Varicella Pneumonia Complicating Pregnancy: A Report of Seven Cases

Background: Pneumonia is the most common complication of varicella-zoster infection in adults and has potentially devastating effects when complicating pregnancy. Due to the significant morbidity and mortality associated with this complication during pregnancy and the small number of reported cases in the literature, we present this report to help educate physicians who care for pregnant women. Cases: Seven patients are presented in this report. These patients presented at various stages in pregnancy, from 17 to 31 weeks of gestation. Three of the patients had unremarkable hospital courses. Three of the patients had hospital stays over 21 days in duration. One patient died from complications of varicella pneumonia after 31 days of hospitalization. The obstetric outcomes of the 7 patients described include 1 non-viable delivery at 20 weeks gestation, 3 term deliveries, 2 preterm deliveries, and 1 patient who has not yet delivered. All of the patients presented were treated with intravenous acyclovir therapy. Of the patients described, 3 required intubation and ventilatory support. Other complications encountered include disseminated intravascular coagulation (DIC), adult respiratory distress syndrome (ARDS), metabolic encephalopathy, pneumothorax, superimposed bacterial pneumonia, and sepsis. Conclusion: The course and treatment of varicella pneumonia complicating pregnancy are discussed. Current recommendations regarding the use of varicella-zoster immune globulin (VZIG) are also reviewed.

varicella-zoster infection in adults is associated with higher morbidity and mortality. The most common complication of varicella infection in adults is pneumonia. Approximately 16% of adults with varicella infection will demonstrate evidence of pulmonary involvement, e Although the incidence of varicella pneumonia does not appear to be increased in pregnancy, it is well established that the morbidity and mortality from this infection in pregnancy are higher. Mortality from varicella pneumonia complicating pregnancy is reported to be as high as 41%. 3 In our institution over the past 5 years, we have observed 7 cases of varicella pneumonia complicating pregnancy, which we now present with a discussion of the pertinent literature.   with diffuse pneumonitis or ARDS (Fig. 2). She was started on 100% oxygen by non-rebreather mask, acyclovir, and erythromycin. Within  and was started on broad spectrum antibiotics. She was delivered of a normal female infant by primary low transverse cesarean section secondary to nonreassuring fetal assessment by non-stress test, biophysical profile, and contraction stress test. The infant had Apgar scores of 2 and 5 at and 5 min, respectively, and a weight of 2,015 g. Her condition slowly improved, and she was extubated on postoperative day 9 and discharged from the hospital on postoperative day 12.
Case 5 L.F. was a 32-year-old white female gravida 5, para 3, who presented at 27 5/7 weeks gestation with a 1-week history of dyspnea cough productive of green sputum. She related a 1-day history of a vesicular rash present on her trunk and face. She had recent exposure to varicella infection. The patient's past medical history was significant for asthma, chronic bronchitis, and insulin-requiring gestational diabetes mellitus. She denied any tobacco use. Initial physical examination revealed a temperature of 38.1C, mild tachycardia, tachypnca, weight of 175.5 kg, mild respiratory distress, diffuse wheezing throughout both lung fields, and vesicular lesions scattered over her face, neck, and trunk. Chest X-ray revealed a diffuse interstitial process bibasilarly consistent with varicella pneumonia. Initial obstetric ultrasound revealed a viable singleton fetus with decreased amniotic fluid volume, but no apparent fetal anomalies. Varicella antibody studies, comprehensive viral studies, sputum culture, and acid-fast bacilli (AFB) studies were all negative. The patient was admitted and started on ceftriaxone, acyclovir, oral clarithromycin, subcutaneous heparin, and intravenous aminophylline. Her hospital course was unremarkable except for the development of thrombocytopenia, which was attributed to her viral syndrome after pregnancy-induced hypertension was excluded. At 32 weeks gestation, she was delivered by low vertical cesarean section secondary to decreased fetal movement, a positive contraction stress test, severe oligohydramnios, and the inability to effectively monitor the patient due to obesity. She was delivered of a normal male infant weighing 1,097 g, with Apgar scores of 5 and 9 at and 5 min, respectively.
The patient had an uncomplicated postpartum course. L.B. was a 18-year-old white primigravid female with an intrauterine pregnancy at 23 weeks gestation who presented with a history of chest congestion, vesicular skin rash, fever, productive cough, and progressively worsening shortness of breath.
Her past medical history was unremarkable with the exception of exposure to varicella-zoster infection 2 weeks prior to the onset of her symptoms and tobacco use. Initial physical examination revealed a temperature of 37.6C, tachycardia, mild tachypnea, and diffuse vesicular rash present on the face, trunk, extremities, abdomen, and back. Auscultation of the lungs revealed only fair air exchange with few bibasilar rales. Initial chest X-ray revealed bilateral patchy nodular infiltrates consistent with varicella pneumonia. An obstetric ultrasound revealed a viable female fetus with no evidence of fetal anomalies. The patient was admitted with a diagnosis of varicella pneumonia. She received acyclovir, oxygen (2 by nasal cannula), VZIG, aerosol treatments, and cefazolin for a concomitant urinary tract infection. The patient recovered without complications. All viral, bacterial, and mycoplasma cultures were reported as negative.
The patient returned at term to have an uncomplicated spontaneous vaginal delivery of a normal female infant weighing 3,033 g.

DISCUSSION
Varicella, which is caused by a DNA virus, is usually a highly contagious benign childhood disease.
In adults the illness is less common but usually more severe. Because varicella infection is highly contagious, it is estimated that only 5% of reproductive age women lack IgG antibody. 4 Only 2% of reported cases occur after the age of 20 years, but 25% of deaths from varicella are in this age group, s

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 343
The most common complication is varicella pneumonitis, occurring in 14-50% of adults with a mortality rate of 3-11%.6,7 The incidence of varicella infection in pregnancy is 1-7/10,000 pregnancies. 1,s Varicella infection is considered to be more severe in pregnancy, 9 with a mortality from varicella pneumonia estimated to be as high as 44% in pregnant women compared to 11% in non-pregnant women. 3,4,6 The mortality from varicella-zoster pneumonia is highest if infection occurs in the third trimester. This increased risk of fatality is postulated to be secondary to advancing immmunosuppression during later pregnancy though this has never been proved, z,l In the cases presented, all women had infection in the second and third trimesters, with the only maternal death occuring in the early second trimester.
Fetal complications of varicella-zoster infection in pregnancy include premature delivery, fetal varicelia syndrome, congenital zoster of infancy, and neonatal varicella. 3,1-14 Fetal varicella syndrome occurs when a fetus is exposed to varicella infection in the first trimester of pregnancy and is characterized by low birth weight, cutaneous scars, hypotrophic limbs, ocular abnormalities including chorioretinitis, cataracts, microphthalmia, and Horner's syndrome, brain damage, and mental retardation. 7,9 The exact incidence of this complication is unknown but has been estimated as 3-6% by prospective studies. 8,11,1e Neonatal varicella is most common and severe when maternal infection occurs within 4 days of delivery or 48 h following delivery. 7,9 This increased severity related to time of delivery is thought to be secondary to a lack of passive immunity from maternal antibodies. 9 Neonatal varicella infection is associated with complications including pneumonia, hepatitis, thrombocytopenia, arthritis, conjunctivitis, carditis, and nephritis, and is estimated to have a case fatality rate of 30-50%. 7,9 None of the neonates presented developed any evidence of varicella infection or fetal varicella syndrome.
Acyclovir is a nucleoside analogue that inhibits replication of herpes virus DNA synthesis. Is Acyclovir is a category C medication and therefore should not be used in pregnancy unless the potential therapeutic benefits outweigh the potential risks to the fetus. 6 Acyclovir does cross the placenta and is found in amniotic fluid and fetal tissue, though no teratogenic effects have been ob-served in 241 pregnant women exposed over 6 years experience with this agent. 6 The first use of intravenous acyclovir in pregnancy for treatment of varicella pneumonia was reported in 1986.17 Prior to the use of acyclovir for varicella pneumonia in pregnancy, the mortality was 36-41%.3,4 A significant reduction in mortality to 13% has been reported since the advent of acyclovir therapy in the treatment of varicella pneumonia. 4 The exact dosages reported in studies have varied from 5 to 30 mg/kg. 17-zz. The dose usually recommended by infectious disease experts for treating disseminated varicella-zoster infections in immunocompromised patients is 10-15 mg/kg given 3 times daily for 7 days. z-z6 It should be noted that the one maternal death in our case series involved a patient who had initially received a low dose of acyclovir (6.5 mg/kg later increased to 10 mg/kg), though whether this contributed to her death is unclear.
VZIG is a product which contains varicellazoster immunoglobulin G and is derived from the plasma of normal volunteer blood donors with high titers of the antibody, s,z7 VZIG has been available in the United States since 1978 and is commonly used successfully to treat infants exposed to varicella infection. It is also indicated in immunocompromised individuals and pregnant patients with no known history of infection and an unknown antibody status when exposed to varicella infection, s VZIG should be administered within 96 h of exposure to varicella to be effective, z7 When VZIG (adult dose 625 units intramuscularly) is administered to exposed adults, it has been shown to prevent or attenuate the course of infection, zT'e8 but it has not been shown to prevent congenital or neonatal varicella, s Varicella vaccine (Varivax) is a live attenuated vaccine which became available in the United States in 1995. e9 The recommended dosage of this vaccine is two intramuscular injections of 0.5 ml given 4-8 weeks apart, e9 In adults, two doses of vaccine are required to achieve a seroconversion rate of greater than 90%. 3 It has been proposed that limitations in adult helper T-cell response to varicella-zoster virus antigens are responsible for this observation. 3 The persistence of antibodies 10 years after vaccination is 95% in healthy children and 75% in adults. z Side effects from the vaccination occur in 5-10% of those vaccinated and usually consists of a mild rash. z Routine use of this vac-344 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY cine will hopefully reduce the number of susceptible women entering pregnancy thereby decreasing the number of congenital/neonatal infections and the risk of significant morbidity and mortality associated with primary varicella infection in pregnancy. None of the patients presented in this report received the varicella vaccine.
In conclusion, primary maternal varicella-zoster infection in pregnancy is associated with significant morbidity and mortality as demonstrated by the cases presented in this report. Given the potential severity of this disease in pregnancy, routine antenatal screening for varicella antibodies and postpartum immunization similar to that of current rubella immunization practices should be considered.
Theoretically, this practice would lower the risks of congenital varicella syndrome, neonatal herpes zoster, neonatal varicella infection, and maternal morbidity and mortality by decreasing the number of primary infections during pregnancy. The cost effectiveness of such an immunization progr.am will need to be researched, but as evident from our case studies, the consequences of varicella-zoster infection in pregnancy can be devastating. The financial burden of caring for women with serious varicella infection in pregnancy also needs to be considered when evaluating the cost effectiveness and benefit of a routine screening and vaccination program.