Detection of major congenital malformations depends on length of follow‐up in Swedish National Health Register Data: Implications for pharmacoepidemiological research on medication safety in pregnancy.

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. [ABSTRACT FROM AUTHOR]