Unexplained stillbirth: can risk factors be identified?

Unexplained stillbirth: can risk factors be identified?

Jessica Page, MD (1,2); Michelle Debbink, MD, PhD (1,2); Karen Gibbins, MD, MSCI (3), Michael Varner, MD (1,2), Robert Silver, MD (1,2)

(1) University of Utah Health, Salt Lake City, UT, USA; (2) Intermountain Healthcare, Salt Lake City, UT, USA; (3) Oregon Health and Science University, Portland, OR, USA

Stillbirth (SB) that remains unexplained despite investigation is a challenging target for prevention. Thus, we sought to identify characteristics and risk factors for unexplained SB.

Study Design
Secondary analysis of a large, multi-center case-control study of SB and representative live births (LB). After excluding fetal anomalies and multiple gestations, we included 411 SB cases with complete evaluation including fetal autopsy, placental pathology and standardized history and laboratory evaluation, as well as 1953 LB. Each SB was assessed using the Initial Causes of Fetal Death (INCODE) classification system. SBs with no probable or possible cause of death (unexplained) were compared to SBs with a possible or probable cause of death identified (explained), as well as to LB using univariable and multivariable regression. Weighting was used to account for over sampling of preterm births and non-Hispanic blacks in the LB population.

Of the 411 SB included, 109 (26.5%) had no probable or possible cause of death and comprised the unexplained group. Unexplained SB were evenly distributed across gestational age groups from 20 through 42 weeks with 16-22% of the population in each group, while explained SBs were skewed toward the 20-23 week gestational age group (35%; p = 0.02). In multivariable analysis, compared to patients with LB, those with an unexplained SB were more likely to be younger and have a low BMI (<18.5). There were no differences in traditional risk factors for SB between unexplained SB and LB (Table 1). In multivariable analysis, women with unexplained SB were younger and less likely to be non-Hispanic black compared to those with explained SB (Table 2).

Women with unexplained SB had similar characteristics to those with LB and had few of the common risk factors for stillbirth overall. Prevention strategies should target the general population since traditional risk factors do not identify most cases of unexplained SB.

Ethics statement
All participants gave written informed consent as part of the original study and the study was approved by the institutional review boards of each clinical site and the data coordinating and analysis center.

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