Intrahepatic cholestasis of pregnancy is a common disorder of pregnancy manifested by pruritus and elevated bile acids. The etiology of cholestasis is poorly understood and management is difficult due to the paucity of data regarding its diagnosis, treatment, and related adverse outcomes. In this article, we review the epidemiology, pathophysiology, risk factors, laboratory findings, complications, treatment, management, and current evidence surrounding intrahepatic cholestasis of pregnancy.

Objective Pregnant women have been historically excluded from clinical trials for nonobstetric conditions, even during prior epidemics. The objective of this review is to describe the current state of research for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Study Design We conducted a search of international trial registries for trials relating to the novel coronavirus. The eligibility criteria for each trial were reviewed for inclusion/exclusion of pregnant women. Relevant data were extracted and descriptive statistics were calculated for individual and combined data. The total number of trials from each registry were compared, as well as the proportions of pregnancy-related trials within each. Results Among 621,370 trials in the World Health Organization International Clinical Trials Registry, 927 (0.15%) were COVID-19 related. Of those, the majority (52%) explicitly excluded pregnancy or failed to address pregnancy at all (46%) and only 16 (1.7%) were pregnancy specific. When categorized by region, 688 (74.2%) of COVID-19 trials were in Asia, followed by 128 (13.8%) in Europe, and 66 (7.2%) in North America. Of the COVID-19 trials which included pregnant women, only three were randomized-controlled drug trials. Conclusion Approximately 1.7% of current COVID-19 research is pregnancy related and the majority of trials either explicitly exclude or fail to address pregnancy. Only three interventional trials worldwide involved pregnant women. The knowledge gap concerning the safety and efficacy of interventions for COVID-19 created by the exclusion of pregnant women may ultimately harm them. While “ethical” concerns about fetal exposure are often cited, it is in fact unethical to habitually exclude pregnant women from research. Key Points

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OBJECTIVE: To evaluate differences between fasting and nonfasting bile acid levels in asymptomatic and symptomatic pregnant women. METHODS: This is a report of two prospective cohort studies describing bile acid levels in the fasting and nonfasting state in pregnancy. The first cohort included asymptomatic women with singleton pregnancies. Women with a diagnosis of cholestasis, symptoms of cholestasis, or intolerance to components of a standardized meal were excluded. Bile acid levels were measured during the second and third trimesters after fasting and again 2 hours after a standardized meal. The second cohort included symptomatic women with singleton pregnancies in whom fasting and nonfasting bile acid levels were measured at the time of symptom evaluation. A cutoff of 10 micromoles/L was used for diagnosis. RESULTS: A total of 27 women were included in the asymptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting levels in both the second trimester (4.65 micromoles/L [1.02–29.57] vs 13.62 micromoles/L [2.03–40.26]; P<.001) and third trimester (8.31 micromoles/L [1.14–51.26] vs 17.35 micromoles/L [1.77–62.93]; P<.001). Bile acid levels exceeded 10 micromoles/L in 21% of the fasting samples and in 58% of the nonfasting samples in the third trimester. A total of 26 women were included in the symptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting values (11.5 micromoles/L [7–56] vs 13.5 micromoles/L [9–142]; P<.001). Six patients in the symptomatic cohort (23%) had nonfasting bile acid levels greater than 10 micromoles/L that dropped below 10 micromoles/L when fasting. CONCLUSION: Fasting bile acid levels are significantly lower when compared with nonfasting values in both asymptomatic and symptomatic pregnant women. In asymptomatic women, nonfasting bile acid levels often exceeded 10 micromoles/L whereas fasting values did not. In symptomatic women, fasting bile acid levels resulted in 23% fewer diagnoses of cholestasis when compared with nonfasting values. These findings suggest that fasting evaluation of bile acid levels or a higher threshold for diagnosis of cholestasis should be considered.