HepB-CpG is a licensed adjuvanted two-dose hepatitis B vaccine for adults, with limited data on exposure during pregnancy. We assessed the risk of pregnancy outcomes among individuals who received HepB-CpG or the 3-dose HepB-alum vaccine ≤28 d prior to conception or during pregnancy at Kaiser Permanente Southern California (KPSC). The pregnancy cohort included KPSC members aged ≥18 y who received ≥1 dose of hepatitis B vaccine (HepB-CpG or HepB-alum) at KPSC outpatient family or internal medicine departments from August 2018 to November 2020. We followed these individuals through electronic health records from the vaccination date until the end of pregnancy, KPSC health plan disenrollment, or death, whichever came first. Among 81 and 125 eligible individuals who received HepB-CpG and HepB-alum, respectively, live births occurred in 84% and 74%, spontaneous abortion occurred in 7% and 17% (adjusted relative risk [aRR] 0.40, 95% CI: 0.16-1.00), and preterm birth occurred in 15% and 14% of liveborn infants (aRR 0.97, 95% CI 0.47-1.99). No major birth defects were identified through 6 months of age. The study found no evidence of adverse pregnancy outcomes for recipients of HepB-CpG in comparison to HepB-alum.

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.
RESULTS: 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.
CONCLUSIONS: 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.

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.

Maternal exposure to extreme ambient temperature during pregnancy has been proposed as a potential risk factor for birth defects. Comprehensive investigations on this association remain limited, particularly in low- and middle-income countries. This study aims to examine the association between ambient temperature exposure during pregnancy and the risk of birth defects in Brazil, contributing to the broader understanding of environmental influences on birth outcomes. Using a large dataset of over 11 million live birth records, we analyzed 12 categories of birth defects, encompassing a time frame from 2001 to 2018. Ambient temperature data were assigned at the municipality level. For the exposure assessment, we considered two biologically driven pregnancy stages by dividing the gestational period into two specific windows: the first trimester (from week 1 to week 12) and the second trimester (from week 13 to week 28). We employed a two-stage case-control design. In the first stage, we applied a conditional logistic regression model to estimate the odds ratio (OR) for specific birth defects and each of the five Brazilian regions (North, Northeast, Midwest, Southeast, and South). The model was adjusted for potential confounding variables, including PM2.5, relative humidity, and socioeconomic status. Temporal trends were addressed using time-stratified sampling. In the second stage, we used mixed-effects meta-analysis to pool region-specific estimates. Our analysis revealed a significant association between maternal exposure to higher ambient temperatures during the first trimester and an increased risk of specific birth defect categories, including those affecting the genital organs (OR = 1.08, 95% CI: 1.02; 1.14), digestive system (OR = 1.12, 95% CI: 1.06; 1.19); circulatory system (OR = 1.08, 95% CI: 1.01; 1.17); eyes, ears, face, and neck (OR = 1.08, 95% CI: 1.02; 1.15); benign neoplasms tumors (OR = 1.17, 95% CI: 1.03; 1.32), musculoskeletal system (OR = 1.03, 95% CI: 1.01; 1.05); and other congenital anomalies (OR = 1.22, 95% CI: 1.15; 1.29). The associations with respiratory system, nervous system, and chromosomal anomalies were null. These findings have significant implications for public health policies aimed at mitigating the impact of environmental factors on birth outcomes, both in Brazil and globally.

Birth defects are the leading cause of mortality in newborn babies and children under five years old. In response, the Chinese government has implemented a three-tiered prevention strategy, which has brought ethical concerns about fetuses with birth defects. This study aims to explore the attitudes toward fetuses with birth defects among health professionals engaged in maternal and child health services.
A qualitative study was conducted among 13 health professionals engaged in maternal and child health services in Hunan Province, China. The questions were designed to elicit the participants\' work experience and attitudes toward fetuses with birth defects. The data were collected through in-depth semi-structured interviews, and NVivo 12 was used for data coding and analysis. A thematic analysis approach was employed following the SRQR checklist.
Five themes and 13 attributes were generated regarding health professionals\' perspectives on fetuses with birth defects. The five themes included: (1) severity and curability of diseases (two attributes), (2) family relations (four attributes), (3) medical assessments (two attributes), (4) social situations (three attributes), (5) self-value orientations (three attributes). The findings showed that the majority of health professionals held the view that a fetus with a curable disease could be born, whereas a fetus with severe disability and teratogenesis should be terminated. Twelve out of the 13 health professionals believed that parents should be the decision-makers, while only one thought that the family should make a decision together.
Attitudes toward birth defects were influenced by various factors, indicating the complexity of real-world cases identified in this study. The findings highlight the dilemmas faced by both families and health professionals regarding birth defects. Adequate medical knowledge and support from society are crucial to inform decision-making among family members. Additionally, standardized norms and policies for birth defects are needed. Establishing an ethics committee for prenatal diagnosis is necessary to address current ethical issues in this field.

BACKGROUND: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants.
METHODS: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI.
RESULTS: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2).
CONCLUSIONS: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.

BACKGROUND: The worldwide incidence of preterm births is increasing, and the risks of adverse outcomes for preterm infants significantly increase with shorter gestation, resulting in a substantial socioeconomic burden. Limited epidemiological studies have been conducted in China regarding the incidence and spatiotemporal trends of preterm births. Seasonal variations in risk indicate the presence of possible modifiable factors. Gender influences the risk of preterm birth.
OBJECTIVE: This study aims to assess the incidence rates of preterm birth, very preterm birth, and extremely preterm birth; elucidate their spatiotemporal distribution; and investigate the risk factors associated with preterm birth.
METHODS: We obtained data from the Guangdong Provincial Maternal and Child Health Information System, spanning from January 1, 2014, to December 31, 2021, pertaining to neonates with gestational ages ranging from 24 weeks to 42 weeks. The primary outcome measures assessed variations in the rates of different preterm birth subtypes over the course of the study, such as by year, region, and season. Furthermore, we examined the relationship between preterm birth incidence and per capita gross domestic product (GDP), simultaneously analyzing the contributing risk factors.
RESULTS: The analysis incorporated data from 13,256,743 live births. We identified 754,268 preterm infants and 12,502,475 full-term infants. The incidences of preterm birth, very preterm birth, and extremely preterm birth were 5.69 per 100 births, 4.46 per 1000 births, and 4.83 per 10,000 births, respectively. The overall incidence of preterm birth increased from 5.12% in 2014 to 6.38% in 2021. The incidence of extremely preterm birth increased from 4.10 per 10,000 births in 2014 to 8.09 per 10,000 births in 2021. There was a positive correlation between the incidence of preterm infants and GDP per capita. In more developed economic regions, the incidence of preterm births was higher. Furthermore, adjusted odds ratios revealed that advanced maternal age, multiple pregnancies, and male infants were associated with an increased risk of preterm birth, whereas childbirth in the autumn season was associated with a protective effect against preterm birth.
CONCLUSIONS: The incidence of preterm birth in southern China exhibited an upward trend, closely linked to enhancements in the care capabilities for high-risk pregnant women and critically ill newborns. With the recent relaxation of China\'s 3-child policy, coupled with a temporary surge in advanced maternal age and multiple pregnancies, the risk of preterm birth has risen. Consequently, there is a pressing need to augment public health investments aimed at mitigating the risk factors associated with preterm birth, thereby alleviating the socioeconomic burden it imposes.

BACKGROUND: A birth population-based study was conducted in Danyang, Jiangsu Province, to evaluate major birth defects in emerging regions in China with similar maternal and neonatal care conditions.
METHODS: We conducted a population-based study in a cohort of infants born in Danyang from 2014 to 2021, including 55 709 perinatal infants. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHDs; n=2138), polydactyly (n=145), cleft lip with or without palate (CL/P; n=76) and accessory auricles (n=93). Infants with congenital malformations were identified by the Chinese Birth Defects Monitoring Network.
RESULTS: Compared with autumn, conception in spring (OR=1.31 [1.16-1.48]) and winter (OR=1.39 [1.23-1.58]) was associated with an increased risk of CHD. Increased risk of CHD, CL/P and accessory auricles was significantly associated with non-local registered residence (OR=1.17 [1.07-1.28], OR=2.73 [1.52-4.88] and OR=2.11 [1.20-3.71], respectively). Individuals of Han nationality were less likely to have polydactyly (OR=0.23 [0.05-0.98]).
CONCLUSIONS: The season of pregnancy was significantly associated with CHDs. Offspring of mothers with non-local registered hometown had greater risks of CHDs, CL/P and accessory auricles.

Human exposure to chromium (Cr) is common but little is known about its adverse effects on pregnancy outcomes. This study aimed to explore the association between Cr exposure and the risk of neural tube defects (NTDs) and the underlying mechanisms of Cr-induced NTDs. 593 controls and 408 NTD cases with placentas were included in this study. Chromium trichloride (Cr(III)) and potassium dichromate (Cr(VI)) were intragastrically administered to pregnant mice and the number of NTDs was recorded. The odds ratio for total NTDs in the highest exposure group in placenta was 4.18 (95% confidence interval (CI), 1.97-8.84). The incidence of fetal NTDs in mice administered with Cr(III) showed a dose-response relationship. Cr(VI) didn\'t show teratogenicity of NTDs whereas increased the stillbirth rate. Prenatal exposure to Cr(III) increased levels of oxidative stress and apoptosis in fetal mice. RNA-sequencing results indicated significant enrichment of the MAPK pathway. RT-qPCR and Western blot analysis revealed that Cr(III) induced increased expression of p-JNK, p-P38, and Casp3. Toxicological effects can be partly antagonized by antioxidant supplementation. High chromium exposure was associated with increased human NTD risks. Excessive Cr(III) exposure can induce NTDs in fetal mice by increasing apoptosis through upgrading oxidative stress and then activating JNK/P38 MAPK signaling pathway.

OBJECTIVE: Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele.
METHODS: NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997-2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results.
RESULTS: Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null.
CONCLUSIONS: We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations.