Effects of prenatal bacterial infection on cognitive performance in early childhood
Abstract
BACKGROUND: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up. OBJECTIVES: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection. METHODS: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models. RESULTS: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters. CONCLUSIONS: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.
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There is extensive evidence in humans showing that prenatal infectious exposure is associated with cognitive and other neurodevelopmental impairments.
“Furthermore, there is extensive evidence in humans showing that prenatal infectious exposure is associated with cognitive and other neurodevelopmental impairments (463, 464).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [463]
Cites
Marginal Structural Models and Causal Inference in Epidemiology
Robins, J. M., Hernán, M. Á., & Brumback, B. (2000) · Epidemiology · doi:10.1097/00001648-200009000-00011 · Cited by 5,581 · see citing works
Causal Diagrams for Epidemiologic Research
Greenland, S., Pearl, J., & Robins, J. M. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00008 · Cited by 3,728 · see citing works
A structural approach to selection bias
Hernán, M. A., Hernández-Díaz, S., & Robins, J. M. (2004) · Epidemiology · doi:10.1097/01.ede.0000135174.63482.43 · Cited by 2,844 · see citing works
Constructing Inverse Probability Weights for Marginal Structural Models
Cole, S. R., & Hernan, M. A. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwn164 · Cited by 2,796 · see citing works
Maternal Pesticide Exposure from Multiple Sources and Selected Congenital Anomalies
Shaw, G. M., Wasserman, C. R., O’Malley, C. D., Nelson, V. E., & Jackson, R. J. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00011 · Cited by 1,783 · see citing works
Analysis of Semiparametric Regression Models for Repeated Outcomes in the Presence of Missing Data
Robins, J. M., Rotnitzky, A. G., & Zhao, L. P. (1995) · Journal of the American Statistical Association · doi:10.1080/01621459.1995.10476493 · Cited by 1,574 · see citing works
van der Laan, M. J., Polley, E., & Hubbard, A. (2007) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1309 · Cited by 1,472 · see citing works
A tutorial on propensity score estimation for multiple treatments using generalized boosted models
McCaffrey, D. F., Griffin, B. A., Almirall, D., Slaughter, M. E., Ramchand, R., & Burgette, L. F. (2013) · Statistics in Medicine · doi:10.1002/sim.5753 · Cited by 1,450 · see citing works
Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies
Brown, A. S., & Derkits, E. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09030361 · Cited by 1,269 · see citing works
Kang, J. D. Y., & Schafer, J. L. (2007) · Statistical Science · doi:10.1214/07-sts227 · Cited by 1,259 · see citing works
Doubly robust estimation of causal effects
Funk, M. J., Westreich, D., Wiesen, C., Stürmer, T., Brookhart, M. A., & Davidian, M. (2011) · American Journal of Epidemiology · doi:10.1093/aje/kwq439 · Cited by 1,158 · see citing works
Rubin, D. B. (2007) · Statistics in Medicine · doi:10.1002/sim.2739 · Cited by 1,047 · see citing works
Controlling Bias in Observational Studies: A Review
Cochran, W. G. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511810725.005 · Cited by 986 · see citing works
Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · see citing works
Increased dopamine transmission in schizophrenia: relationship to illness phases.
Laruelle, M., Abi-Dargham, A., Gil, R. B., Kegeles, L., & Innis, R. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00067-0 · Cited by 744 · see citing works
Identifiability, Exchangeability, and Epidemiological Confounding
GREENLAND, S., & ROBINS, J. M. (1986) · International Journal of Epidemiology · doi:10.1093/ije/15.3.413 · Cited by 686 · see citing works
Snowden, J. M., Rose, S., & Mortimer, K. M. (2011) · American Journal of Epidemiology · doi:10.1093/aje/kwq472 · Cited by 514 · see citing works
Khandaker, G. M., Zimbron, J., Lewis, G., & Jones, P. B. (2012) · Psychological Medicine · doi:10.1017/s0033291712000736 · Cited by 468 · see citing works
Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis
Masi, A., Quintana, D. S., Glozier, N., Lloyd, A. R., Hickie, I. B., & Guastella, A. J. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.59 · Cited by 467 · see citing works
Marginal Structural Models as a Tool for Standardization
Sato, T. S., & Matsuyama, Y. (2003) · Epidemiology · doi:10.1097/01.ede.0000081989.82616.7d · Cited by 456 · see citing works
Intelligence in Schizophrenia: Meta-analysis of the Research
Aylward, E., Walker, E. F., & Bettes, B. A. (1984) · Schizophrenia Bulletin · doi:10.1093/schbul/10.3.430 · Cited by 401 · see citing works
Targeted Maximum Likelihood Estimation for Causal Inference in Observational Studies
Schuler, M. S., & Rose, S. (2016) · American Journal of Epidemiology · doi:10.1093/aje/kww165 · Cited by 395 · see citing works
Kang, J., & Schafer, J. L. (2007) · Statistical Science · Cited by 368 · see citing works
Loss to Follow-up in Cohort Studies
Howe, L. D., Tilling, K. M., Galobardes, B., & Lawlor, D. A. (2012) · Epidemiology · doi:10.1097/ede.0b013e31827623b1 · Cited by 311 · see citing works
Prenatal rubella, premorbid abnormalities, and adult schizophrenia
Brown, A. S., Cohen, P., Harkavy‐Friedman, J., Babulas, V. P., Malaspina, D., Gorman, J., & Susser, E. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01068-x · Cited by 298 · see citing works
Neurotransmitter interactions in schizophrenia–therapeutic implications
Carlsson, A., Waters, N., & Carlsson, M. L. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00117-1 · Cited by 298 · see citing works
Maternal Infection During Pregnancy and Autism Spectrum Disorders
Zerbo, O., Qian, Y., Yoshida, C., Grether, J. K., Van de Water, J., & Croen, L. A. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-2016-3 · Cited by 298 · see citing works
Myrianthopoulos, N. C., & French, K. S. (1968) · Social Science & Medicine (1967) · doi:10.1016/0037-7856(68)90004-8 · Cited by 284 · see citing works
Association Between Prenatal Exposure to Bacterial Infection and Risk of Schizophrenia
Sørensen, H. J., Mortensen, E. L., Reinisch, J. M., & Mednick, S. A. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn121 · Cited by 261 · see citing works
Jones, K. L., Croen, L. A., Yoshida, C. K., Heuer, L., Hansen, R., Zerbo, O., DeLorenze, G. N., Kharrazi, M., Yolken, R., Ashwood, P., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.77 · Cited by 260 · see citing works
Gilmore, J. H., Jarskog, L. F., Vadlamudi, S., & Lauder, J. M. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300446 · Cited by 246 · see citing works
Goldstein, J. M., Seidman, L. J., O’Brien, L. M., Horton, N. J., Kennedy, D. N., Makris, N., Caviness, V. S., Faraone, S. V., & Tsuang, M. T. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.2.154 · Cited by 232 · see citing works
Immune Regulation during Pregnancy and Host–Pathogen Interactions in Infectious Abortion
Entrican, G. (2002) · Journal of Comparative Pathology · doi:10.1053/jcpa.2001.0539 · Cited by 225 · see citing works
Clarke, M. C., Tanskanen, A. J., HUTTUNEN, M. O., Whittaker, J. C., & Cannon, M. D. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.08010031 · Cited by 216 · see citing works
Maternal urinary tract infection: is it independently associated with adverse pregnancy outcome?
Mazor-Dray, E., Levy, A., Schlaeffer, F., & Sheiner, E. (2008) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050802488246 · Cited by 195 · see citing works
The role of the c‐statistic in variable selection for propensity score models
Westreich, D. J., Cole, S. R., Funk, M. J., Brookhart, M. A., & Stürmer, T. (2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.2074 · Cited by 165 · see citing works
Emiru, T., Beyene, G., Tsegaye, W., et al. (2013) · BMC Research Notes · doi:10.1186/1756-0500-6-292 · Cited by 147 · see citing works
Kang, J., & Schafer, J. L. (2008) · doi:10.48550/arxiv.0804.2958 · Cited by 138 · see citing works
Seidman, L. J., Buka, S. L., Goldstein, J. M., & Tsuang, M. T. (2006) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390500360471 · Cited by 132 · see citing works
Self-citationAcute antepartum pyelonephritis in pregnancy: a critical analysis of risk factors and outcomes
Farkash, E., Weintraub, A. Y., Sergienko, R., Wiznitzer, A., Zlotnik, A., & Sheiner, E. (2012) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2012.01.024 · Cited by 130 · see citing works
Seidman, L. J., Cherkerzian, S., Goldstein, J. M., Agnew-Blais, J., Tsuang, M. T., & Buka, S. L. (2013) · Psychological Medicine · doi:10.1017/s0033291712000773 · Cited by 114 · see citing works
Self-citationEllman, L. M., Yolken, R. H., Buka, S. L., Torrey, E. F., & Cannon, T. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.12.015 · Cited by 114 · see citing works
Self-citationMasi, A., Breen, E. J., Alvares, G. A., Glozier, N., Hickie, I. B., Hunt, A. M., Hui, J., Beilby, J. P., Ravine, D., Wray, J. A., et al. (2017) · Molecular Autism · doi:10.1186/s13229-017-0176-2 · Cited by 110 · see citing works
Maternal and fetal immune responses during pregnancy.
Sargent, I. L. (1993) · PubMed · Cited by 106 · see citing works
Seidman, L. J., Buka, S. L., Goldstein, J. M., Horton, N. J., Rieder, R. O., & Tsuang, M. T. (2000) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033455 · Cited by 103 · see citing works
Self-citationSullivan, R. M., Wilson, D. A., Feldon, J., Yee, B. K., Meyer, U., Richter‐Levin, G., Avital, A., Tsoory, M., Gruß, M., Bock, J., et al. (2006) · Developmental Psychobiology · doi:10.1002/dev.20170 · Cited by 98 · see citing works
Lee, Y. A., Cherkerzian, S., Seidman, L. J., Papandonatos, G. D., Savitz, D. A., Tsuang, M. T., Goldstein, J. M., & Buka, S. L. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.18101206 · Cited by 73 · see citing works
Self-citationPrenatal maternal immune disruption and sex-dependent risk for psychoses
Goldstein, J. M., Cherkerzian, S., Seidman, L. J., Donatelli, J.-A. L., Remington, A., Tsuang, M. T., Hornig, M., & Buka, S. L. (2014) · Psychological Medicine · doi:10.1017/s0033291714000683 · Cited by 71 · see citing works
Self-citationG-computation of average treatment effects on the treated and the untreated
Wang, A., Nianogo, R. A., & Arah, O. A. (2017) · BMC Medical Research Methodology · doi:10.1186/s12874-016-0282-4 · Cited by 70 · see citing works
Using Super Learner Prediction Modeling to Improve High-dimensional Propensity Score Estimation
Wyss, R., Schneeweiß, S., van der Laan, M. J., Lendle, S., Ju, C., & Franklin, J. M. (2017) · Epidemiology · doi:10.1097/ede.0000000000000762 · Cited by 70 · see citing works
Lower Urinary Tract Dysfunction in Pregnancy
Mikhail, M. S., & Anyaegbunam, A. (1995) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199509000-00022 · Cited by 61 · see citing works
Goldstein, J. M., Seidman, L. J., Santangelo, S. L., Knapp, P. H., & Tsuang, M. T. (1994) · Journal of Psychiatric Research · doi:10.1016/0022-3956(94)90039-6 · Cited by 58 · see citing works
Schizophrenia in High-Risk Children: Sex Differences in Predisposing Factors.
Mednick, S. A. (1977) · Cited by 54 · see citing works
Risk factors for bacterial vaginosis during pregnancy among African American women
Trabert, B. L., & Misra, D. P. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2007.03.085 · Cited by 53 · see citing works
Kim-Fine, S., Regnault, T. R. H., Lee, J. S., et al. (2012) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2012.684165 · Cited by 53 · see citing works
Agnew‐Blais, J. C., Buka, S. L., Fitzmaurice, G. M., Smoller, J. W., Goldstein, J. M., & Seidman, L. J. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv027 · Cited by 47 · see citing works
Self-citationUsing Non-experimental Data to Estimate Treatment Effects
Stuart, E. A., Marcus, S. M., Horvitz-Lennon, M. V., Gibbons, R. D., Normand, S. T., & Brown, C. H. (2009) · Psychiatric Annals · doi:10.3928/00485713-20090625-07 · Cited by 45 · see citing works
Cognitive ability in childhood and the chronicity and suicidality of depression
Hung, G. C., Pietras, S. A., Carliner, H., Martin, L. T., Seidman, L. J., Buka, S. L., & Gilman, S. E. (2016) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.158782 · Cited by 24 · see citing works
Self-citationMcDermott, S. W., Mann, J. R., & Wu, J. (2009) · Neuroepidemiology · doi:10.1159/000268824 · Cited by 15 · see citing works
Agnew-Blais, J., Seidman, L., Fitzmaurice, G., Smoller, J., Goldstein, J., & Buka, S. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2016.12.010 · Cited by 11 · see citing works
Self-citation
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Maternal prenatal infection and anxiety predict neurodevelopmental outcomes in middle childhood
O'Connor, T. G., Ciesla, A. A., Sefair, A. V., Thornburg, L. L., Brown, A. S., Glover, V., & O'Donnell, K. J. (2022) · Journal of Psychopathology and Clinical Science · doi:10.1037/abn0000746 · Cited by 31 · see citing works
- Authors
- Lee, Y. H., Papandonatos, G. D., Savitz, D. A., Heindel, W. C., & Buka, S. L.
- Affiliations
- Department of Epidemiology Brown University Providence RI USA
- Brown University (US)
- Corresponding author
- Buka, Stephen L.
- Venue
- Paediatric and Perinatal Epidemiology
- Publisher
- Wiley
- Published
- 2019-12-13
- Volume
- 34
- Issue
- 1
- Pages
- 70-79
- ISSN
- 0269-5022 (ISSN-L)
- 1365-3016
- OpenAlex
- W2996465407
- Cited by
- 21
- References
- 60
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Paediatric and Perinatal Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Keywords
- maternal infection, brain development, cognitive performance, intelligence quotient, early childhood, Collaborative Perinatal Project, inverse probability weighting, third trimester exposure, sex differences, performance IQ
- MeSH terms
- Adult, Bacterial Infections, Child, Cognition, Female, Humans, Intelligence, Male, Pregnancy, Pregnancy Complications, Infectious, Prenatal Exposure Delayed Effects, Wechsler Scales, Cohort Studies, Young Adult, Cognitive Dysfunction
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