COVID infection or vaccination during the first trimester of pregnancy is not linked with an increased risk of major birth defects, according to a Scandinavian study in The BMJ.
While it has been established that women who experience COVID during pregnancy were at increased risk of severe illness and had a higher risk of complications, including preterm birth and stillbirth, the risk of birth defects after infection or vaccination was less clear.
To explore this, researchers used national health registries to identify 343,066 liveborn single infants in Sweden, Denmark and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022 and a minimum of nine months postnatal follow-up.
A total of 17,704 (5.2%) of infants were diagnosed with a major congenital anomaly, but the team found no increased risk of any major congenital anomaly after infection with or vaccination against COVID during the first trimester.
Only 4.2% had anomalies in two or more major congenital anomaly subgroups.
Lead author, Dr Stine Urhoj, from the Department of Public Health at the University of Copenhagen, explained that major congenital anomalies were grouped according to EUROCAT definitions and included defects of the heart, nervous and respiratory systems, eye, ear, face and neck anomalies, orofacial clefts, genital and limb anomalies.
“Potentially influential factors such as mother’s age, education, country of birth, weight (BMI), existing chronic conditions, and smoking during pregnancy, were also accounted for in the analyses,” he said.
“Overall, no notable increased risk among offspring of women vaccinated during the first trimester was found for ten of the eleven groups of anomalies evaluated, with an adjusted odds ratio of 1.03.
“Similarly, exposure to the index variant of SARS-COV-2 during the first trimester occurred in 3,124 pregnancies, with 2,065 exposed to alpha and 5,040 to the delta variant, and we observed no notable differences in the risk according to these three viral variants, although the results were associated with a high degree of uncertainty.”
However, there was some heterogeneity in the estimates for the risk of the different congenital anomalies according to exposure to vaccination during the first trimester: 32% for congenital heart defects, 40% for gastrointestinal anomalies, 44% for kidney and urinary anomalies, 76% for nervous system anomalies.
A total of 10,229 infants (3%) had mothers infected with COVID infection during the first trimester. These mothers had higher parity, lower educational level, lower household income level and were more likely to be born in the Middle East or Africa.
Conversely, mothers vaccinated during the first trimester had higher level of education and household income, were more likely to have an underlying chronic disease, and were more likely to be overweight or obese – reflecting typical Western pathologies.
The team noted that as this was an observational study, no firm conclusions could be drawn about cause and effect, and they could not rule out the possibility that other unmeasured factors, such as underlying genetic risk and pre-existing conditions, may have influenced the results.