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Objective: To investigate the association between maternal glycemic control and the risk of congenital malformations in offspring of women with type 1 diabetes and to examine whether there is a hemoglobin A 1C (Hb A 1C ) threshold value at which the risk for malformations increases significantly., Methods: Analyses were performed on data from a multinational, observational cohort of 1,908 liveborn offspring of women with type 1 diabetes recruited in early pregnancy from 17 countries between 2013 and 2018. Offspring with malformations were identified according to European Surveillance of Congenital Anomalies version 1.4 and categorized as having one or more major malformations or minor malformations exclusively. The association between first-trimester Hb A 1C levels and the risk of congenital malformations was investigated with splines in crude and adjusted logistic regression models., Results: In total, 11.9% of the offspring (n=227) of women with type 1 diabetes had congenital malformations, including 2.1% (n=40) with at least one severe malformation. Women giving birth to offspring with malformations had a higher prevalence of psychiatric disorders (13.2% vs 7.2%, P <.01), thyroid disorders (33.0% vs 26.7%, P <.05), and folic acid supplementation (87.1% vs 77.7%, P <.01). The Hb A 1C levels in the first trimester were similar (median 6.8% [interquartile range 6.3-7.6%] vs 6.7% [6.2-7.6%], P =.13) compared with women giving birth to offspring without malformations. The spline analysis illustrated a curvilinear association between Hb A 1C levels and the risk of malformations with no clear threshold values. Higher first-trimester Hb A 1C levels were associated with an increased risk of malformations (crude odds ratio [OR] 1.13, 95% CI, 1.01-1.27, adjusted odds ratio [aOR] 1.29, 95% CI, 1.10-1.51) and major malformations (crude OR 1.49, 95% CI, 1.23-1.81, aOR 1.57, 95% CI, 1.15-2.09)., Conclusion: An increased risk for congenital malformations was curvilinearly associated with higher Hb A 1C levels in early pregnancy among women with type 1 diabetes without any threshold values identified., Clinical Trial Registration: ClinicalTrials.gov , NCT01892319., Competing Interests: Financial Disclosure Ida Holte Thorius is an industrial PhD student, funded by Novo Nordisk and holds shares in Novo Nordisk. Lise Lotte N. Husemoen, Amra C. Alibegovic, and Mari-Anne Gall are employees of and hold shares in Novo Nordisk. Elisabeth R. Mathiesen has received speakers' fees from Novo Nordisk and has participated in steering committee tasks and guidance involving writing protocols for Novo Nordisk. Elisabeth R. Mathiesen and Peter Damm have participated in several multinational clinical studies on the use of insulin in pregnant women with pre-existing diabetes, in collaboration with Novo Nordisk. Janne Petersen did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Previous studies have indicated the association between smooth endoplasmic reticulum aggregates (SERa+) and poorer medically assisted reproduction outcomes. However, the link between SERa+ and neonatal outcomes remains controversial and open for debate. A comprehensive meta-analysis on the relation between SERa+ and the risk of birth defects is needed., Material and Methods: The literature search was conducted using the following databases: PubMed, Embase, Cochrane Libraries, Web of Science, and Chinese databases including China National Knowledge Infrastructure (CNKI) and Wan Fang from inception until July 2023. Risk ratio (RR) and 95% confidence interval (CI) were calculated by a fixed-effected model, while heterogeneity was assessed by forest plots and I 2 statistic. Funnel plot was produced to assess publication bias. This meta-analysis has been registered on PROSPERO (CRD42022313387)., Results: The search resulted in 122 studies, 14 of which met the inclusion criteria. The analysis of birth defects revealed a higher risk (RR = 2.17, 95%CI 1.24 to 3.81, p = 0.007) in children derived from SERa+ cycle compared to SERa- cycles (711 vs. 4633). Meanwhile, in a subgroup analysis, the risk of birth defects was significantly increased in the SERa+ oocytes group as compared with the sibling SERa- oocytes group (RR = 3.53, 95%CI 1.21 to 10.24, p = 0.02)., Conclusions: To conclude, our analysis indicated that SERa+ cycles/oocytes may have a potential risk of increased additional major birth defects comparing with SERa- cycles/oocytes. This conclusion may provide evidence-based support for clinicians in IVF clinical guidance and embryologists in prudent embryo selection strategy., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature., Objective: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols., Study Design: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies., Results: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47)., Conclusion: The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 PM 2.5 , 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., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Background and Objective: An increasing number of observational studies have investigated the risk of using drugs during pregnancy on congenital malformations. However, the credibility of the causal relationships drawn from these studies remains uncertain. This study aims to evaluate the potential methodological issues in existing observational studies., Methods: We used a stepwise approach to investigate this issue. First, we identified observational studies published in 2020 that examined the risk of congenital malformations associated with medication use during pregnancy. We assessed the methodological characteristics for establishing causality, including study design, confounding control, and sensitivity analysis, and compared them between "core clinical journals" and "general journals." For studies reporting an increased risk of congenital malformations in core clinical journals, we searched for subsequent studies addressing the same research question published between January 2021 and May 2023 to assess the consistency of the literature., Results: A total of 40 eligible studies were published in 2020, primarily focused on the safety of vitamin B 12 and folic acid (n = 4), antidepressants (n = 4), and others (n = 32). Our findings suggest that only two (5.00%) studies used causal models to guide the identification of confounding, and only eight (20.00%) studies assessed the potential dose-response relationship. In all, 15 (37.50%) studies used propensity score analysis strategy to achieve "mimic-randomization." In addition, 22 studies (55.00%) performed sensitivity analyses, while 10 (45.45%) showed inconsistency with the primary outcome. Furthermore, 5 studies reported positive outcomes, whereas only 1 out of 11 studies demonstrated a positive correlation between drug usage during pregnancy and major malformations in subsequent studies., Conclusion: A significant portion of the studies has failed to sufficiently consider the essential methodological characteristics required to improve the credibility of causal inferences. The increased risk of congenital malformations documented in core clinical journal was not adequately replicated in subsequent studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To evaluate the association between paternal metformin use and risk of congenital malformations in offspring., Design: Population based, cross national cohort study., Setting: Norway and Taiwan., Participants: 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18., Main Outcome Measures: The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach., Results: Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses., Conclusions: The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this work was supported by the Norwegian Research Council and by the National Science and Technology Council of Taiwan; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The authors had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Possible contamination related to mining activities might contribute with other risk factors in increasing the burden of birth defects (BDs) in many developing countries including the Democratic Republic of Congo. The subsequent prevalence is frequently underestimated. Implementation of focused public health interventions is hindered by the paucity of comprehensive data. We assessed the potential impact of mining on the prevalence and occurrence of visible BDs in neonates in South Kivu (SK)., Methods: A hospital-based cross-sectional study was conducted among 65,474 newborns registered in 7 hospitals in SK from 2016-2021. Hospitals were categorized based on mining activities in their respective catchment areas. Living in a mining zone was the exposure, whereas the outcome was visible BDs. Prevalence was estimated per 100,000 live births, and risk of occurrence with odds ratio (OR) and their 95% confidence interval., Results: 261 neonates with visible BDs were recorded accounting for a prevalence of 399 cases per 100,000 live births. The prevalence ranges between 217 and 1365 cases per 100,000 live births. An increased risk was found in mining zones(OR=2.07; 95%CI=1.59-2.68), Mubumbano(OR=1.72, 95%CI=1.22-2.43), and Mwenga(OR=3.89, 95%CI=2.73-5.54), whereas a reduced risk was reported in non-mining zones(OR=0.48, 95%CI=0.37-0.62) in Katana (OR=0.49, 95%CI=0.33-0.73). Musculoskeletal(28.74%) and central nervous systems(19.92%) were the most common BDs. A significant difference in prevalence for BDs involving the face, GI system and abdominal wall, musculoskeletal, central nervous and genitourinary systems between mining and non-mining zones was found(p<0.001)., Conclusion: There is an excessive risk for visible BDs in areas with hazardous mining activities in SK region.​​ More complex studies are needed to define the possible causal relationship. Moreover, findings generated herein should be corroborated by other research design, periodically monitored by public health authorities, and used to inform initiatives promoting enhanced environmental health, access to pediatric surgical care, and public health campaigns aimed at decreasing risk of BDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cikomola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent evidence shows a shift in neonatal mortality causes, with an increasing proportion due to birth defects. This study aimed to determine the prevalence and treatment outcomes of congenital anomalies (CAs) at a tertiary referral center in Northern India. This retrospective observational study was conducted over 7 years (May 2014-December 2021) and included all inborn and outborn neonates admitted with a diagnosis of CA as per ICD-10 classification in a level 3 NICU in North India. The prevalence of CAs was 8.9% (332 out of 3734 neonates). The most commonly affected systems were cardiovascular (33.4%), gastrointestinal (19.8%), and genitourinary (19.8%). While 57.5% of these defects could potentially be addressed through pediatric and cardiovascular surgery, only a small proportion of eligible neonates received timely surgical intervention due to delayed referrals and financial constraints. The mortality rate was 16.8%. This study highlights the significant burden of CAs in Northern India, emphasizing the need for enhanced capacity building, better facilities, and increased awareness for timely referrals. The findings underscore the importance of multidisciplinary collaborations and upgraded healthcare services to inspire further research and preventive strategies to mitigate birth defects. Given the context of a low- and middle-income country, this study's insights into the prevalence, challenges, and outcomes of CAs are particularly relevant, highlighting the necessity of accessible and affordable healthcare solutions in such settings., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots&#95;16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and nongenetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Purpose: To examine maternal, obstetrical, and neonatal outcomes of pregnancies complicated by major fetal anomalies., Methods: A 10 year retrospective cohort study at a tertiary university hospital compared maternal and obstetrical outcomes between women with singleton pregnancies complicated by major fetal anomalies, and a control group with non-anomalous fetuses., Results: For the study compared to the control group, the median gestational age at delivery was lower: 37.0 vs. 39.4 weeks (p < 0.001); and the preterm delivery rates were higher, both at < 37 weeks (46.2 vs. 6.2%, p < 0.001) and < 32 weeks (15.4 vs. 1.2%, p < 0.001). For the study compared to the control group, the placental abruption rate was higher (6.8 vs. 0.9%, p = 0.002); 87.5 vs. 100% occurred before labor. For the respective groups, the mean gestational ages at abruption were 32.8 ± 1.3 and 39.9 ± 1.7 weeks (p = 0.024); and cesarean section and postpartum hemorrhage rates were: 53.8 vs. 28.3% (p < 0.001) and 11.3 vs. 2.8% (p = 0.001), respectively. For the respective groups, hypertensive disorders of pregnancy rates were 9.5 vs. 2.1% (p = 0.004), stillbirth rates were 17.1 vs. 0.3% (p < 0.001), and neonatal death rates 12.5 vs. 0.0% (p < 0.001). Major fetal anomalies were found to be associated with adverse maternal outcomes (OR = 2.47, 95% CI 1.50-4.09, p < 0.001). Polyhydramnios was identified as an independent risk factor in a multivariate analysis that adjusted for fetal anomalies, conception by IVF, and primiparity for adverse maternal outcomes (OR = 4.7, 95% CI 1.7-13.6, p < 0.001)., Conclusions: Pregnancies with major fetal anomalies should be treated as high-risk due to the increased likelihood of adverse maternal and neonatal outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although it is well-known that the presence of fetal anomalies is associated with maternal morbidity, granular information on these risks by type of anomaly is not available., Objective: To examine adverse maternal outcomes according to the type of fetal anomaly., Study Design: This was a repeated cross-sectional analysis of US vital statistics Live Birth/Infant Death linked data from 2011 to 2020. All pregnancies at 20 weeks or greater were included. Our primary outcome was severe maternal morbidity (SMM), defined as any maternal intensive care unit admission, transfusion, uterine rupture, or hysterectomy. Outcomes were compared between pregnancies with a specific type of fetal anomaly and pregnancies without any fetal anomaly. Fetal anomalies that were available in the dataset included anencephaly, meningomyelocele/spina bifida, cyanotic congenital heart disease, congenital diaphragmatic hernia, omphalocele, gastroschisis, cleft lip and/or palate, hypospadias, limb anomaly, and chromosomal disorders. If a fetus had more than one anomaly, it was classified as multiple anomalies. Adjusted relative risks (aRR) with 99% confidence intervals (99% CI) were calculated using modified Poisson regression. Adjusted risk differences (aRDs) were calculated using the marginal standardization form of predictive margins., Results: Of 35,760,626 pregnancies included in the analysis, 35,655,624 pregnancies had no fetal anomaly and 105,002 had isolated or multiple fetal anomalies. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased risk of SMM except for gastroschisis and limb anomaly in order of aRRs (99% CI): 1.58 (1.29-1.92) with cleft lip and/or palate; 1.75 (1.35-2.27) with multiple anomalies; 1.76 (1.18-2.63) with a chromosomal disorder; 2.19 (1.82-2.63) with hypospadias; 2.20 (1.51-3.21) with spina bifida; 2.39 (1.62-3.53) with congenital diaphragmatic hernia; 2.66 (2.27-3.13) with congenital heart disease; 3.15 (2.08-4.76) with omphalocele; and 3.27 (2.22-4.80) with anencephaly. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased absolute risk of SMM except for gastroschisis and limb anomaly in order of aRDs (99% CI): 0.26 (0.12-0.40) with cleft lip and/or palate, 0.34 (0.13-0.55) with multiple anomalies, 0.34 (0.02-0.66) with a chromosomal disorder, 0.54 (0.36-0.72) with hypospadias, 0.54 (0.17-0.92) with spina bifida, 0.63 (0.21-1.05) with congenital diaphragmatic hernia, 0.75 (0.56-0.95) with congenital heart disease, 0.97 (0.38-1.56) with omphalocele, and 1.03 (0.46-1.59) with anencephaly., Conclusion: The presence of fetal anomalies is associated with adverse maternal health outcomes. The risk of SMM varies according to the type of fetal anomaly. Counseling mothers about the maternal implications of fetal anomalies is paramount to help them make informed decisions regarding their pregnancy outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024 Wiley Periodicals LLC.)

Fetal anomalies among young women and adolescents pose major public health concerns. This systematic review aims to elucidate the relationship between young maternal age and the incidence of fetal abnormalities. According to the systematic review and meta-analysis PRISMA protocol, cohort, cross-sectional and case-control studies were scrutinized to include 80,393,450 participants across diverse regions. The meta-analysis utilized Odds Ratios (OR) as the effect measure, adopting a random-effects model. The screening process involved 157 selected and verified manuscripts, which ultimately resulted in the final inclusion of 20 studied in the meta-analysis. The criterion for young maternal age was the age of ≤ 20 years. The meta-analysis revealed a pooled OR of 0.93 (95% CI: 0.82-1.05, p = 0.252), indicating no statistically significant association between young maternal age (≤ 20 years) and fetal anomalies. However, considerable heterogeneity (I² = 96.21%) was noted, prompting the use of a random-effects model to derive the reported results. The meta-analysis did not find statistically significant differences in the occurrence of congenital anomalies in fetuses of younger women than in overall population. Although due to significant heterogeneity of the analyzed studies, and a risk of bias, caution should be exercised when interpreting the results, further investigation may be warranted to understand the relationship between maternal age and risk of fetal anomalies. Nevertheless, the study shows significant differences, which diminish in collective analysis, suggests that factors beyond age may be influential. Specifically, the limited access to or quality of healthcare in certain regions could be a more critical factor than maternal age itself., (© 2024. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Li, Yan, Xiong, Li, Ding and Mei.)

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

Objective: Birth defect of any type is undesirable and often pose a negative impact on the health and development of the newborn. Birth defects surveillance with datasets from surveillance health-related programs are useful to predict the pattern of birth defects and take preventive measures. In this study, the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects were compared., Methods: Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016-2020. The total prevalence is the number of birth defects (including livebirths, stillbirths, and selective terminations of pregnancy) per 1,000 births (including livebirths and stillbirths). The perinatal prevalence is the number of birth defects (between 28 weeks gestation and 7 days postpartum) per 1,000 births. The livebirth prevalence is the number of liveborn birth defects per 1,000 births (unit: ‰). Underestimated proportion (unit: %) is the reduction level of perinatal prevalence or livebirth prevalence compared to the total prevalence. Prevalence with 95% confidence intervals (CI) was calculated using the log-binomial method. Chi-square tests ( χ 2 ) were used to examine if significant differences existed in prevalence or underestimated proportion between different groups., Results: A total of 847,755 births were included in this study, and 23,420 birth defects were identified, including 14,459 (61.74%) birth defects with gestational age > =28 weeks, and 11,465 (48.95%) birth defects in livebirths. The total prevalence, perinatal prevalence, and livebirth prevalence of birth defects were 27.63‰ (95%CI, 27.27-27.98), 17.06‰ (95%CI, 16.78-17.33), and 13.52‰ (95%CI, 13.28-13.77), respectively, and significant differences existed between them ( χ 2  = 4798.55, p  < 0.01). Compared to the total prevalence, the perinatal prevalence and livebirth prevalence were underestimated by 38.26 and 51.05%, respectively. Significant differences existed between the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects in all subgroups according to year, sex, residence, and maternal age ( p  < 0.05). Significant differences existed between the total prevalence, perinatal prevalence, and livebirth prevalence for 17 specific defects: congenital heart defect, cleft lip-palate, Down syndrome, talipes equinovarus, hydrocephalus, limb reduction, cleft lip, omphalocele, anal atresia, anencephaly, spina bifida, diaphragmatic hernia, encephalocele, gastroschisis, esophageal atresia, bladder exstrophy, and conjoined twins ( p  < 0.05). In comparison, no significant difference existed between the total prevalence, perinatal prevalence, and livebirth prevalence for 6 specific defects: polydactyly, other external ear defects, syndactyly, hypospadias, cleft palate, and anotia/microtia ( p  > 0.05)., Conclusion: The total prevalence and livebirth prevalence of birth defects in Hunan Province, China, was not well studied. A systematic study was conducted to compare the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects. The study reveals that significant differences existed between the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects (including many specific defects), and year, sex, residence, and maternal age had significant impacts on it. The outcomes of the study will help to take preventive measures for birth defects as well as benefit the people involving public health and policymakers to improve the current scenario., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zeng, Fang, He, Kuang, Hua and Wang.)

The purpose of this study was to investigate the pregnancy outcomes with a copper intrauterine device (IUD) in situ after 28 gestational weeks and the association between pregnancy with copper IUDs and neonatal congenital malformations. This retrospective study had compared the singleton pregnancies with the copper IUDs in situ and without after 28 gestational weeks in 1 delivery center of southeast China. The main exposure was a copper IUD in uterine cavity with pregnancy. The pregnant outcomes as preterm birth, premature rupture of membranes, infections were observed and compared. We had also compared neonatal congenital malformations in 2 groups. The statistical analysis was carried out using R (version 4.0.4; R Development Core Team) statistical software. Association between IUD use or duration of IUD use and adverse pregnancy outcomes were estimated using logistic model. Two-tailed P value < .05 was deemed statistically significant. A total of 148 pregnant women were included in our study, 74 with copper IUDs in situ were categorized into case group and 74 without IUDs during pregnancy into control group. No significant difference of maternal age, BMI, birth weight and gender were observed between 2 groups. In case group, the rates of preterm premature rupture of membranes (37.8%) and spontaneous preterm birth (23.0%) were significantly high compared to control group. Odds ratios of premature rupture of membranes and spontaneous preterm birth were 2.86 and 5.22 respectively. Women of elder age (≥35 years) in case group were more likely to experience premature rupture of membranes. The rates of neonatal congenital malformation were 10.8% (8/74) in case group and 1.4% (1/74) in control group respectively. We had found that pregnancy with copper IUD in situ increased the risk of premature rupture of membranes and spontaneous preterm birth after 28 gestation weeks, the risk of spontaneous preterm birth increased 5.22 times. Pregnancy with IUD in situ may be at increased risk of infection and neonatal malformation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

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., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 The Author(s). Birth Defects Research published by Wiley Periodicals LLC.)

Objective: To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States., Design: Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study., Methods: First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders., Results: Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular ( n  = 43) and musculoskeletal ( n  = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones., Conclusions: The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A significant rise in the use of assisted reproductive technology (ART) has been observed, but concerns about its impact on neonatal outcomes have been considered. The aim of this retrospective cohort study is to determine the association between ART and the risk of neonatal complications and congenital anomalies within a recent time period., Methods: This retrospective study enrolled infants born after 20 weeks of gestation at a tertiary hospital in Taiwan between January 2019 and December 2021. The study population was divided into two groups: (1) ART pregnancy group and (2) natural pregnancy group. Maternal and neonatal characteristics, pregnancy complications, and neonatal outcomes were compared between the two groups. Multivariate logistic regression was used to adjust for maternal characteristics, preexisting maternal conditions, pregnancy complications, delivery methods, and infant characteristics., Results: This study enrolled 1770 infants comprising 289 in the ART pregnancy group and 1481 in the natural pregnancy group. The ART pregnancy group showed higher rates of multiple births, preterm births, low birth weights, and longer hospitalization periods. In the stratified analyses that were conducted on singleton births, no significant difference was observed. In the case of multiple births, lower rates of preterm birth, low birth weight, and respiratory support were observed in the ART pregnancy group. After adjusting for maternal and infant characteristics, ART was not considered a significant risk factor for adverse neonatal outcomes, including mortality, complications, and congenital anomalies., Conclusion: Although ART pregnancies were more likely to result in multiple births and furthermore adverse outcomes, ART itself was not associated with an increased risk of poor neonatal outcomes. By implementing measures to control the number of implanted embryos, ensuring appropriate prenatal screening, and providing comprehensive postnatal care, the risks associated with increased multiple pregnancies caused by ART may be reduced., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects., Methods: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories., Results: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings., Conclusions: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We would like to acknowledge Dr. Christina Chambers (Department of Pediatrics, University of California San Diego) and Dr. Jessica Block (University of California San Diego). The study was supported by the San Diego Study of Mothers and Infants at the University of California San Diego, United States. Gretchen Bandoli is funded by a NIH award (K01 AA027811). No specific funding was received for this project, and the funders for the parent study had no input into the design, analysis, interpretations, or preparation of the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL)., Methods: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model., Results: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I 2  = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I 2  = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I 2  = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region., Conclusions: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Observational studies have suggested an association between air pollutants and congenital malformations; however, conclusions are inconsistent and the causal associations have not been elucidated. In this study, based on publicly available genetic data, a two-sample Mendelian randomization (MR) was applied to explore the associations between particulate matter 2.5 (PM2.5), NO X , NO 2 levels and 11 congenital malformations. Inverse variance weighted (IVW), MR-Egger and weighted median were used as analytical methods, with IVW being the main method. A series of sensitivity analyses were used to verify the robustness of the results. For significant associations, multivariable MR (MVMR) was utilized to explore possible mediating effects. The IVW results showed that PM2.5 was associated with congenital malformations of digestive system (OR = 7.72, 95 %CI = 2.33-25.54, P = 8.11E -4 ) and multiple systems (OR = 8.63, 95 %CI = 1.02-73.43, P = 0.048) risks; NO X was associated with circulatory system (OR = 4.65, 95 %CI = 1.15-18.86, P = 0.031) and cardiac septal defects (OR = 14.09, 95 %CI = 1.62-122.59, P = 0.017) risks; NO 2 was correlated with digestive system (OR = 27.12, 95 %CI = 1.81-407.07, P = 0.017) and cardiac septal defects (OR = 22.57, 95 %CI = 2.50-203.45, P = 0.005) risks. Further MVMR analyses suggest that there may be interactions in the effects of these air pollutants on congenital malformations. In conclusion, this study demonstrated a causal association between air pollution and congenital malformations from a genetic perspective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the rate of Mother-to-child-transmission (MTCT) in women living with HIV (WLWH) in a tertiary care institution. Furthermore, we aimed to assess prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection.", Methods: In this single-center study, retrospective data related to pregnancy and childbirth were collected from 420 WLWH. All data were evaluated descriptively., Results: From January 2014 to December 2020, a total number of 420 pregnant WLWH delivered 428 newborns. 415 (98.8%) were receiving antiretroviral therapy (ART) and 88.8% had a viral load of < 50 cop/ml prior delivery. 46 (11%) of the newborns were born prematurely. Low birth weight < 2500 g occurred in 38 (9.1%) of the children. 219 (52.1%) caesarean sections (CS) were performed. The most frequent indication for an elective CS was a previous CS (70.2%). 8 severe malformations were detected using first and second trimester ultrasound. In one child, MTCT was detected postpartum, resulting in an HIV transmission rate of 0.2% in the presented cohort., Conclusions: The low rate of vertical HIV-transmission in our cohort of 0.2% is the result of interdisciplinary prenatal care and high experience of healthcare providers in treatment of WLWH. Despite high ART coverage and adherence, good maternal immune system and very low vertical HIV transmission rate, maternal HIV infection remains a challenge in obstetric care. First and second ultrasound screening should be a part of prenatal care for HIV-infected women and should also be offered to HIV-negative women. A reduction of the rate of unnecessary elective caesarean deliveries in WLWH is necessary to reduce complications in subsequent pregnancies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: More children are surviving through interventions to address the infectious causes of under-5 mortality; subsequently, the proportion of deaths caused by birth defects is increasing. Prevention, diagnosis, treatment and care interventions for birth defects are available but are needed where the burden is highest, low-and-middle-income countries., Objectives: A selection of birth defect focused publications, conferences, and World Health Assembly resolutions from 2000 to 2017 show that global efforts were made to raise the profile of birth defects in global public health. However, recent donor support and national government interest has waned. Without concerted global action to improve primary prevention and care for children born with birth defects, the Sustainable Development Goal targets for child survival will not be met., Results: Birth defects make up 8% and 10% of global under-5 and neonatal deaths respectively, making them significant contributors to preventable loss of life for children. Survivors face long-term morbidity and lifelong disability which compounds the health and economic woes of individuals, families, communities and society as a whole. Demographic changes in sub-Saharan Africa portend a growing number of births with 1.6 billion projected from 2021 to 2050. More births and better survival without effective prevention and treatment for birth defects translates into more mortality and disability from birth defects., Conclusions: We recommend interventions for prevention of birth defects. These are evidenced-based and affordable, but require low- and middle-income countries to strengthened their health systems. Action against birth defects now will prevent premature deaths and long-term disability, and lead to stronger, more resilient health systems.

Background: Globally, birth defects are the fourth most common cause of neonatal mortality. They cause substantial morbidity, and often long-term disability. Despite this, the impact of birth defects on public health has received little attention in low- and middle-income countries., Aims: To report the types, incidence and geographic distribution of birth defects in the East New Britain Province of Papua New Guinea., Methods: Data were collected over 3 years on newborns with birth defects seen at Rabaul Hospital, born anywhere in the province. Each affected newborn was examined, the anomaly diagnosed and classified. The exact home location was recorded to understand geospatial distribution. To calculate incidence, data were collected on all newborns with a congenital anomaly in a cohort of 2000 consecutive live births at Rabaul Hospital in 2019., Results: Over 3 years, 2018-2020, 137 newborns with birth defects were identified, born in any part of the province. Congenital heart defects, hydrocephalus, microcephaly, craniofacial anomalies, imperforate anus, trachea-oesophageal fistula and diaphragmatic hernia were the most common anomalies. Eight cases of Down syndrome and other chromosomal anomalies were identified. The incidence in 2019 was 14 per 1000 live births. Geographic mapping showed the highest number of cases in the region on the Gazelle Peninsula, the area around the active volcanos., Conclusions: This study provides insights into the incidence and types of birth defects in a rural island province and showed it was possible to map geospatial distribution to further explore epidemiology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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

Background: Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures., Methods: We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD., Results: Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD., Conclusions: A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment., (© 2024 The Author(s). Birth Defects Research published by Wiley Periodicals LLC.)

Background: In observational medication pregnancy safety studies, children are often followed from birth to 1 year of age. However, some major congenital malformations (MCM) may take longer to diagnose., Objectives: We aimed to investigate the proportion of children with detected MCMs at different lengths of follow-up and compare them to the proportion detected at 1 year after birth., Methods: This population-based register study included all singleton children liveborn in Sweden from 2006 to 2016. MCM were identified by ICD-10 codes in the Medical Birth Register and National Patient Register, aligned to the EUROCAT classification system. Cumulative proportion of children with detected MCM at birth, 90 days, 1, 2, and 3 years was calculated and compared between children born preterm and at term., Results: In 1,138,113 liveborn children, the cumulative proportion of children with a detected MCM increased from 1.9% at birth to 3.1%, 3.9%, 4.4% and 4.7% at 90 days, 1, 2, and 3 years after birth, respectively, and varied by MCM subgroup. MCMs of the eye, ear-face-neck, nervous system and genitals were detected with the longest delay, with 31%-59% more detected at 3- versus 1-year follow-up. Compared to children born at term, the proportion of children with any MCM was 2.5 times higher amongst preterm children, with a higher proportion detected over the first 90 days for most MCM subgroups., Conclusions: The proportion of children with a detected MCM varied by MCM subgroup and follow-up time. In pharmacoepidemiology studies of medication safety in pregnancy using Swedish national data, the length of child follow-up should be chosen in accordance with the expected age at detection if a specific subgroup of MCM is under investigation, for example, eye and genital MCM require longer follow-up for detection than abdominal wall and digestive system MCM. However, in most circumstances, 1 year of follow-up is sufficient., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Introduction: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion-specific classification system for birth defect registry-based outcome studies., Methods: For Core Cardiac Lesion Outcome Classifications (C-CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control-modified British Pediatric Association (BPA) codes were defined for each C-CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C-CLOC groups, Texas Birth Defect Registry data (1999-2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C-CLOC classification approaches., Results: C-CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C-CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co-occurring CHD). As expected, C-CLOC groups had retained larger sample sizes (i.e., representing presumably better-powered analytic groups) compared to cases with only one CHD code and no occurring CHDs., Discussion: This new CHD classification system for investigators using birth defect registry data, C-CLOC, is expected to balance clinical outcome homogeneity in analytic groups while maintaining sufficiently large case counts within categories, thus improving power for CHD-specific outcome association comparisons. Future outcome studies utilizing C-CLOC-based classifications are planned., (© 2024 Wiley Periodicals LLC.)

Background and Objective: Congenital heart defects are known to be associated with increased odds of severe COVID-19. Congenital anomalies affecting other body systems may also be associated with poor outcomes. This study is an exhaustive assessment of congenital anomalies and odds of severe COVID-19 in pediatric patients., Methods: Data were retrieved from the COVID-19 dataset of Cerner® Real-World Data for encounters from March 2020 to February 2022. Prior to matching, the data consisted of 664,523 patients less than 18 years old and 927,805 corresponding encounters with COVID-19 from 117 health systems across the United States. One-to-one propensity score matching was performed, and a cumulative link mixed-effects model with random intercepts for health system and patients was built to assess corresponding associations., Results: All congenital anomalies were associated with worse COVID-19 outcomes, with the strongest association observed for cardiovascular anomalies (odds ratio [OR], 3.84; 95% CI, 3.63-4.06) and the weakest association observed for anomalies affecting the eye/ear/face/neck (OR, 1.16; 95% CI, 1.03-1.31)., Conclusions and Relevance: Congenital anomalies are associated with greater odds of experiencing severe symptoms of COVID-19. In addition to congenital heart defects, all other birth defects may increase the odds for more severe COVID-19., Impact: All congenital anomalies are associated with increased odds of severe COVID-19. This study is the largest and among the first to investigate birth defects across all body systems. The multicenter large data and analysis demonstrate the increased odds of severe COVID19 in pediatric patients with congenital anomalies affecting any body system. These data demonstrate that all children with birth defects are at increased odds of more severe COVID-19, not only those with heart defects. This should be taken into consideration when optimizing prevention and intervention resources within a hospital., (© 2024. The Author(s).)

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., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

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

Background: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking., Objectives: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS., Methods: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR., Results: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02)., Conclusions: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma., Objective: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes., Search Strategy: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*)., Selection Criteria: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma., Data Collection and Analysis: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined., Main Results: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance., Conclusions: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objectives: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy., Design: Prospective Nordic registry based study., Setting: Sweden, Denmark, and Norway., Participants: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries., Main Outcome Measure: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy., Results: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk., Conclusions: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Research Council of Norway, NordForsk, European Research Council for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects., Methods: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis., Findings: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes)., Conclusions: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lupo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 (χ 2 trend  = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ 2 trend  = 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., (© 2024. The Author(s).)

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., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background and Aim: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs)., Methods: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed., Results: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics., Conclusions: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

Background: Living in high-altitude regions has been associated with a higher prevalence of some birth defects. Moderate altitudes (1500-2500 m) have been associated with some congenital heart diseases and low birth weight. However, no studies have been conducted for other isolated congenital malformations., Objectives: To estimate the prevalence at birth of isolated congenital malformations in low and moderate altitudes and to determine if moderate altitudes are a risk factor, such as high altitudes, for isolated congenital malformations adjusted for other factors., Methods: The study consisted of a case-control multicenter-multiregional study of 13 isolated congenital malformations. Cases included live births with isolated congenital malformations and controls at low (10-1433 m) and moderate altitudes (1511-2426 m) from a Mexican registry from January 1978 to December 2019. Prevalence per 10,000 (95% CI) per altitude group was estimated. We performed unadjusted and adjusted logistic regression models (adjusted for maternal age, parity, malformed relatives, socioeconomic level, and maternal diabetes) for each isolated congenital malformation., Results: Hydrocephaly and microtia had a higher at-birth prevalence, and spina bifida, preauricular tag, and gastroschisis showed a lower at-birth prevalence in moderate altitudes. Moderate altitudes were a risk factor for hydrocephaly (aOR 1.39), microtia (aOR 1.60), cleft-lip-palate (aOR 1.27), and polydactyly (aOR 1.32) and a protective effect for spina bifida (aOR 0.87) compared with low altitudes., Conclusions: Our findings provide evidence that moderate altitudes as higher altitudes are an associated risk or protective factor to some isolated congenital malformations, suggesting a possible gradient effect., (© 2024 Wiley Periodicals LLC.)

Purpose: To analyze postnatal abnormalities in idiopathic polyhydramnios and to estimate whether there was an association between the severity of polyhydramnios and postnatally diagnosed abnormalities., Methods: This was a retrospective cohort study of all idiopathic polyhydramnios cases delivered at our center between 2017 and 2021. Cases were identified as idiopathic after excluding known fetal genetic or structural abnormalities (including soft markers for aneuploidies), Rh isoimmunization, fetal anemia, multifetal pregnancies, pregestational or gestational diabetes, and known infection with TORCH group agents. The primary outcome was the association between polyhydramnios degree and any abnormalities detected after birth. Additional outcomes were the odds of specific groups of abnormalities based on polyhydramnios degree., Results: The prevalence of idiopathic polyhydramnios was 14.7%. Outcomes of 242 pregnancies with idiopathic polyhydramnios were analyzed. At least one neurodevelopmental, structural, or genetic abnormality was diagnosed in 16.1% of children born to women with idiopathic polyhydramnios. Moderate and severe polyhydramnios are significantly associated with at least one abnormality diagnosed after birth (45.9%, and 41.6%, respectively, p < 0.05). Neurodevelopmental disorders were the most frequent abnormality (5.4%), followed by genetic abnormalities (4.1%) and gastrointestinal abnormalities (2%). Odds of genetic abnormalities and neurodevelopmental disorders in moderate polyhydramnios were significantly higher compared to mild [OR 2.6; 95% CI 1.1-4.3 and aOR 2.4 (95% CI 1.1-3.6) respectively]. As expected, gastrointestinal anomalies were significantly associated with severe polyhydramnios [OR 3.2 (95% CI 1.9-5.5)]., Conclusion: Moderate and severe idiopathic polyhydramnios are associated with anomalies diagnosed after birth. Particularly high risks include neurodevelopmental disorders, genetic abnormalities, and gastrointestinal atresias., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: birth defects are defined as structural or functional congenital malformations occurring during intrauterine and detectable prenatally, at birth, or later. Birth defects-awareness creation among women of reproductive age would help in preventing the occurrence of birth defects of known aetiology worldwide. Thus, this study aimed to assess the birth defects knowledge of women of reproductive age., Methods: we adopted a descriptive cross-sectional study design in eleven purposively selected public hospitals. The study population comprised women with children under five years, and attending child-welfare clinics at the study hospitals. Descriptive analyses consisting of means, standard deviations, medians, and ranges were used to summarize continuous variables, whereas, percentages and proportions were used to summarize categorical variables., Results: the median age of the study participants was 26 years with a mean of 27 (Standard Deviation=5, Range=17-42). A majority (77%) achieved at least a secondary level of education, while the median gravidity was 2 with a mean of 2 (Standard Deviation=1, Range; 1-8). The study participants' knowledge was above average (67%), implying in every 10 of reproductive age 3 had sub-optimal knowledge of birth defects., Conclusion: women of reproductive age were substantially deficient in birth defects knowledge in the county. Thus, we would like to recommend to public health policymakers and health care providers to formulate short health messages on birth defects tailored to women attending child welfare and antenatal clinics at all levels of health care including community health services in the county., Competing Interests: The authors declare no competing interests., (Copyright: George Nyadimo Agot et al.)

To describe the prevalence and death rate of birth defects from population-based surveillance in Hunan Province, China. Data were obtained from the population-based Birth Defects Surveillance System in Hunan Province, China (2010-2020). The surveillance population included all live births, stillbirths, infant deaths, and legal terminations of pregnancy from 28 weeks of gestation to 42 days after birth between 2010 and 2020 when the mother resided in the surveillance area (Liuyang County and Shifeng District, Hunan Province). The prevalence of birth defects is the number of birth defects per 1000 infants (‰). The death rate of birth defects is the number of deaths attributable to birth defects per 100 birth defects (%). The prevalence and death rate with 95% confidence intervals (CI) were calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with birth defects. Our study included 228,444 infants, and 4453 birth defects were identified, with a prevalence of 19.49‰ (95%CI 18.92-20.07). Congenital heart defects were the most common specific defects (5.29‰), followed by limb defects (4.01‰). Birth defects were more common in males than females (22.34‰ vs. 16.26‰, OR = 1.38, 95%CI 1.30-1.47), in premature birth than not (91.82‰ vs. 16.14‰, OR = 6.16, 95%CI 5.72-6.65), in birth weight < 2500 g (98.26‰ vs. 16.22‰, OR = 6.61, 95%CI 6.11-7.15) or > 4000 g (19.48‰ vs. 16.22‰, OR = 1.21, 95%CI 1.03-1.42) than birth weight 2500-4000 g, in hospitalized deliveries than other institutions (22.16‰ vs. 11.74‰, OR = 1.91, 95%CI 1.76-2.07), in multiple births than singletons (28.50‰ vs. 19.28‰, OR = 1.49, 95%CI 1.27-1.76), in maternal age < 20 years (26.33‰ vs. 18.69‰, OR = 1.42, 95%CI 1.15-1.76) or >  = 35 years (24.31‰ vs. 18.69‰, OR = 1.31, 95%CI 1.18-1.45) than maternal age 25-29 years, and in number of pregnancies >  = 4 (22.91‰ vs. 18.92‰, OR = 1.22, 95%CI 1.10-1.35) than the first pregnancy. A total of 747 deaths attributable to birth defects were identified, including 603 (80.72%) stillbirths, 75 (10.04%) deaths within 7 days after birth, 46 (6.16%) deaths in 7-27 days after birth, 23 (3.08%) deaths in 28-42 days after birth. The death rate of birth defects was 16.78% (95%CI 15.57-17.98). Deaths attributable to birth defects accounted for 51.09% (747/1462) of all deaths. Central nervous system defects had the highest death rate (90.27%), and neonatal genetic metabolic defects had the lowest death rate (0.39%). In summary, we have described the prevalence and epidemiology of birth defects from population-based surveillance in Hunan Province, China, 2010-2020. There were differences in the prevalence and death rate of birth defects between population-based surveillance and hospital-based surveillance., (© 2024. The Author(s).)

Background: Patients with heart defects are at risk of developing cardiovascular disease. Our objective was to determine if non-cardiac birth defects are associated with the risk of cardiovascular hospitalisation., Methods: We conducted a longitudinal cohort study of 1 451 409 parous women in Quebec, Canada. We compared patients with cardiac and non-cardiac birth defects of the urinary, central nervous and other systems against patients without defects between 1989 and 2022. The main outcome was hospitalisation for coronary artery disease, ischaemic stroke and other cardiovascular outcomes during 33 years of follow-up. We computed cardiovascular hospitalisation rates and used Cox proportional hazards regression models to measure the association (HR; 95% CI) between non-cardiac defects and later risk of cardiovascular hospitalisation, adjusted for patient characteristics., Results: Women with any birth defect had a higher rate of cardiovascular hospitalisation than women without defects (7.0 vs 3.3 per 1000 person-years). Non-cardiac defects overall were associated with 1.61 times the risk of cardiovascular hospitalisation over time, compared with no defect (95% CI 1.56 to 1.66). Isolated urinary (HR 3.93, 95% CI 3.65 to 4.23), central nervous system (HR 3.33, 95% CI 2.94 to 3.76) and digestive defects (HR 2.39, 95% CI 2.16 to 2.65) were associated with the greatest risk of cardiovascular hospitalisation. These anomalies were associated with cardiovascular hospitalisation whether they presented alone or clustered with other defects. Nevertheless, heart defects were associated with the greatest risk of cardiovascular hospitalisation (HR 10.30, 95% CI 9.86 to 10.75)., Conclusion: The findings suggest that both cardiac and non-cardiac birth defects are associated with an increased risk of developing cardiovascular disease among parous women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)