Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study
Issued Date
2022-10-01
Resource Type
ISSN
22138587
eISSN
22138595
Scopus ID
2-s2.0-85138156949
Pubmed ID
36030799
Journal Title
The Lancet Diabetes and Endocrinology
Volume
10
Issue
10
Start Page
710
End Page
719
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet Diabetes and Endocrinology Vol.10 No.10 (2022) , 710-719
Suggested Citation
Villar J., Ochieng R., Gunier R.B., Papageorghiou A.T., Rauch S., McGready R., Gauglitz J.M., Barros F.C., Vatish M., Fernandes M., Zammit V., Carrara V.I., Munim S., Craik R., Barsosio H.C., Carvalho M., Berkley J.A., Ismail L.I.C., Norris S.A., Tshivuila-Matala C.O.O., Nosten F., Ohuma E.O., Stein A., Lambert A., Winsey A., Uauy R., Eskenazi B., Bhutta Z.A., Kennedy S.H. Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study. The Lancet Diabetes and Endocrinology Vol.10 No.10 (2022) , 710-719. 719. doi:10.1016/S2213-8587(22)00215-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83598
Title
Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study
Author(s)
Villar J.
Ochieng R.
Gunier R.B.
Papageorghiou A.T.
Rauch S.
McGready R.
Gauglitz J.M.
Barros F.C.
Vatish M.
Fernandes M.
Zammit V.
Carrara V.I.
Munim S.
Craik R.
Barsosio H.C.
Carvalho M.
Berkley J.A.
Ismail L.I.C.
Norris S.A.
Tshivuila-Matala C.O.O.
Nosten F.
Ohuma E.O.
Stein A.
Lambert A.
Winsey A.
Uauy R.
Eskenazi B.
Bhutta Z.A.
Kennedy S.H.
Ochieng R.
Gunier R.B.
Papageorghiou A.T.
Rauch S.
McGready R.
Gauglitz J.M.
Barros F.C.
Vatish M.
Fernandes M.
Zammit V.
Carrara V.I.
Munim S.
Craik R.
Barsosio H.C.
Carvalho M.
Berkley J.A.
Ismail L.I.C.
Norris S.A.
Tshivuila-Matala C.O.O.
Nosten F.
Ohuma E.O.
Stein A.
Lambert A.
Winsey A.
Uauy R.
Eskenazi B.
Bhutta Z.A.
Kennedy S.H.
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
University of Sharjah
Aga Khan University Hospital, Nairobi
The Aga Khan University
London School of Hygiene & Tropical Medicine
Hospital for Sick Children University of Toronto
Green Templeton College
University of Oxford
University of Southampton, Faculty of Medicine
University of California, Berkeley
Universidade Catolica de Pelotas
The World Bank Group
University of the Witwatersrand, Johannesburg
Wits School of Public Health
Nuffield Department of Medicine
University of Oxford Medical Sciences Division
Warwick Medical School
African Health Research Institute
Sapient Bioanalytics, LLC
University of Sharjah
Aga Khan University Hospital, Nairobi
The Aga Khan University
London School of Hygiene & Tropical Medicine
Hospital for Sick Children University of Toronto
Green Templeton College
University of Oxford
University of Southampton, Faculty of Medicine
University of California, Berkeley
Universidade Catolica de Pelotas
The World Bank Group
University of the Witwatersrand, Johannesburg
Wits School of Public Health
Nuffield Department of Medicine
University of Oxford Medical Sciences Division
Warwick Medical School
African Health Research Institute
Sapient Bioanalytics, LLC
Other Contributor(s)
Abstract
Background: Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. Methods: In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks’ gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto–placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants’ health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. Findings: From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20–25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto–placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. Interpretation: Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity. Funding: Bill & Melinda Gates Foundation.