EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is the most common, reversible, and closely related to pregnancy condition characterized by elevated levels of bile acids (BAs) in blood serum and an increased risk of adverse perinatal outcomes. Due to the complex interactions between the mother and the fetus in metabolism and transplacental BAs transport, ICP is classified as a fetal-maternal disease. The disease is usually mild in pregnant women, but it can be fatal to the fetus, leading to numerous complications, including intrauterine death. The pathophysiology of the disease is based on inflammatory mechanisms caused by elevated BA levels. Although ICP cannot be completely prevented, its early diagnosis and prompt management significantly reduce the risk of fetal complications, the most serious of which is unexpected intrauterine death. It is worth emphasizing that all diagnostics and management of ICP during pregnancy are based on BA levels. Therefore, it is important to standardize the criteria for diagnosis, as well as recommendations for management depending on the level of BAs, which undoubtedly determines the impact on the fetus. The purpose of this review is to present the potential and importance of BAs in the detection and rules of medical procedure in ICP.

/pdf/bile-acids-in-intrahepatic-cholestasis-of-pregnancy-1si6j43u.pdf

Bile Acids in Intrahepatic Cholestasis of Pregnancy

To establish pregnancy‐specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations.

https://doi.org/10.22541/au.164450384.47740695/v1

Intrahepatic cholestasis of pregnancy – Time to redefine the reference range of total serum bile acids: A cross‐sectional study

Abstract Background The initial COVID‐19 pandemic response−related effects on conceptions following the use of assisted reproductive technologies (ART), and on changes in the maternal characteristics of women who conceived during the early vs. pre‐pandemic period, have been understudied. Objectives To examine the effects of ART clinic closures in the United States (US) in March 2020 on the frequency of ART‐conceived live births, multiple births and stillbirths; and to describe changes in the characteristics of women who conceived in the early pandemic period. Methods Population‐based cohort study including all births in the US from January 2015 to December 2020 (22,907,688 live births; 134,537 stillbirths). Interrupted time series (ITS) methodology was used to estimate rate ratios (RR) of expected versus observed rates in December 2020 (i.e., among births conceived mainly in March 2020). Demographic and clinical characteristics were compared between mothers who conceived in March 2020 versus March 2015–2019. Results Overall, 1.1% of live births and 1.7% of stillbirths were conceived by ART. ART‐conceived live births decreased by 57.0% in December 2020 (observed vs. expected RR 0.43, 95% confidence interval [CI] 0.40, 0.45), and these declines occurred in all subgroups of women. Multiple births also declined in December 2020. Stillbirth rates increased in December 2020 in ART‐conceived births (RR 2.55, 95% CI 1.63, 3.92) but remained unchanged in the non‐ART group. Maternal characteristics of women who conceived in the early pandemic versus pre‐pandemic period differed and included an increased prevalence of pre‐pregnancy obesity class 3 and chronic hypertension. Conclusions The early pandemic closure of ART clinics resulted in a substantial decline in ART‐conceived live births and multiple births in December 2020 and an increase in the proportion of stillbirths among ART‐conceived births. Women who conceived in the early pandemic period also had an increased prevalence of obesity and chronic hypertension.

Early coronavirus disease 2019 restrictive measures and changes in maternal characteristics, use of assisted reproductive technology, and stillbirth

Problem Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. Method of the study Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2, non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6–0.8 g/kg was given prior to conception and monthly during pregnancy until 16–20 weeks’ gestation. We compared IVIg treated patient's outcomes to a separate “natural history cohort”. This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. Results Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15–10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. Conclusion IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aji.13737

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss

Amniotic fluid volume assessment has become standard in the surveillance of fetal well-being, especially in high-risk pregnancies. Amniotic fluid disorders are a frequent and important topic in fetal and perinatal medicine. However, although important advances have been achieved, many important and challenging questions remain unanswered to date. An abnormally low amniotic fluid volume, referred to as oligohydramnios, has been traditionally considered a possible indicator of placental insufficiency or fetal compromise and is associated with an increased rate of obstetric interventions. An excess of amniotic fluid, referred to as polyhydramnios, may be secondary to fetal or maternal conditions and has been associated with a variety of adverse pregnancy outcomes, especially when it is severe. The ultrasonographic detection of an amniotic fluid disorder should prompt a proper workup to identify the underlying etiology. Data on the association of isolated oligohydramnios or idiopathic polyhydramnios with adverse obstetric and perinatal outcomes are conflicting. While the management of secondary oligohydramnios is usually guided by the underlying condition, the management of isolated oligohydramnios is poorly defined. Similarly, the management of idiopathic and secondary polyhydramnios is not yet standardized. There is an urgent need for randomized clinical trials to provide stronger recommendations on the management of these two common conditions.

/pdf/amniotic-fluid-disorders-from-prenatal-management-to-1b8sqr20.pdf

Amniotic Fluid Disorders: From Prenatal Management to Neonatal Outcomes

Correlation between first trimester placental growth factor levels and skin microvascular reactivity assessed by laser speckle contrast imaging - a cross-sectional study.

Diagnostic criteria for intrahepatic cholestasis of pregnancy: Should the timing of total bile acids measurement be established?

The familial pattern of spontaneous preterm birth: a case control study

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