Objective. The purpose of this study was to explore individuals’ beliefs, values, and experiences surrounding stillbirth evaluation decisions. Design. Qualitative research Setting. University of Utah Health Population. Parents who experienced a stillbirth in the past 5 years (n=19) were interviewed about their experiences and decision to consent or decline postmortem evaluations Methods. Qualitative content analysis Main outcome measures. Barriers and facilitators to parents’stillbirth postmortem decision-making. Results. Participants communicated several facilitators and barriers that contributed to their stillbirth evaluation decision. Reasons for consenting to evaluations were belief in science, background in medicine, altruism, to inform future pregnancies, thinking about preventing another stillbirth, and how patients viewed the care of their stillborn by the medical team. Reasons for declining evaluations were receiving a diagnosis prior to being offered a postmortem evaluation, intent to avoid causing further harm to the baby, interest to spend more time with their baby, and cost of the evaluation. Conclusion. Participants identified stillbirth as one of their most difficult experiences as a parent. Diagnostic and emotional barriers create further challenges to decision-making for stillbirth postmortem evaluations. Parents often rely on inadequate information and personal values and beliefs during this time-sensitive decision process. Decision support for stillbirth evaluations and training for medical providers could benefit parents, may increase stillbirth evaluation uptake, and potentially prevent decisional regret.

Objective To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 384 stillbirth cases of the SCRN study (2006-2008). Methods FSMs were grouped by anatomic system and specific malformation type (e.g., central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500kb. CNVs were classified into two groups: normal, defined as no CNVs>500kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-squared test. Results The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs compared with those with normal CNVs (46.7% vs. 19.6%; p-value<0.001). The most common organ system-specific FSMs associated with abnormal CNVs were cardiac defects, followed by craniofacial and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g., CHD1L) and a duplication of 21q22.13 involving 4 genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively. Conclusion Specific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counseling and care surrounding pregnancies affected by FSMs at risk for stillbirth.

Objective To determine if stillbirth aggregates in families and quantify its familial risk using extended pedigrees. Design State-wide matched case-control study. Setting Utah, United States. Population Stillbirth cases (n=9 404) and live-birth controls (18 808) between 1978 and 2019. Methods Using the Utah Population Database, a population‐based genealogical resource linked with state fetal death and birth records, we identified high-risk pedigrees with excess familial aggregation of stillbirth using the Familial Standardized Incidence Ratio (FSIR). Stillbirth odds ratio (OR) for first-degree relatives (FDR), second-degree relatives (SDR), and third-degree relatives (TDR) of parents with a stillbirth and live-birth were estimated using logistic regression models. Results We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR≥2.00 and P-value<0.05). FDRs, SDRs and TDRs of affected parents had 1.14-fold (95% confidence interval [CI]: 1.04-1.26), 1.22-fold (95% CI: 1.11-1.33), and 1.15-fold (95% CI: 1.08-1.21) higher stillbirth odds compared to FDRs, SDRs and TDRs of unaffected parents, respectively. Parental sex-specific analyses showed male FDRs, SDRs and TDRs of affected fathers had 1.22-fold (95% CI: 1.02-1.47), 1.38-fold (95% CI: 1.17-1.62), 1.17-fold (95% CI: 1.05-1.30) higher stillbirth odds compared to those of unaffected fathers, respectively. FDRs, SDRs and TDRs of affected mothers had 1.12-fold (95% CI: 0.98-1.28), 1.09-fold (95% CI: 0.96-1.24), and 1.15-fold (95% CI: 1.06-1.24) higher stillbirth odds compared with those of unaffected mothers, respectively. Conclusions We provide evidence for familial aggregation of stillbirth. Our findings warrant investigation into genes associated with stillbirth and underscore the need to design large-scale studies to determine its genetic architecture.

Objective To examine the association of DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 387 stillbirth cases (2006-2008). Methods Using standard definitions, PPLs were categorized by type including maternal and fetal vascular, inflammatory and immune/idiopathic lesions. Using single-nucleotide polymorphism array, CNVs of at least 500 kb were detected. CNVs were classified into two groups: normal, defined as no CNVs>500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without PPLs using the Wald Chi-squared test. Results Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs compared with those with normal CNVs (81.7% vs. 64.2%; p=0.008). The proportions of fetal vascular, maternal/fetal inflammatory, and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs compared to those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several genes with known relevant mechanisms. Conclusions Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillborn fetuses. Findings may provide insight on the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.

Mini-commentary on BJOG-20-0453.R1: Can risk prediction models help us individualise stillbirth prevention? A systematic review and critical appraisal of published risk models