Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network

Harrison, Margo S.; Thorsten, Vanessa; Dudley, Donald J.; Parker, Corette B.; Koch, Matthew; Hogue, Carol J.; Stoll, Barbara J.; Silver, Robert M.; Varner, Michael W.; Pinar, M. Halit; Coustan, Donald R.; Saade, George R.; Bukowski, Radek; Conway, Deborah L.; Willinger, Marian; Reddy, Uma M.; Goldenberg, Robert L.

doi:10.1055/s-0038-1639340

Cited by 15 publications

(13 citation statements)

References 18 publications

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“…A previous study has showed that chorioamnionitis accounts for approximately 10% of the effect of obesity on the risk of stillbirth [15]. Our study showed that inflammation tended to be a mediator on the pathway from BMI to stillbirth.…”

Section: Plos Onesupporting

confidence: 64%

“…Both human and experimental studies support that fetal hyperglycemia and hyperinsulinemia are independent risk factors for fetal hypoxia [ 13 ]. Furthermore, the incidence of cord complications and chorioamnionitis is increased in obese women [ 14 , 15 ], which may jeopardize fetal health. However, research on potential causes of the increased risk of stillbirth in obese women is scarce.…”

Section: Introductionmentioning

confidence: 99%

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Maternal obesity and stillbirth at term; placental pathology—A case control study

et al. 2021

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Objective The aim was to explore the potential role of the placenta for the risk of stillbirth at term in pregnancies of obese women. Methods This was a case-control study comparing placental findings from term stillbirths with placental findings from live born infants. Cases were singleton term stillbirths to normal weight or obese women, identified in the Stockholm stillbirth database, n = 264 and n = 87, respectively. Controls were term singletons born alive to normal weight or obese women, delivered between 2002–2005 and between 2018–2019. Placentas were compared between women with stillborn and live-born infants, using logistic regression analyses. Results A long and hyper coiled cord, cord thrombosis and velamentous cord insertion were stronger risk factors for stillbirth in obese women compared to normal weight women. When these variables were adjusted for in the logistic regression analysis, also adjusted for potential confounders, the odds ratio for stillbirth in obese women decreased from 1.89 (CI 1.24–2.89) to 1.63 (CI 1.04–2.56). Conclusion Approximately one fourth of the effect of obesity on the risk of stillbirth in term pregnancies is explained by umbilical cord associated pathology.

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Section: Plos Onesupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Maternal obesity and stillbirth at term; placental pathology—A case control study

et al. 2021

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“…The reasons behind the increased risk of stillbirth in women with overweight or obesity are not fully understood, however there are probably several different contributing reasons [ 6 ]. There is an association between BMI and stillbirth caused by placental disease, maternal hypertension, umbilical cord complications and antepartum infections [ 5 , 6 , 8 ]. An altered metabolism with potentially elevated risk of fetal hypoxia may contribute, as well as an inflammatory process [ 5 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…There is an association between BMI and stillbirth caused by placental disease, maternal hypertension, umbilical cord complications and antepartum infections [ 5 , 6 , 8 ]. An altered metabolism with potentially elevated risk of fetal hypoxia may contribute, as well as an inflammatory process [ 5 , 9 ]. The adipose tissue is an endocrine organ with production of pro-inflammatory cytokines [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is shown that obese pregnant women have an enhanced inflammatory state which seems to affect the placental inflammatory state [ 11 ]. There is research indicating placental pathology as mediating part of the effect of BMI on stillbirth [ 5 , 8 ]. The reasons behind the elevated risk of stillbirth with increasing BMI are complex due to different mechanisms, however they may be complex also due to different BMI phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002–2018; a case control study

2023

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Introduction Stillbirth is a severe pregnancy complication. Maternal obesity is one of the most important modifiable risk factors of stillbirth, yet the biological mechanisms behind this association remain unclear. The adipose tissue is an endocrine organ which, in persons with obesity, causes a hyperinflammatory state. The aim of this study was to investigate inflammation as a contributing mechanism to the risk of stillbirth in women with obesity and if there are possible signs of different BMI phenotypes with different risk. Material and methods This was a case control study based on all cases of term singleton stillbirth without major fetal malformation in Stockholm County between 2002–2018. Placentas have been examined according to a standardized protocol. Placental inflammatory lesions were compared both between placentas from pregnancies with live born and stillborn infants with different class of body mass index (BMI) as well as among women with stillborn and live born infants with different classes of BMI, respectively. Results All inflammatory placental lesions were more common in placentas from women with stillbirth compared to placentas from women with live born infants. Vasculitis, funisitis and chronic villitis as well as overall fetal and maternal inflammatory response were present with a significantly increased proportion with increasing BMI in placentas from women with term stillbirth however, there were no differences between placentas from women in different BMI classes with term live born infants. Conclusion Both acute and chronic inflammatory placental lesions were more common in cases of stillbirth compared to pregnancies with live born infants. There were increased proportions of both acute and chronic placental inflammation (vasculitis, chronic villitis, funisitis and overall fetal and maternal inflammatory response) with increasing BMI among cases with term stillbirth, however no differences among controls with term live born infants.

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Periconceptional biomarkers for maternal obesity: a systematic review

Hojeij

Rousian

Sinclair

et al. 2022

Rev Endocr Metab Disord

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Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31st, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.

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Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network

Cited by 15 publications

References 18 publications

Maternal obesity and stillbirth at term; placental pathology—A case control study

Maternal obesity and stillbirth at term; placental pathology—A case control study

Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002–2018; a case control study

Periconceptional biomarkers for maternal obesity: a systematic review

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