New research published in PLOS Medicine based on nationwide data from Denmark suggests that common maternal infections during pregnancy are unlikely to have a meaningful effect on children’s cognitive outcomes later in life. In one of the largest studies of its kind, researchers analyzed school grades and intelligence scores among more than 250,000 siblings and found no consistent differences based on whether their mothers had been prescribed antibiotics or hospitalized for infection during pregnancy.
While certain severe infections during pregnancy—such as rubella or toxoplasmosis—are known to pose risks to fetal brain development, the broader implications of more common infections, like urinary tract or respiratory infections, have remained unclear. Some previous studies have suggested these everyday illnesses might influence the child’s future cognitive performance. However, many of these earlier studies were unable to fully account for shared family factors that might bias the results, such as parental intelligence, socioeconomic status, or genetic predispositions.
“Previous studies and anecdotal clinical stories have suggested an negative impact of common maternal infections on offspring cognitive outcomes. However, most previous studies have been small and have not been able to correct for the social biases associated with both the risk of maternal infection during pregnancy and the cognitive outcome of the offspring,” said study author Anders Husby, a resident physician and postdoctoral researcher at the Department of Paediatrics and Adolescent Medicine at Rigshospitalet, and the Department of Congenital Disorders at Statens Serum Institut in Copenhagen.
“Using data from our previous study on gestational age at birth and long-term cognitive outcome, we could investigate the association between common maternal infections during pregnancy and long-term cognitive outcome in a very large nationwide cohort composed of full-siblings. Using the full-sibling design, we could compare siblings where the same mother, who had or hadn’t an infection during pregnancy, and thereby minimize confounding from social factors.
The data for the research came from multiple national Danish registries. The researchers included information on filled antimicrobial prescriptions as a proxy for mild infections and inpatient hospitalizations to represent more severe cases. They then linked these exposure records to standardized school grades in language and mathematics at age 15–16, as well as intelligence test scores from mandatory military conscription assessments taken by adolescent boys.
The cohort included over 274,000 children born between 1996 and 2003, with nearly 81,000 having mothers who had filled at least one prescription for a systemic antimicrobial during pregnancy. A smaller subset—roughly 5,600 children—had mothers who were hospitalized for infections while pregnant. Intelligence scores were available for a sub-cohort of full brothers who had undergone testing for military service.
The results indicated little to no difference in academic or cognitive performance based on maternal infection exposure. For example, among children whose mothers filled one prescription for antibiotics during pregnancy, the average difference in language or math grades was virtually zero once shared family factors were accounted for. Similarly, the estimated IQ difference in adolescent males was only about 0.3 points on average—well within the margin of error.
In contrast, when the researchers looked at models that did not account for shared family factors, they found consistent and statistically significant associations between maternal infections and lower scores. This discrepancy highlights how results may be influenced by family-level confounding, and it underscores the value of sibling-based analyses in addressing such biases.
Even when examining different types of antibiotics or timing of exposure across pregnancy, the results did not point to any consistent effects. The most common antibiotics—such as beta-lactams—showed no meaningful associations with lower academic performance or IQ. Nor did the timing of exposure appear to matter: infections occurring during early gestation, late gestation, or any specific bi-weekly window were not linked to worse outcomes.
“We were open as to whether the exposure (i.e., common maternal infections) had negative or no effects on cognitive outcomes, so we were not surprised by the results,” Husby told PsyPost. “However, it is reassuring to see that our study with large certainty can rule out moderate-or-large negative effects on cognitive outcomes from common maternal infections.”
There were a few small exceptions. For example, there was a slight reduction in mathematics scores among children whose mothers had filled one or two antibiotic prescriptions. But these differences were minimal—about 1–2% of a standard deviation—and the researchers noted that confidence intervals ruled out anything larger than a 3% drop. These findings, they argue, are not likely to be meaningful at the individual or population level.
The study also explored whether more severe infections, indicated by hospitalization, might have a stronger effect. One notable finding was a slight dip in school grades among children whose mothers had been hospitalized for an infection during weeks 24–25 of pregnancy. But this effect disappeared when the analysis was limited to children born at full term, suggesting that the initial association may have been influenced by gestational age rather than the infection itself.
The researchers conducted several sensitivity analyses to test the robustness of their findings. These included restricting the sample to term births, adjusting for maternal smoking, and imputing scores for children who did not participate in school exams. Across these variations, the results remained consistent: there was no evidence of meaningful cognitive harm associated with common infections during pregnancy.
“Our study suggests that common maternal infections and the associated antimicrobial treatment during pregnancy are unlikely to meaningfully impair offspring cognitive outcomes, such as school grades or adolescent IQ,” Husby said. “This provides reassuring evidence supporting the safety of commonly prescribed antimicrobials during gestation, and suggest an minor role of common prenatal infections in cognitive deficits in offspring.”
The study does have limitations. One is that it lacked information on medications administered during hospital stays, which could potentially affect outcomes. However, hospitalization for infection was relatively rare, and the analysis of this group did not show signs of negative cognitive effects. Another limitation is that the researchers could not identify specific pathogens responsible for infections, nor could they account for maternal fever, which is often part of the body’s inflammatory response.
“We hope in future studies to could look a specific infections, which was not possible in the current study which only identified infections by antibiotics prescriptions and diagnostic codes for infectious disease hospitalization,” Husby said.
Still, the absence of dose-response patterns or consistent links between more severe exposure and worse outcomes suggests that any such factors may have minimal impact on cognition.
However, the authors also caution that while their findings apply to common infections and antibiotic use, they do not rule out the well-established effects of rare but serious prenatal infections. Serious diseases can still cause profound developmental disabilities, and preventive measures remain essential for managing those risks.
“Our findings are mainly applicable to common maternal infections identified by maternal antibiotic prescriptions and common hospitalizations for infections, as it was were we had most statistical power to indicate a difference. Furthermore, it is well-documented that certain rare prenatal infection (e.g. rubella, malaria, and toxoplasmosis) can lead to severe cognitive deficits in the fetus.”
In addition to reassuring expectant parents, the study carries broader methodological implications. The researchers noted that earlier studies had hinted at negative outcomes associated with prenatal infection, but these associations often disappeared when sibling comparisons were used. This suggests that family-level confounding may play a larger role than previously thought in shaping observed outcomes.
“Initially, it looked as if infections might be linked to lower school grades and IQ,” Husby explained. “But when we compared within sibling-groups (where one sibling was exposed to maternal infection in the womb and others wasn’t), those differences disappeared. That is a powerful reminder of how critical it is to use study designs that can robustly address the impact of social biases.”
The study, “Maternal infections during pregnancy and offspring cognitive outcome: A nationwide full-sibling cohort study,” was authored by Anders Husby, Kim D. Jakobsen, Jan Wohlfahrt, and Mads Melbye.
