Combined treatment with immunoglobulin and valaciclovir in pregnant women with cytomegalovirus infection and high risk of symptomatic fetal disease

Abstract

Introduction

Congenital cytomegalovirus (CMV) infection is one of the most common during pregnancy. The infection, particularly in the first trimester, is associated with important sequelae in up to half of the children. Valaciclovir and immunoglobulin have been tested separately for the treatment of fetal CMV infection with relative success. Nevertheless, there is no experience with the simultaneous use of both therapies.

Methods

combination therapy (oral valaciclovir 2 g/6h until the end of pregnancy and intravenous hyperimmune gamma globulin 200 UI/kg) was offered to pregnant women with CMV infection acquired during pregnancy and viral load (VL) in amniotic fluid above 10⁵ copies/ml and/or brain injuries in the ultrasonography. Additional immunoglobulin monthly doses were used in case of ultrasonography or MRI evidence of persistent fetal involvement. Neurological and hearing evaluations of infants were performed at birth and every 3 months during follow-up.

Results

15 pregnant women were enrolled: primary infection, 14, non-primary infection, 1; first trimester, 11, second trimester, 4. Mean gestational age at the start of combination treatment were 23.2 weeks and 29.3 weeks, depending on the infection being diagnosed in the first or the second trimester, respectively. Median VL of CMV-DNA in amniotic fluid was 62.5 × 10⁵ copies/ml. Intrauterine progression of fetal brain lesions was only observed in two cases in which the dose of CMV-HIG was repeated, slowing their progression. Although the treatment has failed to reverse ultrasound fetal lesions, only 3 children were born with hearing impairment and their psychomotor development was consistent with chronological age in all patients but one. Combination therapy was not associated with adverse effects in either the mothers or the fetuses.

Conclusion

Combination therapy with immunoglobulin and valaciclovir may be a useful alternative in CMV fetal infection, particularly if changes in cerebral echography or high VL in the amniotic fluid are present.

Keywords:

• Congenital cytomegalovirus infection
• cytomegalovirus-specific immunoglobulins
• valaciclovir
• combination therapy
• fetal therapy
• fetal and placental pathology

Acknowledgements

The authors wish to acknowledge all health professionals involved in the cases described.

Disclosure statement

No potential conflict of interest was reported by the author(s).