However, one recent study did consider comorbidities in ICP-affected pregnancies.21 This was a review of a retrospective multisite cohort of 233 symptomatic women with total bile acids (TBA) levels that ranged from 0 μmol/L to > 100 μmol/L. While the authors found the prevalence of maternal comorbid stillbirth risk factors was not affected by the severity of the disease, it is notable that all 4 stillbirths in the cohort occurred in pregnancies most severely affected by ICP as designated by TBA levels > 100 μmol/L. Although the findings in this study are certainly suggestive of an association between elevated TBA and fetal demise, as in many previous reviews of large data sets, critical relevant obstetric information is missing. In particular, no data are provided concerning gestational age or existence of comorbid conditions complicating the pregnancies that ended in stillbirth. No information is provided about the use of active management of ICP-affected pregnancies during the 2009 to 2014 study period.
Lack of benefit to active management
Active management of ICP has its foundation in reports published between 1964 and 2014 that consisted of only 20 unexplained term stillbirths including 6 pregnancies affected by cardiovascular comorbidities.22-24 A review of the published literature finds no evidence to reject the null hypothesis that there is no difference in stillbirth rates for pregnancies affected and unaffected by ICP.8
In contrast, there is robust evidence that when compared to full-term (FT) infants (39 to 42 weeks’ gestation), ET (37 to 39 weeks’ gestation) and LPT infants (incorrectly dated 34–35 and 36 weeks’ gestation) are at increased risk for short-term respiratory morbidity, admission to neonatal intensive care units, and for the first 8 to 9 years of life, lower lung function as measured by a spirometer.25,26 When compared to FT infants, ET infants are at increased risk for lower cognitive ability; importantly, this is a finding that persists into adulthood.27,28 Several reports indicate that LPT and ET infants are at increased risk for needing special education, achieving less education, and having poorer cognitive abilities than FT infants.29-31 After controlling for socioeconomic confounders, investigators found persistent differences in neurocognitive abilities among LPT and ET children as manifested by generally performing less well on cognitive and language tests than their FT-born counterparts.32 This altered neurocognitive function seems to continue into adulthood as measured by poorer episodic memory performance.33
Whereas there is no evidence to support ICP as an independent risk factor for unexplained term stillbirth, robust data exist that when compared to FT infants born before 39 weeks’ gestation, LPT infants delivered at 34 to 36 weeks and ET infants delivered at 37 to 38 weeks are at increased risk for short- and long-term adverse outcomes.34
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