The Association of Prenatal Diagnoses with Mortality and Long-Term Morbidity in Children with Specific Isolated Congenital Anomalies: A European Register-Based Cohort Study.

OBJECTIVES: To compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally. METHODS: Population-based registers' data were linked to hospital and mortality databases. RESULTS: Children whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06). CONCLUSIONS: Our findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed.

Maternal first trimester COVID-19 vaccination and risk of major non-genetic congenital anomalies.

BACKGROUND: Information regarding the risk of early pregnancy COVID-19 vaccination on the development of major congenital anomalies in the offspring is still limited. Here, we study the association between any COVID-19 vaccination during the 1st trimester and at least one major non-genetic congenital anomaly in the offspring. METHODS: We used data from the Dutch Pregnancy Drug Register, an ongoing cohort study. We selected participants with a pregnancy that ended after at least 20 weeks gestation. Pregnant participants self-reported their COVID-19 vaccination status and the presence of congenital anomalies in the offspring. We used logistic regression analyses to study the association between 1st trimester COVID-19 vaccination (gestational week 2 + 0 to 12 + 6) and the risk of at least one major non-genetic congenital anomaly in the offspring. Clustering of anomalies on the ICD10 level by 1st trimester COVID-19 vaccination status was explored using Fisher exact tests. RESULTS: We included 3721 participants of whom 795 (21.4%) were COVID-19 vaccinated during the 1st trimester. The percentage of participants who gave birth to a child with at least one major non-genetic congenital anomaly was comparable between participants who were 1st trimester vaccinated (1.1%) and participants who were not (1.2%) (adjusted odd ratio 0.78 [95% confidence interval 0.35-1.71]). We found no clustering of major non-genetic congenital anomalies by 1st trimester COVID-19 vaccination status (p > .05). CONCLUSIONS: There were no indications of an increased risk of major non-genetic congenital anomalies in the offspring after maternal 1st trimester COVID-19 vaccination. Our findings suggest COVID-19 vaccines are safe during early pregnancy.

Survival of children with rare structural congenital anomalies: a multi-registry cohort study.

BACKGROUND: Congenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995-2014 in Western Europe. METHODS: Live births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births. RESULTS: Amongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3-76.2% at 1 week; 47.4%, CI: 36.4-61.6% at 1 year; 35.6%, CI: 22.2-56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at 10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs. CONCLUSIONS: Pooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study.

INTRODUCTION: The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. OBJECTIVE: The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. METHODS: A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. RESULTS: The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). CONCLUSION: Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.