Mortality among individuals with congenital malformations who reach adulthood: long-term follow-up of the Jerusalem Perinatal Study cohort

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Abstract
Background: While risks associated with congenital anomalies (CAs) in childhood are well documented, data on the long-term impact of CAs on adult mortality are lacking. We aimed to study mortality risks in adults born with CAs using the population-based Jerusalem Perinatal Study cohort. Methods: Individuals born in 1964–1976 who attained 18 years of age were followed up until 2016 or date of death (median 27.5 years). We categorized anomalies by presence/absence, severity, multiplicity, and body system affected. Cox regression models were constructed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAs and all-cause mortality, adjusting for birth weight, delivery mode, maternal age, socioeconomic status at birth, maternal country of birth, and stratified by offspring sex and maternal education. Results: Of the 91 459 live-born offspring, 2429 (2.7%) died before attaining age 18 years and 1454 (1.6%) died thereafter. Of 87 621 who survived to age 18, 5621 (6.4%) had CAs. Mortality was increased in those bearing any (adjusted HR (HRadj) = 1.53, CI: 1.29–1.83), single (HRadj = 1.51, CI: 1.27–1.81), severe (HRadj = 2.21, CI: 1.75–2.77), and moderate and severe malformations combined (HRadj = 2.19, CI: 1.09–4.40), when compared to individuals without anomalies. Additionally, adult mortality was increased in individuals with cardiovascular (HRadj = 4.81, CI: 2.15–10.70), gastrointestinal (HRadj = 2.74, CI: 1.47–5.11), and genitourinary anomalies (HRadj = 1.51, CI: 1.07–2.14). Conclusion: Increased risks of premature mortality are observed in individuals with CA who reach adulthood and are modified by severity and the body system affected. Long-term and focused follow-up for adults with CAs is warranted.

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