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Objective: Elective induction of labor versus expectant management at 39 weeks gestation in low-risk nulliparous patients was shown in the ARRIVE randomized trial of over 6000 patients to decrease risks of cesarean delivery without significant change in the composite perinatal outcome. We aimed to pragmatically analyze the effect of offering elective induction of labor (eIOL) to all low-risk patients., Methods: Retrospective cohort study of low-risk nulliparous and multiparous patients delivering live, non-anomalous singletons at a single center at greater than or equal to 39 0/7 weeks gestational age. Those with prior or planned cesarean delivery, ruptured membranes, medical comorbidities, or contraindications to vaginal delivery were excluded. Patients were categorized as before (pre-eIOL; 1/2012-3/2014) or after (post-eIOL; 3/2019-12/2021) an institution-wide policy offering eIOL at 39 0/7 weeks. Births occurring April 2014 to December 2018 were allocated to a separate cohort (during-eIOL) given increased exposure to eIOL as our center recruited participants for the ARRIVE trial. The primary outcome was cesarean birth. Secondary outcomes included select maternal (e.g. chorioamnionitis, operative delivery, postpartum hemorrhage) and neonatal morbidities (e.g. birthweight, small- and large-for gestational age, hypoglycemia). Characteristics and outcomes were compared between the pre and during-eIOL, and pre and post-eIOL groups; adjusted OR (95% CI) were calculated using multivariable regression. Subgroup analysis by parity was planned., Results: Of 10,758 patients analyzed, 2521 (23.4%) were pre-eIOL, 5410 (50.3%) during-eIOL, and 2827 (26.3%) post-eIOL. Groups differed with respect to labor type, age, race/ethnicity, marital and payor status, and gestational age at care entry. Post-eIOL was associated with lower odds of cesarean compared to pre-eIOL (aOR 0.83 [95% CI 0.72-0.96]), which was even lower among those specifically undergoing labor induction (aOR 0.58 [0.48-0.70]. During-eIOL was also associated with lower odds of cesarean compared to pre-eIOL (aOR 0.79 [0.69-0.90]). Both during and post-eIOL groups were associated with higher odds of chorioamnionitis, operative delivery, and hemorrhage compared to pre-eIOL. However, only among post-eIOL were there fewer neonates weighing ≥4000 g, large-for-gestational age infants, and neonatal hypoglycemia compared to pre-IOL., Conclusion: An institutional policy offering eIOL at 39 0/7 to low-risk patients was associated with a lower cesarean birth rate, lower birthweights and lower neonatal hypoglycemia, and an increased risk of chorioamnionitis and hemorrhage.

An accumulating body of literature points to a link between spatial reasoning and mathematics learning. The present study contributes to this line of research by investigating sex differences both in spatial representations of magnitude and in the use of arithmetic strategies, as well as the relation between the two. To test the hypothesis that sex differences in spatial-numerical magnitude knowledge mediate sex differences in the use of advanced strategies (retrieval and decomposition), two studies were conducted. Study 1 included 96 US first graders (53% girls); Study 2 included 210 Russian first graders (49% girls). All participants completed a number line estimation task (a spatially based measure of numerical magnitude knowledge) and an arithmetic strategy task (a measure of strategy choice). The studies showed parallel results: boys produced more accurate numerical magnitude estimates on the number line estimation task and used advanced strategies more frequently on the arithmetic task. Critically, both studies provide support for the mediation hypothesis (although there were some differences in the pattern obtained for the two strategies). The results are discussed in the context of broader research about the relation between spatial and mathematical skills.

In mothers who are nursing their infants, increased clearance of plasma metabolites into the mammary gland may reduce ectopic lipid in the liver. No study to date has investigated the role of lactation on liver lipid synthesis in humans, and we hypothesized that lactation would modify fatty acid and glucose handling to support liver metabolism in a manner synchronized with the demands of milk production. Lactating (n = 18) and formula-feeding women (n = 10) underwent metabolic testing at 6-week postpartum to determine whether lactation modified intrahepatic triacylglycerols (IHTGs), measured by proton magnetic resonance spectroscopy. Subjects ingested oral deuterated water to measure fractional de novo lipogenesis (DNL) in VLDL-TG during fasting and during an isotope-labeled clamp at an insulin infusion rate of 10 mU/m 2 /min. Compared with formula-feeding women, we found that lactating women exhibited lower plasma VLDL-TG concentrations, similar IHTG content and similar contribution of DNL to total VLDL-TG production. These findings suggest that lactation lowers plasma VLDL-TG concentrations for reasons that are unrelated to IHTG and DNL. Surprisingly, we determined that the rate of appearance of nonesterified fatty acids was not related to IHTG in either group, and the expected positive association between DNL and IHTG was only significant in formula-feeding women. Further, in lactating women only, the higher the prolactin concentration, the lower the IHTG, while greater DNL strongly associated with elevations in VLDL-TG. In conclusion, we suggest that future studies should investigate the role of lactation and prolactin in liver lipid secretion and metabolism., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Milk production may involve a transient development of insulin resistance in nonmammary tissues to support redistribution of maternal macronutrients to match the requirements of the lactating mammary gland. In the current study, adipose and liver metabolic responses were measured in the fasting state and during a two-step (10 and 20 mU/m 2 /min) hyperinsulinemic-euglycemic clamp with stable isotopes, in 6-week postpartum women who were lactating ( n = 12) or formula-feeding ( n = 6) their infants and who were closely matched for baseline characteristics (e.g., parity, body composition, and intrahepatic lipid). When controlling for the low insulin concentrations of both groups, the lactating women exhibited a fasting rate of endogenous glucose production (EGP) that was 2.6-fold greater and a lipolysis rate that was 2.3-fold greater than the formula-feeding group. During the clamp, the groups exhibited similar suppression rates of EGP and lipolysis. In the lactating women only, higher prolactin concentrations were associated with greater suppression rates of lipolysis and lower intrahepatic lipid and plasma triacylglycerol concentrations. These data suggest that whole-body alterations in glucose transport may be organ specific and facilitate nutrient partitioning during lactation. Recapitulating a shift toward noninsulin-mediated glucose uptake could be an early postpartum strategy to enhance lactation success in women at risk for delayed onset of milk production., (© 2020 by the American Diabetes Association.)

Objective: To assess whether treatment of pregnant women with subclinical hypothyroidism or hypothyroxinemia alters neonatal TSH results., Study Design: A planned secondary analysis of data from two multi-center randomized, double-masked, placebo-controlled thyroxine replacement trials in pregnant women with either subclinical hypothyroidism or hypothyroxinemia. Infant heel-stick specimens were obtained before discharge. We compared TSH levels between neonates born to mothers allocated to treatment or placebo within each trial and between neonates in the placebo groups. Multiples of means were generated for day-of-life-specific data., Results: Neonatal TSH values were available for 573/677 (84.6%) newborns from the subclinical hypothyroidism trial and 461/526 (87.6%) newborns from the hypothyroxinemia trial. Neonatal TSH values did not differ in either trial by treatment group or between placebo groups (P > 0.05 for all comparisons)., Conclusions: Neonatal TSH values did not differ with thyroid hormone replacement in pregnancies diagnosed with subclinical hypothyroidism or hypothyroxinemia.

Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32-36 weeks) pregnancy, and post-partum (6-10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min(-1) and 16 ± 5 vs. 30 ± 3 bursts min(-1) in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min(-1) at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy., (© 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.)

Objective: To evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity., Research Design and Methods: Follow-up study of children (ages 5-10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured., Results: Five hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5-6 and 7-10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels., Conclusions: Although treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The synthesis of 2-tetralones through the cyclization of δ-aryl-β-dicarbonyl substrates by using CAN is described. Appropriately functionalized aromatic substrates undergo intramolecular cyclizations generating 2-tetralone derivatives in moderate to good yields. DFT computational studies indicate that successful formation of 2-tetralones from δ-aryl-β-dicarbonyl radicals is dependent on the stability of the subsequent cyclohexadienyl radical intermediates. Furthermore, DFT computational studies were used to rationalize the observed site selectivity in the 2-tetralone products.

Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.

Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding of the coordinated regulation of myometrial contractions during parturition. The objective of this study was to compare the gene expression profiles of human fundal myometrium from pregnant women before and after the onset of labor using a functional genomics approach, and to further characterize the spatial and temporal expression patterns of three genes believed to be important in parturition. Fundal myometrial mRNA was isolated from five women in labor and five women not in labor, and analyzed using human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain reaction using myometrial RNA from pregnant women in labor or not in labor was used to examine mRNA levels for three of the genes; namely, prostaglandin-endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor (OXTR). The spatial expression pattern of these genes throughout the pregnant uterus before and after labor was also determined. Immunolocalization of cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and myometrium were analyzed by immunohistochemistry. Few genes were differentially expressed in fundal myometrial tissues at term with the onset of labor. However, there appears to be a subset of genes important in the parturition cascade. The cellular properties of S100A9, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor.

Biliary tract disease is a relatively uncommon, heterogenous disease in pregnancy. Specifically, acute cholecystitis can be especially difficult to recognize in pregnancy. However, once diagnosed, the initial management plan should be conservative and include antibiotic therapy. Subsequent management depends on the gestational age at diagnosis. Surgical therapy, when indicated, should not be delayed and a planned intervention during the second trimester appears to offer a better outcome than surgery performed under emergent conditions.