The data on ICP in the United States is extremely limited despite its high frequency. The prevalence of ICP in this retrospective cohort of patients was found to be 1.9%, similar to other data from Central and Western Europe. Previous literature reports 0.3% prevalence in the United States 
. The prevalence is higher in Chile and Bolivia, with rates of 1.5–4%, and 9% 
. In our study, in which women with ICP were identified from an ethnically/racially mixed study population, Latina women had a greater likelihood of having ICP than other women (RR 4.96, 95%CI 2.59, 9.51, p<0.0001), suggesting that genetic factors may play a role in the development of ICP. In a recent study of a largely Latina Los Angeles population, the overall prevalence of ICP was found to be 5.6% 
Although ICP is usually relatively benign to the mother, it is known that the risk of fetal complications is increased in pregnancies affected by ICP. These include increased risks of meconium stained amniotic fluid, preterm delivery, fetal distress and intrauterine fetal demise (IUFD). In this study, we found that 33% of the births had an associated perinatal complication including respiratory distress syndrome, meconium staining of amniotic fluid, fetal distress, congenital anomalies, sepsis, hyperbilirubinemia and pneumonia. There were no episodes of IUFD. Previous studies have reported meconium staining in 24%, and intrauterine fetal demise in 0.4% of ICP cohorts 
. The incidence of meconium staining of amniotic fluid at full term in a normal pregnant population varies between 17–24% and at 37 weeks gestational age is ~5%, compared to the 9% incidence observed in our study 
. Respiratory distress accounted for 52% of the complications observed post-partum.
It has been reported that the incidence of respiratory distress syndrome in neonates born to mothers with ICP is twice that of the normal population 
. This can be due in part to the earlier gestational age at delivery, but neonatal respiratory distress syndrome has been demonstrated to be associated with ICP, based on analysis of bronchoalveolar lavage fluid of neonates born to mothers with ICP 
. Specifically, it has been hypothesized that bile acids can produce surfactant depletion in the alveoli 
. Animal models have shown microscopic findings of atelectasis, poling of eosinophilic substances in intra-alveolar spaces, and formation of hyaline membranes in rabbits after intratracheal instillation of taurocholic acid 
. When treated with surfactant, alveoli responded appropriately, and had increased aeration 
. In another study, bronchial alveolar lavage was performed during necropsy on 12 infants and it was found that there were lower phospholipid levels, and higher bile acid levels 
. This suggests a possible interaction between bile acids and surfactant mediated through the phospholipase A2, which synthesizes surfactant in the lung 
. More details are necessary to determine the effects of bile acids on fetal lung maturity, surfactant production, and respiratory distress.
The risk of fetal morbidity and mortality in ICP is higher than in the general population 
. Even though in this study there were no cases of IUFD, the overall complication rate is still concerning. Current management of ICP is induction of labor at 36–38 weeks gestational age, regardless of TBA levels; however, it has been suggested that expectant management can be considered for those with TBA<40 µmol/L 
. A study by Glantz et al concluded that pregnancies in women with TBA>40 µmol/L had an increased fetal risk of preterm delivery, asphyxia events, meconium staining of amniotic fluid, and green-staining of placenta and membranes, while those with TBA between 10–39 µmol/L had minimal to no increased risk compared to women with pruritus but normal TBA, and that based on these findings the latter women could be managed expectantly, and possibly reduce the costs of medical care. 
It did not, however, provide the odds ratios for these direct comparisons, so the comparability of their results to ours is unclear. In our study, there were no statistically significant clinical or biochemical predictors associated with an increased risk of fetal complications. This may be in part due to differences in clinical practice, where we typically deliver patients with identified ICP at ~37 weeks gestational age, where as in the Glantz et al. study there were no specific instructions given to obstetricians on how to manage the pregnancies or timing of delivery. This may also explain the differences seen in fetal demise, as the majority of cases of IUFD occur late in gestation, usually after 36 weeks of gestation. In our study, only prior history of ICP showed significance, and this was an association with a decreased rate of fetal complication. A history of hepatic/biliary disease, although not statistically significant, may have an important association with increased fetal complications. Those with hepatic or biliary disease may be at increased risk for fetal complications. A maternal history of ICP in a previous pregnancy was estimated to decrease the risk of complication by 80%, suggesting an increase in awareness of ICP in the patient and provider, with possibly increased fetal monitoring, and earlier maternal obstetric care, which can decrease the chance of fetal complications. The mean gestational age in those with a history of ICP was 37 weeks (range 36–39), and the mean gestational age in those that did not have ICP in previous pregnancies was also 37 weeks (range 33–40). The proportion of deliveries with a gestational age greater than 37 weeks was 35% in those with a history of ICP and 26% in those without a history of ICP.
Current pharmacologic treatment includes the use of UDCA upon diagnosis of ICP. UDCA has been shown to have greater efficacy than other treatment modalities, including the use of S-adenosyl-L-methionine, dexamethasone, and cholestyramine, regarding maternal pruritus, and improving TBA and serum transaminases. In a randomized, double-blinded placebo controlled trial by Glantz et al., it was found that UDCA was more effective than dexamethasone in relieving pruritus, and improving serum biochemical markers of ICP, however there was no effect of UDCA or dexamethasone on fetal complication rates. 
In our study, there was no clinically significant effect of UDCA on fetal complications ().
TBA was categorized into four separate groups: normal or less than 10 µmol/L, 10–40 µmol/L, 40–100 µmol/L, and >100 µmol/L. When compared to the reference group of normal (<10), there was no increase in fetal complications in the TBA 10–40 group or TBA 40–100 group, suggesting that elevated TBA up to 100 may not be particularly useful in determining the risk of fetal complications. When TBA was greater than 100 µmoL/L, 60% had reported complications, for an OR 3.90 but with a wide confidence interval (95% CI 0.49, 30.76).
Our study had several limitations. In a retrospective study, it is difficult to control for missing data and uniformity of laboratory studies ordered within a cohort. The majority of the patients did have TBA, AST, and ALT sent. However, not all women were tested for other causes of potential liver disease. Total serum bile acids typically peak 30–90 minutes after meals, and there was no documentation of whether the TBA levels sent were fasting levels. Most likely, they were sent as part of routine laboratory testing done at the time of the clinic visit, or when the patient was admitted for delivery. The criteria for diagnosing ICP are also subjective, as there are no current uniform criteria for the diagnosis of ICP. Most studies use elevated serum bile acids or serum transaminase levels combined with pruritus during pregnancy; however, the serum bile acids may not necessarily be elevated at the time of a blood draw due to fasting versus non fasting state and there may be a greater rise towards the later weeks of pregnancy. In addition, the turnaround time for receiving the laboratory results may be 1–2 weeks, making it difficult to await the result when deciding on induction of labor to reduce potential fetal complications, specifically fetal demise.
In summary, in this cohort of ICP patients, 33% of the pregnancies resulted in perinatal complications, with respiratory distress being the most common complication. A history of liver and biliary disease and TBA greater than 100 may be clinically relevant, but our data were not conclusive. Our results suggest that it may be difficult to use maternal clinical and biochemical features to accurately predict fetal complications.