Prevalence, characteristics and risk factors of birth defects in central China livebirths, 2015-2022.

Objective: This study analyzed the prevalence, epidemiological characteristics and risk factors of birth defects among livebirths in central China, aiming to provide evidences for the prevention of birth defects and government Decision-makings. Methods: Birth data from China's Hubei Province between 2015 and 2022 were collected, including basic information of the livebirths, the mothers and the fathers, as well as information about delivery and each prenatal examination. The livebirths prevalence of birth defects was calculated and the trends were mapped. The basic characteristics of birth defects were evaluated by the difference analysis between case and health groups. Univariate and multivariate Poisson regression was performed to examine the independent risk factors for birth defects. Results: Among 43,568 livebirths, 166 livebirths were born with birth defects, resulted in a total prevalence rate of 3.81 per 1,000 livebirths, showing a remarkable uptrend from 0.41per 1,000 livebirths in 2015 to 9.23 per 1,000 livebirths in 2022. The peak of the prevalence was in January and February. Congenital malformation of the musculoskeletal system was the main type of birth defect in central China livebirths, followed by cleft lip and cleft palate. Overall, newborns with birth defect had significantly earlier delivery gestational age, poorer health and higher proportion of infants with low birth weight than healthy births. The gender of livebirths, excess weight at delivery (≥80 kg) of mothers, more than 2 times of gravidity or parity of mothers, and advanced paternal age (≥40 years) were independent risk factors for birth defects (or specific birth defects). Conclusion: The livebirths prevalence of birth defects shows increasing trend in central China, which deserves the attention of the government and would-be parents. Elevated paternal age, excess maternal weight, gravidity and parity should be considered when planning their families.

Burden of neural tube defects in India: a systematic review and meta-analysis.

BACKGROUND: One of the most common and serious congenital defects is neural tube defect (NTD) in India. The data about the NTDs in India is lacking. The objective of this meta-analysis is to provide an estimate of NTDs in India with regional variations. METHOD: This study was conducted by doing a literature search using PubMed (Medline) and Embase databases for studies published from their inception to 1 October 2023 by using relevant keywords. We have prepared our study protocol by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and our study is registered in PROSPERO. Pooled prevalence was calculated by using the Der Simonian-Liard method and random effect model to find out the burden of NTD in India. Additionally, subgroup and sensitivity analyses were also performed. NHLBI (National Heart, Lung, and Blood Institute) tool was used for assessing the study quality. RESULTS: A total of 1129 articles were identified by using the predefined keywords in which 27 articles were selected which were fitting the selection criteria defined in our study. The prevalence of NTDs in our meta-analysis was found to be 9.46 per 1000 births with a 95% confidence interval of 8.01 to 10.91 per 1000 births with significant heterogeneity with I2 of 99.15%. CONCLUSION: Our study highlights the increasing trend of NTDs over the past decades, with significant regional variation in India. There is an urgent need for comprehensive prevention strategies such as advocacy and awareness, antenatal screening for NTDs, folic acid supplementation, and food fortification. Future research is required for identification and implementation for a target-based approach for region specific.

Congenital Anomalies of the Gastrointestinal Tract in Conjunction of Congenital Heart Diseases in Infants With Trisomy 21.

BACKGROUND: Infants with Trisomy 21 are known to have increased incidence congenital anomalies including congenital heart diseases (CHD) and congenital gastrointestinal anomalies. It is not known if there are patterns of coexistence. OBJECTIVES: To examine the coexistence of CHD with various gastrointestinal anomalies in infants with Trisomy 21. METHODS: We assessed a sample of infants with Trisomy 21 from the National Inpatient Sample (NIS), and its KID subversion, produced by the Healthcare Cost and Utilization Project for 2003-2015. We identified CHD using international classification of diseases version 9 (ICD9) and categorized them into four groups: left sided lesions, right sided lesions, conotruncal lesions, and shunt lesions. We identified small intestinal atresia and Hirschsprung disease with ICD9 codes. RESULTS: The sample included 81,561 newborn infants diagnosed with Trisomy 21; 45% of them had CHD; 4.7% had small intestinal atresia, and 1.6% had Hirschsprung disease. All subcategories of CHD were associated with increased incidence of both small intestinal atresia and Hirschsprung disease, p value < 0.05 compared to infants with Trisomy 21 who did not have CHD. CONCLUSIONS: Among infants with Trisomy 21, the presence of CHD increased the odds of a concomitant congenital GI anomaly.

[Declining Rate of Neural Tube Defects and Outcomes of Defective Infants in Shaanxi Province from 2003 to 2022].

Objective To evaluate the changes in the incidence of neural tube defects (NTDs) in Shaanxi province from 2003 to 2022,investigate the diagnosis time and outcomes of defective infants,and predict the incidence of NTDs in Shaanxi province from 2023 to 2025,thereby providing a basis for improving the birth defects surveillance system. Methods Data were collected from all the perinatal infants from 28 weeks of gestation to 7 days after birth in all the hospitals with obstetrical department in Shaanxi province during 2003-2022.The changes in the incidence of NTDs from 2003 to 2022 were analyzed based on the birth defects surveillance system. Results A total of 1 106 483 perinatal infants in Shaanxi province from 2003 to 2022 were surveyed,among which NTDs occurred in 848 perinatal infants,with an incidence of 7.66/10 000.The incidence was the highest (48.02/10 000) in 2005 and the lowest (0.57/10 000) in 2022.The NTDs in Shaanxi province were mainly spina bifida (55.90%),which was followed by anencephaly (25.71%) and encephalocele (18.40%).The incidences of the three declined with fluctuations (P<0.001).The results of the Joinpoint analysis showed that the incidence of NTDs decreased slowly with the annual percentage change of -4.04 from 2003 to 2014 and declined rapidly with the annual percentage change of -28.05 from 2014 to 2022.From 2003 to 2022,the average proportion of prenatal diagnosis of NTDs in Shaanxi province was 72.88%.Dead fetus (61.91%) was the main birth outcome,followed by live birth (26.77%),stillbirth (8.73%),and death within seven days after birth (2.59%).The incidence of NTDs in Shaanxi province from 2023 to 2025 were predicted by the GM (1,1) model as 0.49/10 000,0.41/10 000,and 0.35/10 000,respectively. Conclusion The incidence of NTDs in Shaanxi province declined significantly during 2003-2022,especially in a rapid manner after 2014.Dead fetus was the primary outcome of perinatal infants with NTDs,followed by live birth.

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.

Evaluating neonatal mortality in Malta compared with other EU countries: Exploring the influence of congenital anomalies and maternal risk factors.

BACKGROUND: Globally, 240,000 babies die in the neonatal period annually due to congenital anomalies (CA). Malta reports the highest neonatal mortality rate (NMR) among EU (European Union) Countries, constituting a public health concern. OBJECTIVES: This study describes the contribution of CA to NMR in Malta, investigating possible associations with known maternal risk factors of maternal age, nationality, and education. Additionally, it provides an update on the contribution of CA to neonatal deaths in Malta and other EU countries. METHODS: Anonymous data for births and neonatal deaths were obtained for 2006-2020 from the National Obstetrics Information System (NOIS) in Malta. Regression analyses adjusting for maternal risk factors were run on this data to explore possible associations with NMR. NMRs published by EUROSTAT 2011-2020 were used to compare mortality by underlying cause of death (CA or non-CA causes) for Malta and other EU countries. RESULTS: Between 2006 and 2020, 63,890 live births with 283 neonatal deaths were registered in Malta, (NMR 4.4 per 1000 live births). CA accounted for 39.6% of neonatal deaths. No time trends were observed in either total NMR, NMR attributed to CA or mortality due to non-CA causes. Adjusted variables revealed associations for women hailing from non-EU, low-income countries. Malta registered high NMRs compared to EU countries, most marked for deaths attributed to CA. CONCLUSIONS: Between 2006 and 2020, Malta's NMR remained stable. Maternal Nationality, from non-EU low-income countries, was associated with higher neonatal mortality. The influx of such migrants may play a partial role in the high NMRs experienced. Malta's high NMR was primarily driven by early neonatal deaths, which included high proportions of deaths due to CA and is linked to the fact that termination of pregnancy is illegal in Malta.

Post-marketing safety study to evaluate pregnancy outcomes among recipients of hepatitis B vaccines.

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.

Loss-of-Function Variant in PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome: Expanded Phenotype of Sex Reversal.

Differences of sex development (DSDs) are a heterogeneous group of congenital conditions in which chromosomal, gonadal, or anatomical sex does not match. The broad spectrum of phenotypes associated with DSDs requires accurate diagnosis, which influences the care and quality of life of affected patients. The decreasing costs of next-generation sequencing (NGS) and international research collaborations in rare diseases have allowed the identification of new genes associated with DSDs. Recently, Hughes et al. in 2020 reported the association of loss-of-function (LoF) variants in PPP1R12A with morphological anomalies of the midline, including holoprosencephaly and urogenital malformations, also known as genitourinary and/or brain malformation syndrome (OMIM #618820). In this report, we describe a Mexican individual with hypertelorism, multiple skin hemangiomas, testicular atrophy, and sex reversal, in whom a c.1880delC frameshift variant in PPP1R12A was detected by exome sequencing. Segregation analysis confirmed it as a de novo variant through Sanger sequencing. The main objective of this report is to expand PPP1R12A-related urogenital and/or brain malformation syndrome.

Survival of Children With Critical Congenital Heart Defects in the National Birth Defects Prevention Study.

BACKGROUND: Critical congenital heart defects (CCHDs) are associated with considerable morbidity and mortality. This study estimated survival of children with nonsyndromic CCHDs and evaluated relationships between exposures of interest and survival by CCHD severity (univentricular or biventricular function). METHODS: This analysis included 4380 infants with CCHDs (cases) born during 1999-2011 and enrolled in the National Birth Defects Prevention Study, a multisite, population-based case-control study of major birth defects. Cases were linked to state death files. Nonparametric Kaplan-Meier survival functions were used to estimate 1- and 5-year survival probabilities overall and by severity group (univentricular/biventricular) stratified by demographic and clinical exposure variables of interest. The log-rank test was used to determine whether stratified survival curves were equivalent. Survival and 95% confidence intervals (CIs) were also estimated using Cox proportional hazards modeling adjusted for maternal age, education, race/ethnicity, study site, and birth year. RESULTS: One- and five-year survival rates were 85.8% (CI 84.7-86.8) and 83.7% (CI 82.5-84.9), respectively. Univentricular 5-year survival was lower than biventricular case survival [65.3% (CI 61.7-68.5) vs. 89.0% (CI 87.8-90.1; p < 0.001)]. Clinical factors (e.g. preterm birth, low birthweight, and complex/multiple defects) were associated with lower survival in each severity group. Sociodemographic factors (non-Hispanic Black race/ethnicity,

Factors related to the occurrence of fetal birth defects and the construction of a Nomogram model.

Objective: To explore the influencing factors of fetal birth defects (BD) and construct a nomogram model. Methods: A total of 341 newborns admitted to Meizhou people's hospital from September 2021 to September 2023 were randomly grouped into a modeling group (239 cases) and a validation group (102 cases). The modeling group fetuses were separated into BD and non-BD groups. Multivariate logistic regression analyzed risk factors for BD; R software constructed a nomogram model; Receiver operating characteristic (ROC) curve evaluated the model's discrimination for BD. Results: The top 5 types of BD were congenital heart disease, polydactyly/syndactyly, cleft lip/palate, ear malformation, and foot malformation, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively. BD incidence was 26.36% (63/239). Significant differences between BD and non-BD groups were found in maternal age, gestational age, history of adverse pregnancy/childbirth, gestational hypertension, adverse emotions during pregnancy, and folic acid intake duration (P<0.05). Logistic regression showed maternal age (OR: 4.125), gestational age (OR: 3.066), adverse pregnancy history (OR: 10.628), gestational hypertension (OR: 5.658), adverse emotions (OR: 5.467), and folic acid intake duration (OR: 4.586) were risk factors for BD (P<0.05). The modeling group's ROC AUC was 0.938, calibration curve slope close to 1, H-L test =8.342, P=0.692; external validation AUC was 0.961, calibration slope close to 1, H-L test =7.634, P=0.635. Conclusion: Identified risk factors include maternal age, gestational age, adverse pregnancy history, gestational hypertension, adverse emotions, and folic acid intake duration. The nomogram model shows good discrimination and consistency for evaluating neonatal BD risk.

A Capacity Audit of Medical Geneticists and Genetic Counsellors in South Africa, 2024: A National Crisis.

Community genetic services were introduced in South Africa almost seven decades ago, with medical geneticists and genetic counsellors being formally recognized for the past 30 years. Initial training platforms were established at academic centres countrywide, and posts for relevant healthcare professionals, including medical geneticists and genetic counsellors were created in the public sector. Despite these early advances, the number of these specialists required to address the rising burden of congenital disorders in the country remains far below required targets established by the National Department of Health. The aim of this study was to analyse the retrospective, current and projected number of medical geneticists and genetic counsellors in South Africa. The results indicate the number of practicing medical geneticists (n = 13) and genetic counsellors (n = 28) are currently at 10% and 5% of capacity targets, respectively. There is unequal distribution of these specialists between the public and private healthcare sectors, and geographical maldistribution. An alarming trend of emigration is particularly prevalent among newly qualified genetic counsellors. With the proportion of congenital disorders expected to continue to rise in coming years, together with the increasing proportion of ageing South Africans, it is imperative that health workforce planning addresses the ever-widening gap between the supply, demand and unmet need for these crucial specialists in South Africa.

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.

Association between Congenital Anomalies and Late-Onset Bacterial Infections in Neonates Admitted to Neonatal Intensive Care Units in Australia and New Zealand: A Population-Based Cohort Study.

INTRODUCTION: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. METHODS: Utilising the population-based Australian and New Zealand Neonatal Network data from 2007 to 2017, bacterial LOS rates were determined in very preterm (VPT, <32 week), moderately preterm (MPT, 32-36 weeks), and term (FT, 37-41 weeks) neonates with or without CA. Stratified by major surgery, the association between CA and bacterial LOS was evaluated. RESULTS: Of 102,808 neonates, 37.7%, 32.8%, and 29.6% were born VPT, MPT, and FT, respectively. Among these, 3.4% VPT, 7.5% MPT, and 16.2% FT neonates had CA. VPT neonates had the highest LOS rate (11.1%), compared to MPT (1.8%) and FT (1.8%) neonates. LOS rates were higher in CA neonates than those without (8.2% versus 5.1% adjusted relative risk [aRR] 1.67, 95% confidence interval [CI]: 1.45-1.92). Neonates with surgery had a higher LOS rate (14.2%) than neonates without surgery (4.4%, p < 0.001). Among the neonates without surgery, CA neonates had consistently higher LOS rates than those without CA (VPT 14.3% vs. 9.6% [aRR 1.32, 95% CI: 1.11-1.57]; MPT 4% vs. 0.9% [aRR 4.45, 95% CI: 3.23-6.14]; and FT 2% vs. 0.7% [aRR 2.87, 95% CI: 1.97-4.18]). For the neonates with surgery, CAs were not associated with additional LOS risks. CONCLUSION: Overall, we reported higher rates of LOS in neonates with CA compared to those without CA. Regardless of gestation, CA was associated with an increased LOS risk among non-surgical neonates. Optimisation of infection prevention strategies for CA neonates should be explored. Future studies are needed to evaluate if the infection risk is caused by CA or associated complications.

Exploring the psychological problems of mothers having the experience of death of children with untreatable genetic disorders: A qualitative study.

BACKGROUND: A newborn with an untreatable genetic disorder could disrupt a family and affect parents' mental health, psycho-social interaction, and parent-child relationships. This study was conducted to explore the psychological problems of mothers having the children with untreatable genetic disorders. MATERIALS AND METHODS: This qualitative study was performed using the conventional content analysis method on 15 mothers having the children with untreatable genetic disorders selected by purposeful sampling. In-depth and semi-structured interviews were used to collect data. The recorded interviews were transcribed verbatim immediately and imported into MAXQDA10 software. Lundman and Granheim's content analysis method and Guba and Lincoln's proposed criteria for assessing rigor of the results were used. RESULTS: Overall, 1067 primary codes were extracted from the interviews and after the integration of similarities grouped into 19 sub-categories and three major categories including psychological reactions before diagnosis, after determined diagnosis, and after the child's death. CONCLUSIONS: The results showed that having the child with untreatable genetic disorder is considered as a notable psychological trauma and causes painful psychological reactions in parents. In this regard, the following approaches are recommended to health professionals: continuous monitoring of mental health of these families, developing a family education program, emotional and psychological support, and genetic counseling.

Safety of Antiretroviral Exposure During Pregnancy: Opportunities to Close Data Gaps.

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.

Spatiotemporal Trends of Birth Defects in North Carolina, 2003-2015.

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.

Embryonic Lethal Phenotyping to Identify Candidate Genes Related with Birth Defects.

Congenital birth defects contribute significantly to preterm birth, stillbirth, perinatal death, infant mortality, and adult disability. As a first step to exploring the mechanisms underlying this major clinical challenge, we analyzed the embryonic phenotypes of lethal strains generated by random mutagenesis. In this study, we report the gross embryonic and perinatal phenotypes of 55 lethal strains randomly picked from a collection of mutants that carry piggyBac (PB) transposon inserts. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested most of the analyzed mutations hit genes involved in heart and nervous development, or in Notch and Wnt signaling. Among them, 12 loci are known to be associated with human diseases. We confirmed 53 strains as embryonic or perinatal lethal, while others were subviable. Gross morphological phenotypes such as body size abnormality (29/55, 52.73%), growth or developmental delay (35/55, 63.64%), brain defects (9/55, 16.36%), vascular/heart development (31/55, 56.36%), and other structural defects (9/55, 16.36%) could be easily observed in the mutants, while three strains showed phenotypes similar to those of human patients. Furthermore, we detected body weight or body composition alterations in the heterozygotes of eight strains. One of them was the TGF-ß signaling gene Smad2. The heterozygotes showed increased energy expenditure and a lower fat-to-body weight ratio compared to wild-type mice. This study provided new insights into mammalian embryonic development and will help understand the pathology of congenital birth defects in humans. In addition, it expanded our understanding of the etiology of obesity.

Maternal exposure to ambient temperature and birth defects in Brazil: a nationwide case-control study of over 11 million newborns.

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.

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.

Orofacial clefts in Costa Rica, 1996-2021: Analysis of surveillance data.

BACKGROUND: Orofacial clefts (OFCs) are among the most common birth defects (BD). In 2008, a series of improvements began in the Costa Rican Birth Defect Register Center (CREC). We aim to explore trends between 1996 and 2021. METHODS: A trend analysis of OFCs from 1996 to 2021 and a descriptive analysis of OFCs from 2010 to 2021 were performed based on data from the CREC, the national BD surveillance system. Prevalence at birth was calculated according to the type: cleft palate (CP), cleft lip with or without CP (CL ± P), and presentation (isolated, multiple non-syndromic, or syndromes). We used joinpoint regression to identify if a significant change in trend occurred; the average annual percent change (AAPC) was determined. Marginal means and prevalence ratios by subperiod (1996-2009 as referent and 2010-2021) were estimated using Poisson regression and compared using Wald's chi-square tests (α ≤.05). RESULTS: We found a significant AAPC for OFCs prevalence of +1.4: +0.6 for isolated, +2.9 for multiple non-syndromic, and +7.7 for syndromes (p < .05). When comparing the OFC's prevalence of the subperiod 2010-2021 (11.86 per 10,000) with 1996-2009 (9.36 per 10,000) the prevalence ratio was 1.3 (p < .01): 1.1 (p < .05) for isolated, 1.6 (p < .01) for multiple non-syndromic, and 3.3 (p < .01) for syndromes. The prevalence of OFCs from 2010 to 2021 was 9.1 for CL ± P and 2.8 for CP. Seventy-one percent of the OFCs were isolated, 22% multiple non-syndromic, and 7% syndromes. CONCLUSION: The trend in OFCs' prevalence is toward increasing, mainly due to improvements in the surveillance system.