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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. Access through your institution Buy or subscribe This is a

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2017;18:350–69. Article  CAS  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Department of Nutritional Sciences, School of Health Professions,

Rutgers University, Newark, NJ, USA Shristi Rawal * Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Danping Liu *

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Jinbo Chen * Department of Laboratory Medicine and

Pathology, University of Minnesota, Minneapolis, MN, USA Michael Y. Tsai Authors * Stefanie N. Hinkle View author publications You can also search for this author inPubMed Google Scholar *

Shristi Rawal View author publications You can also search for this author inPubMed Google Scholar * Danping Liu View author publications You can also search for this author inPubMed Google

Scholar * Jinbo Chen View author publications You can also search for this author inPubMed Google Scholar * Michael Y. Tsai View author publications You can also search for this author

inPubMed Google Scholar * Cuilin Zhang View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Cuilin Zhang. ETHICS

DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ELECTRONIC SUPPLEMENTARY MATERIAL HINKLE ET AL. SUPPLEMENTAL MATERIAL RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 26 March 2018 * Revised: 14 August 2018

* Accepted: 19 August 2018 * Published: 21 November 2018 * Issue Date: July 2019 * DOI: https://doi.org/10.1038/s41366-018-0255-2 SHARE THIS ARTICLE Anyone you share the following link with

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