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Cited by 14Birth, Development, and HealthGestational Diabetes Research and ManagementPrenatal Substance Exposure Effects

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

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Kwok, Janell, Speyer, Lydia Gabriela, Soursou, Georgia, Murray, Aja Louise, Fanti, Kostas A., Auyeung, Bonnie·2023·BMC Medicine
DOI 10.1186/s12916-023-02835-5PMC PMC10071709
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Abstract

Background: There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators. Methods: Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age. Results: In mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models. Conclusions: The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

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  • Exposures during fetal development can cause long-term alterations in gene expression, endocrine activity, and metabolism, thereby affecting susceptibility to disease in late adulthood.

    “Other exposures during fetal development can cause long-term alterations in gene expression, endocrine activity, and metabolism, thereby affecting susceptibility to disease in late adulthood.”

    From Maternal nutritional status and the risk of metabolic syndrome in pregnancy: implications for public health nutrition (2026) · cites this paper as [14]

    The Background (page unavailable) links maternal metabolic state during gestation to fetal programming and describes increased susceptibility to immune and cardiovascular disease from childhood into adolescence. It does not establish long-term alterations in gene expression or endocrine activity, a causal effect of fetal exposures, or disease susceptibility specifically in late adulthood. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Kwok, J., Speyer, L. G., Soursou, G., Murray, A. L., Fanti, K. A., & Auyeung, B.
Affiliations
  • University of Edinburgh (GB)
  • University of Cambridge (GB)
  • University of Cyprus (CY)
Corresponding author
Kwok, Janell
ORCID
Venue
BMC Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-04-03
Volume
21
Issue
1
Pages
124-124
ISSN
1741-7015 (ISSN-L)
DOI
10.1186/s12916-023-02835-5
PMC
PMC10071709
OpenAlex
W4362521278
Cited by
14
References
2
Citations by year
2026: 3 · 2025: 5 · 2024: 2 · 2023: 4
FWCI
5.16
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
Funders
Horizon 2020 Framework Programme (813546)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Keywords
maternal metabolic syndrome, pregnancy, child development, cord blood biomarkers, mediation analysis, HDL cholesterol, leptin, adiponectin, triglycerides, literacy, language development, cardiometabolic risk
MeSH terms
Child Development, Child, Preschool, Cholesterol, Female, Fetal Blood, Humans, Lipoproteins, HDL, Pregnancy, Triglycerides, Body Mass Index, Leptin, Metabolic Syndrome, Adiponectin

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