Serologic and virologic evidence for frequent intrauterine transmission of human parvovirus B19 with a primary maternal infection during pregnancy.

OBJECTIVE: To define the intrauterine viral transmission rate during primary maternal parvovirus B19 infection and identify factors that may influence this rate. METHODS: Forty-three pregnant women at two medical centers were identified with a primary B19 infection and followed to delivery. At delivery maternal and infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR testing. RESULTS: All of the women delivered healthy infants at term and none was hydropic. Overall 22 (51%) of the 43 infants had some evidence of a congenital B19 infection. B19-specific IgM was detected in 11 infants at delivery, B19 IgA was detected in 10 and B19 DNA was detectable by PCR in 11 infants. One infant was negative at birth but became positive for IgM, IgA and PCR at 6 weeks of age. No association was found between the likelihood of intrauterine infection and: maternal age; symptomatic maternal infection; method of delivery; maternal IgG titer at delivery; maternal IgG avidity at delivery; or maternal viremia at delivery. Intrauterine infection was associated with maternal IgM positivity at delivery; this association may have been a result of maternal infection occurring later in gestation. CONCLUSION: Although the incidence of intrauterine hydrops and fetal demise after maternal infection is low, there is a high rate of intrauterine viral infection that occurs throughout gestation and yields newborns who, although infected in utero, are asymptomatic at birth.

Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms.

OBJECTIVE: To assess the risk of maternal parvovirus B19 infection from exposure to various sources and the fetal morbidity of those infections. METHODS: We obtained demographic and occupational information about pregnant women exposed to sources of B19 and about the nature and duration of the exposures. We performed serologic testing 10-14 days after exposure using an indirect capture enzyme-linked immunosorbent assay. Women with immunoglobulin (Ig) M were examined with weekly ultrasound until 12 weeks after exposure, and the outcome of the pregnancy was ascertained from interviews with patients and their obstetricians. Logistic regression analysis was used to determine risk factors for maternal immunity and infection by B19. RESULTS: Of 618 pregnant women exposed, 307 (49.7%) were immune to B19, 259 remained susceptible after exposure, and 52 (16.7% of all susceptibles) contracted B19 infection. None of the 52 fetuses of infected women developed nonimmune hydrops, and there were no fetal deaths attributable to B19 in this group. The relative risk of maternal B19 infection was 2.8 if the source was a related child living in the household (95% confidence interval 1.7, 4.6; P < .001). No significant differences were found for maternal B19 infection in eight categories of maternal occupation. Maternal symptoms of polyarthralgia (46%), fever (19%), and nonspecific rash (38%) were significantly more common (P < .001) in IgM-positive patients than in noninfected women (4.1%, 2.8%, and 5.7%, respectively). Only 17 (33%) of the IgM-positive women were entirely asymptomatic. CONCLUSION: The risk of maternal B19 infection in pregnancy could not be predicted by a gravida's occupation, but it was significantly higher when the source of exposure was her own child. The fetal risk of nonimmune hydrops after maternal B19 infection must be very low. As a consequence, exclusion of pregnant women from the workplace during endemic periods with seasonal clusters of cases is not justified. Weekly fetal ultrasound evaluation in these cases carries a low yield.

Low-dose aspirin and prednisone treatment of pregnancy loss caused by lupus anticoagulants.

The objective of this study was to ascertain the complications and the efficacy of low-dose aspirin (LDA) and prednisone therapy in women with pregnancy loss and "lupus anticoagulants" (LAC). During the period 1985 to 1993, 255 patients with two or more pregnancy losses (RPL) were tested for LAC with an activated partial thromboplastin time (aPTT) and a tissue thromboplastin inhibition index (TTI, normal value < 1.3). The diagnosis of LAC was established if two TTI values were > or = 1.3 or if a prolonged aPTT was measured in the patient's plasma that did not correct to normal by 1:1 mixing with normal plasma. We excluded patients with RPL who had only anticardiolipin antibodies. We treated 28 pregnancies in 21 women with LDA/prednisone for RPL associated with LAC. Therapy with LDA/prednisone was initiated as soon as a viable pregnancy was diagnosed. Therapy was continued until delivery in all but one case. Prednisone dose was minimized by measuring TTI and aPTT every 2 weeks and adjusting the dosage to maintain a TTI < or = 1.2 and to correct the aPTT to less than 36 seconds. Among the 28 pregnancies there were four (14%) first-trimester spontaneous abortions and four (14%) second-trimester fetal deaths. Of 20 surviving neonates (72%), seven were delivered after 37 weeks and 13 before 37 weeks (mean 35.9 +/- 2.3 weeks, range 31.5 to 40.4 weeks). Pre-term premature rupture of membranes occurred in three pregnancies, hypertensive disorders in six, and four small-for-gestational-age neonates were delivered (two stillborn). Mean birth weight of 20 surviving neonates was 2736 +/- 763 gm (range 900 to 3920 gm). Mean daily prednisone dose in 20 live births was 24.1 +/- 8.5 (SD) mg (range 11.3 to 49.3 mg/day) with mean duration of LDA/prednisone therapy of 185 +/- 40 days (range 97 to 223 days). Maximum prednisone dose was 60 mg/day (mean 36.8 +/- 12.7 mg/day). Only one serious maternal complication of LDA/prednisone therapy was observed. One neonate had talipes equinovarus that resolved without surgical therapy. LDA/prednisone therapy seemed effective and reasonably well tolerated in this population. These findings should be confirmed in a prospective, controlled investigation if such a trial can be organized and performed.

Association between familial autoimmune diseases and recurrent spontaneous abortions.

PROBLEM: To examine the aggregation of autoimmune disease in the families of women experiencing recurrent spontaneous abortions. METHOD: The 95 participants in this case-control study were recruited from Magee Womens Hospital, Pittsburgh, Pennsylvania from June 1988 to May 1991. The women having recurrent spontaneous abortions (N = 45) reported at least three early fetal losses, and the controls (N = 50) reported a minimum of three pregnancies with at least two live births and no more than one induced or involuntary pregnancy loss. Data from the participants and from their first-degree and second-degree relatives were obtained by questionnaire and verified by a repeated interview, if necessary. RESULTS: The prevalence of arthritis, thyroid disease, and diabetes mellitus was increased among the relatives of women having recurrent spontaneous abortions compared to normally fertile couples. Several autoimmune diseases occurred concurrently in family members of patients, but not in the family members of normally fertile couples. CONCLUSIONS: Autoimmune diseases occur more frequently in the families of women who have experienced recurrent spontaneous abortions. Both types of diseases involve genes in the class II region of the major histocompatibility complex.

Early postpartum endometritis. Randomized comparison of ampicillin/sulbactam vs. ampicillin, gentamicin and clindamycin.

Seventy-six parturients with a clinical diagnosis of early postpartum endometritis were randomized to be treated with either standard therapy--ampicillin, gentamicin and clindamycin--or a new regimen, ampicillin/sulbactam. We deliberately chose to administer 1.5 g of ampicillin/sulbactam rather than a 3-g dose every six hours in order to accentuate any differences that might occur between the regimens. Failure rates, days of therapy and cost of treatment were compared. There was no statistically significant difference (P > .9) in the failure or recovery rates: 4 of 42 (9.5%) patients failed standard therapy vs. 6 of 34 (17.6%) patients in the ampicillin/sulbactam group. The times to recovery were 3.6 +/- 1.8 SD and 3.3 +/- 1.3 days, respectively. There was no difference in side effects or drug toxicity between the two groups. The cost of standard therapy was $355.32 for 3.6 days, whereas ampicillin/sulbactam cost $139.49 for 3.3 days. Therapy with ampicillin/sulbactam may be an equally effective and efficient way to treat patients with early postpartum endometritis.

Accuracy of the Papanicolaou smear in the diagnosis of asymptomatic infection with Trichomonas vaginalis.

OBJECTIVE: To assess the accuracy of Papanicolaou smears in reporting cytologic evidence of Trichomonas vaginalis in asymptomatic women attending a resident clinic. METHODS: In phase I of this study, we prospectively enrolled 100 asymptomatic gynecologic patients to be screened for vaginal trichomoniasis using wet preparation, vaginal culture, and Papanicolaou smear. During phase II, asymptomatic patients (40 gynecologic and 20 obstetric) whose screening Papanicolaou smears showed cytologic evidence of trichomoniasis returned for wet preparation, culture, and repeat Papanicolaou smear. Patients were considered infected with T vaginalis if either the wet preparation or culture was positive, and uninfected if both tests were negative. The cytopathologist was not informed of the patient's enrollment in this study or of the results of culture or wet preparation. RESULTS: The prevalence of asymptomatic trichomonas infection in gynecologic patients enrolled in phase I was 6%. In asymptomatic gynecologic patients enrolled in phase II, repeat Papanicolaou smear had a sensitivity and specificity of 86 and 83%, respectively, when diagnosing infection. Thirty percent of these patients would have been treated unnecessarily for trichomoniasis based upon screening Papanicolaou smear. In obstetric patients, the sensitivity of repeat Papanicolaou smear was 94% and specificity was 100%. Had therapy been initiated based on screening cytology, 20% of obstetric patients would have received unindicated therapy. The differences in sensitivity and specificity between the groups were statistically significant (P < .05). CONCLUSION: When a screening Papanicolaou smear reports cytologic evidence of T vaginalis infection in the asymptomatic patient, a confirmatory test should be performed before initiating therapy.

Efficacy of hepatitis B screening in a private obstetrical population.

We sought to determine whether the recent Centers for Disease Control recommendation of universal prenatal screening for hepatitis B surface antigen (HBsAg) is necessary or cost-effective in a population of private patients. During the 21 months of our study there were 17,973 deliveries at Magee-Womens Hospital, the largest-volume private obstetrics service in the United States. We screened 12,377 of these patients for HBsAg. Only 11 patients, 0.09% of those screened (5 private and 6 clinic) tested positive. We administered questionnaires regarding historical risk factors for hepatitis B to all 11 patients testing positive for HBsAg and to 100 controls who tested negative for HBsAg. All private patients and 5 of 6 clinic patients testing positive for HBsAg had identifiable risk factors for hepatitis B. In addition, historical risk factors for hepatitis B were identified in 29% of the women testing negative for HBsAg. We found historical risk factors to be excellent predictors of the presence of HBsAg in our private patients. Our data indicate that universal screening for HBsAg is not necessary in private patients.

Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis.

In order to determine the utility of amniocentesis for detecting subclinical chorioamnionitis in asymptomatic afebrile women in preterm labor with intact membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective study. After enrollment, 38 women fulfilled all clinical and laboratory criteria for the study; nine women were excluded because they had a leukocyte count exceeding 15,000/microL. None of the 38 asymptomatic afebrile women had a positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses. Sepsis was not proved in any of the 38 infants delivered to these patients. There was a clear relationship between histologic evidence of chorioamnionitis and failure of tocolytic therapy. Fetal lung profiles were mature in 29% of the amnionic fluid samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples before 30 weeks. Amniocentesis does not seem useful to detect chorioamnionitis in asymptomatic afebrile women with preterm labor and intact membranes at 27-32 weeks' gestation, and should be reserved for those cases in which information about fetal lung maturity would be helpful.

Pregnancy and liver transplantation.

To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential.

Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study.

To assess the association between women with preterm premature rupture of membranes and 41 potential risk factors, we conducted a case-control study in six United States tertiary perinatal centers. The study involved completion of a comprehensive questionnaire for 341 women with preterm premature rupture of membranes in singleton pregnancies from 20 to 36 weeks' gestation and 253 control women matched for maternal age, gestational age, parity, clinic or private patient status, and previous vaginal or cesarean delivery. Univariate analysis revealed 11 variables associated with a significantly (p less than 0.05) increased risk of preterm premature rupture of membranes. After multiple logistic regression analysis, three variables remained in the model as independent risk factors: antepartum vaginal bleeding in more than one trimester (odds ratio 7.4; 95% confidence interval, 2.2, 25.6), current cigarette smoking (odds ratio, 2.1; 95% confidence interval, 1.4, 3.1), and previous preterm delivery (odds ratio, 2.5; 95% confidence interval, 1.4, 2.5). Cessation of cigarette smoking by pregnant women may reduce the risk of preterm premature rupture of membranes. Further study is necessary to determine the nature of the relationship between antepartum vaginal bleeding and preterm premature rupture of membranes.

Neutralizing antibody to herpes simplex in pregnant women and their neonates.

The neutralizing antibody (NAb) titer against herpes simplex virus (HSV) was determined in blood obtained at term delivery in 76 women with documented genital HSV infection. Maternal and cord blood NAb titers against HSV-1 and HSV-2 displayed significant correlation (r = .88 and r = 0.89, respectively). In 33% of the paired samples, the neonatal NAb titer against HSV-1 exceeded the concomitant maternal titer, and in 59% the maternal and neonatal NAb titers against HSV-1 were equal. In 28% of the pairs, neonatal NAb titer against HSV-2 exceeded the concomitant maternal NAb titer against HSV-2, and in 59% the neonatal and maternal titers against HSV-2 were equal. Since maternal NAb titers against HSV accurately predict a minimum neonatal NAb titer against HSV-1 and HSV-2 in 92% and 87% of cases, respectively, such measurements may be useful in the management of delivery in women with recurrent genital HSV infection.

Characteristics of recurrent genital herpes simplex infections in pregnant women.

Longitudinal study of 229 pregnancies in 186 pregnant women with recurrent genital herpes simplex virus (HSV) infections revealed an increased incidence of recurrent episodes in the third trimester compared with the first or second trimesters. The duration of symptomatic recurrences did not change with each trimester. Cervical HSV shedding concomitant with HSV culture-positive vulvar lesions did not change significantly with advancing gestation. The presence of an HSV culture-positive vulvar lesion indicated a significantly (P less than .001) greater risk of concomitant cervical HSV shedding (44 of 333, 13.2%) than in pregnant women with HSV culture-positive remote lesions (zero of 60) or in asymptomatic women (27 of 1460, 1.9%). Comparison of the characteristics among 43 pairs of pregnancies in 34 women revealed no consistent change over time. This study of the natural history of genital HSV recurrences in pregnant women demonstrated no proclivity for an increased rate of preterm delivery (1.3%) or congenital anomalies (2.2%) in a predominantly white, non-Hispanic middle-class population.

The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses: a prospective controlled study.

Because autoimmune diseases are suspected of causing some cases of recurrent pregnancy loss, we sought clinical and serologic evidence of such diseases in a group of 277 women with recurrent pregnancy loss. Using HEp-2 cells as targets for an indirect immunofluorescence test for antinuclear antibodies, we compared the frequency of a positive antinuclear antibody test in the women with recurrent pregnancy loss to that in 299 pregnant controls and 119 nonpregnant controls. The frequency of positive antinuclear antibody tests at a titer of 1:40 or higher was 16.3% in cases, 16.6% in pregnant controls, and 16.8% in nonpregnant controls. Increasing the critical titer to 1:80, however, led to a statistically significant difference between cases (6.9%) and controls (0 and 0.8%, pregnant and nonpregnant, respectively; P less than .0001). Additional serologic tests failed to identify any subclinical autoimmune diseases, although two antinuclear antibody-negative patients later developed systemic lupus erythematosus. Pregnancy outcome in women with antinuclear antibody titers of 1:80 or higher included 52% live births, compared with 65.6% live births in women with three or more pregnancy losses and an entirely normal comprehensive evaluation, a nonsignificant difference. The combination of clinical evaluation and antinuclear antibody tests did not identify new cases of autoimmune disease in this population.

Leukocyte interferon for treating first episodes of genital herpes in women.

Women experiencing their first episodes of genital herpes were treated, beginning within three days of the onset of lesions, with 5 X 10(4) units of human leukocyte interferon/kg of body weight for 12 doses over 14 days (total, approximately 3.6 X 10(7) units) or with placebo in equivalent volumes. Life-table analysis revealed quicker healing and significant reductions in the duration of shedding of virus in interferon-treated patients. Maximum daily geometric mean titers of virus and total area of unhealed lesions also decreased more quickly. No statistically significant difference in resolution of pain was seen between the two groups. Interferon had no effect on onset or frequency of subsequent recurrences recorded over one year of follow-up. Moderate, transient neutropenia occurred in 13 of 34 interferon-treated patients. A therapeutic effect of human leukocyte interferon on initial genital herpes was documented, but the clinical usefulness of interferon treatment of genital herpes is limited at this time.

Changes in the frequency of genital herpes recurrences as a function of time.

To obtain objective information regarding changes in the frequency of recurrent genital Herpes simplex infections, the data from two consecutive pregnancies in 22 women with culture-proved genital Herpes simplex infections were reviewed. The pregnancies studied were separated by a mean of 2.0 years. When only culture-proved recurrences were considered, nine women had fewer recurrences in their second pregnancy than in their first, four had more recurrences in their second than in their first, and nine had the same number of recurrences in both pregnancies. The mean interval between culture-proved recurrences was 58.5 +/- 36.1 (SD) days in first pregnancies and 51.7 +/- 28.6 days in second pregnancies. Mean duration of viral shedding during 14 recurrences in first pregnancies was 4.6 +/- 3.4 days, and 3.2 +/- 2.2 days in 14 recurrences in second pregnancies (differences not significant by Mann-Whitney). Cervical Herpes simplex shedding in asymptomatic women occurred in four of 200 (2.0%) of first pregnancy cultures and zero of 167 second pregnancy cultures (NS). During culture-positive recurrent vulvar infections, 18 of 55 (32.7%) cervical cultures in first pregnancies were positive compared with four of 50 (8%) cervical cultures in second pregnancies (P less than .025). Route of delivery was very similar in the first and second pregnancies with vaginal delivery in 63.6% of first pregnancies and 72.7% of second pregnancies. Overall there was no appreciable difference in the frequency or severity of recurrent genital Herpes simplex infections over time, but more data are needed.