Risks associated with ICP
For both patients and clinicians, the greatest concern among patients with ICP is the increased risk of stillbirth. Stillbirth risk in ICP appears to be related to serum bile acid levels and has been reported to be highest in patients with bile acid levels greater than 100 µmol/L. A systematic review and meta-analysis of ICP studies demonstrated no increased risk of stillbirth among patients with bile acid levels less than 100 µmol/L.12 These results, however, must be interpreted with extreme caution as the majority of studies included patients with ICP who were actively managed with attempts to mitigate the risk of stillbirth.7
In the absence of additional pregnancy risk factors, the risk of stillbirth among patients with ICP and serum bile acid levels between 19 and 39 µmol/L does not appear to be elevated above their baseline risk.11 The same is true for pregnant individuals with ICP and no additional pregnancy risk factors with serum bile acid levels between 40 and 99 µmol/L until approximately 38 weeks’ gestation, when the risk of stillbirth is elevated.11 The risk of stillbirth is elevated in ICP with peak bile acid levels greater than 100 µmol/L, with an absolute risk of 3.44%.11
Management of patients with ICP
Laboratory evaluation
There is no consensus on the need for repeat testing of bile acid levels in patients with ICP. SMFM advises that follow-up testing of bile acid levels may help to guide delivery timing, especially in cases of severe ICP, but the society recommends against serial testing.7 By contrast, the Royal College of Obstetricians and Gynaecologists (RCOG) provides a detailed algorithm regarding time intervals between serum bile acid level testing to guide delivery timing.11 The TABLE lists the strategy for reassessment of serum bile acid levels in ICP as recommended by the RCOG.11
In the United States, bile acid testing traditionally takes several days as the testing is commonly performed at reference laboratories. We therefore suggest that clinicians consider repeating bile acid level testing in situations in which the timing of delivery may be altered if further elevations of bile acid levels were noted. This is particularly relevant for patients diagnosed with ICP early in the third trimester when repeat bile acid levels would still allow for an adjustment in delivery timing.
Antepartum fetal surveillance
Unfortunately, antepartum fetal testing for pregnant patients with ICP does not appear to reliably predict or prevent stillbirth as several studies have reported stillbirths within days of normal fetal testing.13-16 It is therefore important to counsel pregnant patients regarding monitoring of fetal movements and advise them to present for evaluation if concerns arise.
Currently, SMFM recommends that patients with ICP should begin antenatal fetal surveillance at a gestational age when abnormal fetal testing would result in delivery.7 Patients should be counseled, however, regarding the unpredictability of stillbirth with ICP in the setting of a low absolute risk of such.
Medications
While SMFM recommends a starting dose of ursodeoxycholic acid 10 to 15 mg/kg per day divided into 2 or 3 daily doses as first-line therapy for the treatment of maternal symptoms of ICP, it is important to acknowledge that the goal of treatment is to alleviate maternal symptoms as there is no evidence that ursodeoxycholic acid improves either maternal serum bile acid levels or perinatal outcomes.7,17,18 Since publication of the guidelines, ursodeoxycholic acid’s lack of benefit has been further confirmed in a meta-analysis, and thus discontinuation is not unreasonable in the absence of any improvement in maternal symptoms.18
Timing of delivery
The optimal management of ICP remains unknown. SMFM recommends delivery based on peak serum bile acid levels. Delivery is recommended at 36 weeks’ gestation with ICP and total bile acid levels greater than 100 µmol/L as these patients have the greatest risk of stillbirth.7 For patients with ICP and bile acid levels less than 100 µmol/L, delivery is recommended between 36 0/7 and 39 0/7 weeks’ gestation.7 This is a wide gestational age window for clinicians to consider timing of delivery, and certainly the risks of stillbirth should be carefully balanced with the morbidity associated with a preterm or early term delivery.
For patients with ICP who have bile acid levels greater than 40 µmol/L, it is reasonable to consider delivery earlier in the gestational age window, given an evidence of increased risk of stillbirth after 38 weeks.7,12 For patients with ICP who have bile acid levels less than 40 µmol/L, delivery closer to 39 weeks’ gestation is recommended, as the risk of stillbirth does not appear to be increased above the baseline risk.7,12 Clinicians should be aware that the presence of concomitant morbidities, such as preeclampsia and gestational diabetes, are associated with an increased risk of stillbirth and should be considered for delivery planning.19
Postpartum follow-up
Routine laboratory evaluation following delivery is not recommended.7 However, in the presence of persistent pruritus or other signs and symptoms of hepatobiliary disease, liver function tests should be repeated with referral to hepatology if results are persistently abnormal 4 to 6 weeks postpartum.7
CASE Patient follow-up and outcomes
The patient was counseled regarding the diagnosis of ICP. Following shared decision making, the patient opted to undergo twice weekly nonstress tests but was aware to carefully monitor fetal movements due to the unpredictability of stillbirth in ICP. The patient also opted to trial ursodeoxycholic acid for relief of maternal symptoms. Two weeks after her initial diagnosis, repeat total bile acid levels were stable at 22 µmol/L. Therefore, following extensive counseling, the patient opted to undergo induction of labor at 38 weeks’ gestation, with a normal outcome for mother and neonate. ●