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Peer-reviewedCC BY 4.0JAMA Network Open

Maternal Influenza Infection During Pregnancy and Neuropsychiatric Disorders in Offspring

1 more authors
8 affiliations
  1. 1Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
  2. 2Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
  3. 3Department of Precision Medicine, Kyung Hee University School of Medicine, Seoul, South Korea
  4. 4School of Medicine, Universidad Espíritu Santo, Samborondón, Ecuador
  5. 5Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile
  6. 6Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
  7. 7Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
  8. 8Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea

Abstract

Importance: Evidence on maternal influenza infection during pregnancy and offspring neuropsychiatric risk remains inconsistent and limited by methodologic concerns.

Objective: To evaluate the association of maternal influenza infection during pregnancy and offspring neuropsychiatric risk.

Design, Setting, and Participants: This binational cohort study included mother-child pairs from the National Health Insurance Service birth cohort in South Korea (discovery cohort) and the JMDC (previously Japan Medical Data Center) birth cohort in Japan (replication cohort). Children born between January 1, 2010, and December 31, 2017, were included in the study and followed up until December 31, 2023.

Exposure: A first recorded maternal influenza diagnosis during pregnancy.

Main Outcomes and Measures: The primary outcome was first postnatal diagnosis of any neuropsychiatric disorder in offspring, including severe neuropsychiatric disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability. Stabilized inverse probability of treatment weighting was applied to adjust for confounding. Weighted Cox proportional hazards models estimated adjusted hazard ratios (AHRs) and 95% CIs. Subgroup analyses were conducted by trimester and season of infection, and sibling-comparison analyses used exposure-discordant sibling pairs. Data analysis was performed from September 2025 to July 2026.

Results: The discovery cohort included 2 564 435 mother-child pairs (mean [SD] maternal age, 31.9 [4.1] years; 1 293 773 [50.5%] male offspring), of whom 35 973 (1.4%) were exposed to maternal influenza during pregnancy. The replication cohort included 181 681 pairs (92 738 [51.0%] male offspring), of whom 11 198 (6.2%) were exposed. In stabilized inverse probability of treatment weighting–based analyses, maternal influenza infection was associated with an increased risk of any neuropsychiatric disorder in the discovery cohort (AHR, 1.09; 95% CI, 1.04-1.14) and replication cohort (AHR, 1.10; 95% CI, 1.02-1.19). Sibling-comparison analyses included 33 191 and 7842 mother-child pairs in the discovery and replication cohorts, respectively; there was not a statistically significant association in the discovery cohort (AHR, 0.98; 95% CI, 0.89-1.09) and replication cohort (AHR, 1.04; 95% CI, 0.88-1.22).

Conclusions and Relevance: In this binational cohort study of mother-child pairs in South Korea and Japan, the modest population-level association between maternal influenza infection during pregnancy and the risk of any neuropsychiatric disorder in offspring was attenuated and not statistically significant in sibling-comparison analyses in either cohort. These findings suggest that familial factors may account for the association observed in the population-level analysis.

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BibTeX
@article{kong2026maternal,
  title = {{Maternal Influenza Infection During Pregnancy and Neuropsychiatric Disorders in Offspring}},
  author = {Jaehyun Kong and Seohyun Hong and Hyesu Jo and Jaeyu Park and Kyeongeun Kim and Dongjin Yeo and Hyunjee Kim and Tae Hyeon Kim and José Francisco López-Gil and Hanseul Cho and Hyeon Seok Hwang and Selin Woo and Dong Keon Yon},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.37902},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854972},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Maternal Influenza Infection During Pregnancy and Neuropsychiatric Disorders in Offspring
AU  - Jaehyun Kong
AU  - Seohyun Hong
AU  - Hyesu Jo
AU  - Jaeyu Park
AU  - Kyeongeun Kim
AU  - Dongjin Yeo
AU  - Hyunjee Kim
AU  - Tae Hyeon Kim
AU  - José Francisco López-Gil
AU  - Hanseul Cho
AU  - Hyeon Seok Hwang
AU  - Selin Woo
AU  - Dong Keon Yon
PY  - 2026
DA  - 2026/10/08
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.37902
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854972
AB  - Importance: Evidence on maternal influenza infection during pregnancy and offspring neuropsychiatric risk remains inconsistent and limited by methodologic concerns.  Objective: To evaluate the association of maternal influenza infection during pregnancy and offspring neuropsychiatric risk.  Design, Setting, and Participants: This binational cohort study included mother-child pairs from the National Health Insurance Service birth cohort in South Korea (discovery cohort) and the JMDC (previously Japan Medical Data Center) birth cohort in Japan (replication cohort). Children born between January 1, 2010, and December 31, 2017, were included in the study and followed up until December 31, 2023.  Exposure: A first recorded maternal influenza diagnosis during pregnancy.  Main Outcomes and Measures: The primary outcome was first postnatal diagnosis of any neuropsychiatric disorder in offspring, including severe neuropsychiatric disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability. Stabilized inverse probability of treatment weighting was applied to adjust for confounding. Weighted Cox proportional hazards models estimated adjusted hazard ratios (AHRs) and 95% CIs. Subgroup analyses were conducted by trimester and season of infection, and sibling-comparison analyses used exposure-discordant sibling pairs. Data analysis was performed from September 2025 to July 2026.  Results: The discovery cohort included 2 564 435 mother-child pairs (mean [SD] maternal age, 31.9 [4.1] years; 1 293 773 [50.5%] male offspring), of whom 35 973 (1.4%) were exposed to maternal influenza during pregnancy. The replication cohort included 181 681 pairs (92 738 [51.0%] male offspring), of whom 11 198 (6.2%) were exposed. In stabilized inverse probability of treatment weighting–based analyses, maternal influenza infection was associated with an increased risk of any neuropsychiatric disorder in the discovery cohort (AHR, 1.09; 95% CI, 1.04-1.14) and replication cohort (AHR, 1.10; 95% CI, 1.02-1.19). Sibling-comparison analyses included 33 191 and 7842 mother-child pairs in the discovery and replication cohorts, respectively; there was not a statistically significant association in the discovery cohort (AHR, 0.98; 95% CI, 0.89-1.09) and replication cohort (AHR, 1.04; 95% CI, 0.88-1.22).  Conclusions and Relevance: In this binational cohort study of mother-child pairs in South Korea and Japan, the modest population-level association between maternal influenza infection during pregnancy and the risk of any neuropsychiatric disorder in offspring was attenuated and not statistically significant in sibling-comparison analyses in either cohort. These findings suggest that familial factors may account for the association observed in the population-level analysis.
SN  - 2574-3805
ER  -