Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts

doi:10.1017/S204017442500011X

. 2025 May 21:16:e20.

doi: 10.1017/S204017442500011X.

Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts

Michael R Hussey¹, James MacDonald², Theo K Bammler², Fasil Tekola-Ayele³, Kathleen F Kerr⁴, Alison G Paquette^{2

5

6}, Carmen J Marsit⁷, Kaja Z LeWinn⁸, Qi Zhao⁹, Catherine J Karr^{1

2

5}, Sheela Sathyanarayana^{2

5

6}, Daniel A Enquobahrie^{1

10}

Affiliations

¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
² Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
³ Epidemiology Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
⁴ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
⁵ Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, USA.
⁶ Seattle Children's Research Institute, Seattle, WA, USA.
⁷ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁸ Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, CA, USA.
⁹ Department of Preventative Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁰ Department of Health Systems and Population Health, School of Public Health, University of Washington, Seattle, WA, USA.

PMID: 40394751
PMCID: PMC12097519 (available on 2025-11-21)
DOI: 10.1017/S204017442500011X

Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts

Michael R Hussey et al. J Dev Orig Health Dis. 2025.

. 2025 May 21:16:e20.

doi: 10.1017/S204017442500011X.

Authors

Affiliations

¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
² Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
³ Epidemiology Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
⁴ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
⁵ Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, USA.
⁶ Seattle Children's Research Institute, Seattle, WA, USA.
⁷ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁸ Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, CA, USA.
⁹ Department of Preventative Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁰ Department of Health Systems and Population Health, School of Public Health, University of Washington, Seattle, WA, USA.

PMID: 40394751
PMCID: PMC12097519 (available on 2025-11-21)
DOI: 10.1017/S204017442500011X

Abstract

Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)(n = 725) and GAPPS (Seattle and Yakima, WA)(n = 159) cohorts. Maternal ppBMI was assessed at enrollment using interviewer-administered questionnaires. LncRNAs (1,077 and 1,033 for CANDLE and GAPPS, respectively) were sequenced from placental samples collected at birth. Placental lncRNA was regressed on ppBMI, ppOB (ppBMI ≥30kg/m²), or continuous birthweight in cohort-specific weighted linear models controlling for a priori-specified confounders and experimental variables. Potential effect modification by infant-sex was examined in sex-stratified analyses and models including BMI-infant-sex interaction terms. No lncRNA transcripts were significantly associated with ppBMI, ppOB, or birthweight in primary models. Among male infants in CANDLE, expression of three lncRNA transcripts (ERVH48-1, AC139099.1, CEBPA-DT) was associated with ppBMI and one transcript (AC104083.1) with birthweight. In GAPPS, ppBMI was associated with two lncRNA transcripts (AP000879.1 and AL365203.2) among males, and birthweight was associated with 17 lncRNA transcripts (including LINC02709, KANSL1-AS1, DANCR, EPB41L4A-AS1, and GABPB1-AS1) among females. No BMI-infant-sex interactions were observed. Though many of these potential associations are for uncharacterized transcripts, several identified lncRNAs (e.g., ERVH48-1 and CEBPA-DT) have been linked to pathways controlling cancer or placental growth, trophoblast differentiation, and gene expression. These associations warrant validation in future studies.

Keywords: Long non-coding RNA; birthweight; placenta; pre-pregnancy obesity.

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Conflict of interest statement

Conflicts of Interest: None

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References

1. Barker DJP, Thornburg KL, Osmond C, Kajantie E, Eriksson JG. Beyond birthweight: the maternal and placental origins of chronic disease. Journal of Developmental Origins of Health and Disease. 2010;1(6):360–364. doi:10.1017/S2040174410000280 - DOI - PubMed
1. Huda SS, Brodie LE, Sattar N. Obesity in pregnancy: prevalence and metabolic consequences. Seminars in Fetal and Neonatal Medicine. 2010;15(2):70–76. doi:10.1016/j.siny.2009.09.006 - DOI - PubMed
1. Fowden AL, Camm EJ, Sferruzzi-Perri AN. Effects of Maternal Obesity On Placental Phenotype. CVP. 2020;19(2):113–131. doi:10.2174/1570161118666200513115316 - DOI - PubMed
1. Winder NR, Krishnaveni GV, Veena SR, et al. Mother’s lifetime nutrition and the size, shape and efficiency of the placenta. Placenta. 2011;32(11):806–810. doi:10.1016/j.placenta.2011.09.001 - DOI - PMC - PubMed
1. Kovo M, Zion-Saukhanov E, Schreiber L, et al. The Effect of Maternal Obesity on Pregnancy Outcome in Correlation With Placental Pathology. Reprod Sci. 2015;22(12):1643–1648. doi:10.1177/1933719115592712 - DOI - PubMed

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[1] Barker DJP, Thornburg KL, Osmond C, Kajantie E, Eriksson JG. Beyond birthweight: the maternal and placental origins of chronic disease. Journal of Developmental Origins of Health and Disease. 2010;1(6):360–364. doi:10.1017/S2040174410000280 - DOI - PubMed

[2] Barker DJP, Thornburg KL, Osmond C, Kajantie E, Eriksson JG. Beyond birthweight: the maternal and placental origins of chronic disease. Journal of Developmental Origins of Health and Disease. 2010;1(6):360–364. doi:10.1017/S2040174410000280 - DOI - PubMed

[3] Huda SS, Brodie LE, Sattar N. Obesity in pregnancy: prevalence and metabolic consequences. Seminars in Fetal and Neonatal Medicine. 2010;15(2):70–76. doi:10.1016/j.siny.2009.09.006 - DOI - PubMed

[4] Huda SS, Brodie LE, Sattar N. Obesity in pregnancy: prevalence and metabolic consequences. Seminars in Fetal and Neonatal Medicine. 2010;15(2):70–76. doi:10.1016/j.siny.2009.09.006 - DOI - PubMed

[5] Fowden AL, Camm EJ, Sferruzzi-Perri AN. Effects of Maternal Obesity On Placental Phenotype. CVP. 2020;19(2):113–131. doi:10.2174/1570161118666200513115316 - DOI - PubMed

[6] Fowden AL, Camm EJ, Sferruzzi-Perri AN. Effects of Maternal Obesity On Placental Phenotype. CVP. 2020;19(2):113–131. doi:10.2174/1570161118666200513115316 - DOI - PubMed

[7] Winder NR, Krishnaveni GV, Veena SR, et al. Mother’s lifetime nutrition and the size, shape and efficiency of the placenta. Placenta. 2011;32(11):806–810. doi:10.1016/j.placenta.2011.09.001 - DOI - PMC - PubMed

[8] Winder NR, Krishnaveni GV, Veena SR, et al. Mother’s lifetime nutrition and the size, shape and efficiency of the placenta. Placenta. 2011;32(11):806–810. doi:10.1016/j.placenta.2011.09.001 - DOI - PMC - PubMed

[9] Kovo M, Zion-Saukhanov E, Schreiber L, et al. The Effect of Maternal Obesity on Pregnancy Outcome in Correlation With Placental Pathology. Reprod Sci. 2015;22(12):1643–1648. doi:10.1177/1933719115592712 - DOI - PubMed

[10] Kovo M, Zion-Saukhanov E, Schreiber L, et al. The Effect of Maternal Obesity on Pregnancy Outcome in Correlation With Placental Pathology. Reprod Sci. 2015;22(12):1643–1648. doi:10.1177/1933719115592712 - DOI - PubMed

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Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts

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Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts

Authors

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Abstract

Conflict of interest statement

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