Parental Multiple Endocrine Neoplasia Type 1 (MEN 1) Is Associated with Increased Offspring Childhood Mortality

Context: Information regarding the impact of parental multiple endocrine neoplasia type 1 (MEN 1) on neonatal outcomes is limited to case reports. Objective: To determine the impact of parental MEN 1 on neonatal outcomes. Methods: Retrospective cohort analysis of the Tasman 1 MEN 1 kindred stratified by whether birth occurred before ("historical cohort") or after ("contemporary cohort") prospective screening commenced. The historical cohort included kindred members born between 1825 and 1984 (n = 341 children with a MEN 1 positive (MEN 1(+)) parent and n = 314 children with MEN 1 negative (MEN 1(-)) parents). The contemporary cohort included neonates (n = 52) of MEN 1(+) women (n = 21) managed at a tertiary referral hospital between 1985 and 2018. Results: Historical cohort: compared with MEN 1- parents, children of MEN 1(+) parents were more likely to die postpartum (HR 4.6, P=.046 at 6 months of age). Excess mortality at 15 years of age was observed for children of MEN 1(+) mothers (HR 8.50, P=.002) and fathers (HR 3.82, P=.03). Contemporary cohort: neonates of MEN 1(+) mothers were more likely to have low birth weight (28.9% vs 6.7%, P=.01), be admitted to a higher care nursery (40.4% vs 17%, P=.02), and require a longer median postnatal stay (5 vs 4 days, P=.009) than the Australian average. Isolated antenatal hypercalcemia did not significantly alter neonatal outcomes. Conclusion: Children with a MEN 1(+) parent are disproportionately vulnerable postpartum. Neonates of MEN 1(+) mothers remain vulnerable despite contemporary care. The excess risk was not fully explained by maternal MEN 1 or antenatal hypercalcemia.