K.S. LUGOVYKH¹, S.YU. ZAKHAROVA¹, L.A. PESTRYAEVA¹, T.B. TRETYAKOVA^1, 2, E.G. DERYABINA^1, 2

 ¹Ural Scientific Research Institute of Maternity and Child Care, Yekaterinburg

²Urals State Medical University, Yekaterinburg

Contact details:

Lugovykh K.S. — neonatologist of the Department of Pathology of Newborns and Premature Babies

Address: 1 Repin St., 1620028 Yekaterinburg, Russian Federation, tel.: +7-908-906-68-78, е-mail: karina01.00@mail.ru

Children born to mothers with gestational diabetes mellitus (GDM) are at a high risk for metabolic syndrome, obesity, insulin resistance, and dyslipidemia. These outcomes may be associated with genetic characteristics, including polymorphisms in genes regulating lipid metabolism.

The purpose — to identify the features of lipid metabolism and genetic markers of its regulation in infants during the first year of life born to women with GDM.

Material and methods. We conducted a prospective comparative study of 125 infants of 34/0–40/0 weeks gestational age (main group — 95 children born to mothers with GDM; control group — 30 children born to mothers without glucose metabolism disorders). The clinical examination of children was carried out in the neonatal period, at the age of 6 and 12 months of life.

All children underwent blood lipid profile analysis, including total cholesterol (TC), triglycerides, high- and low-density lipoprotein cholesterol (LDL-C), non-esterified fatty acids, and apolipoproteins A1 and B. Genotyping of lipoprotein lipase LPL (rs328), cholesteryl ester transfer protein CETP (rs5882), and apolipoprotein E ApoE (rs429358) gene polymorphisms was performed. Statistical analysis (IBM SPSS Statistics 27.0) included assessment of distribution (Kolmogorov — Smirnov test), Pearson’s and Fisher’s tests, odds ratio calculation (OR; 95% CI), and Hardy — Weinberg equilibrium verification. The critical significance level was set at p < 0.05.

Results. Infants born to women with GDM exhibited less favorable physical development indicators at birth and at 12 months of age, as well as signs of dyslipidemia. By the age of 12 months, the main group showed a significant increase in TC (p = 0.01) and LDL-C (p = 0.0007) levels compared to the control group. An association between lipid metabolism disorders and the LPL 447 C>G (rs328) gene polymorphism was established. The LPL 447 C allele was associated with an increased risk of metabolic disturbances (OR = 4.36), whereas the LPL 447 G allele demonstrated a protective effect. The CETP 1264 G>A polymorphism showed differences in allele distribution between groups. The ApoE 388 T>C gene polymorphism did not significantly influence the lipid profile in this cohort.

Conclusion. It was established that infants in their first year of life born to mothers with GDM are prone to dyslipidemia. The genetic determinant of these disturbances is linked to the LPL 447 C>G polymorphism (highlighting the protective role of the G allele), while the CETP and ApoE gene variants demonstrated no significant impact on the lipid profile in this cohort.

Key words: gestational diabetes mellitus, newborn, lipid metabolism, lipid transport system, genetic polymorphisms

REFERENCES

1. Klinicheskiye rekomendatsii: Gestatsionnyy sakharnyy diabet, 2024. [Clinical guidelines: Gestational diabetes mellitus. 2024], available at: https://cr.minzdrav.gov.ru/preview-cr/1.8411._1.1
2. Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy. Geneva: World Health Organization; 2013.
3. HAPO Study Cooperative Research Group; Metzger B.E., Lowe L.P., Dyer A.R., Trimble E.R., Chaovarindr U., Coustan D.R. et al. Hyperglycemia and adverse pregnancy outcomes. N. Engl. J. Med, 2008, vol. 358 (19), pp. 1991–2002. DOI: 10.1056/NEJMoa0707943
4. Barker D.J.P. Sir Richard Doll Lecture. Developmental origins of chronic disease. Public Health, 2012, vol. 126 (3), pp. 185–189. DOI: 10.1016/j.puhe.2011.11.014
5. Catalano P.M., Shankar K. Obesity and pregnancy: mechanisms of short term and long-term adverse consequences for mother and child. BMJ, 2017, vol. 356, p. j1. DOI: 10.1136/bmj.j1
6. Scholtens D.M., Kuang A., Lowe L.P. et al. Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal glycemia and childhood glucose metabolism. Diabetes Care, 2019, vol. 42 (3), pp. 381–392. DOI: 10.2337/dc18-2021
7. Innis S.M. Dietary lipids in early development: relevance to obesity, immune and inflammatory disorders. Curr. Opin. Endocrinol. Diabetes Obes, 2007, vol. 14 (5), pp. 359–364. DOI: 10.1097/MED.0b013e3282be90b9
8. Herrera E., Ortega-Senovilla H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr. Pharm. Biotechnol, 2014, vol. 15 (1), pp. 24–31. DOI: 10.2174/1389201015666140330192345
9. Segura M.T., Demmelmair H., Krauss-Etschmann S., Nathan P., Dehmel S., Padilla M.C. et al. Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition. Placenta, 2017, vol. 57, pp. 144–151. DOI: 10.1016/j.placenta.2017.07.001
10. Uhl O., Demmelmair H., Segura M.T., Florido J., Rueda R., Campoy C., Koletzko B. Effects of obesity and gestational diabetes mellitus on placental phospholipids. Diabetes Res. Clin. Pract, 2015, vol. 109 (2), pp. 364–371. DOI: 10.1016/j.diabres.2015.05.032
11. Schaefer-Graf U.M., Graf K., Kulbacka I., Kjos S.L., Dudenhausen J., Vetter K., Herrera E. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care, 2008, vol. 31 (9), pp. 1858–1863. DOI: 10.2337/dc08-0039
12. Thomas B.A., Ghebremeskel K., Lowy C., Offley-Shore B., Crawford M.A. Plasma fatty acids of neonates born to mothers with and without gestational diabetes. Prostaglandins Leukot Essent Fatty Acids, 2005, vol. 72 (5), pp. 335–341. DOI: 10.1016/j.plefa.2005.01.001
13. Barbour L.A., Hernandez T.L. Maternal non-glycemic contributors to fetal growth in obesity and gestational diabetes: spotlight on lipids. Curr. Diab. Rep, 2018, vol. 18 (6), p. 37. DOI: 10.1007/s11892-018-1008-2
14. Koletzko B., Brands B., Poston L., Godfrey K., Demmelmair H.; Early Nutrition Project. Early nutrition programming of long-term health. Proc. Nutr. Soc, 2012, vol. 71 (3), pp. 371–378. DOI: 10.1017/S0029665112000596
15. Alves M., Laranjera F., Correia-da-Silva G. Understanding hypertriglyceridemia: integrating genetic data. Genes (Basel), 2024, vol. 15 (2), p. 190. DOI: 10.3390/genes15020190
16. Rip J., Nierman M.C., Ross C.J., Jukema J.W., Hayden M.R., Kastelein J.J. et al. Lipoprotein lipase S447X: a naturally occurring gain-of-function mutation. Arterioscler. Thromb. Vasc. Biol, 2006, vol. 26 (6), pp. 1236–1245. DOI: 10.1161/01.ATV.0000219283.10832.43
17. Wang H., Eckel R.H. Lipoprotein lipase: from gene to obesity. Am. J. Physiol. Endocrinol. Metab, 2009, vol. 297 (2), pp. E271-88. DOI: 10.1152/ajpendo.90920.2008
18. Turktan I., Erdeve O., Kostekci E., Okulu E., Atasay B., Arsan S. Comparison between INTERGROWTH-21ST and Fenton charts for extrauterine growth in very low birth weigth infants. Ital. J. Pediatr, 2025, vol. 51 (1), p. 176. DOI: 10.1186/s13052-025-01939-3
19. Perepelitsa S.A. Lipid metabolism disorders in newborns in the early neonatal period. Obshchaya reanimatologiya, 2018, no. 2 (in Russ.).
20. Klinicheskiye rekomendatsii Ozhireniye u detey, 2024 [Clinical guidelines Obesity in children, 2024], available at: https://cr.minzdrav.gov.ru/preview-cr/HYPERLINK «https://cr.minzdrav.gov.ru/preview-cr/229_3″229HYPERLINK «https://cr.minzdrav.gov.ru/preview-cr/229_3″_HYPERLINK «https://cr.minzdrav.gov.ru/preview-cr/229_3″3
21. Melkozerova O.A., Okulova E.O., Mikhel′son A.A., Tret′yakova T.B. Molecular genetic predictors and the state of ovarian reserve in deep infiltrating endometriosis. Akusherstvo i ginekologiya, 2021, no. 11, pp. 175–186 (in Russ.).
22. Vlasov V.V. Vvedeniye v dokazatel′nuyu meditsinu [Introduction to evidence-based medicine]. Moscow: Media Sfera, 2001. 392 p., il.
23. Glants S. Mediko-biologicheskaya statistika [Medical and Biological Statistics]. Moscow, Praktika, 1998. 459 p.
24. Fletcher R., Fletcher S., Vagner E. Klinicheskaya epidemiologiya. Osnovy dokazatel′noy meditsiny [Clinical Epidemiology. Fundamentals of Evidence-Based Medicine]. Moscow: Media Sfera, 1998. 352 p., il.
25. Yunkerov V.I., Grigor′yev S.G. Matematiko-statisticheskaya obrabotka dannykh meditsinskikh issledovaniy [Mathematical and statistical processing of medical research data]. Saint Petersburg: VMedF, 2002. 266 p.
26. Natsional′naya programma optimizatsii vskarmlivaniya detey pervogo goda zhizni v Rossiyskoy Federatsii, 2019 [National program for optimizing infant feeding in the Russian Federation. 2019], available at: https://www.pediatr-russia.ru/information/dokumenty/other-docs/nacprog1year_2019.pdf