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

Ochieng, Roseline; Gunier, Robert B.; Papageorghiou, A.T.; McGready, Rose; Gauglitz, Julia M.; Barros, Fernando C.; Vatish, Manu; Fernandes, Michelle; Zammit, Victor A.; Carrara, Verena I.; Munim, Shama; Craik, Rachel; Barsosio, Hellen C.; Carvalho, Maria; Berkley, James A.; Ismail, Leila I Cheikh; Norris, Shane A; Tshivuila-Matala, Chrystelle O O; Nosten, F; Ohuma, Eric O; Stein, Alan; Lambert, Ann; Winsey, Adele; Uauy, Ricardo; Eskenazi, Brenda; Bhutta, Zulfiqar A; Kennedy, Stephen

doi:10.1016/s2213-8587(22)00215-7

Cited by 19 publications

(6 citation statements)

References 51 publications

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“…Plasma oxylipin profiling was conducted by Sapient Bioanalytics, using a rapid liquid chromatography-mass spectrometry (rLC-MS) methodology that has been described in detail previously 22 ( Supplementary Methods ). Oxylipins and fatty acids were annotated by aligning experimental accurate mass-to-charge ratio (m/z), retention time (RT) and MS2 spectra with an in-house curated library of commercial standards as well as alignment with previously reported structural isomers.…”

Section: Methodsmentioning

confidence: 99%

“…8 However, recent advancements in mass spectrometry-based metabolomics and annotation approaches have enabled the improved detection, quantification, and annotation of oxylipins. 20–22…”

Section: Introductionmentioning

confidence: 99%

“…8 However, recent advancements in mass spectrometry-based metabolomics and annotation approaches have enabled the improved detection, quantification, and annotation of oxylipins. [20][21][22] To address this research gap, we estimated the heritability and performed a genome-wide association study (GWAS) of n=81 oxylipins and related fatty acids quantified via directed, nontargeted liquid chromatography-mass spectrometry (LC-MS) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Moreover, motivated by the fact that central adiposity is associated with other markers of low-grade inflammation (e.g., C-reactive protein and interleukin-6) [23][24][25][26] and may influence oxylipin biosynthesis, 27 we also extended our models to include interactions with waist circumference and performed two-degree-of-freedom joint tests, increasing our power to identify additional loci that have both main and interaction effects.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Downie,

Highland,

Alotaibi

et al. 2024

Preprint

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Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years, standard deviation = 13.8 years). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Heritability estimates ranged from 0% to 47.9%, and 48 of the 81oxylipins and fatty acids were significantly heritable. Moreover, 40 (49.4%) of the 81 oxylipins and fatty acids had at least one genome-wide significant (p< 6.94E-11) variant resulting in 19 independent genetic loci involved in fatty acid and oxylipin synthesis, as well as downstream pathways. Four loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including the desaturase-encoding FADS and the OATP1B1 transporter protein-encoding SLCO1B1, exhibited associations with four or more fatty acids and oxylipins. The majority of the 15 remaining loci (87.5%) (lead variant MAF range = 0.03-0.45, mean = 0.23) were only associated with one oxylipin or fatty acid, demonstrating evidence of distinct genetic effects. Finally, while most loci identified in two-degree-of-freedom tests were previously identified in our main effects analyses, we also identified an additional rare variant (MAF = 0.002) near CARS2, a locus previously implicated in inflammation. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating future multi-omics work to characterize these compounds and elucidate their roles in disease pathways.

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Section: Methodsmentioning

confidence: 99%

“…8 However, recent advancements in mass spectrometry-based metabolomics and annotation approaches have enabled the improved detection, quantification, and annotation of oxylipins. 20–22…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Downie,

Highland,

Alotaibi

et al. 2024

Preprint

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“…In the present study, we will apply untargeted metabolomics approaches to analyze maternal and infant blood, as well as targeted and untargeted metabolomics approaches to analyze breast milk. The untargeted metabolomics analyses will be conducted via rapid liquid chromatography-mass spectrometry (rLC-MS), using a previously developed method [42] (Villar et al, 2022), and targeted metabolomics analyses will be conducted using LC-MS-MS and FIA-MS/MS [52] (Langsdorf et al, 2023).…”

Section: Metabolomicsmentioning

confidence: 99%

A Multi-Omics and Human Biomonitoring Approach to Assessing the Effectiveness of Fortified Balanced Energy–Protein Supplementation on Maternal and Newborn Health in Burkina Faso: A Study Protocol

Bastos-Moreira,

Ouédraogo,

De Boevre

et al. 2023

Nutrients

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Fortified balanced energy–protein (BEP) supplementation is a promising intervention for improving maternal health, birth outcomes and infant growth in low- and middle-income countries. This nested biospecimen sub-study aimed to evaluate the physiological effect of multi-micronutrient-fortified BEP supplementation on pregnant and lactating women and their infants. Pregnant women (15–40 years) received either fortified BEP and iron–folic acid (IFA) (intervention) or IFA only (control) throughout pregnancy. The same women were concurrently randomized to receive either a fortified BEP supplement during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention) or the postnatal standard of care, which comprised IFA alone for 6 weeks postpartum (i.e., control). Biological specimens were collected at different timepoints. Multi-omics profiles will be characterized to assess the mediating effect of BEP supplementation on the different trial arms and its effect on maternal health, as well as birth and infant growth outcomes. The mediating effect of the exposome in the relationship between BEP supplementation and maternal health, birth outcomes and infant growth were characterized via biomonitoring markers of air pollution, mycotoxins and environmental contaminants. The results will provide holistic insight into the granular physiological effects of prenatal and postnatal BEP supplementation.

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“…The disruptions of these mechanisms may critically affect normal fetal growth and development. Metabolites transmitted from the maternal body to the embryonal/fetal body through the placenta can be both crucial regulators and critical insults (Bowman et al, 2021; Villar et al, 2022; Gleason et al, 2023). The fetal livers are not fully matured, requiring the maternal body to compensate for essential metabolic activity during the pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Maternal sterol 27-hydroxylase is crucial for securing fetal development

Suzuki,

Nakano,

Miharada

et al. 2023

Preprint

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SummaryThe maternal body helps in providing nutrients and degrading toxic metabolites instead of the fetal body; disruptions in these mechanisms affect normal fetal development. Sterol 27-hydroxylase (Cyp27a1) is involved in the alternative pathway of bile acid synthesis, which is enhanced during pregnancy. However, its role in fetal development remains unclear. Here, we demonstrate that maternal Cyp27a1 activity is essential for progression of normal pregnancy and fetal organ formation. Depletion of maternalCyp27a1reduced the pregnancy rate and litter size. Newborn mice died of respiratory distress syndrome resulting from the absence of mature alveolar epithelial cells. These phenotypes were caused by 7α-hydroxycholesterol (7α-HC) accumulating inCyp27a1-deficient mice. Mechanistically, 7α-HC destabilized the Fau protein, mediating ribosome assembly, the downregulation of which caused poor polysome formation, lower protein synthesis, and impaired lung maturation. Overall, this study revealed an essential mechanism of securing fetal development by degrading a toxic metabolite in the maternal body.

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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

Cited by 19 publications

References 51 publications

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

A Multi-Omics and Human Biomonitoring Approach to Assessing the Effectiveness of Fortified Balanced Energy–Protein Supplementation on Maternal and Newborn Health in Burkina Faso: A Study Protocol

Maternal sterol 27-hydroxylase is crucial for securing fetal development

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