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.

Stillbirth has a great impact on contemporary and future generations. Increasing evidence show that ambient air pollution exposure is associated with stillbirth. However, previous studies showed inconsistent findings. To clarify the effect of maternal air pollution exposure on stillbirth, we searched for studies examining the associations between air pollutants, including particulate matter (diameter ≤ 2.5 μm [PM₂.₅] and ≤10 μm [PM₁₀]) and gaseous pollutants (sulfur dioxide [SO₂], nitrogen dioxide [NO₂], carbon monoxide [CO] and ozone [O₃]), and stillbirth published in PubMed, Web of Science, Embase and Cochrane Library until December 11, 2020. The pooled effect estimates and 95% confidence intervals (CI) were calculated, and the heterogeneity was evaluated using Cochran’s Q test and I² statistic. Publication bias was assessed using funnel plots and Egger’s tests. Of 7546 records, 15 eligible studies were included in this review. Results of long-term exposure showed that maternal third trimester PM₂.₅ and CO exposure (per 10 μg/m³ increment) increased the odds of stillbirth, with estimated odds ratios (ORs) of 1.094 (95% CI: 1.008–1.180) and 1.0009 (95% CI: 1.0001–1.0017), respectively. Entire pregnancy exposure to PM₂.₅ was also associated with stillbirth (OR: 1.103, 95% CI: 1.074–1.131). A 10 μg/m³ increment in O₃ in the first trimester was associated with stillbirth, and the estimated OR was 1.028 (95% CI: 1.001–1.055). Short-term exposure (on lag day 4) to O₃ was also associated with stillbirth (OR: 1.002, 95% CI: 1.001–1.004). PM₁₀, SO₂ and NO₂ exposure had no significant effects on the incidence of stillbirth. Additional well-designed cohort studies and investigations regarding potential biological mechanisms are warranted to elaborate the suggestive association that may help improve intergenerational inequality.

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.

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.

Severe methylmercury poisoning occurred in Minamata and neighboring communities in Japan during the 1950s and 1960s, causing what is known as Minamata disease. Although an increase in stillbirths and a reduced male proportion at birth (i.e., reduced sex ratio) have been reported, no studies have evaluated the impact of exposure on an entire set of infant and birth outcomes. We therefore evaluated the temporal trends of these outcomes in the Minamata area from 1950 to 1974. We focused on the spontaneous/artificial stillbirth rate, crude fertility rate, male proportion at birth, male proportion among stillbirths, and infant mortality. We obtained the number of stillbirths, live births, and infant deaths in Minamata City and Kumamoto Prefecture (as a reference) from 1950 to 1974. After plotting annual figures for each outcome, we divided the study period into five intervals and compared them between Minamata City and Kumamoto Prefecture using the chi-squared test. We observed a slightly increased spontaneous stillbirth rate and decreased artificial stillbirth rate in Minamata City, followed by a reduced crude fertility rate. The crude fertility rates in Minamata City during the period 1955–1965 were significantly lower compared with those in Kumamoto Prefecture (p < 0.001). An increase in the male proportion among stillbirths was observed, corresponding to a reduction in the proportion of males at birth in the late 1950s. The impact on infant mortality was equivocal. These descriptive analyses demonstrate a severe regional impact of methylmercury exposure on a series of birth outcomes in the Minamata area.

Maternal exposure to ambient air pollution has been related to oral clefts in offspring; however, the epidemiologic evidence is equivocal. Especially, the association between high levels of exposure to ambient air pollution during pregnancy and oral clefts remains unclear. The objective of this study was to evaluate whether high levels of maternal exposure to PM2.5, PM10, O3, CO and SO2 are related to increased risk of oral clefts in Wuhan, China. A population-based study was conducted using cohort of 105,927 live-born infants, fetal deaths, and stillbirths during a two-year period from 2011 to 2013. For each participant, weekly and monthly averages of daily mean concentrations for each pollutant were estimated. Multiple logistic regression analyses were constructed to quantify the adjusted odds ratios (aORs) for the relationship between each air pollutant and oral clefts while controlling for key covariates. Using monthly averages, a cleft lip with or without cleft palate (CLP) was associated with PM2.5 (aORs 2nd month = 1.34, CI:1.19–1.49; aORs 3rd month=1.14, CI:1.02–1.28), PM10 (aORs 2nd month = 1.11, CI:1.00–1.23) and CO (aORs 2nd month = 1.31, CI:1.14–1.51; aORs 3rd month = 1.17, CI:1.03–1.33). A cleft palate only (CPO) was associated with PM2.5 (aORs 2nd month = 1.24, CI: 1.03–1.48), and O3 (aORs 2nd month = 1.21, CI: 1.03–1.42; aORs 3rd month = 1.18, CI: 1.02–1.37). Our findings reveal an association between air pollutants exposure and the risk of oral clefts. Future studies are needed to confirm these associations, and clarify the causality related to specific pollutants during the most relevant vulnerable exposure time windows for oral clefts during pregnancy.

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

The continuous exposure to conventional pesticides leads to severe health and environmental issues especially at prenatal stage during developmental period. Herein, we aimed to investigate the anomalies due to repeated exposure of pyriproxyfen in pregnant female mice and their neonates. Twenty-four pregnant female mice were repeatedly administered with pyriproxyfen at 30, 100, 300, and 1000 mg/kg by oral gauge from gestation day (GD) 7 to gestation day 17 and six females were given distilled water in the control group. All the live pups were euthanized at postnatal day (PND) 7 and their organs (heart, liver, kidney, and brain) were dissected out, weighed, and assessed for further histopathological examinations. The results exhibited a significant (P < 0.001) decrease in the body weight gain of all treated pregnant mice in comparison to the controls and a significant increase in the gestational length was observed in group IV (P < 0.01) and group V (P < 0.001). In addition, no live pups were born in groups IV and V and one pregnant female mouse was also found dead in both treatments. The body weights of the pups were significantly decreased in group II (P < 0.05) and group III (P < 0.001) and the relative organ (liver, heart, and kidney) weight of the pups was increased significantly (P < 0.001, P < 0.01, P < 0.05) due to prenatal exposure in group II as compared to group I. The relative brain weights of the pups were decreased significantly (P < 0.001) in groups II and III as compared to group I. The liver, kidney, heart, and brain sections exhibited various histological alterations in groups II and III by hematoxylin and eosin staining. Furthermore, immunohistochemical staining of the coronal sections of pup’s brain showed significant (P < 0.001) reduction in cortical radial thickness and total neural count in group II and III as compared to group I. Therefore, the prenatal exposure to pyriproxyfen provoked the damage to various organs in mice offspring and an increase in fetal death at higher doses.

Accumulating evidence has shown that prenatal ambient air pollution exposure is associated with elevated stillbirth risk; however, the results are inconsistent. This population-based prospective cohort study aimed to explore the association between prenatal air pollution exposure and stillbirth rate in the coastal area in China. Data of air pollution and birth outcomes between January 1, 2015, and December 31, 2017, were collected. Among the 59,868 eligible births, there were 587 stillbirths and 59,281 live births. Although the air quality in this study was relatively better than most of the major cities in China, a positive association was still found between prenatal air pollution exposure and stillbirth rate. Every 10 μg/m³ increase of fine particulate matters (PM₂.₅) in each trimester, as well as in the entire pregnancy, was associated with increased stillbirth rate (RR = 1.14, 1.11, 1.15, and 1.14 for the first, second, third trimester, and entire pregnancy, respectively). In addition, every 10 μg/m³ increase of PM₁₀ in the first trimester (RR = 1.09, 95% CI: 1.04–1.14), and 10 μg/m³ increase of O₃ in the first (RR = 1.05, 95% CI: 1.01–1.09) and third (RR = 1.04, 95% CI: 1.00–1.08) trimesters was also associated with increased stillbirth rate. The effects of PM₂.₅ on stillbirth rate were found to be robust in the two-pollutant models. The findings of this study especially underscored the adverse effects of prenatal exposure of high levels of PM₂.₅ on stillbirth. More studies are needed to verify our findings and further investigate the underlying mechanisms.

Organochlorine pesticides (OCPs) were determined by gas chromatography in 241 placentas from cotton-growing regions, 121 placentas from an urban area (city of Osh), and 146 placentas from unpolluted mountain regions of Kyrgyzstan. Manifestations of disease were recorded in the mothers during pregnancy and parturition and in their newborns during the first 6 days of life. OCPs were detected in 240 out of 508 placentas (47.2%), with increased incidence in the two polluted regions (65%), particularly in placentas from women living near former pesticide storehouses and agro air-strips (99%), but only in 2.7% of placentas from the unpolluted region. α-, β-, and γ-hexachlorocyclohexane (HCH); DDT; DDE; aldrin; and heptachlor were detected. The sum of concentrations of all OCPs (total OCPs) was calculated for each of the 240 placentas with detectable OCPs (median 9.5 μg/kg placenta, mean 88.3 μg/kg, range 0.1–3070 μg/kg). The incidence of health problems in four subgroups of this data set, with increasing levels of total OCPs, was compared with the incidence of health problems in the group of 268 placentas, where OCPs were undetectable. Relative risk of health problems in both, mothers and newborns, increased significantly, in a concentration-dependent manner, with increasing levels of total OCPs (p < 0.0001). Health complications with increased incidence in OCP-exposed newborns included, i.a., low birth weight, congenital malformations, infections, and stillbirths, in OCP-exposed mothers preterm delivery, (pre-)eclampsia/gestosis, and frequency of hospitalizations after delivery (infections). Women living near former pesticide storehouses and agro airstrips should be considered as being at risk. Reduction of exposure is urgently needed.