Pregnancy Exposure Research Articles

Long term links between maternal diet during pregnancy and offspring health.

The developmental origins of health and disease hypothesis propose that lifelong health is programmed during foetal development, in utero. The world's population is ageing due to increased longevity but expanding morbidity and the associated burden on health systems around the planet, are associated with this. Consequently, resources are strained and spent largely on treating patients rather than preventing chronic diseases at their source. Research on early life exposures, starting in the womb, is needed to identify new potential biomarkers linked with the development of chronic diseases during adulthood. Evidence from maternal-offspring cohorts investigating associations between pregnancy exposures and childhood metabolic health is reviewed (The GUSTO study in Singapore, the Copenhagen Prospective Studies on Asthma in Childhood, a mother-child cohort in rural Gambia, the MINIMat study in Bangladesh, The Iodine Status in Pregnancy and Offspring Health Cohort in China, the OBESO cohort in Mexico, the Pune Nutrition study in India, The Reus-Tarragona Birth Cohort study in Spain). Collectively, evidence from prospective observational studies, randomised controlled trials and animal studies, supports the hypothesis that maternal diet, lifestyle and nutritional status during pregnancy are associated with childhood metabolic health in the offspring. However, the evidence is scant and further research is needed.

Intergenerational crosstalk of brain-gut axis in parental Nd2O3 exposure-induced offspring neurotoxicity and cognitive dysfunction: a mechanistic study

IntroductionRare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood–brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd2O3) during pregnancy, and its involved mechanism of BGA injury.MethodsWe used rat model to investigated the mechanisms of the offspring’s neural damage that Nd2O3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators.ResultsMaternal Nd2O3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring’s neural development and weakening their spatial learning ability. Nd2O3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd2O3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability.ConclusionMaternal exposure to Nd2O3 affects the offspring’s BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children’s gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd2O3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd2O3, such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention.

Impact of symptomatic multiple sclerosis therapy on pregnancy outcome.

Information on symptomatic therapy (ST) use in women of childbearing age with multiple sclerosis is sparse, and data on the impact of ST pregnancy exposure on pregnancy outcome are lacking. To investigate (1) ST use patterns pre-conception, during pregnancy and postpartum and (2) pregnancy outcomes. Pregnancy data from the German Multiple Sclerosis and Pregnancy Registry were analyzed for the ST use from pre-conception to postpartum. Pregnancy outcomes were compared between ST-exposed (n = 282) and matched (disease modifying therapy and age) ST-naive (n = 536) pregnancies. Of 2,449 pregnancies, 1,053 (43.0%) received ST anytime between pre-conception and postpartum, 282 (11.5%) at pre-conception and during pregnancy. The most commonly used drug classes were antidepressants (24.8%), analgetics (31.0%), and anticonvulsives (8.7%). Exposure to ST during pregnancy did not result in an increased incidence of adverse pregnancy outcomes, major congenital abnormalities, or pregnancy complications. Nearly 50% of women used ST between pre-conception and postpartum, but only 12% pre-conception and during pregnancy. ST use during pregnancy did not adversely affect pregnancy outcomes in our cohort. More data are needed to analyze the effect of ST on pregnancy and fetal outcomes stratified by drug to improve recommendations for ST use in family planning.

Critical periods of maternal exposure to ambient fine particulate matter and the risks of stillbirth and spontaneous preterm birth in Western Australia

Few studies have investigated weekly or monthly exposure-lag-response association between fine particulate matter (PM2.5) and preterm birth, and there has been no known such study for stillbirth. We aimed to identify potential critical susceptible periods of the association between monthly PM2.5 exposure during pregnancy and stillbirth and spontaneous preterm birth (sPTB). A total of 414,771 singleton births, of which 0.5% and 3.9% were stillbirth and sPTB respectively, between 1st January 2000 and 31st December 2015 in Western Australia were linked to fine spatiotemporal monthly PM2.5 concentrations. Monthly distributed lag linear and non-linear Cox regressions were performed to investigate PM2.5 exposure during pregnancy and covariate-adjusted hazards of stillbirth and sPTB. The mean PM2.5 exposure during pregnancy was 8.1 μg/m3. Pregnancy PM2.5 exposure showed small dose-response associations with stillbirth and sPTB with critical susceptible periods spanning the 3rd–6th gestational months. Relative to 5 μg/m3, the strongest hazards of PM2.5 exposure were 1.04 (95% CI 0.99, 1.08) and 1.03 (95% CI 1.02, 1.05) during the 4th gestational month for stillbirth and sPTB, respectively. Monthly exposures at late pregnancy were associated with lower hazards. The average pregnancy exposure hazards were 1.08 (95% CI 0.88, 1.32) and 1.07 (95% CI 0.99, 1.15) per 5 μg/m3 increment for stillbirth and sPTB, respectively. The average entire pregnancy exposure showed potential attributable burden, synergistic interaction effects with biothermal stress, and comparatively higher hazards for female births and births to mothers who were Caucasian, < 35 years old, high SES, nulliparous, and smoked during pregnancy.

Associations of exposure to outdoor PM2.5 and NO2 during pregnancy with childhood asthma, rhinitis, and eczema in a predominantly rural French mother-child cohort

Uncertainty remains regarding the effects of outdoor air pollution in rural areas on childhood asthma, rhinitis, and eczema. Although these diseases often coexist, few studies have examined the effects of air pollution on their multimorbidity. The objective of this study was to investigate the associations of pregnancy exposure to outdoor fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with childhood asthma, rhinitis, eczema, and their multimorbidity. We included children from the 6-year (n = 1322) and 12-year (n = 1118) follow-up of the Pélagie mother-child cohort in Brittany, France where 64% of the participants lived in rural areas. Asthma, rhinitis, eczema, and a multimorbidity phenotype (concomitant presence of ≥2 diseases) were defined by validated questionnaires. PM2.5 and NO2 concentrations during pregnancy were modeled at residential address using land use regression. We assessed associations using logistic regressions per interquartile range (PM2.5: 3 μg/m3; NO2: 10 μg/m3). We also performed stratification by type of area (urban and rural). Asthma, rhinitis, eczema, and the multimorbidity phenotype prevalence were 12%, 20%, 22% and 12% at 6-years, and 10%, 23%, 19% and 11% at 12-years of follow-up. At 6-years, for eczema, a tendency of an association was observed with NO2 (OR = 1.15, 95% CI = 0.97–1.36, p-value = 0.10), and stratification by type of area showed statistically significant associations for PM2.5 (1.49 (1.03–2.13), p = 0.03) and NO2 (1.40 (1.08–1.82), p = 0.01) in the urban stratum. At 12-years, main analyses showed a tendency of associations of PM2.5 (1.38 (0.98–1.93), p = 0.07) and NO2 (1.25 (0.98–1.59), p = 0.07) with asthma, and of NO2 with the multimorbidity phenotype (1.23 (0.97–1.56), p = 0.09). While overall results were not statistically significant, associations in urban settings were stronger than in rural ones at 6-years suggesting that possible differences between the effects in urban and rural areas should be further explored.

The Association of Antidepressants in Late Pregnancy with Postpartum Hemorrhage: Systematic Review of Controlled Observational Studies.

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

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

EV-miRNA associated with environmental air pollution exposures in the MADRES cohort.

Air pollution is a hazardous contaminant, exposure to which has substantial consequences for health during critical periods, such as pregnancy. MicroRNA (miRNA) is an epigenetic mechanism that modulates transcriptome responses to the environment and has been found to change in reaction to air pollution exposure. The data are limited regarding extracellular-vesicle (EV) miRNA variation associated with air pollution exposure during pregnancy and in susceptible populations who may be disproportionately exposed. This study aimed to identify EV-miRNA expression associated with ambient, residential exposure to PM2.5, PM10, NO2, O3 and with traffic-related NOx in 461 participants of the MADRES cohort, a low income, predominantly Hispanic pregnancy cohort based in Los Angeles, CA. This study used residence-based modeled air pollution data as well as Nanostring panels for EVmiRNA extracted with Qiagen exoRNeasy kits to evaluate 483 miRNA in plasma in early and late pregnancy. Average air pollution exposures were considered separately for 1-day, 1-week, and 8-week windows before blood collection in both early and late pregnancy. This study identified 63 and 66 EV-miRNA significantly associated with PM2.5 and PM10, respectively, and 2 miRNA associated with traffic-related NOX (False Discovery Rate-adjusted P-value < .05). Of 103 unique EV-miRNA associated with PM, 92% were associated with lung conditions according to HMDD (Human miRNA Disease Database) evidence. In particular, EV-miRNA previously identified with air pollution exposure also associated with PM2.5 and PM10 in this study were: miR-126, miR-16-5p, miR-187-3p, miR200b-3p, miR486-3p, and miR-582-3p. There were no significant differences in average exposures in early vs late pregnancy. Significant EV-miRNAs were only identified in late pregnancy with an 8-week exposure window, suggesting a vulnerable timeframe of exposure, rather than an acute response. These results describe a wide array of EV-miRNA for which expression is affected by PM exposure and may be in part mediating the biological response to ambient air pollution, with potential for health implications in pregnant women and their children.

The Safety of Alcohol Pharmacotherapies in Pregnancy: A Scoping Review of Human and Animal Research.

Alcohol pharmacotherapies pose unknown teratogenic risks in pregnancy and are therefore recommended to be avoided. This limits treatment options for pregnant individuals with alcohol use disorders (AUD). The information on the safety of these medications during pregnancy is uncertain, prompting a scoping review. The objective of this review was to investigate available information on the safety of alcohol pharmacotherapies in pregnancy. Studies published between January 1990 and July 2023 were identified through searches in BIOSIS, Embase, PsycINFO and MEDLINE databases, using terms related to pregnancy and alcohol pharmacotherapies. The alcohol pharmacotherapies investigated were naltrexone, acamprosate, disulfiram, nalmefene, baclofen, gabapentin and topiramate. Studies were screened by two independent reviewers. Covidence software facilitated the management, screening and extraction of studies. A total of 105 studies were included in the review (naltrexone: 21, acamprosate: 4, disulfiram: 3, baclofen: 3, nalmefene: 0, topiramate: 55, gabapentin: 32) with some studies investigating multiple medications. Studies investigating naltrexone's safety in pregnancy focussed on opioid use disorders, with limited evidence regarding its safety in the context of AUD. Despite concerns about higher rates of some pregnancy complications, studies generally indicate naltrexone as a safer option compared with opioid agonists or alcohol during pregnancy. Acamprosate was not clearly associated with adverse effects of exposure in pregnancy, with two pre-clinical studies suggesting potential neuroprotective properties. Disulfiram has a high risk of congenital anomalies when used in pregnancy, believed to be due to its mechanism of action. Prenatal topiramate has also been associated with an increased risk of congenital anomalies, particularly oral clefts. There were mixed results concerning the safety of prenatal gabapentin and little to no literature investigating the safety of baclofen or nalmefene during pregnancy. There is insufficient research on the safety of alcohol pharmacotherapies in pregnancy. Despite this, given alcohol's teratogenic effects, naltrexone could be considered to help maintain abstinence in pregnant individuals with AUD, particularly when psychosocial treatments have failed.

Quantifying the effect of interpregnancy maternal weight and smoking status changes on childhood overweight and obesity in a UK population-based cohort.

Maternal preconception and pregnancy exposures have been linked to offspring adiposity. We aimed to quantify the effect of changes in maternal weight and smoking status between pregnancies on childhood overweight/obesity (≥ 85th centile) and obesity (≥ 95th centile) rates in second children. Records for 5612 women were drawn from a population-based cohort of routinely collected antenatal healthcare records (2003-2014) linked to measured child body mass index (BMI) age 4-5 years. We applied the parametric G-formula to estimate the effect of hypothetical changes between pregnancy-1 and pregnancy-2 compared to the natural course scenario (without change) on child-2 BMI. Observed overweight/obesity and obesity in child-2 at age 4-5 years were 22.2% and 8·5%, respectively. We estimated that if all mothers started pregnancy-2 with BMI 18·5-24·9 kg/m² and all smokers stopped smoking, then child-2 overweight/obesity and obesity natural course estimates of 22.3% (95% CI 21.2-23.5) and 8·3% (7·6-9·1), would be reduced to 18.5% (17.4-19.9) and 6.2% (5.5-7.0), respectively. For mothers who started pregnancy-1 with BMI 18·5-24·9 kg/m², if all smokers stopped smoking, child-2 overweight/obesity and obesity natural course estimates of 17.3% (16.0-18.6) and 5·9% (5·0-6·7) would be reduced to 16.0% (14.6-17.3) and 4·9% (4·1-5·7), respectively. For mothers who started pregnancy-1 with BMI ≥30 kg/m², if BMI was 18·5-24·9 kg/m² prior to pregnancy-2, child-2 overweight/obesity and obesity natural course estimates of 38.6% (34.7-42.3) and 17·7% (15·1-20·9) would be reduced to 31.3% (23.8-40.0) and 12.5 (8.3-17.4), respectively. If BMI was 25.0-29.9 kg/m² prior to pregnancy-2, these estimates would be 34.5% (29.4-40.4) and 14.6% (11.2-17.8), respectively. Interventions supporting women to lose/maintain weight and quit smoking between pregnancies could help reduce rates of overweight/obesity and obesity in second children. The most effective interventions may vary by maternal BMI prior to the first pregnancy.

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 between gestational hypnotic benzodiazepine receptor agonists exposure and adverse pregnancy outcomes: a systematic review and meta-analysis.

Hypnotic benzodiazepine receptor agonists (HBRA) are frequently prescribed in pregnancy but little is known about their effects on pregnancy outcomes. Herein, we systematically reviewed the evidence on the effects of HBRA exposure during pregnancy and risk of preterm birth (PTB), small for gestational age (SGA), birth defects, and low birth weight (LBW). We reviewed the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science from the earliest possible date to 17th May 2024 and included all studies examining adverse pregnancy outcomes with gestational exposure to HBRA. Nine studies were included. Meta-analysis showed that HBRA exposure led to a significant increase in the risk of PTB (OR: 1.28 95% CI: 1.05, 1.56 I2 = 73%), SGA (OR: 1.24 95% CI: 1.18, 1.30 I2 = 0%), and LBW (OR: 1.51 95% CI: 1.27, 1.78 I2 = 26%). We noted no significant association between HBRA exposure in pregnancy and subsequent birth defects (OR: 0.90 95% CI: 0.63, 1.28 I2 = 56%). Subgroup analysis based on exposure time, type of HBRA, method of assessment of exposure, control of psychiatric diagnosis, and psychotropic drugs altered the results of PTB and SGA but not for birth defects. HBRA exposure during pregnancy may lead to a small but significant increase in the risk of PTB, SGA, and LBW. HBRA is not associated with an increased risk of birth defects. There are several limitations of current evidence especially with regards to adjustment for psychiatric illness and co-mediations which need to be overcome by future studies.

Biomonitoring and determinants of mycotoxin exposures from pregnancy until post-lactation in HIV-infected and HIV-uninfected women from Harare, Zimbabwe

The human immunodeficiency virus (HIV) heavily affects women from resource-limited settings who are vulnerable to potentially harmful mycotoxins including aflatoxin B1 (AFB1), fumonisin B1 (FB1) and ochratoxin A (OTA). We aimed to conduct biomonitoring and ascertain the determinants of maternal mycotoxin exposure in pregnancy, lactation and post-lactation periods. We conducted a retrospective longitudinal study in HIV-infected and HIV-uninfected women from Harare, Zimbabwe. 175 and 125 random urine samples in pregnancy and 24 months after delivery (post-lactation) respectively were analysed for aflatoxin M1 (AFM1) and FB1 by ELISA. 6 weeks after delivery (lactation), 226 and 262 breast milk (BM) samples were analysed for AFM1 and OTA respectively by ELISA. The association of demographics and food consumption with mycotoxins was evaluated using multivariable logistic regression. In HIV-infected, urinary AFM1 was detected in 46/94 (Median: 0.05; Range: 0.04–0.46 ng mL−1) in pregnancy and 47/66 (Median: 0.05; Range: 0.04–1.01 ng mL−1) post-lactation. Urinary FB1 was detected in 86/94 (Median: 1.39; Range: 0.17–6.02 ng mL−1) in pregnancy and 56/66 (Median: 0.72; Range: 0.20–3.81 ng mL−1) post-lactation. BM AFM1 was detected in 28/110 (Median: 7.24; Range: 5.96–29.80 pg mL−1) and OTA in 11/129 (Median: 0.20; Range: 0.14–0.65 ng mL−1). In HIV-uninfected, urinary AFM1 was detected in 48/81 (Median: 0.05; Range: 0.04–1.06 ng mL−1) in pregnancy and 41/59 (Median: 0.05; Range: 0.04–0.52 ng mL−1) post-lactation. Urinary FB1 was detected in 74/81 (Median: 1.15; Range: 0.17–6.16 ng mL−1) in pregnancy and 55/59 (Median: 0.96; Range: 0.20–2.82 ng mL−1) post-lactation. BM AFM1 was detected in 38/116 (Median: 7.70; Range: 6.07–31.75 pg mL−1) and OTA in 4/133 (Median: 0.24; Range: 0.18–0.83 ng mL−1). Location, wealth, and peanut butter consumption were determinants of AFB1 exposure. HIV infection, BMI, location, rainy season, unemployment, and age were determinants of FB1 exposure. Women especially those pregnant and/or HIV-infected are at risk of adverse effects of mycotoxins.

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.

Looking beyond the neonatal: what does administrative data tell us about the preschool health and developmental outcomes of children exposed to opioids in utero?

BackgroundThe world is facing an opioid epidemic. Children of women who use opioids in pregnancy are difficult to follow-up over long periods using traditional research methods due to the complexity of their lives. Resultingly, we have little robust evidence on their longer-term outcomes. ObjectiveThis study aimed to explore the impact of illicit and prescription opioid exposure in pregnancy on preschool health and developmental outcomes. ApproachData identified 6,408 children (born 2009-2019 in Scotland) exposed to opioids through illicit use and/or medication assisted treatment (MAT), alongside a matched control group (n.19,089). Regression models will examine associations between opioid exposure and key outcomes up to age 5, including the Ages and Stages Questionnaire, accidents and injuries, and chronic health conditions such as asthma, controlling for other risk factors (e.g. alcohol use in pregnancy, gestation). ResultsEarly results indicated differences in neonatal outcomes, with poorer outcomes for the illicit opioid/MAT cohort in terms of being born early, having lower birthweight, length and head circumference, and being more likely to be removed from their mother prior hospital discharge. Modelling of preschool outcomes is underway and will be finished in June 2024. ConclusionsHaving proven that we can identify these children in administrative data, this paper will present cutting-edge data on the impact of exposure to illicit and prescription opioids on preschool outcomes. This will provide robust evidence on these impacts, and highlight where additional support might be required for these children from birth to starting school.

Fetal Growth Following Electronic Cigarette Use in Pregnancy.

Electronic cigarette (e-cig) use in pregnancy is common, but potential effects on fetal development are largely unknown. This study's goal was to examine the association between e-cig exposure and fetal growth. Data were extracted from medical charts in this single-site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used e-cigs throughout pregnancy and non-e-cig user controls. Fetal size measurements from second- and third-trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for e-cig exposure compared to controls. By the third trimester, the femur length difference was 28.5 points, with the fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal e-cig exposure, becoming larger and impacting more parameters with increasing gestation. While additional studies are warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following e-cig exposure in pregnancy and suggests that e-cigs may not be a "safer" alternative to combustible cigarette smoking in pregnancy.

Distinct Trajectories of Prescription Opioid Exposure in Pregnancy and Risk of Adverse Birth Outcomes.

The aim of this study was to identify distinct trajectories of prescription opioid exposure in pregnancy-encompassing both medication for opioid use disorder (MOUD) and opioid analgesics-and explore their associations with birth outcomes. Trajectories were identified using latent class analysis among Wisconsin Medicaid-insured live births 2011-2019. Logistic regression estimated associations between these trajectories and neonatal opioid withdrawal syndrome (NOWS), small for gestational age, preterm birth, birth weight, and gestational age. Of 138,123 births, 27,293 (19.8%) had prenatal opioid exposure. Five trajectory classes were identified: (1) stable MOUD treatment (5.8%), (2) inconsistent MOUD treatment (3.9%), (3) chronic analgesic use (4.2%), (4) intermittent analgesic use (7.8%), and (5) low-level use of MOUD and analgesics (78.3%). NOWS incidence per 1000 infants was 667 for class 1 (adjusted odds ratio [aOR]: 21.74, 95% confidence interval [CI]: 17.89, 26.41), 570 for class 2 (aOR: 15.35, 95% CI: 12.49, 18.87), 235 for class 3 (aOR: 19.42, 95% CI: 15.93, 23.68), 67 for class 4 (aOR: 6.23, 95% CI: 4.99, 7.76), and 12 for class 5 (aOR: 1.73, 95% CI: 1.47, 2.02). Classes 1-4 had elevated risk of small for gestational age, preterm birth, lower birth weight, and shorter gestational age, with no significant differences among these classes. Among individuals with opioid use disorder, stable MOUD treatment was associated with higher birth weights and longer gestational ages compared to inconsistent treatment, despite higher odds of NOWS. Early initiation and consistent MOUD treatment may improve birth weight and gestational age. For pregnant individuals with opioid use disorder using chronic analgesics, transition to MOUD may promote birth outcomes.

Mirtazapine in pregnancy and lactation: A systematic review of adverse outcomes.

Peripartum depression is common and treatment with mirtazapine may be indicated. However, evidence on its safety in pregnancy and lactation is fragmented. The objective of this systematic review was to evaluate the literature on the safety of mirtazapine in pregnancy and lactation. PubMed, Embase, Medline, PsycInfo, and clinicaltrials.gov were searched for 'antidepressants' or 'mirtazapine' in combination with 'pregnancy', 'lactation' or 'offspring'. No restrictions on type of study were applied and selection was performed by two independent reviewers using Covidence. Two reviewers extracted data and performed risk of bias assessment and evidence synthesis was performed for each outcome individually. The protocol was registered at PROSPERO (registration number CRD42021275127). The initial search yielded 15,380 articles after removal of duplicates. After screening based on title and abstract, 431 articles remained for full text review. Of these, 41 studies were included (15 cohort studies, one case-control study, 11 case series, and 14 case reports). In most studies, the outcomes in mirtazapine-exposed pregnancies were comparable to controls. However, results on congenital malformations and spontaneous abortion were conflicting. Neonatal adaptation syndrome was reported after mirtazapine exposure in late pregnancy. Data on mirtazapine exposure during lactation were scarce. We identified no substantial evidence indicating that mirtazapine exposure is associated with adverse outcomes in pregnancy or in offspring, other than neonatal adaptation syndrome. However, overall quality of evidence was low, and results on congenital malformations and spontaneous abortions were conflicting. Data on mirtazapine exposure through breastfeeding were limited and did not allow for conclusions.

Gestational exposure to wildfire PM2.5 and its specific components and the risk of gestational hypertension and eclampsia in the southwestern United States

In the southwestern United States, the frequency of summer wildfires has elevated ambient PM2.5 concentrations and rates of adverse birth outcomes. Notably, hypertensive disorders in pregnancy (HDP) constitute a significant determinant associated with maternal mortality and adverse birth outcomes. Despite the accumulating body of evidence, scant research has delved into the correlation between chemical components of wildfire PM2.5 and the risk of HDP. Derived from data provided by the National Center for Health Statistics, singleton births from >2.68 million pregnant women were selected across 8 states (Arizona, AZ; California, CA, Idaho, ID, Montana, MT; Nevada, NV; Oregon, OR; Utah, UT, and Wyoming, WY) in the southwestern US from 2001 to 2004. A spatiotemporal model and a Goddard Earth Observing System chemical transport model were employed to forecast daily concentrations of total and wildfire PM2.5-derived exposure. Various modeling techniques including unadjusted analyses, covariate-adjusted models, propensity-score matching, and double robust typical logit models were applied to assess the relationship between wildfire PM2.5 exposure and gestational hypertension and eclampsia. Exposure to fire PM2.5, fire-sourced black carbon (BC) and organic carbon (OC) were associated with an augmented risk of gestational hypertension (ORPM2.5 = 1.125, 95 % CI: 1.109,1.141; ORBC = 1.247, 95 % CI: 1.214,1.281; OROC = 1.153, 95 % CI: 1.132, 1.174) and eclampsia (ORPM2.5 = 1.217, 95 % CI: 1.145,1.293; ORBC = 1.458, 95 % CI: 1.291,1.646; OROC = 1.309, 95 % CI: 1.208,1.418) during the pregnancy exposure window with the strongest effect. The associations were stronger that the observed effects of ambient PM2.5 in which the sources primarily came from urban emissions. Social vulnerability index (SVI), education years, pre-pregnancy diabetes, and hypertension acted as effect modifiers. Gestational exposure to wildfire PM2.5 and specific chemical components (BC and OC) increased gestational hypertension and eclampsia risk in the southwestern United States.