Early Pregnancy Exposure Research Articles

Titanium exposure and gestational diabetes mellitus: associations and potential mediation by perturbation of amino acids in early pregnancy

BackgroundSeveral recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce.MethodsThe present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways.ResultsAs parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk.ConclusionsIn this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.Graphical

Early pregnancy exposure to Microcystin-LR compromises endometrial decidualization in mice via the PI3K/AKT/FOXO1 signaling pathway

Previous experimental studies have found that exposure to Microcystin-leucine arginine can impact pregnancy outcomes in female mice. The impact of MC-LR on early pregnancy in mammals is not yet well understood. Both mice and humans need to undergo decidualization to maintain pregnancy. In this study, we tried to evaluate whether MC-LR affects decidualization process in mice. Our research showed that MC-LR decreased maternal weight gain, uterine weight, and implantation site weight. These findings suggested that MC-LR exerted adverse effects on decidualization. In mice, we examined decreased number of polyploid decidual cells, but marked proliferation of mouse endometrial stromal cells the expression levels of prolactin (PRL)and insulin-like growth factor binding protein 1 (IGFBP1) were significantly downregulated in the decidual tissue and primary endometrial stromal cells following MC-LR treatment. Furthermore, further in vitro experiments identified that MC-LR promoted endometrial stromal cell division and cycle transition. Lastly, our study demonstrated that MC-LR impaired decidualization through the PI3K/AKT/FOXO1 pathway. Collectively, these data suggested that exposure to MC-LR impaired decidualization during early pregnancy.

Association of PM2.5 exposure in early pregnancy and maternal liver function: A retrospective cohort study in Shenzhen, China

ObjectiveStudies have shown that fine particulate matter (PM2.5) has adverse effects on the liver function, but epidemiological evidence is limited, especially regarding pregnant women. This study aims to investigate the association between PM2.5 exposure in early pregnancy and maternal liver function during pregnancy. MethodsThis retrospective cohort study included 13,342 pregnant participants. PM2.5 and Ozone (O3) exposure level, mean temperature, and relative humidity for each participant were assessed according to their residential address. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were measured during the second and third trimesters. Data on PM2.5 and O3 exposure level were sourced from Tracking Air Pollution in China (TAP), while the mean temperature and relative humidity were obtained from the ERA5 dataset. The Generalized Additive Model (GAM) was used to analyze the associations between PM2.5 exposure and maternal liver function during pregnancy, adjusting for potential confounding factors. ResultsAccording to the results, each 10 μg/m3 increase in PM2.5 was associated with an increase of 3.57% (95% CI: 0.29%, 6.96%) in ALT and 4.25% (95% CI: 2.33%, 6.21%) in TBIL during the second trimester and 4.51% (95% CI: 2.59%, 6.47%) in TBIL during the third trimester, respectively. After adjusting for O3, these associations remained significant, and the effect of PM2.5 on ALT during the second trimester was further strengthened. No significant association observed between PM2.5 and AST. ConclusionsPM2.5 exposure in early pregnancy is associated with increasement of maternal ALT and TBIL, suggesting that PM2.5 exposure may have an adverse effect on maternal liver function. Although this finding indicates an association between PM2.5 exposure and maternal liver function, more research is needed to confirm our findings and explore the underlying biological mechanisms.

The relationship between maternal environmental temperature exposure and preterm birth: A Risk prediction based on machine learning

Global warming and the risk of preterm birth are both major factors that impact population health. This study investigated the impact of environmental temperature during different stages of pregnancy on the probability of preterm birth (PTB) in Wuhan, China through 2014 to 2016. The results revealed that temperature exposure throughout the entire pregnancy exhibited a U-shaped relationship with the risk of PTB; when temperature exposure during the entire pregnancy was below 14 °C or above 20 °C, the risk of PTB increased. Early pregnancy exposure to temperatures below 7 °C or above 22 °C, and late pregnancy exposure to temperatures below 7 °C or above 26 °C, were associated with an increased risk of PTB. Additionally, elevated PM2.5 exposure increased PTB risk, while O3 exposure exhibited a U-shaped relationship with preterm birth. Compared to non-high-risk pregnancies, high-risk pregnancies exhibited a higher risk of preterm birth across all stages of pregnancy. Notably, when late pregnancy temperature exposure exceeded 28 °C, the risk of PTB rapidly increased for non-high-risk pregnancies. This research has significant implications for improving maternal and new-born health by future sustainable city planning and the optimization of temperature forecast warning systems, particularly under the dual pressures of rapid urbanization and climate change.

Studying early pregnancy exposures and outcomes in routinely collected healthcare data: Conceiving of target trials.

Studying early pregnancy exposures and outcomes in routinely collected healthcare data: Conceiving of target trials.

Associations Between Heat Exposure in Early Pregnancy and Anemia, Inflammation and Iron Status Among Women in Rural Pakistan

Associations Between Heat Exposure in Early Pregnancy and Anemia, Inflammation and Iron Status Among Women in Rural Pakistan

Metal exposure and blood lipid biomarkers in early pregnancy: A cross-sectional study

Recognizing the risk factors for dyslipidemia during pregnancy is crucial for safeguarding the health of both the mothers and the offspring. Growing evidence emerged and suggested links between environmental factors, including metals, and alteration in lipid levels or dyslipidemia in general populations. However, knowledge of the associations during pregnancy remains extremely lacking. Herein, we aimed to explore whether elevated metal exposure constitutes a risk factor for dyslipidemia in pregnant women. Based on the Tongji-Shuangliu Birth Cohort (TSBC), a total of 663 pregnant women were recruited and their urinary levels of 17 metals and blood lipid biomarkers in early pregnancy were measured, namely triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The multivariable linear regression models revealed that exposure to selected metals during early pregnancy was significantly associated with some important biomarkers. In particular, after natural log-transformed for the levels of lipid biomarkers and metals, copper (Cu) exposure was positively associated with HDL-C (β = 0.024, 95% CI: 0.001, 0.046), while zinc (Zn) was associated with TG (β = 0.062, 95% CI: 0.013, 0.110) and selenium with TC (β = 0.028, 95% CI: 0.004, 0.054). Exposure to rubidium (Rb) was positively associated with multiple lipid biomarkers, including HDL-C (β = 0.020, 95% CI: 0.002, 0.037) and LDL-C (β = 0.022, 95% CI: 0.001, 0.042). Mixture exposure analysis further identified significant associations between Cu and HDL-C, Zn and TG, Rb and HDL-C, when multiple metal exposures were considered in the Bayesian kernel machine regression model simultaneously. Our findings showed that exposure to several metals during early pregnancy was associated with an increased prevalence of blood lipid abnormalities in pregnant women. These findings underscore the potential impact of metal combinations on lipid metabolism and increase our understanding of the risk factors associated with abnormal lipid metabolism during pregnancy.

BMI-specific inflammatory response to phthalate exposure in early pregnancy: findings from the TMCHESC study.

Studies that have evaluated associations between phthalate metabolites and inflammation have reported inconsistent results among pregnant women, and it is unclear how body mass index (BMI) affects such relationships. Therefore, the present study aimed to examine the association between urinary phthalate metabolite concentrations and the levels of inflammatory biomarkers in the general circulation among 394 pregnant women selected from the Tianjin Maternal and Child Health Education and Service Cohort (TMCHESC) and to determine the role that BMI plays in the relationship. The concentrations of eight inflammatory biomarkers and three phthalate metabolites were measured in serum and urine samples, respectively. Multivariable linear modeling was conducted to examine the association between each phthalate and inflammatory biomarker while controlling for potential confounding factors in BMI-stratified subgroups. Restricted cubic splines were also utilised to explore potential non-linear relationships. In the high-BMI group, positive associations were observed between the levels of mono-n-butyl phthalate (MBP) and interleukin 1 beta (IL-1β) (β = 0.192; 95% CI: 0.033, 0.351), monoethyl phthalate (MEP), and C-reaction protein (CRP) (β = 0.129; 95% CI 0.024, 0.233), and mono-ethylhexyl phthalate (MEHP) and interleukin 6 (IL-6) (β = 0.146; 95% CI 0.016, 0.277). Restricted cubic spline models also revealed non-linear associations between the levels of MBP and interleukins 10 and 17A (IL-10 and IL-17A) and between MEP and interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in pregnant women. These results suggest that phthalate exposure plays a potential role in promoting inflammation in the high-BMI group. While the precise mechanisms underlying the proinflammatory effects of phthalates are not fully understood, these findings suggest that BMI may play a role.

Early pregnancy exposure of maternal triglyceride levels and its effects on birth weight.

The aim of this study was to evaluate the early pregnancy exposure of maternal triglyceride (mTG) and its effects on birthweight, which was an important indicator fornutritional status of newborns, and even its long-term health. A retrospective cohort study was designed to investigate the relationship between mTG in early pregnancy and birth weight. Totally 32,982 women who had a singleton pregnancy and underwent serum lipids screening during early pregnancy were included in thisstudy. Logistic regressions were used to evaluate the correlations between mTG levels and small for gestational age (SGA) or large for gestational age (LGA), and the restricted cubic spline models were applied to explore the dose-response relationship. The increased mTG levels during early pregnancy decreased the risk of SGA and increased the risk of LGA. Thehigh mTG (>90th, 2.05 mM) was showed associated with higher risk of LGA (AOR, 1.35; 95 %CI, 1.20 to 1.50), and lower risk of SGA (AOR, 0.78; 0.68 to 0.89). Lower risk of LGA (AOR,0.81; 0.70 to 0.92) was found in those cases of low mTG (<10th, 0.81 mM), but no correlation was found between low mTG levels and the risk of SGA. The results remained robust after excluding women with high or low body mass index (BMI) and pregnancy complications. This study suggested that early pregnancy exposure of mTG were related to the occurrence of SGA and LGA. mTG levels higher than 2.05 mM (>90th) were suggested to be avoid because of its risk for LGA, while mTG lower than 0.81 mM (<10th) showed its benefits for ideal birthweight range.

Association of hypothyroidism during pregnancy with preconception and early pregnancy exposure to ambient particulate matter

BackgroundLimited research has been conducted on the association between preconception exposure to ambient particulate matter (PM) and hypothyroidism. This study aimed to investigate the relationship between preconception PM exposure and hypothyroidism.MethodsA retrospective case–control study at China-Japan Friendship Hospital was performed. Fine particulate matter (PM2.5) and inhalable particulate matter (PM10) were obtained from the China High Air Pollution Dataset. Buffer analysis methods were used to calculate the exposure of pregnant women to PM in a circular area of 250, 500, and 750 m in diameter at preconception and in early pregnancy. Logistic regression models were used to assess the relationship between PM and hypothyroidism. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the effect of PM on the risk of hypothyroidism.ResultsA total of 3,180 participants were studied, and they comprised 795 hypothyroid patients and 2,385 matched controls. The mean age was 31.01 years (standard deviation: 3.66) in the control group and 31.16 years (standard deviation: 3.71) in the case group. Logistic regression analysis showed that exposure to PM2.5 and PM10 in the 60-day period before the last menstrual period month (LMPM), 30-day period before the LMPM, and LMP, across all distance buffers, was associated with an increased risk of hypothyroidism (all P < 0.05). The most pronounced effect was observed during the LMPM, with PM2.5 (OR: 1.137, 95% CI: 1.096–1.180) and PM10 (OR: 1.098, 95% CI: 1.067–1.130) in the 250-m buffer. Subgroup analysis in the Changping District yielded consistent results with the main analysis.ConclusionOur study shows that preconception PM2.5 and PM10 exposure increases the risk of hypothyroidism during pregnancy.

Safety of benzodiazepine or Z-hypnotic exposure in early pregnancy

Safety of benzodiazepine or Z-hypnotic exposure in early pregnancy

Association between maternal benzodiazepine or Z-hypnotic use in early pregnancy and the risk of stillbirth, preterm birth, and small for gestational age: a nationwide, population-based cohort study in Taiwan

Benzodiazepines and Z-hypnotics are commonly prescribed for anxiety and insomnia during pregnancy, but the evidence regarding potential adverse neonatal outcomes is insufficient because of poor control for confounding factors in previous studies. We therefore aimed to evaluate the association between the use of benzodiazepines or Z-hypnotics during early pregnancy and adverse neonatal outcomes (stillbirth, preterm birth, and small for gestational age). We did a nationwide, population-based cohort study in Taiwan using three data sources: Taiwan's National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database. The study cohort included all singleton pregnancies of females aged 15-50 years who gave birth between Jan 1, 2004, and Dec 31, 2018. Pregnancies without valid information were excluded. Benzodiazepine and Z-hypnotic use was defined as at least one benzodiazepine or Z-hypnotic prescription during early pregnancy (the first 20 weeks of pregnancy). The primary outcomes were stillbirth (fetal death at or after 20 weeks' gestation), preterm birth (<37 weeks' gestation), and small for gestational age (birthweight below the 10th percentile for gestational age by sex). Logistic regression models with propensity score fine stratification weighting were used to control for potential confounders and examine the association between benzodiazepines or Z-hypnotics use during early pregnancy and the risk of adverse neonatal outcomes. Odds ratios (ORs) and 95% CIs were reported. We used confounding by indication control analyses, a sibling control study, and a paternal negative control design to account for unmeasured confounders. The risk associated with exposure during late pregnancy was also assessed. Between Oct 7, 2021, and June 10, 2022, we analysed the study data. The cohort included 2 882 292 singleton pregnancies; of which, 75 655 (2·6%) of the mothers were dispensed one or more benzodiazepines or Z-hypnotics during early pregnancy. Women exposed during pregnancy were older (mean age at delivery was 31·0 years [SD 5·3] for exposed women vs 30·6 years [4·9] for unexposed women), had a higher prevalence of psychiatric disorders, and were more likely to have unhealthy lifestyle behaviours than unexposed women. Information about ethnicity was not available. Early pregnancy exposure was associated with adverse neonatal outcomes compared with non-exposure. The propensity score-weighted OR was 1·19 (95% CI 1·10-1·28) for stillbirth, 1·19 (1·16-1·23) for preterm birth, and 1·16 (1·13-1·19) for small for gestational age. After controlling for confounding by indication, there was no significant association between drug exposure and stillbirth risk; however, this attenuation was not observed for preterm birth and small for gestational age. In models with sibling controls that accounted for familial confounding and genetic factors, early exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of stillbirth and preterm birth, but it remained significantly associated with small for gestational age. The paternal negative control analyses with point estimates close to the null indicated no strong evidence of unmeasured confounding shared by the mother and the father. Substantially increased risks of stillbirth and preterm birth were observed for late pregnancy exposure. Benzodiazepine or Z-hypnotic use in early pregnancy is not associated with a substantial increase in the risk of stillbirth and preterm birth after accounting for unmeasured confounding factors. Clinicians should be aware of the increased risk of small for gestational age and caution should be taken when prescribing these medications during late pregnancy. National Science and Technology Council, Taiwan. For the Taiwanese translation of the abstract see Supplementary Materials section.

Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes

Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes. To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort. In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022. Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy. Birth weight and gestational age, abstracted from delivery records; birth weight z score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks. The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight z score only among mothers whose dietary folate intake (birth weight: β, -89.13 g; 95% CI, -166.84 to -11.42 g; birth weight z score: -0.13; 95% CI, -0.26 to -0.003) or plasma folate concentration (birth weight: -87.03 g; 95% CI, -180.11 to 6.05 g; birth weight z score: -0.14; 95% CI, -0.30 to 0.02) were below the 25th percentile (dietary: 660 μg/d, plasma: 14 ng/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups. In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study

BackgroundPregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. ObjectiveCharacterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. MethodsAnalyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017–2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. ResultsMono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (β: -0.36 [95% confidence interval: -0.56, −0.15]) and abdominal circumference (−0.31 [-0.49, −0.12]) z-scores. This association was mainly driven by phthalate biomarkers. ConclusionsUrine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.

Atomoxetine exposure in early pregnancy does not increase risk of malformations

The Brown University Psychopharmacology UpdateVolume 34, Issue 5 p. 6-8 Research Roundup Atomoxetine exposure in early pregnancy does not increase risk of malformations First published: 03 April 2023 https://doi.org/10.1002/pu.31015Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume34, Issue5May 2023Pages 6-8 RelatedInformation

Critical windows of exposure to air pollution and gestational diabetes: assessing effect modification by maternal pre-existing conditions and environmental factors

BackgroundAmbient air pollution has been associated with gestational diabetes (GD), but critical windows of exposure and whether maternal pre-existing conditions and other environmental factors modify the associations remains inconclusive.MethodsWe conducted a retrospective cohort study of all singleton live birth that occurred between April 1st 2006 and March 31st 2018 in Ontario, Canada. Ambient air pollution data (i.e., fine particulate matter with a diameter ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2) and ozone (O3)) were assigned to the study population in spatial resolution of approximately 1 km × 1 km. The Normalized Difference Vegetation Index (NDVI) and the Green View Index (GVI) were also used to characterize residential exposure to green space as well as the Active Living Environments (ALE) index to represent the active living friendliness. Multivariable Cox proportional hazards regression models were used to evaluate the associations.ResultsAmong 1,310,807 pregnant individuals, 68,860 incident cases of GD were identified. We found the strongest associations between PM2.5 and GD in gestational weeks 7 to 18 (HR = 1.07 per IQR (2.7 µg/m3); 95% CI: 1.02 – 1.11)). For O3, we found two sensitive windows of exposure, with increased risk in the preconception period (HR = 1.03 per IQR increase (7.0 ppb) (95% CI: 1.01 – 1.06)) as well as gestational weeks 9 to 28 (HR 1.08 per IQR (95% CI: 1.04 –1.12)). We found that women with asthma were more at risk of GD when exposed to increasing levels of O3 (p- value for effect modification = 0.04). Exposure to air pollutants explained 20.1%, 1.4% and 4.6% of the associations between GVI, NDVI and ALE, respectively.ConclusionAn increase of PM2.5 exposure in early pregnancy and of O3 exposure during late first trimester and over the second trimester of pregnancy were associated with gestational diabetes whereas exposure to green space may confer a protective effect.

Neural tube defects: a review of global prevalence, causes, and primary prevention.

Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is a primer on prevalence, causes, and evidence-based prevention strategies for NTDs. The estimated average global prevalence of NTDs is two cases per 1000 births, amounting toapproximately 214,000-322,000 affected pregnancies worldwide annually. Prevalence and associated adverse outcomes are disproportionately high in developing countries. NTDs have multiple risk factors including genetic and non-genetic (i.e., maternal nutritional status, pre-pregnancy diabetes, early pregnancy exposure to valproic acid (anti-epileptic medication), and a previous pregnancy affected by aNTD) factors. Maternal folate insufficiency before and during early pregnancy is the most common risk factor and is preventable. Folic acid (vitamin B9) is required for formation of the neural tube early in pregnancy, around 28days after conception, when most women are unaware of their pregnancies. Current guidelines recommend that all women planning or capable of pregnancy take a daily supplement containing 400-800μg of folic acid. Mandatory folic acid fortification of staple foods (e.g., wheat flour, maize flour, rice) is safe, economical, and the effective intervention for primary prevention of NTDs. Currently, about 60 countries are implementing mandatory folic acid fortification of staple foods, preventing just a quarter of all preventable NTD cases worldwide. There is an urgent need for active champions, including neurosurgeons and other healthcare providers, to generate political will and promote effective mandatory food fortification with folic acid, and reach equitable primary prevention of NTDs in all countries.

Abstract P245: Early Pregnancy Exposure to Per- And Polyfluoroalkyl Substances and Thyroid Function Throughout Gestation: A Longitudinal Study

Introduction: Thyroid function during pregnancy is pivotal for both maternal and fetal health. Data on environmental determinants of thyroid function in pregnancy are yet limited. We prospectively investigated associations of early pregnancy per- and polyfluoroalkyl substances (PFAS), known environmental endocrine disruptors, with thyroid function longitudinally measured throughout pregnancy. Hypothesis: Early pregnancy PFAS exposure adversely affects thyroid function. Methods: Within the NICHD Fetal Growth Studies-Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks (gw) 10-14 and measured concentrations of 9 PFAS (NMeFOSAA, PFDA, PFDoDA, PFDS, PFHpA, PFHxS, PFNA, PFOA, PFOS, PFOSA, PFUnDA) in plasma samples collected at enrollment. In a subsample of 321 pregnant women, we determined thyroid markers (fT3, fT4, TSH) at gw 10-14, 15-26, 23-31, 33-39. Associations were assessed with multivariable regressions per standard deviation increase in ln-transformed PFAS (ng/ml), adjusting for age, body mass index, diet, lifestyle and socio-economic factors, and plasma lipids. Results: Plasma PFAS in early pregnancy were associated with markers of thyroid function throughout pregnancy. The associations varied by gestational age. Higher levels of several PFAS were associated with lower TSH and higher fT3 and fT4 levels at gw 10-14. Adjusted beta coefficients [95%CI] with TSH (mIU/L) were: -1.13 [-2.30, 0.05] for PFOS, -3.15 [-4.45, -1.86] for PFDA, -1.75 [-2.95, -0.55] for NMeFOSAA, -1.68 [-3.00, -0.37] for PFNA, -1.29 [-2.62, 0.03] for PFDoDA, -2.07 [-3.30, -0.83] for PFOA, but 1.11 [0.12, 2.09] for PFHxS. Most of these associations were attenuated to non-significant or changed the direction of the association in later pregnancy (for instance, PFOS-TSH association at gw 10-14: -1.13 [-2.30, 0.05], gw 15-26: 0.98 [0.18, 1.78], gw 23-31: 1.31 [0.50, 2.13], PFDA-TSH association at gw 10-14: -3.15 [-4.45, -1.86], at gw 23-31: 1.13 [0.16, 2.11]). Consistent and positive associations across pregnancy were observed for PFOA-fT3 (at gw 10-14: 0.48 [0.05, 0.91], gw 15-26: 0.41 [0.04, 0.78], gw 23-31: 0.42 [0.02, 0.80] pmol/L) and PFHxS-fT4 (at gw 10-14: 0.12 [0.02, 0.21], gw 15-26: 0.67 [0.54, 0.81], gw 23-31: 0.22 [0.12, 0.33], gw 33-39: 0.14 [0.02, 0.26] ng/dL). Conclusions: Plasma levels of selected PFAS congeners in early pregnancy are significantly associated with thyroid markers in pregnancy. The associations varied by gestational timing. These findings indicate a potential environmental impact on thyroid function. In perspective, multiple assessments of PFAS and thyroid markers throughout pregnancy might be necessary and relevant for conducting gestational age-specific interventional trials.

Association of maternal snuff use and smoking with Sudden Infant Death Syndrome: a national register study

BackgroundThe aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks.MethodsThis was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999–2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs).ResultsMaternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of continuous usage.ConclusionsMaternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. Nicotine is the common substance in cigarette smoke and snuff. These findings support the hypothesis that nicotine contributes to an elevated risk of SIDS.ImpactMaternal snuff use and smoking in early pregnancy were associated with increased risks of post neonatal mortality, SIDS, and SUID.Cessation of smoking and snuff use before the first antenatal visit was associated with reduced risks of SIDS and SUID.The common substance in cigarette smoke and snuff is nicotine. Our findings suggest that nicotine contributes to an elevated risk of SIDS and SUID.The implication of our findings is that all forms of nicotine should be avoided in pregnancy.

Plasticizer DEHP exposure in early pregnancy affects the endometrial decidualization in mice through reducing lncRNA RP24-315D19.10 expression.

To explore the effect of exposure to di (2-ethyl) hexyl phthalate (DEHP) in early pregnancy on endometrial decidualization in mice and its relation with lncRNA RP24-315D19.10. Early pregnancy mice were exposed to DEHP (1000 mg·kg－1·d－1) to construct the model. The uterus was collected on day 6 of pregnancy to detect its effect on decidualization by HE staining and immunofluorescence. A decidualization induction model of mouse endometrial stromal cells exposed to DEHP (0.1, 0.5, 2.5, 12.5, 62.5 μmol/L) was constructed. The changes of cell morphology were observed by light microscopy and phalloidin staining, and the expression of decidual reaction related molecular markers were detected by immunofluorescence, realtime RT-PCR and Western blotting. The expression of RP24-315D19.10 in decidua tissue and cells was detected by realtime RT-PCR. Cellular localization of RP24-315D19.10 was determined by lncLocator database and RNA FISH. AnnoLnc2 database was used to predict miRNAs bound to RP24-315D19.10. The number of embryo implantation sites, uterine weight and uterine area were significantly lower in the DEHP exposed group than those in the control group, and the expression of the decidual reaction related molecular markers matrix metalloprotein 9 and homeobox A10 in the DEHP exposure group were also significantly lower than those in the control group (all P<0.05). With the increase of DEHP concentration, the expression of dtprp in decidua cells was gradually decreased. 2.5 μmol/L DEHP exposed stromal cells failed to be fully decidualized in vitro, andphalloidin staining showed abnormal cytoskeleton morphology. The expression levels of homeobox A10, bone morphogenetic protein 2 and proliferating cell nuclear antigen in the DEHP exposure group were significantly lower than those in the control group (all P<0.05). The expression of RP24-315D19.10 in DEHP exposed decidua tissue and cells was significantly reduced (both P<0.05). RP24-315D19.10 is mainly localized in the cytoplasm and RP24-315D19.10 might bind to 45 miRNAs, among them, miR-138-5p, miR-155-5p, miR-183-5p and miR-223-3p were associated with endometrial decidualization. DEHP exposure in early pregnancy may impair endometrial decidualization, and the damage may be associated with the down-regulation of RP24-315D19.10.