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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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(2022) 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 & Endocrinology, 10 (10). pp. 710-719. doi:10.1016/S2213-8587(22)00215-7 ISSN 2213-8587.
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WRAP-Association-between-fetal-abdominal-growth-trajectories-maternal-metabolite-signatures-early-in-pregnancy-and-childhood-growth-and-adiposity-Zammit-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2048Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/S2213-8587(22)00215-7
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.
| Item Type: | Journal Article | ||||||||
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| Subjects: | R Medicine > RJ Pediatrics | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Obesity in children, Obesity in children -- Prevention , Fetus -- Abnormalities, Pregnancy -- Complications, Newborn infants -- Growth | ||||||||
| Journal or Publication Title: | The Lancet Diabetes & Endocrinology | ||||||||
| Publisher: | The Lancet Publishing Group | ||||||||
| ISSN: | 2213-8587 | ||||||||
| Official Date: | 1 October 2022 | ||||||||
| Dates: |
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| Volume: | 10 | ||||||||
| Number: | 10 | ||||||||
| Page Range: | pp. 710-719 | ||||||||
| DOI: | 10.1016/S2213-8587(22)00215-7 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 13 September 2022 | ||||||||
| Date of first compliant Open Access: | 14 September 2022 | ||||||||
| RIOXX Funder/Project Grant: |
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