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BACKGROUND: Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence. METHODS: We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates. RESULTS: There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged. CONCLUSIONS: We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Objectives: To elucidate the burden and clinico-epidemiological attributes of congenital and hereditary anomalies (CA) in the extended Peshawar Valley of Pakistan. Method: This is a multicenter cross sectional study carried out in Buner, Charsadda, Mardan, Nowshera, Peshawar and Swabi districts, during 2017-2021. The pediatric and adult patients with CA were recruited from hospitals, public places and through door-to-door surveys. The anomalies were classified with the help of specialized clinicians. Descriptive statistics was employed. Results: In this study, 1065 independent subjects with certain types of CA from independent households were included. The index males were 71%; the majority of subjects originated from rural areas (72%), and spoke Pashto (96%). The CA were categorized into 10 major and at least 104 minor categories. There was highest representation of neurological disorders, n=375 (proportion.: 0.352; 95% CI: 0.323-0.381), followed by limb defects (n=281; prop.: 0.264), sensorineural defects (n=128; prop.: 0.120), musculoskeletal defects (n=84; prop.: 0.079), visual impairments (n=67; prop.: 0.063), hemoglobinopathies (n=40; prop.: 0.038), ectodermal disorders (n=34; prop.: 0.032), cardiovascular anomalies (n=19; prop.: 0.018), and orofacial anomalies (n=19; prop). Among the neurological disorder, intellectual disabilities and cerebral palsy were highly prevalent. The majority of the cases had a sporadic presentation (68%), and isolated occurrence (72%), whereas parental consanguinity was witnessed in 58% of cases. Conclusion: A wide range of CA were witnessed in this cohort with a preponderance of neurological disorders. The majority of the anomalies are of severe nature rendering a high morbidity burden in the population and requiring early detection, intervention and management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Annually, 3-8 million infants are born with congenital anomalies worldwide, ranging from 3% to 7% of births in different countries. This study aimed to investigate the nationwide epidemiological features of birth defects in Iran. Methods: This cross-sectional study was conducted in six major regions across Iran. The data sources were the maternity facilities affiliated with regional universities of medical sciences. All children were examined by obstetricians, pediatricians, or midwives at birth, and newborns were followed until discharge from the facility for health status, maturity, and congenital defects. Results: A total of 138,643 births were registered in the maternity facilities across the study regions. Among these newborns, 3,458 cases were diagnosed with congenital anomalies, representing an overall prevalence rate of 249.4 per 10 000 births (95% CI: 241.2-257.8). Genital organ anomalies exhibited the highest rates of defects in the country with 92.7 per 10 000 births (95% CI: 86.4-98.9), followed by limb anomalies at 83.3 per 10 000 births (95% CI: 77.4-89.3). The prevalence of respiratory system, chromosomal, and urinary tract anomalies was less than 10 per 10 000 births. Conclusion: Until a national registry for congenital anomalies is established, this study provides essential data on the magnitude of the health problems caused by congenital anomalies in Iran. The findings would be vital for planning and evaluating antenatal screening for birth defects, particularly for high-risk groups and regions in the country. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal demographics based on occupation coding status and evaluate potential bias by excluding manually coded occupations. Methods: This case-control study assessed cases with clefts obtained from the Texas Birth Defects Registry. The NIOSH Industry and Occupation Computerized Coding Systemautomatically coded occupations, withmanual coding for unclassified cases. Maternal demographics were tabulated by occupation coding status (manual vs. automatic). Logistic regression examined associations between major occupation groups and clefts. Results: Automatic coding covered over 90% of all mothers. Building, grounds cleaning, and maintenance occupations, and office and administrative support occupations were significantly associated with cleft lip with or without cleft palate, even after excluding manually coded occupations. Conclusion: We found consistent associations before and after excluding manually coded data for most comparisons, suggesting that machine learning can facilitate occupation-related birth defects research. [ABSTRACT FROM AUTHOR]

Objectives: This study was aimed to report the prevalence-pattern of hereditary and congenital anomalies (CA) in general population of Balochistan province of Pakistan, and to elucidate the familial/sporadic presentations and parental consanguinity of CA. Methods: In a multi-center cross-sectional study, patients with CA were ascertained from various district hospitals and public places throughout Balochistan from 2019 to 2023. Online Mendelian Inheritance in Man (OMIM) and International Classification of Diseases (ICD-10) databases were utilized for uniformity in classification. Descriptive statistics was employed. Results: A cohort of 1185 independent patients diagnosed with CA was recruited and the index males were 71%. The CA were classified into nine major and 118 minor entities. In the major categories, neurological disorders had the highest prevalence (n=317; 27%), followed by limb defects (n=161; 14%), blood-heart defects (n=159; 13%), neuromuscular anomalies (n=156; 13%), sensorineural/ear defects (n=140; 12%), eye/visual impairments (n=90; 8%), musculoskeletal defects (n=83; 7%), ectodermal defects (n=31; 3%), and others (48; 4%). Sixty one percent CA were sporadic in nature and 39% were familial; and parental consanguinity was observed in 51% cases. Several rare CA were witnessed. Conclusions: High preponderance of sporadic presentations in neuromuscular anomalies and musculoskeletal defects and low incidence of parental consanguinity in ectodermal defects and musculoskeletal defects may depict a significant etiological role of non-genetic/environmental factors such as prenatal exposures and maternal conditions. In this context, it is important to increase health education, enhance antenatal and perinatal care, and strengthen the health-care system in Balochistan to reduce the burden of CA. [ABSTRACT FROM AUTHOR]

Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co‐occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999–2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions 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.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.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.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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data," such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are such an outcome, for which specificity of exposure timing is critical. Studies with primary data collection can be designed to query details about the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world." Because birth defects are rare, etiologic studies are typically case‑control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy Exposures, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information about both prescription and over-the-counter medication use and other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case‑control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

Background: Precise regulation of cell-cell communication is vital for cell survival and normal function during embryogenesis. The Wnt protein family, a highly conserved and extensively studied group, plays a crucial role in key cell-cell signaling events essential for development and regeneration. Congenital anomalies of the kidney and urinary tract (CAKUT) represent a leading cause of chronic kidney disease in children and young adults, and include a variety of birth abnormalities resulting from disrupted genitourinary tract development during embryonic development. The incidence and progression of CAKUT may be related to the Wnt signal transduction mechanism. Summary: This review provides a comprehensive overview of the classical Wnt signaling pathway’s role in CAKUT, explores related molecular mechanisms and provides new targets and intervention methods for the future treatment of the disease. Key Messages: The Wnt signal is intricately engaged in a variety of differentiation processes throughout kidney development.

Xiaoqin Chen,1 Lifang Lin,2 Qiuping Zhong,1 Heming Wu,2 Zhiyuan Zheng,2 Baisen Zhang,3 Liubing Lan1 1Department of Maternity, Meizhou People’s Hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of China; 2Department of Central Laboratory, Meizhou People’s hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of maternity, Meizhou People’s hospital, No. 63, Huang Tang Road, Meijiang District, Meizhou City, Guangdong Province, 514031, People’s Republic of China, Email hipiing1284@sina.comObjective: 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.Keywords: fetus, birth defects, influencing factors, nomogram

Shukri Said Mohamed,1 Adem Küçük,2 Omar Adam Sheikh,3 Ahmet SARAÇ,4 Mesut Kayse Adam,1 Ismail Gedi Ibrahim,5 Marian Muse Osman,6 Naima Abukar Ali,7 Abdirahman Ahmed Mohamud8 1Department of Pediatric Surgery, Mogadishu Somali Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 2Düzce Atatürk Devlet Hastanesi, Düzce, Turkey; 3Faculty of Medicine, Department of Basic Medical Science, Somali National University, Mogadishu, Somalia; 4Department of Pediatric Surgery, Samsun Training and Research Hospital, Samsung, Turkey; 5Department of Radiology, Mogadishu Somali Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 6Department of Public Health, Mogadishu Somali Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 7Department of Pediatric, Mogadishu Somali Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 8Department of General Surgery, Mogadishu Somali Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, SomaliaCorrespondence: Shukri Said Mohamed, Email sagalsaid2@gmail.comBackground: Birth defects of the digestive system are a phenotypically and etiologically different category common birth defects caused by various causes during fetal development.Objective: The study’s goal was to evaluate patient demographics, related abnormalities, atresia location, operational management, postoperative care, and results of patients with gastrointestinal atresia and compare them with other research.Methods: A 5-year retrospective study in cases with gastrointestinal atresia at a tertiary hospital in Mogadishu, Somalia, was carried out by the pediatric surgery department from January 2017 to January 2022.Results: A165 cases were operated due to gastrointestinal atresia in five-year period., 105 were male (63.6%) and 60 were female (36.4%), giving the male to female ratio of 1.75:1. According to the age group of the study population, the majority of cases (48.5%) were aged less than 1 month. The esophageal atresia, duodenal atresia, high jejunal atresia, jejunoileal atresia, and colon atresia, anorectal malformations were 9.7%, 9.1%, 0.6%, 7.3%, 73.3%, respectively; the anorectal malformations has resulted in the majority of cases (73.3%). 20 % of cases had no follow-up, while 80% arrived as planned. 52.1% got well and had no complications and some developed different complications like peristomal skin irritation (14%), rectal and urethral fistula (4.8%), rectal prolapse (1.8%), rectal stenosis (2.4%), rectal adhesions (1.2%), esophageal stricture (1.2%), wound infection (3.6%), anastomosis dehiscence (0.6%), abdominal distension (0.6%), recto-perineal fistula (1.2%), urethral damage and urinary retention (0.6%). Mortality for this study was 24.8% (41 patients).Conclusion: Children with gastrointestinal atresia present late in the course of their illness, with substantial morbidity and death due to poor economic conditions, poor nutrition, surgical problems, and likely related anomalies, rather than surgical morbidity alone.Keywords: birth defects, fetal development, digestive system, intestinal obstruction

The prolonging war actions in Iraq have given rise to cumulative increase in environmental pollutions across country. Areas which have been extensively polluted include air, land, water and the health infrastructure to a greater extend. War has been ongoing for over two decades and the environmental damage couldn’t be avoided. War in Iraq contaminated the sand through the military actions that reconfigured the desert sands raising dust and causing air and land pollution simultaneously. The dust storms generated by military actions would reach the cities such as Erbil and Baghdad contaminating environmental surfaces and infrastructure. Evidence from experiments conducted by measuring the amount uranium levels in animal organs show that there is the presence of depleted uranium the Iraqi food chains and webs. Results further shows that the highest depleted uranium concentration is found in the Southern part of Iraq. Places like the Al-Twaitha nuclear research site are considered to be extensively polluted because of the destruction of nuclear reactors in the Gulf war of 1991. Furthermore, more barrels which had radioactive materials were stolen from the site in 2001. Soil samples around the site exhibited a high amount of CS-137 and Co-60 which are damaging to human beings and biodiversity. Health complications which have been observed include birth defects and cancer due to the radioactive chemicals emitted during war. As noted above, environmental damage in form of infrastructural damage remains an outcome of Iraq’s long war, and rapid industrialization in oil extraction and urbanization. The most affected cities in Iraq are Erbil, Basrah, Faluja, Baghdad, Mosul, and Thi-qar. This analysis concludes that the presence of an extensively contaminated environment due to the past and current wars, rapid industrialization is directly connected to the health complications being sustained.

Background: Contemporary understanding of the pattern of congenital anomalies is both important in its clinical management as well as in improving the overall health of the community. Methodology: All infants presenting from January to December 2102 at the centre were prospectively studied. Results: A total of 5010 infants were screened, of which 108 have congenital anomalies giving a prevalence of 2.2%. Major anomalies were noted in 101 (93.5%) infants. Only two (1.9%) were preterm. Consanguineous relationship was observed in 2 (1.9%) cases. Pre natal Ultrasound scan was done in 33(30.8%), but in only 7 (6.5%) was any anomaly detected Onitsha, a densely populated urban area contributed 45(42%) of the cases. Only 7(6.5%) of the mothers took herbal prescriptions in the first trimester of pregnancy. Risk of anomaly progressively rises, reaching a peak of 48% in the maternal age group of 26-30 years and drops steadily after. Gastrointestinal tract anomalies were most common (no. =28, 25.9%). Residences close to dump sites, telecom masts/base stations, electricity cables, industries and heavy motorised highways contributed to risk factors in 9-12 % of cases. Conclusion: More of younger mothers were affected with gastro intestinal malformations predominating. The location of home environment is a potential risk factor that will require further characterisation.

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Abstract 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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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 Conclusions: 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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Children born with major congenital anomalies (CAs) have lower academic achievement compared with their peers, but the existing evidence is restricted to a number of specific CAs. Objectives: To investigate academic outcomes at ages 11 and 16 in children with major isolated structural CAs and children with Down or Turner syndromes. Methods: This population‐based cohort study linked data on approximately 11,000 school‐aged children born with major CAs in 1994–2004 registered by four regional CA registries in England with education data from the National Pupil Database (NPD). The comparison group was a random sample of children without major CAs from the background population recorded in the NPD that were frequency matched (5:1) to children with CAs by birth year, sex and geographical area. Results: Overall, 71.9%, 73.0% and 80.9% of children with isolated structural CAs achieved the expected attainment level at age 11 compared to 78.3%, 80.6% and 86.7% of the comparison group in English language, Mathematics and Science, respectively. Children with nervous system CAs as a whole had the lowest proportion who achieved the expected attainment at age 11. At age 16, 46.9% of children with CAs achieved the expected level compared to 52.5% of their peers. Major CAs were associated with being up to 9% (95% confidence interval [CI] 8%, 11%) and 12% (95% CI 9%, 14%) less likely to achieve expected levels at ages 11 and 16, respectively, after adjustment for socioeconomic deprivation. Conclusions: Although many children with isolated CAs achieved the expected academic level at ages 11 and 16, they were at higher risk of underachievement compared to their peers. These stark yet cautiously encouraging results are important for counselling parents of children with specific CAs and also highlight the possible need for special education support to reduce potential academic difficulties. [ABSTRACT FROM AUTHOR]

Objective To analyze the epidemiological characteristics of perinatal birth defects in Henan Province from 2011 to 2020 and to provide basis for the prevention of birth defects. Methods Perinatal birth defect surveillance data from 37 national monitoring sites in Henan Province were collected for newborns delivered from 2011 to 2020. Joinpoint regression was used to describe the trends in birth defect incidence, and Chi-square tests compared incidence rates among different groups (including region, infant sex, and maternal age). Results A total of 29 418 cases of birth defects were monitored in Henan Province from 2011 to 2020, resulting in a total incidence rate of 216.81 per 10 000 births. The annual incidence showed a significant upward trend (AAPC=20.07%, P < 0.001). Incidence rates were significantly higher in urban areas compared to rural areas, in boys compared to girls, and in mothers aged ≥ 35 years compared to those < 35 years (χ²=5 545.926, 257.052, and 403.326 respectively, all P < 0.001). The top 10 birth defects were congenital heart disease (118.47 per 10 000), other malformations (47.62 per 10 000), polydactyly (14.34 per 10 000), cleft lip and palate (10.23 per 10 000), other malformations of the external ear (9.74 per 10 000), syndactyly (5.73 per 10 000), congenital hydrocephalus (5.32 per 10 000), hypospadias (5.24 per 10 000), equinovarus (4.35 per 10 000), and limb shortening (2.69 per 10 000). Conclusion The incidence of birth defects in Henan Province demonstrated a significant upward trend from 2011 to 2020. Comprehensive measures for birth defect prevention and treatment are essential to reduce incidence rates and enhance the quality of the population. [ABSTRACT FROM AUTHOR]

Objective Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. Study Design We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. Results The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. Conclusion Prevalence of BE varied by program and showed a decreasing trend from 2000 to –2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. Key Points Total prevalence of BE was 2.58 per 100,000 births. Prevalence decreased from 2000 to 2014. The first-week mortality was 9.3%. [ABSTRACT FROM AUTHOR]

Background: Although birth defects are of great concern globally, the latest national prevalence has not yet been quantified in China. We conducted a systematic review and meta-analysis to estimate the perinatal prevalence of birth defects in the Mainland of China between 2000 and 2021. Methods: We performed a systematic literature search of six databases for relevant articles published between January 1, 2000, and March 1, 2023. We included published studies that reported data on the perinatal prevalence of birth defects in the Mainland of China. The DerSimonian and Laird random-effects models were used to estimate the pooled prevalence and its 95% confidence interval (CI). We also conducted subgroup analyses and univariable meta-regressions to explore differences in prevalence by time period, geographic region, and other characteristics. Results: We included 254 studies reporting the perinatal prevalence of birth defects and 86 studies reporting only the prevalence of specific types of birth defects. Based on 254 studies covering 74,307,037 perinatal births and 985,115 cases with birth defects, the pooled perinatal prevalence of birth defects was 122.54 (95% CI 116.20–128.89) per 10,000 perinatal births in the Mainland of China during 2000–2021. Overall, the perinatal prevalence of birth defects increased from 95.60 (86.51–104.69) per 10,000 in 2000–2004 to 208.94 (175.67–242.22) per 10,000 in 2020–2021. There were also significant disparities among different geographical regions. Congenital heart defects (33.35 per 10,000), clefts of the lip and/or palate (13.52 per 10,000), polydactyly (12.82 per 10,000), neural tube defects (12.82 per 10,000), and inborn errors of metabolism (11.41 per 10,000) were the five most common types of birth defects. The perinatal prevalence among males was significantly higher than that among females (β = 2.44 × 10−3, P = 0.003); a higher perinatal prevalence of birth defects was observed among perinatal births whose mothers were ≥ 35 years (β = 4.34 × 10−3, P < 0.001). Conclusion: Comprehensive and sustained efforts are needed to strengthen surveillance and detection of birth defects, improve prenatal and postnatal healthcare, and promote rehabilitation, especially in underdeveloped areas. [ABSTRACT FROM AUTHOR]

Introduction: Between 2019–2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. Methods: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. Results: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. Discussion: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred. [ABSTRACT FROM AUTHOR]

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). Conclusion: Variation in the genes identified in this population‐based study may help to further explain the genetics of PCG. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59–1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21–1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly. [ABSTRACT FROM AUTHOR]

Purpose: Antiretrovirals (ARVs) are life‐saving drugs used for the treatment and prevention of HIV infection and antiviral drugs (AVs) for the treatment of chronic HBV infection. ARVs have proven highly effective in reducing perinatal HIV transmission, however the risk of birth defects from prenatal exposure to ARVs/AVs is an ongoing concern. The Antiretroviral Pregnancy Registry (APR), an international, prospective exposure‐registration cohort study, monitors ARV and AV use in pregnancy for early signals of teratogenicity. This communication reports results of 30‐years' experience of ARV/AV exposure during pregnancy and lessons learned through continuous quality improvement. Methods and Results: Birth defect prevalence is estimated and compared to internal and external groups. Statistical inference is based on exact methods for binomial proportions. Between 2006 and 2023, cumulative enrollment more than tripled from 6893 to 25 960 pregnancies and ARVs/AVs monitored increased from 29 to 222. Through January 2023, there were 21 636 live births and 631 outcomes with birth defects, for overall prevalence of 2.9/100 live births (95% CI 2.7, 3.2). The birth defect prevalence was 3.0% (95% CI 2.7%, 3.3%) among first trimester exposures and 2.8% (95% CI 2.5%, 3.2%) among second/third trimester exposures (prevalence ratio 1.04 [95% CI 0.89, 1.21]). Conclusions: Birth defect prevalence is not statistically significantly different between first trimester ARV/AV pregnancy exposures compared to second/third trimester exposures and is also not different from two population‐based surveillance systems: 2.72/100 live births reported in the Metropolitan Atlanta Congenital Defects Program (MACDP); and 4.17/100 live births from the Texas Birth Defects Registry (TBDR). [ABSTRACT FROM AUTHOR]

ObjectiveThis 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.MethodsBirth 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.ResultsAmong 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).ConclusionThe 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.

Background: Congenital hypothyroidism (CH) is one of the most prevalent endocrine disorders in children. According to the literature, there is a high prevalence of other anomalies and syndromes in infants diagnosed with CH. Objectives: This study finds the prevalence of concurrent anomalies and the prevalence of each one. Methods: This was a systematic review study based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA). The research question was the comparison of children with and without CH in terms of having extra-thyroidal congenital anomalies. A systematic literature search through PubMed, Science Direct, Scopus, and the Web of Science databases was done using the following key words: Congenital hypothyroidism, birth defects, congenital anomalies. Results: From the 655 initially retrieved articles, 24 articles remained, and 4 additional references were found by reviewing the references of the final articles. Finally, 28 articles were selected. The prevalence of extra-thyroidal anomalies ranged from 5% to 50% in girls and from 4% to 80% in boys. Meanwhile, 20% of the permanent CH patients and 13% of the patients with transient CH had extra-thyroidal congenital malformations. Cardiac anomalies were more prevalent in girls (female to male ratio=1.6 [0.7 to 5.5]), and urogenital anomalies were more reported in boys. Most of the studies did not report the association between non-thyroidal anomalies and thyroid stimulating hormone, gender, etiology of CH, and transient and permanent CH. Conclusions: Congenital anomalies are more common in CH patients compared with the general population, even in the absence of congenital syndromes or chromosomal abnormalities. The most common anomalies are cardiac, craniofacial, urogenital, and nervous system.

Abstract With the development of next-generation sequencing technology, de novo variants (DNVs) with deleterious effects can be identified and investigated for their effects on birth defects such as congenital heart disease (CHD). However, statistical power is still limited for such studies because of the small sample size due to the high cost of recruiting and sequencing samples and the low occurrence of DNVs. DNV analysis is further complicated by genetic heterogeneity across diseased individuals. Therefore, it is critical to jointly analyze DNVs with other types of genomic/biological information to improve statistical power to identify genes associated with birth defects. In this review, we discuss the general workflow, recent developments in statistical methods, and future directions for DNV analysis.