Cargando…

Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study

BACKGROUND: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quanti...

Descripción completa

Detalles Bibliográficos
Autores principales: Welch, Barrett M., Keil, Alexander P., van ‘t Erve, Thomas J., Deterding, Leesa J., Williams, Jason G., Lih, Fred B., Cantonwine, David E., McElrath, Thomas F., Ferguson, Kelly K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428021/
https://www.ncbi.nlm.nih.gov/pubmed/32797061
http://dx.doi.org/10.1371/journal.pmed.1003271
_version_ 1783570997916467200
author Welch, Barrett M.
Keil, Alexander P.
van ‘t Erve, Thomas J.
Deterding, Leesa J.
Williams, Jason G.
Lih, Fred B.
Cantonwine, David E.
McElrath, Thomas F.
Ferguson, Kelly K.
author_facet Welch, Barrett M.
Keil, Alexander P.
van ‘t Erve, Thomas J.
Deterding, Leesa J.
Williams, Jason G.
Lih, Fred B.
Cantonwine, David E.
McElrath, Thomas F.
Ferguson, Kelly K.
author_sort Welch, Barrett M.
collection PubMed
description BACKGROUND: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery. METHODS AND FINDINGS: Our data come from a case–control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women’s Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m(2)). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%–97% higher among SGA cases and 33%–39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth. CONCLUSIONS: In this nested case–control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes.
format Online
Article
Text
id pubmed-7428021
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-74280212020-08-20 Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study Welch, Barrett M. Keil, Alexander P. van ‘t Erve, Thomas J. Deterding, Leesa J. Williams, Jason G. Lih, Fred B. Cantonwine, David E. McElrath, Thomas F. Ferguson, Kelly K. PLoS Med Research Article BACKGROUND: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery. METHODS AND FINDINGS: Our data come from a case–control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women’s Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m(2)). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%–97% higher among SGA cases and 33%–39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth. CONCLUSIONS: In this nested case–control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes. Public Library of Science 2020-08-14 /pmc/articles/PMC7428021/ /pubmed/32797061 http://dx.doi.org/10.1371/journal.pmed.1003271 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Welch, Barrett M.
Keil, Alexander P.
van ‘t Erve, Thomas J.
Deterding, Leesa J.
Williams, Jason G.
Lih, Fred B.
Cantonwine, David E.
McElrath, Thomas F.
Ferguson, Kelly K.
Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title_full Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title_fullStr Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title_full_unstemmed Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title_short Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study
title_sort longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: a nested case-control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428021/
https://www.ncbi.nlm.nih.gov/pubmed/32797061
http://dx.doi.org/10.1371/journal.pmed.1003271
work_keys_str_mv AT welchbarrettm longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT keilalexanderp longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT vantervethomasj longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT deterdingleesaj longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT williamsjasong longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT lihfredb longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT cantonwinedavide longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT mcelraththomasf longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy
AT fergusonkellyk longitudinalprofilesofplasmaeicosanoidsduringpregnancyandsizeforgestationalageatdeliveryanestedcasecontrolstudy