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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m 2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 +). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 10 3 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalAmerican Journal of Perinatology
Volume35
Issue number11
DOIs
StatePublished - Apr 2 2018

Fingerprint

Stillbirth
Obesity
Research
Chorioamnionitis
Ferritins
Body Mass Index
Live Birth
Leukocyte Count
Logistic Models
Serum
C-Reactive Protein
Mothers
Confidence Intervals
Term Birth
Inflammation
Weights and Measures

Keywords

  • biomarkers
  • body mass index
  • inflammation
  • obesity
  • stillbirth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Harrison, M. S., Thorsten, V. R., Dudley, D. J., Parker, C. B., Koch, M. A., Hogue, C. J. R., ... Goldenberg, R. L. (2018). Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network. American Journal of Perinatology, 35(11), 1071-1078. https://doi.org/10.1055/s-0038-1639340

Stillbirth, Inflammatory Markers, and Obesity : Results from the Stillbirth Collaborative Research Network. / Harrison, Margo S.; Thorsten, Vanessa R.; Dudley, Donald J.; Parker, Corette B.; Koch, Matthew A.; Hogue, Carol J.R.; Stoll, Barbara J.; Silver, Robert M.; Varner, Michael W.; Pinar, M. Halit; Coustan, Donald R.; Saade, George; Bukowski, Radek K.; Conway, Deborah L.; Willinger, Marian; Reddy, Uma M.; Goldenberg, Robert L.

In: American Journal of Perinatology, Vol. 35, No. 11, 02.04.2018, p. 1071-1078.

Research output: Contribution to journalArticle

Harrison, MS, Thorsten, VR, Dudley, DJ, Parker, CB, Koch, MA, Hogue, CJR, Stoll, BJ, Silver, RM, Varner, MW, Pinar, MH, Coustan, DR, Saade, G, Bukowski, RK, Conway, DL, Willinger, M, Reddy, UM & Goldenberg, RL 2018, 'Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network', American Journal of Perinatology, vol. 35, no. 11, pp. 1071-1078. https://doi.org/10.1055/s-0038-1639340
Harrison, Margo S. ; Thorsten, Vanessa R. ; Dudley, Donald J. ; Parker, Corette B. ; Koch, Matthew A. ; Hogue, Carol J.R. ; Stoll, Barbara J. ; Silver, Robert M. ; Varner, Michael W. ; Pinar, M. Halit ; Coustan, Donald R. ; Saade, George ; Bukowski, Radek K. ; Conway, Deborah L. ; Willinger, Marian ; Reddy, Uma M. ; Goldenberg, Robert L. / Stillbirth, Inflammatory Markers, and Obesity : Results from the Stillbirth Collaborative Research Network. In: American Journal of Perinatology. 2018 ; Vol. 35, No. 11. pp. 1071-1078.
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abstract = "Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m 2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 +). Overweight (COR, 1.48; 95{\%} confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95{\%} CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 10 3 or greater) was associated with stillbirth (21.2{\%} SB vs. 10.0{\%} live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2{\%} vs. 15.7{\%}, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10{\%} when adjusting for histologic chorioamnionitis (AOR, 1.38; 95{\%} CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.",
keywords = "biomarkers, body mass index, inflammation, obesity, stillbirth",
author = "Harrison, {Margo S.} and Thorsten, {Vanessa R.} and Dudley, {Donald J.} and Parker, {Corette B.} and Koch, {Matthew A.} and Hogue, {Carol J.R.} and Stoll, {Barbara J.} and Silver, {Robert M.} and Varner, {Michael W.} and Pinar, {M. Halit} and Coustan, {Donald R.} and George Saade and Bukowski, {Radek K.} and Conway, {Deborah L.} and Marian Willinger and Reddy, {Uma M.} and Goldenberg, {Robert L.}",
year = "2018",
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language = "English (US)",
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pages = "1071--1078",
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TY - JOUR

T1 - Stillbirth, Inflammatory Markers, and Obesity

T2 - Results from the Stillbirth Collaborative Research Network

AU - Harrison, Margo S.

AU - Thorsten, Vanessa R.

AU - Dudley, Donald J.

AU - Parker, Corette B.

AU - Koch, Matthew A.

AU - Hogue, Carol J.R.

AU - Stoll, Barbara J.

AU - Silver, Robert M.

AU - Varner, Michael W.

AU - Pinar, M. Halit

AU - Coustan, Donald R.

AU - Saade, George

AU - Bukowski, Radek K.

AU - Conway, Deborah L.

AU - Willinger, Marian

AU - Reddy, Uma M.

AU - Goldenberg, Robert L.

PY - 2018/4/2

Y1 - 2018/4/2

N2 - Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m 2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 +). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 10 3 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

AB - Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m 2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 +). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 10 3 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

KW - biomarkers

KW - body mass index

KW - inflammation

KW - obesity

KW - stillbirth

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