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Background: While ambient air pollution has been associated with fetal growth in singletons, its correlation among twins is not well-established due to limited research in this area., Methods: The effects of exposure to PM 2.5 particulate matter and its main components during pregnancy on birth weight and the incidence of large for gestational age (LGA) were investigated in 6177 twins born after in vitro fertilization at the Center for Reproductive Medicine of Shanghai Ninth People's Hospital (Shanghai, China) between 2007 and 2021. Other birth weight-related outcomes included macrosomia, low birth weight, very low birth weight, and small for gestational age (SGA). The associations of PM 2.5 exposure with birth weight outcomes were analyzed using linear mixed-effect models and random-effect logistic regression models. Distributed lag models were incorporated to estimate the time-varying associations., Results: The findings revealed that an interquartile range (IQR) increase (18 μg/m 3 ) in PM 2.5 exposure over the entire pregnancy was associated with a significant increase (57.06 g, 95 % confidence interval [CI]: 30.91, 83.22) in the total birth weight of twins. The effect was more pronounced in larger fetuses (34.93 g, 95 % CI: 21.13, 48.72) compared to smaller fetuses (21.77 g, 95 % CI: 6.94, 36.60) within twin pregnancies. Additionally, an IQR increase in PM 2.5 exposure over the entire pregnancy was associated with a 34 % increase in the risk of LGA (95 % CI: 11 %, 63 %). Furthermore, specific chemical components of PM 2.5 , such as sulfate (SO 4 2- ), exhibited effect estimates comparable to the PM 2.5 total mass., Conclusion: Overall, the findings indicate that exposures to PM 2.5 and its specific components are associated with fetal overgrowth in twins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Australia's 2019/20 bushfire season was one of the most severe on record, from both land mass burned and the economic impact. This extreme weather season allowed the researchers to examine the effect of high PM 2.5 exposure during high bushfire days on birthweight and gestational age. It is well known that bushfire smoke is harmful to human health. However, the impact this has on the developing fetus is not yet clear. 25,346 births were assessed, their exposure calculated based on location data, and outcomes analyzed. Mothers exposed to high PM 2.5 (measured by a 24-hour average PM 2.5 greater than 25 µg/m 3 ) demonstrated a significant birthweight reduction of 0.77 g per day of exposure. Those who were also self-identified as having smoked at any time during their pregnancy were at higher risk, with a 1.33 g reduction in birthweight per day of exposure. Gestational age was reduced by 0.01 days per day of exposure in the total cohort, with no significant difference demonstrated in those who smoked. The compounded effects of high PM 2.5 exposure may result in birthweight reduction, with neonates born to mothers who smoked at increased risk., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Growth restriction has been associated with the risk of none communicable disease. Many anthropometric determinants like birth weight, birth length, and pondoral Index, are related to maternal suboptimal nutrition and infants' deficiency of some essential heavy metals., Objective: The specific objective of this study is to determine the extent of toxic metals in the cord blood, birth outcomes, and their effect on the biophysical profiles of neonates., Methods: The cord blood of 30 preterm, 30 term newborns, and 60 maternal veinous blood were analysed using an Atomic Absorption Spectrometer (Analyst 200 Perkin-Elmer, USA). Metals such as aluminum, antimony, arsenic, cadmium, lead, and mercury were determined by measuring the levels of these metals in cord blood and maternal blood respectively., Results: Findings thus suggest that preterms are particularly susceptible to toxicity on somatic parameters., Conclusions: Therefore, safety measures should be taken to prevent human contamination and exposure during pregnancy., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: Aflatoxins are various poisonous carcinogens and mutagens produced by Aspergillus species. Exposure to aflatoxins during pregnancy results in adverse birth outcomes. This meta-analysis was carried out to determine the estimates of how much aflatoxin is harmful to the pregnancy and its outcome, including birthweight, birth length, low birthweight (LBW), small for gestational age (SGA), stunting, poverty, food insecurity, income, pesticides and stillbirth, in an African context., Methods: Both published and unpublished studies in Africa were searched on MEDLINE, PubMed, Embase, SCOPUS, Web of Science and Google Scholar. Stata version 18.2 software was used for cleaning and analysis. The prevalence with a 95% confidence interval (CI) was estimated using the random effects model and a forest plot was used to present the findings. In addition, the heterogeneity of the study was assessed using Cochrane I2 statistics and publication bias was assessed using Egger's intercept and funnel plot., Results: This review included 28 studies with a total of 6283 pregnant women and newborns. The analysis showed the overall level of exposure to aflatoxins was 64% (95% CI 48 to 78, τ2=0.66, I2=99.34%, p=0.001). In the subgroup analysis by publication year, the highest level of exposure to aflatoxins (82% [95% CI 69 to 92]) was observed among studies published from 2020 to 2023. This study also found that exposure to aflatoxins during pregnancy had an association with prematurity, LBW, SGA and stillbirth., Conclusions: The data analysed in this study indicated that three of every five pregnant women had exposure to aflatoxins in Africa. Moreover, pregnant women exposed to aflatoxins had a higher likelihood of having a LBW and SGA newborn. Thus governments and all stakeholders should initiate policies that mitigate the toxicity of aflatoxins in pregnant women, foetuses and newborns., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Astronomical Society of Japan.)

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association., (© 2024. The Author(s).)

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose-response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: -1.748, -0.319), 0.647 days (95 % CI: -1.076, -0.219), 0.845 days (95 % CI: -1.430, -0.260), and 0.888 days (95 % CI: -1.398, -0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose-response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study aims to analyze the effects of developmental exposure to phthalates at environmentally relevant doses on the neural control of male and female reproduction. For this purpose, C57Bl/6J mice were exposed to di-(2-ethylexyl) phthalate (DEHP) alone (5 or 50 μg/kg/d), or DEHP (5 μg/kg/d) in a phthalate mixture. Exposure through diet started 6 weeks before the first mating and lasted until weaning of litters from the second gestation (multiparous dams). Analyses of offspring born from multiparous dams exposed to DEHP alone or in a phthalate mixture showed that females experienced a delayed pubertal onset, and as adults they had prolonged estrous cyclicity and reduced Kiss1 expression in the preoptic area and mediobasal hypothalamus. Male littermates showed a reduced anogenital distance and delayed pubertal onset compared with controls. However, in adulthood the weight of androgen-sensitive organs and hypothalamic Kiss1 expression were unaffected, suggesting normal functioning of the male gonadotropic axis. Developmental exposure to DEHP alone or in a phthalate mixture reduced the ability of intact males and ovariectomized and hormonally primed females to attract a sexual partner and to express copulatory behaviors. In addition, females were unable to discriminate between male and female stimuli in the olfactory preference test. Social interaction was also impaired in females, while locomotor activity and anxiety-like behavior in both sexes were unaffected by the treatment. The sexual deficiencies were associated with reduced expression of the androgen receptor in the preoptic area and progesterone receptor in the mediobasal hypothalamus, the key regions involved in male and female sexual behavior, respectively. Thus, the neural structures controlling reproduction are vulnerable to developmental exposure to phthalates at environmentally relevant doses in male and female mice. Adult females had an impaired gonadotropic axis and showed more affected behaviors than adult males., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2 µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95-1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16-5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33-9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures., (© 2024. The Author(s).)

Background: Nationwide evidence linking maternal ozone exposure with fetal growth restriction (FGR) was extensively scarce, especially in the Middle East with dry climate and distinct religious culture., Methods: We carried out a national retrospective birth cohort study using registry-based records from 749 hospitals across 31 provinces in Iran from 2013 to 2018. Monthly concentrations of maximum daily average 8-hour (MDA8) ozone at 0.125° × 0.125° resolution were extracted from well-validated spatiotemporal grid dataset. Linear and logistic regression models were employed to evaluate associations of maternal MDA8 ozone exposure with birthweight outcomes. Assuming causality, the comparative risk assessment framework was utilized to estimate the burden of low birthweight (LBW), small for gestational age (SGA), and birthweight loss per livebirth (BLL) attributable to ambient ozone pollution., Results: Of 4030383 livebirths included in the study, 264304 (6.6%) were LBW and 484405 (12.0%) were SGA. Each 10-ppb increase in MDA8 ozone exposure was associated with an odds ratio of 1.123 (95% confidence interval [CI]: 1.104 to 1.142) for LBW and 1.210 (95% CI: 1.197 to 1.223) for SGA, and a 30.5-g (95% CI: 29.0 to 32.0) reduction in birthweight. We observed approximately linear exposure-response relationships of maternal MDA8 ozone exposure with LBW (P nonlinear = 0.786), SGA (P nonlinear = 0.156), and birthweight reduction (P nonlinear = 0.104). Under the premise of causal association, we estimated 6.6% (95% CI: 5.7 to 7.5) of LBW, 10.1% (95% CI: 9.6 to 10.6) of SGA, and 18.8 g (95% CI: 17.9 to 19.7) of BLL could be attributable to maternal ozone exposure in Iran. Considerably greater risk and burden of ozone-related FGR were observed among younger, less-educated, and rural-dwelling mothers., Conclusions: Our study provided compelling evidence that maternal ozone exposure was associated with heightened FGR risk and burden, particularly among socioeconomically disadvantaged mothers. These findings underscored the urgent need for government to incorporate socioeconomic factors into future ozone-related health policies, not only to mitigate pollution, but also minimize inequality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It has been well-investigating that individual phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affect public health. However, there is still a gap that the mixture of PAEs and PAHs impacts birth outcomes. Through innovative methods for mixtures in epidemiology, we used a metabolome Exposome-Wide Association Study (mExWAS) to evaluate and explain the association between exposure to PAEs and PAHs mixtures and birth outcomes. Exposure to a higher level of PAEs and PAHs mixture was associated with lower birth weight (maximum cumulative effect: 143.5 g) rather than gestational age. Mono(2-ethlyhexyl) phthalate (MEHP) (posterior inclusion probability, PIP = 0.51), 9-hydroxyphenanthrene (9-OHPHE) (PIP = 0.53), and 1-hydroxypyrene (1-OHPYR) (PIP = 0.28) were identified as the most important compounds in the mixture. In mExWAS, we successfully annotated four overlapping metabolites associated with both MEHP/9-OHPHE/1-OHPYR and birth weight, including arginine, stearamide, Arg-Gln, and valine. Moreover, several lipid-related metabolism pathways, including fatty acid biosynthesis and degradation, alpha-linolenic acid, and linoleic acid metabolism, were disturbed. In summary, these findings may provide new insights into the underlying mechanisms by which PAE and PAHs affect fetal growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Several studies have explored the association between fish consumption during pregnancy and favorable neonatal outcomes, although some yield conflicting results. The American College of Obstetricians and Gynecologists recommends two to three servings of low-mercury fish per week for pregnant or breastfeeding women. However, fish can be a source of pollutants, like methylmercury, impacting neurological development. Conflicting studies on docosahexaenoic acid (DHA) supplementation exist in the literature, possibly due to varied supplement dosages. This survey, involving 501 women, investigated fish consumption and DHA supplement intake concerning gestational and neonatal outcomes. Notably, 92.1% of participants consumed fish weekly, with significant differences observed in gestational weight gain, birth weight, and length for those eating fish ≥3 times weekly compared to non-consumers. This study supports the recommendation for pregnant women to include fish in their diet while limiting exposure to environmental pollutants. Omega-3 fatty acid supplements are suggested to attain nutritional benefits without mercury risk.

Introduction: This study investigates the association between maternal exposure to particulate matter (PM 10 ) and nitric dioxide (NO 2 ) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth., Methods: Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression., Results: In the third trimester, for each 10 μm/m 3 increase in PM 10 or NO 2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM 10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84)., Discussion: The association of PM 10 and NO 2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Question: Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population?, Summary Answer: Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (

Objective: In this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these., Method: We divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs., Results: We used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable., Conclusion: We found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions., Competing Interests: Declaration of competing interest None of the authors has anything to declare., (Copyright © 2023. Published by Elsevier Inc.)

Rationale Clinical research has shown that prenatal exposure to nicotine may result in increased obesity risk later in life. Preclinical research has corroborated this finding, but few studies have investigated inhaled nicotine or the interaction with diet on obesity risk. Objective The aim of this study was to investigate the effects of prenatal nicotine exposure on both direct and indirect obesity measures, with both sex and diet as factors. Methods Pregnant rats were exposed to either vehicle or nicotine vapor (24 mg/mL or 59 mg/mL) throughout the entire gestational period. Offspring from each treatment group were given either a normal diet or a high fat diet starting at postnatal day 22. Caloric intake, body weight, spontaneous locomotion, sleep/wake activity, and voluntary exercise were measured throughout adolescence. Pregnancy weight gain and pup birthweights were collected to further measure developmental effects of prenatal nicotine exposure. Results Both maternal weight gain during pregnancy and pup weight at birth were decreased with prenatal nicotine exposure. Early adolescent males showed increased spontaneous activity in the open field following prenatal nicotine exposure compared to vehicle counterparts, particularly those given high-fat diet. Additionally, high dose nicotine prenatal treated males ran significantly less distance on the running wheel in late adolescence compared to vehicle counterparts, in the normal diet group only. Conclusion The results presented here show decreased birthweight, hyperactivity, and decreased voluntary exercise in adolescence following prenatal nicotine exposure in dose, sex, and diet dependent manners, which could lead to increased obesity risk in adulthood., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The use of alprazolam in pregnancy can adversely affect maternal and neonatal health. This study examined neonatal outcomes following exposure to alprazolam in pregnancy. Women prescribed alprazolam during pregnancy ( n  = 48) between 2014 and 2018 were identified from routinely-collected state administrative prescribing records and perinatal data. Two comparison groups of women; 1) prescribed alprazolam outside of pregnancy ( n  = 96) and 2) women never prescribed alprazolam ( n  = 96) were also identified. The health of women and their children was examined using administrative hospital, mortality and perinatal data and compared to the comparison groups using generalized linear models. Prenatal alprazolam exposure was not associated with a reduction in average birth weight or gestational age. However, neonates prenatally exposed to alprazolam were more likely be classified as having low birth weight for gestational age compared with alprazolam comparison group (OR: 4.46, 95% CI: 1.54-12.95) and the non-alprazolam comparison group (OR: 3.27, 95% CI: 1.22-8.79). There were no cases of perinatal mortality or floppy baby syndrome in alprazolam-exposed neonates. While the use of alprazolam during pregnancy was not associated with an increased risk of severe adverse neonatal outcomes (e.g. perinatal mortality), it was associated with neonates being born with a low birth weight for gestational age.

Background: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study., Methods: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size., Results: Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth., Conclusion: Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA)., Methods: A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion., Results: Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores., Conclusions: In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethical approval This study involved human participants. It was approved by the Ethic Committees of the Children’s Hospital of Fudan University ([2015]-124). Consent to participate Written informed consent was not obtained from each patient or their family guardian because this study was a single-centre, retrospective, real-world study. Consent to publish The manuscript contains no individual person’s data., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Progestin-only pills (POPs) have been used for contraception in breastfeeding women for years. The existing guidelines allow the use of these contraceptives., Methods: Multicenter study with a single visit and retrospective data review. The study involved 100 women who used a drospirenone-only pill (DRSP) for contraception for at least 5 months during breastfeeding. The study aimed to analyze for those successful users the impact on new-born development, the bleeding profile and evaluate user satisfaction., Results: Analysis of the newborns showed that their growth parameters length and weight, were within the expected range of standard development. The mean birth weight was 3368 g, with the lowest recorded weight being 2860 g and the highest 5040 g. The median length of the newborns was 55 cm, ranging from 35 to 65 cm. All new-borns demonstrated appropriate growth within the established percentiles. Acceptability with the bleeding profile was rated with a VAS score: the mean acceptability rating was 82.8. Women aged 35 years or older reported significantly higher acceptability compared to younger women (≥35 years: mean = 88.4, SD = 16.5; <35 years: mean = 80.3, SD = 20.2) ( p  = 0.02). Sixty-one patients ( N  = 61; 61.0%; 95% CI: 50.7 - 70.4%) expressed willingness to continue using DRSP after breastfeeding., Conclusion: Among those patients who continued the use of the DRSP only-pill for 5 months, this study shows no negative impact for new-borns, with no clinical influence observed on their growth. Additionally, those users expressed high satisfaction with the bleeding profile of the pill.Clinical trial registration number: DRKS00028438 .

Background: Arsenic pollution is widespread worldwide. The association between gestational arsenic exposure and adverse birth outcomes has been demonstrated in previous studies; however, few investigations have examined whether gestational arsenic exposure has adverse effects on infant growth and development after birth., Objective: Our study was designed to evaluate particular associations between gestational arsenic exposure during pregnancy and newborn birth size and to investigate whether these associations continue to affect infants after birth., Methods: An ongoing prospective cohort study of 1100 pregnant women was conducted at the Wuxi Maternity and Child Health Care Hospital. The total urinary arsenic concentrations in the 2nd and 3rd trimester were determined using atomic fluorescence spectrometry. The relationships between urinary arsenic concentration and foetal growth parameters (birth weight, head circumference, length, and ponderal index), SGA (Small for gestational age), and physical growth of infants within one year after birth were analysed., Results: Urinary arsenic concentration in the 3rd trimester was associated with an increased incidence of SGA [adjusted model: OR = 2.860 (95% CI: 1.168, 7.020), P = 0.021)]. Arsenic exposure in late pregnancy had an adverse effect on the physical development of infants before the age of 1 year, and there was an interaction effect with the sex of infants. The weight and length of boys at 6 and 12 months negatively correlated with maternal urinary arsenic levels during late pregnancy., Conclusions: In addition to affecting foetal growth, exposure to arsenic in the 3rd trimester also negatively affected the growth of offspring within the first year of life., (© 2024. The Author(s).)

Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly ( p < 0.05) and negatively associated with birth weight (β = -39.9, 95% CI: -73.8, -6.1), birth length (β = -0.19, 95% CI: -0.34, -0.04), head circumference (β = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (β = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (β = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.

It remains unclear whether and how maternal exposure to biomass fuel influences infant anthropometry or body proportionality at birth, which are linked to their survival, physical growth, and neurodevelopment. Therefore, this study seeks to explore the association between household-level exposure to biomass cooking fuels and infant size and body proportionality at birth among women in rural Bangladesh. A total of 909 women were derived from the Pregnancy Weight Gain study, which was conducted in Matlab, a rural area of Bangladesh. Infant's weight (g), length (cm), head circumference (cm), small for gestational age (SGA W ), short for gestational age (SGA L ), low head circumference for gestational age (SGA HC ), ponderal index, and cephalization index at birth were the outcomes studied. Of the women, 721 (79.3%) were dependent on biomass fuel. Compared to infants born to mothers who used gas for cooking, those born to biomass users had lower weight (β - 94.3, CI - 155.9, - 32.6), length (β - 0.36, 95% CI - 0.68, - 0.04), head circumference (β - 0.24, CI - 0.47, - 0.02) and higher cephalization index (β 0.03, CI 0.01, 0.05) at birth. Maternal biomass exposure is more likely to lead to symmetric SGA, although there is evidence for some brain-sparing effects., (© 2024. The Author(s).)

Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy., Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy., Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW., Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

This study aimed to investigate the effects of prenatal docosahexaenoic acid (DHA) supplementation on pregnancy outcomes through a systematic review and meta-analysis. We hypothesized that prenatal DHA intake through supplements will improve pregnancy outcomes. Detailed literature search was performed using online databases such as PubMed, EMBASE, and Google Scholar till November 2022, to identify the randomized controlled trials (RCT) with maternal intake of DHA supplementation during the latter half of pregnancy compared to the placebo/control. Based on the inclusion and exclusion criteria, nine RCTs involving 5710 subjects were included. This meta-analysis showed that DHA supplementation (450-800 mg/day) was associated with a significantly higher birth weight of infants (Inverse variance [IV]: 101.71 [57.36-146.06] at 95% CI, P = .00001, I 2 = 0%), and fewer low birth weights (LBWs) (Mantel-Haenszel [M-H]: 0.53 [0.33-0.86] at 95% CI, P = .01, I 2 = 72%), with lesser but statistically insignificant pre-term births (PTB) (M-H: -0.02 [-0.04 to 0.00] at 95% CI, P = .07, I 2 = 0%) compared to the placebo. However, the DHA supplementation has no effect on gestational length (IV: -2.26 [-9.64 to 5.12] at 95% CI, P = .55, I 2 = 100%) compared to the placebo. In conclusion, the outcomes of this meta-analysis showed that prenatal DHA supplementation (450-800 mg/day) may reduce the risk of preterm births and increase infant birth weight., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Environmental phenols are endocrine disrupting chemicals hypothesized to affect early life development. Previous research examining the effects of phenols on fetal growth has focused primarily on associations with measures of size at delivery. Few have included ultrasound measures to examine growth across pregnancy., Objective: Investigate associations between prenatal exposure to phenols and ultrasound and delivery measures of fetal growth., Methods: Using the LIFECODES Fetal Growth Study (n = 900), a case-cohort including 248 small-for-gestational-age, 240 large-for-gestational age, and 412 appropriate-for-gestational-age births, we estimated prenatal exposure to 12 phenols using three urine samples collected during pregnancy (median 10, 24, and 35 weeks gestation). We abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-average phenol biomarker concentrations and repeated ultrasound measures of fetal growth using linear mixed effects models and associations with birthweight using linear regression models. We also used logistic regression models to estimate associations with having a small- or large-for-gestational birth., Results: We observed positive associations between 2,4-dichlorophenol, benzophenone-3, and triclosan (TCS) and multiple ultrasound measures of fetal growth. For example, TCS was associated with a 0.09 (95 % CI: 0.01, 0.18) higher estimated fetal weight z-score longitudinally across pregnancy. This effect size corresponds to a 21 g increase in estimated fetal weight at 30 weeks gestation. Associations with delivery measures of growth were attenuated, but TCS remained positively associated with birthweight z-scores (mean difference: 0.13, 95 % CI: 0.02, 0.25). Conversely, methylparaben was associated with higher odds of a small-for-gestational age birth (odds ratio: 1.45, 95 % CI: 1.06, 1.98)., Discussion: We observed associations between some biomarkers of phenol exposure and ultrasound measures of fetal growth, though associations at the time of delivery were attenuated. These findings are consistent with hypotheses that phenols have the potential to affect growth during the prenatal period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Early life events and environmental factors are associated with type 2 diabetes (T2D) development. We assessed the combined effect of birth weight andambient air pollutants, and effect of their interaction on T2D risk. Totally, 6,474 T2D incidents were recorded over an 8.7-year follow-up period. The adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were 1.31 (1.26, 1.36) for each kilogram decrease in birth weight, and 1.08 (1.05, 1.11) for each standard deviation increase in air pollution score (APS). Birth weight<3000 g amplified the T2D risk associated with high APS. A combination of the lowest birth weight (<2500 g) and the highest quintile of APS led to over two-fold increase in T2D risk (aHR: 2.17; 95% CI: 1.79-2.64). There was a significant additive interaction between them. In conclusion, ambient air pollutants increase the risk for T2D, particularly in populations with low birth weight.

Background: Several meta-analyses assessed the relationship between exposure to PM with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) during pregnancy and birth weight (BW), but results were inconsistent and substantial unexplained heterogeneity was reported. We aimed to investigate the above association and to explore sources of heterogeneity across studies., Methods: We systematically reviewed the current worldwide evidence examining the association between PM 2.5 and BW. The review protocol was registered on the PROSPERO website (CRD42020188996) and followed PRISMA guidelines. We extracted association measures for BW and low birth weight (LBW, BW < 2500 g) from each study to evaluate pooled summary measures and to explore sources of between-study heterogeneity., Findings: Of the 2677 articles identified, 84 met the inclusion criteria (~42 M births). Our random effects meta-analyses revealed substantial heterogeneity among included studies (I 2  = 98.4 % and I 2  = 77.7 %, for BW and LBW respectively). For LBW, the heterogeneity decreased (I 2  = 59.7 %) after excluding four outlying studies, with a pooled odds ratio 1.07 (95 % confidence interval, CI: 1.05, 1.09) per a 10-μg/m 3 increase in mean PM 2.5 exposure over the entire pregnancy. Further subgroup analysis revealed geographic heterogeneity with higher association in Europe (1.34, (1.16, 1.55)) compared to Asia (1.06, (1.03, 1.10)) and US (1.07, (1.04, 1.10))., Conclusion: The association between PM 2.5 and birth weight varied depending on several factors. The sources of heterogeneity between studies included modifiers such as study region and period. Hence, it is advisable not to pool summary measures of PM 2.5 -BW associations and that policy would be informed by local evidence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 μg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [β] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; β = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (β = 0.035 kg/mouth, 95% CI: 0.00-0.064; β = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (β = 0.054 kg/mouth, 95% CI: 0.015-0.093; β = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.

The impact of prenatal exposure to a mixture of heavy metals on birth weight in newborns has been a topic of ongoing interest. In this study, 258 mothers and infants from the New Hampshire Birth Cohort Study (NHBCS) were selected as the study subjects, and the concentrations of seven heavy metals in the placenta, including Aluminum (Al), Cobalt (Co), Chromium (Cr), Nickel (Ni), Plumbum (Pb), Selenium (Se) and Arsenic (As) were collected. And the birth weight of newborns, the relevant covariates of mothers and newborns were collected. Three analytical methods, Weighted Quantile Sum (WQS) regression, Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were employed. After adjusting for maternal gestational age, pre-pregnancy BMI, smoking status, education level, parity, gestational age and newborn gender, the combined three methods showed that the total effect of mixed exposure of seven heavy metals on birth weight was negative. Specifically, the WQS analysis revealed that Se had the greatest impact on birth weight, followed by Al. The QGC results showed that the heavy metal associated with the reduction of birth weight was mainly Se and Al in female and male infants, respectively. The BKMR analysis demonstrated a negative combined effect of the seven heavy metals on birth weight in both male and female infants, with Se having the highest posterior inclusion probabilities (PIPs) for female infants (0.45), and Al having the highest PIPs for male infants (0.64) after stratification by gender. In summary, mixed exposure to heavy metals during pregnancy was associated with a decrease in newborn birth weight. Furthermore, there are gender effects with Se and Al associated with decreased birth weight in female and male infants, respectively. These findings provide a theoretical basis for the development of public health policies aimed at preventing adverse pregnancy outcomes and improving the health of newborns.

Background: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships., Methods: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation., Results: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (β = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (β = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (β = 23 g; 95% CI: -25, 71) compared to those with higher educational status (β = -9 g; 95% CI: -24, 6)., Conclusions: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight., (© 2024. The Author(s).)

Purpose: In a cohort of pregnant women using antihypertensive drugs, we compared exposure to antidepressants versus no exposure and the possible association with birth weight, APGAR scores, NICU admission, and maternal admission to an obstetrical intensive care unit (OHC). It was hypothesized that pregnant women with hypertensive disorders using antidepressants are at greater risk of complications., Methods: A retrospective cohort study in a general teaching hospital in Zwolle, in the Middle-Northern part of The Netherlands. Finally, 58 pregnancies in the exposed group and 273 pregnancies in the reference group met all inclusion and exclusion criteria. We compared the neonate's birthweight between the exposed to antidepressants group and the reference group as the primary outcome. Secondary outcomes were the APGAR score at 1 and 5 min and obstetric high care (OHC) admission of the mother and neonatal intensive care unit (NICU) admission of the child., Results: We found no differences in birth weight in neonates of mothers with hypertensive disorders and whether or not to use antidepressants. Besides a possible higher risk of admission to an OHC in women with hypertension-complicated pregnancies using antidepressants, we found no other maternal or neonatal risks in this population., Conclusion: We found no additional maternal or neonatal risks of using antidepressants prescribed to women with hypertension disorders during pregnancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity., Objectives: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z -score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth., Methods: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case-cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models., Results: Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; 1.31  ng / mL ) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z -scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: - 0.08 , 0.17). At delivery, an IQR ( 1.00  ng / mL ) increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94)., Conclusions: In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647.

Traffic-related air pollution (TRAP) poses a significant public health risk that is associated with adverse birth outcomes. Large roadway infrastructure projects present a natural experiment to examine how resulting congestion change is associated with adverse birth outcomes for nearby populations. This study is designed to examine the influence of living close to a roadway before, during, and after a construction project using a difference-in-differences design. We integrated data on all large roadway construction projects (defined as widening of existing roads, building new roads, improving bridges, installing intelligent transportation systems, improving intersections, and installing or upgrading traffic signals) in Texas from 2007 to 2016 with Vital Statistic data for all births with residential addresses within 1 km of construction projects. Our outcomes included term low birth weight, term birth weight, preterm birth, and very preterm birth. Using a difference-in-differences design, we included births within 3 years of construction start and 2 years of construction end. In our main model, the exposed group is limited to pregnant individuals residing within 300 m of a construction project, and the control group includes those living within 300-1000 m from a project. We used regression models to estimate the influence of construction on infant health. We included 1,360 large roadway construction projects linked to 408,979 births. During construction, we found that the odds of term low birth weight increased by 19% (95% CI: 1.05, 1.36). However, we saw little evidence of an association for other birth outcomes. Contrary to our hypothesis of decreased TRAP after construction ends, we did not observe consistent improvements post-construction for pregnant individuals living within 300 m. Continued consideration of the influence of traffic congestion programs on birth outcomes is necessary to inform future policy decisions., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Benzophenone (BP)-type UV filters are commonly added to sunscreens and cosmetics to protect against UV radiation for human skin and hair. As a result, BPs are ubiquitous in the environment and human body, and their endocrine-disrupting characteristics have been a hot topic of discussion. However, our knowledge regarding the detrimental effects of prenatal exposure to BPs on pregnant women and their offspring remains limited. To fill this gap, we determined five BP derivatives in 600 serum samples obtained from pregnant women. All the target analytes, except 2,4-dihydroxybenzophenone (BP-1), have achieved a 100 % detection rate. The most prevalent compound was 2-hydroxy-4-methoxybenzophenone (BP-3), with a median concentration of 0.545 ng/mL. Significant and positive correlations were observed among BP derivatives, indicating both endogenous metabolism and common external sources. Utilizing Bayesian kernel machine regression (BKMR) and quantile-based g-computation (QGC) models, we found relationships between BP exposure and reduced neonatal birth weight (BW) and birth chest circumference (BC) during the third trimester. Notably, the adverse effect of BPs on birth size was sex-specific. Moreover, triglyceride (TG) was identified as a potential mediator of the effect of BPs on blood pressure, and co-exposure to BPs was linked to disruptions in thyroid hormone levels and glucose regulation. Further research is warranted to unravel the toxicity of BPs and their detrimental effects on pregnant women and fetuses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Epidemiological studies addressing the combined effects of exposure to chemical mixtures at different stages of pregnancy on birth size are scarce., Objective: To evaluate the association between prenatal exposure to chemical mixtures and birth size., Methods: Our previous study repeatedly measured the urinary concentrations of 34 chemical substances among 743 pregnant women and identified three distinct clusters of exposed population and six dominant principal components of exposed chemicals in each trimester. In this study, we assessed the associations of these exposure profiles with birth weight, birth length, and ponderal index using multivariable linear regression., Results: We found that compared with women in cluster 1 (lower urinary chemical concentrations), women in cluster 2 (higher urinary concentrations of metals, benzothiazole, benzotriazole, and some phenols), and women in cluster 3 (higher urinary concentrations of phthalates) were more likely to give birth to children with higher birth length [0.23 cm (95% CI: -0.03, 0.49); 0.29 cm (95%CI: 0.03, 0.54), respectively]. This association was observed only in 1st trimester. In addition, prenatal exposure to PC3 (higher benzophenones loading) was associated with reduced birth length across pregnancy [-0.07 cm (95% CI: -0.18, 0.03) in 1st and 2nd trimester; -0.13 cm (95% CI: -0.24, -0.03) in 3rd trimester]. Exposure to PC6 (higher thallium and BPA loading in 2nd trimester) was associated with increased birth length [0.15 cm (95% CI: 0.05, 0.26)]. Compared with other outcomes, associations of both clusters and PCs with birth length were stronger, and these associations were more pronounced in boys., Impact Statement: Exposure to multiple chemicals simultaneously, the actual exposure situation of pregnant women, was associated with birth size, indicating that chemical mixtures should be taken more seriously when studying the health effects of pollutants., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Phthalates are common endocrine disruptors. The placental barrier can be crossed by phthalates and may have a negative impact on the health of the fetus. However, the association between prenatal exposure to phthalates and birth size is still debatable. Here, we performed this meta-analysis to assess the relationship between prenatal phthalates exposure and birth size. Eighteen studies were finally included by searching PubMed, Embase, Scopus, Ovid, and Web of Science databases and standardized regression coefficients and standard errors were used to pool effect size. Our results showed that prenatal exposure to MMP (=-0.04, 95%CI: -0.08, -0.01) and MEP (=-0.01, 95%CI: -0.01, -0.002) was significantly associated with birth weight. However, no significant associations were identified for phthalate exposure with birth length, head circumference and chest circumference. Because the limiting of studies, more high-quality case-control studies or cohort studies are urgently needed to draw the best conclusions.

Background: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards., Objective: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs., Methods: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86)., Results: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations., Signifance: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs., Impact: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes., Objectives: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California., Methods: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7  ppm (the current level recommended by the US Department of Health and Human Services) and 0.5  ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z -scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers., Results: Fluoride levels ranged from 0 to 2.5  ppm , with a median of 0.51  ppm . There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7  ppm [ - 2.2 g ; 95% confidence interval (CI): - 4.4 , 0.0] and to 0.5  ppm ( - 5.8 g ; 95% CI: - 10.0 , - 1.6 ). There were small negative associations with birth-weight-for-gestational-age z -scores for both hypothetical interventions ( 0.7  ppm : - 0.004 ; 95% CI: - 0.007 , 0.000 and 0.5  ppm : - 0.006 ; 95% CI: - 0.013 , 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7  ppm [ risk difference  ( RD ) = - 0.001 ; 95% CI: - 0.002 , 0.000 and 0.5  ppm ( - 0.001 ; 95% CI: - 0.003 , 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention., Conclusion: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z -scores in California. https://doi.org/10.1289/EHP13732.

Background: Single-pollutant models have linked prenatal PM 2.5 exposure to lower birthweight. However, analyzing air pollutant mixtures better captures pollutant interactions and total effects. Unfortunately, strong correlations between pollutants restrict traditional methods., Objectives: We explored the association between exposure to a mixture of air pollutants during different gestational age windows of pregnancy and birthweight., Methods: We included 4,635 mother-infant dyads from a New York State birth cohort born 2008-2010. Air pollution data were sourced from the EPA's Community Multiscale Air Quality model and matched to the census tract centroid of each maternal home address. Birthweight and gestational age were extracted from vital records. We applied linear regression to study the association between prenatal exposure to PM 2.5 , PM 10 , NO X , SO 2 , and CO and birthweight during six sensitive windows. We then utilized Bayesian kernel machine regression to examine the non-linear effects and interactions within this five-pollutant mixture. Final models adjusted for maternal socio-demographics, infant characteristics, and seasonality., Results: Single-pollutant linear regression models indicated that most pollutants were associated with a decrement in birthweight, specifically during the two-week window before birth. An interquartile range increase in PM 2.5 exposure (IQR: 3.3 µg/m 3 ) from the median during this window correlated with a 34 g decrement in birthweight (95 % CI: -54, -14), followed by SO 2 (IQR: 2.0 ppb; β: -31), PM 10 (IQR: 4.6 µg/m 3 ; β: -29), CO (IQR: 60.8 ppb; β: -27), and NO X (IQR: 7.9 ppb; β: -26). Multi-pollutant BKMR models revealed that PM 2.5 , NO X , and CO exposure were negatively and non-linearly linked with birthweight. As the five-pollutant mixture increased, birthweight decreased until the median level of exposure., Discussion: Prenatal exposure to air pollutants, notably PM 2.5 , during the final two weeks of pregnancy may negatively impact birthweight. The non-linear relationships between air pollution and birthweight highlight the importance of studying pollutant mixtures and their interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth., Objectives: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA)., Materials and Methods: We included all births in Sweden during 2012-2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture., Results: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight., Discussions: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt-1 (soluble Fms-like tyrosine kinase-1), PlGF (placental growth factor), or their impact on birthweight., Methods and Results: sFlt-1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt-1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt-1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester-related variation in levels of sFlt-1 and PlGF, after correction for relevant confounders, the sFlt-1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt-1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54-26.29], P =0.79; sFlt-1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73-22.50], P =0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P =0.03), and sFlt-1 displayed a negative correlation with birthweight ( r =-0.462, P <0.001) and birthweight percentile ( r =-0.332, P =0.008). In TNFi users, these correlations were absent., Conclusions: TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt-1/PlGF ratio., Registration: http://clinicaltrials.gov. Unique identifier: NCT01345071.

Background: Most previous studies investigating the associations between prenatal exposure to phthalates and fetal growth relied on measurements of phthalate metabolites at a single time point. They also focused on weight at birth without assessing growth over pregnancy, preventing the identification of potential periods of fetal vulnerability. We examined the associations between pregnancy urinary phthalate metabolites and fetal growth outcomes measured twice during pregnancy and at birth., Methods: For 484 pregnant women, we assessed 13 phthalate and two 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) metabolite concentrations from two within-subject weekly pools of up to 21 urine samples (median of 18 and 34 gestational weeks, respectively). Fetal biparietal diameter, femur length, head and abdominal circumferences were measured during two routine pregnancy follow-up ultrasonographies (median 22 and 32 gestational weeks, respectively) and estimated fetal weight (EFW) was calculated. Newborn weight, length, and head circumference were measured at birth. Associations between phthalate/DINCH metabolite and growth parameters were investigated using adjusted linear regression and Bayesian kernel machine regression models., Results: Detection rates were above 99 % for all phthalate/DINCH metabolites. While no association was observed with birth measurements, mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were positively associated with most fetal growth parameters measured at the second trimester. Specifically, MiBP was positively associated with biparietal diameter, head and abdominal circumferences, while MnBP was positively associated with EFW, head and abdominal circumferences, with stronger associations among males. Pregnancy MnBP was positively associated with biparietal diameter and femur length at third trimester. Mixture of phthalate/DINCH metabolites was positively associated with EFW at second trimester., Conclusions: In this pregnancy cohort using repeated urine samples to assess exposure, MiBP and MnBP were associated with increased fetal growth parameters. Further investigation on the effects of phthalates on child health would be relevant for expanding current knowledge on their long-term effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study compared milk replacer either remaining unsupplemented (CON) or supplemented with 0.5 g L-carnitine plus 16.7 g L-arginine/kg (CarArg) and fed to 48 low-birth weight (L-BtW) artificially reared piglets (24 per group) from days 7 to 28 of age. Eight farrowing series were needed to complete the study. On day 28, the lightest piglets were slaughtered, and the heaviest pigs were weaned. The heaviest pigs were weaned on day 28 and offered free access to a starter (weaning to 25 kg body weight [BW]), grower (25 to 60 kg BW), and finisher diet (60 to 96 kg BW on day 170 of age). After euthanization on days 28 and 170, blood was sampled for assessment of serum metabolite and hormone concentrations, and the semitendinosus muscle (STM) was weighed, and later subjected to enzyme activity analysis and assessment of myofiber characteristics. In the 170-d-old pigs carcass and meat quality traits were assessed. Growth data were analyzed accordingtoatwo-way analysis of variance (ANOVA), with dietary treatment and farrowing series as fixed effects, while remaining data were analyzed with dietary treatment, sex, their interaction, and farrowing series as main factors. Dietary treatments affected (P ≤ 0.049) muscle enzyme activity at both day 28, with greater citrate synthase (CS) and LDH activities and lower HAD:CS ratio in STM light portion, and lower LDH:CS ratio in STM dark portion, and 170 of age with lower HAD:CS ratio. In the starter period, CarArg pigs had greater average daily gain (P = 0.021) and average daily feed intake (P = 0.010). At slaughter, these pigs had lower (P = 0.013) glucose and greater (P = 0.022) urea serum concentrations. However, supplementing the milk replacer with carnitine and arginine had no long-term effects on growth performance, carcass composition, and meat quality of L-BtW pigs. In addition, muscle morphology and myofiber-related properties remained unaffected by the supplementation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Introduction: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking., Methods: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized inverse probability of treatment weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST., Results: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio, 95% confidence interval, 1.03, 0.93-1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group., Conclusions: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women., Study Design: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores., Results: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery., Conclusions: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabetes and birthweight using the Mendelian randomization paradigm., Methods: Genetic association estimates for systolic blood pressure (SBP) were extracted from summary data of a genome-wide association study (GWAS) on 757,601 participants. Uncorrelated single-nucleotide polymorphisms (SNPs) associated with SBP (p < 5 × 10 -8 ) in BB and CCB drug target gene regions were selected as proxies for drug target perturbation. Genetic association estimates for the outcomes were extracted from GWASs on 4743 cases and 136,325 controls (women without a hypertensive disorder in pregnancy) for pre-eclampsia or eclampsia, 7676 cases and 130,424 controls (women without any pregnancy-related morbidity) for gestational diabetes, and 155,202 women (who have given birth at least once) for birthweight of the first child. All studies were in European ancestry populations. Mendelian randomization estimates were generated using the two-sample inverse-variance weighted model., Results: Although not reaching the conventional threshold for statistical significance, genetically-proxied BB was associated with reduced risk of pre-eclampsia (OR per 10 mmHg SBP reduction 0.27, 95%CI 0.06-1.19, p = 0.08) and increased risk of gestational diabetes (OR per 10 mmHg SBP reduction 2.01, 95%CI 0.91-4.42, p = 0.08), and significantly associated with lower birthweight of first child (beta per 10 mmHg SBP reduction - 0.27, 95%CI - 0.39 to - 0.15, p = 1.90 × 10 -5 ). Genetically-proxied CCB was associated with reduced risk of pre-eclampsia and eclampsia (OR 0.62, 95%CI 0.43-0.89, p = 9.33 × 10 -3 ), and was not associated with gestational diabetes (OR 1.05, 95% CI 0.76-1.45, p = 0.76) or changes in birthweight of first child (beta per 10 mmHg SBP reduction 0.02, 95%CI - 0.04-0.07, p = 0.54)., Conclusions: While BB and CCB antihypertensive drugs may both be efficacious for lowering blood pressure in pregnancy, this genetic evidence suggests that BB use may lower birthweight. Conversely, CCB use may reduce risk of pre-eclampsia and eclampsia without impacting gestational diabetes risk or birthweight. These data support further study on the effects of BBs on birthweight., (© 2022. The Author(s).)

Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes.

Introduction: A high number of women are exposed to acetaminophen during pregnancy worldwide. This drug safety during pregnancy regarding preterm birth, birth weight, and fetal development has not been well described. This study investigated the effect of acetaminophen use during pregnancy on selected adverse pregnancy outcomes., Areas Covered: Databases were searched to identify studies reporting the effects of acetaminophen use during pregnancy on preterm birth, low birth weight, and small for gestational age. The studies' quality was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies. Risk ratios with 95% confidence intervals were estimated using a fixed or random-effects model. Six studies were included for final review, four cohort and two case-control studies. We found no increased risk of preterm birth (RR 0.97; 95% CI 0.59-1.58), and decreased risks of low birth weight (RR 0.65; 95% CI 0.59-0.72) and small for gestational age (RR 0.69; 95% CI 0.50-0.97). Acetaminophen exposure during the third trimester revealed non-significantly in the outcomes., Expert Opinion: Exposure to acetaminophen during pregnancy appears to not increase the risk of the outcomes analyzed. However, there is a lack of information regarding the exposure dose and frequency of acetaminophen use.

The most common complication during pregnancy, gestational diabetes mellitus (GDM), can cause adverse pregnancy outcomes and result in the mother and infant having a higher risk of developing type 2 diabetes after pregnancy. However, existing therapies for GDM remain scant, with the most common being lifestyle intervention and appropriate insulin treatment. MOTS-c, a mitochondrial-derived peptide, can target skeletal muscle and enhance glucose metabolism. Here, we demonstrate that MOTS-c can be an effective treatment for GDM. A GDM mouse model was established by short term high-fat diet combined with low-dose streptozotocin (STZ) treatment while MOTS-c was administrated daily during pregnancy. GDM symptoms such as blood glucose and insulin levels, glucose and insulin tolerance, as well as reproductive outcomes were investigated. MOTS-c significantly alleviated hyperglycemia, improved insulin sensitivity and glucose tolerance, and reduced birth weight and the death of offspring induced by GDM. Similar to a previous study, MOTS-c also could activate insulin sensitivity in the skeletal muscle of GDM mice and elevate glucose uptake in vitro. In addition, we found that MOTS-c protects pancreatic β-cell from STZ-mediated injury. Taken together, our findings demonstrate that MOTS-c could be a promising strategy for the treatment of GDM., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement., (Copyright © 2021 Elsevier B.V. All rights reserved.)