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Background Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential nutrients for feto-placental development. We aimed to evaluate the associations between maternal pregestational BMI, mid-pregnancy LC-PUFA status, and delivery outcomes in non-obese pregnancies. Methods This was a secondary analysis of two Italian cohorts including healthy non-obese women with singleton spontaneous pregnancies previously studied for maternal nutritional habits, multivitamin supplementation, blood biomarkers and infant biometry/measures. In the present analysis, included women were stratified according to pregestational BMI (normal weight (NW) versus overweight (OW) groups). Fasting venous blood samples were collected between 24 and 34 gestational weeks for fatty acid (FA) analysis. Pregnancy outcomes were recorded at delivery. Multi-adjusted generalized linear models were applied to first assess the associations between BMI-based groups and mid-pregnancy LC-PUFA concentrations, and second to evaluate the associations between the LC-PUFA profile and pregnancy outcomes. Results 283 pregnancies were included. The OW group showed lower eicosapentaenoic acid (EPA) levels (β= -0.09; 95%CI= -0.16; -0.03) and a higher arachidonic acid/EPA ratio (β = 8.06; 95%CI = 0.00; 16.3) compared with the NW group in multi-adjusted models. After excluding women with gestational diabetes mellitus ( n  = 13), a significant association between LC-PUFA status and birth weight was also proved with increased birth weights in case of lower LC-PUFA n-6/n-3 ratio (β= -78.9; 95%CI= -148.5; -9.2) and higher docosahexaenoic acid (DHA) (β = 26.5; 95%CI = 0.4; 52.6), total LC-PUFA n-3 (β = 22.9; 95%CI = 0.7; 45.1) and n-3 index (β = 24.9; 95%CI = 0.03; 49.8). A positive association was further detected between LC-PUFA n-6 and neonatal ponderal index (β = 0.01; 95%CI = 0.00; 0.02). No associations were detected between LC-PUFAs and gestational age at delivery. Conclusions These findings underscore significant associations between maternal pregestational BMI and mid-pregnancy LC-PUFA n-3 and n-6 status, with further associations with birth weight and neonatal ponderal index. Our results suggest that LC-PUFA n-3 and n-6 series may serve as valuable clinical biomarkers, particularly among OW women, and may act as predictors of intrauterine growth. Trial registration NCT04438928.

Among residents living close to agricultural fields who are potentially exposed to pesticides, pregnant women and their fetuses are of particular concern for their vulnerability to environmental chemicals. In this collaborative multicenter study, we covered a wide distribution of participants in the most important fruit production zone of north Patagonia (Argentina) to investigate whether maternal residential proximity to fruit croplands with intense pesticide applications (rural group –RG-) is associated with pregnancy complications and alterations in their newborn parameters compared to the urban population (urban group –UG-). A total of 776 pregnant women met the inclusion criteria. The percentage of threatened miscarriage was significantly higher in the RG than in the UG. The percentage of miscarriage, threat of premature labor, intrauterine fetal death, preterm premature rupture of membranes, and intrauterine growth retardation were similar in both groups. Newborn anthropometric parameters were corrected by sex and gestational age prior to statistical analysis. Length at birth and head circumference were lower in the RG than in the UG. Birth weight was similar in both groups. The percentage of head circumference less than the 5th percentile and the ponderal index were greater in the RG than in the UG. Our results suggest that proximity to pesticide applications may increase the risk of pregnancy complications and altered newborn parameters. Graphical abstract

The significance of vitamin A during pregnancy for fetal growth and development has garnered increasing attention. However, the dose–response relationship between vitamin A concentration in late pregnancy and the offspring's ponderal index (PI) remains unclear. This study aims to investigate this relationship and determine the optimal supplementation level of vitamin A, providing a scientific basis for clinical nutritional interventions. This study selected pregnant women and their offspring who voluntarily participated and established records at the Obstetrics Department of Shandong Second Medical University Affiliated Hospital from March 1, 2023, to September 1, 2024. A self‐designed questionnaire was utilized to collect demographic characteristics of the pregnant women, as well as factors influencing offspring growth. Fasting venous blood samples were collected from the pregnant women during late pregnancy (28 to 40 weeks), and high‐performance liquid chromatography (HPLC) was employed to measure serum concentrations of vitamins A, E, and C. Standard physical measurement methods were used to assess the offspring's birth weight and length. Data analysis was conducted using R programming language and EmpowerStats software, employing segmented linear regression analysis to determine the threshold of vitamin A concentration and its impact on PI. Analysis of 442 mother–infant pairs showed a nonlinear relationship between maternal vitamin A levels in the third trimester and the neonatal ponderal index (PI). An inverted U‐shaped curve was observed, with two key inflection points at 0.65 μmol/L (lower threshold) and 1.65 μmol/L (upper threshold). Within the optimal range of 0.65 to 1.65 μmol/L, each 0.5 μmol/L increase in vitamin A raised PI by 0.47 kg/m3 (95% CI: 0.42–0.52, p < 0.001), while concentrations above 1.65 μmol/L decreased PI (β = −0.44 per 0.5 μmol/L, 95% CI: −0.53 to −0.34, p < 0.001). This triphasic pattern remained consistent even after adjusting for 17 covariates, such as fetal sex, gestational age, and maternal nutritional status (adjusted R2 = 0.81). Male infants consistently demonstrated superior growth parameters (+225 g weight, +0.40 cm length vs. females, p < 0.05), while maternal vitamin E supplementation independently increased birth weight by 401 g (p < 0.05). This study determines that the ideal range of maternal vitamin A during late pregnancy is 0.65–1.65 μmol/L for optimal neonatal growth. Levels above 1.65 μmol/L diminish growth benefits, whereas levels below 0.65 μmol/L restrict developmental potential. Our findings call into question the routine practice of vitamin A supplementation. Instead, we advocate for personalized monitoring to maintain the target range. This approach is vital for precision perinatal nutrition, as it helps prevent both growth restriction and the risks associated with vitamin overdose. This provides a valuable reference for nutritional health interventions during pregnancy. This cohort study of 442 mother–infant pairs revealed a triphasic relationship between late‐pregnancy maternal vitamin A levels and neonatal ponderal index (PI), with optimal PI gains observed at 0.65–1.65 μmol/L (+0.47 kg/m3 per 0.5 μmol/L increment) but reversed effects beyond this therapeutic window. Threshold analysis demonstrated significant inflection points (0.65 μmol/L: β = 0.94, p < 0.001; 1.65 μmol/L: β = −0.44, p < 0.001), challenging current supplementation practices and advocating personalized monitoring to balance growth optimization with overdose risks.

Background/Aims Childhood obesity and associated metabolic comorbidities is a major global health concern. Metabolically healthy obesity (MHO) may represent a subgroup of individuals in which excessive body fat accumulation does not lead to adverse metabolic effects. We aimed to determine the prevalence of MHO among obese Israeli children and adolescents and to find predictors for metabolically unhealthy obesity (MUO). Methods In a retrospective study, demographic, anthropometric, lifestyle, and cardiometabolic data were retrieved from medical records of patients with a body mass index (BMI) >95th percentile aged 6 to 17.6 years, attending a tertiary pediatric obesity clinic between 2008 and 2015, with at least 1 year of follow‐up. Participants were dichotomized as either MHO or MUO based on cardiometabolic risk factor clustering (blood pressure, serum lipids, and glucose). Multivariable logistic regression was used to determine predictors of MUO. Results Of the 230 children (median age 9.9 years) fulfilling study criteria, 48 (20.9%) were classified as MHO. Occurrence of MUO was associated with male gender, Arabic ethnicity, higher BMI‐SD score, higher tri‐ponderal mass index (TMI), and higher insulin resistance (IR) (presence of acanthosis nigricans and a higher level of homeostasis model assessment‐IR [HOMA‐IR]). Male gender (odds ratio [OR] 2.27, P = .033), presence of acanthosis nigricans at baseline (OR 2.35, P = .035), and a greater increase in BMI‐SDS during follow‐up (OR 2.82, P = .05) were the best predictors of MUO. Conclusions The MHO phenotype was present in only 20.9% of obese Israeli children. MUO was significantly associated with male gender, with presence of acanthosis nigricans, and with a greater increase in BMI‐SDS during follow‐up.

Aim: A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. Design: We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. Results: In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0; P=0.02). Protein intake was also associated negatively with ponderal index ((beta)=-0.01; 95% CI: -0.02, -0.00; P=0.01). A 1% increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. Conclusions: This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.

Birth weight is a common measure of fetal growth that is associated with a range of health outcomes. It is directly affected by the fetal genome and indirectly by the maternal genome. We performed genome-wide association studies on birth weight in the genomes of the child and parents and further analyzed birth length and ponderal index, yielding a total of 243 fetal growth variants. We clustered those variants based on the effects of transmitted and nontransmitted alleles on birth weight. Out of 141 clustered variants, 22 were consistent with parent-of-origin-specific effects. We further used haplotype-specific polygenic risk scores to directly test the relationship between adult traits and birth weight. Our results indicate that the maternal genome contributes to increased birth weight through blood-glucose-raising alleles while blood-pressure-raising alleles reduce birth weight largely through the fetal genome. Genome-wide association analyses using parental and offspring genotypes provide insights into fetal and maternal genetic effects on fetal growth. The results show that maternal and fetal genomes influence birth weight through distinct mechanisms.

While there is evidence that being born large-for-gestational-age (LGA) is associated with an increased risk of obesity later in life, the data are conflicting. Thus, we aimed to examine the associations between proportionality at birth and later obesity risk in adulthood. This was a retrospective study using data recorded in the Swedish Birth Register. Anthropometry in adulthood was assessed in 195,936 pregnant women at 10–12 weeks of gestation. All women were born at term (37–41 weeks of gestation). LGA was defined as birth weight and/or length ≥2.0 SDS. Women were separated into four groups: appropriate-for-gestational-age according to both weight and length (AGA – reference group; n = 183,662), LGA by weight only (n = 4,026), LGA by length only (n = 5,465), and LGA by both weight and length (n = 2,783). Women born LGA based on length, weight, or both had BMI 0.12, 1.16, and 1.08 kg/m 2 greater than women born AGA, respectively. The adjusted relative risk (aRR) of obesity was 1.50 times higher for those born LGA by weight and 1.51 times for LGA by both weight and height. Length at birth was not associated with obesity risk. Similarly, women born LGA by ponderal index had BMI 1.0 kg/m 2 greater and an aRR of obesity 1.39 times higher than those born AGA. Swedish women born LGA by weight or ponderal index had an increased risk of obesity in adulthood, irrespective of their birth length. Thus, increased risk of adult obesity seems to be identifiable from birth weight and ignoring proportionality.

Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown. Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth. The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend -values ( ) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

Expelled placentas and calf size at birth were collected from crossbred beef cows during Spring 2017 (n = 27; age: 2-7 yr), Fall 2017 (n = 24; age: 3-6 yr), and Fall 2018 (n = 22; age: 2-4 yr) to determine the relationships of placental characteristics with cow parameters, calf sex, and fetal growth. Placentas deemed complete were dissected (cotyledonary vs. intercotyledonary) and dry weights determined. Mixed linear models were used to individually determine main effects of peripartum BCS category (< 5, =5, or ≥6), cow age category (2, 3-4, or 5-7 yr), and calf sex on placental measures. Study was included in all models. Correlations were determined for placental characteristics with pre-calving cow BWand calf size. Cow BCS and calf sex had no effect (P ≥ 0.25) on placental characteristics. Primiparous cows had less (P ≤ 0.02) total placental and average cotyledon weights compared with young cows. Cow BW and calf BW had moderate positive correlations (P < 0.001) with intercotyledonary and total placental weights and weak positive correlations (P ≤ 0.01) with cotyledonary weight. Cow BW had a weak negative correlation (P = 0.05) with placental efficiency [calf BW/placental weight]. Average cotyledon weight had a moderate positive correlation (P < 0.001) with cow BW and a weak positive correlation (P = 0.001) with calf BW. Shoulder to tailhead length had a weak positive correlation (P = 0.001) with placental efficiency. Heart girth had moderate positive correlations (P < 0.001) and abdominal girth had weak positive correlations (P ≤ 0.04) with cotyledonary, intercotyledonary, total placental, and average cotyledon weights. Ponderal index [calf BW/length3] had a weak positive correlation (P ≤ 0.06) with cotyledonary, intercotyledonary, and total placental weights. These data suggest that fetal and placental growth occur in concert; however, which imparts more influence on the other is unknown.

Fetal growth in gestational diabetes mellitus (GDM) is directly linked to maternal glycaemic control; however, this relationship may be altered by oral anti-hyperglycaemic agents. Unlike insulin, such drugs cross the placenta and may thus have independent effects on fetal or placental tissues. We investigated the association between GDM treatment and fetal, neonatal, and childhood growth. PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and Cochrane databases were systematically searched (inception to 12 February 2020). Outcomes of GDM-affected pregnancies randomised to treatment with metformin, glyburide, or insulin were included. Studies including preexisting diabetes or nondiabetic women were excluded. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Maternal outcome measures were glycaemic control, weight gain, and treatment failure. Offspring anthropometric parameters included fetal, neonatal, and childhood weight and body composition data. Thirty-three studies (n = 4,944), from geographical locations including Europe, North Africa, the Middle East, Asia, Australia/New Zealand, and the United States/Latin America, met eligibility criteria. Twenty-two studies (n = 2,801) randomised women to metformin versus insulin, 8 studies (n = 1,722) to glyburide versus insulin, and 3 studies (n = 421) to metformin versus glyburide. Eleven studies (n = 2,204) reported maternal outcomes. No differences in fasting blood glucose (FBS), random blood glucose (RBS), or glycated haemoglobin (HbA1c) were reported. No studies reported fetal growth parameters. Thirty-three studies (n = 4,733) reported birth weight. Glyburide-exposed neonates were heavier at birth (58.20 g, 95% confidence interval [CI] 10.10-106.31, p = 0.02) with increased risk of macrosomia (odds ratio [OR] 1.38, 95% CI 1.01-1.89, p = 0.04) versus neonates of insulin-treated mothers. Metformin-exposed neonates were born lighter (-73.92 g, 95% CI -114.79 to -33.06 g, p < 0.001) with reduced risk of macrosomia (OR 0.60, 95% CI 0.45-0.79, p < 0.001) than insulin-exposed neonates. Metformin-exposed neonates were born lighter (-191.73 g, 95% CI -288.01 to -94.74, p < 0.001) with a nonsignificant reduction in macrosomia risk (OR 0.32, 95% CI 0.08-1.19, I2 = 0%, p = 0.09) versus glyburide-exposed neonates. Glyburide-exposed neonates had a nonsignificant increase in total fat mass (103.2 g, 95% CI -3.91 to 210.31, p = 0.06) and increased abdominal (0.90 cm, 95% CI 0.03-1.77, p = 0.04) and chest circumferences (0.80 cm, 95% CI 0.07-1.53, p = 0.03) versus insulin-exposed neonates. Metformin-exposed neonates had decreased ponderal index (-0.13 kg/m3, 95% CI -0.26 to -0.00, p = 0.04) and reduced head (-0.21, 95% CI -0.39 to -0.03, p = 0.03) and chest circumferences (-0.34 cm, 95% CI -0.62 to -0.05, p = 0.02) versus the insulin-treated group. Metformin-exposed neonates had decreased ponderal index (-0.09 kg/m3, 95% CI -0.17 to -0.01, p = 0.03) versus glyburide-exposed neonates. Study limitations include heterogeneity in dosing, heterogeneity in GDM diagnostic criteria, and few studies reporting longitudinal growth outcomes. Maternal randomisation to glyburide resulted in heavier neonates with a propensity to increased adiposity versus insulin- or metformin-exposed groups. Metformin-exposed neonates were lighter with reduced lean mass versus insulin- or glyburide-exposed groups, independent of maternal glycaemic control. Oral anti-hyperglycaemics cross the placenta, so effects on fetal anthropometry could result from direct actions on the fetus and/or placenta. We highlight a need for further studies examining the effects of intrauterine exposure to antidiabetic agents on longitudinal growth, and the importance of monitoring fetal growth and maternal glycaemic control when treating GDM. This review protocol was registered with PROSPERO (CRD42019134664/CRD42018117503).