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/m2) 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 × 103 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
stillbirth - obesity - body mass index - inflammation - biomarkers
