Previous studies have indicated that maternal exposure to particles with aerodynamic diameter <2.5 μm (PM₂.₅) is associated with adverse birth outcomes. However, the critical exposure windows remain inconsistent. A retrospective cohort study was conducted in Huai River Basin, Henan, China during 2013–2018. Daily PM₂.₅ concentration was collected using Chinese Air Quality Reanalysis datasets. We calculated exposures for each participant based on the residential address during pregnancy. Binary logistic regression was used to examine the trimester-specific association of PM₂.₅ exposure with preterm birth (PTB), low birth weight (LBW) and term LBW (tLBW), and we further estimated monthly and weekly association using distributed lag models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for each 10 μg/m³ increase in PM₂.₅ exposure. Stratified analyses were performed by maternal age, infant gender, parity, and socioeconomic status (SES). In total, 196,780 eligible births were identified, including 4257 (2.2%) PTBs, 3483 (1.8%) LBWs and 1770 (0.9%) tLBWs. Maternal PM₂.₅ exposure during the second trimester were associated with the risk of PTB and LBW. At the monthly level, the PTB and LBW risks were associated with PM₂.₅ exposure mainly in the 4th -6th month. By estimating the weekly-specific association, we observed that critical exposure windows of PM₂.₅ exposure and PTB were in the 18th- 27th gestational weeks. Stronger associations were found in younger, multiparous mothers and those with a female baby and in low SES. In conclusion, the results indicate that maternal PM₂.₅ exposure during the second trimester was associated with PTB and LBW. Younger, multiparous mothers and those with female babies and in low SES were susceptible.

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

Thallium (Tl) is a well-recognized hazardous toxic heavy metal that has been reported to have embryotoxicity and fetotoxicity. However, little is known about its association with preterm birth (PTB) in humans. We aimed to evaluate the predictors of Tl exposure and assessed its relation with PTB. The study population included 7173 mother-infant pairs from a birth cohort in Wuhan, China. Predictors of Tl concentrations were explored using linear regression analyses, and associations of Tl exposure with risk of PTB or gestational age at birth were estimated using logistic regression or generalized linear models. The geometric mean and median values of urinary Tl concentrations were 0.28 μg/L (0.55 μg/g creatinine) and 0.29 μg/L (0.53 μg/g creatinine). We found that maternal urinary Tl concentrations varied by gestational weight gain, educational attainment, multivitamin and iron supplementations. Women with Tl concentrations higher than 0.80 μg/g creatinine were at higher risk of giving birth prematurely versus those with Tl concentrations lower than 0.36 μg/g creatinine [adjusted odds ratio (95% confidence interval (CI)): 1.55 (1.05, 2.27)], and the association was more pronounced in PTB with premature rupture of membranes (PROM) rather than in PTB without PROM. About 3-fold increase in creatinine-corrected Tl concentrations were associated with 0.99-day decrease in gestational length (95% CI: −1.36, −0.63). This is the first report on the associations between maternal Tl exposure and the risk of PTB.

Triclosan (TCS) is a suspected endocrine disrupting chemical which is widely used in consumer products as an antibacterial agent. But findings in human studies focusing on the fetal developmental effects of prenatal TCS exposure were rare and inconsistent. This study aimed to determine maternal urinary TCS and investigate its association with birth outcomes. Pregnant women (n = 1006) were randomly selected from the prospective Healthy Baby Cohort (HBC) enrolled in 2014. TCS levels were determined in maternal urine samples collected at delivery and recorded birth outcomes were obtained from the medical records. Multiple linear regressions were applied to evaluate associations of maternal urinary TCS levels with birth outcomes including birth weight, birth length, and gestational age. Logistic regressions were used to evaluate associations with preterm birth, late term birth, and low birth weight. The geometric mean concentrations for TCS and specific gravity (SG) adjusted TCS in maternal urines were 0.73, 0.78 ng/mL, respectively. In the crude model, one ln-unit increase of urinary SG-adjusted TCS concentration was associated with a 0.30-day [95% confidence interval (CI): 0.00, 0.60] increase in gestational age; however, the associations were not statistically significant after adjustment for covariates. No significant associations of SG-adjusted TCS concentrations with birth weight and birth length were observed. Maternal SG-adjusted TCS concentrations were not related to preterm birth, late term birth, and low birth weight (all p > 0.10). Our findings reported a relatively low level of TCS among Chinese pregnant women. With such exposure level, we did not find strong evidence for associations between maternal TCS exposure and birth outcomes. Longitudinal studies concerning about different potential effects of TCS on perinatal health are necessary.

Lead (Pb) is a well-known developmental toxicant. The aim of the present study was to analyze the association between maternal serum Pb level and risk of preterm birth in a population-based birth cohort study. The present study analyzed a sub-study of the China-Anhui Birth Cohort that recruited 3125 eligible mother-and-singleton-offspring pairs. Maternal serum Pb level was measured by graphite furnace atomic absorption spectrometry. All subjects were classified into three groups by tertile division according to serum Pb level: Low-Pb (L-Pb, <1.18 μg/dl), Medium-Pb (M-Pb, 1.18–1.70 μg/dl), and High-Pb (H-Pb, ≥1.71 μg/dl). The rate of preterm birth was 2.8% among subjects with L-Pb, 6.1% among subjects with M-Pb, and 8.1% among subjects with H-Pb, respectively. After controlling confounding factors, the adjusted OR for preterm birth was 2.33 (95%CI: 1.49, 3.65) among subjects with M-Pb and 3.09 (95%CI: 2.01, 4.76) among subjects with H-Pb. Of interest, maternal Pb exposure in early gestational stage than in middle gestational stage was more susceptible to preterm birth. Moreover, maternal serum Pb level was only associated with increased risk of late preterm birth. The present study provides evidence that maternal serum Pb level during pregnancy is positively associated with risk of preterm birth in a Chinese population.

Cadmium (Cd) was a developmental toxicant that induces fetal malformation and growth restriction in mice. However, epidemiological studies about the association of maternal serum Cd level with risk of preterm birth were limited. This study was to investigate whether maternal serum Cd level during pregnancy is associated with risk of preterm birth in a Chinese population. Total 3254 eligible mother-and-singleton-offspring pairs were recruited. Maternal serum Cd level was measured by GFAAS. Based on tertiles, maternal serum Cd concentration was classified as low (LCd, <0.65 μg/L), medium (MCd, 0.65–0.94 μg/L) and high (HCd, ≥0.95 μg/L). Odds ratio (OR) for preterm birth was estimated using multiple logistic regression models. Results showed the rate of preterm birth among LCd, M-Cd and HCd was 3.5%, 3.8%, and 9.4%, respectively. Subjects with HCd had a significantly higher risk for preterm birth (OR: 2.86; 95%CI: 1.95, 4.19; P < 0.001) than did those with LCd. Adjusted OR for preterm birth was 3.02 (95%CI: 2.02, 4.50; P < 0.001) among subjects with HCd compared to subjects with LCd. Taken together, the above results suggest that maternal serum Cd level during pregnancy is positively associated with risk of preterm birth.

Multiple systematic reviews and meta-analyses linked prenatal exposure to ambient air pollutants to adverse birth outcomes with mixed findings, including results indicating positive, negative, and null associations across the pregnancy periods. The objective of this study was to systematically summarise systematic reviews and meta-analyses on air pollutants and birth outcomes to assess the overall epidemiological evidence. Systematic reviews with/without meta-analyses on the association between air pollutants (NO₂, CO, O₃, SO₂, PM₂.₅, and PM₁₀) and birth outcomes (preterm birth; stillbirth; spontaneous abortion; birth weight; low birth weight, LBW; small-for-gestational-age) up to March 30, 2022 were included. We searched PubMed, CINAHL, Scopus, Medline, Embase, and the Web of Science Core Collection, systematic reviews repositories, grey literature databases, internet search engines, and references of included studies. The consistency in the directions of the effect estimates was classified as more consistent positive or negative, less consistent positive or negative, unclear, and consistently null. Next, the confidence in the direction was rated as either convincing, probable, limited-suggestive, or limited non-conclusive evidence. Final synthesis included 36 systematic reviews (21 with and 15 without meta-analyses) that contained 295 distinct primary studies. PM₂.₅ showed more consistent positive associations than other pollutants. The positive exposure-outcome associations based on the entire pregnancy period were more consistent than trimester-specific exposure averages. For whole pregnancy exposure, a more consistent positive association was found for PM₂.₅ and birth weight reductions, particulate matter and spontaneous abortion, and SO₂ and LBW. Other exposure-outcome associations mostly showed less consistent positive associations and few unclear directions of associations. Almost all associations showed probable evidence. The available evidence indicates plausible causal effects of criteria air pollutants on birth outcomes. To strengthen the evidence, more high-quality studies are required, particularly from understudied settings, such as low-and-middle-income countries. However, the current evidence may warrant the adoption of the precautionary principle.

Recent studies suggests that air pollution, from among others road traffic, can influence growth and development of the human foetus during pregnancy. The effects of air pollution from heavy industry on birth outcomes have been investigated scarcely.Our aim was to investigate the associations of air pollution from heavy industry on birth outcomes.A cross-sectional study was conducted among 4488 singleton live births (2012–2017) in the vicinity of a large industrial area in the Netherlands. Information from the birth registration was linked with a dispersion model to characterize annual individual-level exposure of pregnant mothers to air pollutants from industry in the area. Associations between particulate matter (PM₁₀), nitrogen oxides (NOX), sulphur dioxide (SO₂), and volatile organic compounds (VOC) with low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) were investigated by logistic regression analysis and with gestational age, birth weight, birth length, and head circumference by linear regression analysis.Exposures to NOX, SO₂, and VOC (per interquartile range of 1.16, 0.42, and 0.97 μg/m³ respectively) during pregnancy were associated with LBW (OR 1.20, 95%CI 1.06–1.35, OR 1.20, 95%CI 1.00–1.43, and OR 1.21, 95%CI 1.08–1.35 respectively). NOX and VOC were also associated with PTB (OR 1.14, 95%CI 1.01–1.29 and OR 1.17, 95%CI 1.04–1.31 respectively). Associations between exposure to air pollution and birth weight, birth length, and head circumference were statistically significant. Higher exposure to PM₁₀, NOX, SO₂ and VOC (per interquartile range of 0.41, 1.16, 0.42, and 0.97 μg/m³ respectively) was associated with reduced birth weight of 21 g to 30 g.The 90th percentile industry-related PM₁₀ exposure corresponded with an average birth weight decrease of 74 g.

While the effects of ambient pollutants on adverse perinatal outcomes have been studied, most studies have focused on preterm birth, stillbirth, and low birthweight. Few studies have examined the effects of ambient pollutants on prelabor rupture of membranes (PROM). This study was designed to explore the acute effects of ambient pollutants on both term PROM (TPROM) and preterm PROM (PPROM). We enrolled pregnant women receiving antenatal care between October 2013 and December 2019 at the International Peace Maternity and Child Health Hospital (IPMCHH). The effects of ambient pollutants (including PM₂.₅, PM₁₀, SO₂, CO, NO₂, and 8-h O₃) on TPROM and PPROM were estimated using generalized additive models (GAMs). Exposure-response relationship curves were also evaluated using GAMs after adjustment for confounding factors. Potential lagged effects were examined using various lag models. The data of 100,200 pregnant women who delivered at IPMCHH were analyzed. The fitted spline curves for PPROM were similar to the temporal trends of PM₂.₅, PM₁₀, SO₂, CO and NO₂ but not O₃, while those for TPROM were different from the temporal trends of all six air pollutants. An increased risk of PPROM was associated with increased concentrations of PM₂.₅, PM₁₀, SO₂ and CO on lag days 2 and 3, while no association was found between PPROM and daily concentration of O₃. After adjustment for confounding factors, there was a shift in the exposure-response curves, indicating associations between PPROM and PM₂.₅, PM₁₀, SO₂, and CO on lag days 2–3. Interaction effects of PM₂.₅, PM₁₀, SO₂, and CO were also found to increase the risk of PPROM. In conclusion, acute exposures to six critical air pollutants were not associated with an increased risk of TPROM; however, PM₂.₅, PM₁₀, SO₂, and CO were found to interact, increasing the risk for PPROM on lag days 2 and 3.

The ongoing transition to renewable fuel sources has led to increased use of wood and other biomass fuels. The physiochemical characteristics of biomass combustion derived aerosols depends on appliances, fuel and operation procedures, and particles generated during incomplete combustion are linked to toxicity. Frequent indoor wood burning is related to severe health problems such as negative effects on airways and inflammation, as well as chronic hypoxia and pathological changes in placentas, adverse pregnancy outcome, preterm delivery and increased risk of preeclampsia. The presence of combustion-derived black carbon particles at both the maternal and fetal side of placentas suggests that particles can reach the fetus. Air pollution particles have also been shown to inhibit trophoblast migration and invasion, which are vital functions for the development of the placenta during the first trimester. In this study we exposed a placental first trimester trophoblast cell line to wood smoke particles emitted under Nominal Burn rate (NB) or High Burn rate (HB). The particles were visible inside exposed cells and localized to the mitochondria, causing ultrastructural changes in mitochondria and endoplasmic reticulum. Exposed cells showed decreased secretion of the pregnancy marker human chorionic gonadotropin, increased secretion of IL-6, disrupted membrane integrity, disrupted proliferation and contained specific polycyclic aromatic hydrocarbons (PAHs) from the particles. Taken together, these results suggest that wood smoke particles can enter trophoblasts and have detrimental effects early in pregnancy by disrupting critical trophoblast functions needed for normal placenta development and function. This could contribute to the underlying mechanisms leading to pregnancy complications such as miscarriage, premature birth, preeclampsia and/or fetal growth restriction. This study support the general recommendation that more efficient combustion technologies and burning practices should be adopted to reduce some of the toxicity generated during wood burning.