Viral infections during pregnancy: A guide for the emergency physician

FORUM pregnancy, complications; virus

Viral Infections During Pregnancy: A Guide for the Emergency Physician Emergency physicians are frequently called on to treat or advise pregnant patients. When faced with a pregnant patient who has clinical evidence of or exposure to a viral illness, the emergency physician must be aware of the potential maternal and fetal risks posed by various viral agents. This review provides current, accurate information and guidance for the pregnant patient. [Ellis GL, Melton J, Filkins K: Viral infections during pregnancy: A guide for the e m e r g e n c y physician. A n n Emerg M e d July 1990;19:802-811.] INTRODUCTION Emergency physicians frequently see patients with viral illnesses. They also are often called on to treat pregnant patients. Not uncommonly, these two patient groups overlap, and the emergency physician must treat the pregnant patient who has contracted or has been exposed to a viral illness. In general, viral infections cause problems for the pregnant patient in three ways. First, the pregnant patient may suffer a more severe infection than a nonpregnant adult. Second, the fetus may be infected in utero with a subsequent chronic infection and birth defects. Third, the fetus may acquire infection in the perinatal period and develop a more severe infection than other newborns because of the lack of maternal antibody protection. ]-a While many of the common viral illnesses pose little or no risk to the mother and fetus, others may cause significant morbidity and mortality. It is essential that the emergency physician be well informed as to the potential risks posed by the various viral agents so that he can reassure, refer, or institute therapy appropriately.

George L Ellis, MD, FACEP* Pittsburgh, Pennsylvania James Melton, MDt Lakeland, Florida Karen Filkins, MDt Pittsbu[gh, Pennsylvania From the Departments of Emergency Medicine,* and Medical Genetics and Obstetrics/Gynecology,¢ Western Pennsylvania Hospital, Pittsburgh; and the Department of Emergency Medicine, Lakeland Regional Medical Center, Lakeland, Florida.t Received for publication June 27, 1989. Revision received December 18, 1989. Accepted for publication January 30, 1990. Address for reprints: George L Ellis, MD, 4800 Friendship Avenue, Pittsburgh, Pennsylvania 15224.

H U M A N IMMUNE DEFICIENCY VIRUS H u m a n immune deficiency virus (HIV) is the etiologic agent in acquired immunodeficiency syndrome (AIDS). It is a retrovirus (RNA virus) that can incorporate into the host genome and preferentially infect T4 cells (helper lymphocytes), macrophages, and cells of the central nervous system. HIV can cause progressive debilitation of the immune system; when patients develop opportunistic infections, neoplasias such as Kaposi's sarcoma (which are unusual in patients with intact immune systems), dementia, or wasting syndrome, the diagnosis of AIDS is applied. Although HIV has been isolated from various body fluids, including vaginal fluid, saliva, tears, and breast milk, 4 the usual modes of transmission involve blood (as is the case with IV drug abusers who share needles, hemophiliacs who receive Factor VIII concentrates, and patients who receive blood transfusions from donors infected with HW) and sexual contact with HIV-positive partners. Perinata] transmission of HIV is well documented and accounts for more than 75% of pediatric AIDS cases. 4

Maternal Risk In pregnancy, there is a physiologic immune suppression with a decrease in T4 lymphocytes and a decrease in cell-mediated immune responsiveness. Concerns have been raised that this immune suppression of pregnancy may be additive or synergistic with the immune deficiencies associated with HIV infection. Follow-up studies of women who were identified

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as infected with HIV because they delivered children w h o developed AIDS have reported a high incidence in these w o m e n of progression to clinical illness.S, 6 However, the patients in these studies may represent a subgroup that was prone to both perinatal transmission to the fetus and development of clinical illness. Large studies comparing HIV-infected pregnant w o m e n with matched HIV-infected n o n p r e g n a n t w o m e n are needed before the question of accelerated disease progression during pregnancy can be answered. Pregnancy m a y m a s k the symptoms and delay the diagnosis of HIV infection because m a n y of the early s y m p t o m s of HIV such as fatigue, weight loss, and anemia may be dismissed as normal during pregnancy. Pregnancy m a y also necessitate modifications in the treatment of certain opportunistic infections.

Fetal Risk Attempts to define the rate of perinatal HIV transmission have been hampered by the persistence of passively acquired maternal antibody for as long as 15 months in the neonate. Specific tests for neonatal infection, such as IgM and viral antigen, have not demonstrated sufficient accuracy to be useful indicators. Recent prospective studies, however, have shown relatively uniform results with a transmission rate of 20% to 50%. 7 The prognosis for infected children is extremely poor. A constellation of congenital abnormalities has been described in association with intrauterine HIV infection and includes growth failure, microcephaly, and craniofacial abnorm a l i t i e s s u c h as h y p e r t e l o r i s m , prominent boxlike forehead, flat nasal bridge, long palpebral fissures with blue sclerae, mild upward or d o w n w a r d o b l i q u i t y of the eyes, short nose with flattened columella, p r o m i n e n t p h i l t r u m , or p a t u l o u s lips. s

Management Pregnant patients with known HIV infection or at high risk for developi n g s u c h i n f e c t i o n s h o u l d be promptly referred for adequate counseling as to the maternal and fetal risks outlined above. In those who are at high risk but not found to be seropositive, the modes of transmission and means of prevention should 114/803

obviously be stressed. If the HW-infected patient decides to continue her pregnancy, she should be referred to appropriate psychosocial support services to help handle the tremendous psychologic stress. Because HIV is sexually transmitt e d , t h e s e p a t i e n t s s h o u l d be screened for other sexually transmitted diseases such as chlamydia trachomatis and hepatitis B as well as syphilis and gonorrhea. Because cytomegalovirus and toxoplasma infections are relatively common in H/Vinfected patients and m a y result in congenital infection and fetal anomalies, baseline antibody titers should be o b t a i n e d to aid in d i a g n o s i s should the p a t i e n t develop symptoms suggestive of such infection during her pregnancy. Mycobacterium tuberculosis infection should also be ruled out. z Throughout the pregnancy, the clinician m u s t pay close attention to nonspecific s y m p t o m s such as fatigue, anorexia, and weight loss that are common in early pregnancy but that m a y represent disease progression in the setting of HIV infection. T r e a t m e n t of o p p o r t u n i s t i c infections should be undertaken in consultation with an infectious disease specialist. In cases of life-threatening o p p o r t u n i s t i c i n f e c t i o n s , s u c h as Pneumocystis carinii p n e u m o n i a , standard treatment is generally undertaken because the inherent risks of the disease to the mother far outweigh the risks to the fetus posed by such therapy. Modifications of standard treatment m a y be appropriate, however, with less lethal opportunistic infections. Available i n f o r m a t i o n does not suggest decreased transmission of infection to infants delivered by cesarean section; therefore, the usual obstetric criteria should be used in determining the mode of delivery. In vaginal delivery, however, direct contact between the infected vaginal secretions and the fetal blood (as might occur with placement of scalp electrodes or fetal scalp sampling) should be avoided if possible. 9 Although the risk of HIV transmission by breastfeeding is unknown, there has been one such case reported, m and HIVinfected mothers should be advised against breast-feeding.~ Obviously, in the postpartum period, the patient should be referred to a physician familiar with the management of HIV Annals of Emergency Medicine

infections for c o n t i n u i n g m e d i c a l surveillance and care. Because many HIV-infected w o m e n m a y remain a s y m p t o m a t i c and undiagnosed throughout pregn a n c y , it is r e c o m m e n d e d t h a t health-care providers observe universal precautions while caring for patients in labor and delivery. The use of water-resistant gowns and gloves during delivery, gloves while handling the neonate as long as any maternal secretions remain, frequent hand-washing, and p r o t e c t i v e eye covers in situations with the potential for conjunctival contact are recommended. The use of mouth-operated suction devices for clearing secretions from the neonatal airway IDeLee suction devices) poses a theoretical risk to the operator; wall or bulb suction should be used if possible, and when mouth suction cannot be avoided, a trap should be placed in the line. 9

RUBELLA Epidemiology Rubella (German measles) is usually a mild illness characterized by fever, arthralgias, erythematous rash, and p o s t a u r i c u l a r or s u b o c c i p i t a l lymphadenopathy. The rash typically begins on the face and develops 16 to 18 days after exposure. It is spread by droplets or direct contact with infected persons. Before vaccination became available in 1969, rubella occurred in sixto n i n e - y e a r cycles. 12 Vaccination programs in the United States have concentrated on young children as they enter school and have dramatically decreased the incidence of disease. Most adults of child-bearing age reached the age for immunization before 1969; as a result, a pool of susceptible adults still exists. Recently, vaccination programs aimed at the young adult population have been developed to address this problem. During the next 20 to 30 years, the incidence of rubella in the United States is expected to fall to very low levels. Because the rubella vaccine is a live attenuated virus vaccine, there is the theoretical risk of the virus crossing the placenta and causing congenital rubella syndrome. The Centers for Disease Control has received reports of more than 1,100 women who received live attenuated rubella vaccine within three months before or three m o n t h s after their presumed 19:7 July 1990

dates of conception and for whom no cases of congenital rubella syndrome were found. Nevertheless, pregnancy is considered a contraindication to rubella vaccination; if such vaccinat i o n s h o u l d i n a d v e r t e n t l y occur, however, this is not considered a reason to interrupt the pregnancy.

Maternal Risk The pregnant patient who is infected with rubella will generally have a mild illness and is at no greater risk of c o m p l i c a t i o n t h a n the general adult population.

munoglobulin (20 mL IM), although evidence of efficacy is lacking. While i m m u n o g l o b u l i n given after exposure m a y alter symptoms, it prevents neither infection nor viremia, and children with congenital defects have been born to mothers who received immunoglobulin in a timely fashion. H e m a g g l u t i n a t i o n inhibition antibody testing should be repeated in four weeks. A fourfold rise in titers is p r e s u m p t i v e evidence of infection, and the patient should be referred for counseling.14A 7 CYTOMEGALOVIRUS

Fetal Risk

Epidemiology

If fetal infection occurs during the period of organogenesis, one or more organ systems may be involved, and a chronic infection usually occurs. 13 This is in marked contrast to the brief, mild infection that occurs postnatally. Typically, the congenital rubella syndrome involves the ocular system (eg, cataracts, glaucoma), the central nervous system (eg, mental retardation, microcephaly, hearing loss), and cardiac system (eg, patent ductus arteriosus). 14-2° Spontaneous abortion, stillbirth, low birth weight, and prematurity may result. The overall risk of developing congenital rubella syndrome when primary maternal infection occurs during the first trimester of pregnancy is quoted as 20% to 25%. This varies, however, from approximately 50% when the infection occurs during the first month to 10% by the 16th week and is quite rare after the 20th week. Additional subtle defects (eg, diabetes) have been detected in infants appearing normal at birth when they were followed for several years. 17-21

C y t o m e g a l o v i r u s (CMV) is endemic throughout the world and m a y be the m o s t c o m m o n congenitally acquired viral infection. From 1% to 2% of all newborns have been found to be infected at birth, 23-2s and approximately 5% of all pregnant patients shed the virus sometime during pregnancy. 26 CMV infection is u s u a l l y subclinical, w i t h approximately 10% presenting with a mononucleosislike illness. It causes serious illness only in fetuses, i m m u nodeficient individuals, and patients receiving immunosuppressive therapy. In developed countries, the highest rate of seroconversion occurs between the ages of 15 and 35 years, whereas in u n d e r d e v e l o p e d countries, the infection is generally acquired in early childhood. Infection does not confer lifelong immunity, and recurrences and reinfections can

Management Unfortunately, once a pregnant patient develops rubella, little can be done. In this situation, the patient should be advised of the risk and referred to her obstetrician or family physician for more definitive counseling and consideration of therapeutic abortion. 14,17,22 For those susceptible patients who have been exposed to rubella but have not developed the disease, blood should be obtained for h e m a g g l u t i n a t i o n i n h i b i t i o n antibody testing. Elevated levels indicate previous immunity, and the mother should be reassured. If the levels are low, some recommend standard ira19:7 July 1990

The cerebral calcifications are characteristically periventricular in the subependymal region and are a useful feature in diagnosis. Long-term follow-up studies have d e m o n s t r a t e d progressive sensorineural hearing loss, l o w e r e d IQ, and b e h a v i o r a l problems in infected children who w e r e a s y m p t o m a t i c at birth. 27-29 CMV has been isolated from the cervix of as many as 30% of pregnant patients.3O, 31 Cervical infection has not been shown to cause congenital infection but does result in significant perinatal infection. Perinatal infection transmitted from the mother rarely causes significant problems, 28 but CMV from other sources (eg, blood transfusion in neonatal ICU) may cause mortality. 27

Management CMV infection is rarely diagnosed during pregnancy because it is usually asymptomatic. However, if a primary CMV infection is documented during the first 20 weeks of pregnancy, the patient should be referred for counseling and consideration of therapeutic abortion. Several antibody tests are available; however, because approximately 50% of adults have antibody, a single positive test is not sufficient to indicate recent infection. D e m o n s t r a t i o n of seroconversion is the best way to document primary infection. IgM-specific antibody detected in the serum implies infection within the previous 60 days but is not a widely available test. 32,33

OCCUr.

Maternal Risk The pregnant patient does not appear to be at increased risk of morbidity or mortality, although recurrences of disease are more frequent during pregnancy. 14

Fetal Risk In u t e r o infection during the first two trimesters has clearly been associated with congenital infection and birth defects. The spectrum of illness is quite broad, ranging from asympt o m a t i c infection at birth {90% to 95%) to cytomegalic inclusion disease (CID). In severely affected neonates, the clinical features of CID include hepatosplenomegaly, jaundice, thrombocytopenia with petechial rash, microcephaly, deafness, chorioretinitis, optic atrophy, mental retardation, and cerebral calcifications.

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HERPES SIMPLEX VIRUSES Epidemiology Herpes simplex virus types 1 and 2 (HSV 1 and HSV 2) are among the most widely distributed viruses on earth. HSV 1 is usually associated with oropharyngeal and ocular disease, whereas HSV 2 is usually associated with genital disease (although either type may cause symptoms in either location). Infection does not confer immunity, and reactivation of latent disease occurs often.

Maternal Risk HSVs generally cause self-limited disease in healthy adults. Pregnancy is associated with an increased frequency of recurrence but not with increased mortality. 14

Fetal Risk

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to cause the greatest risk early in pregnancy and near term. Maternal infection early in pregnancy is associated with an increased risk of central nervous system malformation and abortion. 34-36 Primary maternal infection near term is associated with a significant risk of perinatal infection, which often results in morbidity and mortality. Recurrent HSV infections also pose the risk of perinatal infections, which are usually symptomatic and can be divided into three presentations: disseminated disease (eg, hepatitis, pneumonitis, disseminated intravascular coagulation, with or without central nervous s y s t e m involvement), central nervous system involvement alone, and disease localized to the skin, mouth, or eyes. Acyelovir has reduced the mortality associated with perinatal HSV infection, but morbidity is still high.34,37,3s

HEPATITIS There are three agents that cause viral hepatitis: hepatitis A, hepatitis B, and non-A, non-B hepatitis. Hepatitis A is transmitted by the fecaloral route. Hepatitis B and non-A, non-B hepatitis are transmitted by intimate personal contact, transfusion, and sharing of needles in the setting of IV drug abuse. There are antigen/antibody markers for hepatitis A and hepatitis B, but there is now no marker for uon-A,non-B hepatitis. In patients with hepatitis B, it seems likely that the presence of the antigen signifies high infectivity and greater risk of transmitting hepatitis B virus.

Maternal Risk Mortality from any type of hepatitis is no greater in the pregnant than in the uonpregnant patient.

Fetal Risk Management P r e g n a n t p a t i e n t s w h o develop HSV infectious can be reassured that congenital defects are quite rare. However, measures to prevent perinatal infection are very important. Until recently, cultures were recommended weekly beginning at 34 to 36 weeks for patients with a history of or exposure to genital HSV infection; if positive the week before labor, cesarean section was considered. This policy had little impact on the incidence of neonatal HSV infection. It has been found that there is little correlation between these anteparturn cultures obtained from asymptomatic patients and cultures done at the time of delivery. 31 Also, it has been f o u n d that the m a j o r i t y of w o m e n who deliver infants with neonatal HSV infection have no history of HSV infection and no lesions at the time of delivery and thus would not have been cultured anyway. 32 The current r e c o m m e n d a t i o n is that patients who have visible lesions at term and are in labor or who have ruptured membranes should undergo cesarean delivery, 32 whereas in those without visible lesions, vaginal delivery should be permitted. In patients with active HSV infections and premature rupture of membranes remote from term, the risk of extreme immaturity must be weighed against the risk of neonatal HSV infection.a2 116/805

T h e i n c i d e n c e of s p o n t a n e o u s abortion during the first trimester in patients with acute viral hepatitis and of preterm labor when hepatitis occurs during the third trimester is reportedly increased. The increased incidences, however, are probably no greater w i t h h e p a t i t i s than with other febrile illnesses occurring at these times. There is no convincing evidence that any type of hepatitis is associated with fetal malformation, even though transplacental transmission of the virus has been established. 39-46 Maternal-infant transmission of hepatitis can occur transplacentally, during delivery, or postpartum (including by breast milk). Hepatitis A is not associated with a significant risk of perinatal infection unless the mother is infected at the time of delivery. 47-49 Chronic hepatitis B infection and acute infection during the first two trimesters are associated with a low rate of vertical transmission to the newborn. Acute maternal hepatitis B infection in the third trimester is associated with a high risk of perinatal transmission. The presence of the e antigen marks a group that is particularly likely to transmit infection to their offspring. Little is known about non-A, non-B hepatitis, but there appears to be a significant risk of perinatal infection if the mother is infected during the third trimester. 4z M o s t i n f e c t e d n e w b o r n s are asymptomatic; infection can be diagAnnals of Emergency Medicine

nosed by demonstrating the presence of hepatitis B surface antigen in the blood. These infants will usually have mild-to-moderate elevation of serum transaminase levels, and liver biopsy will reveal histologic evidence of unresolved hepatitis, s°-s3

Management Pregnant women exposed to hepatitis A infection should be given imm u n e serum globulin at a dose of 0.02 to 0.05 mL/kg for short-duration exposure and 0.06 to 0.14 mL/kg for prolonged exposure to modify the disease. Pregnant women exposed to hepatitis B virus should be given hepatitis B immune globulin (HBIG) at a dose of 0.05 to 0.07 mL/kg within a seven-clay period after exposure. A second dose is given 30 days after the first. Infants born to mothers with hepatitis A do not require therapy unless the mother develops hepatitis A within two weeks of birth. Under these circumstances, the immune ser u m globulin (0.5 mL) should be given. 54 Infants born to mothers who have acute hepatitis B during pregnancy or who are e antigen positive at term should be given HBIG at birth at a dose of 0.5 mL. This is repeated at three m o n t h s and at six months. I m m u n i z a t i o n with hepatitis B vaccine should also be started to provide protection against chronic exposure to hepatitis B virus. There are no vaccination recommendations available regarding cases of non-A, non-B hepatitis.

VARICELLA-ZOSTER Epidemiology Varicella-zoster often affects children in the 2- to 8-year-old age group. Epidemics occur sporadically without periodicity. The incubation period of varicella ranges from ten to 20 days. In adults, fever and general malaise precede the characteristic rash by several days; in children, fever and rash occur simultaneously. Most of the adult p o p u l a t i o n has a c h i e v e d i m m u n i t y before childbearing age, including 80% of those without a known history of varicella.

Maternal Risk Varicella is accompanied by a significantly higher risk of morbidity and mortality in adults as compared with the risk in children. Most of the increased mortality is secondary to the increased incidence of varicella 19:7 July 1990

pneumonia. 5s-6o Studies in the 1950s and 1960s indicated that varicella p n e u m o n i a is more c o m m o n and more often fatal in pregnant patients than in other adults.61, 62 However, the current consensus is that varicella p n e u m o n i a is neither more c o m m o n nor more serious in pregnant patients than in other adults. The fatality rate has been in the 10% to 30% range for adults who develop varicella pneumonia, ss-s9 With recent i m p r o v e m e n t s in respiratory care and the use of acyclovir, the mortality is now probably less than 10%.

Fetal Risk Maternal infection during the first trimester may produce a congenital varicella syndrome consisting of hypoplastic limbs, rudimentary digits, ocular abnormalities (eg, optic atrophy, micro-ophthalmia, cataracts), cerebral cortical atrophy and mental retardation, low birth weight, and cutaneous scars. The incidence of this syndrome is too low to allow accurate qum~titation of risk, but the risk is believed to be small. 63 65 If maternal varicella infection occurs four days or less before delivery, the child may develop congenital varicella infection with a mortality rate as high as 30%. 5s-57 The high mortality is a result of the lack of m a t e r n a l antibody f o r m a t i o n and transplacental transfer in the first four or five days of infection. 66 After five days, maternal antibodies result in either mild varicella or no apparent infection in the newborn.

Management Varicella-zoster i m m u n o g l o b u l i n (VZIG) is now available through the American Red Cross to provide passive i m m u n i z a t i o n to susceptible p r e g n a n t w o m e n and p r o t e c t the fetus during the viremia when given within 72 hours of exposure to chickenpox. It may modify the disease if given within five days after exposure, but it has not been shown to prevent b i r t h defects.SS,SS, 67 A n o t h e r approach would be to check varicella antibody titers before giving VZIG because 80% of patients without a k n o w n history of varicella will be found to be immune. 6s However, the results must be rapidly available if this approach is to be practical. Follow-up with the family physician or o b s t e t r i c i a n will be n e c e s s a r y to 19:7 July 1990

watch for development of varicella and to counsel the patient. In the pregnant patient presenting with clinical evidence of varicella infection, the e m e r g e n c y p h y s i c i a n must rule out the possibility of varicella p n e u m o n i a . Rare complica tions of varicella infection include encephalitis, meningitis, myocarditis, glomerulonephritis, and arthritis. The patient with evidence of varicella pneumonia should be adm i t t e d to the hospital, and those w i t h o u t current evidence of pneumonia should be cautioned to contact their physician should any sign of pulmonary involvement occur. If labor occurs within four days of maternal infection, the mother should receive VZIG before delivery and the child should receive VZIG soon after delivery. If maternal infection developed more than four days before delivery, therapy is not required for mother or child.55,58,6z

Zoster Infection Because herpes zoster represents the reactivation of latent varicella zoster virus, maternal antibodies are present in normal healthy women. Zoster therefore poses no threat to the fetus or neonate.

MEASLES Measles (rubeola) is an acute viral exanthem most often affecting children between 2 and 6 years old. It is characterized by fever, coryza, conjunctivitis, cough, generalized maculopapular rash, and pathognomonic Koplik's spots in the oral cavity. It is spread mainly by respiratory droplets, and its incubation time is between ten and 14 days. Before the introduction of the attenuated rubeola vaccine, epidemics occurred in twoto three-year cycles. Vaccination of school-age children has resulted in dramatic declines in the incidence of m e a s l e s . A p p r o x i m a t e l y 10% of adults from rural areas and those immunized with the killed vaccine of the early 1960s may be susceptible to the disease. In 1988, there were 3,386 cases reported in the United States. O t i t i s media and bacterial pneumonia are the most common complications, but encephalitis, myocarditis, and thrombocytopenia purpura may also occur.

Maternal Risk It is unclear whether pregnant paAnnals of Emergency Medicine

tients are at greater risk for serious morbidity and mortality than nonpregnant adults. Most of the available information was published more than 30 years ago, but it indicates that the pregnant patient may be at slightly greater risk of p n e u m o n i a and heart failure than the nonpregnant patient with measles.

Fetal Risk It appears that prematurity is more common in pregnancies complicated by measles. The risk of spontaneous abortion and congenital defects is less clear. No common constellation of abnormalities has been found; if an increased risk of congenital defects does exist, it is small. Infection with measles (transmitted transplacentally in the antenatal period) becomes clinically apparent during the first ten days of life and is associated with a mortality as high as 33%. Insufficient data are available to determine whether transplacental transfer of maternal antibodies m a y d i m i n i s h the m o r t a l i t y rate from congenital measles.55, 69-71

Management Because there is little experience with measles in pregnancy, recommendations for management are difficult. Passive i m m u n i z a t i o n with immune serum globulin can prevent or modify the disease. 7° When faced with a pregnant patient exposed to measles, immune serum globulin can be given, but no evidence is available on the protective effect this m a y have on the fetus. In the pregnant patient who develops measles in the a n t e p a r t u m period, t h e m o t h e r s h o u l d be g i v e n i m m u n e s e r u m globulin before birth and the infant s h o u l d be given i m m u n e s e r u m globulin after birth at a dose of 0.25 mL/kg. Obviously, the newborn should be observed for development of measles. 55

MUMPS Epidemiology Mumps is worldwide in distribution and is most common in the 5- to 15-year-old age group. It is an acute generalized infection with a predilection for the parotid and salivary glands. The usual incubation period is 14 to 18 days, and it is transmitted by saliva and droplet contamination. Since the introduction of the live attenuated mumps vaccine, the num808/117

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ber of cases reported has decreased dramatically.

the pregnant patient than in nonpregnant adults.

Maternal Risk

Fetal Risk

The m o r b i d i t y and m o r t a l i t y of mumps is no greater in the pregnant patient than in the nonpregnant patient. Mumps generally follows a benign course.55, 72

Infection w i t h i n the first three months of pregnancy has been shown to increase the risk of spontaneous abortion, p r e m a t u r i t y , and intrauterine growth retardation. 77 There is no clear evidence that Epstein-Barr virus causes congenital malformation. 78

Fetal Risk Mumps has been linked to a twofold increase in the s p o n t a n e o u s abortion rate when the infection occurs in the first trimester. 4s No significant association has been found w i t h l o w b i r t h w e i g h t or prematurity. 46 While there are data from studies in animals suggesting that mumps may cause congenital abnormalities, ss there is no c o n v i n c i n g h u m a n evidence of teratogenic potential. A link between mumps infection and endocardial fibroelastosis has been suggested based on a high proportion of children with this diagnosis having positive m u m p s skin tests; subsequent studies have not confirmed this association. 73-75 R e s o l u t i o n of the c o n t r o v e r s y must await further data, which will be slow in coming due to the low incidence of m u m p s in pregnancy. Congenital mumps acquired in the antenatal period has rarely been reported and does not appear to pose a major risk to the neonate.SS, s7

Management The treatment of mumps is symptomatic with analgesics, bedrest, and application of cold or heat to the parotids. The patient should be reassured that the risk of congenital abnormality is small. MONONUCLEOSIS

Epidemiology The Epstein-Barr virus is worldwide in distribution and endemic to most urban areas. In underdeveloped countries, young children are primarily infected, but the disease is usually subclinically manifested. In developed nations, it is usually young adults who are infected, and the disease is more often clinically apparent. T h e r e is no v a c c i n e at this time.76

Maternal Risk Mononucleosis is rarely fatal and does not appear to be more severe in 118/807

Management The diagnosis m a y be confirmed serologically. The patient can be reassured and referred to her obstetrician or family physician for followup. INFLUENZA

Epidemiology Influenza is an epidemic disease caused by myxoviruses. There are three antigenically different influenza viruses: types A, B, and C. Influenza A is responsible for most epidemics and is associated with more severe disease. Epidemics are associated with major antigenic changes that occur at ten- to 30-year intervals. The incubation period for influenza is one to four days, and it presents clinically with abrupt onset of respiratory infection, fever, malaise, myalgias, and headache.

Maternal Risk The major risk to the mother is the development of pneumonia. During the 1918 and 1957 pandemics, maternal mortality rates were significantly higher than mortality rates in lionpregnant women. While it is not clear that pregnant women are more likely to develop influenzal infection or that they are more likely to have pneumonia complicate this disease, it does appear that if influenzal pneumonia develops in pregnancy, it is a more severe disease than in the nonpregnant patient. Maternal mortality may result from secondary bacterial infection (such as Staphylococcus aureus, S pneumoniae, or Klebsiella) but also may result from primary influenzal pneumonia without bacterial superinfection.

Fetal Risk There have been reports of an increased incidence of neural tube defects and of cardiac anomalies in infants born to mothers with a history Annals of Emergency Medicine

of influenza during pregnancy. These studies, however, did not use serologic Confirmation of influenza infection. Other studies have shown no increase in fetal abnormalities. While the data are conflicting, it can be said that the vast majority of pregnant women who contract influenza during pregnancy have normal outcomes and that there is little risk of congenital anomalies, intrauterine growth retardation, prematurity, or stillbirth.79-ss

Management Uncomplicated cases can be managed w i t h bed rest, f l u i d s , and acetaminophen for fever control. The physician must be alert for the develo p m e n t of pneumonia. Pneumonia complicating influenza requires hospitalization and broad-spectrum antibiotic coverage for bacterial superinfection. While amantadine can prevent s y m p t o m s and s h o r t e n the clinical course, it has been associated with teratogenic effects in animals and is not recommended to be used during pregnancy. During epidemics, it is advisable to vaccinate pregnant women; the influenza vaccines are killed virus preparations and therefore safe during pregnancy.

PARVOVIRUS Epidemiology Human parvovirus B19 was discovered in 1975. Subsequently, it has been found to cause erythema infectiosum, fetal demise, acute polyarthralgia syndrome, and aplastic crisis in patients with underlying hem o l y t i c anemias. E r y t h e m a infeetiosum (fifth disease) is a relatively benign disease that occurs in epidemics with four- to seven-year cycles. The highest attack rate occurs in 5- to 9-year-olds, followed by the 10- to 14-year-old age group. The classic rash of erythema infectiosum consists of a "slapped cheek" appearance; the rash sometimes progresses to involve the extremities with a reticular lacy rash. Children sometimes have headache and fever, but it is unusual to have joint pain in children. In adults, parvovirus B19 causes an acute polyarthralgia syndrome with involvement of the hands, wrists, and k n e e s b e i n g m o s t c o m m o n . There is a strong female predominance, and involvement is typically symmetrical. Less than half of adults 19:7 July 1990

FIGURE. Hot lines. Arizona Arizona Teratogen Information Service, Arizona Health Science Center, Tucson. (800) 626-6016 (in Arizona) or (602) 795-5675. California California Teratogen Registry, University of California, San Diego. (800) 532-3749 (in California) or (619) 294-3984. Colorado Teratology Service/Genetics Unit, University of Colorado Health Science Center, Denver. (303) 861-6395. Connecticut Connecticut Pregnancy Exposure Information Service, University of Connecticut Health Center, Farmington. (800) 325-5391 (in Connecticut) or (203) 679-2676. Florida Teratogen Information Service/Genetics Division, University of Florida, Gainesville. (904) 392-4104. Teratology Service/Genetics Division, University of Miami School of Medicine, Coral Gables. (305) 547-6006. Illinois Teratogen Helpline/Genetics Department, Michael Reese Hospital and Medical Center, Chicago. (312) 791-4451. Iowa Teratogen Information Service/Pediatric Genetics Division, UniveF sity of Iowa, Iowa City. (319) 356-2674. Massachusetts Teratogen Information Service, Pregnancy and Environmental Hotline, National Birth Defects Center, Kennedy Memorial Hospital, Brighton. (800) 322-5014 (in Massachusetts) or (617) 787-4957. Missouri Obstetrics/Gynecology, Genetics Dept, Washington University School of Medicine, St Louis. (314) 454-7700. Nebraska Nebraska Teratogen Project, University of Nebraska Medical Center, Omaha. (800) 642-6274 (in Nebraska) or (402) 559-5070. New Jersey Teratology Information Network/Pediatrics Department, University of Medicine and Dentistry of New Jersey, Camden. (609) 757-7869. New York Genetics and Teratogen Hotline/Obstetrics and Gynecology, New York State Health Science Center, Brooklyn. (718) 270-2072. Prenatal Information Hotline, Suffolk County Dept of Health Services, Happauge. (516) 348-2708. Pennsylvania Pregnancy Safety Hotline, Western Pennsylvania Hospital, Pittsburgh. (412) 687-SAFE. Pregnancy Healthline/Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia. (215) 829-KIDS. Department of Reproductive Genetics, Magee-Womens Hospital, Pittsburgh. (412) 647-4168. Texas Texas Teratogen Service, Genetic Screening and Counseling SeF vice, Texas Dept of Mental Health and Mental Retardation, Denton. (8t7) 383-3561. Utah Pregnancy Riskiine, University of Utah Medical Center, Salt Lake City. (800) 822-BABY (in Utah), (800) 521-2229 (in Montana), or (801) 583-2229. Vermont Vermont Teratogen Information Network, Genetics Dept, University of Vermont, Burlington. (800) 531-9800 (in Vermont) or (802) 658-4310. Washington Washington State Poison Control Network, University of Washington, Seattle. (800) 732-6985 (in Washington) or (206) 526-2121 (in Alaska and rest of continental US). Wisconsin Wisconsin Teratogen Project/Genetics, University of Wisconsin, Madison. (800) 362-3020 (in Wisconsin) or (608) 263-1991. Teratology Information Project, Birth Defects Center, Children's Hospital, Milwaukee. (414) 931-4172. Ontario Motherisk, Division of Pharmacology, Hospital for Sick Children, Toronto. (416) 598-5781. Quebec Pregnancy Healthline/Medical Genetics, Children's Hospital, Montreal. (514) 934-4427.

19:7 JuLy1990

Annals of Emergency Medicine

develop a rash. The joint symptoms are self-limited and usually disappear within two weeks, although symptoms lasted four years in one patient. The pathogenesis of the arthritis is unclear. Parvovirus B19 has also been found to cause aplastic crisis in patients with hemolytic anemias, particularly those w i t h sickle cell disease. It causes cessation of erythropoiesis by direct viral cytopathic effect on the erythroid precursor cells. Recently, it has also been shown to cause severe anemia in patients with impaired immune response, s9

Maternal Risk To date, there is no evidence of increased morbidity or mortality in the pregnant patient.

Fetal Risk From studies available, it appears that the risk of fetal death after maternal parvovirus infection is approximately 30% to 40% and that the fetus is at risk at any gestational age. The pathogenetic sequence is likely to be a maternal infection leading to an aplastic crisis in the fetus; this is followed by congestive heart failure, h y d r o p s fetalis, and fetal death. There is no current evidence of other congenital abnormalities, and the o u t c o m e after maternal infection seems to be an all-or-nothing phenomenon resulting in either hydrops fetalis and fetal death or a normal birth.9O-96

Management If a pregnant patient presents with exposure to or symptoms consistent with parvovirus infection, she can be tested for IgG and IgM antibodies. The presence of IgG antibodies and absence of IgM antibodies indicates distant infection and, therefore, immunity, whereas the presence of IgM antibodies indicates recent infection and risk to the fetus. In those pregnancies that are complicated by maternal parvovirus infection, serial measurement of maternal a-fetoprotein seems to serve as an indicator of fetal i n v o l v e m e n t . In those cases with confirmed maternal parvovirus infection or elevated c~-fetoprotein levels, serial ultrasound can be used to detect hydrops fetalis, thereby 808/119

VIRAL INFECTIONS Ellis, Melton & Filkins

confirming fetal i n v o l v e m e n t and predicting fetal demise. The possible use of intrauterine blood transfusion for the treatment of the aplastic crisis and prevention of hydrops fetalis and fetal death is being investigated. O T H E R VIRUSES The enteroviruses consist of three major groups: polioviruses, coxsackieviruses, and echoviruses. It has been demonstrated that poliovirus infections during pregnancy can result in spontaneous abortion, low birth weight, stillbirth, and neonatal poliomyelitis. There is no evidence that polioviruses are capable of causing congenital malformations, however, and the majority of pregnant women with clinically apparent poliomyelitis will deliver normal fullterm infants. The coxsackieviruses are divided into two groups: A and B. Coxsackieviruses A rarely cause perinatal illness. However, coxsackieviruses B have been shown to cross the plac e n t a . V a r i o u s t y p e s of c o x sackieviruses B and coxsackievirus A-9 have been found to cause congenital malformation of the cardiovascular, urogenital, and digestive systems. There is no evidence of an increase in spontaneous abortion or preterm birth. N e o n a t a l infection with coxsackievirus can result in myocarditis and central nervous system manifestations. Echovirus infection during pregnancy has not been found to cause spontaneous abortion, premature delivery, or congenital malformations. Neonatally acquired infections may result in a syndrome comprised of fever, splenomegaly, lymphadenopathy, diarrhea, vomiting, rashes, pncumonitis, otitis media, and septic meningitis; these infections may be severe and life threatening. Adenoviruses and respiratory syncytial viruses do not result in viremia and are not believed to represent a risk to the fetus. 79 SUMMARY While some viral infections, such as rubella, are diminishing in importance because of aggressive vaccination programs, the effects of other viruses on fetal development and outcome are just now becoming known. When faced with a female patient of child-bearing age who presents with 120/809

symptoms of or exposure to a viral infection posing fetal or maternal risk, the emergency physician must consider the possibility of coincident or unsuspected pregnancy and question the patient regarding this possibility. The emergency physician can serve as a valuable source of information and, in some circumstances, of preventive therapy to the pregnant p a t i e n t if t h e i m p o r t a n c e o f v i r a l i n f e c t i o n s d u r i n g p r e g n a n c y is c o n s i d ered. There are telephone hot lines available throughout the United States to help both physicians and patients when questions arise. These h o t l i n e s (Figure) c a n b e h e l p f u l i n a wide range of instances, including infectious disease exposures, occupational exposures, and environmental exposures.

REFERENCES 1. Remington J8, Klein JO (eds): Infectious Dis eases of the Fetus a~d Newborn Infant. Philadelphia, WB Saunders, 1983. 2. Krugman 8, Gershon AA (eds): Infections of the Fetus and Newborz~. New York, AR Liss, 1975. 3. Krugman S, Katz SL, Gershon AA, et al: In fectious Diseases of Children. St Louis, CV Mosby, 1985. 4. Weber A, Alger LS: HIV in women and their pregnancies. Md Med ] 1988~37:717-724. 5. Minkoff H, Nanda D, Menez R, et al: Pregnancies resulting in infants with acquired imm u n o d e f i c i e n c y s y n d r o m e or AIDS-related complex: Follow-up of mothers, children, and subsequently born siblings. Obstet Gynecol 1987;69:288-291. 6. Scott GB, Fischl MA, Klimas N, et al: Mothers of infants with the acquired i m m u nodeficiency s y n d r o m e : Evidence for both symptomatic and asymptomatic carriers. JAMA 1985;253:363-366. 7. Minkoff H: Care of pregnant women infected with h u m a n immunodeficiency virus. JAMA 1987;258:2714-2717. 8. Marion RW, Wiznia AA, Hutcheon G, et al: H u m a n T-cell l y m p h o t r o p i c v i r u s type IlI (HTLV-III) e m b r y o p a t h y . A m J Dis C h i l d 1986; 140; 638 -640. 9: American College of Obstetricians and Gynecologists (ACOG}: Hurrlan I m m u n e Deftciency Virus Infections (ACOG Tech Bull 123). Washington, DC, ACOG, 1988. 10. Ziegler JB, Cooper DA, Johnson RO, et al: Postnatal transmission of AIDS - Associated retrovirus from mother to infant. Lancet 1985; 1:896-899. 11. Peckham CS, Senturia YD, Ades AE: Obstetric and perinatal consequences of h u m a n immu~ nodeficiency virus (HIV) infection: A review. Br f Obstet Gynaecol 1987;94:403-407. 12. Witte JJ, Karchmer AW, Hermann KL, et al: The Epidemiology of Rubella. Atlanta, Georgia, N a t i o n a l C o m m u n i c a b l e D i s e a s e Center,

Annals of Emergency Medicine

Health Services and Mental Health Administration, 1969. 13. Alford CA, Neva FA, Weller TH: Virologic and serologic studies on h u m a n products of conception after maternal rubella. N Engl J Med 1964;271:1275-1281. 14. Taina E, Hanninen P, Gronroos M: Viral infections in pregnancy. Acta Obstet Gynecol Scand 1985;64:167-173. 15. Greenberg M, Pelliteri O, Barton J: Frequency of defect in infants whose mothers have rubella during pregnancy. JAMA 1957;165: 675-678. 16. Pitt DB, Kerr EH: Results of rubella during pregnancy. Med ] Aust 1965;2:647-651. 17. Krugman S, Katz SL, Gershon AA, et al: Rubella, in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p 307-319. 18. Alford CA, Griffiths PD: Rubella, in Remington J8, Klein JO (eds): Infectdous Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 69-103. 19. Peckham GS: Clinical and laboratory study of children exposed in utero to maternal rubella. Arch Dis Child 1972;47:571-577. 20. Sheridan MD: Final report of a prospective study of children whose mothers had rubella in early pregnancy. Br Med J 1964;2:536-539. 21. Centers For Disease Control: Rubella and congenital rubella - U n i t e d States 1983. MMWR 1984;33:237-242. 22. Carlstrom G: Viral infections and birth defects. Acta Obstet Gynecol Scand 1977;(suppl 67):21-31. 23. Stagno S, Reynolds DW, Huang ES, et al: Congenital cytomegalovirus infection: Occurrence in an immune population. N Engl f Med 1977;296:1254-1258. 24. Birnbamn G, Lynch JI, Margileth AM, et aI: Cytomegalovirus infections in newborn infants. J Pediatr 1969;75:789-795. 25. Starr JG, Bart RD, Gold E: Inapparent congenital cytomegalovirus infection: Clinical and epidemiologic characteristics in early infancy. N Engl f Med 1970;282:1075-1078. 26. Hanshaw JB, Shultz FW, Melish MM, et al: Congenital cytomegalovirus infection, in [ntrauterine Infections. Ciba Foundation Symposium 10. A m s t e r d a m , Associated Scientific Pubfishers, 1973, p 22-23. 27. Krugman 8, Katz SL, Gershon AA, et al: Cytomegalovirus infections, in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p 8-21. 28. Hanshaw JB: Cytomegalovirus, in Remington JS, Klein JO [eds): Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 104-142. 29. Stagno S, Reynolds DW, Pass RF, et al: Congenital cytomegalovirus infection: Consecutive occurrence with similar antigenic viruses. Pediattics 1977;59:669-678. 30. Alexander ER: Maternal and neonatal infection with cytomegalovirus in Taiwan. Ped Res 1967;1:210-211. 31. Diosi P, Babascera L, Nevinglovschi O, et al: Cytomegalovirus infection associated with pregnancy. Lancet 1967;2:1063-1066. 32. Griffiths PD, 8tagno S, Pass RF, et al: Infection with cytomegalovirus during pregnancy: Specific IgM antibodies as a marker of recent

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p r i m a r y infection. J Infect Dis 1982;145: 647-653. 33. Griffiths PD, Stagno S, Pass RF, et al: Congenital cytomegalovirus infection: Diagnostic and prognostic significance of detection of specific IgM antibodies in cord serum. Pediatrics 1982;69:544-549.

51. Schweitzer IL, Wing A, McPeak C, et al: Hepatitis and hepatitis associated antigen in 56 m o t h e r - i n f a n t pairs, lAMA 1972;220:10921095.

perinatal mortality among mothers exposed to measles during pregnancy. Lancet 1988;1: 516-519.

52. Cossart YE: Acquisition of hepatitis B antigen in the newborn period. Postgrad Med J 1974;50:334-337.

72. Krugman S, Katz SL, Gershon AA, et al: Mumps {Epidemic parotitis), in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p 192-201.

53. Merrill DA, DuBois RS, Kohler PF: Neonatal onset of hepatitis-associated antigen carrier state. N Engl J Med 1972;287:1280-1282.

73. Noren GR, Adams P, Anderson RL: Positive skin reactivity to mumps virus antigen in endocardial fibroelastosis. J Pediatr 1963;62:604-606.

54. Stevens CE, Krugman S, Szmtmess W, et ah Viral hepatitis in pregnancy: Problems for the clinician dealing with the infant. Pediatr Rev 1980;2:121-125.

74. St Geme JW, Noren GR, Adams P: Proposed embryopathic relation between mumps virus and primary endocardial fibroelastosis. N Engl J Med 1966;275:339-347.

36. South MA, Tompkins WAF, Mornas CR, et ah Congenital malformations of the central ner~ vous system associated with type 2 herpes virus. J Pediatr 1969;75:13d8.

55. Young NA, Gershon AA: Chickenpox, measles, and mumps, in Remington JS, Klein JO {eds}: Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 375-427.

75. Vosburgh JB, Diehl AM, Liu C, et al: Relationship of mumps to endocardial fibroelastosis. A m J Dis Child 1965;109:69-73.

37. Krugman S, Katz S'L, Gershon AA, et al: Herpes virus infections, in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p 139-148.

56. Krugman S, Katz SL, Gershon AA, et al: Varicella-zoster infections, in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p 433-453.

38. Stagno S, Whitley RJ: Herpes virus infections of pregnancy: II. Herpes simplex virus and Varicella-zoster virus infections. N Engl J Med 1985;313:1327-1330.

57. Weller TH: Varicella and herpes zoster: Changing concepts of the natural history, control, and importance of a not-so-benign virus. N Engl J Med 1983;309:1434-1440.

39. Arvin AM, Hensleigh PA, Prober CG, et al: Failure of antepartum maternal cultures to predict the infant's risk of exposure to herpes sim plex virus at delivery. N Engl J Med 1986; 315: 796-800.

58. Enders G: Varicella-zoster infections in pregnancy. Prog Med Virol 1984;29:166-196.

34. Nahmias AJ: Herpes simplex, in Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 636-687. 35. Florman A, Gershon AA, Blackett PR, et al: Intrauterine infection with herpes simplex virus: Resultant congenital malformations. JAMA 1973;225:129-132.

40. American College of Obstetricians and Gynecologists (ACOG): Perinatal Herpes Simplex Virus Infections (ACOG Tech Bull 122). Washington, DC, ACOG, 1988. 41. Report of the Committee of Infectious Diseases, American Academy of Pediatrics, Evanston, Illinois, 1982. 42. Crumpacker CS: Hepatitis, in Remington JS, Klein JO (eds}: hffectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 591-618. 43. Krugman S, Katz SL, Gershon AA, et al: Viral hepatitis, in hffectious Diseases of Children. St Louis, CV Mosby, 1985, p 103-138. 44. Siegel M: Congenital malformations following chickenpox, measles, mumps, and hepatitis. JAMA 1973;226:1521-1524. 45. Siegel M, Fuerst HT, Peress NS: Comparative fetal mortality in maternal virus diseases: A prospective study of rubella, measles, mumps~ chickenpox, an d hepatitis. N Engl J Med 1966;274: 768-771. 46. Siegel M, Fuerst HT: Low birth weight and maternal virus infection: A prospective study of rubella, measles, mumps, chickenpox, and hepatatis. JAMA 1966;197:88-92. 47. Tong MJ, T h u r s b y M, Rakela J, et al: Studies in the maternal-infant transmission of the viruses which cause acute hepatitis. Gastroenterology 1981;80:999-1004. 48. Schwer M, Moosa A: Effects of hepatitis A and B in pregnancy on mother and fetus. S Aft Med J 1978;54:1092-1095. 49. Heiber JP, Dalton D, Shorey J, et al: Hepatitis and pregnancy. J Pediatr 1977;91:545-549. 50. 8chweitzer IL, Moseley JW, Ashcavai M, et al: Factors influencing neonatal infection by hepatitis B virus. Gastroenterology 1973;65: 227-283.

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59. Plotkin SA: Clinical and pathogenetic aspects of varicella-zoster. Postgrad Med J 1985;61(suppl 4):7-14. 60. Landsberger EJ, Kayer WD, Grossman JH: Successful management of varicella pneumonia complicating pregnancy: A report of three cases. J Reprod Med 1986;31:3ll-314.

76. Krugman S, Katz SL, Gershon AA, et ah Epstein-Barr virus infections, in Infectious Diseases of Children. St Louis, CV Mosby, 1985, p

58-70. 77. Icart J, Didier J: Infections due to EpsteinBarr v i r u s during pregnancy. J Infect Dis 1981;143:499-500. 78. Yeager AS: Viruses uncommonly associated with infections of the fetus or newborn infant, in Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, 1983, p 544-554. 79. Sweet RL, Gibbs RS: Perinatal infections, in Infectious Disease of the Female Genital Tract. Baltimore, Maryland, williams and Wilkins, 1985, p 181-226. 80. Coffey VP, Jessop WJE: Maternal influenza and congenital deformities. Lancet 1959;2: 935-938.

61. Mendelow DA, Lewis GC: Varicella pneum o n i a during pregnancy. O b s t e t Gynecol 1969;33:98-99.

81. Doll R, Hill AB: Asian influenza in pregnancy and congenital defects. Br J Prey Soc Med 1960;14:167-172.

62. Harris RE, Rhoades ER: Varicella pneumonia complicating pregnancy: Report of a case and a review of the literature. Obstet Gynecol 1965;25:734-740.

82. Hakosalo J, Saxen L: Influenza epidemic and congenital defects. Lancet 1971;2:1346.-1347.

63. Akalay A, Pomerance JJ, Rimoin DL: Fetal varicella syndrome. J Pediatr 1982;111:320-323. 64. Asha Bai PV, John TJ: Congenital skin ulcers following varicella in later pregnancy. J Pediatr 1979;94:65-67. 65. Fox MJ, Krumpiegel ER, Teresi JL: Maternal measles, mumps and chickenpox as a cause of congenital anomalies. Lancet 1948;1:746. 66. Brunell PA: Placental transfer of varicellazoster antibody. Pediatr 1966;38:1034-1038.

83. Record RG: Anencephalus in Scotland. Br J Prey Soc Med 1961;15:93-105. 84. Leck I: Incidence of malformations following influenza epidemics. Br J Prey Soc Med 1963;17:70-80. 85. Wilson ML, Stein AM: Teratogenic effects of Asian influenza. JAMA 1969;210:336-337. 86. Hardy JMB, Azarowicz EN, Mannini A, et al: The effect of Asian influenza on the outcome of pregnancy, Baltimore 1957 - 1958. A m J Public Health 1961;51:1182-1188.

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70. Christensen PE, Schmidt H, Bang HO, et al: An epidemic of measles in southern Greenland, 1951: Measles in virgin soil: II. The epidemic proper. Acta Med Scand 1953;144:431-440. 71. Aaby P, Bakh J, Lisse IM, et al: Increased

Annals of Emergency Medicine

90. Brown T, Anand A, Ritchie LD, et al: Intrauterine parvovirus infection associated with hy drops fetalis. Lancet 1984;2:1033-1034. 91. Knott PD, Welply GA, Anderson MJ: Se n rologicalty proved intrauterine infection with parvovirus. Br Med J 1984;289:1660.

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92. Carrington D, Gilmore DH, Whittle MJ, et al: Maternal serum alpha-fetoprotein - A marker of fetal aplastic crisis during intrauterine h u m a n parvovirus infection. Lancet 1987;1:433-435. 93. Woernle CH, Anderson LJ, Tattersall P, et

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al: Human parvovirus B19 infection during pregnancy. ] Infect Dis 1987;156:17-20.

95. Weiland HT, Vermey-Keers C, Salimans MM, et at: Parvovims B19 associated with fetal abnormality. Lancet 1987;1:682-683.

94. Mortimer PP, Cohen BJ, Buckley MM, et al: Human parvovirus and the fetus. Lancet 1985; 2:1012.

96. Anand A, Gray ES, Brown T, et al: Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 1987;316:183-186.

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19:7 July 1990