Abstract

Summary Emerging evidence suggests that maternal food intake and nutritional status may modify the relationship between environmental toxicants and early-life health risks, potentially mitigating their adverse effects. However, the interplay between nutritional status, environmental exposures, and health outcomes remains poorly characterized in the literature. Notably, foods can serve as the dual source of toxins (e.g., methylmercury in fish) and protective nutrients (e.g., omega-3 fatty acids), which complicate their role in risk reduction. This scoping review aims to evaluate the extent of research on how maternal nutrition (from both dietary intake and supplements) modify the risk of adverse early-life outcomes associated with environmental exposures. We also identified critical research gaps to guide future investigations. Our search included identified English-language, free full-text articles from PubMed and Google Scholar published up to November 2025. Among the 60 included studies (55 observational and 5 interventional), most were conducted in the USA (42%), with toxic metals (33%) and endocrine disrupting chemicals (EDCs) (20%) as the primary exposures. Folate (28%) and fish/fatty acids (15%) were the most frequently studied nutrients/food sources. Neurodevelopmental/behavioral disorders (42%) and adverse birth outcomes (32%) were the predominant endpoints. Maternal nutrition, particularly folate, fish, vitamins, and minerals, may mitigate environmental exposure-related risks. The findings suggest that folate may modify health risks from air pollution, toxic metals, and smoking, whereas fish intake, fatty acids, selenium, and vitamins A, B, C, D, and E may modify the effects of air pollution, EDCs, toxic metals, and smoking. Future research should prioritize mechanistic studies, optimal dosages, and longitudinal designs in diverse populations.

Abstract

Background Maternal exposure to chemical fertilizer and disadvantaged maternal socio-economic status (SES) have been found to associate with increased risk of low birth weight (LBW). However, whether the two factors would interact to elevate the risk of LBW remains unknown. The present study aimed to explore the interactive effects of maternal exposure to chemical fertilizer during pregnancy and low SES on the risk of term LBW (tLBW). Methods In this population-based case–control study, 179 tLBW cases (birthweight < 2500 g and gestational age ≥ 37 weeks) and 204 controls (birthweight ≥ 2500 g and gestational age ≥ 37 weeks) were chosen from the Perinatal Health Care Surveillance System of Pingding County, Shanxi Province, China between 2007 and 2012. Data on basic socio-demographic, dietary and lifestyle characteristics and environmental exposure were directly extracted from the system. Maternal exposure to chemical fertilizer was measured at both household level and village level. Household-level exposure was indicated by household chemical fertilizer use in farming during pregnancy and the data was collected by trained healthcare workers after the selection of cases and controls in 2013. Village-level exposure was indicated by annual amount of village chemical fertilizer consumption per acre and the data came from the Annals of National Economics Statistics of Pingding County in 2010. Interactions between maternal exposure to chemical fertilizer and SES were assessed in logistic regressions using relative excess risk due to interaction (RERI), which indicates an additive interaction if larger than 0. Results The combination of low maternal SES and high exposure to village-level chemical fertilizer consumption was associated with increased risk of tLBW (aOR = 2.62, 95%CI: 1.44 ~ 4.77); The combination of low maternal SES and exposure to household chemical fertilizer use was associated with elevated risk of tLBW (aOR = 2.18, 95%CI: 1.24 ~ 3.83). Additive interactions were detected between high exposure to village-level chemical fertilizer consumption and low maternal SES (RERI:1.79, P  < 0.001) and between exposure to household chemical fertilizer use and low maternal SES (RERI:0.77, P  < 0.05). Conclusions Our study suggested negative impacts of potential agricultural pollutants on adverse pregnancy outcomes, especially in disadvantaged socio-economic populations.

Abstract

Prenatal exposure to air pollution has been associated with an increased risk of low birth weight. Disrupted metabolism may serve as an underlying mechanism, but the specific metabolic pathways involved remain unclear. In the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, 382 third-trimester maternal serum samples were analyzed for untargeted metabolomics using liquid chromatography with Fourier transform high-resolution mass spectrometry. Ambient concentrations of fine particulate matter (PM2.5), particulate matter ≤ 10 μm in diameter (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using inverse-distance-squared weighted spatial interpolation based on daily residential histories. Birth weight was retrieved from medical records. Linear regression identified metabolomic features associated with air pollution exposure or birth weight, followed by Mummichog pathway enrichment and mediation analyses for the selected features. Second-trimester PM2.5 exposure was associated with lower birth weight. Fourteen metabolic pathways were significantly associated with second-trimester PM2.5 exposure, with C21-steroid hormone biosynthesis and metabolism showing the most significant association. Sixteen metabolic pathways were significantly associated with birth weight, with vitamin A (retinol) metabolism being the most significantly enriched pathway. Seven pathways were associated with both PM2.5 exposure and birth weight, including C21-steroid hormone biosynthesis and metabolism, bile acid biosynthesis, tyrosine metabolism, ascorbate (vitamin C) and aldarate metabolism, vitamin D3 (cholecalciferol) metabolism, vitamin A (retinol) metabolism, and pyrimidine metabolism. Overweight or obese women exhibited more metabolomic features and metabolic pathways associated with PM2.5 exposure compared to underweight or normal-weight women. No associations were observed between PM10, NO2, or O3 and birth weight. Maternal metabolic pathways involving steroid metabolism, oxidative stress and inflammation, vitamin metabolism, and DNA damage may link prenatal PM2.5 exposure to lower birth weight, with overweight or obese women potentially more susceptible to these metabolic disruptions.

Abstract

Prenatal exposure to air pollution has been associated with an increased risk of low birth weight. Disrupted metabolism may serve as an underlying mechanism, but the specific metabolic pathways involved remain unclear. In the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, 382 third-trimester maternal serum samples were analyzed for untargeted metabolomics using liquid chromatography with Fourier transform high-resolution mass spectrometry. Ambient concentrations of fine particulate matter (PM2.5), particulate matter ≤ 10 μm in diameter (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using inverse-distance-squared weighted spatial interpolation based on daily residential histories. Birth weight was retrieved from medical records. Linear regression identified metabolomic features associated with air pollution exposure or birth weight, followed by Mummichog pathway enrichment and mediation analyses for the selected features. Second-trimester PM2.5 exposure was associated with lower birth weight. Fourteen metabolic pathways were significantly associated with second-trimester PM2.5 exposure, with C21-steroid hormone biosynthesis and metabolism showing the most significant association. Sixteen metabolic pathways were significantly associated with birth weight, with vitamin A (retinol) metabolism being the most significantly enriched pathway. Seven pathways were associated with both PM2.5 exposure and birth weight, including C21-steroid hormone biosynthesis and metabolism, bile acid biosynthesis, tyrosine metabolism, ascorbate (vitamin C) and aldarate metabolism, vitamin D3 (cholecalciferol) metabolism, vitamin A (retinol) metabolism, and pyrimidine metabolism. Overweight or obese women exhibited more metabolomic features and metabolic pathways associated with PM2.5 exposure compared to underweight or normal-weight women. No associations were observed between PM10, NO2, or O3 and birth weight. Maternal metabolic pathways involving steroid metabolism, oxidative stress and inflammation, vitamin metabolism, and DNA damage may link prenatal PM2.5 exposure to lower birth weight, with overweight or obese women potentially more susceptible to these metabolic disruptions.

Abstract

Background Inorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes. Methods Data from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012)  with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10). Results Among urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise. Conclusions Tissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.

Abstract

Maternal exposure to air pollution during pregnancy has a substantial public health impact. Epidemiological evidence supports an association between maternal exposure to air pollution and low birth weight. A popular method to estimate this association while identifying windows of susceptibility is a distributed lag model (DLM), which regresses an outcome onto exposure history observed at multiple time points. However, the standard DLM framework does not allow for modification of the association between repeated measures of exposure and the outcome. We propose a distributed lag interaction model that allows modification of the exposure‐time‐response associations across individuals by including an interaction between a continuous modifying variable and the exposure history. Our model framework is an extension of a standard DLM that uses a cross‐basis, or bi‐dimensional function space, to simultaneously describe both the modification of the exposure‐response relationship and the temporal structure of the exposure data. Through simulations, we showed that our model with penalization out‐performs a standard DLM when the true exposure‐time‐response associations vary by a continuous variable. Using a Colorado, USA birth cohort, we estimated the association between birth weight and ambient fine particulate matter air pollution modified by an area‐level metric of health and social adversities from Colorado EnviroScreen.

Abstract

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord serum total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [β = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 μg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 μg/L) (all p-values for interaction<0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Abstract

Prenatal ozone (O3) exposure may trigger systemic inflammation and oxidative stress. These effects could contribute to adverse pregnancy outcomes. We conducted a prospective cohort study involving 235 pregnant women in Ningxia, China. Maternal O3 exposure during pregnancy and prior to conception was assessed using high-resolution spatiotemporal models. Multivariable logistic and linear regression analyses were employed to evaluate the associations between O3 exposure and adverse pregnancy outcomes. Mediation and interaction models were further applied to examine the potential modifying roles of gestational diabetes mellitus (GDM) and inflammatory biomarkers. In multivariable analyses adjusted for maternal and environmental covariates, higher prenatal O3 exposure was significantly associated with an increased risk of preterm birth (PTB) (OR = 1.24, 95% CI: 1.05~1.45, p = 0.010) and low birth weight (LBW) (OR = 1.29, 95% CI: 1.09~1.54, p = 0.004). Similarly, elevated maternal SAA and CRP levels were positively associated with these adverse pregnancy outcomes (p < 0.05). Notably, higher TNF-α levels were inversely associated with the risks of PTB (OR = 0.15, 95% CI: 0.03~0.85, p = 0.032) and LBW (OR = 0.05, 95% CI: 0.01~0.39, p = 0.005). IL-17A levels were inversely associated with neonatal length-for-age Z scores (β = −0.28, 95% CI: −0.55~−0.01, p = 0.043). Our findings suggest that prenatal O3 exposure is associated with increased risks of PTB and LBW. Alterations in systemic inflammatory markers and metabolic dysfunction during pregnancy were related to adverse pregnancy outcomes and fetal growth deficits, but they did not mediate these associations, with O3 remaining an independent predictor after adjustment.

Abstract

Introduction Low birth weight (LBW) is one of the major predictors of perinatal survival, infant morbidity, and mortality, as well as the risk of developmental disabilities and illnesses in future lives. The effect of the nutritional status of pregnant women on birth outcomes is becoming a common research agenda, but evidence on the level of low birth weight (LBW) and its association with prenatal iron status in Ethiopia, particularly among rural residents, is limited. Thus, this study aimed to assess the prevalence, predictors of LBW, and its association with maternal iron status using serum ferritin concentration in Haramaya district, eastern Ethiopia, 2021. Methods A community-based prospective cohort study design was conducted. Of a total of 427 eligible pregnant women followed until birth, 412 (96.48%) were included in the final analysis. Iron status was determined using serum ferritin (SF) concentration from venous blood collected aseptically from the ante-cubital veins analyzed on a fully automated Cobas e411 (German, Japan Cobas 4000 analyzer series) immunoassay analyzer. Iron deficiency(ID) and iron deficiency anemia (IDA) were classified as having SF less than 15 μg/L and SF less than 15 μg/L and Hb level of < 11.0 g/dl during the first or third trimester or < 10.5 g/dl during the second trimester as well, respectively. Birthweight was measured within 72 h of birth and < 2500 g was considered LBW. Birthweight was measured within 72 h of birth and < 2500 g was considered as LBW. A Poisson regression model with robust variance estimation was used to investigate the factors associated with LBW and the association between maternal iron status and LBW. An adjusted prevalence ratio with a 95% confidence interval was reported to show an association using a p -value < 0.05. Results About 20.2% (95% CI: 16%-24%) of neonates were born with LBW. The prevalence of LBW was 5.04 (95% CI = 2.78–9.14) times higher among women who were iron deficient during pregnancy compared to those who were normal. The neonates of women who were iron deficient during pregnancy had lower birth weight (aPR=5.04; 95% CI = 2.78–9.14) than the neonates of women who were normal. Prevalence of LBW was higher among mothers who were undernourished (MUAC < 23cm) (aPR = 1.92; 95% CI= 1.33–2.27), stunted (height <145cm) (aPR=1.54; 95% CI=1.04–2.27) and among female neonates (aPR=3.70; 95% CI= 2.28–6.00). However, women who were supplemented with iron and folic acid (IFAS) during pregnancy had a 45% decreased chance of delivering low birth weight (aPR= 0.55; 95% CI=0.36–0.84). Conclusion We found that LBW is of public health significance in this predominantly rural setting. ID during pregnancy is found to have a negative effect on birth weight. IFA supplementation, the maternal under-nutrition, height, and sex of neonates were identified as predictors of low weight at birth. To improve maternal nutritional status, health interventions must address targeted strategies promoting desirable food behavior and nutritional practices. These include; promoting the consumption of diversified and rich iron food to improve the maternal nutritional status. A continued effort is needed in enhancing universal access and compliance with IFA supplementation to improve maternal health. Intervention strategies that are complementary and comprehensive across the vulnerable periods for women during pregnancy and their neonates that are based on a life-cycle approach are suggested.

Abstract

Background: Low birth weight (lbw) is one of the main causes of infant mortality. Globally, 2.5 million infants die in the first month after birth, and about 1 million die in the first day of birth. This study aimed to determine the biopsycho­social and contextual factors of com­­­munity health centers that cause low birth weight in Gunung­­­kidul Regency, Special Region of Yogya­karta, Indonesia. Case Report : This case-control study was conduc­ted at 25 community health centers in Gunung­kidul, Yogyakarta, Indonesia, from January to Febru­ary 2020. A sample of 200 infants, consisting of 50 infants with LBW (case) and 150 infants with normal birth weight (control) was selected by simple random sampling. The dependent variable was low birth weight. The independent variables were mater­nal edu­cation, early marriage, family in­come, frequency of ANC visits, maternal age at preg­nancy, household cigarette smoke exposure, gestational stress, anemia, and maternal nutri­­tional status. Data were collected using medical records, maternal and child health books, and questionnaires. Data were analy­zed us­ing multi­ple multi­­level logistic regression analysis. Results: The risk of LBW increased with maternal age at pregnancy <20 years or ≥35 years (b= 1.9; 95% CI= 0.01 to 3.73; p= 0.050), cigarette smoke exposure (b= 1.9; 95% CI= 0.33 to 3.49; p= 0.018), high gestational stress (b= 1.8; 95% CI= -0.01 to 3.67; p= 0.050), and anemia (b= 3.1; 95% CI= 1.24 to 4.90; p= 0.001). The risk of LBW decreased with mater­nal education ≥Senior High School (b= -1.8; 95% CI= -3.14 to -0.53; p= 0.006), family in­­come ≥Rp1,706,525 (b= -2.6; 95% CI= -3.94 to -1.27; p <0.001), and maternal MUAC ≥23.5 cm (b= -1.7; 95% CI = -3.25 to -0.17; p= 0.029). Conclusion: The risk of LBW increases with maternal age at pregnancy <20 years or ≥35 years, cigarette smoke exposure, high gesta­tio­nal stress, and anemia. The risk of LBW de­creases with mater­nal education ≥Senior High School, family in­­come ≥Rp1,706,525, and maternal MUAC ≥23.5 cm. Keywords: biopsychosocial, contextual effect, low birth weight Correspondence:  Isne Susanti. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: isne­susanti­­@gmail.com. Mobile: +628­5271128121. Journal of Maternal and Child Health (2020), 05(04): 446-455 https://doi.org/10.26911/thejmch.2020.05.04.12.

Abstract

Introduction Low birth weight (LBW) is one of the major predictors of perinatal survival, infant morbidity, and mortality, as well as the risk of developmental disabilities and illnesses in future lives. The effect of the nutritional status of pregnant women on birth outcomes is becoming a common research agenda, but evidence on the level of low birth weight (LBW) and its association with prenatal iron status in Ethiopia, particularly among rural residents, is limited. Thus, this study aimed to assess the prevalence, predictors of LBW, and its association with maternal iron status using serum ferritin concentration in Haramaya district, eastern Ethiopia, 2021. Methods A community-based prospective cohort study design was conducted. Of a total of 427 eligible pregnant women followed until birth, 412 (96.48%) were included in the final analysis. Iron status was determined using serum ferritin (SF) concentration from venous blood collected aseptically from the ante-cubital veins analyzed on a fully automated Cobas e411 (German, Japan Cobas 4000 analyzer series) immunoassay analyzer. Iron deficiency(ID) and iron deficiency anemia (IDA) were classified as having SF less than 15 μg/L and SF less than 15 μg/L and Hb level of < 11.0 g/dl during the first or third trimester or < 10.5 g/dl during the second trimester as well, respectively. Birthweight was measured within 72 h of birth and < 2500 g was considered LBW. Birthweight was measured within 72 h of birth and < 2500 g was considered as LBW. A Poisson regression model with robust variance estimation was used to investigate the factors associated with LBW and the association between maternal iron status and LBW. An adjusted prevalence ratio with a 95% confidence interval was reported to show an association using a p -value < 0.05. Results About 20.2% (95% CI: 16%-24%) of neonates were born with LBW. The prevalence of LBW was 5.04 (95% CI = 2.78–9.14) times higher among women who were iron deficient during pregnancy compared to those who were normal. The neonates of women who were iron deficient during pregnancy had lower birth weight (aPR=5.04; 95% CI = 2.78–9.14) than the neonates of women who were normal. Prevalence of LBW was higher among mothers who were undernourished (MUAC < 23cm) (aPR = 1.92; 95% CI= 1.33–2.27), stunted (height <145cm) (aPR=1.54; 95% CI=1.04–2.27) and among female neonates (aPR=3.70; 95% CI= 2.28–6.00). However, women who were supplemented with iron and folic acid (IFAS) during pregnancy had a 45% decreased chance of delivering low birth weight (aPR= 0.55; 95% CI=0.36–0.84). Conclusion We found that LBW is of public health significance in this predominantly rural setting. ID during pregnancy is found to have a negative effect on birth weight. IFA supplementation, the maternal under-nutrition, height, and sex of neonates were identified as predictors of low weight at birth. To improve maternal nutritional status, health interventions must address targeted strategies promoting desirable food behavior and nutritional practices. These include; promoting the consumption of diversified and rich iron food to improve the maternal nutritional status. A continued effort is needed in enhancing universal access and compliance with IFA supplementation to improve maternal health. Intervention strategies that are complementary and comprehensive across the vulnerable periods for women during pregnancy and their neonates that are based on a life-cycle approach are suggested.

Abstract

Background Despite many efforts, preterm birth (PTB) is poorly understood and remains a major public health problem in the United States. Toxicological work suggests gestational parent (GP) diet may modify the effect of ambient pollutants on birth outcomes. We assessed risk of PTB in humans in relation to fine particulate matter (PM_2.5), ozone (O_3), and nitrogen dioxide (NO_2) and variation by diet. Methods 684 GP-singleton infant pairs in the Newborn Epigenetics Study prospective birth cohort were attributed ambient air pollutant exposures for each trimester based on residence. Total energy intake, percent of energy intake from saturated fat, and percent of energy intake from total fat were dichotomized at the 75th percentile. >We used log binomial regressions to estimate risk ratios (RR (95%CI)) for PTB by pollutant interquartile ranges, adjusting for GP age, pre-pregnancy body mass index, GP race/ethnicity, GP education, season of conception, household income, and each diet factor. We assessed departure from additivity using interaction contrast ratios (ICRs). We addressed missing covariate data with multiple imputation. Results Point estimates suggest that O_3 may be inversely associated with PTB when exposure occurs in trimester 2 (min RR: 0.77, 95% CI: 0.39, 1.49), but may be harmful when exposure occurs in trimester 3 (max RR: 1.51, 95% CI: 0.62, 3.64). Additionally, PM_2.5 may be inversely associated with PTB when considered with total fat and saturated fat in trimester 2. Imprecise ICRs suggest departure from additivity (evidence of modification) with some pollutant-diet combinations. Conclusions While confidence intervals are wide, we observed potential modification of pollutant associations by dietary factors. It is imperative that large cohorts collect the required data to examine this topic, as more power is necessary to investigate the nuances suggested by this work.

Abstract

INTRODUCTION: Vitamin D deficiency and anemia are examples of nutritional problems of global health significance. When these health issues effect pregnant women, they may become a threat to the fetus’ potention for intrauterine growth. It has been known that the first trimester is the golden period of fetal programming which influences the fetuses and their life after birth. This study was aiming to analyze the association between first trimester maternal vitamin D, serum ferritin, hemoglobin level and neonatal birth weight. METHODS: From July 2016 a prospective cohort of pregnant women had been observed in four cities in West Java, Indonesia. Two hundred ninety four pregnant women were recuited in the first trimester and 203 of them had complete follow up until delivery. Collected data included maternal demography, blood analysis for ferritin, 25(OH) vitamin D in the first trimester of pregnancy and the birth weight of neonates. Associations were analyzed with multiple regression models. RESULTS: Vitamin D deficiency was highly prevalent among pregnant women in this study (approximately 75%) while anemia was found in 7.5 %, a little above the target of 5 %. However, no significant association was found between maternal serum vitamin D, serum ferritin, hemoglobin level in the first trimester and birth weight of the neonates, before and after adjustment for maternal age, pre-pregnancy body mass index, and parity. CONCLUSION: There were no associations found between vitamin D, ferritin, and hemoglobin level in the first trimester and neonatal birth weight. The negative results in this study should not diminish the benefit of nutritional supplementation during pregnancy. The possibility of other explanatory variables that influence these associations warrants further studies.

Abstract

Background Maternal exposure to chemical fertilizer and disadvantaged maternal socio-economic status (SES) have been found to associate with increased risk of low birth weight (LBW). However, whether the two factors would interact to elevate the risk of LBW remains unknown. The present study aimed to explore the interactive effects of maternal exposure to chemical fertilizer during pregnancy and low SES on the risk of term LBW (tLBW). Methods In this population-based case–control study, 179 tLBW cases (birthweight < 2500 g and gestational age ≥ 37 weeks) and 204 controls (birthweight ≥ 2500 g and gestational age ≥ 37 weeks) were chosen from the Perinatal Health Care Surveillance System of Pingding County, Shanxi Province, China between 2007 and 2012. Data on basic socio-demographic, dietary and lifestyle characteristics and environmental exposure were directly extracted from the system. Maternal exposure to chemical fertilizer was measured at both household level and village level. Household-level exposure was indicated by household chemical fertilizer use in farming during pregnancy and the data was collected by trained healthcare workers after the selection of cases and controls in 2013. Village-level exposure was indicated by annual amount of village chemical fertilizer consumption per acre and the data came from the Annals of National Economics Statistics of Pingding County in 2010. Interactions between maternal exposure to chemical fertilizer and SES were assessed in logistic regressions using relative excess risk due to interaction (RERI), which indicates an additive interaction if larger than 0. Results The combination of low maternal SES and high exposure to village-level chemical fertilizer consumption was associated with increased risk of tLBW (aOR = 2.62, 95%CI: 1.44 ~ 4.77); The combination of low maternal SES and exposure to household chemical fertilizer use was associated with elevated risk of tLBW (aOR = 2.18, 95%CI: 1.24 ~ 3.83). Additive interactions were detected between high exposure to village-level chemical fertilizer consumption and low maternal SES (RERI:1.79, P  < 0.001) and between exposure to household chemical fertilizer use and low maternal SES (RERI:0.77, P  < 0.05). Conclusions Our study suggested negative impacts of potential agricultural pollutants on adverse pregnancy outcomes, especially in disadvantaged socio-economic populations.

Abstract

Observational epidemiological studies have demonstrated that maternal exposure to air pollution increases the risk of adverse pregnancy outcomes. However, interactions among multiple environmental exposures remain underexplored. In this study, we performed an epidemiological analysis on 147,979 pregnant women recruited from nine provinces in southeastern China between 2013 and 2023, focusing on the risk of low birth weight (LBW). We found that the critical exposure windows for PM2.5 and ozone (O3) extend from six months prior to conception through the end of second trimester, with hazard ratio of HR = 1.152 (95 % confidence interval [CI]: 1.128-1.177) per 10-μg/m3 incremental PM2.5 exposure and HR = 1.028 (95 % CI: 1.024-1.031) per 10-ppb increase in O3. Our estimates indicate that in 2021, approximately 47,500 (95 % uncertainty interval [UI]: 41,200-53,600) live-born LBW infants nationwide in China could be attributed to ambient air pollution, declining from 79,800 (95 % UI: 71,700-87,900) in 2002. We observed statistically significant synergistic risk effects, neglecting which could lead to an underestimation of 11,600 (95 % UI: 9,300-13,900) LBW cases. Although air pollution-associated LBW burden is decreasing, the rapidly rising LBW prevalence remains a significant public health concern, particularly as China is implementing the "three-child policy". Therefore, our study offers precisely quantified, evidence-based policy guidance for safeguarding reproductive health.

Abstract

INTRODUCTION: Vitamin D deficiency and anemia are examples of nutritional problems of global health significance. When these health issues effect pregnant women, they may become a threat to the fetus’ potention for intrauterine growth. It has been known that the first trimester is the golden period of fetal programming which influences the fetuses and their life after birth. This study was aiming to analyze the association between first trimester maternal vitamin D, serum ferritin, hemoglobin level and neonatal birth weight. METHODS: From July 2016 a prospective cohort of pregnant women had been observed in four cities in West Java, Indonesia. Two hundred ninety four pregnant women were recuited in the first trimester and 203 of them had complete follow up until delivery. Collected data included maternal demography, blood analysis for ferritin, 25(OH) vitamin D in the first trimester of pregnancy and the birth weight of neonates. Associations were analyzed with multiple regression models. RESULTS: Vitamin D deficiency was highly prevalent among pregnant women in this study (approximately 75%) while anemia was found in 7.5 %, a little above the target of 5 %. However, no significant association was found between maternal serum vitamin D, serum ferritin, hemoglobin level in the first trimester and birth weight of the neonates, before and after adjustment for maternal age, pre-pregnancy body mass index, and parity. CONCLUSION: There were no associations found between vitamin D, ferritin, and hemoglobin level in the first trimester and neonatal birth weight. The negative results in this study should not diminish the benefit of nutritional supplementation during pregnancy. The possibility of other explanatory variables that influence these associations warrants further studies.

Abstract

UNLABELLED There are reports linking maternal nutritional status, smoking and environmental chemical exposures to adverse pregnancy outcomes. However, biological bases for association between some of these factors and birth outcomes are yet to be established. The objective of this preliminary work is to test the capability of a new high-throughput shotgun plasma proteomic screening in identifying maternal changes relevant to pregnancy outcome. A subset of third trimester plasma samples (N=12) associated with normal and low-birth weight infants were fractionated, tryptic-digested and analyzed for global proteomic changes using a MALDI-TOF-TOF-MS methodology. Mass spectral data were mined for candidate biomarkers using bioinformatic and statistical tools. Maternal plasma profiles of cytokines (e.g. IL8, TNF-α), chemokines (e.g. MCP-1) and cardiovascular endpoints (e.g. ET-1, MMP-9) were analyzed by a targeted approach using multiplex protein array and HPLC-Fluorescence methods. Target and global plasma proteomic markers were used to identify protein interaction networks and maternal biological pathways relevant to low infant birth weight. Our results exhibited the potential to discriminate specific maternal physiologies relevant to risk of adverse birth outcomes. This proteomic approach can be valuable in understanding the impacts of maternal factors such as environmental contaminant exposures and nutrition on birth outcomes in future work. BIOLOGICAL SIGNIFICANCE We demonstrate here the fitness of mass spectrometry-based shot-gun proteomics for surveillance of biological changes in mothers, and for adverse pathway analysis in combination with target biomarker information. This approach has potential for enabling early detection of mothers at risk for low infant birth weight and preterm birth, and thus early intervention for mitigation and prevention of adverse pregnancy outcomes. This article is part of a Special Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

Abstract

Women experiencing armed conflict during pregnancy face a significantly higher risk of maternal and neonatal complications, including low-birthweight (LBW) babies, due to factors such as violence, stress, food insecurity, and limited access to healthcare. This study aims to explore maternal and neonatal health, as well as antenatal care (ANC) access during the war in Gaza. This cross-sectional study involved 500 consecutive women and newborns delivered at the three largest obstetric centers in the Gaza Strip over a three-week span in late October and early November 2024. The research collected sociodemographic details, maternal obstetric histories, maternal nutrition variables, maternal stress effects, and other impacts from the conflict, as well as neonatal outcomes, including birthweight. Frequencies, percentages, and the median and interquartile range (IQR) were used to describe the data. The Mann-Whitney test was applied to compare birthweights between populations based on sex and geographical location. The median maternal age was 28. Nearly half (52.63%) had a normal baseline body mass index (BMI). Most (84.03%) reported a very low monthly income. The prevalence of maternal anemia was 50.4%. A majority of participants (62.73%) reported an insufficient quantity of food, while 73.6% noted a lack of dietary diversity. Over half consumed, on average, only two full meals daily, and their diets largely lacked animal protein. Only 36.68% attended eight or more ANC visits, and just 58.4% established their first ANC contact during the first trimester. The most common reason for the lack of ANC was the inability to afford transportation. Moreover, 69.46% adhered to folic acid and iron supplementation. Most (90.42%) participants reported moderate to high stress levels, with 40.92% and 33.93% feeling almost always or often endangered. The prevalence of LBW was 10.8%, and the median weight was 3100 g. This study illustrates the vulnerability of pregnant women during conflicts and emphasizes the responsibility of those involved in conflicts to protect pregnant women and newborns and safeguard their future development and health.

Abstract

Maternal PM2.5 exposure and lipid levels during pregnancy were independently detected associated with birth weight. Potential mediating factors still remain unclear. This study aimed to examine the association of maternal PM2.5 exposure and birth weight, and explore the potential mediation effect of maternal blood lipids in the relationship between PM2.5 exposure and birth weight. 5,162 pregnant women from Zhejiang, China were included in the study during 2013–2014. We measured blood lipids for each participant in the second and third trimesters. Air pollution exposure in residential districts was estimated based on satellite data for each individual throughout three trimesters in pregnancy. Linear mixed-effects models were employed to examine associations between PM2.5 and birth weight. Using a mediation analysis approach, we decomposed the total effect of PM2.5 on birth weight into natural direct and indirect effects via blood lipid concentration. After adjusting for covariates, a 10 µg/m3 increment in PM2.5 during the second trimester was directly associated with an 11.65 g increase in birth weight (95% CI: 2.99, 20.31 g). The indirect effects of PM2.5 exposure (each 10 µg/m3 increase) on birth weight, mediated through elevated maternal lipid levels, were − 2.35 g (95% CI: -4.07, -0.63 g) for total cholesterol to high-density lipoprotein cholesterol ratio (TC: HDL ratio), -0.69 g (95% CI: -1.16, -0.22 g) for Triglycerides (TG), and − 1.80 g (95% CI: -3.19, -0.41 g) for HDL-C, during the second trimester. Findings suggest prenatal PM2.5 exposure may impact term birth weight via direct biological effects and lipid-mediated pathways, underscoring the importance of incorporating air pollution mitigation into perinatal care and advancing biomarker-driven fetal monitoring. Future research should clarify PM2.5 component-specific effects, decode placental-fetal lipid regulatory mechanisms, and validate pollution-metabolism-outcome relationships through multi-regional cohorts to inform precision environmental health interventions and clinical risk management.

Abstract

Abstract Background Almost two billion people who are deficient in vitamins and minerals are women and children in low‐ and middle‐income countries (LMIC). These deficiencies are worsened during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child. To reduce micronutrient deficiencies, several strategies have been implemented, including diet diversification, large‐scale and targeted fortification, staple crop bio‐fortification and micronutrient supplementation. Objectives To evaluate and summarize the available evidence on the effects of micronutrient supplementation during pregnancy in LMIC on maternal, fetal, child health and child development outcomes. This review will assess the impact of single micronutrient supplementation (calcium, vitamin A, iron, vitamin D, iodine, zinc, vitamin B12), iron‐folic acid (IFA) supplementation, multiple micronutrient (MMN) supplementation, and lipid‐based nutrient supplementation (LNS) during pregnancy. Search Methods We searched papers published from 1995 to 31 October 2019 (related programmes and good quality studies pre‐1995 were limited) in CAB Abstracts, CINAHL, Cochrane Central Register of Controlled Trials, Embase, International Initiative for Impact Evaluations, LILACS, Medline, POPLINE, Web of Science, WHOLIS, ProQuest Dissertations & Theses Global, R4D, WHO International Clinical Trials Registry Platform. Non‐indexed grey literature searches were conducted using Google, Google Scholar, and web pages of key international nutrition agencies. Selection Criteria We included randomized controlled trials (individual and cluster‐randomized) and quasi‐experimental studies that evaluated micronutrient supplementation in healthy, pregnant women of any age and parity living in a LMIC. LMIC were defined by the World Bank Group at the time of the search for this review. While the aim was to include healthy pregnant women, it is likely that these populations had one or more micronutrient deficiencies at baseline; women were not excluded on this basis. Data Collection and Analysis Two authors independently assessed studies for inclusion and risk of bias, and conducted data extraction. Data were matched to check for accuracy. Quality of evidence was assessed using the GRADE approach. Main Results A total of 314 papers across 72 studies (451,723 women) were eligible for inclusion, of which 64 studies (439,649 women) contributed to meta‐analyses. Seven studies assessed iron‐folic acid (IFA) supplementation versus folic acid; 34 studies assessed MMN vs. IFA; 4 studies assessed LNS vs. MMN; 13 evaluated iron; 13 assessed zinc; 9 evaluated vitamin A; 11 assessed vitamin D; and 6 assessed calcium. Several studies were eligible for inclusion in multiple types of supplementation. IFA compared to folic acid showed a large and significant (48%) reduction in the risk of maternal anaemia (average risk ratio (RR) 0.52, 95% CI 0.41 to 0.66; studies = 5; participants = 15,540; moderate‐quality evidence). As well, IFA supplementation demonstrated a smaller but significant, 12% reduction in risk of low birthweight (LBW) babies (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). MMN supplementation was defined as any supplement that contained at least 3 micronutrients. Post‐hoc analyses were conducted, where possible, comparing the differences in effect of MMN with 4+ components and MMN with 3 or 4 components. When compared to iron with or without FA, MMN supplementation reduced the risk of LBW by 15% (average RR 0.85, 95% CI 0.77 to 0.93; studies = 28; participants = 79,972); this effect was greater in MMN with >4 micronutrients (average RR 0.79, 95% CI 0.71 to 0.88; studies = 19; participants = 68,138 versus average RR 1.01, 95% CI 0.92 to 1.11; studies = 9; participants = 11,834). There was a small and significant reduction in the risk of stillbirths (average RR 0.91; 95% CI 0.86 to 0.98; studies = 22; participants = 96,772) and a small and significant effect on the risk of small‐for‐gestational age (SGA) (average RR 0.93; 95% CI 0.88 to 0.98; studies = 19; participants = 52,965). For stillbirths and SGA, the effects were greater among those provided MMN with 4+ micronutrients. Children whose mothers had been supplemented with MMN, compared to IFA, demonstrated a 16% reduced risk of diarrhea (average RR 0.84; 95% CI 0.76 to 0.92; studies = 4; participants = 3,142). LNS supplementation, compared to MMN, made no difference to any outcome; however, the evidence is limited. Iron supplementation, when compared to no iron or placebo, showed a large and significant effect on maternal anaemia, a reduction of 47% (average RR 0.53, 95% CI 0.43 to 0.65; studies = 6; participants = 15,737; moderate‐quality evidence) and a small and significant effect on LBW (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). Zinc and vitamin A supplementation, each both compared to placebo, had no impact on any outcome examined with the exception of potentially improving serum/plasma zinc (mean difference (MD) 0.43 umol/L; 95% CI −0.04 to 0.89; studies = 5; participants = 1,202) and serum/plasma retinol (MD 0.13 umol/L; 95% CI −0.03 to 0.30; studies = 6; participants = 1,654), respectively. When compared to placebo, vitamin D supplementation may have reduced the risk of preterm births (average RR 0.64; 95% CI 0.40 to 1.04; studies = 7; participants = 1,262), though the upper CI just crosses the line of no effect. Similarly, calcium supplementation versus placebo may have improved rates of pre‐eclampsia/eclampsia (average RR 0.45; 95% CI 0.19 to 1.06; studies = 4; participants = 9,616), though the upper CI just crosses 1. Authors' Conclusions The findings suggest that MMN and vitamin supplementation improve maternal and child health outcomes, including maternal anaemia, LBW, preterm birth, SGA, stillbirths, micronutrient deficiencies, and morbidities, including pre‐eclampsia/eclampsia and diarrhea among children. MMN supplementation demonstrated a beneficial impact on the most number of outcomes. In addition, MMN with >4 micronutrients appeared to be more impactful than MMN with only 3 or 4 micronutrients included in the tablet. Very few studies conducted longitudinal analysis on longer‐term health outcomes for the child, such as anthropometric measures and developmental outcomes; this may be an important area for future research. This review may provide some basis to guide continual discourse around replacing IFA supplementation with MMN along with the use of single micronutrient supplementation programs for specific outcomes.

Abstract

Women experiencing armed conflict during pregnancy face a significantly higher risk of maternal and neonatal complications, including low-birthweight (LBW) babies, due to factors such as violence, stress, food insecurity, and limited access to healthcare. This study aims to explore maternal and neonatal health, as well as antenatal care (ANC) access during the war in Gaza. This cross-sectional study involved 500 consecutive women and newborns delivered at the three largest obstetric centers in the Gaza Strip over a three-week span in late October and early November 2024. The research collected sociodemographic details, maternal obstetric histories, maternal nutrition variables, maternal stress effects, and other impacts from the conflict, as well as neonatal outcomes, including birthweight. Frequencies, percentages, and the median and interquartile range (IQR) were used to describe the data. The Mann-Whitney test was applied to compare birthweights between populations based on sex and geographical location. The median maternal age was 28. Nearly half (52.63%) had a normal baseline body mass index (BMI). Most (84.03%) reported a very low monthly income. The prevalence of maternal anemia was 50.4%. A majority of participants (62.73%) reported an insufficient quantity of food, while 73.6% noted a lack of dietary diversity. Over half consumed, on average, only two full meals daily, and their diets largely lacked animal protein. Only 36.68% attended eight or more ANC visits, and just 58.4% established their first ANC contact during the first trimester. The most common reason for the lack of ANC was the inability to afford transportation. Moreover, 69.46% adhered to folic acid and iron supplementation. Most (90.42%) participants reported moderate to high stress levels, with 40.92% and 33.93% feeling almost always or often endangered. The prevalence of LBW was 10.8%, and the median weight was 3100 g. This study illustrates the vulnerability of pregnant women during conflicts and emphasizes the responsibility of those involved in conflicts to protect pregnant women and newborns and safeguard their future development and health.

Abstract

Both interpregnancy intervals (IPI) and environmental factors might contribute to low birth weight (LBW). However, the extent to which air pollution influences the effect of IPIs on LBW remains unclear. We aimed to investigate whether IPI and air pollution jointly affect LBW. A retrospective cohort study was designed in this study. The data of birth records was collected from the Jiangsu Maternal Child Information System, covering January 2020 to June 2021 in Nantong city, China. IPI was defined as the duration between the delivery date for last live birth and date of LMP for the subsequent birth. The maternal exposure to ambient air pollutants during pregnancy—including particulate matter (PM) with an aerodynamic diameter of ≤ 2.5 μm (PM2.5), PM10, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)—was estimated using a hybrid kriging-LUR-RF model. A novel air pollution score was proposed, assessing combined exposure to five pollutants (excluding CO) by summing their concentrations, weighted by LBW regression coefficients. Multivariate logistic regression models were used to estimate the effects of IPI, air pollution and their interactions on LBW. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP) and synergy index (S) were utilized to assess the additive interaction. Among 10, 512 singleton live births, the LBW rate was 3.7%. The IPI-LBW risk curve exhibited an L-shaped pattern. The odds ratios (ORs) for LBW for each interquartile range increase in PM2.5, PM10, O3 and the air pollution score were 1.16 (95% CI: 1.01–1.32), 1.30 (1.06–1.59), 1.22 (1.06–1.41), and 1.32 (1.10–1.60) during the entire pregnancy, respectively. An additive interaction between IPI and PM2.5 was noted during the first trimester. Compared to records with normal IPI and low PM2.5 exposure, those with short IPI and high PM2.5 exposure had the highest risk of LBW (relative risk = 3.53, 95% CI: 1.85–6.49, first trimester). The study demonstrates a synergistic effect of interpregnancy interval and air pollution on LBW, indicating that rational birth spacing and air pollution control can jointly improve LBW outcomes.

Abstract

The associations between maternal pre-pregnancy obesity and low birth weight (LBW, <2500 g) remain inconclusive. Therefore, birth weight in a Polish prospective cohort of 912 mothers was investigated depending on the pre-pregnancy body mass index (BMI). The whole cohort and the subgroup of gestational weight gain (GWG) in the range of the Institute of Medicine (IOM) recommendations, as well as ‘healthy’ women (who did not develop diabetes or hypertension in this pregnancy) were investigated. Adjusted odds ratios (AOR) of the newborn outcomes (with 95% confidence intervals, CI) for obesity (BMI ≥ 30 kg/m2) vs. normal BMI (18.5−24.9 kg/m2) were calculated using multiple logistic regression. Risk profiles (in the Lowess method) were presented for BMI values (kg/m2) and threshold BMI values were calculated. (1) In the cohort, LBW affected 6.6% of pregnancies, fetal growth restriction (FGR) 2.3%, and macrosomia 10.6%. (2) The adjusted risk of macrosomia was more than three-fold higher for obesity compared to normal BMI in the whole cohort (AOR = 3.21 (1.69−6.1), p < 0.001) and the result was maintained in the subgroups. A 17-fold higher adjusted LBW risk for obesity was found (AOR = 17.42 (1.5−202.6), p = 0.022), but only in the normal GWG subgroup. The FGR risk profile was U-shaped: in the entire cohort, the risk was more than three times higher for obesity (AOR = 3.12 (1.02−9.54), p = 0.045) and underweight (AOR = 3.84 (1.13−13.0), p = 0.031). (3) The risk profiles showed that the highest BMI values were found to be associated with a higher risk of these three newborn outcomes and the threshold BMI was 23.7 kg/m2 for macrosomia, 26.2 kg/m2 for LBW, and 31.8 kg/m2 for FGR. These results confirm the multidirectional effects of obesity on fetal growth (low birth weight, fetal growth restriction, and macrosomia). The results for LBW were heavily masked by the effects of abnormal gestational weight gain.

Abstract

PURPOSE To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000 mg/day compared to 200 mg/day on early preterm birth (<34 weeks gestation). METHODS A secondary aim of the phase III randomised trial was to explore the relationships among pregnancy outcomes (maternal red blood cell phospholipid (RBC-PL) DHA at delivery, preterm birth, gestational age at delivery, labor type, birth anthropometric measures, low birth weight, gestational diabetes, pre-eclampsia, and admission to a neonatal intensive care unit) in participants (n = 1100). We used Bayesian multiple imputation and linear and logistic regression models to conduct an analysis of five general classes of predictor variables collected during the trial: a) DHA intake, b) nutrient intake from food and supplements, c) environmental exposure to tobacco and alcohol, d) maternal demographics, and e) maternal medical history. RESULTS DHA supplementation lowered the risk of preterm birth and NICU admission, and increased gestation and birth weight as observed in the primary analysis. Higher maternal RBC-PL-DHA at delivery was associated with DHA supplementation and formal education of a bachelor's degree or higher. DHA supplementation and maternal age were associated with a higher risk of gestational diabetes. Total vitamin A intake was associated with longer gestation, while fructose and intake of the long chain omega-6 fatty acid, arachidonic acid, were associated with shorter gestation. Risk of preterm birth was associated with a history of low birth weight, preterm birth, pre-eclampsia, and NICU admission. CONCLUSION Bayesian models provide a comprehensive approach to relationships among DHA intake, nutrient intake, maternal characteristics, and pregnancy outcomes. We observed previously unreported relationships between gestation duration and fructose, vitamin A, and arachidonic acid that could be the basis for future research. TRIAL REGISTRATION NUMBER AND DATE ClinicalTrials.gov (NCT02626299); December 10, 2015.