Risk Of Birth Defects Research Articles

Pregnancy outcomes in women with panhypopituitarism: a population-based study

Research questionWhat are the consequences of panhypopituitarism on pregnancy outcomes? DesignRetrospective population-based study using data from the Healthcare Cost and Utilization Project – Nationwide Inpatient Sample (HCUP-NIS). A dataset was created of all deliveries between 2004 and 2014 inclusive. Within this group, all deliveries to women who had a diagnosis of panhypopituitarism during pregnancy were identified as part of the study group (n = 120), and the remaining deliveries comprised the reference group (n = 8,732,641). A multivariate logistic regression analysis, controlling for confounding effects, was conducted to explore associations between panhypopituitarism and pregnancy complications, delivery and neonatal outcomes. ResultsNo significant differences were found in the risk of developing gestational hypertension, gestational diabetes mellitus, placental abruption, or preterm delivery delivering a small for gestational age neonate, or in the mode of delivery. There was a higher risk of developing maternal infection (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.46–6.74) and congenital anomalies (OR 6.97, 95% CI 2.57–18.95); however, due to the small number of cases these results should be interpreted with caution. ConclusionsPregnancy outcomes of women with panhypopituitarism are comparable to those of the general population. Further studies are needed to assess the risk of congenital anomalies and maternal infection in pregnant women with panhypopituitarism.

Knowledge and consumption of folic acid among teachers in Jammu region: a cross-sectional study

Background: Folic acid reduces the risk of birth defects, including neural tube defects (NTDs). It reduces the risk of miscarriage and fetal death as well as folate-deficiency anemia. Folate status is particularly important before conception and during the first 12 weeks of pregnancy. Objective was to assess knowledge and consumption of folic acid among teachers in the reproductive age group.Methods: 336 school teachers selected from government and private schools (primary/middle/secondary/higher secondary) by simple random sampling technique. Teacher’s knowledge and consumption of folic acid and associated factors was studied using a pre- tested; self- administered questionnaire.Results: 95% teachers had heard about folic acid, 57% knew about neural tube defects. 53% were aware of the role of folic acid in NTDs. 66% had knowledge about the best timing for its intake. 56% were aware about the sources rich in folic acid. 75% believed that foods are the best source of folic acid, 80% believed that taking foods rich in folic acid and tablets are sufficient to maintain body stores.49% were taking folic acid presently. 66% of the participants were taking folic acid under medical advice, 29% due to the recommendations by their family/friends while self-initiation was reported in only 5% of the individuals.Conclusions: IEC activities needs to be conducted among different strata of population so that the intake of folic acid could be increased and associated factors effecting its intake and absorption could be taken care of.

Neuraminidase Inhibitors During Pregnancy and Adverse Birth Outcomes: A Meta-Analysis

Neuraminidase inhibitors (NAIs) are commonly used to treat influenza and are also considered the potential treatment for COVID-19. The association of using NAIs during pregnancy with the risk of adverse birth defects has been investigated repeatedly by epidemiological studies; however, results are largely inconsistent. We herein performed this meta-analysis to investigate the true association of NAIs with adverse birth defects, including preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). A systematic search was performed through PubMed, Scopus, and Embase to indentify all pertinent studies; The ORs with their corresponding 95% CIs were extracted or calculated. Heterogeneity was assessed using the Cochran Q test and the I2 statistic. A random-effect model was used for this meta-analysis due to existing heterogeneity. Overall, eight studies were included in our analysis, meta-analysis using a random-effect model showed that NAIs during pregnancy reduced the risk of LBW (OR=0.78, 95% CI=0.66–0.91) and SGA (OR=0.76, 95% CI=0.67–0.86) but is not associated with PTB (OR=1.01, 95% CI=0.87–1.16). Results of the present study suggested that NAIs during pregnancy are safe and may reduce the risk of LBW and SGA. However, further studies from different ethnic populations are warranted to confirm our results.

Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity.

The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.

The Human STAT2 Coiled-Coil Domain Contains a Degron for Zika Virus Interferon Evasion.

The ability of viruses to evade the host antiviral immune system determines their level of replication fitness, species specificity, and pathogenic potential. Flaviviruses rely on the subversion of innate immune barriers, including the type I and type III interferon (IFN) antiviral systems. Zika virus infection induces the degradation of STAT2, an essential component of the IFN-stimulated gene transcription factor ISGF3. The mechanisms that lead to STAT2 degradation by Zika virus are poorly understood, but it is known to be mediated by the viral NS5 protein that binds to STAT2 and targets it for proteasome-mediated destruction. To better understand how NS5 engages and degrades STAT2, functional analysis of the protein interactions that lead to Zika virus and NS5-dependent STAT2 proteolysis were investigated. Data implicate the STAT2 coiled-coil domain as necessary and sufficient for NS5 interaction and proteasome degradation after Zika virus infection. Molecular dissection reveals that the first two α-helices of the STAT2 coiled-coil domain contain a specific targeting region for IFN antagonism. These functional interactions provide a more complete understanding of the essential protein-protein interactions needed for Zika virus evasion of the host antiviral response and identify new targets for antiviral therapeutic approaches. IMPORTANCE Zika virus infection can cause mild fever, rash, and muscle pain and in rare cases can lead to brain or nervous system diseases, including Guillain-Barré syndrome. Infections in pregnant women can increase the risk of miscarriage or serious birth defects, including brain anomalies and microcephaly. There are no drugs or vaccines for Zika disease. Zika virus is known to break down the host antiviral immune response, and this research project reveals how the virus suppresses interferon signaling, and may reveal therapeutic vulnerabilities.

A Genetic study in assisted reproduction and the risk of congenital anomalies

In vitro fertilization is one of the most common and effective procedure for thousands of couples worldwide who want to have a child and are unable to do so for various reasons. Diverse studies show that couples who conceive naturally after one year of trying had newborns with an increased risk of prematurity and low birth weight, compared with couples who conceived before completing one year of trying. Children from assisted reproduction (AR), have a 30% increased risk of prematurity and low birth weight, compared with children from infertile fathers. Regarding the conflicting results the present study aimed to record the frequency of genetic, congenital anomalies in children and adolescents who had examined in the last decade to the Clinical Genetics Clinic of the National and Kapodistrian University of Athens whose mothers had undergone assisted reproduction. The research process was conducted at the "Aghia Sofia" Children's Hospital based in Athens. However, the cases that were studied came from all over Greece. Initially, the researcher recorded the cases that came to the clinic of Clinical Genetics and whose conception occurred after technical assisted reproduction. After telephone communication and the consent of the parents, a live appointment was scheduled. In this meeting-interview all the provisions of the investigation and the protocol were asked and some elements of the medical history of the cases were confirmed. The total sample included 230 children and adolescents. The resulting data were recorded on a printed form/questionnaire. Then, they were registered electronically in the program SPSS 25.0 (Statistical Package for Social Sciences) with a specific unit code for each case/patient, followed by the processing and statistical analysis of the data as well as the recording of the results. The gender of the participants was male for 118 participants (51.3%) and 112 females (48.7%). Mean and standard deviation (SD) of maternal, paternal (at the time of delivery) age was equal to 36.38 (5.94) and 39.94 (6.58) respectively. The observed abdormalities were 35.53% psychomotor retardation, 23.68% facial abnormalities, 23.68% spinal cord abnormalities, 21.05% morphological abnormalities, 20.61% short stature, 19.74% developmental disorders, 19.30% heart disease, 16.67% neurological diseases, 14.47% genetic syndromes, 11.40% genital abnormalities, 8.33% limb abnormalities, 7.46% dermatological abnormalities, 6.14% eye abnormalities, 6.14% hypothyroidism, 5.70% endocrine disorders, 5.26%otolaryngology abnormalities, 2.63% disease of kidney, intestine, 2.19% vascular malformations. Regarding the karyotype chromosome analysis by G-banding technique, from the 230 children in: 24 (10.43%) a pathological result was found, in 158 children (68.70%) it was found normal (46, XX or 46, XY by case) without other findings, while in 48 children (20.87%) the test was not performed for various reasons. Regarding the results of molecular analysis (DNA) from the 230 children, in 50 (21.74%) a pathological finding was found, in 56 children (24.35%) no abnormalities were found and in 124 children (53.91%) no molecular analysis was performed for various reasons. In conclusion, the sample of this descriptive study is characterized as uniform in terms of the method of assisted reproduction since 96.24% had followed the classic IVF. Full-term pregnancy was associated with the appearance of malignancy and head morphological abnormalities (64.6%), normal pregnancy was associated with genetic syndromes (18.2%) and facial abnormalities (11.1%). It is recommended the screening oocyte and sperm donors in order to help protect the safety and health of donors, recipients, and future offspring. The present study confirms the association of the presence of congenital anomalies after in vitro fertilization (IVF). However, the absolute risk of developing severe dysplasias after an IVF procedure is limited.

THE DIFFERENCES OF BEHAVIOUR TOWARDS PREGNANCY READINESS AMONG PREGNANT WOMEN BASED ON PARITY

Abstract Background : Low pregnancy planning can cause unwanted pregnancy, abortion, loss of reproductive health, domestic violence until death. 40% of 85 million pregnancies in the world are unplanned and 38% end with abortions, miscarriage and unplanned childbirth. Unplanned pregnancy are associated with an increased risk of birth outcomes, including preterm birth, low birth weight (LBW), high risk of congenital anomalies, and developmental delay. Most woman who have plan to get pregnant don’t prepare their pregnancy as well. Women who have children (Multiparous) having unreadiness of pregnancy as same as women who do not have children (Nulliparous). Therefore, pregnancy planning is required to avoid risks so that women become more prepared on facing the pregnancy. This study aimed to analyze the differences behaviour toward readiness of pregnancy among pregnancy women based on parity. Method : This study used observational analytical research with cross sectional approach. The sampling technique used was total sampling which was conducted for 2 months and the sample obtained 92 pregnant women (include nulliparous, primiparous and multiparous) who met the inclusion criteria. The collected data was analyzed by Fisher Exact levels with a degree of α = 0.05. Result : The study showed there were 12 respondents who ready to face pregnancy. Meanwhile, there were 80 respondents who were not ready enough to face pregnancy, it was based on the result of Fisher Exact test with the value obtained was P value = 0.223 (P &gt; 0.223). Conclusion : This showed that there was no difference of attitudes about pregnancy readiness of nulliparous, primiparous and multiparous woman

Initial data on the safety of metopimazine during pregnancy and the risk of major birth defects and pregnancy loss – An observational study using the EFEMERIS database

Metopimazine is an anti-emetic drug used to treat nausea and vomiting of pregnancy. However, no animal or clinical data are available regarding its safety in pregnant women. The aim of this study was, therefore, to assess the risk of birth defects and pregnancy loss associated with the use of metopimazine during pregnancy in a population-based cohort study. The study focused on the EFEMERIS database including the prescription and dispensation of drugs for pregnant women in Haute-Garonne, France, between July 2004 and December 2017. This was an observational, retrospective, comparative study. Pregnancy loss and major birth defects were compared between women exposed to metopimazine during pregnancy and those with no exposure using multivariate logistic regression and Cox proportional risk models. Among 135,574 pregnant women, 11,402 (8.2%) were exposed to metopimazine during pregnancy, mostly in the first trimester (more than 70% of women). No association was found between major birth defects and exposure to metopimazine in the first trimester of pregnancy (ORa=[95% CI]=1.06 [0.92-1.23]). Pregnancy loss was negatively associated with metopimazine use during pregnancy (HRa [95% CI]=0.80 [0.72-0.88]), taking into account major potential confounders. Comparable rates were recorded between women exposed to metopimazine and those unexposed to the drug in terms of prematurity (6.7% vs. 6.4%), low birth weight (6.2% vs. 6.2%) and small for gestational age (1.2% vs. 1.4%). This study illustrates the wide use of metopimazine during pregnancy in France although no studies on efficacy or safety in pregnant women are available. The results of this study do not indicate any teratogenic effect or an increased risk of pregnancy loss of metopimazine.

Exposure to air pollution is associated with congenital anomalies in the population born by in vitro fertilization

BackgroundCongenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. MethodsWe conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014–2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. ResultsWe found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10–12 weeks (OR: 1.05, 95% CI: 1.02–1.09, p = 0.013 for a 10 μg/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01–1.06, p = 0.021 for a 10 μg/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find an association between chromosome abnormalities and air pollution exposure. ConclusionsWe concluded that ambient air pollution was a risk factor for congenital anomalies in the fetuses conceived through IVF, especially exposure in early fetal period.

Gadolinium-based contrast: risk of congenital abnormalities, stillbirth?

Gadolinium-based contrast: risk of congenital abnormalities, stillbirth?

VP13.01: Low‐dose aspirin use in the first trimester of pregnancy and risk of congenital anomalies: a systematic review and meta‐analysis of randomised trials

VP13.01: Low‐dose aspirin use in the first trimester of pregnancy and risk of congenital anomalies: a systematic review and meta‐analysis of randomised trials

History of pandemic H1N1-containing influenza vaccination and risk for spontaneous abortion and birth defects

BackgroundOne recent study suggested an association between receipt of pandemic H1N1 (pH1N1)-containing vaccines in consecutive influenza seasons and spontaneous abortion, but corroborating scientific evidence is limited. In the present study, we leveraged a population of vaccine-compliant pregnant military women to examine history of pH1N1-containing influenza vaccination and adverse pregnancy outcomes. Because seasonal influenza vaccination is compulsory for military service, safety concerns regarding repeat vaccination are particularly relevant in this population. MethodsPregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to identify women vaccinated with a pH1N1-containing vaccine in pregnancy prior to 21 6/7 weeks’ gestation, October 2009–April 2015. Cox and modified Poisson regression models estimated associations between vaccination with pH1N1- versus non–pH1N1-containing influenza vaccine in the season prior to the index pregnancy, and spontaneous abortion and birth defects, respectively. Cox models were calculated for two periods of follow-up: through (1) 21 6/7 weeks’ gestation and (2) 28 days postvaccination. ResultsOf 26,264 pregnancies, 21,736 (82.8%) were among women who received a dose of pH1N1-containing vaccine in the prior influenza season and 4,528 (17.2%) were among women who received non–pH1N1-containing vaccine in the prior influenza season. Among 23,121 infants, 19,365 (83.8%) and 3,756 (16.2%) had mothers exposed and unexposed to pH1N1-containing vaccine in the prior influenza season, respectively. The adjusted hazard ratio (aHR) for spontaneous abortion approximated 1.0 across the complete follow-up period (95% confidence interval [CI]: 0.89–1.13) and was slightly elevated when censored at 28 days postvaccination, though the CI was imprecise (aHR: 1.19; 95% CI: 0.97–1.46). No associations with birth defects were observed. ConclusionThis work lends additional safety evidence and support for vaccination against pH1N1 in pregnancy, regardless of the vaccine received in the prior influenza season.

Prenatal exposure to wildfire-related air pollution and birth defects in Brazil.

Birth defects are a major cause of poor health outcomes during both childhood and adulthood. A growing body of evidence demonstrated associations between air pollution exposure during pregnancy and birth defects. To date, there is no study looking at birth defects and exposure to wildfire-related air pollution, which is suggested as a type of air pollution source with high toxicity for reproductive health. Our study addresses this gap by examining the association between birth defects and wildfire smoke exposure in Brazil between 2001 and 2018. Based on known differences of impacts of wildfires across different regions of Brazil, we hypothesized differences in risks of birth defects for different regions. We used a logistic regression model to estimate the odds ratios (ORs) for individual birth defects (12 categories) associated with wildfire exposure during each trimester of pregnancy. Among the 16,825,497 birth records in our study population, there were a total of 7595 infants born in Brazil between 2001 and 2018 with birth defects in any of the selected categories. After adjusting for several confounders in the primary analysis, we found statistically significant OR for three birth defects, including cleft lip/cleft palate [OR: 1.007 (95% CI: 1.001; 1.013)] during the second trimester of exposure, congenital anomalies of the respiratory system [OR: 1.013 (95% CI: 1.002; 1.023)] in the second trimester of exposure, and congenital anomalies of the nervous system [OR: 1.002 (95% CI: 1.001; 1.003)] during the first trimester of exposure for the regions South, North, and Midwest, respectively. Our results suggest that maternal exposure to wildfire smoke during pregnancy may increase the risk of an infant being born with some congenital anomaly. Considering that birth defects are associated with long-term disability, impacting families and the healthcare system (e.g., healthcare costs), our findings should be of great concern to the public health community. Our study focused on the association between maternal exposure to wildfire smoke in Brazil during pregnancy and the risk of an infant being born with congenital anomalies, which presents serious public health and environmental challenges.

Meta-analyses of maternal exposure to atmospheric particulate matter and risk of congenital anomalies in offspring.

Congenital anomalies are the main causes of infant death and disability. Previous studies have suggested that maternal exposure to particulate matter is related to congenital malformation. However, the conclusions of this study remain controversial. Hence, meta-analyses were performed to assess the relationship between maternal exposure to particulate matter and the risk of congenital anomalies. The Medline, Embase, and Web of Science databases were systemically searched from inception until August 2020 to find articles related to birth defects and particulate matter. The pooled risk estimated for the combination of pollution outcomes was calculated for each study by performing fixed effects or random effects models. The existence of heterogeneity and publication bias in relevant studies was also examined. Thirty studies were included in the analysis. A statistically increased summary risk valuation was found. PM10 exposure was associated with an increased risk of congenital heart disease, neural tube defects, and cleft lip with or without cleft palate (OR per 10 μg/m3 = 1.05, 95% CI, 1.03-1.07; OR per 10 μg/m3 = 1.04, 95% CI, 1.01-1.06; OR per 10 μg/m3 = 1.03, 95% CI, 1.01-1.06). Maternal exposure to particulate matter might be associated with an increased risk of congenital anomalies. Our results indicate the dangers of particulate matter exposure on fetal development and the importance of protection against exposure to such particles during pregnancy. The schematic representation of the association between maternal exposure to PM2.5/PM10 and congenital anomalies in offspring, and geographic distribution of the included reports in the meta-analyses.

Review Highlights Gaps in Knowledge of Perinatal Mental Health

Review Highlights Gaps in Knowledge of Perinatal Mental Health

Protocol of a prospective and multicentre China Teratology Birth Cohort (CTBC): association of maternal drug exposure during pregnancy with adverse pregnancy outcomes

BackgroundAs reported, 27-93 % of pregnant women take at least one drug during pregnancy. However, drug exposure during pregnancy still lacks sufficient foetal safety evidence of human origin. It is urgent to fill the knowledge gap about medication safety during pregnancy for optimization of maternal disease treatment and pregnancy drug consultation.Methods and analysisThe China Teratology Birth Cohort (CTBC) was established in 2019 and is a hospital-based open-ended prospective cohort study with the aim of assessing drug safety during pregnancy. Pregnant women who set up the pregnancy health records in the first trimester or who seek drug consultation regardless of gestational age in the member hospitals are recruited. Enrolled pregnant women need to be investigated four times, namely, 6–14 and 24–28 weeks of gestational age, before discharge after hospital delivery, and 28–42 days after birth.Maternal medication exposure during pregnancy is the focus of the CTBC. For drugs, information on the type, name, and route of medication; start and end time of medication; single dose; frequency of medication; dosage form; manufacturer; and reason for medication is collected. The adverse pregnancy outcomes collected in the study include birth defects, stillbirth, spontaneous abortion, preterm birth, post-term birth, low birth weight, macrosomia, small for gestational age, large for gestational age and low Apgar score. CTBC uses an electronic questionnaire for data collection and a cloud system for data management. Biological samples are collected if informed consents are obtained. Multi-level logistic regression, mixed-effect negative binomial distribution regression and spline function regression are used to explore the effect of drugs on the occurrence of birth defects.DiscussionThe findings of the study will assist in further understanding the risk of birth defects and other adverse pregnancy outcomes associated with maternal drug exposure and developing the optimal treatment plans and drug counselling for pregnant women.Trial registrationThis study was approved by the Research Ethics Committee of the West China Second Hospital of Sichuan University and registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx, registration number ChiCTR1900022569).

Nitrate in drinking water and risk of birth defects: Findings from a study of over one million births in Denmark

BACKGROUND AND AIM: A few epidemiologic studies have reported an association between nitrate in drinking water and the risk of birth defects (BD). Our objective was to examine this association in a large, population-based study with individual-level exposure estimates. METHODS: We studied a cohort of all Danish singletons liveborn to Danish-born parents from 1991–2013 (N=1,018,914). In total, 33,182 BD diagnosed until the age of two were identified. Nitrate concentrations during pregnancy were analyzed using continuous and categorical variables. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression with generalized estimating equations and controlling for parental age, birth year, birth order, maternal smoking, education, employment, and income. Analyses were conducted for ten major BD categories, and for subcategories that were of interest. RESULTS:Nitrate pregnancy concentrations were generally low (median=1.9 mg/L NO3-) and below US and European limits (44 and 50 mg/L NO3-). An association was observed between nitrate and eye BD in the highest exposure group (OR for 25 versus 0 to 2 mg/L (OR25)=1.29 95% CI=1.00, 1.66), and there was evidence of an exposure-response relationship (p=0.004). A large excess risk for the eye subcategory of congenital cataracts was observed among children with young mothers (25) (OR25= 4.20 95% CI=1.87, 9.45). An interaction (p0.005) was also observed between maternal age and nervous system BD indicating an effect among young mothers (OR25=1.19, 95% CI=1.06, 1.35), particularly for spina bifida (OR25=1.23, 95%CI=1.03, 1.48). No evidence of an association was observed for other BD categories. CONCLUSIONS:Our study is the first to report an association between nitrate and eye BD and provides support to prior reports of an association between nitrate in drinking water and nervous system BD. Our findings raise serious concerns about the adequacy of current regulatory standards for nitrate in drinking water given the low levels of exposures in our study. KEYWORDS: nitrate, drinking water, birth defects, congenital malformations

The role of education and migration background in explaining differences in folic acid supplementation intake in pregnancy: results from a German birth cohort study.

Official German recommendations advise women to start taking folic acid supplementation (FAS) before conception and continue during the first pregnancy trimester to lower the risk of birth defects. Women from lower socio-economic background and ethnic minorities tend to be less likely to take FAS in other European countries. As little is known about the determinants of FAS in Germany, we aimed to investigate the association between FAS and formal education and migration background, adjusting for demographic factors. We used data (2013-2016) on nutrition and socio-economic and migration background from the baseline questionnaire of the BaBi cohort study. We performed multivariate regressions and mediation analyses. Bielefeld, Germany. Nine-hundred forty-seven women (pregnant or who had given birth in the past 2 months). 16.7% of the participants (158/947) did not use FAS. Migration-related variables (e.g. language, length of stay) were not associated with FAS in the adjusted models. FAS was lower in women with lower level of formal education and in unplanned pregnancies. Reasons given by women for not taking FAS were unplanned pregnancy and lack of knowledge of FAS. Health practitioners may be inclined to see migrant women as an inherently at-risk group for failed intake of FAS. However, it is primarily women who did not plan their pregnancy, and women of lower formal education level, who are at risk. Different public health strategies to counter low supplementation rates should be supported, those addressing the social determinants of health (i.e. education) and those more focused on family planning.

Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects

BACKGROUND AND AIM: Previous research suggests gestational exposure to particulate matter ≤ 2.5 μm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies the associations between PM2.5 exposure and specific congenital heart defects (CHDs). METHODS: We identified live-birth, stillborn, and induced termination CHD cases (n = 2,824) and non-malformed live-birth controls (n = 4,033) from pregnancies ending between October 1997 and December 2011 in the National Birth Defects Prevention Study (NBDPS). We assigned mothers 6-week averages for 24-hour PM2.5 exposure during the cardiac critical period (gestational weeks 3-8) using the closest monitor within 50 kilometers of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile from daily maximum temperature distribution for region, year, and season) during this period using the closest weather station. Using generalized additive models (GAMs), we explored logit-nonlinear exposure-outcome relationships, observing that linearity assumptions were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for critical period regional mean dewpoint and maternal age, education, and race/ethnicity. In final models, we assessed multiplicative and additive effect modification. RESULTS:In adjusted models, conditional on mothers experiencing the highest observed EHD count (17), each 5 μg/m³ increase in average PM2.5 exposure was associated with increased odds of any septal defect (OR: 1.52 [95% CI: 1.04, 2.23]) and perimembranous ventricular septal defects (OR: 1.68 [95% CI: 1.02, 2.83]). Associations conditional on low/median maternal EHDs were null or inverse. Multiplicative and additive effect modification estimates were consistently positive when considering septal defects. CONCLUSIONS:Results suggest cumulative extreme temperature exposure during early pregnancy may modify associations between PM2.5 and some CHDs. Specifically, maternal extreme heat and PM2.5 exposure may jointly increase risk of offspring septal defects. Abstract does not represent EPA/CDC policy. KEYWORDS: particulate matter, temperature extremes, birth outcomes, cardiovascular diseases

27275 Atopic dermatitis treated safely with dupilumab during pregnancy: A case report and review of the literature

Dupilumab is currently the only biologic treatment approved for moderate-to-severe atopic dermatitis (AD). Though limited, available clinical data describing dupilumab use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. According to the position paper from the European Task Force on Atopic Dermatitis, systemic treatment in pregnant women with AD should be restricted to corticosteroids, cyclosporine and azathioprine.