Maternal Glycemia and Its Pattern Associated with Offspring Neurobehavioral Development: A Chinese Birth Cohort Study

Overview

Journal Nutrients

Date 2025 Jan 25

PMID 39861387

Authors

Zhichao Yuan

Tao Su

Li Yang

Lei Xi

Hai-Jun Wang

Yuelong Ji

Affiliations

Soon will be listed here.

Abstract

Background/objectives: This study investigates the impact of maternal glycemic levels during early and late pregnancy on offspring neurodevelopment in China.

Methods: Fasting plasma glucose (FPG) and triglyceride (TG) levels were measured in maternal blood during pregnancy, and the TyG index was calculated to assess insulin resistance. Hyperglycemia was defined as FPG > 5.1 mmol/L. Neurodevelopmental outcomes in offspring aged 6-36 months were evaluated using the China Developmental Scale for Children, focusing on developmental delay (DD) and developmental quotient (DQ). Mothers were categorized into four glycemic groups: healthy glycemia group (HGG), early pregnancy hyperglycemia group (EHG), late pregnancy hyperglycemia group (LHG), and full-term hyperglycemia group (FHG). Linear and logistic regression models were applied.

Results: Among 1888 mother-child pairs, hyperglycemia and FPG were associated with an increased risk of overall DD (aOR = 1.68; 95% CI 1.07-2.64) and lower DQ (aBeta = -1.53; 95% CI -2.70 to -0.36). Elevated FPG was linked to DD in fine motor and social behaviors. Compared to HGG, LHG and FHG significantly increased the risk of overall DD (aOR = 2.18; 95% CI 1.26-3.77; aOR = 2.64; 95% CI 1.38-5.05), whereas EHG did not. Male offspring were particularly vulnerable to early pregnancy hyperglycemia (aBeta = -2.80; 95% CI -4.36 to -1.34; aOR = 2.05; 95% CI 1.10-3.80).

Conclusions: Maternal glycemic levels during pregnancy influence offspring neurodevelopment, with persistent hyperglycemia significantly increasing DD risk. Early pregnancy hyperglycemia particularly affects male offspring, underscoring the need for glycemic management during pregnancy.

References

Dubois J, Dehaene-Lambertz G, Kulikova S, Poupon C, Huppi P, Hertz-Pannier L . The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants. Neuroscience. 2014; 276:48-71. DOI: 10.1016/j.neuroscience.2013.12.044. View

Rucklidge J . Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2010; 33(2):357-73. DOI: 10.1016/j.psc.2010.01.006. View

Simental-Mendia L, Rodriguez-Moran M, Guerrero-Romero F . The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008; 6(4):299-304. DOI: 10.1089/met.2008.0034. View

Robinson E, Lichtenstein P, Anckarsater H, Happe F, Ronald A . Examining and interpreting the female protective effect against autistic behavior. Proc Natl Acad Sci U S A. 2013; 110(13):5258-62. PMC: 3612665. DOI: 10.1073/pnas.1211070110. View

Metzger B, Gabbe S, Persson B, Buchanan T, Catalano P, Damm P . International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3):676-82. PMC: 2827530. DOI: 10.2337/dc09-1848. View

Bronson S, Chan J, Bale T . Sex-Specific Neurodevelopmental Programming by Placental Insulin Receptors on Stress Reactivity and Sensorimotor Gating. Biol Psychiatry. 2017; 82(2):127-138. PMC: 5483189. DOI: 10.1016/j.biopsych.2016.12.025. View

OHare A, Bremner L . Management of developmental speech and language disorders: Part 1. Arch Dis Child. 2015; 101(3):272-7. DOI: 10.1136/archdischild-2014-307394. View

Nahum Sacks K, Friger M, Shoham-Vardi I, Abokaf H, Spiegel E, Sergienko R . Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring. Am J Obstet Gynecol. 2016; 215(3):380.e1-7. DOI: 10.1016/j.ajog.2016.03.030. View

May T, Adesina I, McGillivray J, Rinehart N . Sex differences in neurodevelopmental disorders. Curr Opin Neurol. 2019; 32(4):622-626. DOI: 10.1097/WCO.0000000000000714. View

10.

Cortes-Albornoz M, Garcia-Guaqueta D, Velez-Van-Meerbeke A, Talero-Gutierrez C . Maternal Nutrition and Neurodevelopment: A Scoping Review. Nutrients. 2021; 13(10). PMC: 8538181. DOI: 10.3390/nu13103530. View

11.

Sonaglioni A, Bordoni T, Naselli A, Nicolosi G, Grasso E, Bianchi S . Influence of gestational diabetes mellitus on subclinical myocardial dysfunction during pregnancy: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2023; 292:17-24. DOI: 10.1016/j.ejogrb.2023.11.007. View

12.

Hardy S, Haisley L, Manning C, Fein D . Can Screening with the Ages and Stages Questionnaire Detect Autism?. J Dev Behav Pediatr. 2015; 36(7):536-43. PMC: 4563819. DOI: 10.1097/DBP.0000000000000201. View

13.

Nivins S, Giesbrecht G, Tomfohr-Madsen L, Lebel C . Prenatal maternal diabetes, comorbidities, and risk for neurodevelopmental impairment in the first two years. Pediatr Res. 2024; . DOI: 10.1038/s41390-024-03620-7. View

14.

Sonagra A, Biradar S, K D, Murthy D S J . Normal pregnancy- a state of insulin resistance. J Clin Diagn Res. 2015; 8(11):CC01-3. PMC: 4290225. DOI: 10.7860/JCDR/2014/10068.5081. View

15.

Tau G, Peterson B . Normal development of brain circuits. Neuropsychopharmacology. 2009; 35(1):147-68. PMC: 3055433. DOI: 10.1038/npp.2009.115. View

16.

Marban-Castro E, Vazquez Guillamet L, Pantoja P, Casellas A, Maxwell L, Mulkey S . Neurodevelopment in Normocephalic Children Exposed to Zika Virus in Utero with No Observable Defects at Birth: A Systematic Review with Meta-Analysis. Int J Environ Res Public Health. 2022; 19(12). PMC: 9223424. DOI: 10.3390/ijerph19127319. View

17.

Ferri S, Abel T, Brodkin E . Sex Differences in Autism Spectrum Disorder: a Review. Curr Psychiatry Rep. 2018; 20(2):9. PMC: 6477922. DOI: 10.1007/s11920-018-0874-2. View

18.

Ikenoue S, Waffarn F, Sumiyoshi K, Ohashi M, Ikenoue C, Tanaka M . Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study. Am J Obstet Gynecol. 2022; 228(4):455.e1-455.e8. DOI: 10.1016/j.ajog.2022.10.015. View

19.

Jiang N, Cowan M, Moonah S, Petri Jr W . The Impact of Systemic Inflammation on Neurodevelopment. Trends Mol Med. 2018; 24(9):794-804. PMC: 6110951. DOI: 10.1016/j.molmed.2018.06.008. View

20.

Bethlehem R, Seidlitz J, White S, Vogel J, Anderson K, Adamson C . Brain charts for the human lifespan. Nature. 2022; 604(7906):525-533. PMC: 9021021. DOI: 10.1038/s41586-022-04554-y. View