Skip to main content

Advertisement

SpringerLink
Log in

Prenatal environmental adversity and child neurodevelopmental delay: the role of maternal low-grade systemic inflammation and maternal anti-inflammatory diet

  • Original Contribution
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

Maternal inflammation has been proposed as a possible pathway connecting prenatal environmental adversity (PEA), which includes maternal overweightness or obesity, diabetes, hypertensive disorders, and mood or anxiety disorders, to child neurodevelopmental delay. However, effective preventive measures have not yet been reported. Herein, we aimed to investigate whether a maternal anti-inflammatory diet reduced the risk of PEA-induced neurodevelopmental delay, by inhibiting inflammation. This prospective study included 7438 mother–child pairs. Maternal overweightness or obesity, diabetes, and hypertensive disorders were diagnosed before 28 week gestation. Maternal depression disorders were identified using the Edinburgh postnatal depression survey (EPDS) during mid-pregnancy. During mid- and late pregnancy, maternal high-sensitivity C-reactive protein (hs-CRP) levels were measured to evaluate systemic inflammation. The inflammatory potential of the diet was evaluated using the food-based empirical dietary inflammatory pattern (EDIP) score during mid-pregnancy. Pregnant women were classified into high- or low-score groups based on the median EDIP score. The outcomes of neurodevelopmental delay at 6–36 month postpartum were extracted from the Register of Child Healthcare. Among the 7438 mother–child pairs, 2937 (39.5%) were exposed to PEA, and neurodevelopmental delay occurred in 540 (7.3%). Children exposed to PEA had a higher risk of neurodevelopmental delay than those not exposed. PEA exposure was associated with increased hs-CRP during pregnancy in a PEA monotonic manner, an interquartile range increase in hs-CRP in mid- and late pregnancy was associated with an increased risk of child neurodevelopmental delay. Higher maternal persistent inflammation partially mediated the effect of PEA exposure on child neurodevelopmental delay by 17.19%. An increased risk of PEA-related neurodevelopmental delay was observed only in the children of mothers with high-EDIP rather than low-EDIP. These results suggest that increased systemic inflammation through mid- and late pregnancy mediates the association between PEA and child neurodevelopmental delay. A maternal anti-inflammatory diet may improve PEA-induced neurodevelopmental delay, by inhibiting inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The original contributions presented in the study are included in the article/Supplementary material, futher inquiries can be directed to the corresponding author.

References

  1. Bolduc ME, Du Plessis AJ, Sullivan N et al (2011) Spectrum of neurodevelopmental disabilities in children with cerebellar malformations. Dev Med Child Neurol 53(5):409–416

    Article  PubMed  Google Scholar 

  2. Miguel PM, Pereira LO, Silveira PP, Meaney MJ (2019) Early environmental influences on the development of children’s brain structure and function. Dev Med Child Neurol 61(10):1127–1133

    Article  PubMed  Google Scholar 

  3. Girchenko P, Lahti-Pulkkinen M, Heinonen K et al (2020) Persistently high levels of maternal antenatal inflammation are associated with and mediate the effect of prenatal environmental adversities on neurodevelopmental delay in the offspring. Biol Psychiatry 87(10):898–907

    Article  CAS  PubMed  Google Scholar 

  4. Bodnar TS, Raineki C, Wertelecki W, et al. Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure. J Neuroinflammation. Jan 28 2020;17(1):39.

  5. Herrera EA, Krause B, Ebensperger G et al (2014) The placental pursuit for an adequate oxidant balance between the mother and the fetus. Front Pharmacol 5:149

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jeve YB, Konje JC, Doshani A (2015) Placental dysfunction in obese women and antenatal surveillance strategies. Best Pract Res Clin Obstet Gynaecol 29(3):350–364

    Article  PubMed  Google Scholar 

  7. Moon KC, Park CW, Park JS, Jun JK. Fetal Growth Restriction and Subsequent Low Grade Fetal Inflammatory Response Are Associated with Early-Onset Neonatal Sepsis in the Context of Early Preterm Sterile Intrauterine Environment. J Clin Med. May 8 2021;10(9).

  8. Zhou D, Pan YX (2015) Pathophysiological basis for compromised health beyond generations: role of maternal high-fat diet and low-grade chronic inflammation. J Nutr Biochem 26(1):1–8

    Article  PubMed  Google Scholar 

  9. Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107(3):499–511

    Article  PubMed  Google Scholar 

  10. Kushner I, Rzewnicki D, Samols D (2006) What does minor elevation of C-reactive protein signify? Am J Med 119(2):166.e117–128

    Article  Google Scholar 

  11. Su X, Zhang S, Lin Q, et al. (2022) Prenatal exposure to air pollution and neurodevelopmental delay in children: a birth cohort study in Foshan, China. Sci Total Environ 816:151658

  12. Haß U, Herpich C, Norman K (2019) Anti-inflammatory diets and fatigue. Nutrients 11(10).

  13. Wang Q, Yuan J, Yu Z et al (2018) FGF21 attenuates high-fat diet-induced cognitive impairment via metabolic regulation and anti-inflammation of obese mice. Mol Neurobiol 55(6):4702–4717

    Article  CAS  PubMed  Google Scholar 

  14. Wang X, Yang J, Zhang H, Yu J, Yao Z (2019) Oral probiotic administration during pregnancy prevents autism-related behaviors in offspring induced by maternal immune activation via anti-inflammation in mice. Autism Res 12(4):576–588

    Article  PubMed  Google Scholar 

  15. Chen CM (2008) Overview of obesity in Mainland China. Obes Rev 9(Suppl 1):14–21

    Article  PubMed  Google Scholar 

  16. Cox J (2019) Thirty years with the Edinburgh Postnatal Depression Scale: voices from the past and recommendations for the future. Br J Psychiatry 214(3):127–129

    Article  PubMed  Google Scholar 

  17. Frankenburg WK, Dodds J, Archer P, Shapiro H, Bresnick B (1992) The Denver II: a major revision and restandardization of the Denver developmental screening test. Pediatrics 89(1):91–97

    Article  CAS  PubMed  Google Scholar 

  18. Zheng H, Lin WX, Hu HY, Huang JH, Huang MN, He YS (2008) Effects of low-level lead exposure on the neurobehavioral development of infants and early intervention. Zhonghua Yu Fang Yi Xue Za Zhi 42(3):165–168

    CAS  PubMed  Google Scholar 

  19. Chang LY, Huang LM, Gau SS et al (2007) Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 356(12):1226–1234

    Article  CAS  PubMed  Google Scholar 

  20. Zhou Q, Wang C, Xu H, Li X (2020) Impact of Preconception Treatment Initiation for Hypothyroidism on Neurocognitive Function in Children. J Clin Endocrinol Metab 105(11).

  21. Lo CH, Lochhead P, Khalili H et al (2020) Dietary inflammatory potential and risk of crohn’s disease and ulcerative colitis. Gastroenterology 159(3):873-883.e871

    Article  CAS  PubMed  Google Scholar 

  22. Tabung FK, Smith-Warner SA, Chavarro JE et al (2017) An empirical dietary inflammatory pattern score enhances prediction of circulating inflammatory biomarkers in adults. J Nutr 147(8):1567–1577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Willett WC, Sampson L, Stampfer MJ et al (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122(1):51–65

    Article  CAS  PubMed  Google Scholar 

  24. Yuan C, Spiegelman D, Rimm EB et al (2018) Relative validity of nutrient intakes assessed by questionnaire, 24-h recalls, and diet records as compared with urinary recovery and plasma concentration biomarkers: findings for women. Am J Epidemiol 187(5):1051–1063

    Article  PubMed  Google Scholar 

  25. Tabung FK, Smith-Warner SA, Chavarro JE et al (2016) Development and Validation of an Empirical Dietary Inflammatory Index. J Nutr 146(8):1560–1570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu L, Tabung FK, Zhang X et al (2018) Diets that promote colon inflammation associate with risk of colorectal carcinomas that contain fusobacterium nucleatum. Clin Gastroenterol Hepatol 16(10):1622-1631.e1623

    Article  PubMed  PubMed Central  Google Scholar 

  27. Miller ES, Apple CG, Kannan KB et al (2019) Chronic stress induces persistent low-grade inflammation. Am J Surg 218(4):677–683

    Article  PubMed  PubMed Central  Google Scholar 

  28. Edlow AG (2017) Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat Diagn 37(1):95–110

    Article  PubMed  Google Scholar 

  29. Lautarescu A, Craig MC, Glover V (2020) Prenatal stress: Effects on fetal and child brain development. Int Rev Neurobiol 150:17–40

    Article  PubMed  Google Scholar 

  30. Fraser A, Nelson SM, Macdonald-Wallis C, Lawlor DA (2012) Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. Exp Diabetes Res 2012:963735

    Article  PubMed  PubMed Central  Google Scholar 

  31. Girchenko P, Lahti-Pulkkinen M, Lahti J et al (2018) Neonatal regulatory behavior problems are predicted by maternal early pregnancy overweight and obesity: findings from the prospective PREDO Study. Pediatr Res 84(6):875–881

    Article  PubMed  Google Scholar 

  32. Wang H, László KD, Gissler M et al (2021) Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two Nordic countries. Eur J Epidemiol 36(5):519–530

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wang P, Xie J, Jiao XC et al (2021) Maternal glycemia during pregnancy and early offspring development: a prospective birth cohort study. J Clin Endocrinol Metab 106(8):2279–2290

    Article  PubMed  Google Scholar 

  34. Georgieff MK, Ramel SE, Cusick SE (2018) Nutritional influences on brain development. Acta Paediatr 107(8):1310–1321

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gumusoglu SB, Stevens HE (2019) Maternal inflammation and neurodevelopmental programming: a review of preclinical outcomes and implications for translational psychiatry. Biol Psychiatry 85(2):107–121

    Article  PubMed  Google Scholar 

  36. Paolicelli RC, Bolasco G, Pagani F et al (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333(6048):1456–1458

    Article  CAS  PubMed  Google Scholar 

  37. Bailey MA, Holscher HD (2018) Microbiome-mediated effects of the mediterranean diet on inflammation. Adv Nutr 9(3):193–206

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wu PY, Chen KM, Tsai WC (2021) The mediterranean dietary pattern and inflammation in older adults: a systematic review and meta-analysis. Adv Nutr 12(2):363–373

    Article  PubMed  Google Scholar 

  39. Laouali N, Mancini FR, Hajji-Louati M et al (2019) Dietary inflammatory index and type 2 diabetes risk in a prospective cohort of 70,991 women followed for 20 years: the mediating role of BMI. Diabetologia 62(12):2222–2232

    Article  CAS  PubMed  Google Scholar 

  40. Xue J, Li X, Liu P et al (2019) Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr J 66(10):859–870

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the Department of Obstetrics and Gynecology, Anhui Maternal and Child Health Hospital, Hefei First People’s Hospital, and The First Affiliated Hospital of Anhui Medical University, Hefei, China, for assistance and support in the study.

Funding

This research received financial support from the National Key R&D Program of China (2022YFC2702901), the National Natural Science Foundation of China (81872631, 82173531), and the Foundation for Scientific Research Improvement of Anhui Medical University (2021xkjT009).

Author information

Author notes

  1. Haixia Wang and Wanjun Yin contributed equally to this work.

Authors and Affiliations

  1. Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, China

    Haixia Wang, Wanjun Yin, Shuangshuang Ma, Peng Wang, Lei Zhang & Peng Zhu

  2. MOE Key Laboratory of Population Health Across Life Cycle, Hefei, China

    Haixia Wang, Wanjun Yin, Peng Wang, Lei Zhang & Peng Zhu

  3. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, China

    Haixia Wang, Wanjun Yin, Peng Wang, Lei Zhang & Peng Zhu

  4. Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, China

    Haixia Wang, Wanjun Yin, Peng Wang, Lei Zhang & Peng Zhu

  5. Anhui Mental Health Centre, Hefei, China

    Shuangshuang Ma

  6. Hefei Maternal and Child Health Service Centre, Hefei, China

    Peipei Li & Ziyu Shao

  7. Department of Obstetrics and Gynecology, Anhui Maternal and Child Health Hospital, 15 Yimin Street, Hefei, China

    Xianxia Chen

Authors
  1. Haixia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanjun Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuangshuang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peipei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ziyu Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xianxia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HXW, PZ, and XXC designed the research; HXW, WJY, SSM, PW, LZ, PPL, ZYS, and PZ oversaw data collection, and analysed data or performed the statistical analysis; HXW, PZ, and XXC had primary responsibility for the final content; and all authors read and approved the final manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Xianxia Chen or Peng Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol of MIH-Hefei was approved by the Ethics Committee of Anhui Medical University (reference: 2015002), and all participants provided written informed consent. Signed consent was obtained from all potential participants under conditions of privacy in a manner that ensured understanding of the voluntary nature of the study.

Informed consent

Written informed consent was obtained from parents/legal guardians before including children in the study.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 665 KB)

Supplementary file2 (DOC 27 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Yin, W., Ma, S. et al. Prenatal environmental adversity and child neurodevelopmental delay: the role of maternal low-grade systemic inflammation and maternal anti-inflammatory diet. Eur Child Adolesc Psychiatry (2023). https://doi.org/10.1007/s00787-023-02267-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00787-023-02267-9

Keywords

Search

Navigation