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.

  • Article
  • Published:

Alterations in infant adipokine concentrations in the first postnatal week with exposure to diabetes in pregnancy

Journal of Perinatology volume 45, pages 622–627 (2025)Cite this article

Subjects

Abstract

Objective

Characterize changes in neonatal energy metabolism hormones in first postnatal week.

Study design

Concentrations of leptin, adiponectin, insulin, resistin, and ghrelin were measured in cord and infant blood collected in the first postnatal week in a prospective cohort of term and preterm infants. Change over time in each hormone was modeled using linear mixed effects regression.

Result

Among 106 infants, 65 (61%) were preterm and 44 (42%) were exposed to diabetes (DM) in pregnancy. DM group had higher leptin [between group difference β 2.5 (95%CI: 1.72–3.70)] and resistin [β 1.5 (95%CI:1.14, 1.92)] and lower ghrelin [β 0.49] [95%CI: (0.32–0.76)] versus non-DM group. Preterm infants had lower adiponectin [β 0.80 (95%CI: 0.67–0.96)] versus term group. Insulin varied by DM and prematurity (interaction-term p value < 0.05).

Conclusion

In this cohort, hormone concentrations varied by DM and prematurity. Early alterations in energy metabolism hormones may reflect changes in developmental programming which persist in the early postnatal period.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Fig. 1: Study flow diagram.
Fig. 2: Change in adipokine concentrations over time.

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler WC. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N. Engl J Med. 1983;308:242–5.

    Article  CAS  PubMed  Google Scholar 

  2. Tam WH, Ma RCW, Ozaki R, Li AM, Chan MHM, Yuen LY, et al. In utero exposure to maternal hyperglycemia increases childhood cardiometabolic risk in offspring. Diab Care. 2017;40:679–86.

    Article  CAS  Google Scholar 

  3. Lowe WL, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, et al. Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism. Diab Care. 2019;42:372–80.

    Article  CAS  Google Scholar 

  4. Raju TNK, Buist AS, Blaisdell CJ, Moxey-Mims M, Saigal S. Adults born preterm: a review of general health and system-specific outcomes. Acta Paediatr. 2017;106:1409–37.

    Article  PubMed  Google Scholar 

  5. Buck CO, Shabanova V, Taylor SN. Growth patterns among late preterm infants of mothers with diabetes. J Matern Fetal Neonatal Med. 2022;35:10116–23.

    Article  PubMed  Google Scholar 

  6. Buck CO, Shabanova V, Clark RH, Taylor SN. Diabetes in pregnancy, neonatal morbidities, and early growth in moderate or late preterm infants. Pediatrics. 2023;152:e2023061285.

    Article  PubMed  Google Scholar 

  7. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharm Sin. 2018;39:1176–88.

    Article  CAS  Google Scholar 

  8. Teague AM, Fields DA, Aston CE, Short KR, Lyons TJ, Chernausek SD. Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus. Reprod Biol Endocrinol. 2015;13:68.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shang M, Dong X, Hou L. Correlation of adipokines and markers of oxidative stress in women with gestational diabetes mellitus and their newborns. J Obstet Gynaecol Res. 2018;44:637–46.

    Article  CAS  PubMed  Google Scholar 

  10. Sivan E, Mazaki-Tovi S, Pariente C, Efraty Y, Schiff E, Hemi R, et al. Adiponectin in human cord blood: relation to fetal birth weight and gender. J Clin Endocrinol Metab. 2003;88:5656–60.

    Article  CAS  PubMed  Google Scholar 

  11. Ng PC, Lee CH, Lam CWK, Wong E, Chan IHS, Fok TF. Plasma ghrelin and resistin concentrations are suppressed in infants of insulin-dependent diabetic mothers. J Clin Endocrinol Metab. 2004;89:5563–8.

    Article  CAS  PubMed  Google Scholar 

  12. Buck CO, Eliot MN, Kelsey KT, Chen A, Kalkwarf H, Lanphear BP, et al. Neonatal adipocytokines and longitudinal patterns of childhood growth. Obes (Silver Spring). 2019;27:1323–30.

    Article  CAS  Google Scholar 

  13. Tan K, Tint MT, Michael N, Yap F, Chong YS, Tan KH, et al. Determinants of cord blood adipokines and association with neonatal abdominal adipose tissue distribution. Int J Obes. 2022;46:637–45.

    Article  CAS  Google Scholar 

  14. Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, et al. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Clin Endocrinol Metab. 1999;84:1145–8.

    Article  CAS  PubMed  Google Scholar 

  15. Arroyo-Jousse V, Jaramillo A, Castaño-Moreno E, Lépez M, Carrasco-Negüe K, Casanello P. Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity. Biochimica et Biophys Acta (BBA) - Mol Basis Dis. 2020;1866:165558.

    Article  CAS  Google Scholar 

  16. Takaya J, Yamato F, Higashino H, Kaneko K. Intracellular magnesium and adipokines in umbilical cord plasma and infant birth size. Pediatr Res. 2007;62:700–3.

    Article  CAS  PubMed  Google Scholar 

  17. Simpson J, Smith ADAC, Fraser A, Sattar N, Lindsay RS, Ring SM, et al. Programming of Adiposity in Childhood and Adolescence: Associations With Birth Weight and Cord Blood Adipokines. J Clin Endocrinol Metab. 2017;102:499–506.

    PubMed  Google Scholar 

  18. Wallace AM. Measurement of leptin and leptin binding in the human circulation. Ann Clin Biochem. 2000;37:244–52.

    Article  CAS  PubMed  Google Scholar 

  19. Rutkowski JM, Scherer PE. Isolation and quantitation of adiponectin higher order complexes. Methods Enzymol. 2014;537:243–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Martin RM, Patel R, Zinovik A, Kramer MS, Oken E, Vilchuck K, et al. Filter Paper Blood Spot Enzyme Linked Immunoassay for Insulin and Application in the Evaluation of Determinants of Child Insulin Resistance. PLoS ONE. 2012;7:e46752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hosoda H, Kangawa K. Ghrelin Measurement: Present and Perspectives. In: Ghigo E, Benso A, Broglio F (eds). Ghrelin. Kluwer Academic Publishers: Boston, 2004, pp 225-36.

  22. CDC. Disability and Obesity | CDC. Centers for Disease Control and Prevention. 2020. https://www.cdc.gov/ncbddd/disabilityandhealth/obesity.html (accessed 20 Sep 2024).

  23. Anscombe FJ, Barron BA. Treatment of outliers in samples of size three. J RES NATL BUR STAN SECT B MATH MATH PHYS. 1966;70B:141.

    Article  Google Scholar 

  24. Molenberghs G, Beunckens C, Sotto C, Kenward MG. Every Missingness not at Random Model Has a Missingness at Random Counterpart with Equal Fit. J R Stat Soc Ser B: Stat Methodol. 2008;70:371–88.

    Article  Google Scholar 

  25. Rubin DB. Inference and missing data. Biometrika. 1976;63:581–92.

    Article  Google Scholar 

  26. Erler NS, Rizopoulos D, Lesaffre EMEH. JointAI: Joint Analysis and Imputation of Incomplete Data in R. J Stat Softw. 2021;100:1–56.

    Article  Google Scholar 

  27. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2024. https://www.r-project.org/.

  28. Donato JJ. Programming of metabolism by adipokines during development. Nat Rev Endocrino. 2023;19:385–97.

    Article  Google Scholar 

  29. Schubring C, Siebler T, Kratzsch J, Englaro P, Blum WF, Triep K, et al. Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight. Clin Endocrinol (Oxf). 1999;51:199–204.

    Article  CAS  PubMed  Google Scholar 

  30. Martos-Moreno GÁ, Barrios V, Sáenz de Pipaón M, Pozo J, Dorronsoro I, Martínez-Biarge M, et al. Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism. Eur J Endocrinol. 2009;161:381–9.

    Article  CAS  PubMed  Google Scholar 

  31. Ertl T, Funke S, Sárkány I, Szabó I, Rascher W, Blum WernerF, et al. Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone. Biol Neonate. 1999;75:167–76.

    Article  CAS  PubMed  Google Scholar 

  32. Buck CO, Li N, Eaton CB, Kelsey KT, Cecil KM, Kalkwarf HJ, et al. Neonatal and adolescent adipocytokines as predictors of adiposity and cardiometabolic risk in adolescence. Obes (Silver Spring). 2021;29:1036–45.

    Article  CAS  Google Scholar 

  33. Siahanidou T, Mandyla H, Papassotiriou G-P, Papassotiriou I, Chrousos G. Circulating levels of adiponectin in preterm infants. Arch Dis Child - Fetal Neonatal Ed. 2007;92:F286–F290.

    Article  PubMed  Google Scholar 

  34. Yoshida T, Nagasaki H, Asato Y, Ohta T. The ratio of high-molecular weight adiponectin and total adiponectin differs in preterm and term infants. Pediatr Res. 2009;65:580–3.

    Article  CAS  PubMed  Google Scholar 

  35. Han L, Li B, Xu X, Liu S, Li Z, Li M, et al. Umbilical cord blood adiponectin, leptin, insulin, and ghrelin in premature infants and their association with birth outcomes. Front Endocrinol. 2021; 12.https://www.frontiersin.org/articles/10.3389/fendo.2021.738964 (accessed 4 Apr 2023).

  36. Johnson MJ, Wootton SA, Leaf AA, Jackson AA. Preterm birth and body composition at term equivalent age: a systematic review and meta-analysis. Pediatrics. 2012;130:e640–649.

    Article  PubMed  Google Scholar 

  37. Devaskar SU, Chu A. Intrauterine growth restriction: hungry for an answer. Physiology. 2016;31:131–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Limesand SW, Rozance PJ, Macko AR, Anderson MJ, Kelly AC, Hay WW. Reductions in insulin concentrations and β-cell mass precede growth restriction in sheep fetuses with placental insufficiency. Am J Physiol-Endocrinol Metab. 2013;304:E516–E523.

    Article  CAS  PubMed  Google Scholar 

  39. Frost MS, Zehri AH, Limesand SW, Hay WW, Rozance PJ. Differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic β -cells. J Pregnancy. 2012;2012:1–8.

    Article  Google Scholar 

  40. Gray IP, Cooper PA, Cory BJ, Toman M, Crowther NJ. The intrauterine environment is a strong determinant of glucose tolerance during the neonatal period, even in prematurity. J Clin Endocrinol Metab. 2002;87:4252–6.

    Article  CAS  PubMed  Google Scholar 

  41. Garg M, Devaskar SU. Glucose metabolism in the late preterm infant. Clin Perinatol. 2006;33:853–70.

    Article  PubMed  Google Scholar 

  42. Cho GJ, Yoo SW, Hong SC, Oh M-J, Kim T, Kim HJ, et al. Correlations between umbilical and maternal serum resistin levels and neonatal birth weight. Acta Obstetricia et Gynecologica Scand. 2006;85:1051–6.

    Article  CAS  Google Scholar 

  43. Nava-Salazar S, Flores-Pliego A, Pérez-Martínez G, Parra-Hernández S, Vanoye-Carlo A, Ibarguengoitia-Ochoa F, et al. Resistin modulates low-density lipoprotein cholesterol uptake in human placental explants via PCSK9. Reprod Sci. 2022;29:3242–53.

    Article  CAS  PubMed  Google Scholar 

  44. Savino F, Lupica MM, Liguori SA, Fissore MF, Silvestro L. Ghrelin and feeding behaviour in preterm infants. Early Hum Dev. 2012;88:S51–S55.

    Article  CAS  PubMed  Google Scholar 

  45. Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes during pregnancy: a maternal disease complicating the course of pregnancy with long-term deleterious effects on the offspring. a clinical review. Int J Mol Sci. 2021;22:2965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bellone S, Baldelli R, Radetti G, Rapa A, Vivenza D, Petri A, et al. Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake. J Clin Endocrinol Metab. 2006;91:1929–33.

    Article  CAS  PubMed  Google Scholar 

  47. Mericq V, Martinez-Aguayo A, Uauy R, Iñiguez G, Van der Steen M, Hokken-Koelega A. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol. 2017;13:50–62.

    Article  CAS  PubMed  Google Scholar 

  48. Ng PC, Lee CH, Lam CWK, Chan IHS, Wong E, Fok TF. Ghrelin in preterm and term newborns: relation to anthropometry, leptin and insulin. Clin Endocrinol. 2005;63:217–22.

    Article  CAS  Google Scholar 

  49. Shimizu T, Kitamura T, Yoshikawa N, Suganuma H, Hisata K, Tanaka K, et al. Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures. Arch Dis Child Fetal Neonatal Ed. 2007;92:F291–F292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lis-Kuberka J, Pupek M, Orczyk-Pawiłowicz M. The mother-child dyad adipokine pattern: a review of current knowledge. Nutrients. 2023;15:4059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank the Yale Neonatal NOuRISH Research Team at Yale School of Medicine for their work in enrolling subjects in this study and their involvement in the conduction of body composition assessments for subjects enrolled in this study.

Funding

This publication was in part made possible by CTSA Grant Number UL1TR001863 from NCATS, a component of the NIH; the COVID-19 Fund to Retain Clinical Scientists at Yale, sponsored by the Doris Duke Charitable Foundation award #2021266, and the Yale Center for Clinical Investigation; the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award, Bank of America, Private Bank, Trustee; and the Society for Pediatric Research Bridging to Success Award. Research reported in this publication was also supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number T35DK104689. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA

    Caroline G. Borden, Veronika Shabanova, Sarah N. Taylor & Catherine O. Buck

Authors
  1. Caroline G. Borden
    View author publications

    Search author on:PubMed Google Scholar

  2. Veronika Shabanova
    View author publications

    Search author on:PubMed Google Scholar

  3. Sarah N. Taylor
    View author publications

    Search author on:PubMed Google Scholar

  4. Catherine O. Buck
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Study conceptualization, COB, CGB, SNT; Methodology, COB, VS; Formal Analysis CGB, VS; Investigation, COB; Writing – Original Draft Preparation, CGB; Writing – Review & Editing, COB, VS, SNT; Supervision, COB, SNT; Funding Acquisition, COB.

Corresponding author

Correspondence to Catherine O. Buck.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was performed in accordance with the declaration of Helsinki and was approved by the Institutional Review Board at Yale University.

Additional information

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

Supplementary information

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

Borden, C.G., Shabanova, V., Taylor, S.N. et al. Alterations in infant adipokine concentrations in the first postnatal week with exposure to diabetes in pregnancy. J Perinatol 45, 622–627 (2025). https://doi.org/10.1038/s41372-025-02269-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41372-025-02269-2

Search

Advanced search

Quick links