Advances in the treatment of fetal demise in the second and third trimester

Fetal size 14w0d to 28w6d gestation: Cervical preparation and induction of labor

Treatment of fetal demise at 14w0d to 28w6d gestation with the goal of the vaginal birth of an intact fetus is optimized by the administration of mifepristone for cervical preparation followed by induction of labor with misoprostol.^26,27

In one clinical trial, 66 patients with fetal demise between 14w0d and 28w6d gestation were randomly assigned to receive mifepristone 200 mg or placebo followed 24 to 48 hours later with initiation of misoprostol induction of labor.²⁶ Among the patients from 14w0d to 24 weeks’ gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24w0d to 28 weeks’ gestation, the misoprostol dose was 200 µg vaginally every 4 hours. At 24 hours, a consultant obstetrician determined if additional misoprostol should be given. The median time from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups was 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P= .002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage, 4 in the placebo group and 1 in the mifepristone group.²⁶

In a second clinical trial, 105 patients with fetal demise after 20 weeks of gestation were randomly assigned to receive mifepristone 200 mg or placebo.²⁷ In this study, 86% of the patients were ≥26w0d gestation, with a mean gestational age of approximately 32w2d. Thirty-six to 48 hours later, misoprostol induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostoldose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients from ≥26 weeks’ gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours, respectively (P=.001). Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg; P<.001). Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²⁷

Fetal size ≥29w0d gestation

At a fetal size ≥29w0d gestation, if the cervix is ripe with a Bishop score of ≥7, oxytocin induction of labor is often used as a first-line treatment. If the cervix is not ripe, misoprostol induction of labor may be considered at doses less than those used in the second trimester of pregnancy.³² TABLES 1,^{1, 26, 33–36} 2,³⁷ and 3³⁷ summarize regimens proposed for fetal size ≥29w0d. One regimen begins with an initial misoprostol dose of 50 µg. If adequate uterine contractions occur, the 50 µg dose is repeated every 4 hours up to 6 total doses. If contractions are inadequate, the dose can be increased to 100 µg every 4 hours for 5 additional doses.

For fetal demise after 28w0d gestation, the American College of Obstetricians and Gynecologists (ACOG)¹ recommends standard obstetric protocols for induction of labor, including standard protocols for induction of labor following a previous cesarean birth. For a patient with a history of a prior cesarean birth or major uterine surgery, ACOG recommends that management of fetal demise should prioritize the use of mechanical cervical ripening, for example with a balloon catheter, and induction of uterine contractions with oxytocin.³⁸ ACOG recommends against the use of misoprostol for cervical ripening or labor induction for patients with a stillbirth at term with a history of a cesarean birth.³⁸ Preliminary experience suggests that stillbirth protocols using misoprostol doses modestly greater than those used in the management of a pregnancy with a viable fetus may be safe.⁹ See TABLES 2 and 3.

A multidisciplinary approach can optimize compassionate care

There are many gaps in the holistic care of patients and partners experiencing fetal demise. Patients with fetal demise often report that they did not receive sufficient information about the cause of the demise and wanted more opportunity to be involved in decision making about their care.³⁹ The patient’s partner often reports feeling unacknowledged as a grieving parent.⁴⁰ Fetal demise is experienced by many patients as a tragedy, triggering feelings of grief, anger, denial, anxiety and depression, sometimes resulting in isolation and substance misuse.

Using a 5-round Delphi process, experts identified 8 core goals in the care of patients with fetal demise:

1. reduce stigma
2. provide respectful care
3. involve patients in care planning
4. attempt to provide an explanation for the demise¹
5. acknowledge the depth of the grief response and provide emotional support
6. offer information about ongoing psychological support
7. provide information about future pregnancy planning
8. provide opportunities for specialized training and support for care providers.⁴¹

Management of stillbirth is optimized by a multidisciplinary approach that includes the expert care of obstetrician-gynecologists, obstetric nurses, anesthesiologists, and expert consultation from social work, chaplaincy, and pathology. A heart-to-heart connection between clinician and patient is a key component of stillbirth care. ●