Misoprostol-augmented induction of labour for third trimester fetal demise in a patient with prior hysterotomies

Abstract

A 31-year-old G3P2002 with history of two prior caesarean sections presented with influenza-like illness, requiring intubation secondary to acute respiratory distress syndrome. Investigations revealed intrauterine fetal demise at 30-week gestation.

She soon deteriorated with sepsis and multiple organs impacted. Risks of the gravid uterus impairing cardiopulmonary function appeared greater than risks of delivery, including that of uterine rupture. Vaginal birth after caesarean was achieved with misoprostol and critical care status rapidly improved.

Current guidelines for management of fetal demise in patients with prior hysterotomies are mixed: although the American College of Obstetricians and Gynecologists recommends standard obstetric protocols rather than misoprostol administration for labour augmentation, there is limited published data citing severe maternal morbidity associated with misoprostol use. This case report argues misoprostol-augmented induction of labour can be a reasonable option in a medically complex patient with fetal demise and prior hysterotomies.

Background

This case report describes the hospital course of a pregnant woman infected with influenza resulting in acute respiratory distress (ARDS) and intrauterine fetal demise (IUFD), and reflects on the medical decision-making of augmenting vaginal delivery in a patient with a history of hysterotomies. Classically, induction of labour (IOL) in women with prior caesareans has been complicated by the risk of uterine rupture at the hysterotomy site, with a reported prevalence ranging anywhere from 1% to 5%.^1–3 While the American College of Obstetricians and Gynecologists (ACOG) supports IOL in cases of IUFD, a recent March 2020 revision now recommends standard obstetric protocols rather than misoprostol administration in cases of women with previous hysterotomy.⁴ However, there are limited published data citing severe maternal morbidity associated with misoprostol-induced vaginal birth after caesarean (VBAC) in the setting of IUFD. This case report highlights a case of successful prostaglandin-augmented IOL for third trimester IUFD in a critically ill patient intubated due to ARDS.

ARDS in pregnancy remains rare, although influenza pneumonia is a common contributor to the physiology, as was documented by high mortality rates experienced during the 2009 H1N1 influenza pandemic.^{5 6} Under the Berlin definition, ARDS is characterised by the acute onset of respiratory insufficiency with radiographic findings and oxygenation deficits not explained by cardiac failure.⁷ Management in pregnancy includes treating the direct aetiology, using mechanical ventilation with a low tidal volume and higher PEEP, and, in some cases, delivery to help relieve reduced lung distensibility associated with a gravid uterus.⁵ Overall, guidelines show patients of this critical care status benefit from clear and frequent communication between high-risk obstetricians and intensive specialists.

Case presentation

Our patient was a 31-year-old woman with morbid obesity and type 2 diabetes who presented to the emergency department (ED) with 2 weeks of influenza-like illness including subjective fevers, cough and chills that worsened acutely over the prior 48 hours. The patient reported her daughters had been previously ill with similar symptoms, although they had not been tested for influenza. On presentation, she was tachycardic and tachypneic with a leucocytosis (white count of 30 with left shift) and rising creatinine (2.6, with baseline 0.5) consistent with acute kidney injury. Chest radiograph identified left base consolidation with an effusion attributable to superimposed bacterial pneumonia (figure 1). Nasopharyngeal swab was positive for influenza type B.

Figure 1.

Patient chest radiograph on presentation to hospital, requiring intubation secondary to acute respiratory distress. Left lower lobe consolidation identified, secondary to presumed bacterial superimposed influenza pneumonia.

Investigations

In the ED, she reported that her menses had been irregular in the setting of her Mirena intrauterine device (IUD), which had been placed after her second caesarean section 2 years prior. She believed she had no indication she was pregnant. Her obstetric history was notable for two prior low transverse caesareans sections, both secondary to the development of pre-eclampsia with severe features.

The patient quickly decompensated in the ED due to sepsis and presumed ARDS. Her lactate rose to 6.0, with an anion gap of 24, and she showed inadequate respiratory compensation on arterial blood gas (pH 7.28). She required intubation within 6 hours of presentation, and was admitted to the intensive care unit (ICU). She developed atrial fibrillation with a rapid ventricular response and heart rate in the 180 s, and was started on an amiodarone drip. She was also begun on pressors due to severe hypotension and a combination of intravenous tamiflu, ceftriaxone and flagyl for influenza and superimposed pneumonia.

Soon after intubation, the patient’s admission urine pregnancy test returned as positive, with a quantitative beta-Human chorionic gonadotropin (b-HCG) of 33 850. A formal transvaginal ultrasound identified a single intrauterine pregnancy at at 30-week gestational age with oligohydramnios. No cardiac activity was appreciated.

Treatment

Given the patient’s deteriorating status, her multidisciplinary teams, including obstetrics, critical care, pulmonology and nephrology, engaged in a detailed coordination of an optimal care plan. Delivery of the IUFD was recommended in order to optimise her ventilation and perfusion capacity in a number of ways, including by reducing the effect of arterial-venous blood shunting across the gravid uterus and placenta bed, improving tidal volume and vital capacity, and potentially offsetting the development of chorioamnionitis and disseminated intravascular coagulation (DIC).

At the time, her cervix was closed, long and high. Her estimated success for VBAC was less than 22%, given her body mass index and lack of previous vaginal deliveries (based on the Society of Maternal Fetal Medicine calculator that does not include the patient’s race nor her ethnicity).⁸ Despite this, induction was still favoured over repeat caesarean section, as surgery would be complex given her critical cardiovascular haemodynamics. In particular, the risks of IOL with misoprostol, including the risk for uterine rupture with potential for severe maternal haemorrhage and surgical intervention, were weighed against the risk of moving directly to caesarean section and the likely development of infection and DIC if induction were delayed.

While the patient was still intubated, IOL was begun with the placement of vaginal misoprostol every 4 hours, planned for a maximum of four doses. Out of abundance of caution given our patient’s deteriorating clinical status, we began with 50 μg misoprostol vaginally and then doubled subsequent doses to 100 µg when the first dose did not lead to cervical change. Cervical ripening was also achieved with a transcervical Foley catheter. After an 18-hour labour, the patient spontaneously delivered the demised fetus without complication.

Outcome and follow-up

The patient’s critical care status improved significantly following delivery and decompression of the uterus (figure 2). After more than a week in the ICU, the patient was successfully extubated after delivery. The patient confirmed that she did not know she was pregnant, but she reported she believed her IUD had self-expelled the year prior. To optimise her grieving process, she and her family were able to bond with the demised fetus at bedside. Physical examination, which revealed significant skin maceration and overlapping suture lines, suggested demise likely occurred prior to patient’s presentation to the ED. The fetal and placental findings showed acute on chronic inflammation consistent with fetal demise associated with severe sepsis due to pervasive superimposed bacterial pneumonia.

Figure 2.

Patient chest radiograph following delivery of fetus and extubation. Atelectasis with interval improvement in diffuse pulmonary oedema.

The patient was seen by the medical team at a postpartum visit 3 months after recovery. Given the acuity of her presentation, including her rapid decline in cardiopulmonary status and self-reported loss of taste and smell prior to admission, she was tested for SARS-CoV-2 IgG/IgM. Surprisingly given her time course and acuity, all her results were negative. At clinic visits, the patient expressed she had been recovering well, but was still coping with the emotional stress of her loss. She has been seen several times since then, continuing to connect with her medical team on her path to healing.

Discussion

Roughly 1% of all pregnancies end in IUFD. Of these, the vast majority will spontaneously deliver within 3 weeks of intrauterine death.⁹ As a result, expectant management can be an informed, evidence-based response to IUFD. Yet, haemodynamic instability and high likelihood of development of DIC—as was the case with our patient—often favour delivery over expectant management. For delivery management, ACOG’s most recent Consensus Statement for Management of Stillbirth recommends both ‘labour and dilation and evacuation (as) options for women with a previous hysterotomy’.⁴ These standards follow recent research suggesting high rates of VBAC success in the case of IUFD, with lower than expected rates of rupture and no maternal mortality reported.^{1–3 10}

Yet, for IUFD in women with uterine scar, current ACOG guidelines favour standard obstetric protocols over misoprostol administration.^{4 11} These are historic protocols that may be relying on dated data, with one seminal trial from the early 2000s showing uterine rupture rates were lower in spontaneous labour achieved without prostaglandins.^{12 13} More recently, however, guidelines acknowledge there are limited updated data to guide clinical practice in this respect, especially for patients in whom the IUFD occurs in the third trimester. A meta-analysis from 2015 shows overall low rates of rupture among a series of six retrospective cohort studies examining the effect of misoprostol-augmented labour on uterine rupture.¹⁴ According to other key bodies in the field, such as RCOG, delivery plans should instead be individualised based on patient preferences, and women should be made aware of the potentially higher risk of IOL augmented with prostaglandins.^{11 15}

A review of the existing literature shows mixed outcomes with varying dosages and timing intervals of misoprostol. A case of a 34-year-old with three prior caesareans was induced for vaginal delivery for second trimester IUFD secondary to anencephaly: her misoprostol dose was doubled from 200 µg every 12 hours to 400 µg every 8 hour with successful expulsion of the fetus and no uterine rupture.¹⁶ Other successful case reports include that of a 27-year-old woman at 31 weeks with IUFD: she received two doses of 50 µg misoprostol and labour was induced without any complications.¹⁷ In contrast, a case report of a 35-year-old patient also with prior caesareans was started on 25 µg of vaginal misoprostol, which was later doubled to 50 µg but terminated when uterine rupture was identified on ultrasound scan and confirmed on emergency laparotomy.¹⁸

Thus, to date, optimal timing and dose of intravaginal misoprostol remains unknown. In 2017, International Federation of Gynecology and Obstetrics (FIGO) updated its misoprostol recommendations to suggest using 100 µg of misoprostol every 4 hours for gestations above 26 weeks; however, with mixed outcomes to date, the group is unable to make a recommendation in cases of uterine scar, revoking 2012 recommendations which suggested halving the misoprostol dose in cases of hysterotomy.¹⁹ Meanwhile, the ACOG practice bulletin supports the administration of 50 µg misoprostol vaginally and then repeating the dose every 4 hours for a maximum of six doses.¹¹ Existing literature does not support varying dosages of misoprostol for nulliparous versus multiparous women, although findings demonstrate induction of vaginal delivery occurs more quickly in 12 and 24 hours for multiparous women.²⁰ It does, however, support the combined use of vaginal misoprostol with mechanical ripening of the cervix with a balloon catheter, with randomised trials showing combined methods resulting in successful vaginal delivery more quickly, with no adverse effect on maternal or neonatal health outcomes.^{21 22} Finally, in the USA, while mifepristone is used for early-term terminations, it is generally avoided for third trimester induction, as there is less evidence to support this indication, in part due to its restrictive regulation under the Food and Drug Administration’s Risk Evaluation and Mitigation Strategy.²³

In summary, we report on the use of vaginal misoprostol at 100 µg every 4 hours to safely induce labour in a critically ill patient with an IUFD and history of hysterotomies. To date, the use of vaginal misoprostol in the context of the risk of uterine rupture for IUFD remains debated. This is particularly the case in third-trimester IUFD, which altogether creates a rare clinical picture. The strength of this case report is its suggestion that misoprostol can be a reasonable option in third-trimester IUFD with uterine scar. Yet, more research is needed on the exact timing and dosage of vaginal misoprostol on patients with prior uterine scars, especially in those with IUFD.

Learning points.

• Urine pregnancy test should be performed on every woman in reproductive years who presents to the emergency department, even if pregnancy or pregnancy complication is not acutely suspected.

• Prompt induction of labour and delivery may support haemodynamic stability of a critically ill patient with intrauterine fetal demise (IUFD).

• In critical care settings, vaginal misoprostol may be a reasonable option to induce labour in patients with IUFD and prior hysterotomies, even for whom the risk of uterine rupture is possible.

• Critically ill pregnant patients benefit from a multidisciplinary approach to care that incorporates all relevant medical teams.