Dataset Information

Metabolomic Pathways Predicting Labor Dystocia by Maternal Body Mass Index.

ABSTRACT: Objectives ?The purpose of this study was to evaluate the metabolic pathways activated in the serum of African-American women during late pregnancy that predicted term labor dystocia. Study Design ?Matched case-control study ( n ?=?97; 48 cases of term labor dystocia and 49 normal labor progression controls) with selection based on body mass index (BMI) at hospital admission and maternal age. Late pregnancy serum samples were analyzed using ultra-high-resolution metabolomics. Differentially expressed metabolic features and pathways between cases experiencing term labor dystocia and normal labor controls were evaluated in the total sample, among women who were obese at the time of labor (BMI???30?kg/m2), and among women who were not obese. Results ?Labor dystocia was predicted by different metabolic pathways in late pregnancy serum among obese (androgen/estrogen biosynthesis) versus nonobese African-American women (fatty acid activation, steroid hormone biosynthesis, bile acid biosynthesis, glycosphingolipid metabolism). After adjusting for maternal BMI and age in the total sample, labor dystocia was predicted by tryptophan metabolic pathways in addition to C21 steroid hormone, glycosphingolipid, and androgen/estrogen metabolism. Conclusion ?Metabolic pathways consistent with lipotoxicity, steroid hormone production, and tryptophan metabolism in late pregnancy serum were significantly associated with term labor dystocia in African-American women.

SUBMITTER: Carlson NS

PROVIDER: S-EPMC7056397 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Metabolomic Pathways Predicting Labor Dystocia by Maternal Body Mass Index.

Carlson Nicole S NS Frediani Jennifer K JK Corwin Elizabeth J EJ Dunlop Anne A Jones Dean D

AJP reports 20200101 1

Objectives The purpose of this study was to evaluate the metabolic pathways activated in the serum of African-American women during late pregnancy that predicted term labor dystocia. Study Design Matched case-control study ( n = 97; 48 cases of term labor dystocia and 49 normal labor progression controls) with selection based on body mass index (BMI) at hospital admission and maternal age. Late pregnancy serum samples were analyzed using ultra-high-resolution metabolomics ...[more]

PMID: 32140295

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Project description:Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4-12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7-65.6%, and hence the predictive significance of the model, and mediated 60.8-75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

Project description:ImportanceAlthough high body mass index (BMI) is associated with adverse birth outcomes, the association with severe maternal morbidity is unclear.ObjectiveTo examine the association between prepregnancy BMI and severe maternal morbidity.Design, setting, and participantsRetrospective population-based cohort study including all singleton hospital births in Washington State, 2004-2013. Demographic data and morbidity diagnoses were obtained from linked birth certificates and hospitalization files.ExposuresPrepregnancy BMI (weight in kilograms divided by height in meters squared) categories included underweight (<18.5), normal BMI (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40).Main outcomes and measuresComposite severe maternal morbidity or mortality included life-threatening conditions and conditions leading to serious sequelae (eg, amniotic fluid embolism, hysterectomy), complications requiring intensive care unit admission, and maternal death. Logistic regression was used to obtain adjusted odds ratios (ORs) and adjusted rate differences with 95% confidence intervals, adjusted for confounders (eg, maternal age and parity).ResultsOverall, 743 630 women were included in the study (mean age, 28.1 [SD, 6.0] years; 41.4% nulliparous). Prepregnancy BMI was distributed as follows: underweight, 3.2%; normal weight, 47.5%; overweight, 25.8%; obesity class 1, 13.1%; obesity class 2, 6.2%; and obesity class 3, 4.2%. Rates of severe maternal morbidity or mortality were 171.5, 143.2, 160.4, 167.9, 178.3 and 202.9 per 10 000 women, respectively. Adjusted ORs were 1.2 (95% CI, 1.0-1.3) for underweight women; 1.1 (95% CI, 1.1-1.2) for overweight women; 1.1 (95% CI, 1.1-1.2) for women with class 1 obesity; 1.2 (95% CI, 1.1-1.3) for women with class 2 obesity; and 1.4 (95% CI, 1.3-1.5) for women with class 3 obesity compared with women with normal BMI. Absolute risk increases (adjusted rate differences per 10 000 women, compared with women with normal BMI) were 28.8 (95% CI, 12.2-47.2) for underweight women, 17.6 (95% CI, 10.5-25.1) for overweight women, 24.9 (95% CI, 15.7-34.6) for women with class 1 obesity, 35.8 (95% CI, 23.1-49.5) for women with class 2 obesity, and 61.1 (95% CI, 44.8-78.9) for women with class 3 obesity.Conclusions and relevanceAmong pregnant women in Washington State, low and high prepregnancy BMI, compared with normal BMI, were associated with a statistically significant but small absolute increase in severe maternal morbidity or mortality.

Dataset Information

Metabolomic Pathways Predicting Labor Dystocia by Maternal Body Mass Index.

Publications

Metabolomic Pathways Predicting Labor Dystocia by Maternal Body Mass Index.

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