A neonate with macrosomia, cardiomyopathy and hepatomegaly born to an HIV-infected mother

Abstract

Perinatal treatment with highly active antiretroviral drugs (HAART) is effective to prevent mother-to-childtransmission of HIV-1; however, adverse effects on the fetus may occur. We present a neonate with macrosomia, hypertrophic cardiomyopathy, and hepatomegaly, whose mother used HAART during pregnancy. The mother has been HIV infected since 1992. During her first pregnancy (1997) she used zidovudine and lamivudine; a healthy HIV-negative daughter was born. Good viral suppression and immune reconstitution was achieved with stavudine, didanosine and nelfinavir (Fig. 1). Severe lipodystrophy developed and from 1999 the viral load became detectable. In 2000 she was pregnant again; HAART was continued with a temporary switch in the 7th month, unsuccessful because of vomiting. Resistance testing showed mutations in the reverse transcriptase and protease gene leading to resistance to zidovudine and nelfinavir, respectively. At 40 weeks of gestation, decreased fetal movements and a non-reactive CTG necessitated an emergency caesarean section. An asphyctic girl was born. Macrosomia (birth weight 5290 g, >P97; length 57 cm, >P97; head circumference 37 cm, >P97) was present without dysmorphic signs. Physical examination revealed hepatomegaly and red skin lesions on the arms, back and armpits. A chest X-ray film demonstrated cardiomegaly, but no lung abnormalities. Echocardiography showed concentric hypertrophic cardiomyopathy. In the mother, normal values of glucose, HbA1c, insulin, and C-peptide excluded diabetes mellitus. Liver and kidney functions were normal and serology for syphilis, hepatitis A, B and C was negative. In the neonate, abnormal haematology, liver tests, clotting, and extreme hypoglycaemia were present (Table 1). Metabolic disorders were meticulously investigated in blood, urine, and CSF (Table 1). The plasma amino acid profile showed increased glutamine (1103 lmol/l) and decreased arginine levels (13 lmol/l) with a normal carnitine concentration (18.7 lmol/l) and high urinary lactate excretion. These biochemical abnormalities were ascribed to the coexistent asphyxia. Muscle biopsy did not show any biochemical or enzymatic abnormality compatible with a mitochondrial respiratory chain defect. Chromosomal karyotype was 46XX. All microbiological cultures of blood and secretions were negative. Serology and PCR tests excluded recent infection with Toxoplasma, enteroviruses, adenovirus, rubella, CMV and other herpes viruses. HIV-RNA was undetectable at day 5. Severe complications, including hypoglycaemia, intra-cerebral haemorrhages and seizures developed. The clinical condition worsened and the neonate died 7 days postnatally. At autopsy, the brain showed postnatally acquired ischaemic lesions and bilateral intraventricular haemorrhage. No microorganisms were found. The heart was enlarged with long-standing subendocardial ischaemia (weeks). No evidence was found for mitochondrial damage (intact cytochrome-c-oxidase components on histochemistry and electron microscopy). Hepatomegaly with extreme cholestasis compatible with long-standing drug-induced toxicity was found. There was subcutaneous fat necrosis in both armpits. A term infant with macrosomia, skin lesions, hepatomegaly and concentric hypertrophic cardiomegaly is described. These clinical findings could not be explained by asphyxia, chromosomal abnormality or any known M. H. Godfried Department of Internal Medicine, AMC, Amsterdam, The Netherlands