Maternal exposure to air pollution has been associated with a higher birth defect (BD) risk. Previous studies suffer from inaccurate exposure assessment methods, confounding individual-level variations, and classical analytical modelling. This study aimed to examine the association between maternal exposure to criteria air pollutants and BD risk. A total of 553 cases and 10,214 controls were identified from private and public databases. Two subgroups were then formed: one for a matched case-control design, and another for Feature Selection (FS) analysis. Exposure assessment was based on the mean air pollutant-specific levels in the mother’s residential area during the specific BD gestational time window of risk (GTWR) and other time intervals. Multivariate regression models outcomes consistently showed a significant protective effect for folic acid intake and highlighted parental consanguinity as a strong BD risk factor. After adjusting for these putative risk factors and other covariates, results show that maternal exposure to PM₂.₅ during the first trimester is significantly associated with a higher overall BD risk (OR:1.05, 95%CI:1.01–1.09), and with a higher risk of genitourinary defects (GUD) (OR:1.06, 95%CI:1.01–1.11) and neural tube defects (NTD) (OR:1.10, 95%CI:1.03–1.17) during specific GTWRs. Maternal exposure to NO₂ during GTWR exhibited a significant protective effect for NTD (OR:0.94, 95%CI:0.90–0.99), while all other examined associations were not statistically significant. Additionally, maternal exposure to SO₂ during GTWR showed a significant association with a higher GUD risk (OR:1.17, 95%CI:1.08–1.26). When limiting selection to designated monitor coverage radiuses, PM₂.₅ maintained significance with BD risk and showed a significant gene-environment interaction for GUD (p = 0.018), while NO₂ protective effect expanded to other subtypes. On the other hand, FS analysis confirmed maternal exposure to PM₂.₅ and NO₂ as important features for GUD, CHD, and NTD. Our findings, set the basis for building a novel BD risk prediction model.

The potential risks of phthalates affecting human and animal health as well as the environment are emerging as serious concerns worldwide. However, the mechanism by which phthalates induce developmental effects is under debate. Herein, we found that embryonic exposure of zebrafish to di-(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) increased the rate of heart defects including abnormal heart rate and pericardial edema. Changes in the transcriptional profile demonstrated that genes involved in the development of the heart, such as tbx5b, nppa, ctnt, my17, cmlc1, were significantly altered by DEHP and DBP at 50 μg/L, which agreed with the abnormal cardiac outcomes. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) further showed that significant hypomethylation of nppa and ctnt was identified after DEHP and DBP exposure, which was consistent with the up-regulation of these genes. Notably, hypermethylation on the promoter region (<1 kb) of tbx5b was found after DEHP and DBP exposure, which might be responsible for its decrease in transcription. In conclusion, phthalates have the potential to induce cardiac birth defects, which might be associated with the transcriptional regulation of the involved developmental factors such as tbx5b. These findings would contribute to understand the molecular pathways that mediated the cardiac defects caused by phthalates.

In Iraq, war contamination is the result of dispensed bombs, bullets, detonation of chemical and conventional weapons, and burn-pit emissions by US bases. Increases in congenital anomalies were reported from Iraqi cities post-2003. These cities were heavily bombed and encircled by US bases with burn-pits. Thorium is a radioactive compound and a direct depleted-uranium decay-product. Radioactive materials, including depleted uranium, are routinely stored in US bases and they have been shown to leak into the environment. We conducted a case-control study to investigate associations of residential proximity to Tallil Air Base, a US military base near Nasiriyah, as well as levels of uranium and thorium in hair and deciduous teeth with congenital anomalies. The study was based on a sample of 19 cases and 10 controls who were recruited during late Summer and early Fall of 2016. We developed mixed effects logistic regression models with village as the random effect, congenital anomaly as the outcome and distance to the US base and hair metal levels (one at a time) as the predictor variable, controlling for child's age, sex and paternal education. We also explored the mediation of the association between proximity to the base and congenital anomalies by hair metal levels. We found an inverse association between distance to Tallil Air Base and risk of congenital anomalies and hair levels of thorium and uranium. The results of our mediation analyses were less conclusive. Larger studies are necessary to understand the scope of war contamination and its impact on congenital anomalies in Iraq.

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004–2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25–1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.

Noise is associated with poor reproductive health. A number of animal studies have suggested the possible effects of exposure to high noise levels on fertility; to date, a little such research has been performed on humans.We examined an association between daytime and nocturnal noise exposures over four years (2002–2005) and subsequent male infertility.We used the National Health Insurance Service-National Sample Cohort (2002–2013), a population-wide health insurance claims dataset. A total of 206,492 males of reproductive age (20–59 years) with no history of congenital malformations were followed up for an 8-year period (2006–2013). Male infertility was defined as per ICD-10 code N46. Data on noise exposure was obtained from the National Noise Information System. Exposure levels of daytime and night time noise were extrapolated using geographic information systems and collated with the subjects' administrative district code, and individual exposure levels assigned.During the study period, 3293 (1.6%) had a diagnosis of infertility. Although there was no association of infertility with 1-dB increments in noise exposure, a non-linear dose-response relationship was observed between infertility and quartiles of daytime and night time noise after adjustment for confounding variables (i.e., age, income, residential area, exercise, smoking, alcohol drinking, blood sugar, body mass index, medical histories, and particulate pollution). Based on WHO criteria, adjusted odds for infertility were significantly increased (OR = 1.14; 95% CI, 1.05–1.23) in males exposed to night time noise ≥ 55 dB.We found a significant association between exposure to environmental noise for four years and the subsequent incidence of male infertility, suggesting long-term exposure to noise has a role in pathogenesis of male infertility.

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.

The levels of nitrate in 52 drinking water wells in rural Central Java, Indonesia were evaluated in April 2014, and the results were used for a health risk assessment for the local populations by using probabilistic techniques. The concentrations of nitrate in drinking water had a range of 0.01–84 mg/L, a mean of 20 mg/L and a medium of 14 mg/L. Only two of the 52 samples exceeded the WHO guideline values of 50 mg/L for infant methaemoglobinaemia. The hazard quotient values as evaluated against the WHO guideline value at the 50 and 95 percentile points were HQ50 at 0.42 and HQ95 at 1.2, respectively. These indicated a low risk of infant methaemoglobinaemia for the whole population, but some risk for the sensitive portion of the population. The HQ50 and HQ95 values based on WHO acceptable daily intake dose for adult male and female were 0.35 and 1.0, respectively, indicating a generally a low level of risk. A risk characterisation linking birth defects to nitrate levels in water consumed during the first three months of pregnancy resulted in a HQ50/50 values of 1.5 and a HQ95/5 value of 65. These HQ values indicated an elevated risk for birth defects, in particular for the more sensitive population. A sanitation improvement program in the study area had a positive effect in reducing nitrate levels in wells and the corresponding risk for public health. For example, the birth defect HQ50/50 values for a subset of wells surveyed in both 2014 and 2015 was reduced from 1.1 to 0.71.

In 2014, as an attempt to address the Zika health crisis by controlling the mosquito population, Brazil took the unprecedented action of applying a chemical larvicide, pyriproxyfen, to drinking water sources. The World Health Organization has established an acceptable daily intake of pyriproxyfen to be 100 μg per kg of body weight per day, but studies have demonstrated that at elevated doses (>5000 mg/kg), there are adverse effects in mice, rats and dogs. To better understand the potential developmental toxicity of pyriproxyfen, we utilized the embryonic zebrafish. Our results demonstrate that the concentration resulting in 50% of animals presenting adverse morphological effects (EC50), including craniofacial defects, was 5.2 μM for daily renewal exposure, and above this concentration, adverse behavioral effects were also observed in animals that followed a static exposure regimen. Thus, zebrafish data suggest that the developmental toxicity of pyriproxyfen may not be limited to insects.

We performed an exploratory analysis of ozone (O3) and fine particulate matter (PM2.5) concentrations during early pregnancy and multiple types of birth defects. Data on births were obtained from the Texas Birth Defects Registry (TBDR) and the National Birth Defects Prevention Study (NBDPS) in Texas. Air pollution concentrations were previously determined by combining modeled air pollution concentrations with air monitoring data. The analysis generated hypotheses for future, confirmatory studies; although many of the observed associations were null. The hypotheses are provided by an observed association between O3 and craniosynostosis and inverse associations between PM2.5 and septal and obstructive heart defects in the TBDR. Associations with PM2.5 for septal heart defects and ventricular outflow tract obstructions were null using the NBDPS. Both the TBDR and the NBPDS had inverse associations between O3 and septal heart defects. Further research to confirm the observed associations is warranted.

The Madín Dam is a reservoir located in the municipalities of Naucalpan and Atizapán, in the metropolitan area adjacent to Mexico City. The reservoir supplies drinking water to nearby communities and provides an area for various recreational activities, including kayaking, sailing and carp fishing. Over time, the number of specimens of common carp has notably diminished in the reservoir, which receives direct domestic drainage from two towns as well as numerous neighborhoods along the Tlalnepantla River. Diverse studies have demonstrated that the pollutants in the water of the reservoir produce oxidative stress, genotoxicity and cytotoxicity in juvenile Cyprinus carpio, possibly explaining the reduction in the population of this species; however, it is necessary to assess whether these effects may also be occurring directly in the embryos. Hence, surface water samples were taken at five sites and pharmaceutical drugs, personal care products (especially sunscreens), organophosphate and organochlorine pesticides, and other persistent organic pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) were identified. Embryos of C. carpio were exposed to the water samples to evaluate embryolethality, modifications in embryonic development, lipoperoxidation, the quantity of hydroperoxide and oxidized proteins, and antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase). It was found that the polluted water of the Madín Dam gave rise to embryolethality, embryotoxicity, congenital abnormalities, and oxidative stress on the common carp embryos.