Sarah J. Pugh

Patterns of gestational weight gain and birthweight outcomes in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons: a prospective study

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 (relative risk, 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.

Preconception maternal lipoprotein levels in relation to fecundability

STUDY QUESTION Are maternal preconception lipid levels associated with fecundability? SUMMARY ANSWER Fecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels. WHAT IS KNOWN ALREADY Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity. STUDY DESIGN, SIZE, DURATION A secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C <50 mg/dl and triglycerides ≥150 mg/dl. MAIN RESULTS AND THE ROLE OF CHANCE There were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (FOR: 0.76, 95% CI: 0.59, 0.97) and 29% (FOR: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol <200 mg/dl. There was a 19-36% decrease in the probability of conception per cycle for women with abnormal lipoprotein levels, though additional adjustment for central adiposity and BMI attenuated observed associations. LIMITATIONS, REASONS FOR CAUTION Although the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability. WIDER IMPLICATIONS OF THE FINDINGS Our results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability. STUDY FUNDING AND COMPETING INTEREST(S) This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist. TRIAL REGISTRATION NUMBER #NCT00467363.

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.

Combined Influence of Gestational Weight Gain and Estimated Fetal Weight on Risk Assessment for Small‐ or Large‐for‐Gestational‐Age Birth Weight: A Prospective Cohort Study

To evaluate the frequency with which gestational weight gain and estimated fetal weight do not track across gestation and to assess the risk of small‐for‐gestational‐age (SGA) and large‐for‐gestational‐age (LGA) birth weight as a function of tracking.

Estimating gestational age at birth from fundal height and additional anthropometrics: a prospective cohort study

Accurate assessment of gestational age (GA) is critical to paediatric care, but is limited in developing countries without access to ultrasound. Our objectives were to assess the accuracy of prediction of GA at birth and preterm birth classification using routinely collected anthropometry measures.