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.

  • Original Article
  • Published:

Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth

Journal of Perinatology volume 35, pages 547–552 (2015)Cite this article

Subjects

Abstract

Objective:

Leptin is an adipokine that regulates energy homeostasis. The objective of this study was to establish a gestational age-specific standard for amniotic fluid leptin (AFL) levels and examine the relationship between AFL, maternal overweight and fetal growth restriction.

Study Design:

Amniotic fluid was obtained at mid-gestation from singleton gravidas, and leptin was quantified using enzyme-linked immunosorbent assay. Amniotic fluid samples from 321 term pregnancies were analyzed. Clinical data, including fetal ultrasound measurements and maternal and infant characteristics, were available for a subset of patients (n=45).

Results:

The median interquartile range AFL level was significantly higher at 14 weeks’ gestation (2133 pg ml−1 (1703 to 4347)) than after 33 weeks’ gestation (519 pg ml−1 (380 to 761), P trend<0.0001), an average difference of 102 pg ml−1 per week. AFL levels were positively correlated with maternal pre-pregnancy body mass index (BMI) (r=0.36, P=0.03) adjusting for gestational age at measurement, but were not associated with fetal growth.

Conclusions:

AFL levels are higher at mid-gestation than at late gestation, and are associated with maternal pre-pregnancy BMI.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Bernstein I, Gabbe SG et al. Intrauterine growth restriction In: Gabbe SG, Niebyl JR, Simpson JL, Annas GJ (eds). Obstetrics: Normal and Problem Pregnancies 6th edn Elsevier: New York, NY, USA, 2012 pp 857–865.

    Google Scholar 

  2. Creasy RK, Resnik R . Intrauterine growth restriction In: Creasy RK, Resnik R (eds). Maternal-Fetal Medicine: Principles and Practice 4th edn. Saunders: Philadelphia, PA, USA, 2004 pp 495–512.

    Google Scholar 

  3. Alkalay AL, Graham JM, Pomerance JJ . Evaluation of neonates born with intrauterine growth retardation: review and practice guidelines. J Perinatol 1998; 18: 142–151.

    CAS  PubMed  Google Scholar 

  4. McIntire DD, Bloom SL, Casey BM, Leveno KJ . Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999; 340: 1234–1238.

    Article  CAS  Google Scholar 

  5. Godfrey KM, Barker DJ . Fetal programming and adult health. Public Health Nutr 2001; 4: 611–624.

    Article  CAS  Google Scholar 

  6. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM . Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36: 62–67.

    Article  CAS  Google Scholar 

  7. Neerhof MG . Causes of intrauterine growth restriction. Clin Perinatol 1995; 22: 375–385.

    Article  CAS  Google Scholar 

  8. Szentpéteri I, Rab A, Kornya L, Kovács P, Joó JG . Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction. J Matern Fetal Neonatal Med 2013; 26: 984–989.

    Article  Google Scholar 

  9. Vrachnis N, Kalampokas E, Sifakis S, Vitoratos N, Kalampokas T, Botsis D et al. Placental growth factor (PlGF): a key to optimizing fetal growth. J Matern Fetal Neonatal Med 2013; 26: 995–1002.

    Article  CAS  Google Scholar 

  10. Briana DD, Malamitsi-Puchner A . Intrauterine growth restriction and adult disease: the role of adipocytokines. Eur J Endocrinol 2009; 160: 337–347.

    Article  CAS  Google Scholar 

  11. Ornoy A . Biomarkers of maternal diabetes and its complication in pregnancy. Reprod Toxicol 2012; 34: 174–179.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Popovic V, Casanueva FF . Leptin, nutrition and reproduction: new insights. Hormones 2002; 1: 204–217.

    Article  Google Scholar 

  14. Senaris R, Garcia-Caballero T, Casabiell X, Gallego R, Castro R, Considine RV et al. Synthesis of leptin in human placenta. Endocrinology 1997; 138: 4501–4504.

    Article  CAS  Google Scholar 

  15. Lepercq J, Challier JC, Guerre-Millo M, Cauzac M, Vidal H, Hauguel-de Mouzon S . Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab 2001; 86: 2409–2413.

    Article  CAS  Google Scholar 

  16. Rasmussen KM, Yaktine AL (eds). Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. National Academies Press (US): Washington (DC), CO, USA, 2009.

  17. Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS . New intrauterine growth curves based on United States data. Pediatrics 2010; 125: e214–e224.

    Article  Google Scholar 

  18. Alexopoulos A, Bravou V, Peroukides S, Kaklamanis L, Varakis J, Alexopoulos D et al. Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves. Int J Cardiol 2010; 139: 142–149.

    Article  Google Scholar 

  19. Cole TJ, Green PJ . Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992; 11: 1305–1319.

    Article  CAS  Google Scholar 

  20. Henson MC, Castracane VD . Leptin in pregnancy: an update. Biol Reprod 2006; 74: 218–229.

    Article  CAS  Google Scholar 

  21. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H et al. Nonadipose tissue production of leptin: leptin as a novel placenta derived hormone in humans. Nat Med 1997; 3: 1029–1033.

    Article  CAS  Google Scholar 

  22. 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: 150–163.

    Article  Google Scholar 

  23. Chan TF, Su JH, Chung YF, Hsu YH, Yeh YT, Yuan SS . Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia. Acta Obstet Gynecol Scand 2006; 85: 171–174.

    Article  CAS  Google Scholar 

  24. Cagnacci A, Arangino S, Caretto S, Mazza V, Volpe A . Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth. Eur J Obstet Gynecol Reprod Biol 2006; 124: 53–57.

    Article  CAS  Google Scholar 

  25. Tessier DR, Ferraro ZM, Gruslin A . Role of leptin in pregnancy: Consequences of maternal obesity. Placenta 2013; 34: 205–211.

    Article  CAS  Google Scholar 

  26. Oktem O, Dedeoğlu N, Oymak Y, Sezen D, Köksal L, Pekin T et al. Maternal serum, amniotic fluid and cord leptin levels at term: their correlations with fetal weight. J Perinat Med 2004; 32: 266–271.

    Article  Google Scholar 

  27. 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: 763–769.

    Article  CAS  Google Scholar 

  28. Lappas M, Permezel M, Rice GE . Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology 2005; 146: 3334–3342.

    Article  CAS  Google Scholar 

  29. Misra VK, Trudeau S . The influence of overweight and obesity on longitudinal trends in maternal serum leptin levels during pregnancy. Obesity 2011; 19: 416e21.

    Google Scholar 

  30. Catalano PM, Presley L, Minium J, Hauguel-de Mouzon S . Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 2009; 32: 1076e80.

    Article  Google Scholar 

  31. Alexe DM, Syridou G, Petridou ET . Determinants of early life leptin levels and later life degenerative outcomes. Clinl Med Res 2006; 4: 326–335.

    Article  CAS  Google Scholar 

  32. Nagy GR, Gyõrffy B, Galamb O, Molnár B, Nagy B, Papp Z . Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders. Clin Chem 2006; 52: 2013–2020.

    Article  CAS  Google Scholar 

  33. Misra VK, Straughen JK, Trudeau S . Maternal serum leptin during pregnancy and infant birth weight: the influence of maternal overweight and obesity. Obesity (Silver Spring) 2013; 21: 1064–1069.

    Article  CAS  Google Scholar 

  34. Molvarec A, Szarka A, Walentin S, Beko G, Karádi I, Prohászka Z et al. Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia. Reprod Biol Endocrinol 2011; 9: 124.

    Article  CAS  Google Scholar 

  35. Bloomfield FH, Oliver MH, Harding JE . The late effects of fetal growth patterns. Arch Dis Child Fetal Neonatal Ed 2006; 91: F299–F304.

    Article  CAS  Google Scholar 

  36. McCormack RT, Armstrong J, Leonard D . Codevelopment of genome-based therapeutics and companion diagnostics: insights from an Institute of Medicine roundtable. JAMA 2014; 311: 1395–1396; Erratum in: JAMA 2014; 311: 1396.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Michelle Faust (Heart Institute Research Core) and Peggy Walsh (Hatton Research Center) for their assistance. Funding. We disclosed receipt of the following financial support for the research, authorship and/or publication of this article: the Cincinnati Children’s Research Foundation (RBH).

Author information

Author notes

  1. M Scott-Finley and J G Woo: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Maternal Fetal Medicine, Obstetrics and Gynecology, Good Samaritan Hospital, Cincinnati, OH, USA

    M Scott-Finley, M Habli, A C Hinton & W J Polzin

  2. Division of Cardiology, The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    J G Woo, M Habli, O Ramos-Gonzales, J F Cnota & R B Hinton

  3. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    J G Woo & Y Wang

  4. Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    B D Kamath-Rayne

  5. Fetal Care Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    W J Polzin & T M Crombleholme

Authors
  1. M Scott-Finley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J G Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Habli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Ramos-Gonzales
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J F Cnota
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B D Kamath-Rayne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A C Hinton
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W J Polzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T M Crombleholme
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R B Hinton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R B Hinton.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scott-Finley, M., Woo, J., Habli, M. et al. Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth. J Perinatol 35, 547–552 (2015). https://doi.org/10.1038/jp.2015.39

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2015.39

Search

Advanced search

Quick links