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Disparity in fetal growth between twin and singleton gestation: the role of adipokines

Journal of Perinatology volume 38, pages 35–40 (2018)Cite this article

Subjects

Abstract

Objective:

Twin pregnancies are characterized by unique pattern of attenuated fetal weight gain during late gestation compared with singleton gestation. The mechanism(s) responsible for regulating twin growth has not yet elucidated. Leptin and adiponectin are two adipocytokines implicated in metabolism and energy balance of fetuses, newborns and adults. Moreover, these hormones have been suggested to play a role in fetal growth. The objective of the study was to determine cord blood adiponectin and leptin in twins and singletons, with and without growth impairment.

Study design:

This was a case-control study. It included two groups of newborns, matched for gestational age and birth weight percentile: singleton (n=60 newborns) and twins (n=44 newborns). Adiponectin and leptin were determined in cord blood, and compared between the groups according to clinical and demographic characteristics. Non-parametric and parametric statistical methods were employed.

Results:

Median adiponectin and leptin concentrations were lower in twins vs singletons (P<0.001 for both comparisons). Among small for gestational age newborns (SGA), median concentration of adiponectin (P=0.04), but not leptin (P=0.1), was lower in twins compared to singletons. In pooled analysis (singleton plus twins), cord blood adiponectin and leptin were strongly correlated with gestational age (P<0.001 and P=0.005, respectively) and birth weight (P<0.001 and P<0.001, respectively). Regression analysis revealed that plurality (P=0.02) was significantly and independently associated with cord blood adiponectin concentrations, after adjustment for confounding variables. Similar regression in which leptin was the independent variable revealed that only birth weight (P=0.01) was significantly and independently associated with cord blood leptin concentrations.

Conclusions:

Twin pregnancies are associated with lower cord blood concentrations of adiponectin and leptin compared with singleton gestations. However, only cord blood adiponectin, but not leptin, was lower in SGA neonates. Collectively, these data suggest that adiponectin may be implicated in the mechanism accounting for the growth disparity between twins and singletons.

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References

  1. Hall JG . Twinning. Lancet 2003; 362 (9385): 735–743.

    Article  Google Scholar 

  2. Blickstein I . Is it normal for multiples to be smaller than singletons? Best Pract Res Clin Obstet Gynaecol 2004; 18 (4): 613–623.

    Article  Google Scholar 

  3. Sooranna SR, Ward S, Bajoria R . Fetal leptin influences birth weight in twins with discordant growth. Pediatr Res 2001; 49 (5): 667–672.

    Article  CAS  Google Scholar 

  4. Onal EE, Uysal FK, Cinaz P, Bideci A, Dilmen U . Serum leptin levels in twins and singleton newborns. J Pediatr Endocrinol Metab 2003; 16 (5): 733–739.

    Article  Google Scholar 

  5. Ahima RS, Flier JS . Leptin. Annu Rev Physiol 2000; 62: 413–437.

    Article  CAS  Google Scholar 

  6. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269 (5223): 543–546.

    Article  CAS  Google Scholar 

  7. Hoggard N, Hunter L, Duncan JS, Williams LM, Trayhurn P, Mercer JG . Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. Proc Natl Acad Sci USA 1997; 94 (20): 11073–11078.

    Article  CAS  Google Scholar 

  8. Forhead AJ, Fowden AL . The hungry fetus? Role of leptin as a nutritional signal before birth. J Physiol 2009; 587 (Pt 6): 1145–1152.

    Article  CAS  Google Scholar 

  9. Koistinen HA, Koivisto VA, Andersson S, Karonen SL, Kontula K, Oksanen L et al. Leptin concentration in cord blood correlates with intrauterine growth. J Clin Endocrinol Metab 1997; 82 (10): 3328–3330.

    CAS  PubMed  Google Scholar 

  10. Varvarigou A, Mantzoros CS, Beratis NG . Cord blood leptin concentrations in relation to intrauterine growth. Clin Endocrinol 1999; 50 (2): 177–183.

    Article  CAS  Google Scholar 

  11. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Schiff E, Sivan E . Cord blood adiponectin in large-for-gestational age newborns. Am J Obstet Gynecol 2005; 193 (3 Pt 2): 1238–1242.

    Article  CAS  Google Scholar 

  12. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF . A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270 (45): 26746–26749.

    Article  CAS  Google Scholar 

  13. Aye IL, Powell TL, Jansson T . Review: Adiponectin—the missing link between maternal adiposity, placental transport and fetal growth? Placenta 2013; 34 (Suppl): S40–S45.

    Article  CAS  Google Scholar 

  14. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001; 86 (8): 3815–3819.

    Article  CAS  Google Scholar 

  15. Corbetta S, Bulfamante G, Cortelazzi D, Barresi V, Cetin I, Mantovani G et al. Adiponectin expression in human fetal tissues during mid- and late gestation. J Clin Endocrinol Metab 2005; 90 (4): 2397–2402.

    Article  CAS  Google Scholar 

  16. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Wiser A, Schiff E et al. Maternal serum adiponectin levels during human pregnancy. J Perinatol 2007; 27 (2): 77–81.

    Article  CAS  Google Scholar 

  17. Worda C, Leipold H, Gruber C, Kautzky-Willer A, Knofler M, Bancher-Todesca D . Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus. Am J Obstet Gynecol 2004; 191 (6): 2120–2124.

    Article  CAS  Google Scholar 

  18. Mazaki-Tovi S, Romero R, Vaisbuch E, Erez O, Mittal P, Chaiworapongsa T et al. Maternal serum adiponectin multimers in gestational diabetes. J Perinat Med 2009; 37 (6): 637–650.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. D'Anna R, Baviera G, Corrado F, Giordano D, De VA, Nicocia G et al. Adiponectin and insulin resistance in early- and late-onset pre-eclampsia. BJOG 2006; 113 (11): 1264–1269.

    Article  CAS  Google Scholar 

  20. Mazaki-Tovi S, Romero R, Vaisbuch E, Kusanovic JP, Erez O, Gotsch F et al. Maternal serum adiponectin multimers in preeclampsia. J Perinat Med 2009; 37 (4): 349–363.

    Article  CAS  Google Scholar 

  21. Kotani Y, Yokota I, Kitamura S, Matsuda J, Naito E, Kuroda Y . Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight. Clin Endocrinol 2004; 61 (4): 418–423.

    Article  CAS  Google Scholar 

  22. Aydin HI, Eser A, Kaygusuz I, Yildirim S, Celik T, Gunduz S et al. Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers. J Perinat Med 2016; 44 (6): 669–676.

    Article  CAS  Google Scholar 

  23. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Yinon Y, Wiser A et al. Adiponectin and leptin concentrations in dichorionic twins with discordant and concordant growth. J Clin Endocrinol Metab 2009; 94 (3): 892–898.

    Article  CAS  Google Scholar 

  24. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Efraty Y, Schiff E et al. Determining the source of fetal adiponectin. J Reprod Med 2007; 52 (9): 774–778.

    CAS  PubMed  Google Scholar 

  25. Finucane FM, Luan J, Wareham NJ, Sharp SJ, O'Rahilly S, Balkau B et al. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia 2009; 52 (11): 2345–2349.

    Article  CAS  Google Scholar 

  26. Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K et al. Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004; 27 (10): 2488–2490.

    Article  CAS  Google Scholar 

  27. Zhuo Q, Wang Z, Fu P, Piao J, Tian Y, Xu J et al. Comparison of adiponectin, leptin and leptin to adiponectin ratio as diagnostic marker for metabolic syndrome in older adults of Chinese major cities. Diabetes Res Clin Pract 2009; 84 (1): 27–33.

    Article  CAS  Google Scholar 

  28. Lausten-Thomsen U, Christiansen M, Hedley PL, Holm JC, Schmiegelow K . Adipokines in umbilical cord blood from children born large for gestational age. J Pediatr Endocrinol Metab 2016; 29 (1): 33–37.

    Article  CAS  Google Scholar 

  29. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES . Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005; 7 (5): 311–314.

    Google Scholar 

  30. Palcevska-Kocevska S, Aluloska N, Krstevska M, Shukarova-Angelovska E, Kojik L, Zisovska E et al. Correlation of serum adiponectin and leptin concentrations with anthropometric parameters in newborns. Srp Arh Celok Lek 2012; 140 (9-10): 595–599.

    Article  Google Scholar 

  31. Blickstein I . Normal and abnormal growth of multiples. Semin Neonatol 2002; 7 (3): 177–185.

    Article  Google Scholar 

  32. Lea RG, Howe D, Hannah LT, Bonneau O, Hunter L, Hoggard N . Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod 2000; 6 (8): 763–769.

    Article  CAS  Google Scholar 

  33. Jaquet D, Leger J, Levy-Marchal C, Oury JF, Czernichow P . Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations. J Clin Endocrinol Metab 1998; 83 (4): 1243–1246.

    Article  CAS  Google Scholar 

  34. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Kuint J, Yinon Y et al. Cord blood adiponectin and infant growth at one year. J Pediatr Endocrinol Metab 2011; 24 (7-8): 411–418.

    Article  CAS  Google Scholar 

  35. Gohlke BC, Huber A, Bartmann P, Fimmers R, Hecher K, Bouret SG et al. Cord blood leptin and IGF-I in relation to birth weight differences and head circumference in monozygotic twins. J Pediatr Endocrinol Metab 2006; 19 (1): 3–9.

    Article  CAS  Google Scholar 

  36. Gohlke BC, Bartmann P, Fimmers R, Huber A, Hecher K, Roth CL . Fetal adiponectin and resistin in correlation with birth weight difference in monozygotic twins with discordant growth. Horm Res 2008; 69 (1): 37–44.

    CAS  PubMed  Google Scholar 

  37. Lee SM, Park JS, Norwitz ER, Panyavatthanasinh S, Kim SM, Lee J et al. Levels of adipokines in amniotic fluid and cord blood collected from dichorionic-diamniotic twins discordant for fetal growth. PLoS ONE 2016; 11 (5): e0154537.

    Article  Google Scholar 

  38. Sooranna SR, Ward S, Bajoria R . Discordant fetal leptin levels in monochorionic twins with chronic midtrimester twin-twin transfusion syndrome. Placenta 2001; 22 (5): 392–398.

    Article  CAS  Google Scholar 

  39. Berg AH, Scherer PE . Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96 (9): 939–949.

    Article  CAS  Google Scholar 

  40. 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 (12): 5656–5660.

    Article  CAS  Google Scholar 

  41. Oshima K, Nampei A, Matsuda M, Iwaki M, Fukuhara A, Hashimoto J et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun 2005; 331 (2): 520–526.

    Article  CAS  Google Scholar 

  42. Qiao L, Yoo HS, Madon A, Kinney B, Hay WW Jr., Shao J . Adiponectin enhances mouse fetal fat deposition. Diabetes 2012; 61 (12): 3199–3207.

    Article  CAS  Google Scholar 

  43. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341 (12): 879–884.

    Article  CAS  Google Scholar 

  44. Dawczynski K, de VH, Beck JF, Schleussner E, Wittig S, Proquitte H . Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin. J Pediatr Endocrinol Metab 2014; 27 (3-4): 273–278.

    Article  CAS  Google Scholar 

  45. Yura S, Sagawa N, Mise H, Mori T, Masuzaki H, Ogawa Y et al. A positive umbilical venous-arterial difference of leptin level and its rapid decline after birth. Am J Obstet Gynecol 1998; 178 (5): 926–930.

    Article  CAS  Google Scholar 

  46. Koebnick C, Shaibi GQ, Kelly LA, Roberts CK, Lane CJ, Toledo-Corral C et al. Leptin-to-adiponectin ratio as independent predictor of insulin sensitivity during growth in overweight Hispanic youth. J Endocrinol Invest 2007; 30 (7): RC13–RC16.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by grants from the Talpiot Medical Leadership Program, Sheba Medical Center, TelHashomer (M-TS), Israel.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel

    R Zemet, B Brandt, E Sivan & S Mazaki-Tovi

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    R Zemet, R Hemi, B Brandt, E Sivan, H Kanety & S Mazaki-Tovi

  3. Department of Obstetrics and Gynecology, Lis Maternity Hospital, Sourasky Medical Center, Tel Aviv, Israel

    Y Shulman

  4. Institute of Endocrinology, Sheba Medical Center, Tel-Hashomer, Israel

    R Hemi & H Kanety

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  1. R Zemet
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Correspondence to S Mazaki-Tovi.

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Zemet, R., Shulman, Y., Hemi, R. et al. Disparity in fetal growth between twin and singleton gestation: the role of adipokines. J Perinatol 38, 35–40 (2018). https://doi.org/10.1038/jp.2017.152

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  • DOI: https://doi.org/10.1038/jp.2017.152

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