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.

Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4–22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma–mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60–3.43), 2.42 (95%CI: 1.06–5.55) and 2.46 (95%CI: 1.08–5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57–25.71) and AG (3.04, 95%CI: 1.59–5.80) of rs2758352, with CC (2.34, 95%CI: 1.31–4.18) of rs699473, and with GG (2.26, 95%CI: 1.22–4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.

Heat stress (HS) during gestation has been associated with negative outcomes, such as preterm birth or postnatal metabolic syndromes. The intestinal microbiota is a unique ecosystem playing an essential role in mediating the metabolism and health of mammals. Here we hypothesize late gestational HS alters maternal microbial transmission and structures offspring’s intestinal microbiota and serum metabolic profiles. Our results show maternal HS alters bacterial β-diversity and composition in sows and their piglets. In the maternal intestine, genera Ruminococcaceae UCG-005, [Eubacterium] coprostanoligenes group and Halomonas are higher by HS (q < 0.05), whereas the populations of Streptococcus, Bacteroidales RF16 group_norank and Roseburia are decreased (q < 0.05). In the maternal vagina, HS mainly elevates the proportions of phylum Bacteroidetes and Fusobacteria (q < 0.05), whereas reduces the population of Clostridiales Family XI (q < 0.05). In the neonatal intestine, maternal HS promotes the population of Proteobacteria but reduces the relative abundance of Firmicutes (q < 0.05). Moreover, the core Operational taxonomic units (OTU) analysis indicates the proportions of Clostridium sensu stricto 1, Romboutsia and Turicibacter are decreased by maternal HS in the intestinal and vaginal co-transmission, whereas that of phylum Proteobacteria and Epsilonbacteraeota, such as Escherichia-Shigella, Klebsiella, Acinetobacter, and Comamonas are increased in both the intestinal and vaginal co-transmission and the vagina. Additionally, Aeromonas is the only genus that is transmitted from environmental sources. Lastly, we evaluate the importance of neonatal differential OTU for the differential serum metabolites. The results indicate Acinetobacter significantly contributes to the differences in the adrenocorticotropic hormone (ACTH) and glucose levels due to HS (P < 0.05). Further, Stenotrophomonas is the most important variable for Cholesterol, low-density lipoprotein (LDL), diamine oxidase (DAO), blood urea nitrogen (BUN) and 5-hydroxytryptamine (5-HT) (P < 0.10). Overall, our data provides evidence for the maternal HS in establishing the neonatal microbiota via affecting maternal transmission, which in turn affects the maintenance of metabolic health.

Pregnant women and their fetuses represent susceptible populations to environmental contaminants. Exposure to polycyclic aromatic hydrocarbons (PAHs) among pregnant women may contribute to adverse birth outcomes such as preterm birth. Multiple previous studies have assessed airborne sources of PAHs among pregnant women but few have measured urinary PAH metabolites which can capture total exposure through multiple routes. The aim of this study was to bridge this knowledge gap by assessing longitudinal urinary PAH metabolite concentrations over two time points in pregnancy cohorts in Boston (N = 200) and Puerto Rico (N = 50) to better understand exposure distributions throughout pregnancy and how they relate to demographic factors. Urine samples were analyzed for 1-NAP, 2-NAP, 2-FLU, 1-PHE, 2,3-PHE, 4-PHE, 9-PHE, and 1-PYR. Concentrations of 2-NAP, 1-PYR, and 4-PHE were higher in Puerto Rico, while all other metabolites were present in higher concentrations in Boston. In Puerto Rico, intraclass correlation coefficients (ICC) were weak to moderate, ranging from 0.06 to 0.42. PAH metabolite concentrations were significantly higher among younger, heavier (except 1-NAP and 9-PHE), and less educated individuals in Boston only. Consistent significant associations between PAH concentrations and measured covariates were not found in Puerto Rico. Our results suggest that potentially important differences in PAH exposure exist between these two populations. Additionally, our results indicate that multiple urinary measurements are required to accurately assess PAH exposure throughout pregnancy.

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.

An increasing number of studies have been conducted to determine a possible linkage between maternal exposure to ambient fine particulate matter and effects on the developing human fetus that can lead to adverse birth outcomes, but, the present results are not consistent. A total of 23 studies published before July 2016 were collected and analyzed and the mean value of reported exposure to fine particulate matter (PM2.5) ranged from 1.82 to 22.11 We found a significantly increased risk of preterm birth with interquartile range increase in PM2.5 exposure throughout pregnancy (odds ratio (OR) = 1.03; 95% conditional independence (CI): 1.01–1.05). The pooled OR for the association between PM2.5 exposure, per interquartile range increment, and term low birth weight throughout pregnancy was 1.03 (95% CI: 1.02–1.03). The pooled ORs for the association between PM2.5 exposure per 10 increment, and term low birth weight and preterm birth were 1.05 (95% CI: 0.98–1.12) and 1.02 (95% CI: 0.93–1.12), respectively throughout pregnancy. There is a significant heterogeneity in most meta-analyses, except for pooled OR per interquartile range increase for term low birth weight throughout pregnancy. We here show that maternal exposure to fine particulate air pollution increases the risk of preterm birth and term low birth weight. However, the effect of exposure time needs to be further explored. In the future, prospective cohort studies and personal exposure measurements needs to be more widely utilized to better characterize the relationship between ambient fine particulate exposure and adverse birth outcomes.

Seasonal patterns of birth outcomes have been observed worldwide, and there was increasing evidence that ambient temperature played as a trigger of adverse birth outcomes, such as preterm birth (PTB), low birth weight (LBW), and stillbirth. To systematically review updated epidemiological evidence about the relationship between temperature exposure during pregnancy and PTB, LBW, and stillbirth, we searched for related studies published in English from electronic databases and references of identified papers. We only included original articles that directly reported the effects of prenatal temperature exposure on birth outcomes. The characteristics and main findings of included studies were examined. A total of 36 epidemiological studies were finally included in this review. Most of these studies focused on PTB and LBW, while less attention has been paid to stillbirth that was relatively rare in the occurrence. Several designs including ecological (e.g., descriptive and time-series) and retrospective cohort studies (e.g., case-crossover and time-to-event) were applied to assess temperature effects on birth outcomes. Temperature metrics and exposure windows varied greatly in these investigations. Exposure to high temperature was generally found to be associated with PTB, LBW, and stillbirth, while several studies also reported the adverse impact of low temperature on birth outcomes of PTB and LBW. Despite no conclusive causality demonstrated, the current evidence for adverse effect on birth outcomes was stronger for heat than for cold. In summary, the evidence linking birth outcomes with ambient temperature was still very limited. Consequently, more related studies are needed worldwide and should be conducted in diversified climate zones, so as to further ascertain the association between temperature and birth outcomes. Future studies should focus on more sophisticated study designs, more accurate estimation of temperature exposure during pregnancy, and more efficient methods to find out the exposure windows, as well as cold-related effects on birth outcomes.

Low birth weight (<2500 g) (LBW), premature birth (<37 weeks of gestation) (PB), and late foetal death (<24 h of life) (LFD) are causes of perinatal morbi-mortality, with short- and long-term social and economic health impacts. This study sought to identify gestational windows of susceptibility during pregnancy and to analyse and quantify the impact of different air pollutants, noise and temperature on the adverse birth outcomes.Time-series study to assess the impact of mean daily PM2.5, NO2 and O3 (μg/m3), mean daily diurnal (Leqd) and nocturnal (Leqn) noise levels (dB(A)), maximum and minimum daily temperatures (°C) on the number of births with LBW, PB or LFD in Madrid across the period 2001–2009. We controlled for linear trend, seasonality and autoregression. Poisson regression models were fitted for quantification of the results. The final models were expressed as relative risk (RR) and population attributable risk (PAR).Leqd was observed to have the following impacts in LBW: at onset of gestation, in the second trimester and in the week of birth itself. NO2 had an impact in the second trimester. In the case of PB, the following: Leqd in the second trimester, Leqn in the week before birth and PM2.5 in the second trimester. In the case of LFD, impacts were observed for both PM2.5 in the third trimester, and minimum temperature. O3 proved significant in the first trimester for LBW and PB, and in the second trimester for LFD.Pollutants concentrations, noise and temperature influenced the weekly average of new-borns with LBW, PB and LFD in Madrid. Special note should be taken of the effect of diurnal noise on LBW across the entire pregnancy. The exposure of pregnant population to the environmental factors analysed should therefore be controlled with a view to reducing perinatal morbi-mortality.

Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of ∑DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean ∑DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation.

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.