What are the common causes of stillbirth?

Causes of Stillbirth

Placental vascular abnormalities and maternal vascular malperfusion represent the leading cause of stillbirth, accounting for approximately 23-36% of cases, followed by obstetric complications (particularly asphyxia from prolonged labor, hemorrhage, and hypertensive disorders), infections, fetal genetic/structural abnormalities, and umbilical cord problems. 1, 2

Major Categories of Stillbirth Causes

Placental and Vascular Pathology (Most Common)

• Placental abnormalities cause 23.6-36% of stillbirths, with maternal vascular malperfusion and small placenta being the predominant histologic findings 1, 2
• Maternal vascular malperfusion strongly associates with preeclampsia and hypertensive disorders 3
• Placental vascular anomalies often present with both maternal and fetal vascular lesions, suggesting a distinct "vascular stillbirth" phenotype 1

Obstetric Complications and Asphyxia

• Asphyxia accounts for 29.3-46.6% of stillbirths, making it the single most common immediate mechanism of fetal death 4, 2
• Within asphyxia cases: 38% involve prolonged or obstructed labor, 19% antepartum hemorrhage, and 18% preeclampsia/eclampsia 4
• Intrahepatic cholestasis of pregnancy (ICP) increases stillbirth risk 2.5-3-fold, with risk escalating dramatically when bile acids exceed 100 mmol/L (hazard ratio 30.50) 5
• The median gestational age for ICP-related stillbirth is 38 weeks, with most occurring after 37 weeks 5

Infections

• Infections cause 9-20.8% of stillbirths, with higher rates in African populations and low-income settings 6, 4, 2
• Maternal infections including syphilis, HIV (particularly with low CD4 counts), hepatitis B/C with cirrhosis, and malaria significantly elevate risk 3, 7
• Neonatal sepsis frequently appears as an immediate cause even when infection is not the underlying etiology 6

Fetal Genetic and Structural Abnormalities

• Chromosomal abnormalities and major congenital malformations account for 8.4-13.7% of stillbirths 2, 7
• These abnormalities contribute to approximately 20% of fetal growth restriction cases resulting in intrauterine death 3

Fetal Growth Restriction

• Fetuses below the 10th percentile carry a 1.5% stillbirth risk (double that of appropriately grown fetuses) 3
• Risk escalates to 2.5% below the 5th percentile 3
• Poorest outcomes occur below the 3rd percentile or with abnormal Doppler studies 3

Umbilical Cord Abnormalities

• Cord problems account for 10.4-11% of stillbirths 1, 2

High-Risk Maternal Factors

Substance Use

• Tobacco smoking increases stillbirth risk through placental abruption, placenta previa, fetal growth restriction, and preterm premature rupture of membranes 3
• Cocaine or methamphetamine use precipitates severe maternal hypertension and cardiovascular complications 3
• Intravenous opiate use heightens infection risk (HIV, hepatitis C, endocarditis, sepsis) 3

Medical and Obstetric History

• Multiple prior cesarean deliveries elevate risk via placenta accreta spectrum and hemorrhagic complications 3
• Short interpregnancy intervals (<18 months) increase morbidity and mortality, especially in women >35 years 3
• Chronic hepatitis B/C with cirrhosis links to higher maternal and perinatal mortality 3

Demographic Risk Factors

• Maternal age >35 or <20 years 7
• High parity (≥5) or primiparity 7
• Lack of antenatal care 7
• Poverty and lack of education 7

Critical Clinical Considerations

Racial Disparities

• Non-Hispanic Black women experience significantly higher rates of stillbirth from obstetric complications (43.5% vs 23.7%, difference 19.8%) and infections (25.2% vs 7.8%, difference 17.4%) compared to non-Hispanic White and Hispanic women 2
• Intrapartum stillbirths and early gestational losses occur more frequently in Black women 2

Timing Patterns

• Approximately 67% of stillbirths show no signs of maceration, indicating acute or recent events 4
• Most ICP-related stillbirths cluster around 38 weeks gestation 5

Unexplained Cases

• Despite systematic evaluation, 17-24% of stillbirths remain unexplained even after comprehensive workup 1, 2
• The proportion of unclassified stillbirths ranges from 3.8-57.4% depending on classification system rigor and completeness of evaluation 7

Essential Diagnostic Evaluations

The highest-yield investigations for determining cause include:

• Placental histopathology (positive findings in 52.3% of cases) 2
• Complete perinatal postmortem examination (contributory in 31.4%) 2
• Fetal karyotype (definitive findings in 9% when obtained) 2