Maternal obesity impacts fetal neuroinflammation in a murine model of preterm birth

Abstract Background Preterm (< 37 weeks gestation) and post–term birth (≥42 weeks gestation) are associated with increased morbidity and mortality for mother and infant. Obesity (body mass index (BMI) ≥30 kg/m2) is increasing in women of reproductive age. Maternal obesity has been associated with adverse pregnancy outcomes including preterm and post–term birth. However, the effect sizes vary according to the subgroups of both maternal BMI and gestational age considered. The aim of this retrospective analysis was to determine the association between maternal obesity classes and gestational age at delivery. Methods A secondary data analysis of 13 maternity units in England with information on 479,864 singleton live births between 1990 and 2007. BMI categories were: underweight (< 18.5 kg/m2), recommended weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity classes I (30.0–34.9 kg/m2), II (35.0–39.9 kg/m2), IIIa (40–49.9 kg/m2) and IIIb (≥50 kg/m2). Gestational age at delivery categories were: Gestational age at delivery (weeks): extreme preterm (20–27), very preterm (28–31), moderately preterm (32–36), early term (37, 38), full term (39–40), late term (41) and post–term (≥42). The adjusted odds of births in each gestational age category (compared to full-term birth), according to maternal BMI categories were estimated using multinomial logistic regression. Missing data were estimated using multiple imputation with chained equations. Results There was a J-shaped association between the absolute risk of extreme, very and moderate preterm birth and BMI category, with the greatest effect size for extreme preterm. The absolute risk of post-term birth increased monotonically as BMI category increased. The largest effect sizes were observed for class IIIb obesity and extreme preterm birth (adjusted OR 2.80, 95% CI 1.31–5.98). Conclusion Women with class IIIb obesity have the greatest risks for inadequate gestational age. Combining obesity classes does not accurately represent risks for many women as it overestimates the risk of all preterm and post-term categories for women with class I obesity, and underestimates the risk for women in all other obesity classes.

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The causal influence of maternal obesity on preterm birth

The Lancet Diabetes & Endocrinology ◽

10.1016/s2213-8587(19)30406-1 ◽

2020 ◽

Vol 8 (2) ◽

pp. 101-103 ◽

Cited By ~ 1

Author(s):

Christoph F Kurz ◽

Adriana N König

Keyword(s):

Preterm Birth ◽

Maternal Obesity ◽

Causal Influence

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Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.64.03.264 ◽

2018 ◽

Vol 64 (3) ◽

pp. 264-271

Author(s):

Iramar Baptistella do Nascimento ◽

Guilherme Dienstmann ◽

Matheus Leite Ramos de Souza ◽

Thiago Ribeiro e Silva ◽

Raquel Fleig ◽

...

Keyword(s):

Preterm Birth ◽

Maternal Obesity ◽

Placental Transfer ◽

Cochrane Library ◽

First Year ◽

Premature Births ◽

Lipid Transfer ◽

High Lipid ◽

Obesity In Pregnancy ◽

First Year Of Life

Summary Objective: To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn. Method: Systematic review based on the Medline, Lilacs, Embase and Cochrane library databases between 1996 and 2016. The search for studies included the following keywords: “dyslipidemia, pregnancy, obesity, preterm birth.” A protocol was programmed and a protocol for inclusion/exclusion of studies was implemented. Results: Of the 5,789 articles initially selected between March 1996 and July 2016, only 32 were in accordance with the established criteria. Of these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer. Conclusion: There is a reduced adaptation of obese pregnant women to the metabolic changes of gestation. This favors dyslipidemic intercurrences in the mother, which, directly or indirectly, suggests the occurrence of premature births and high lipid transfer to the fetus. Therefore, preterm newborns, whose mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat, both in early (first year of life) and in later (adult) phases of life.

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The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor

Cell Death and Disease ◽

10.1038/s41419-019-2196-7 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Sarah M. Estrada ◽

Andrew S. Thagard ◽

Mary J. Dehart ◽

Jennifer R. Damicis ◽

Elisabeth M. Dornisch ◽

...

Keyword(s):

Preterm Birth ◽

Brain Injury ◽

Murine Model ◽

Inflammatory Factors ◽

Orphan Nuclear Receptor ◽

Perinatal Brain Injury ◽

Reporter Mice ◽

Injury Screening ◽

Genetic Modulators

AbstractPrematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO4) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO4/BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO4/BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO4/BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.

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Association among Maternal Obesity, Cervical Length, and Preterm Birth

American Journal of Perinatology ◽

10.1055/s-0036-1593350 ◽

2016 ◽

Vol 34 (05) ◽

pp. 471-479 ◽

Cited By ~ 4

Author(s):

Emily Miller ◽

Moeun Son ◽

Michelle Kominiarek ◽

Anna Palatnik

Keyword(s):

Preterm Birth ◽

Maternal Obesity ◽

Cervical Length

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