Maternal Herpes Suppression Does Not Always Prevent Neonatal Transmission

Daniel M. Keller, PhD

October 27, 2010

October 27, 2010 (Vancouver, British Columbia) — A practice bulletin of the American Congress of Obstetricians and Gynecologists (ACOG; Obstet Gynecol. 2007 Jun;109(6):1489-1498) recommends offering antiviral drugs during the last 4 weeks of gestation for women who have a history of recurrent genital herpes — the idea being that the drugs will prevent transmission of the virus from mother to newborn. However, said Swetha Pinninti, MD, fellow in pediatric infectious diseases at the University of Alabama at Birmingham: "Maternal antiviral suppressive therapy during pregnancy does not prevent herpes disease in the newborn."

Reporting the results of her retrospective multicenter chart review study here at the Infectious Diseases Society of America 48th Annual Meeting, Dr. Pinninti noted that drugs such as acyclovir and valacyclovir taken during the last few weeks of pregnancy appear to reduce active lesions and the need for cesarean delivery, but even subclinical or asymptomatic infections are associated with cervical shedding of virus.

Dr. Pinninti said the use of herpes suppressive therapy is an "increasing practice," and her study involved 7 cases of infants infected with herpes whose mothers received therapy in the final few weeks of their pregnancies. None of the women had genital lesions during delivery, and most of them reported a remote history only of genital herpes.

A limitation of the study is that it looked only at infected newborns, not at all babies born to mothers who had received antiviral therapy. Therefore, it is not possible from this study to determine the risk for herpes transmission and neonatal infection among all babies whose mothers were on antiviral therapy. Nonetheless, the study does show that maternal antiviral suppressive therapy is not completely effective in eliminating transmission.

Of the 7 infants studied, 2 were delivered by cesarean section. Five had skin, eye, or mucous membrane disease; 1 had central nervous system disease; and 1 had disseminated disease. Disease onset was in the first week after delivery for 6 cases and at 27 days for 1 case.

Three mothers had genital disease 3 weeks before rupture of membranes, 1 had disease at 20 weeks' gestation and on postpartum day 2, 1 had herpes labialis 3 weeks before rupture of membranes, and 2 had no active disease. Antiviral therapy consisted of acyclovir or valacyclovir lasting from 3 days to 4 weeks. Six of the 7 mothers were treated for 1 week or longer.

Dr. Pinninti concluded, "It is very important for physicians involved in the care of neonates to continue to consider herpes as a cause of illness in a sick neonate born to a mother who received antiviral suppressive therapy during pregnancy, and appropriate evaluation and treatment should be initiated in a sick infant."

Richard Whitley, MD, president of the IDSA and director of the Division of Pediatric Infectious Diseases at the University of Alabama at Birmingham, emphasized that it is "exceedingly important" to recognize that obstetricians can get complacent about neonatal herpes simplex infection and to assume that putting a woman with known recurrent genital herpes on suppressive therapy will prevent disease in the newborn. "And that's exactly what it didn't do and what [Dr. Pinninti] has presented," he said.

When the ACOG recommendation appeared, a group of authors including Dr. Whitley wrote an editorial urging ACOG to rethink its recommendation on antiviral suppressive therapy, as it could change the spectrum of neonatal herpes, "and that's exactly what happened under these circumstances," he said. Because babies may clear drugs transmitted to them through the placenta more slowly than an adult would, they may present with herpes infection at 18 to 20 days of life, rather than at 7 to 12 days of life, and a pediatrician may not expect to see the disease so late, complicating the diagnosis.

Dr. Whitley also cited an article (N Engl J Med. 2004;350:11-20) showing that suppressive therapy in adults reduced the risk for heterosexual transmission of genital herpes by 75% but did not eliminate it. "And now we've just shown it with babies as well," he said.

He said the ACOG recommendation was made "with limited data in probably 5 studies that used antiviral drugs that showed decreased shedding...ergo decreased shedding would mean decreased transmission," which has been shown not to be universally true. Another problem, he said, is whether patients take their drugs.

Dr. Pinninti and Dr. Whitley have disclosed no relevant financial relationships.

Infectious Diseases Society of America 48th Annual Meeting: Abstract 570. Presented October 22, 2010.


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