Perinatal outcomes with a copper intrauterine device in situ after 28 gestational weeks: A retrospective study of sole center in southeast China.

The purpose of this study was to investigate the pregnancy outcomes with a copper intrauterine device (IUD) in situ after 28 gestational weeks and the association between pregnancy with copper IUDs and neonatal congenital malformations. This retrospective study had compared the singleton pregnancies with the copper IUDs in situ and without after 28 gestational weeks in 1 delivery center of southeast China. The main exposure was a copper IUD in uterine cavity with pregnancy. The pregnant outcomes as preterm birth, premature rupture of membranes, infections were observed and compared. We had also compared neonatal congenital malformations in 2 groups. The statistical analysis was carried out using R (version 4.0.4; R Development Core Team) statistical software. Association between IUD use or duration of IUD use and adverse pregnancy outcomes were estimated using logistic model. Two-tailed P value < .05 was deemed statistically significant. A total of 148 pregnant women were included in our study, 74 with copper IUDs in situ were categorized into case group and 74 without IUDs during pregnancy into control group. No significant difference of maternal age, BMI, birth weight and gender were observed between 2 groups. In case group, the rates of preterm premature rupture of membranes (37.8%) and spontaneous preterm birth (23.0%) were significantly high compared to control group. Odds ratios of premature rupture of membranes and spontaneous preterm birth were 2.86 and 5.22 respectively. Women of elder age (≥35 years) in case group were more likely to experience premature rupture of membranes. The rates of neonatal congenital malformation were 10.8% (8/74) in case group and 1.4% (1/74) in control group respectively. We had found that pregnancy with copper IUD in situ increased the risk of premature rupture of membranes and spontaneous preterm birth after 28 gestation weeks, the risk of spontaneous preterm birth increased 5.22 times. Pregnancy with IUD in situ may be at increased risk of infection and neonatal malformation.

Birth defects and epidemiological factors in Tunisia.

AIM: To identify the birth defects listed in the embryo-fetopathology department of the maternity and neonatology center of Tunis (Tunisia), and to study the epidemiological factors. METHODS: We carried out a retrospective study on 2489 malformed cases including fetuses, stillborns and deceased newborns among 5750 ones autopsied in the embryo-fetopathology department of the maternity and neonatology center of Tunis. RESULTS: The sex ratio of autopsied cases was 1.06. 41% of them weighed less than 500 grams. The gestational age was between 22-28 weeks of amenorrhea in 41.3% of cases. Among the maternal characteristics, we noted an average maternal age of 30.1 years old (with extremes ranging from 16 to 51 years old), and a predominance of O blood group. Parental consanguinity and history of reproductive failure were found respectively in 37.4% and 32.5% of cases. Antenatal diagnosis was established in 62% of cases. It was positive in 59.5% of cases (all types of malformations combined). Among the 2489 malformed cases, 4568 birth defects were identified. Neurological anomalies were the most common (26.01%) followed by nephro-urological anomalies (13.16%) and cardiovascular anomalies (11.47%). During the study period, 164 cases of polymalformative syndromes were counted and 217 cases of chromosomal aberrations were classified. CONCLUSION: This study allowed us to assess the frequency of birth defects, categorize them based on their type and determine the different epidemiological factors during a long period of nine years, even though our nation does not have a national register of birth defects. In Tunisia, it is important to carry out a national multicenter study in order to set a national register representing the real statistics of these anomalies.

A Comparison of Active and Passive Surveillance Strategies for Selected Birth Defects in New York.

BACKGROUND: The New York State Birth Defects Registry (BDR) has passive and active components. As part of statewide passive ascertainment, the BDR receives reports of International Classification of Diseases, Tenth Revision (ICD-10) codes and descriptive narratives on a wide range of birth defects. The BDR conducts enhanced active surveillance for selected birth defects in 14 counties, which includes medical record abstraction and clinician review. We sought to quantify agreement between the two surveillance approaches. METHODS: The analysis included live-born infants born with one of the 16 birth defects in 2018-2021 in the active surveillance counties (n = 1069 infants). We calculated positive predictive values (PPV) and 95% confidence intervals for each defect, defined as the percentage of cases confirmed in active surveillance among those in passive surveillance. Additionally, we calculated the percentage with each birth defect missed by passive surveillance. RESULTS: The PPV varied greatly by birth defect. The PPV was >90% for gastroschisis and cleft lip, but <70% for spina bifida, diaphragmatic hernia, truncus arteriosus, tricuspid atresia, hypoplastic left heart syndrome, coarctation of the aorta, and pulmonary atresia. The percentage missed by passive surveillance ranged from 2% for tetralogy of Fallot to 39% for tricuspid atresia. CONCLUSIONS: Active surveillance is an important strategy for ruling out false positive case reports for certain birth defects that we assessed, but not all of them. Passive surveillance programs can use our findings to develop targeted strategies for improving data quality of specific birth defects using active surveillance methods, thus optimizing limited resources.

Enhancing the Classification of Congenital Heart Defects for Outcome Association Studies in Birth Defects Registries.

INTRODUCTION: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion-specific classification system for birth defect registry-based outcome studies. METHODS: For Core Cardiac Lesion Outcome Classifications (C-CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control-modified British Pediatric Association (BPA) codes were defined for each C-CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C-CLOC groups, Texas Birth Defect Registry data (1999-2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C-CLOC classification approaches. RESULTS: C-CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C-CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co-occurring CHD). As expected, C-CLOC groups had retained larger sample sizes (i.e., representing presumably better-powered analytic groups) compared to cases with only one CHD code and no occurring CHDs. DISCUSSION: This new CHD classification system for investigators using birth defect registry data, C-CLOC, is expected to balance clinical outcome homogeneity in analytic groups while maintaining sufficiently large case counts within categories, thus improving power for CHD-specific outcome association comparisons. Future outcome studies utilizing C-CLOC-based classifications are planned.

Fetal major anomalies and related maternal, obstetrical, and neonatal outcomes.

PURPOSE: To examine maternal, obstetrical, and neonatal outcomes of pregnancies complicated by major fetal anomalies. METHODS: A 10 year retrospective cohort study at a tertiary university hospital compared maternal and obstetrical outcomes between women with singleton pregnancies complicated by major fetal anomalies, and a control group with non-anomalous fetuses. RESULTS: For the study compared to the control group, the median gestational age at delivery was lower: 37.0 vs. 39.4 weeks (p < 0.001); and the preterm delivery rates were higher, both at < 37 weeks (46.2 vs. 6.2%, p < 0.001) and < 32 weeks (15.4 vs. 1.2%, p < 0.001). For the study compared to the control group, the placental abruption rate was higher (6.8 vs. 0.9%, p = 0.002); 87.5 vs. 100% occurred before labor. For the respective groups, the mean gestational ages at abruption were 32.8 ± 1.3 and 39.9 ± 1.7 weeks (p = 0.024); and cesarean section and postpartum hemorrhage rates were: 53.8 vs. 28.3% (p < 0.001) and 11.3 vs. 2.8% (p = 0.001), respectively. For the respective groups, hypertensive disorders of pregnancy rates were 9.5 vs. 2.1% (p = 0.004), stillbirth rates were 17.1 vs. 0.3% (p < 0.001), and neonatal death rates 12.5 vs. 0.0% (p < 0.001). Major fetal anomalies were found to be associated with adverse maternal outcomes (OR = 2.47, 95% CI 1.50-4.09, p < 0.001). Polyhydramnios was identified as an independent risk factor in a multivariate analysis that adjusted for fetal anomalies, conception by IVF, and primiparity for adverse maternal outcomes (OR = 4.7, 95% CI 1.7-13.6, p < 0.001). CONCLUSIONS: Pregnancies with major fetal anomalies should be treated as high-risk due to the increased likelihood of adverse maternal and neonatal outcomes.

Association of the national level of human development with the incidence and mortality of congenital birth defects in 2019: A cross-sectional study from 189 countries.

Congenital birth defects (CBD) play a significant role in causing child mortality globally. The incidence and mortality of CBD vary widely across countries, and the underlying causes for this divergence remain incompletely comprehended. We conducted an analysis to investigate the relationship between the incidence and mortality of CBD in 189 countries and their Human Development Index (HDI). In this study, CBD data from 189 countries was used from the Global Burden of Diseases Study (GBD) 2019, and HDI data was collected for the same countries. Later, the relationship between CBD and HDI was analyzed, and the impact of gross national income (GNI) per capita, expected years of schooling, mean years of schooling and life expectancy at birth was quantified using principal component regression. The age-standardized incidence rate (ASIR) varied between 66.57 to 202.24 per 100,000, with a 95% uncertainty interval (UI) of 57.20-77.51 and 165.87-241.48 respectively. The age-standardized mortality rate (ASMR) also showed a rang from 1.38 to 26.53 (14.03-39.90) per 100,000, with the 95%UI of 0.91-2.09 and 14.03-39.90 respectively. Both the incidence and mortality rates of CBD decreased with the increased HDI (incidence: r = -0.38, p < 0.001, mortality: r = -0.77, p < 0.001). Our investigation revealed significant variations in the incidence and mortality of CBD among countries with different development levels. In conclusion, the global incidence and mortality of CBD vary significantly among countries, possibly due to differences in the accessibility of health services.

Lead brownfields and birth defects in North Carolina 2003-2015: A cross-sectional case-control study.

BACKGROUND: Brownfields consist of abandoned and disused sites, spanning many former purposes. Brownfields represent a heterogenous yet ubiquitous exposure for many Americans, which may contain hazardous wastes and represent urban blight. Neonates and pregnant individuals are often sensitive to subtle environmental exposures. We evaluate if residential exposure to lead (Pb) brownfields is associated with birth defects. METHODS: Using North Carolina birth records from 2003 to 2015, we sampled 169,499 births within 10 km of a Pb brownfield with 3255 cardiovascular, central nervous, or external defects identified. Exposure was classified by binary specification of residing within 3 km of a Pb brownfield. We utilized multivariable logistic regression models adjusted for demographic covariates available from birth records and 2010 Census to estimate odds ratios (OR) and 95% confidence intervals (CI). Effect measure modification was assessed by inclusion of interaction terms and stratification for the potential modifiers of race/ethnicity and diabetes status. RESULTS: We observed positive associations between cardiovascular birth defects and residential proximity to Pb brownfields, OR (95%CI): 1.15 (1.04, 1.26), with suggestive positive associations for central nervous 1.16 (0.91, 1.47) and external defects 1.19 (0.88, 1.59). We did observe evidence of effect measure modification via likelihood ratio tests (LRT) for race/ethnicity for central nervous and external defect groups (LRT p values 0.08 and 0.02). We did observe modification by diabetes status for the cardiovascular group (LRT p value 0.08). CONCLUSIONS: Our results from this analysis indicate that residential proximity to Pb brownfields is associated with cardiovascular birth defects with suggestive associations for central nervous and external defects. In-depth analyses of individual defects and other contaminants or brownfield site functions may reveal additional novel associations.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

BACKGROUND: Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. METHODS: We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. RESULTS: Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. CONCLUSIONS: A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

Climate Change and Congenital Anomalies: A Population-Based Study of the Effect of Prolonged Extreme Heat Exposure on the Risk of Neural Tube Defects in France.

BACKGROUND: Exposure to long-lasting extreme ambient temperatures in the periconceptional or early pregnancy period might increase the risk of neural tube defects (NTDs). We tested whether prolonged severe heat exposure as experienced during the 2003 extreme heatwave in France, affected the risk of NTDs. METHODS: We retrieved NTD cases spanning from January 1994 to December 2018 from the Paris Registry of Congenital Malformations. The 2003 heatwave was characterized by the long duration and high intensity of nine consecutive days with temperatures ≥35°C. We classified monthly conceptions occurring in August 2003 as "exposed" to prolonged extreme heat around conception (i.e., periconceptional period). We assessed whether the risk of NTDs among cohorts exposed to the prolonged severe heatwave of 2003 in the periconceptional period differed from expected values using Poisson/negative binomial regression. FINDINGS: We identified 1272 NTD cases from January 1994 to December 2018, yielding a monthly mean count of 4.24. Ten NTD cases occurred among births conceived in August 2003. The risk of NTD was increased in the cohort with periconceptional exposure to the August 2003 heatwave (relative risk = 2.14, 95% confidence interval: 1.46 to 3.13), compared to non-exposed cohorts. Sensitivity analyses excluding July and September months or restricting to summer months yielded consistent findings. INTERPRETATION: Evidence from the "natural experiment" of an extreme climate event suggests an elevated risk of NTDs following exposure to prolonged extreme heat during the periconceptional period.

Exploring potential causal links between air pollutants and congenital malformations: A two-sample Mendelian Randomization study.

Observational studies have suggested an association between air pollutants and congenital malformations; however, conclusions are inconsistent and the causal associations have not been elucidated. In this study, based on publicly available genetic data, a two-sample Mendelian randomization (MR) was applied to explore the associations between particulate matter 2.5 (PM2.5), NOX, NO2 levels and 11 congenital malformations. Inverse variance weighted (IVW), MR-Egger and weighted median were used as analytical methods, with IVW being the main method. A series of sensitivity analyses were used to verify the robustness of the results. For significant associations, multivariable MR (MVMR) was utilized to explore possible mediating effects. The IVW results showed that PM2.5 was associated with congenital malformations of digestive system (OR = 7.72, 95 %CI = 2.33-25.54, P = 8.11E-4) and multiple systems (OR = 8.63, 95 %CI = 1.02-73.43, P = 0.048) risks; NOX was associated with circulatory system (OR = 4.65, 95 %CI = 1.15-18.86, P = 0.031) and cardiac septal defects (OR = 14.09, 95 %CI = 1.62-122.59, P = 0.017) risks; NO2 was correlated with digestive system (OR = 27.12, 95 %CI = 1.81-407.07, P = 0.017) and cardiac septal defects (OR = 22.57, 95 %CI = 2.50-203.45, P = 0.005) risks. Further MVMR analyses suggest that there may be interactions in the effects of these air pollutants on congenital malformations. In conclusion, this study demonstrated a causal association between air pollution and congenital malformations from a genetic perspective.

Moderate altitude as a risk factor for isolated congenital malformations. Results from a case-control multicenter-multiregional study.

BACKGROUND: Living in high-altitude regions has been associated with a higher prevalence of some birth defects. Moderate altitudes (1500-2500 m) have been associated with some congenital heart diseases and low birth weight. However, no studies have been conducted for other isolated congenital malformations. OBJECTIVES: To estimate the prevalence at birth of isolated congenital malformations in low and moderate altitudes and to determine if moderate altitudes are a risk factor, such as high altitudes, for isolated congenital malformations adjusted for other factors. METHODS: The study consisted of a case-control multicenter-multiregional study of 13 isolated congenital malformations. Cases included live births with isolated congenital malformations and controls at low (10-1433 m) and moderate altitudes (1511-2426 m) from a Mexican registry from January 1978 to December 2019. Prevalence per 10,000 (95% CI) per altitude group was estimated. We performed unadjusted and adjusted logistic regression models (adjusted for maternal age, parity, malformed relatives, socioeconomic level, and maternal diabetes) for each isolated congenital malformation. RESULTS: Hydrocephaly and microtia had a higher at-birth prevalence, and spina bifida, preauricular tag, and gastroschisis showed a lower at-birth prevalence in moderate altitudes. Moderate altitudes were a risk factor for hydrocephaly (aOR 1.39), microtia (aOR 1.60), cleft-lip-palate (aOR 1.27), and polydactyly (aOR 1.32) and a protective effect for spina bifida (aOR 0.87) compared with low altitudes. CONCLUSIONS: Our findings provide evidence that moderate altitudes as higher altitudes are an associated risk or protective factor to some isolated congenital malformations, suggesting a possible gradient effect.

Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study.

OBJECTIVES: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. DESIGN: Prospective Nordic registry based study. SETTING: Sweden, Denmark, and Norway. PARTICIPANTS: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. MAIN OUTCOME MEASURE: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. RESULTS: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. CONCLUSIONS: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.

Newborn screening analytes and structural birth defects among 27,000 newborns.

BACKGROUND: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects. METHODS: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis. FINDINGS: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes). CONCLUSIONS: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects.

Fetal deaths from birth defects in Hunan Province, China, 2016-2020.

To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016-2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13-51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of < 20 weeks, 59.05% (7059 cases) were at a gestational age of 20-27 weeks, and 25.17% (3009 cases) were at a gestational age of ≥ 28 weeks. Fetal death rate of birth defects was higher in females than in males (OR = 1.25, 95% CI 1.18-1.32), in rural than in urban areas (OR = 1.43, 95% CI 1.36-1.50), in maternal age 20-24 years (OR = 1.35, 95% CI 1.25-1.47), and ≥ 35 years (OR = 1.19, 95% CI 1.11-1.29) compared to maternal age of 25-29 years, in diagnosed by chromosomal analysis than ultrasound (OR = 6.24, 95% CI 5.15-7.55), and lower in multiple births than in singletons (OR = 0.41, 95% CI 0.36-0.47). The fetal death rate of birth defects increased with the number of previous pregnancies (χ2trend = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ2trend = 4318.91, P < 0.01). Many fetal deaths were associated with birth defects. We found several demographic characteristics associated with fetal deaths from birth defects, which may be related to the severity of the birth defects, economic and medical conditions, and parental attitudes toward birth defects.

Birth defects in a rural province in Papua New Guinea.

BACKGROUND: Globally, birth defects are the fourth most common cause of neonatal mortality. They cause substantial morbidity, and often long-term disability. Despite this, the impact of birth defects on public health has received little attention in low- and middle-income countries. AIMS: To report the types, incidence and geographic distribution of birth defects in the East New Britain Province of Papua New Guinea. METHODS: Data were collected over 3 years on newborns with birth defects seen at Rabaul Hospital, born anywhere in the province. Each affected newborn was examined, the anomaly diagnosed and classified. The exact home location was recorded to understand geospatial distribution. To calculate incidence, data were collected on all newborns with a congenital anomaly in a cohort of 2000 consecutive live births at Rabaul Hospital in 2019. RESULTS: Over 3 years, 2018-2020, 137 newborns with birth defects were identified, born in any part of the province. Congenital heart defects, hydrocephalus, microcephaly, craniofacial anomalies, imperforate anus, trachea-oesophageal fistula and diaphragmatic hernia were the most common anomalies. Eight cases of Down syndrome and other chromosomal anomalies were identified. The incidence in 2019 was 14 per 1000 live births. Geographic mapping showed the highest number of cases in the region on the Gazelle Peninsula, the area around the active volcanos. CONCLUSIONS: This study provides insights into the incidence and types of birth defects in a rural island province and showed it was possible to map geospatial distribution to further explore epidemiology.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Birth defects among offspring of California firefighters, 2007-2019.

PURPOSE: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. METHODS: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. RESULTS: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. CONCLUSIONS: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: a meta-analysis of cohort studies.

PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.

Trend of Mortality Due to Congenital Anomalies in Children Younger Than 5 Years in Eastern China, 2012-2021: Surveillance Data Analysis.

BACKGROUND: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. OBJECTIVE: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. METHODS: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. RESULTS: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90). CONCLUSIONS: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances.