk was associated with increased twin abdominal circumference (AC) and biparietal diameter at 21 wk. Maternal weight gain from 21 to 27 wk was associated with increased femur and humerus lengths at 28 wk.Conclusion: Maternal weight gain was associated with dichorionic twin fetal growth in the second trimester only, driven by an association with AC earlier in second trimester and long bones later in the second trimester.

Beyond Body Mass Index: Using Anthropometric Measures and Body Composition Indicators to Assess Odds of an Endometriosis Diagnosis.

BACKGROUND: Body mass index (BMI) and endometriosis have been inversely associated. To address gaps in this research, we examined associations among body composition, endometriosis, and physical activity. MATERIALS AND METHODS: Women from 14 clinical sites in the Salt Lake City, Utah and San Francisco, California areas and scheduled for laparoscopy/laparotomy were recruited during 2007-2009. Participants (N = 473) underwent standardized anthropometric assessments to estimate body composition before surgery. Using a cross-sectional design, odds of an endometriosis diagnosis (adjusted odds ratio [aOR]; 95% confidence interval [CI]) were calculated for anthropometric and body composition measures (weight in kg; height in cm; mid upper arm, waist, hip, and chest circumferences in cm; subscapular, suprailiac, and triceps skinfold thicknesses in mm; arm muscle and fat areas in cm2; centripetal fat, chest-to-waist, chest-to-hip, waist-to-hip, and waist-to-height ratios; arm fat index; and BMI in kg/m2). Physical activity (metabolic equivalent of task-minutes/week) and sedentariness (average minutes sitting on a weekday) were assessed using the International Physical Activity Questionnaire-Short Form. Measures were modeled continuously and in quartiles based on sample estimates. Adjusted models were controlled for age (years, continuous), site (Utah/California), smoking history (never, former, or current smoker), and income (below, within 180%, and above of the poverty line). Findings were standardized by dividing variables by their respective standard deviations. We used adjusted models to examine whether odds of an endometriosis diagnosis were moderated by physical activity or sedentariness. RESULTS: Inverse relationships were observed between endometriosis and standardized: weight (aOR = 0.71, 95% CI 0.57-0.88); subscapular skinfold thickness (aOR = 0.79, 95% CI 0.65-0.98); waist and hip circumferences (aOR = 0.79, 95% CI 0.64-0.98 and aOR = 0.76, 95% CI 0.61-0.94, respectively); total upper arm and upper arm muscle areas (aOR = 0.76, 95% CI 0.61-0.94 and aOR = 0.74, 95% CI 0.59-0.93, respectively); and BMI (aOR = 0.75, 95% CI 0.60-0.93), despite similar heights. Women in the highest versus lowest quartile had lower adjusted odds of an endometriosis diagnosis for: weight; mid-upper arm, hip, and waist circumferences; total upper arm and upper arm muscle areas; BMI; and centripetal fat ratio. There was no evidence of a main effect or moderation of physical activity or sedentariness. CONCLUSION: In a surgical cohort, endometriosis was inversely associated with anthropometric measures and body composition indicators.

Maternal stress and neonatal anthropometry: the NICHD Fetal Growth Studies.

BACKGROUND: The effect of maternal mood disorders on neonatal measurements is not well-defined. The Fetal Growth Studies-Singletons provide a unique opportunity to evaluate the relationship between perceived maternal stress and neonatal growth measurements. OBJECTIVE: The purpose of this study was to determine whether perceived maternal stress during pregnancy is associated with anthropometric measurements in the neonate. STUDY DESIGN: This analysis was based on a prospective, multicenter longitudinal study of fetal growth. Women 18-40 years old with a body mass index of 19.0-29.9 kg/m2 were screened at 8+0 to 13+6 weeks gestation for low-risk status associated with optimal fetal growth (eg, healthy, nonsmoking) and underwent serial sonographic examination at 6 study visits throughout gestation. At each study visit, women completed the Cohen's Perceived Stress Survey, which could have a score that ranges from 0-40. We used a latent class trajectory model to identify distinct groupings (ie, classes) of the Perceived Stress Survey trajectories over pregnancy. Trend analysis was used to determine whether neonatal measurements including birthweight, length, head circumference, and abdominal circumference differed by Perceived Stress Survey class and whether this relationship was modified by maternal race/ethnicity, after adjustment for gestational age at delivery, maternal height, age, and parity. RESULTS: Of the 2334 women enrolled in the study, 1948 women had complete neonatal anthropometry and were included in the analysis. Latent class analysis identified 3 Perceived Stress Survey trajectory classes, with mean Perceived Stress Survey scores of 2.82 (low), 7.95 (medium), and 14.80 (high). Neonatal anthropometric measures of birthweight, length, head circumference and abdominal circumference were similar (P=.78, =.10, =.18, and =.40 respectively), regardless of the participants' Perceived Stress Survey class. There was no effect modification by maternal race/ethnicity. CONCLUSION: Neonatal measurements did not differ by levels of perceived stress among low-risk pregnant women.

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

OBJECTIVES: 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. METHODS: After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. RESULTS: The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (>0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. CONCLUSIONS: Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth.

Dichorionic twin trajectories: the NICHD Fetal Growth Studies.

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.

Comprehensive Safety Monitoring of 12-Month Daily 7000-IU Vitamin D3 Supplementation in Human Immunodeficiency Virus-Infected Children and Young Adults.

BACKGROUND: There is uncertainty whether long-term daily dosing with vitamin D3 (cholecalciferol) supplementation (vitD3) above the 4000-IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo-controlled trial, we determined if supplementation with 7000-IU/d vitD3 for 12 months in human immunodeficiency virus (HIV)-Infected subjects was safe and/or associated with metabolic outcomes. MATERIAL AND METHODS: A total of 58 HIV-infected subjects-aged 9-24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)-were recruited, randomized to 7000-IU/d vitD3 or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25-hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study-defined serious adverse events-that is, elevated serum calcium plus 25(OH)D >160 ng/mL-and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. RESULTS: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. CONCLUSIONS: Safety of daily 7000-IU vitD3 supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High-dose daily vitD3 supplementation was efficacious in improving vitamin D status, and there were no safety events.

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.

In utero exposure to cigarette smoking, environmental tobacco smoke and reproductive hormones in US girls approaching puberty.

BACKGROUND/AIMS: Evidence is unclear whether prenatal smoking affects age at menarche and pubertal development, and its impact upon hormones has not been well studied. We aim to identify potential pathways through which prenatal smoking and environmental tobacco smoke (ETS) affect reproductive hormones in girls approaching puberty. METHODS: We examined the association between prenatal smoking, current ETS and luteinizing hormone (LH) and inhibin B (InB) in 6- to 11-year-old girls in the 3rd National Health and Nutrition Examination Survey, 1988-1994. Parents/guardians completed interviewer-assisted questionnaires on health and demographics at the time of physical examination. Residual blood samples were analyzed for reproductive hormones in 2008. RESULTS: Of 660 girls, 19 and 39% were exposed to prenatal smoke and current ETS, respectively. Accounting for multiple pathways in structural equation models, prenatally exposed girls had significantly lower LH (ß = -0.205 log-mIU/ml, p < 0.0001) and InB (ß = -0.162, log-pg/ml, p < 0.0001). Prenatal smoking also influenced LH positively and InB negatively indirectly through BMI-for-age. ETS was positively associated with LH, but not with InB. CONCLUSION: Exposure to maternal smoking may disrupt reproductive development manifesting in altered hormone levels near puberty.

High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.

BACKGROUND: Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 (vitD3) versus placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. METHODS: This was a double-blind trial of perinatally acquired HIV (PHIV)-infected subjects or behaviorally acquired HIV (BHIV)-infected subjects (5.0-24.9 years). Safety, 25(OH)D-related parameters and immune status were assessed at baseline, 3, 6 and 12 months. RESULTS: Fifty-eight subjects enrolled (67% male, 85% African American and 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6 and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P < 0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P < 0.001). Percentage of naive T-helper cells (Th naive%) were significantly (P < 0.01) and T-helper cells (CD4%) marginally (P < 0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P < 0.05). CONCLUSIONS: Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation.

Age at hormonal onset of puberty based on luteinizing hormone, inhibin B, and body composition in preadolescent U.S. girls.

BACKGROUND: Hormonal indicators could be useful for detecting early pubertal onset, but there is little research on how they are related to puberty in U.S. girls. We determined median age at hormonal onset of puberty based on luteinizing hormone (LH) and inhibin B (InB) and explored the extent to which body composition moderates this timing process. METHODS: We analyzed anthropometric and hormone data of 698 US peri-pubertal girls ages 6-11.99 y who had participated in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. RESULTS: Median age of hormonal onset of puberty was 10.43 y by LH and 10.08 y by InB cut-offs (1.04 mIU/ml for LH and 17.89 pg/ml for InB). Postnatal weight gain modulated onset, making it earlier by 10-11 mo among the highest (greater than +1 SD) relative to normal weight gainers. Onset occurred first in non-Hispanic black (NHB) girls, 10.08 y (95% confidence interval (CI): 10.07-10.09), followed by Mexican-American (MXAM) at 10.64 y (95% CI: 10.63-10.65), and at 10.66 y (95% CI: 10.66-10.67) for non-Hispanic white (NHW) girls using LH. With InB, onset occurred first in MXAM girls at 9.9 y, and at 10.3 y and 10.4 y for their NHB and NHW peers, respectively. CONCLUSION: Preadolescent weight gain lowers the age at hormonal onset as defined by LH concentrations. Preventing obesity in childhood may also avert the earlier initiation of the maturation process even at the hormonal level.

Methodology for establishing a population-based birth cohort focusing on couple fertility and children's development, the Upstate KIDS Study.

BACKGROUND: Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. METHODS: We utilised the Upstate New York livebirth registry (n = 201,063) to select births conceived with (n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without (n = 14,455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. RESULTS: Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies (ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly (P < 0.01) earlier gestations than unexposed infants (38.3 ± 2.8 and 38.7 ± 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 ± 2.7 and 38.7 ± 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 ± 704 and 3194 ± 679 g, respectively), but differed using maternal report (3167 ± 692 and 3224 ± 661, respectively P < 0.05). CONCLUSIONS: The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings.

Trace elements and endometriosis: the ENDO study.

There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.