Background Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic
review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and
reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcoholexposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and healthrelated problems.
Methods Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed
up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and
births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up.
Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient
Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population
Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal
alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her
child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy.
Findings Of 1407 689 identified singleton births, 219 186 were excluded for reasons including they were born to
immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal
alcohol exposure and 1 183704 (99·6%) were classified as non-alcohol-exposed births. 578179 (48·6%) babies were
female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with
fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%,
predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest
standardised risk differences were found for low birthweight (4·70% [95% CI 3·70–5·71]), small for gestational age
(4·63% [3·72–5·55]), delayed milestone (3·81% [2·99–4·64]), and other preterm infants (2·69% [1·71–3·68]). Of
previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at
least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities.
Interpretation Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and
previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with
a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the
profound degree to which pre-conceptional care is mandatory