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Epidemiology and Population Health

Maternal adipokines longitudinally measured across pregnancy and their associations with neonatal size, length, and adiposity

International Journal of Obesity volume 43, pages 1422–1434 (2019)Cite this article

Subjects

Abstract

Background/objectives

Maternal obesity impacts fetal growth as early as second trimester of pregnancy, yet little is known about the molecular mechanisms involved. We aimed to examine associations between maternal adipokines throughout pregnancy and neonatal size by prepregnancy obesity status.

Methods

In a prospective cohort of 2802 U.S. pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort (2009–2013), biospecimens were analyzed in a matched case−control subset of 321 women. Blood was collected at 10–14, 15–26 (fasting), 23–31, and 33–39 gestational weeks. Plasma leptin and soluble leptin receptor (sOB-R) and total and high-molecular-weight (HMW)-adiponectin were measured. Free leptin was calculated as leptin/sOB-R. Birthweight was abstracted from medical records. Neonatal length and skinfolds were measured.

Results

Leptin and sOB-R in late pregnancy tended to be positively and negatively associated with neonatal length, respectively, while free leptin throughout pregnancy tended to be positively associated with length. Free leptin associations with neonatal length were differential by obesity (i.e., inversely among women without obesity and positively among women with obesity). A per unit increase in free leptin at 33–39 weeks was associated with a shorter neonatal length by −0.55 cm (95%CI, −0.83, −0.28) in women without obesity and longer length by 0.49 cm (95%CI, 0.34, 0.65) in women with obesity. HMW-adiponectin at 33–39 weeks was inversely associated with neonatal length (β = −1.29 cm; 95%CI, −1.74, −0.85) and skinfold thickness (β = −1.46 mm; 95%CI, −1.58, −0.56) among women with obesity. Free leptin across pregnancy tended to be negatively associated with neonatal skinfold thickness among women without obesity, while free leptin in early pregnancy was positively associated with skinfold thickness.

Conclusions

Maternal adipokines were associated with multiple pathways that influence neonatal size including length and adiposity, which differed in timing across pregnancy and by prepregnancy obesity. These findings provide new potential insights into mechanisms and timing by which maternal obesity may impact fetal growth.

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References

  1. Yu Z, Han S, Zhu J, Sun X, Ji C, Guo X. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS ONE. 2013;8:e61627.

    Article  CAS  Google Scholar 

  2. Zhang C, Hediger ML, Albert PS, Grewal J, Sciscione A, Grobman WA, et al. Association of maternal obesity with longitudinal ultrasonographic measures of fetal growth: findings rom the NICHD fetal growth studies—singletons. JAMA Pediatr. 2018;172:24–31.

    Article  Google Scholar 

  3. King JC. Physiology of pregnancy and nutrient metabolism. Am J Clin Nutr. 2000;71:1218s–25s.

    Article  CAS  Google Scholar 

  4. Allison MB, Myers MG,Jr.. 20 years of leptin: connecting leptin signaling to biological function. J Endocrinol. 2014;223:T25–35.

    Article  CAS  Google Scholar 

  5. Schaab M, Kratzsch J. The soluble leptin receptor. Best Pract Res Clin Endocrinol Metab. 2015;29:661–70.

    Article  CAS  Google Scholar 

  6. Misra VK, Straughen JK, Trudeau S. Maternal serum leptin during pregnancy and infant birth weight: the influence of maternal overweight and obesity. Obes (Silver Spring). 2013;21:1064–9.

    Article  CAS  Google Scholar 

  7. Hauguel-de Mouzon S, Lepercq J, Catalano P. The known and unknown of leptin in pregnancy. Am J Obstet Gynecol. 2006;194:1537–45.

    Article  CAS  Google Scholar 

  8. Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int. 2014;2014:658913.

    Article  CAS  Google Scholar 

  9. Hauguel-de Mouzon S, Catalano P. Adiponectin: are measurements clinically useful in pregnancy? Diabetes Care. 2013;36:1434–6.

    Article  CAS  Google Scholar 

  10. Catov JM, Patrick TE, Powers RW, Ness RB, Harger G, Roberts JM. Maternal leptin across pregnancy in women with small-for-gestational-age infants. Am J Obstet Gynecol. 2007;196:558 e1–8.

    Article  CAS  Google Scholar 

  11. Papastefanou I, Samolis S, Panagopoulos P, Tagia M, Bale C, Kouskoukis A, et al. Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women. J Matern Fetal Neonatal Med. 2010;23:1435–43.

    Article  Google Scholar 

  12. Tamura T, Goldenberg RL, Johnston KE, Cliver SP. Serum leptin concentrations during pregnancy and their relationship to fetal growth. Obstet Gynecol. 1998;91:389–95.

    Article  CAS  Google Scholar 

  13. Nanda S, Akolekar R, Sarquis R, Mosconi AP, Nicolaides KH. Maternal serum adiponectin at 11 to 13 weeks of gestation in the prediction of macrosomia. Prenat Diagn. 2011;31:479–83.

    Article  CAS  Google Scholar 

  14. Valdes ER, Lattes KA, Munoz HS, Barja PY, Papapietro KV. First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction. Gynecol Obstet Invest. 2011;72:152–6.

    Article  CAS  Google Scholar 

  15. Wang J, Shang LX, Dong X, Wang X, Wu N, Wang SH, et al. Relationship of adiponectin and resistin levels in umbilical serum, maternal serum and placenta with neonatal birth weight. Aust N Z J Obstet Gynaecol. 2010;50:432–8.

    Article  Google Scholar 

  16. Godfrey K, Walker‐Bone K, Robinson S, Taylor P, Shore S, Wheeler T, et al. Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy. J Bone Miner Res. 2001;16:1694–703.

    Article  CAS  Google Scholar 

  17. Fewtrell MS, Cole TJ, Bishop NJ, Lucas A. Neonatal factors predicting childhood height in preterm infants: evidence for a persisting effect of early metabolic bone disease? J Pediatr. 2000;137:668–73.

    Article  CAS  Google Scholar 

  18. Hediger ML, Overpeck MD, Kuczmarski RJ, McGlynn A, Maurer KR, Davis WW. Muscularity and fatness of infants and young children born small-or large-for-gestational-age. Pediatrics. 1998;102:e60–e.

    Article  CAS  Google Scholar 

  19. Catalano PM, Farrell K, Thomas A, Huston-Presley L, Mencin P, De Mouzon SH, et al. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr. 2009;90:1303–13.

    Article  CAS  Google Scholar 

  20. Grewal J, Grantz KL, Zhang C, Sciscione A, Wing DA, Grobman WA, et al. Cohort profile: NICHD fetal growth studies—singletons and twins. Int J Epidemiol. 2017;47:25–l.

    Article  Google Scholar 

  21. Buck Louis GM, Grewal J, Albert PS, Sciscione A, Wing DA, Grobman WA, et al. Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies. Am J Obstet Gynecol. 2015;213:449e1–e41.

    Article  Google Scholar 

  22. Zhu Y, Mendola P, Albert PS, Bao W, Hinkle SN, Tsai MY, et al. Insulin-like growth factor axis and gestational diabetes mellitus: a longitudinal study in a multiracial cohort. Diabetes. 2016;65:3495–504.

    Article  CAS  Google Scholar 

  23. World Health Organization. Training course on child growth assessment. Geneva: WHO; 2008. p. 17−25.

  24. Ulijaszek SJ, Kerr DA. Anthropometric measurement error and the assessment of nutritional status. Br J Nutr. 1999;82:165–77.

    Article  CAS  Google Scholar 

  25. Johnson TS, Engstrom JL, Gelhar DK. Intra- and interexaminer reliability of anthropometric measurements of term infants. J Pediatr Gastroenterol Nutr. 1997;24:497–505.

    Article  CAS  Google Scholar 

  26. de Onis M, Onyango AW, Van den Broeck J, Chumlea WC, Martorell R. Measurement and standardization protocols for anthropometry used in the construction of a new international growth reference. Food Nutr Bull. 2004;25(1 Suppl):S27–36.

    Article  Google Scholar 

  27. Schmelzle HR, Fusch C. Body fat in neonates and young infants: validation of skinfold thickness versus dual-energy X-ray absorptiometry. Am J Clin Nutr. 2002;76:1096–100.

    Article  CAS  Google Scholar 

  28. Weile B. Caliper skinfold measurements in newborns: analysis of a method. Biol Neonate. 1986;50:192–9.

    Article  CAS  Google Scholar 

  29. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin no. 190: gestational diabetes mellitus. Obstet Gynecol. 2018;131:e49–64.

  30. Samuelsen SO. A psudolikelihood approach to analysis of nested case-control studies. Biometrika. 1997;84:379–94.

    Article  Google Scholar 

  31. Zhou XH, Eckert GJ, Tierney WM. Multiple imputation in public health research. Stat Med. 2001;20:1541–9.

    Article  CAS  Google Scholar 

  32. Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr. 2003;3:6.

    Article  Google Scholar 

  33. Ananth CV, Schisterman EF. Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics. Am J Obstet Gynecol. 2017;217:167–75.

    Article  Google Scholar 

  34. Nagin DS. Analyzing developmental trajectories: a semiparametric, group-based approach. Psychol Methods. 1999;4:139.

    Article  Google Scholar 

  35. Karakosta P, Chatzi L, Plana E, Margioris A, Castanas E, Kogevinas M. Leptin levels in cord blood and anthropometric measures at birth: a systematic review and meta‐analysis. Paediatr Perinat Epidemiol. 2011;25:150–63.

    Article  Google Scholar 

  36. Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metab-Clin Exp. 2015;64:105–13.

    Article  CAS  Google Scholar 

  37. Geary M, Pringle PJ, Persaud M, Wilshin J, Hindmarsh PC, Rodeck CH, et al. Leptin concentrations in maternal serum and cord blood: relationship to maternal anthropometry and fetal growth. Br J Obstet Gynaecol. 1999;106:1054–60.

    Article  CAS  Google Scholar 

  38. Sørensen HT, Sabroe S, Rothman KJ, Gillman M, Steffensen FH, Fischer P, et al. Birth weight and length as predictors for adult height. Am J Epidemiol. 1999;149:726–9.

    Article  Google Scholar 

  39. Jones IE, Williams SM, Goulding A. Associations of birth weight and length, childhood size, and smoking with bone fractures during growth: evidence from a birth cohort study. Am J Epidemiol. 2004;159:343–50.

    Article  Google Scholar 

  40. Cooper C, Westlake S, Harvey N, Javaid K, Dennison E, Hanson M. Review: developmental origins of osteoporotic fracture. Osteoporos Int. 2006;17:337–47.

    Article  Google Scholar 

  41. Josefson JL, Zeiss DM, Rademaker AW, Metzger BE. Maternal leptin predicts adiposity of the neonate. Horm Res Paediatr. 2014;81:13–9.

    Article  CAS  Google Scholar 

  42. Patenaude J, Lacerte G, Lacroix M, Guillemette L, Allard C, Doyon M, et al. Associations of maternal leptin with neonatal adiposity differ according to pregravid weight. Neonatology. 2017;111:344–52.

    Article  CAS  Google Scholar 

  43. Valsamakis G, Papatheodorou DC, Naoum A, Margeli A, Papassotiriou I, Kapantais E, et al. Neonatal birth waist is positively predicted by second trimester maternal active ghrelin, a pro-appetite hormone, and negatively associated with third trimester maternal leptin, a pro-satiety hormone. Early Hum Dev. 2014;90:487–92.

    Article  CAS  Google Scholar 

  44. Symonds ME, Mostyn A, Pearce S, Budge H, Stephenson T. Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol. 2003;179:293–9.

    Article  CAS  Google Scholar 

  45. Aye IL, Powell TL, Jansson T. Review: Adiponectin—the missing link between maternal adiposity, placental transport and fetal growth? Placenta. 2013;34(Suppl):S40–5.

    Article  CAS  Google Scholar 

  46. Gilbert WM, Young AL, Danielsen B. Pregnancy outcomes in women with chronic hypertension: a population-based study. J Reprod Med. 2007;52:1046–51.

    PubMed  Google Scholar 

  47. Headen I, Cohen AK, Mujahid M, Abrams B. The accuracy of self-reported pregnancy-related weight: a systematic review. Obes Rev. 2017;18:350–69.

    Article  CAS  Google Scholar 

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Acknowledgements

Funding

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding as well as the American Recovery and Reinvestment Act funding (contract numbers HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, and HHSN275201000001Z).

Author contributions

SNH had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conception or design of the paper: SNH, CZ. Acquisition, analysis, or interpretation of data: All authors. Statistical analysis: SNH, DL, JC. Obtaining funding: CZ. Administrative, technical, or material support: CZ, MYT. Critical revision of the manuscript for important intellectual content: All authors.

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Authors and Affiliations

  1. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Stefanie N. Hinkle, Shristi Rawal, Danping Liu & Cuilin Zhang

  2. Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark, NJ, USA

    Shristi Rawal

  3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Danping Liu

  4. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Jinbo Chen

  5. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Michael Y. Tsai

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Correspondence to Cuilin Zhang.

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Hinkle, S.N., Rawal, S., Liu, D. et al. Maternal adipokines longitudinally measured across pregnancy and their associations with neonatal size, length, and adiposity. Int J Obes 43, 1422–1434 (2019). https://doi.org/10.1038/s41366-018-0255-2

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