Sims and coworkers (1995) observed that some homozygous LCHAD-deicient children with Reye-like syndromes had heterozygous mothers with fatty liver. This was also seen in women with a compound heterozygous fetus. Although some conclude that ony heterozygous LCHAD-deicient mothers are at risk when their fetus is homozygous, this is not always true (Baskin, 2010).
There is a controversial association between fatty acid 3-oxidation enzyme defects and severe preeclampsia-especially in women with HELLP syndrome (Chap. 40, p. 721). Most of these observations derive from retrospective study of mothers delivered of a child who later developed Reye-like syndrome. For example, one case-control study compared 50 mothers of children with a fatty-acid oxidation defect and 1250 mothers of matched control infants (Browning, 2006). During their pregnancy, 16 percent of mothers with an afected child developed liver problems compared with only 0.9 percent of control women. Problems included HELLP syndrome in 12 percent and fatty liver in 4 percent. Despite these indings, the clinical, biochemical, and histopathological findings are suiciently disparate to suggest that severe preeclampsia, with or without HELLP syndrome, and fatty liver are distinct syndromes (American College of Obstetricians and Gynecologists, 2015; Sibai, 2007).
Acute fatty liver almost always manifests late in pregnancy. Nelson and colleagues (2013) described 51 afected women at Parkland Hospital with a mean gestational age of 37 weeks (range 31.7 to 40.9). Almost 20 percent were delivered at 34 weeks' gestation or earlier. Of these 51 women, 41 percent were nulliparous, and two thirds carried a male fetus. From other data, 10 to 20 percent of cases are in women with a multifetal gestation (Fesenmeier, 2005; Vigil-De Gracia, 2011).
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Fatty liver has a clinical spectrum of severity. In the worst cases, symptoms usually develop over several days. Persistent nausea and vomiting are major complaints, and degrees of mal aise, anorexia, epigastric pain, and progressive jaundice vary.
Perhaps half of afected women have hypertension, protein uria, and edema, alone or in combination-signs suggestive of preeclampsia. As shown in Tables 55-1 and 55-2, degrees of moderate to severe liver dysfunction are manifest by hypofi brinogenemia, hypoalbuminemia, hypocholesterolemia, and prolonged clotting times. Serum bilirubin levels usually are < 10 mgl dL, and serum transaminase levels are modestly ele vated and usually < 1000 U/L.
In almost all severe cases, profound endothelial cell activation with capillary leakage causes hemoconcentration, acute kidney injury, ascites, and sometimes pulmonary permeability edema (Bernal, 2013). With severe hemoconcentration, uteroplacental perfusion is reduced and this, along with maternal acidosis, can cause fetal death even before presentation for care. Both maternal and fetal acidemia are associated with a high incidence of fetal jeopardy and a concordantly high cesarean delivery rate.