Rubella in pregnancy: Intrauterine transmission and perinatal outcome during a Brazilian epidemic

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Abstract

Sixty pregnant women with clinical signs of rubella and specific rubella antibodies were studied between January 1999 and December 2002 in order to determine the intrauterine rubella transmission rate and the presence of the virus in amniotic fluid and fetal tissues by nested PCR. Thirty-three patients presented rubella before 12 weeks of gestation and 27 after 12 weeks. Gestational age at the time of acute rubella was determined on the basis of the date of last menstruation and the first trimester ultrasound scan. Thirteen patients with clinical features of rubella before 12 weeks of gestation were submitted to amniocentesis. Three products of conception were analyzed. The presence of the rubella virus was determined by nested PCR. IgM and IgG antibodies were analyzed in neonatal samples at birth and at 3 months of age using a capture immunoassay. Newborn follow-up was based on the presence of congenital rubella syndrome-compatible defects, anti-rubella antibodies, echocardiographic alterations, brainstem evoked response audiometry, and ophthalmological pathology. Five miscarriages and four fetal deaths were observed in the group of patients presenting clinical features before 12 weeks of gestation. IgM antibodies were detected in seven neonates at birth and at 3 months of age. Deafness was observed in three cases and pigmentary retinopathy in one case. Fourteen of the 16 samples (13 amniotic fluid and 3 fetal tissue samples) submitted to virological analysis tested positive. Four fetal deaths, five miscarriages (one with negative virology) and seven newborns with anti-rubella IgM at birth and/or at 3 months age were observed in the group with rubella before 12 weeks of gestation. There were three cases in which virological analysis of the amniotic fluid samples was positive (infected) while the newborn showed no signs of congenital rubella syndrome and anti-rubella IgM were absent. When maternal rubella occurred after 12 weeks of gestation, no fetal or neonatal rubella signs were observed.

Eradication of congenital rubella syndrome is possible since vaccination campaigns continue and all services related to the health care of children, adolescents and women have become aware of the significance of the problem and are collaborating. All pregnant women in Brazil should be screened for the rubella antibody and the susceptible group should be vaccinated after giving birth.

Introduction

The rubella virus is one of the most teratogenic agents for humans, affecting fetal development and leading to the well-known congenital rubella syndrome (CRS). The first report regarding the fetal consequences of maternal rubella infection was published by Gregg in 1941 (Gregg, 1941). Since then, a number of articles have reported techniques for the isolation of the virus from human fetal and placental tissues and for the detection of specific IgM antibodies in fetal blood (Daffos et al., 1984, Enders and Jonathan, 1987). More recently, the polymerase chain reaction (PCR) has been applied to both fetuses and neonates in order to establish fetal risks after maternal rubella infection (Bosma et al., 1995b, Macé et al., 2004, Revelo et al., 1997, Tanemura et al., 1996).

Some studies have shown that the rubella infection rate is higher than the rate of CRS because not every infection leads to fetal damage. The frequency of congenital infection is more than 80–90% when maternal infection occurs during the first trimester, 54% at 13–14 weeks, and 25% at the end of the second trimester (Miller et al., 1982). The reported rates of CRS or CRS-compatible defects range from 10 to 90% in the first trimester and from 5% to as much as 50% in the second trimester (Daffos et al., 1984, Figueroa-Damian et al., 1999, Hardy et al., 1969, Hwa et al., 1994, Miller et al., 1982, Peckham and Marshall, 1979, Tanemura et al., 1996).

The Fetal Medicine Unit of the São Paulo University Hospital, as a referral center, received a large number of rubella infection cases during an epidemic of the disease in Brazil. All cases were submitted to clinical and laboratory analyses and a complete follow-up involving neonatal care in pediatric units by otorhinolaryngologists, ophthalmologists and cardiologists was carried out, thus providing a unique opportunity for the study of the intrauterine transmission of rubella and its consequences to the fetus and newborn.

Section snippets

Study population

Sixty patients with clinical signs and serological evidence of rubella (IgM and IgG antibodies) were studied prospectively between 1999 and 2002 at the Fetal Medicine Unit of the Obstetric Clinic, University Hospital, Sao Paulo University. No termination of pregnancy was performed since Brazilian law does not permit it. Maternal age ranged from 16 to 39 years (mean: 25 years) and 63.6% of the patients were primigravidas.

Gestational age at the time of acute rubella was obtained on the basis of

Results

A total of 13 amniotic fluid samples, two fetal blood samples and three products of conception were analyzed. Virus isolation and RT-PCR were positive in 11 of the 13 amniotic fluid samples analyzed, and in the three products of conception. Fetal blood samples were not submitted to virus isolation or RT-PCR. Anti-rubella IgM antibodies were negative in two fetal blood samples.

Fetal death occurred in four cases. Gestational age at fetal death ranged from 30 to 36 weeks. In two of these cases,

Discussion

Rubella and CRS are public health problems. A rubella epidemic was observed in Brazil between 1999 and 2001, which caused a significant rise in the incidence of CRS. Most of the rubella cases were notified in the State of São Paulo, with an incidence of 7.5 in 100,000 inhabitants between 1999 and 2000. Sixty pregnancies were studied because only patients with clinical signs and serological confirmation were included.

As the clinical diagnosis of rubella is unreliable, serological tests are

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