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  • Clinical Research Article
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Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh

Pediatric Research (2024)Cite this article

Abstract

Background

There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants.

Methods

Population-based, prospective birth cohort study of 288 infants from July 2016–March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1β, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders.

Results

248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1β with lower expressive communication and motor z-scores.

Conclusions

In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction.

Impact

  • Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh.

  • 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants.

  • Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

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Fig. 1: Conceptual diagram.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the Projahnmo research and field staff for implementing the study, and the mothers and children who participated in the study. Dr. Lee would like to thank K23 mentors and advisors (Terrie Inder, Abdullah Baqui, Raina Fichorova, Charles Nelson, Emily Oken and Wafaie Fawzi), the WHO AMANHI Study group, and Tessa Kehoe for assisting with formatting the manuscript for submission. This research was funded by the National Institutes of Child Health and Development (grant number 5K23HD091390). This work co-funded by the Bill & Melinda Gates Foundation through a grant to the World Health Organization/Johns Hopkins University.

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Author notes

  1. These authors contributed equally: Abdullah H. Baqui, Terrie Inder.

Authors and Affiliations

  1. Department of Pediatrics, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Anne CC Lee, Sara Cherkerzian, Lian V. Folger & Ingrid Olson

  2. Harvard Medical School, Boston, MA, 02115, USA

    Anne CC Lee, Sara Cherkerzian, Emily Oken, Raina Fichorova & Charles A. Nelson

  3. Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, 1212, Bangladesh

    Fahmida Tofail

  4. Projahnmo Research Foundation, Banani, Dhaka, 1213, Bangladesh

    Salahuddin Ahmed, Sayedur Rahman & Nabid H. Chowdhury

  5. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA

    Rasheda Khanam & Abdullah H. Baqui

  6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA

    Emily Oken

  7. Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA

    Emily Oken

  8. Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Raina Fichorova

  9. Boston Children’s Hospital, Boston, MA, 02115, USA

    Charles A. Nelson

  10. Harvard Graduate School of Education, Boston, MA, 02138, USA

    Charles A. Nelson

  11. Center for Neonatal Research, Children’s Hospital of Orange County, Orange, CA, 92868, USA

    Terrie Inder

  12. Department of Pediatrics, University of California Irvine, Irvine, CA, 92697, USA

    Terrie Inder

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Contributions

A.C.L., A.H.B., T.I., C.A.N., E.O., and R.F. contributed to the conceptualization and design of the study. F.T., S.R., S.A., R.K., A.H.B., and A.C.L. contributed to acquisition of data. R.F. conducted laboratory analyses. N.H.C. and R.K. contributed to data curation. S.C., A.C.L., L.V.F., and I.O. contributed to the analysis and interpretation of data. A.C.L. drafted the manuscript. A.C.L., S.C., F.T., L.V.F., S.A., S.R., N.H.C., R.K., I.O., E.O., R.F., C.A.N, A.H.B, and T.I. critically revised the manuscript for important intellectual content. All authors have approved of the final version to be published.

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Correspondence to Anne CC Lee.

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Lee, A.C., Cherkerzian, S., Tofail, F. et al. Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03101-x

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