Background Nulliparity is associated with lower birthweight, but few studies have examined how within mother changes in risk-factors impact this association. Methods We used longitudinal electronic medical record data from a hospital-based cohort of consecutive singleton live births from 2002–2010 in Utah. To reduce bias from unobserved pregnancies primary analyses were limited to 9,484 women who entered nulliparous from 2002–2004 with 23,380 pregnancies up to parity 3. Unrestricted secondary analyses used 101,225 pregnancies from 45,212 women with pregnancies up to parity 7. We calculated gestational age and sex-specific birthweight z-scores with nulliparas as the reference. Using linear mixed models, we estimated birthweight z-score by parity adjusting for pregnancy-specific sociodemographics, smoking, alcohol, prepregnancy body mass index, gestational weight gain, and medical conditions. Results Compared to nulliparas, infants of primiparas were larger by 0.20 unadjusted z-score units [95% confidence interval (CI) 0.18, 0.22]; the adjusted increase was similar at 0.18 z-score units [95% CI 0.15, 0.20]. Birthweight continued to increase up to parity 3, but with a smaller difference, (parity 3 vs. 0 β=0.27 [95% CI 0.20, 0.34]). In the unrestricted secondary sample, there was significant departure in linearity from parity 1 to 7 (P<0.001); birthweight increased only up to parity 4, (parity 4 vs. 0 β=0.34 [95% CI 0.31, 0.37]). Conclusions The association between parity and birthweight was non-linear with the greatest increase observed between first and second-born infants of the same mother. Adjustment for changes in weight or chronic diseases did not change the relationship between parity and birthweight.

IMPORTANCE Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.OBJECTIVE To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. DESIGN, SETTING, AND PARTICIPANTSThe Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged Ն18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.INTERVENTIONS Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. MAIN OUTCOMES AND MEASURESThe co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. RESULTS Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).CONCLUSIONS AND RELEVANCE Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

Among healthy fecund women with a history pregnancy loss, TSH levels ≥ 2.5 mIU/L or the presence of antithyroid antibodies were not associated with fecundity, pregnancy loss, or live birth. Thus, women with subclinical hypothyroidism or thyroid autoimmunity can be reassured that their chances of conceiving and achieving a live birth are likely unaffected by marginal thyroid dysfunction.

Objectives To determine neonatal morbidity rates for early term birth compared to full term birth by precursor leading to delivery. Study Design This was a retrospective study of 188,809 deliveries from 37 0/7 to 41 6/7 weeks of gestation with electronic medical record data from 2002 to 2008. Precursors for delivery were categorized as spontaneous labor, premature rupture of membranes (PROM), indicated, and no recorded indication. After excluding anomalies, rates of neonatal morbidities by precursor were compared at each week of delivery. Results Early term births (37 0/7 – 38 6/7 weeks) accounted for 34.1% of term births. Overall, 53.6% of early term births were due to spontaneous labor, followed by 27.6% indicated, 15.5% with no recorded indication, and 3.3% with PROM. Neonatal intensive care unit (NICU) admission and respiratory morbidity were lowest at or beyond 39 weeks compared to the early term period for most precursors, although indicated deliveries had the highest morbidity compared to other precursors. The greatest difference in morbidity was between 37 and 39 weeks for most precursors, while most differences in morbidities between 38 and 39 weeks were not significant. Respiratory morbidity was higher at 37 than 39 weeks regardless of route of delivery. Conclusion Given the higher neonatal morbidity at 37 compared to 39 weeks regardless of delivery precursor, our data support recent recommendations for designating early term to include 37 weeks. Prospective data is urgently needed to determine the optimal timing of delivery for common pregnancy complications.

In youth, increased plasma AA concentrations are not associated with a heightened metabolic risk profile for T2DM; rather, they are positively associated with β-cell function relative to insulin sensitivity. These contrasting observations between adults and youth may be a reflection of developmental differences along the lifespan dependent on the combined impact of the aging process together with the impact of progressive obesity.

Objective To assess the glucose disposition index (DI) using an oral glucose tolerance test (OGTT; oDI) compared with the DI measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance. Study design Overweight/obese adolescents (n=185) with varying glucose tolerance (87 normal [NGT], 54 impaired [IGT], 31 with type 2 diabetes [T2DM] and 13 with type 1 diabetes [OT1DM]) completed an OGTT and both a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Indices of insulin sensitivity and β-cell function were calculated, and four different oDI estimates were calculated as the products of insulin and C-peptide-based sensitivity and secretion indices. Results Mirroring the differences across groups by cDI, the oDI estimates were greatest in NGT and lowest in T2DM and OT1DM. The insulin-based oDI estimates correlated with cDI overall (r≥0.74, P<0.001) and within each glucose tolerance group (r≥0.40, P<0.001). Also, oDI and cDI predicted 2-h OGTT glucose similarly. Conclusions Oral disposition index is a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose tolerance in large-scale studies where the applicability of clamp studies is limited due to feasibility, cost and labor intensiveness.

Clinical and biochemical LPD were evident among regularly menstruating women. Estradiol was lower in LPD cycles under either criterion, but LH and FSH were lower only in association with shortened luteal phase (ie, clinical LPD), indicating that clinical and biochemical LPD may reflect different underlying mechanisms. Identifying ovulation in combination with a well-timed luteal progesterone measurement may serve as a cost-effective and specific tool for LPD assessment by clinicians and researchers.

National Institutes of Health and Doris Duke Charitable Foundation.