Gestational age and infection are greater predictors of placental histopathology than maternal prepregnancy BMI.

The placenta undergoes morphological and functional adaptions to adverse exposures during pregnancy. The effects of suboptimal maternal body mass index (BMI), preterm birth, and infection on placental histopathological phenotypes remain unclear, despite the association between these conditions and poor offspring outcomes. We hypothesized that suboptimal maternal prepregnancy BMI and preterm birth (with and without infection) would associate with altered placental maturity and morphometry, and that altered placental maturity would associate with poor birth outcomes. Clinical data and human placentae were collected from 96 pregnancies where mothers were underweight, normal weight, overweight, or obese, without other major complications. Placental histopathological characteristics were scored with an anatomical pathologist. Associations between maternal BMI, placental pathology (immaturity and hypermaturity), placental morphometry, and infant outcomes were investigated at term and preterm, with and without infection. Fetal vascular endothelium volumetric proportion was decreased, whereas syncytial knot volumetric proportion was increased, in placentae from preterm pregnancies with chorioamnionitis compared to term placentae. At term and preterm, pregnancies with overweight and obesity had a high percentage increase in proportion of immature placentae compared to normal weight. Placental maturity did not associate with infant birth outcomes. We observed placental hypermaturity and altered placental morphometry among preterm pregnancies with chorioamnionitis, suggestive of altered placental development, which may inform about pregnancies susceptible to preterm birth and infection. Our data increase our understanding of how common metabolic exposures and preterm birth, in the absence of other comorbidities or perinatal events, potentially contribute to poor pregnancy outcomes and the programming of offspring development.

Preterm Birth and Small-for-Gestational Age Neonates among Prepregnancy Underweight Women: A Case-Controlled Study

The aim of our study was to investigate whether prepregnancy underweight body mass index (BMI) is associated with preterm birth (PTB) and small-for-gestational age (SGA). This retrospective case-control study included 814 women with live singleton fetuses in vertex presentation that gave birth between January 2016 and November 2016 in two tertiary care hospitals. The study group (n = 407) comprised all women whose prepregnancy BMI was underweight (<18.5 kg/m2) and who delivered during the study period. A control group (n = 407) was established with women whose prepregnancy BMI was normal (18.5–24.9 kg/m2) by matching age and parity. Univariate and multivariate analyses were performed to compare PTB and SGA associated with prepregnancy underweight BMI. Compared with the control group, the study group had higher rates of overall PTB (10.1% vs. 5.7%, p = 0.02), iatrogenic PTB (4.2% vs. 1.5%, p = 0.02), and SGA (22.1% vs. 11.1%, p < 0.001). In a multivariable analysis, prepregnancy underweight BMI was associated with PTB (aOR 2.32, 95% CI 1.12–4.81) and with SGA (aOR 2.38, 95% CI 1.58–3.58). In singleton pregnancies, women’s prepregnancy underweight compared with normal BMI was associated with an increase in PTB and in SGA neonates. Identifying this specific high-risk group is pragmatic and practical for all physicians, and they should be aware about perinatal outcome among underweight women.

Association of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles: a retrospective cohort study

Background Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles. Methods We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women’s Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect. Results In singletons, couples with prepregnancy BMI ≥25 kg/m2 had higher odds of LGA than those with BMI < 25 kg/m2. The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m2 in IVF cycles (aOR 1.82, 95% CI 1.06–3.10) and maternal BMI ≥25 kg/m2 in ICSI cycles (aOR 4.89, 95% CI 1.45–16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m2 (aOR 4.55, 95% CI 1.32–15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants. Conclusions Parental prepregnancy BMI ≥25 kg/m2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m2, particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments.

Preterm birth associates with increased placental expression of MDR transporters irrespective of prepregnancy BMI

Context Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition, however few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected pro-inflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype. Objective To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and pro-inflammatory cytokine levels are altered by PTB and maternal BMI. Design and Outcomes A cross-sectional study was conducted to assess the effect of PTB (+/- chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin [IL]-6 and 8 expression in 60 preterm and 36 term pregnancies. Results ABCB1 expression was increased in preterm compared to term placentae (p=0.04). P-gp (p=0.008) and BCRP (p=0.01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, p=0.007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (p=0.0005), and PTC associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes. Conclusions PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.

A 646C > G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy—data from an observational study

Aim Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP. Method The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189). Results A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014. Conclusions The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

Predictive Value of Homeostasis Model Assessment of Insulin Resistance, Visceral Fat Index, and Prepregnancy Body Mass Index in Gestational Metabolic Syndrome

Objective. To explore the diagnostic value of homeostasis model assessment of insulin resistance (HOMA-IR), visceral fat index (VAI), and prepregnancy body mass index (BMI) in gestational metabolic syndrome (GMS). Methods. From December 2019 to March 2021,122 GMS high-risk pregnant women who received routine antenatal clinic visits and planned to give birth in our hospital were selected as the research objects. Pregnant women were divided into the GMS group (n = 79) and the control group (n = 43) according to GMS diagnostic criteria during the gestation period of 32–36 weeks. The general information such as age and gestational week of pregnant women as well as HOMA-IR, VAI, and BMI before pregnancy were compared between the two groups. The glucose and lipid metabolism indexes of pregnant women in two groups were analyzed, the detection rates of HOMA-IR, VAI, and prepregnancy BMI in GMS between the two groups were compared. Logistic regression was used to analyze the risk factors for GMS in pregnant women, and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of HOMA-IR, VAI, prepregnancy BMI, and the combination of the three for GMS. Results. The body weight, systolic blood pressure, and diastolic blood pressure of the GMS group were higher than those of the control group, and the differences were statistically significant ( P < 0.05 ). There was no significant difference in age, gestational week, and height between the two groups ( P > 0.05 ). The levels of FPG, FINS, TC, TG, LDL-C, and FFA in the GMS group were higher than the control group, the level of HDL-C in the GMS group was lower than the control group, and the difference was statistically significant ( P < 0.05 ). The levels of HOMA-IR, VAI, and prepregnancy BMI in the GMS group were higher than those in the control group, and the differences were statistically significant ( P < 0.05 ). The positive detection rates of HOMA-IR, VAI, and prepregnancy BMI in the GMS group were 83.54%, 86.07%, and 81.01%, respectively. There was no significant difference in the positive detection rates of HOMA-IR, VAI, and prepregnancy BMI between the two groups ( P > 0.05 ). High levels of HOMA-IR, VAI, and prepregnancy BMI were risk factors for GMS in pregnant women ( P < 0.05 ). ROC curve showed area under the curve for HOMA-IR was 0.810, area under the curve for VAI was 0.771, and area under the curve for prepregnancy BMI was 0.749. The AUC for the combination of HOMA-IR, VAI, and prepregnancy BMI was 0.918. Conclusion. HOMA-IR, VAI, and prepregnancy BMI in GMS have a high detection rate and certain diagnostic value, and the combination of the three has higher clinical value.

The effect of prepregnancy body mass index on maternal micronutrient status: a meta-analysis

The relationship between prepregnancy body mass index (BMI) and maternal micronutrient status is inconsistent and has not received sufficient attention. This meta-analysis aimed to evaluate the effect of prepregnancy BMI on micronutrient levels in pregnant women. PubMed, Embase, Web of Science, and the Cochrane Library were searched for articles that contained information on micronutrient levels and prepregnancy BMI. A random-effects model was used to determine the association between prepregnancy BMI and maternal micronutrient status. Sixty-one eligible articles were eventually included, with 83,554 participants. Vitamin B12, folate, vitamin D, iron and ferritin were the main micronutrients evaluated in our meta-analysis. Prepregnancy obesity and overweight may lead to an increased risk of micronutrient deficiency, including vitamin B12, folate and vitamin D deficiency, while prepregnancy obesity or overweight may have no significant association with ferritin deficiency. Additionally, the results of the dose–response analyses demonstrated a possible significant inverse correlation between prepregnancy BMI and levels of micronutrient, except for iron and ferritin. Compared with women with normal weight, women who were overweight or obese prepregnancy have lower micronutrient concentrations and are more likely to exhibit micronutrient deficiency during pregnancy, which is harmful to both mothers and neonates.

Gestational body weight gain and risk of low birth weight or macrosomia in women of Japan: a nationwide cohort study

Objective Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan. Methods This cohort study (n = 98,052) used data from the Japan Environment and Children’s Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI. Results GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively. Conclusions The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.

Maternal body mass index, early-pregnancy metabolite profile and birthweight

Context Maternal prepregnancy BMI has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown. Objective First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations. Design, setting and participants Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study. Main outcome measures Maternal non-fasting targeted amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight, obtained from medical records. Results A higher prepregnancy BMI was associated with 72 altered amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress and lipid metabolic processes (p-values&lt;0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios, based on its association with birthweight in addition to prepregnancy BMI. The adjusted R 2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations and 12.9% after addition of the metabolite profile. Conclusions A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, non-esterified fatty acids, phospholipids and carnitines. Using these metabolites, we identified a maternal metabolite profile which improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations.

Preterm birth increases placental expression of multidrug resistance (MDR) transporters irrespective of prepregnancy body mass index (BMI)

Context: Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition, however few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected pro-inflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype. Objective: To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and pro-inflammatory cytokine levels are altered by PTB and maternal BMI. Design and Outcomes: A cross-sectional study was conducted to assess the effect of PTB (+/- chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin [IL]-6 and 8 expression in 60 preterm and 36 term pregnancies. Results: ABCB1 expression was increased in preterm compared to term placentae (p=0.04). P-gp (p=0.008) and BCRP (p=0.01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, p=0.007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (p=0.0005), and PTC was associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes. Conclusions: PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.