Pregnancy Exposure Research Articles

Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms.

Pregnancy exposure to PM2.5 from wildland fire smoke and preterm birth in California

BackgroundWildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown. MethodsWe assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007–2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM2.5) attributable to wildland fires from United States Environmental Protection Agency’s Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent. ResultsFor the 5,155,026 births, higher wildland fire PM2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m3 of average wildland fire PM2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m3 increase in average wildland fire PM2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth. ConclusionsPreterm birth is sensitive to wildland fire PM2.5; therefore, we must reduce exposure during pregnancy.

Exposure of Pregnancy to Pregestational Diabetes, Gestational Diabetes, and Antidiabetic Medications With Especial Focus on Major Congenital and Cardiac Malformations in Offspring.

The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. T2DM is more common in patients with psychiatric disorders and those who take certain psychotropic drugs. T2DM occurs in 2%-7% of women of reproductive age. The prevalence of pregestational diabetes is 0.5%-2.4%, and that of gestational diabetes is 7%-28%, depending on geographical region. About 20%-50% of pregnancies, across the world, are unplanned; this figure is higher, at about 65%, in women with psychiatric disorders. As a result, many women of reproductive age who have diabetes, including women who do not know that they have diabetes, may unintentionally become pregnant, thus unknowingly exposing their pregnancy to diabetes and its treatment. Exposure of pregnancy to pregestational and gestational diabetes is associated with risks to the mother as well as risks to the child. Risks to the mother include obesity, hypertension, and preeclampsia. Risks to the child include spontaneous abortion, fetal death, macrosomia, major congenital malformations (MCMs), preterm delivery, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome. A recent large retrospective cohort study with data from 6 countries in Europe, Asia, and North America found that, in about 51,000 women with pregestational T2DM, neither MCMs nor cardiac malformations were more prevalent in offspring of children periconceptionally exposed to second-line antidiabetic treatments relative to exposure to insulin. These findings are reassuring but have limitations that are discussed. A reasonable conclusion from a reading of the reviewed literature is that pregestational and gestational diabetes are best treated during pregnancy, that insulin is a first-line treatment, that metformin is an increasingly accepted alternative, and that safety data on second-line antidiabetic treatments are, so far, reassuring.

Impact of perinatal exposure counseling on patient reported emotional outcomes and decisional empowerment.

Exposures during pregnancy are common and most pregnant patients utilize at least one medication during pregnancy. The lack of reliable information on medication safety during pregnancy available to providers and patients is a stressor and obstacle to decision-making about medication use in pregnancy. Previous studies showed that exposures in pregnancy are associated with guilt, worry, and decisional conflict. Although prior research has evaluated changes in patient knowledge after teratogen counseling, studies have not examined emotional outcomes or patients' decisional empowerment. This quasi-experimental study measured changes in patients' feelings of guilt, anxiety, and decisional empowerment after receiving exposure counseling from trained teratogen information specialists. We administered pre- and post-counseling surveys to patients referred to a perinatal exposure clinic in Tampa, Florida. Validated scales were used to measure anxiety and guilt, and the 'SURE' measure was used to assess decisional empowerment. Paired samples t-tests evaluated changes in anxiety and guilt and a McNemar test assessed for changes in empowered decision making. Among the 34 participants who completed both surveys, anxiety, and guilt scores decreased significantly (p < .001). While only 21% felt informed and empowered to make a decision related to their exposure(s) before counseling, this increased to 85% (p < .001) on the post-survey. Comprehensive counseling with a trained teratogen information specialist improves patient emotional outcomes as well as feelings of empowerment to make an informed decision regarding medication use in pregnancy. This study highlights that patient-centered teratogen counseling goes beyond simple changes in patient knowledge.

Pregnancy outcomes in Chinese women with mechanical heart valves receiving warfarin treatment throughout pregnancy: 14-year experience

ObjectiveThe purpose was to evaluate pregnancy outcomes and risk factors associated with fetal complications in Chinese pregnant women with mechanical heart valves (MHVs) taking low-dose warfarin, aiming to fill in the research gap of this area. MethodsBetween June 2010 and Aug 2023, 122 patients with MHVs who had 151 pregnancies and received warfarin throughout pregnancy were included. We compared them with 302 paired pregnancies without warfarin treatment. Binary logistic regression analyses were performed to explore risk predictors of fetal complications. ResultsPregnancy loss rate was 37.1 % in women taking warfarin, compared to only 4.6 % for those without warfarin exposure in pregnancy (RR = 8.00, 95 % CI: 4.61–13.90). In pregnant women with MHVs, there were 34 spontaneous abortions, 22 stillbirths and 1 neonatal malformation. In the first, second and third pregnant trimesters of women with MHVs, fetal complication incidences were 19.2 %, 9.9 % and 8.0 %, respectively. 86.0 % of fetal complications occurred in women taking a warfarin dose ≤5 mg/d, accounting for 94.0 % of the total population. The newborns' birth weight, gestational age and 1-minute Apgar score were significantly lower in pregnancies treated with warfarin compared to those without warfarin exposure. Only 2.0 % of postpartum hemorrhage and no thrombosis or maternal mortality data were collected in pregnant women on warfarin in this study. ConclusionMost Chinese pregnant women take a warfarin daily dose ≤5 mg and they might have only around 60 % chance of giving birth to a live baby without maternal complications.

Associations between sun exposure, skin pH, and epidermal permeability in pregnancy: A longitudinal observational study.

Little is known about how sun exposure may affect the maternal skin barrier during pregnancy when many hormonal and physiological changes occur. In this longitudinal observational study, 50 pregnant women were recruited at 18-24 weeks' gestation, 25 in summer-autumn, and 25 in winter-spring. At three time points in pregnancy at 18-24, 28-30, and 36-38 weeks' gestation, participants completed a validated sun exposure questionnaire and had skin permeability and surface pH measured on the volar forearm. We identified an association between increased sun exposure and increased skin permeability at 18-24 weeks' gestation (β = 0.85, p = 0.01). Lower transepidermal water loss (decreased skin permeability), mean = 12.1 (SD = 5.1) at 28-30 weeks' gestation was observed, compared to mean = 12.6 (SD = 4.0) at 18-24 weeks' and mean = 13.7 (SD = 8.5) at 36-38 weeks' gestation (n = 27, β = -1.83, p = 0.007). Higher skin pH readings, mean = 5.80 (SD = 0.58) were found at 28-30 weeks' gestation, compared to mean = 5.25 (SD = 0.62) at 18-24 weeks' and mean = 5.47 (SD = 0.57) at 36-38 weeks' gestation (n = 27, β = 0.40, p = 0.004). These gestational fluctuations remained after adjusting for Fitzpatrick skin type, season, and sun exposure. We observed gestational fluctuations in both skin permeability and skin pH, with 28-30 weeks' gestation being a significant point of difference compared to mid- and late-pregnancy periods.

Building a Sustainable Learning Health Care System for Pregnant and Lactating People: Interview Study Among Data Access Providers.

In many areas of health care, learning health care systems (LHSs) are seen as promising ways to accelerate research and outcomes for patients by reusing health and research data. For example, considering pregnant and lactating people, for whom there is still a poor evidence base for medication safety and efficacy, an LHS presents an interesting way forward. Combining unique data sources across Europe in an LHS could help clarify how medications affect pregnancy outcomes and lactation exposures. In general, a remaining challenge of data-intensive health research, which is at the core of an LHS, has been obtaining meaningful access to data. These unique data sources, also called data access providers (DAPs), are both public and private organizations and are important stakeholders in the development of a sustainable and ethically responsible LHS. Sustainability is often discussed as a challenge in LHS development. Moreover, DAPs are increasingly expected to move beyond regulatory compliance and are seen as moral agents tasked with upholding ethical principles, such as transparency, trustworthiness, responsibility, and community engagement. This study aims to explore the views of people working for DAPs who participate in a public-private partnership to build a sustainable and ethically responsible LHS. Using a qualitative interview design, we interviewed 14 people involved in the Innovative Medicines Initiative (IMI) ConcePTION (Continuum of Evidence from Pregnancy Exposures, Reproductive Toxicology and Breastfeeding to Improve Outcomes Now) project, a public-private collaboration with the goal of building an LHS for pregnant and lactating people. The pseudonymized transcripts were analyzed thematically. A total of 3 themes were identified: opportunities and responsibilities, conditions for participation and commitment, and challenges for a knowledge-generating ecosystem. The respondents generally regarded the collaboration as an opportunity for various reasons beyond the primary goal of generating knowledge about medication safety during pregnancy and lactation. Respondents had different interpretations of responsibility in the context of data-intensive research in a public-private network. Respondents explained that resources (financial and other), scientific output, motivation, agreements collaboration with the pharmaceutical industry, trust, and transparency are important conditions for participating in and committing to the ConcePTION LHS. Respondents also discussed the challenges of an LHS, including the limitations to (real-world) data analyses and governance procedures. Our respondents were motivated by diverse opportunities to contribute to an LHS for pregnant and lactating people, primarily centered on advancing knowledge on medication safety. Although a shared responsibility for enabling real-world data analyses is acknowledged, their focus remains on their work and contribution to the project rather than on safeguarding ethical data handling. The results of our interviews underline the importance of a transparent governance structure, emphasizing the trust between DAPs and the public for the success and sustainability of an LHS.

Abstract WP39: Stroke Risk Factor and Prevention Considerations in Women Veterans

Background: Stroke is a significant health burden for Veterans and the fifth leading cause of death for women. Beyond traditional stroke risk factors, female sex hormones and pregnancy exposures are risk factors for women. Compared to civilian women, women Veterans have significant multimorbid physical and mental health conditions contributing to their stroke risk. Stroke risk factors specific to women Veterans have not been elucidated. Purpose: This scoping review aimed to summarize evidence on the stroke risk factors specific to United States women Veterans. Methods: The search strategy was run across six databases: MEDLINE and EMBASE via Ovid, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. A total of 1,218 records were uploaded to Covidence for screening. Criteria for included studies were peer-reviewed primary research and articles written in English about women Veterans and cardiovascular disease and stroke risk factors. No restrictions were placed on publication date. Results: Seventeen articles met inclusion criteria. Cohorts were 30 years and older. Data originated from national and individual Veterans Affairs studies. When comparing White Veterans and civilian counterparts, Black Veterans had a higher incidence of stroke; stroke incidence was higher in Veterans with post-traumatic stress disorder with insomnia, restless leg syndrome, traumatic brain injury, constipation with laxative use, egg consumption, frailty, and systemic sclerosis. Women Veterans, starting at age 30, had steadily increasing positive association with stroke risk indicating a need to screen earlier than recommended 45 years of age. Conclusions: Research is needed on stroke risk factors specific to the female sex as they connect to Veteran exposures (chemical, physical, and environmental). Nurses play a crucial role in interdisciplinary collaboration to recognize and support risk factor reduction for stroke prevention. The knowledge gained from this scoping review helps identify and treat women Veteran's specific stroke risk factors. This, in turn, can reduce the incidence of stroke and help reach equitable sex-specific care that women Veterans need.

Prenatal maternal glucocorticoid exposure modifies sperm miRNA profiles across multiple generations in the guinea-pig.

Maternal stress and glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain. In the present study, we hypothesized that maternal prenatal synthetic glucocorticoid (sGC) exposure in the F0 pregnancy will result in differences in miRNA levels in testes germ cells and sperm across multiple generations, and that these changes will associate with modified microRNA (miRNA) profiles and gene expression in the prefrontal cortex (PFC) of subsequent generations. Pregnant guinea-pigs (F0) were treated with multiple courses of the sGC betamethasone (Beta) (1mgkg-1; gestational days 40, 41, 50, 51, 60 and 61) in late gestation. miRNA levels were assessed in testes germ cells and in F2 PFC using the GeneChip miRNA 4.0 Array and candidate miRNA measured in epididymal sperm by quantitative real-time PCR. Maternal Beta exposure did not alter miRNA levels in germ cells derived from the testes of adult male offspring. However, there were significant differences in the levels of four candidate miRNAs in the sperm of F1 and F2 adult males. There were no changes in miRNA levels in the PFC of juvenile F2 female offspring. The present study has identified that maternal Beta exposure leads to altered miRNA levels in sperm that are apparent for at least two generations. The fact that differences were confined to epididymal sperm suggests that the intergenerational effects of Beta may target the epididymis. KEY POINTS: Paternal glucocorticoid exposure prior to conception leads to profound epigenetic changes in the brain and somatic tissues in offspring, and microRNAs (miRNAs) in sperm may mediate these changes. We show that there were significant differences in the miRNA profile of epididymal sperm in two generations following prenatal glucocorticoid exposure that were not observed in germ cells derived from the testes. The epididymis is a probable target for intergenerational programming. The effects of prenatal glucocorticoid treatment may span multiple generations.

Investigating the effect of exposure to monosodium glutamate during pregnancy on development of autism in male rat offspring

In present study, we investigated the relationship between the pregnancy exposure to monosodium glutamate (MSG) and autism development in male offspring of rats.Pregnant Wistar rats were allocated into five groups. The first group was control group that pregnant animals received normal saline orally from day 1–18 of pregnancy. Group 2, 3 and 4 pregnant rats received different doses (1.5, 5 and 10 g/kg) of MSG by the same way respectively. Group 5 received 500 mg/kg of Valproic acid (VPA) on the 12.5th day of pregnancy. Different behavioral tests including marble burying, self-grooming, and Barnes maze test were performed on offspring. The levels of glutamate and GSH markers were also measured.The results showed that MSG similar to VPA led to induction of autistic anxiety and repetitive behaviors. It could also deteriorate the spatial memory. Besides we found that behavioral symptoms potentiated with increasing the MSG dosage. Similarly, we had an increase in glutamate and a reduction in GSH levels in offspring.Findings indicated that MSG was able to induce autism in offspring of rats in a dose-dependent way. This effect could be through increasing of glutamate and reduction of GSH. Consequently, MSG should be avoided during pregnancy.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort

BackgroundFluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. ObjectivesWe examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. MethodsWe measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. ResultsA 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results. DiscussionFluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.

The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis.

To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies. Four primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy, and siblings) born between 1 January 1990 and 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured. The NDD incidence rate among (1) children exposed during or outside of pregnancy and (2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders. The analysis included 410 461 children of 297 426 mothers and 2 793 018 person-years of follow-up with 8900 NDD cases (incidence rate = 3.2/1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy-adjusted HR = 1.58, 95% CI 1.46-1.72; 1-year adj. HR = 1.49, 95% CI 1.39-1.60; 2-year adj. HR = 1.62, 95% CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR = 1.16, 95% CI 1.10-1.22; 1-year adj. HR = 1.20, 95% CI 1.14-1.27; 2-year adj. HR = 1.19, 95% CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR = 0.97, 95% CI 0.77-1.21 or infection HR = 0.99, 95% CI 0.90-1.08. Maternal risk appears to be unspecific to pregnancy: our study provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.

N-acetylcysteine protects against neurodevelopmental injuries induced by methylmercury exposure during pregnancy and lactation

As an extremely dangerous environmental contaminant, methylmercury (MeHg) results in detrimental health effects in human brain nervous system, one of its main targets. However, as a developmental toxicant, the brain of offspring is vulnerable to MeHg during pregnancy and lactation exposure. Unfortunately, mechanisms of neurodevelopmental injuries induced by MeHg have not been fully elucidated. N-acetylcysteine (NAC) has been used for several decades as an antioxidant to antagonize oxidative stress. However, the molecular mechanisms of NAC alleviating MeHg-induced neurodevelopmental toxicity are not clear. Here, for evaluation of the dose-dependent effects of MeHg exposure on neurodevelopmental injuries of offspring, and the possible protective effects of NAC, the pregnant female mice were exposed to MeHg (4, 8, 12 mg/L, respectively) and NAC (50, 100, 150 mg/kg, respectively) from gestational day 1 (GD1) to postnatal day 21 (PND21). Our results indicated that administering MeHg caused behavioral impairment and neuronal injuries in the cerebral cortex of newborn mice. MeHg dose-dependently caused reactive oxygen species (ROS) overproduction and oxidative stress aggravation, together with expression of Nrf2, HO-1, Notch1, and p21 up-regulation, and CDK2 inhibition. NAC treatment dose-dependently antagonized MeHg-induced oxidative stress that may contribute to alleviating neurobehavioral and neurodevelopmental impairments. These results give insight into that NAC can protect against MeHg-induced neurodevelopmental toxicity by its antioxidation capacity.

Dwelling proximity to wildfire and spina bifida risk in offspring

Objective To evaluate the association between wildfire exposure in pregnancy and spina bifida risk. Methods This retrospective cohort study used the California Office of Statewide Health Planning and Development Linked Birth File with hospital discharge data between 2007 and 2010. The Birth File data were merged with the California Department of Forestry and Fire Protection data of the same year. Spina bifida was identified by its corresponding ICD-9 code listed on the hospital discharge of the newborn. Wildfire exposure was determined based on the zip code of the woman’s home address. Pregnancy was considered exposed to wildfire if the mother lived within 15 miles of a wildfire during the pregnancy or within 30 days prior to pregnancy. Results There were 2,093,185 births and 659 cases of spina bifida between 2007 and 2010. The births were analyzed using multivariable logistic regression models and adjusted for potential confounders. Exposure to wildfire in the first trimester was associated with higher odds of spina bifida (aOR= 1.43 [1.11–1.84], p-value = 0.01). Wildfire exposure 30 days before the last menstrual period and during the second and third trimesters were not associated with higher spina bifida risk. Conclusion Wildfire exposure has shown an increased risk of spina bifida during the early stages of pregnancy.

Timing of selective serotonin reuptake inhibitor use and risk for preterm birth and related adverse events: with a consideration of the COVID-19 pandemic period

Objective There is uncertainty around the safety of SSRIs for treating depression during pregnancy. Nevertheless, the use of SSRIs has been gradually increasing, especially during the COVID-19 pandemic period. We aimed to (1) characterize maternal depression rate and use of SSRIs in a recent 10-year period, (2) address confounding by indication, as well as socioeconomic and environmental factors, and (3) evaluate associations of the timing of SSRI exposure in pregnancy with risk for preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) infants among women with depression before pregnancy. Methods We conducted propensity score-adjusted regression to calculate odds ratios (ORs) of PTB, LBW, and SGA. We accounted for maternal/pregnancy characteristics, comorbidity, depression severity, time of delivery, social vulnerability, and rural residence. Results There were 50.3% and 40.3% increases in the prevalence rate of prenatal depression and prenatal SSRI prescription rate during the pandemic. We identified women with depression ≤180 days before pregnancy (n = 8406). Women with no SSRI order during pregnancy (n = 3760) constituted the unexposed group. The late SSRI exposure group consisted of women with an SSRI order after the first trimester (n = 3759). The early-only SSRI exposure group consisted of women with SSRI orders only in the first trimester (n = 887). The late SSRI exposure group had an increased risk of PTB of OR = 1.5 ([1.2,1.8]) and LBW of OR = 1.5 ([1.2,2.0]), relative to the unexposed group. Associations between late SSRI exposure and risk of PTB/LBW were similar among a subsample of patients who delivered during the pandemic. Conclusions These findings suggest an association between PTB/LBW and SSRI exposure is dependent on exposure timing during pregnancy. Small for gestational age is not associated with SSRI exposure.

Examining modification of the associations between air pollution and birth outcomes by neighborhood deprivation in a North Carolina birth cohort, 2011-2015.

Evidence from studies of air pollutants and birth outcomes suggests an association, but uncertainties around geographical variability and modifying factors still remain. As neighborhood-level social characteristics are associated with birth outcomes, we assess whether neighborhood deprivation level is an effect measure modifier on the association between air pollution and birth outcomes in a North Carolina birth cohort. Using birth certificate data, all North Carolina residential singleton live births from 1 January 2011 to 31 December 2015 with gestational ages of 20-44 weeks (n = 566,799) were examined for birth defect diagnoses and preterm birth. Exposures were daily average fine particulate matter (PM2.5), daily 8-h maximum nitrogen dioxide (NO2), and daily 8-h maximum ozone (O3) modeled concentrations, and the modifier of interest was the neighborhood deprivation index (NDI). Linear binomial models were used to estimate the prevalence differences and 95% confidence intervals (CI) for the association between ambient air pollution and birth defect diagnoses. Modified Poisson regression models were used to estimate risk differences (RDs) and 95% CIs for air pollution and preterm birth. Models were stratified by the neighborhood deprivation index group (low, medium, or high) to assess potential modification by NDI. Approximately 3.1% of the study population had at least one birth defect and 8.18% were born preterm. For preterm birth, associations with PM2.5 and O3 did not follow a conclusive pattern and there was no evidence of modification by NDI. The associations between NO2 and preterm birth were generally negative across exposure windows except for a positive association with NO2 and preterm birth for high NDI [RD: 34.70 (95% CI 4.84-64.56)] for entire pregnancy exposure. There was no evidence of associations between pollutants examined and birth defects. There may be differences in the association between NO2 exposure and preterm birth by NDI but we did not observe any evidence of associations for birth defects. Our results support the public health protection afforded by reductions in air pollution, even in areas of neighborhood deprivation, but future research conducted in areas with higher levels of air pollution and evaluating the potential for modification by neighborhood deprivation level would be informative.

Associations of maternal urinary rare earth elements individually and in mixtures with neonatal size at birth

Prenatal rare earth elements (REEs) exposure is linked to unfavorable health consequences. Epidemiologic research on repeated measurements of REEs during gestation correlated with fetal growth is exiguous. Until now, few studies have characterized exposure characteristics of REEs in pregnant women. We aimed to ascertain the characteristics and predictors of REEs exposure over three trimesters among pregnant women and examine the possible effects of prenatal REEs exposure on size at birth. Urinary REEs concentrations exhibited considerable within-subject variation with intraclass correlation coefficients ranging from 0.16 to 0.58. Maternal age, household income, gestational weight gain, passive smoking during pregnancy, parity, and neonatal gender were associated with maternal urinary REEs concentrations. Elevated maternal urinary holmium and thulium concentrations in the 3rd trimester were significantly related to reductions in birth weight. Weighted quantile sum (WQS) regression model identified that urinary REEs mixture in the 3rd trimester were negatively related to birth weight (WQSREEs β = −26.22; 95% confidence interval [CI]: −47.62, −4.82), with holmium (40%) and thulium (24%) receiving the highest weights. Male infants received the most weight (>50%) related to decreased birth weight. This study revealed a significant association between individual and mixture REE exposure in late pregnancy with a reduction in birth weight.

Effects of air pollution on adverse birth outcomes and pregnancy complications in the U.S. state of Kansas (2000–2015)

Neonatal mortality and morbidity are often caused by preterm birth and lower birth weight. Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are the most prevalent maternal medical complications during pregnancy. However, evidence on effects of air pollution on adverse birth outcomes and pregnancy complications is mixed. Singleton live births conceived between January 1st, 2000, and December 31st, 2015, and reached at least 27 weeks of pregnancy in Kansas were included in the study. Trimester-specific and total pregnancy exposures to nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5), and ozone (O3) were estimated using spatiotemporal ensemble models and assigned to maternal residential census tracts. Logistic regression, discrete-time survival, and linear models were applied to assess the associations. After adjustment for demographics and socio-economic status (SES) factors, we found increases in the second and third trimesters and total pregnancy O3 exposures were significantly linked to preterm birth. Exposure to the second and third trimesters O3 was significantly associated with lower birth weight, and exposure to NO2 during the first trimester was linked to an increased risk of GDM. O3 exposures in the first trimester were connected to an elevated risk of GH. We didn’t observe consistent associations between adverse pregnancy and birth outcomes with PM2.5 exposure. Our findings indicate there is a positive link between increased O3 exposure during pregnancy and a higher risk of preterm birth, GH, and decreased birth weight. Our work supports limiting population exposure to air pollution, which may lower the likelihood of adverse birth and pregnancy outcomes.

The effect of cold exposure on the levels of glucocorticoids, 11-hydroxysteroid dehydrogenase 2, and placental vascularization in a rat model.

Cold exposure (CE) before birth is one of the initial stressors that may impact mammalian pregnancy, changing placental and fetal development and affecting the health of the offspring. While glucocorticoids (GCs) participate in the body's response to the stress of CE, the specific mechanisms of their action are unclear. This study aims to determine the effect of CE stress on the placenta and to test whether stress, caused by cold exposure in pregnancy impairs fetal development by changing placental angiogenesis via excessive GC expression. CE rat model was created by exposing 30 SD rats to cold preconception, or during the first, second, and third weeks of pregnancy. Serum cortisol and soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels, physiological index changes (food intake, body weight change and blood pressure), and pregnancy outcomes (fetal rat weight, number of live fetal rats, and placental weight) were collected at baseline and at different time points after the conception. Protein expression levels of 11 β-hydroxysteroid dehydrogenase 2 (11β-HSD2), glucocorticoid receptor, vascular endothelial growth factor A (VEGF-A), placental growth factor (PIGF), and sFlt-1 in placental tissues were measured by western blotting. Cytokeratin (CK) and laminin (LN) in trophoblasts, and α-actin in vascular smooth muscle of the spiral arteries of pregnant rats after the systemic cold treatment were assessed by immunofluorescence and visualized by fluorescent microscopy. To test the effect of 11β-HSD2 levels on the placental recasting, human first-trimester extravillous trophoblast cells (HTR8/SVneo) underwent knockdown using specific 11β-HSD2 siRNA constructs. Expression levels of 11β-HSD2 were analyzed by quantitative real-time PCR (qPCR) and into HTR8 cells, and the expression levels of the 11β-HSD2 gene in each group were measured using qPCR. Cell migration and invasion was assessed by Transwell migration assay, and sFlt-1 levels in HTR8 cells were measured by ELISA. CE pre-conception led to consistently increasing serum corticosterone and sFlt-1 levels throughout pregnancy, and persistently increased diastolic blood pressure (DBP) in rat CE model compared to control animals. CE during the second week of gestation (Gp.3) was associated with significantly lower placental weight (p=0.0003). Cold exposure in the third week (Gp.4) was associated with significantly (p=0.001) lower fetal weight. CE pre-conception was associated with significantly decreased placental levels of 11β-HSD2, glucocorticoid receptor, VEGF-A, PIGF, and sFlt-1 proteins and α-actin compared to the control group. Silencing 11β-HSD2 by siRNA led to reduced cell migrations and invasion, and markedly increased expression levels of sFlt-1 in HTR8/SVneo cells (p<0.05). Pre-conception cold exposure and during early pregnancy leads to increased GCs levels and impaired placental 11β-HSD2 activity. We suggest that the subsequent 11β-HSD2-induced increase in the sFlt-1expression during early pregnancy may affect placental vascular remodeling and change placental morphological structure and function.

Residential mobility in pregnancy and potential exposure misclassification of air pollution, temperature, and greenness.

Epidemiological studies commonly use residential addresses at birth to estimate exposures throughout pregnancy, ignoring residential mobility. Lack of consideration for residential mobility during pregnancy might lead to exposure misclassification that should be addressed in environmental epidemiology. We investigated potential exposure misclassification from estimating exposure during pregnancy by residence at delivery utilizing a prospective cohort of pregnant women in New York, United States (n = 1899; 2016-2019). We calculated exposure during pregnancy corresponding to each address for fine particles (PM2.5), temperature, and greenness (Enhanced Vegetation Index [EVI]). Twenty-two percent of participants moved at least once during pregnancy; 82.3% of movers changed residences during the second or third trimesters. Participants with better health, lower parity, and higher socioeconomic status were more likely to move. Exposures based on address at delivery rather than residential history overestimated exposure for PM2.5 (exposure error: range -5.7 to 4.6 µg/m3, average -0.6 µg/m3) and EVI (range -0.305 to 0.307, average -0.013), but not temperature. Overestimations were significantly larger for mothers with higher socioeconomic status. Our findings indicate that the error for prenatal exposure can occur when residential mobility is not considered and is disproportional by maternal characteristics. Epidemiological studies should consider residential mobility in exposure assessments based on geolocation when possible, and results based on mother's residence at birth should be interpreted with understanding of potential differential exposure misclassification.