Perfluorooctane sulfonic acid (PFOS) is a ubiquitous environmental pollutant. In humans, PFOS exposure has been associated with a number of adverse health outcomes, including reduced birth weight. Whether PFOS is capable of affecting angiogenesis and thus possibly fetal development is unknown. Therefore, we investigated 1) the metabolic activity of PFOS-exposed endothelial cells (human umbilical vein endothelial cells, HUVECs), fibroblasts (normal colon fibroblasts, NCFs), and epithelial cells (human colorectal carcinoma cells, HCT116), 2) PFOS-specific inhibition of vascular endothelial growth factor receptor (VEGFR)2 stimulation in KDR/NFAT-RE HEK293 cells, and 3) the antiangiogenic potential of PFOS in a 3D in vitro angiogenesis model of HUVECs and NCFs. In terms of metabolic activity, endothelial cells (HUVECs) were much more sensitive to PFOS than fibroblasts (NCFs) or epithelial cells (HCT116). VEGFR2 signaling in KDR/NFAT-RE HEK293 cells decreased with increasing PFOS concentrations. In co-culture (angiogenesis assay), PFOS treatment resulted in a dose-dependent reduction in tip and branch formation, tip length (μm), and total structural area (μm²) with stable metabolic activity of HUVECs up to high concentrations. We conclude that PFOS possesses antiangiogenic properties. Inhibition of VEGFR2 signaling indicates a possible mechanism of action that can be linked to an existing Adverse Outcome Pathway (AOP43) containing the AO reduced birth weight. Further studies are needed to confirm PFOS-specific adverse effects on angiogenesis, placental perfusion, and fetal growth.

The presence of polycyclic aromatic hydrocarbons (PAHs) in the fetal environment is a high-priority concern due to the fetus being more sensitive than adults to these ubiquitous xenobiotics. The aim of the present study was to compare the maternal and fetal serum levels of ΣPAHs and their effects on fetal growth in an industrial and an urban area in Southwest Iran. The industrial area was the petrochemical and gas area (PGA) of the Central District of Asaluyeh County and the urban area (UA) was the Central District of Bushehr County, Ninety-nine maternal serum (MS) and 99 cord serum (CS) samples from the PGA and 100 MS and 100 CS samples from the UA were collected during May 2018 to February 2019. The mean concentrations of ΣPAHs were significantly (p < 0.05) higher in the PGA than the UA in both MS (157.71 vs. 93.56 μg/L) and CS (155.28 vs. 93.19 μg/L) samples. Naphthalene (NAP) was the predominant PAH detected in all the studied samples. Significant negative associations were found between birth weight and anthracene (ANT) level in MS (β = −22.917, p = 0.032; weight decrement = 22.917 g for a 1 μg/L increase in ANT); head circumference and chrysene (CHR) level in MS (β = −0.206, p = 0.023; head circumference decrement = 0.206 cm for a 1 μg/L increase in CHR); and birth height and NAP level in CS (β = −0.20, p = 0.005; height decrement = 0.20 cm for a 1 μg/L increase in NAP). Maternal diet had a significant effect on the serum levels of PAHs. The results of this study showed that transmission of PAHs from mother to fetus through the cord blood is an important issue and mothers who live in industrial areas and consume PAH-containing foodstuffs, and their fetuses, are more at risk than those living in a non-industrial urban area.

Ambient carbon monoxide (CO) and particulate matters (PMs) are two important air pollutants in urban areas with known impacts on fetuses. Hence, this study measured some biochemistry factors of 200 neonates with birth dates from January 19 to October 12, 2020, including the birth weight and height and the serum levels of ALT, AST, ALP, GGT, and TSH. The Support Vector Machine-fitted land-use regression approach was used to predict the spatio-temporal variability of intra-urban PM 2.5 and CO concentrations by month during the pregnancy period of the cases employing 5 variables of Digital Elevation Model (DEM), slope, and distance from Compressed Natural Gas (CNG) stations, Bus Rapid Transit (BRT) stations, and mines and industries. Spearman correlation analysis (p < 0.05) was performed between the neonate indices and mean monthly PM 2.5 and CO concentrations at the exact residential address of maternal cases and their nearby areas in 250, 500, 1000, 1500, and 2000 m-radius buffer rings. All modeling efforts succeeded in predicting CO and PM 2.5 levels with acceptable adjusted r² values. Northern Isfahan had relatively higher CO and PM 2.5 concentrations due to its adjacency to low-vegetated open lands and its high traffic load as compared to southern areas. The correlation results between the neonate biochemistry indices and mean PM 2.5 and CO concentrations were mostly positive in most buffer rings, especially in the >500 m-radius buffer rings for PM 2.5 and in the 2000 m-radius rings for CO. Although the correlation results of PM 2.5 followed a detectable trend in the buffer rings, the associations between CO and the neonate biochemistry indices differed significantly between the buffer rings. Results showed that increasing mean monthly concentration of CO and PM 2.5 may stimulate further production of liver enzymes while decreasing the birth weight and height.

Maternal blood glucose level is associated with fetal growth, therefore, its role in the associations between air pollution and birth weight deserves investigation. We examined the mediation effect of maternal blood glucose on the associations between maternal air pollution exposure and birth weight. A total of 10,904 pregnant women in Foshan, China during 2015–2019 were recruited. Oral glucose tolerance test (OGTT) was administered to each participant after late trimester 2. Air pollution data at the monitoring stations in residential districts was used to estimate exposures of each participant during trimester 1 and trimester 2. Mixed-effects linear models were used to estimate the associations between air pollution and birth weight. After controlling for ten covariates, the direct effect of PM₂.₅ and SO₂ (each 10 μg/m³ increment) on birth weight was −15.7 g (95% CI: −29.4, −4.8 g) and −83.6 g (95% CI: −134.8, −33.0 g) during trimester 1. The indirect effect of PM₂.₅ and SO₂ (each 10 μg/m³ increment) on birth weight by increasing maternal fasting glucose level was 6.6 g (95% CI: 4.6, 9.1 g) and 22.0 g (95% CI: 4.1, 44.0 g) during trimester 1. Our findings suggest that air pollution might affect the birth weight through direct and indirect pathway, and the indirect effect might be mediated by maternal blood glucose.

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 μg/kg) above the spline knot of 0.50 μg/kg was associated with reduced birth weight (B: −191 g; 95% CI: −315, −68) and length (−0.67 cm; −1.2, −0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 μg/kg, mainly MeHg) above 1.0 μg/kg, was associated with decreased birth weight (−59 g; −115, −3.0), and length (−0.29 cm; −0.54, −0.047). Maternal Pb (median 11 μg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.

Exposure to phthalates during gestation has been associated with decreased birth weight among offspring. However, the associations between preconception phthalate metabolites in follicular fluid (FF) and offspring birth weight among women undergoing in vitro fertilization (IVF) remain largely unknown. Here, we explored the associations between preconception phthalate metabolite concentrations in FF and the birth weights of singletons and twins among women undergoing IVF. We recruited 147 female participants who gave birth to 90 singletons and 57 twin infants at the Reproductive Medicine Center, Tongji Hospital, Wuhan, between November and December 2016. Each participant was asked to complete a questionnaire at the time of recruitment and provide a FF sample on the day of oocyte retrieval. The FF concentrations of eight phthalate metabolites were determined using high-performance liquid chromatography and tandem mass spectrometry. Birth outcomes were abstracted from medical records. The associations between phthalate metabolites in FF and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs). We found that birth weight in the twin group had negative dose-response associations with maternal preconception monobenzyl phthalate (MBzP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) in FF (both P for trends < 0.05) and that birth weight in the singleton group had positive dose-response associations with monoethyl phthalate (MEP) and mono(2-ethyl-5 hydroxyhexyl) phthalate (MEHHP) in FF (both P for trends < 0.05). These associations persisted when we modeled as continuous variables. In addition, we observed male-specific association between decreased twin birth weight and MEOHP and MBzP and a female-specific associations between increased singleton birth weight and MEP, MEHHP and the sum of di(2-ethylhexyl) phthalate (∑DEHP) (all P for interactions < 0.05). Preconception phthalate metabolites in maternal FF may affect the birth weights of both singleton and twin newborns.

Previous studies have suggested a change of birth weight linked with elevated ambient air pollutant concentrations during the pregnancy. However, investigations of the influence of higher pollutant levels on birth weight change are limited. The goal of this study is to evaluate whether the air pollution of Ningbo is associated with birth weight, and which trimester could be a window period for maternal exposure to air pollution. A total of 170,008 live births were selected in the Ningbo city of Zhejiang, China, from 2015 to 2017. We estimated the association between the decreased birth weight and the increased air pollutant concentrations in the three trimesters and full gestation. The effects of interaction among pollutants were identified using a co-pollutant adjustment model. An interquartile range increases in PM2.5 (10.55 μg/m3), SO2(4.6 μg/m3), CO (125.59 μg/m3), and O3 (14.54 μg/m3) concentrations during the entire gestation were associated with 3.65 g (95% confidence interval: −6.02 g, −1.29 g), 5.02 g (−6.89 g, −3.14 g), 2.64 g (−4.65 g, −0.63 g) and 2.9 g (−4.8 g, 1 g) decreases, respectively, in birth weight. With each interquartile range increment in NO2 concentration was associated with an 8.05 g (6.24 g, 9.85 g) increase in birth weight. In the first trimester, only the PM2.5 exposure seemed to be associated with the greatest decline in birth weight. After adjustment for co-pollutant, both PM2.5 and SO2 were still associated with birth weight, except for CO for O3 adjustment, O3 for SO2 adjustment, and O3 for NO2 adjustment. Maternal exposure to air pollution may be associated with a decrease of birth weight, but the contribution of various pollutants is necessary to verify by future research.

Particulate matter 2.5 (PM₂.₅) exposures during pregnancy could lead to declined birth weight, intrauterine developmental restriction, and premature delivery, however, the underlying mechanisms are still not elucidated. There are few studies concerning the effects of PM₂.₅ exposure on maternal and child health in Xi'an (one of the cities with severe air pollution of PM₂.₅ in North China). Then, this study aimed to investigate the effect of PM₂.₅ exposure in Xi'an on the offspring birth weights and the possibly associated epigenetic mechanisms. We found the Low and High groups: the offspring with declined birth weights; the decreased mRNA and protein expression of the estrogen receptor (ERs) and eNOs in the uterus; the decreased endometria vascular diameter maximum (EVDM); the increased mRNA and protein expressions of the DNMT1 and 3b in the uterus; the elevated methylation levels of the CpG sites in the CpG island of ERα promoter region in the uterus. However, no differences were observed in the mRNA or protein expressions of ERβ and DNMT3a between the Clean and PM₂.₅ exposure groups, as well as endometriavascular density (EVD). Additionally, PM₂.₅ level was negatively correlated with the ERα protein expression, EVDM and offspring birth weight, as well as the methylation level of the CpG sites in the CpG island of ERα promoter region and the ERα protein expression in the uterus; whereas the ERα protein expression was positively correlated with the offspring birth weight, as well as PM₂.₅ level and the methylation level of the CpG sites in the CpG island of ERα promoter region in the uterus. Taken together, elevated methylation level of the CpG sites in the CpG island of ERα promoter region reduces ERα expression in the uterus, which could be one of the epigenetic mechanisms that pregnant PM₂.₅ exposure reduces the offspring birth weights.

Exposure to 4-tert-octylphenol (tOP) has been linked with adverse health outcomes in animals and humans, while epidemiological studies about associations between prenatal exposure to tOP and fetal growth are extremely limited. We measured urinary tOP concentrations in 1100 pregnant women before their delivery, and examined whether tOP levels were associated with birth outcomes, including weight, length, head circumference and ponderal index at birth. tOP could be detected in all samples, and the median uncorrected and creatinine-corrected tOP concentrations were 0.90 μg/L (range from 0.25 to 20.05 μg/L) and 1.33 μg/g creatinine (range from 0.15 to 42.49 μg/g creatinine), respectively. Maternal urinary log-transformed tOP concentrations were significantly negatively associated with adjusted birth weight [β (g) = −126; 95% confidence interval (CI): −197, −55], birth length [β (cm) = −0.53; 95% CI:−0.93, −0.14], and head circumference [β (cm) = −0.30; 95% CI: −0.54, −0.07], respectively. Additionally, considering sex difference, these significant negative associations were also found among male neonates, while only higher maternal tOP concentrations were associated with a significant decrease in birth weight among female neonates. This study suggested significant negative associations between maternal urinary tOP concentrations and neonatal sizes at birth, and they differed by neonatal sex. Further epidemiological studies are required to more fully elaborate the associations between prenatal tOP exposure and birth outcomes.

Exposure to lead early in life may be a risk factor for fetal growth, but little is known about the effects of low-level prenatal lead exposure on birth outcomes. We measured maternal and cord blood lead levels and examined their associations with birth outcomes. Mother–infant pairs (n = 252) were recruited from a rural area located on the south coast of Laizhou Bay between 2010 and 2011. The median levels of maternal and cord blood lead were 3.20 and 2.52 μg/dL, respectively. Increasing maternal blood lead exposure was associated with decreasing birth weight (β = −148.99; 95% CI, −286.33 to −11.66), and a significant negative relationship was found between cord blood lead levels and birth length (β = −0.84; 95% CI, −1.52 to −0.16). Low-level prenatal lead exposure may adversely affect fetal growth. These results may be important for public health and have implications regarding the recommended blood lead levels.