Causes of Death Among Stillbirths

Supplementary Online Content

Stillbirth Collaborative Research Network Writing Group. Causes of death among stillbirths. JAMA. 2011;306(22):2459-2468.

eTable 1. Possible/Probable Causes Within Broad Groups

eTable 2. Probable and Possible Causes of Death1 Stratified by Race/Ethnicity2 Showing P Values Accounting for Dependencies in the Data for 12 Sets of Twin Stillbirths3

This supplementary material has been provided by the authors to give readers additional information about their work.

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eTable 1. Possible/Probable Causes Within Broad Groups

Among 512 SBs Findings n % Placental disease (n=121) Circulation - fetal - Thromboembolism 42 8.2 Circulation - maternal, vascular - Villous (parenchymal) infarcts 31 6.1 Uteroplacental insufficiency 24 4.7 Placental Disc - abnormal villous parenchyma - delayed maturation 12 2.3 Circulation - maternal nonvascular - Massive perivillous parcenchymal fibrin 11 2.1 deposition Placental Disc - abnormal villous parenchyma - accelerated maturation 9 1.8 Circulation - maternal nonvascular - Maternal floor fibrin deposition 9 1.8 Circulation - maternal, vascular - Massive subchorionic hematoma 8 1.6 Circulation - maternal, vascular - Intraplacental thrombi (hematoma) 5 1 Other placental abnormalities 1 0.2 Placental Disc - implantation site abnormality - Placenta previa 0 0 Placental Disc - implantation site abnormality - Placenta percreta, increta, accreta 0 0 Placental Disc - abnormal villous parenchyma - partial mole 0 0 Placental membranes - Circumvallate insertion 0 0 Circulation - maternal, vascular - Decidual vasculopathy 0 0 Circulation - maternal, vascular - Subamnionic hemorrhage 0 0 Circulation - maternal nonvascular - Minor perivillous parenchymal fibrin deposition 0 0 Infection (n=66) Fetal infection involving vital organs 43 8.4 Fetal membranes and placental inflammatory disorders 21 4.1 Fetal infection causing congenital anomaly or other fetal condition 6 1.2 Placental infection likely leading to decreased placental function 5 1 Severe maternal infection 2 0.4 Infection-related fetal death by other or unknown mechanisms 2 0.4

Downloaded From: https://jamanetwork.com/ on 09/23/2021 Among 512 SBs Findings n % Fetal genetic/structural (n=70) Chromosomal – Aneuploidy 25 4.9 Other chromosomal, genetic or structural abnormalities 15 2.9 Structural without chromosomal - Non-immune hydrops 12 2.3 Structural without chromosomal - Cardiac anomaly with hydrops 5 1 Structural without chromosomal - Urogenital anomaly with anhydramnios 4 0.8 Chromosomal - Confined placental mosiacism with small for gestational age 3 0.6 Structural without chromosomal - Neural tube defects, brain stem comp 3 0.6 Chromosomal - Unbalanced translocation, deletions 2 0.4 Structural without chromosomal - Abdominal wall defects 2 0.4 Structural without chromosomal - Intrathoracic anomaly with hydrops 1 0.2 Structural without chromosomal - Fetal or placental tumors with hydrops 1 0.2 Structural without chromosomal - Other neurologic abnormalities 1 0.2 Structural without chromosomal - Fetal lung abnormalities 1 0.2 Structural without chromosomal - Other not otherwise specified 1 0.2 Fetal metabolic disorders 1 0.2 Autosomal recessive - Alpha thalassemia with hydrops 0 0 Autosomal recessive - Storage disease with hydrops 0 0 Autosomal recessive - Amino acid disorders 0 0 Autosomal recessive - Peroxisomal disorders 0 0 X-linked dominant disorders in males 0 0 Structural without chromosomal - Pentalogy of Cantrell/ectopia cordis 0 0 Structural without chromosomal - Cardiac anomaly with no hydrops 0 0 Structural without chromosomal - Lethal type skeletal dysplasia 0 0 Structural without chromosomal - Neural tube defects, no brain stem comp 0 0 Structural without chromosomal - Endocrine gland 0 0 agenesis/hypoplasia/dysfunction Structural without chromosomal - Neuromuscular disorders 0 0 Medical complications (n=40) Diabetes during pregnancy 21 4.1 Antiphospholipid syndrome 10 2 Maternal substance abuse 5 1 Intrahepatic cholestasis of pregnancy 2 0.4 Heritable thrombophilias 2 0.4 Thyroid disorders during pregnancy 1 0.2 Systemic lupus erythematosus 0 0 Renal disease during pregnancy 0 0 Shock during pregnancy 0 0 Asthma during Pregnancy 0 0 Seizure disorders during pregnancy 0 0 Other maternal medical condition 0 0 Hypertensive disorder (n=47) Hypertensive disorder of pregnancy 47 9.2 Cord abnormalities (n=53) Umbilical Cord - entrapment 27 5.3 Umbilical Cord - knots, torsions, strictures 23 4.5 Umbilical Cord - prolapse 5 1 Umbilical Cord - vasa previa 0 0

Downloaded From: https://jamanetwork.com/ on 09/23/2021 Among 512 SBs Findings n % Obstetric complications (n=150) Intrapartum fetal death with labor <=26 wks 78 15.2 Abruptio placentae 38 7.4 Complications of multiple gestation 31 6.1 Hypoxic intrapartum fetal death >26 wks 9 1.8 Fetal maternal hemorrhage 5 1 Uterine rupture 1 0.2 Cervical insufficiency with antepartum death 0 0 Preterm labor with antepartum death 0 0 Preterm premature rupture of membranes with antepartum death 0 0 Clinical chorioamnionitis with antepartum death 0 0 Other obstetric complications 0 0 Other (n=6) Circulation - placental and/or fetal hydrops 10 2 Placental membranes - Early amnion rupture sequence 3 0.6 Other pertinent condition not otherwise specified 2 0.4 Other maternal or fetal hematologic conditions 1 0.2 Maternal trauma during pregnancy 0 0 Red cell isoimmunization 0 0 Platelet alloimmunization 0 0 Placental membranes - Amnion nodosa 0 0

Circumvallate, velamentous, or furcated cord insertion with compromise was classified as a possible cause of death in INCODE as published, but is included in this analysis as a condition present.

Downloaded From: https://jamanetwork.com/ on 09/23/2021 eTable 2. Probable and Possible Causes of Death,1 Stratified by Race/Ethnicity2 Showing P Values Accounting for Dependencies in the Data for 12 Sets of Twin Stillbirths3 Non- Non- Pearson GEE Score Cause of Death Hispanic Hispanic Hispanic Other Chi-square Statistic White Black P – value P - value Placental Disease 40 (21.9%) 22 (19.1%) 47 (26.7%) 11 (29.7%) 0.35 0.36 Infection 13 (7.1%) 29 (25.2%) 15 (8.5%) 8 (21.6%) < 0.0001 0.0004 Fetal Genetic / Structural 25 (13.7%) 9 (7.8%) 31 (17.6%) 5 (13.5%) 0.13 0.09 Medical Complications 15 (8.2%) 8 (7.0%) 12 (6.8%) 5 (13.5%) 0.56 0.71 Hypertensive Disorders 16 (8.7%) 14 (12.2%) 13 (7.4%) 4 (10.8%) 0.56 0.63 Umbilical Cord Abnormalities 23 (12.6%) 5 (4.3%) 23 (13.1%) 2 (5.4%) 0.05 0.01 Obstetric Complications 41 (22.4%) 50 (43.5%) 44 (25.0%) 15 (40.5%) 0.0003 0.0017 Other 3 (1.6%) 5 (4.3%) 7 (4.0%) 1 (2.7%) 0.51 0.43 Any cause 131 (71.6%) 94 (81.7%) 135 (76.7%) 29 (78.4%) 0.24 0.24 Total N 183 115 176 37

1Some stillbirths had more than one probable or possible cause.

2One case missing race/ethnicity classification.

3Results from the analysis included in Table 4 of the paper are reproduced with a column added for p-values from logistic regression that account for the correlated observations within pregnancies using generalized estimating equations (GEE) score statistics. Using GEE, the conclusions were the same as those shown in Table 4 of the paper. Differences in the two sets of p-values are due to: the dependencies that are taken into account in the GEE models but not the Chi-square tests for 12 sets of twin stillbirths; and the use of different statistical techniques.

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