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.