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.

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.

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.