Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Population Study Article
  • Published:

Maternal protein intake in early pregnancy and child development at age 3 years

Pediatric Research volume 94, pages 392–399 (2023)Cite this article

Abstract

Background

The current study aimed to assess the association between low maternal protein intake during pregnancy and child developmental delay at age 3 years.

Methods

This research used data obtained from the Japan Environment and Children’s Study. In total, we analyzed 77,237 mother–child pairs. Dietary intake was assessed using the Food Frequency Questionnaire. Developmental outcomes at age 3 years were evaluated with the Japanese version of the Ages and Stages Questionnaire, Third Edition. A multivariate logistic regression analysis was performed to assess the association between maternal protein intake during pregnancy and child development delays at age 3 years.

Results

Based on the protein-to-total energy intake ratio during early pregnancy, the participants were categorized into three groups: <9.39% (>2 standard deviation below the mean), the severely low protein (SLP) group; 9.39–<13%, the low protein group; and ≥13%, the normal protein group. After adjusting for potential confounding factors, SLP intake was found to be significantly correlated with a higher risk of developmental delay according to the communication, fine motor and problem-solving skill domains.

Conclusions

SLP intake caused by inadequate diet during early pregnancy was associated with a higher risk of child developmental delay at age 3 years.

Impact

  • Animal studies have shown that maternal protein restriction during pregnancy and lactation causes abnormal brain development among offspring.

  • Birth cohort studies to date have not assessed the effects of maternal low protein exposure during pregnancy on child development.

  • Severely low protein intake during early pregnancy was associated with a higher risk of child developmental delay at age 3 years.

  • Since nutritional imbalance in early pregnancy affects not only fetal growth but also postnatal neurodevelopment, nutritional management before pregnancy is considered important.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Comparison of breakfast intake frequency before and in early pregnancy among the three groups.

Similar content being viewed by others

Data availability

Data are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of May 30, 2003, amendment in September 9, 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Medical and Health Research Involving Human Subjects enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restrict the open sharing of epidemiologic data. All inquiries about access to data should be sent to: jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.

References

  1. Walker, S. P. et al. Inequality in early childhood: risk and protective factors for early child development. Lancet 378, 1325–1338 (2011).

    PubMed  Google Scholar 

  2. Suchdev, P. S. et al. Assessment of neurodevelopment, nutrition, and inflammation from fetal life to adolescence in low-resource settings. Pediatrics 139, S23–S37 (2017).

    PubMed  Google Scholar 

  3. Vrijheid, M., Casas, M., Gascon, M., Valvi, D. & Nieuwenhuijsen, M. Environmental pollutants and child health: a review of recent concerns. Int. J. Hyg. Environ. Health 219, 331–342 (2016).

    CAS  PubMed  Google Scholar 

  4. Barker, D. J. The origins of the developmental origins theory. J. Intern. Med. 261, 412–417 (2007).

    CAS  PubMed  Google Scholar 

  5. Bianco-Miotto, T., Craig, J. M., Gasser, Y. P., van Dijk, S. J. & Ozanne, S. E. Epigenetics and DOHaD: from basics to birth and beyond. J. Dev. Orig. Health Dis. 8, 513–519 (2017).

    CAS  PubMed  Google Scholar 

  6. Miguel, P. M., Pereira, L. O., Silveira, P. P. & Meaney, M. J. Early environmental influences on the development of children’s brain structure and function. Dev. Med. Child. Neurol. 61, 1127–1133 (2019).

    PubMed  Google Scholar 

  7. Miyake, K. et al. DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children’s Health. Clin. Epigenetics 13, 74 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Yakoob, M. Y. & Lo, C. W. Nutrition (micronutrients) in child growth and development: a systematic review on current evidence, recommendations and opportunities for further research. J. Dev. Behav. Pediatr. 38, 665–679 (2017).

    PubMed  Google Scholar 

  9. Bhutta, Z. A. et al. Severe childhood malnutrition. Nat. Rev. Dis. Prim. 3, 17067 (2017).

    PubMed  Google Scholar 

  10. Odhiambo, J. F., Pankey, C. L., Ghnenis, A. B. & Ford, S. P. A review of maternal nutrition during pregnancy and impact on the offspring through development: evidence from animal models of over- and undernutrition. Int. J. Environ. Res. Public Health 17, 6926 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wu, G., Imhoff-Kunsch, B. & Girard, A. W. Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr. Perinat. Epidemiol. 26, 4–26 (2012).

    PubMed  Google Scholar 

  12. Herring, C. M., Bazer, F. W., Johnson, G. A. & Wu, G. Impacts of maternal dietary protein intake on fetal survival, growth, and development. Exp. Biol. Med. 243, 525–533 (2018).

    CAS  Google Scholar 

  13. Dodd, J. M. et al. Prenatal diet and child growth at 18 months. Pediatrics 142, e20180035 (2018).

    PubMed  Google Scholar 

  14. Maslova, E. et al. Maternal protein intake in pregnancy and offspring metabolic health at age 9–16 y: results from a Danish cohort of gestational diabetes mellitus pregnancies and controls. Am. J. Clin. Nutr. 106, 623–636 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Barbeito-Andrés, J., Gleiser, P. M., Bernal, V., Hallgrímsson, B. & Gonzalez, P. N. Brain structural networks in mouse exposed to chronic maternal undernutrition. Neuroscience 380, 14–26 (2018).

    PubMed  Google Scholar 

  16. Bautista, C. J. et al. Effects of maternal protein restriction during pregnancy and lactation on milk composition and offspring development. Br. J. Nutr. 122, 141–151 (2019).

    CAS  PubMed  Google Scholar 

  17. Gould, J. M. et al. Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. Proc. Natl Acad. Sci. USA 115, E7398–E7407 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Furuse, T. et al. Protein-restricted diet during pregnancy after insemination alters behavioral phenotypes of the progeny. Genes Nutr. 12, 1 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kawamoto, T. et al. Rationale and study design of the Japan Environment and Children’s Study (JECS). BMC Public Health 14, 25 (2014).

    PubMed  PubMed Central  Google Scholar 

  20. Michikawa, T. et al. Baseline profile of participants in the Japan Environment and Children’s Study (JECS). J. Epidemiol. 28, 99–104 (2018).

    PubMed  PubMed Central  Google Scholar 

  21. Yokoyama, Y. et al. Validity of short and long self-administered Food Frequency Questionnaires in ranking dietary intake in middle-aged and elderly Japanese in the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Protocol Area. J. Epidemiol. 26, 420–432 (2016).

    PubMed  Google Scholar 

  22. Mezawa, H. et al. Psychometric profile of the Ages and Stages Questionnaires, Japanese translation. Pediatr. Int. 61, 1086–1095 (2019).

    PubMed  PubMed Central  Google Scholar 

  23. Black, M. M. et al. Early childhood development coming of age: science through the life course. Lancet 389, 77–90 (2017).

    PubMed  Google Scholar 

  24. Donald, K. A. et al. Risk and protective factors for child development: an observational South African birth cohort. PLoS Med. 16, e1002920 (2019).

    PubMed  PubMed Central  Google Scholar 

  25. Wu, X. et al. The effect of parenting quality on child development at 36–48 months in China’s urban area: evidence from a birth cohort study. Int J. Environ. Res. Public Health 17, 8962 (2020).

    PubMed  PubMed Central  Google Scholar 

  26. Ministry of Health, Labour and Welfare. Dietary reference intakes for Japanese. https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/0000208954.pdf (2020).

  27. Hennig, M. et al. Dietary protein restriction throughout intrauterine and postnatal life results in potentially beneficial myocardial tissue remodeling in the adult mouse heart. Sci. Rep. 9, 15126 (2019).

    PubMed  PubMed Central  Google Scholar 

  28. Takimoto, H., Yokoyama, T., Yoshiike, N. & Fukuoka, H. Increase in low-birth-weight infants in Japan and associated risk factors, 1980–2000. J. Obstet. Gynaecol. Res. 31, 314–322 (2005).

    PubMed  Google Scholar 

  29. Gluckman, P. D., Seng, C. Y., Fukuoka, H., Beedle, A. S. & Hanson, M. A. Low birthweight and subsequent obesity in Japan. Lancet 369, 1081–1082 (2007).

    PubMed  Google Scholar 

  30. Morisaki, N. et al. Optimal protein intake during pregnancy for reducing the risk of fetal growth restriction: the Japan Environment and Children’s Study. Br. J. Nutr. 120, 1432–1440 (2018).

    CAS  PubMed  Google Scholar 

  31. Mathews, F., Yudkin, P. & Neil, A. Influence of maternal nutrition on outcome of pregnancy: prospective cohort study. BMJ 319, 339–343 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Lagiou, P. et al. Diet during pregnancy in relation to maternal weight gain and birth size. Eur. J. Clin. Nutr. 58, 231–237 (2004).

    CAS  PubMed  Google Scholar 

  33. Chong, M. F. et al. Maternal protein intake during pregnancy is not associated with offspring birth weight in a multiethnic Asian population. J. Nutr. 145, 1303–1310 (2015).

    CAS  PubMed  Google Scholar 

  34. Ji, Y. et al. Fetal and neonatal programming of postnatal growth and feed efficiency in swine. J. Anim. Sci. Biotechnol. 8, 42 (2017).

    PubMed  PubMed Central  Google Scholar 

  35. Nätt, D. et al. Perinatal malnutrition leads to sexually dimorphic behavioral responses with associated epigenetic changes in the mouse brain. Sci. Rep. 7, 11082 (2017).

    PubMed  PubMed Central  Google Scholar 

  36. Switkowski, K. M. et al. Maternal protein intake during pregnancy and linear growth in the offspring. Am. J. Clin. Nutr. 104, 1128–1136 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Geraghty, A. A. et al. Maternal protein intake during pregnancy is associated with child growth up to 5 years of age, but not through insulin-like growth factor-1: findings from the ROLO study. Br. J. Nutr. 120, 1252–1261 (2018).

    CAS  PubMed  Google Scholar 

  38. Shiraishi, M., Haruna, M. & Matsuzaki, M. Effects of skipping breakfast on dietary intake and circulating and urinary nutrients during pregnancy. Asia Pac. J. Clin. Nutr. 28, 99–105 (2019).

    CAS  PubMed  Google Scholar 

  39. Gressens, P. et al. Maternal protein restriction early in rat pregnancy alters brain development in the progeny. Brain Res. Dev. Brain Res. 103, 21–35 (1997).

    CAS  PubMed  Google Scholar 

  40. Belluscio, L. M., Berardino, B. G., Ferroni, N. M., Ceruti, J. M. & Cánepa, E. T. Early protein malnutrition negatively impacts physical growth and neurological reflexes and evokes anxiety and depressive-like behaviors. Physiol. Behav. 129, 237–254 (2014).

    CAS  PubMed  Google Scholar 

  41. Batista, T. H., Veronesi, V. B., Ribeiro, A. C. A. F., Giusti-Paiva, A. & Vilela, F. C. Protein malnutrition during pregnancy alters maternal behavior and anxiety-like behavior in offspring. Nutr. Neurosci. 20, 437–442 (2017).

    CAS  PubMed  Google Scholar 

  42. Wu, G. Functional amino acids in nutrition and health. Amino Acids 45, 407–411 (2013).

    CAS  PubMed  Google Scholar 

  43. Elango, R. & Ball, R. O. Protein and amino acid requirements during pregnancy. Adv. Nutr. 7, 839S–844S (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wakai, K. A review of Food Frequency Questionnaires developed and validated in Japan. J. Epidemiol. 19, 1–11 (2009).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the participants and co-operating healthcare providers for their contribution to the JECS.

Funding

This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors and do not represent the official views of the above government.

Author information

Authors and Affiliations

  1. Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan

    Kunio Miyake, Yuka Akiyama, Tadao Ooka, Reiji Kojima, Hiroshi Yokomichi & Zentaro Yamagata

  2. Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Kofu, Yamanashi, Japan

    Kazuki Mochizuki

  3. Center for Birth Cohort Studies, University of Yamanashi, Chuo, Yamanashi, Japan

    Megumi Kushima, Ryoji Shinohara, Sayaka Horiuchi, Sanae Otawa & Zentaro Yamagata

  4. Nagoya City University, Nagoya, Japan

    Michihiro Kamijima

  5. National Institute for Environmental Studies, Tsukuba, Japan

    Shin Yamazaki

  6. National Center for Child Health and Development, Tokyo, Japan

    Yukihiro Ohya

  7. Hokkaido University, Sapporo, Japan

    Reiko Kishi

  8. Tohoku University, Sendai, Japan

    Nobuo Yaegashi

  9. Fukushima Medical University, Fukushima, Japan

    Koichi Hashimoto

  10. Chiba University, Chiba, Japan

    Chisato Mori

  11. Yokohama City University, Yokohama, Japan

    Shuichi Ito

  12. University of Yamanashi, Chuo, Japan

    Zentaro Yamagata

  13. University of Toyama, Toyama, Japan

    Hidekuni Inadera

  14. Kyoto University, Kyoto, Japan

    Takeo Nakayama

  15. Osaka University, Suita, Japan

    Hiroyasu Iso

  16. Hyogo College of Medicine, Nishinomiya, Japan

    Masayuki Shima

  17. Tottori University, Yonago, Japan

    Youichi Kurozawa

  18. Kochi University, Nankoku, Japan

    Narufumi Suganuma

  19. University of Occupational and Environmental Health, Kitakyushu, Japan

    Koichi Kusuhara

  20. Kumamoto University, Kumamoto, Japan

    Takahiko Katoh

Authors
  1. Kunio Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuki Mochizuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Megumi Kushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryoji Shinohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sayaka Horiuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sanae Otawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuka Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tadao Ooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Reiji Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiroshi Yokomichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zentaro Yamagata
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Japan Environment and Children’s Study Group

  • Michihiro Kamijima
  • , Shin Yamazaki
  • , Yukihiro Ohya
  • , Reiko Kishi
  • , Nobuo Yaegashi
  • , Koichi Hashimoto
  • , Chisato Mori
  • , Shuichi Ito
  • , Zentaro Yamagata
  • , Hidekuni Inadera
  • , Takeo Nakayama
  • , Hiroyasu Iso
  • , Masayuki Shima
  • , Youichi Kurozawa
  • , Narufumi Suganuma
  • , Koichi Kusuhara
  •  & Takahiko Katoh

Contributions

K.M. conceived and designed the study, drafted the initial manuscript, and revised the manuscript. K.Mo. designed the study and reviewed and revised the manuscript. R.S., S.H., M.K., S.O., Z.Y., and the JECS group collected data and critically reviewed and revised the manuscript. Y.A., T.O., R.K., and H.Y. critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Kunio Miyake.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The Japan Environment and Children’s Study (JECS) protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and the Ethics Committees of all participating institutions. The JECS was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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

Miyake, K., Mochizuki, K., Kushima, M. et al. Maternal protein intake in early pregnancy and child development at age 3 years. Pediatr Res 94, 392–399 (2023). https://doi.org/10.1038/s41390-022-02435-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-022-02435-8

This article is cited by

Search

Advanced search

Quick links