Heavy prenatal alcohol exposure and overall morbidities: a Danish nationwide cohort study from 1996 to 2018

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 alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related 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 1 407 689 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 (0middot4%) had heavy prenatal alcohol exposure and 1 183 704 (99middot6%) were classified as non-alcohol-exposed births. 578 179 (48middot6%) babies were female and 610 324 (51middot4%) 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 0middot5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4middot70% [95% CI 3middot70-5middot71]), small for gestational age (4middot63% [3middot72-5middot55]), delayed milestone (3middot81% [2middot99-4middot64]), and other preterm infants (2middot69% [1middot71-3middot68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1middot0%, 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.Funding The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Moller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Automated summary

This Danish study investigated the morbidity risk in children exposed to heavy prenatal alcohol and found an increased risk of various diseases and health problems, particularly related to brain function, behavioral disorders, infections, and neonatal conditions. The findings highlight the importance of addressing prenatal alcohol exposure as a key public health issue and emphasizing pre-conceptional care.