Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study

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dc.contributor.authorJose Villar
dc.contributor.authorRoseline Ochieng
dc.contributor.authorRobert B Gunier
dc.contributor.authorAris T Papageorghiou
dc.contributor.authorStephen Rauch
dc.contributor.authorRose McGready
dc.contributor.authorJulia M Gauglitz
dc.contributor.authorFernando C Barros
dc.contributor.authorManu Vatish
dc.contributor.authorMichelle Fernandes
dc.contributor.authorVictor Zammit
dc.contributor.authorVerena I Carrara
dc.contributor.authorShama Munim
dc.contributor.authorRachel Craik
dc.contributor.authorHellen C Barsosio
dc.contributor.authorMaria Carvalho
dc.contributor.authorJames A Berkley
dc.contributor.authorLeila I Cheikh Ismail
dc.contributor.authorShane A Norris
dc.contributor.authorChrystelle O O Tshivuila-Matala
dc.contributor.authorFrancois Nosten
dc.contributor.authorEric O Ohuma
dc.contributor.authorAlan Stein
dc.contributor.authorAnn Lambert
dc.contributor.authorAdele Winsey
dc.contributor.authorRicardo Uauy
dc.contributor.authorBrenda Eskenazi
dc.contributor.authorZulfiqar A Bhutta
dc.contributor.authorStephen H Kennedy
dc.date.accessioned2024-05-16T10:56:23Z
dc.date.available2024-05-16T10:56:23Z
dc.date.issued2022-08-20
dc.description.abstractBackground: 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.
dc.description.librarianPM2023
dc.facultyFaculty of Health Sciences
dc.identifier.urihttps://hdl.handle.net/10539/38485
dc.language.isoen
dc.schoolPublic Health
dc.titleAssociation between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study
dc.typeArticle
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