Sudden fetal death in a patient with intrahepatic cholestasis of pregnancy complicated with gestational diabetes mellitus

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease unique to pregnancy, which is characterized by pruritus and abnormal liver function tests (LFTs). It occurs in the second half of pregnancy and resolves quickly after delivery. It is associated with an increased risk of spontaneous preterm delivery, fetal distress and sudden fetal death [1–3]. The cause of ICP and pathophysiology of the fetal complications still remains elusive. Its prevalence varies according to ethnicity and geography. ICP affects 4-10 % of pregnancies in China and the reported incidence of ICP in Chongqing area has risen from 0.32 % in 1986 to 6.0 % in 2004 [4]. This may be attributed to an increased alertness by obstetricians and a better access to bile acids measurement than before. However, in clinical practice, how to prevent fetal death in pregnant women with ICP is one of the biggest challenges to clinicians. A 23-year-old woman at 34 weeks’ gestation (WG), gravida 3 para 1, was transferred to our obstetric division at 22:48 on 1 February 2012 for preterm premature rupture of membranes (PPROM). The membranes had already ruptured for over 12 h, and ultrasonography performed in a clinic showed that the fetus was about 5 weeks smaller than gestational age, and fetal growth restriction (FGR) was under suspicion. Prenatal care was performed irregularly during pregnancy. At 30 WG, she was accidentally found to be hyperglycemic with plasma glucose level being 21 mmol/L for the first time. No treatment was initiated. 2 weeks later, she went to see an endocrinologist in a hospital in the city of Yibin in Sichuan province. Diagnosis of GDM was made, and insulin therapy was started since then. She had a prior obstetric history of one term stillbirth at home in 2008. The cause of stillbirth was unclear. In 2010, one spontaneous abortion occurred at 12 WG. Capillary blood glucose was 5.2 mmol/L on admission, and diagnosis of PPROM was confirmed by the test of insulinlike growth factor-binding protein-1. Fetal heart rate (FHR) monitoring was performed immediately after admission. However, the FHR had a baseline of 140 bpm with minimal variability and no acceleration (Fig. 1). Oxygen therapy was given for 30 min. At 03:00 am on 2 February 2012, no FHR was detected on the monitor. Intrauterine fetal death was subsequently confirmed by ultrasound examination. Laboratory results on admission showed abnormal LFTs, with hyperbilirubinemia (total bilirubin 66.2 lmol/L, direct bilirubin 57.5 lmol/L) but a normal level of transaminases (aspartate transaminase 29 UI/L, alanine transaminase 25 UI/L). The serum biochemical analysis obtained during hospitalization is shown in Table 1. A review of the detailed history revealed that the patient had severe skin itching all over the body 2 weeks prior to admission, particularly at night; however, pruritus was less in the recent 2 days. On examination, scratches were found on her trunk and extremities with no rash (Fig. 2). Abdominal ultrasonography was normal. Tests for viral and autoimmune hepatitis were negative. Maternal total bile acids (TBA) level at day 2 of hospitalization was 94.9 lmol/L. The diagnosis of severe ICP was therefore confirmed retrospectively by elevated levels of TBA. After informed consent, induction of labor was performed by J. Lu Department of Obstetrics and Gynecology, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China