Stillbirth, defined as fetal death at 20 weeks or more of gestation, remains a common adverse pregnancy outcome worldwide, affecting 2.6 million third-trimester pregnancies in 2015.¹ Significant disparities exist with 98% of stillbirths occurring in low-income and middle-income countries: 77% in South Asia and sub-Saharan Africa.² As of 2015, the global rate of stillbirth was approximately 18 per 1000 births, exceeding the target set by the World Health Organization’s (WHO’s) Every Newborn Action Plan of 12 or fewer stillbirths per 1000 births in every country by 2030.^2,3

In the United States, approximately 24,000 stillbirths occur annually, a rate of 5.96 per 1000 births in 2013, evenly dispersed between “early” stillbirth (20-27 weeks’ gestation) and “late” stillbirth (≥28 weeks’ gestation).⁴ This rate has changed minimally since 2006, while infant mortality has declined by 11%.⁴

In the United States, there is significant racial/ethnic variation among stillbirth rates. In 2013, the highest stillbirth rate occurred among non-Hispanic black women of 10.53 per 1000 births compared with 4.88 per 1000 births for non-Hispanic white women.⁴ In order to understand the reasons for this racial/ethnic disparity, the Stillbirth Collaborative Research Network (SCRN) conducted a population-based, case-controlled study involving 59 tertiary care and community hospitals across five geographic catchment areas. Compared with non-Hispanic white women, non-Hispanic black women were significantly more likely to have stillbirth occur prior to 24 weeks, intrapartum, and secondary to an infection or obstetric complication.⁵ Because of the shared pathophysiology with spontaneous preterm birth (see Chapter 49), a condition with well-documented racial disparity, interventions that reduce rates of early spontaneous preterm birth may also address this subset of stillbirths.

Stillbirth rates vary by maternal age in a parabolic distribution, with the lowest occurring in women aged 25 to 29 years (5.34 per 1000 births) and highest occurring in women younger than 15 years (15.88 per 1000 births).⁴ Advanced maternal age (AMA) also increases the risk of stillbirth—increases 2-fold from ages 40 to 44 years and 2.5-fold with maternal age 45 years and older (13.76 per 1000 births).⁴ This association persists after adjusting for maternal medical disease, race/ethnicity, and parity.^6,7 A meta-analysis evaluating the effect of AMA on pregnancy outcomes noted that the increased risk of stillbirth parallels an increased risk of placental abruption, preeclampsia, and fetal growth restriction, highlighting placental dysfunction as a possible contributor to the age-related increase in stillbirth.⁸

Obesity also increases the risk of stillbirth in a dose-dependent fashion with a meta-analysis of 38 cohort studies revealing a relative risk of 1.21 for every increase of 5 units of maternal body mass index (BMI).⁹ Women with a BMI over 30 kg/m² are twice as likely to experience stillbirth. Causes of obesity-related stillbirth include placental diseases, hypertension, fetal anomalies, and cord abnormalities (see Chapter 32).¹⁰

Other obstetric risk factors, such as increased parity, are associated with an increased risk of stillbirth, with rates more than doubled in women with four or more prior pregnancies.¹¹ Stillbirth also occurs more frequently in multifetal gestations, with approximately a 2.5-fold increased risk in twins and 5.5-fold increased risk in triplet or higher order gestations (see Chapter 5).⁴ Smoking, alcohol
use, illicit drug use (see Chapter 8), low education, and inadequate prenatal care (see Chapter 54) are also associated with elevated risks of stillbirth.¹²

In the SCRN review of 512 stillbirths, 17% occurred intrapartum. These are generally secondary to preterm labor, premature prelabor rupture of membranes, cervical insufficiency, intra-amniotic infection, or placental abruption at a previable or periviable gestational age.⁵

Accurate, consistent reporting of causes of stillbirth is needed to guide further efforts aiming to reduce the risk of stillbirth. Over 80 classification systems have been proposed with no current uniformly used system for stillbirth reporting.¹³ The SCRN developed a classification system based on the evidence in the existing literature entitled “Initial Causes of Fetal Death” or INCODE.¹⁴ This system assigned levels of certainty to causes of stillbirth, ranging from “probable,” to “possible,” and “present.” Using INCODE to analyze 512 stillbirths that had a complete evaluation, including autopsy and placental pathology, the SCRN assigned a probable cause of death in 60.9% of cases and a possible or probable cause in 76.2% of cases, with multiple probable or possible causes in 31.4% of cases.⁵ The most frequent cause of stillbirth (29.3% of cases) was obstetric complications, a category that included abruption, complications of multiple gestations, preterm labor, preterm rupture of membranes, and cervical insufficiency predominantly at a pre- or periviable gestation. The second most frequent category (23.6% of cases) was placental complications, which included uteroplacental insufficiency and maternal vascular disorders.⁵ Other etiologies of stillbirth included fetal genetic or structural anomalies (13.7% of cases), infection (12.9% of cases), umbilical abnormalities (10.4% of cases), hypertensive disorders (9.2% of cases), and maternal medical complications (7.8% of cases).⁵

Maternal infections increase the risk of stillbirth by causing severe maternal illness, direct fetal infection, placental dysfunction, or preterm labor at a previable gestation. Worldwide, maternal infections, including syphilis and malaria, are associated with a substantial number of stillbirths, up to 50% depending on the area.^1,15,16 In developed nations, this rate decreases to 10% to 20%, occurring most commonly in the setting of ascending bacterial infections in the setting of preterm premature rupture of membranes.^5,17

Pathogens, including group B Streptococcus and Escherichia coli, enter the amniotic fluid either after membrane rupture or after ascension from the vagina.¹⁶ Alternatively, bacteria, such as Listeria, may spread hematogenously and reach the placental villi causing microabscesses and villous necrosis.¹⁶ Viral pathogens, such as enteroviruses, cytomegalovirus, Zika virus, and parvovirus, have also been implicated in stillbirth through both placental and fetal mechanisms.^16,18 A more detailed discussion of infectious diseases affecting pregnancy is presented in Chapter 39.