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.

Birth defects are a leading cause of infant mortality in the United States, but little is known about causes of many types of birth defects. Spatiotemporal disease mapping to identify high-prevalence areas, is a potential strategy to narrow the search for potential environmental and other causes that aggregate over space and time. We described the spatial and temporal trends of the prevalence of birth defects in North Carolina during 2003-2015, using data on live births obtained from the North Carolina Birth Defects Monitoring Program. By employing a Bayesian space-time Poisson model, we estimated spatial and temporal trends of non-chromosomal and chromosomal birth defects. During 2003-2015, 52,524 (3.3%) of 1,598,807 live births had at least one recorded birth defect. The prevalence of non-chromosomal birth defects decreased from 3.8% in 2003 to 2.9% in 2015. Spatial modeling suggested a large geographic variation in non-chromosomal birth defects at census-tract level, with the highest prevalence in southeastern North Carolina. The strong spatial heterogeneity revealed in this work allowed to identify geographic areas with higher prevalence of non-chromosomal birth defects in North Carolina. This variation will help inform future research focused on epidemiologic studies of birth defects to identify etiologic factors.

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.

Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission. As active members of this task force, we urge all healthcare providers who care for pregnant individuals to prioritize reporting all ARV exposures to the registry.

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

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.

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.

The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling.

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.