As discussed, some evidence supports that high serum bile acid levels may contribute to fetal death. Bile acids typically remain < 10 ILmol/L throughout normal pregnancy (Egan, 2012). Elevated levels have been associated with meconium passage and stillbirth. For example, in the prior study of 693 Swedish women, stillbirths were limited to women with bile acid levels >40 ILmollL (Glantz, 2004). More recent data indicate that adverse outcomes are associated with even higher bile acid levels. For instance, Brouwers and coworkers (2015) reported high rates of spontaneous preterm birth (19 percent), meconium-stained amnionic fluid (48 percent), and perinatal death (10 percent) with bile acids levels > 100 ILmollL despite active management leading to earlier delivery. Kawakita and colleagues (2015) found a similar stillbirth link. In particular, among 233 women followed with cholestasis of pregnancy, there were four stillbirths, all of which were among women with bile acid levels > 100 LmollL. Gao and associates (2014) implicated bile acids in cardiac dysfunction. Namely, in an exvivo preparation of cardiac myocytes, cholic acid lowered the beating rates in a dose-dependent manner, while increasing intracellular calcium levels. Intriguingly, studies have shown prolongations in the PR interval during fetal echocardiography among afected women (Rodriguez, 2016; Strehlow, 2010).
• Acute Fatty Liver of Pregnancy
The most frequent cause of acute liver failure during pregnancy is acute fatty liver-also called acute aty metamorphosis or acute yellow atrophy. It is characterized by accumulation of microvesicular fat that literally "crowds out" normal hepatocytic function (Fig.
Grossly, the liver is small, soft, yellow, and greasy. In its worst form, the incidence approximates 1 case in 10,000 pregnancies (Nelson, 2013). Fatty liver recurring in subsequent pregnancy is rare, but a few cases have been described (Usta, 1994).
Although much has been learned about this disorder, interpretation of conflicting data has led to incomplete but interesting observations. For example, some if not most cases of maternal fatty liver are associated with recessively inherited mitochondrial abnormalities of fatty acid oxidation. These are similar to those in children with Reye-like syndromes. Several mutations have been described for the mitochondrial trifunctional
FIGURE 55-1 Acute fatty liver of pregnancy. Cross section of the liver from a woman who died as the result of pulmonary aspiration and respiratory failure. The liver has a greasy yellow appearance, which was present throughout the entire specimen. Inset: Electron photomicrograph of one swollen hepatocyte containing numerous microvesicular fat droplets (*). The nuclei (N) remain centered within the cell, in contrast to the case with macrovesicular fat deposition. (Used with permission from Dr. Don Wheeler.) protein enzyme complex that catalyzes the last oxidative steps in the pathway. The most common are the G1528C and
E474Q mutations of the gene on chromosome 2 that codes for long-chain-3-hydroxyacyl-CoA-dehydrogenase-known as
LCHAD. here are other mutations for medium-chain acyl
CoA dehydrogenase-MCAD, as well as for carnitine palmito yltransferase 1 (CPT1) deficiency (Santos, 2007; Ylitalo, 2005).