Rubella in pregnancy: Intrauterine transmission and perinatal outcome during a Brazilian epidemic
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.
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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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Viral Infections of the Fetus and Newborn
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2022, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingCitation Excerpt :Maternal infection, and particularly intrauterine infection, activates the fetal inflammatory response syndrome, a condition associated with adverse neurologic outcomes (4,63). The underlying mechanisms on how inflammation impacts fetal brain development remain unclear, but several mechanisms have been proposed, including direct teratogenicity of hyperthermia and toxins (64,65), medication exposure, activation of cytokines such as IL-6 (66–68) and IL-17 (69,70), and interaction between environmental factors, epigenetic factors, and genetic susceptibility (71). Numerous infectious agents are known to cause direct and indirect toxicity to the developing brain, including Zika virus (72), Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, and parvovirus B19 (73,74).
Safety profile of rubella vaccine administered to pregnant women: A systematic review of pregnancy related adverse events following immunisation, including congenital rubella syndrome and congenital rubella infection in the foetus or infant
2020, VaccineCitation Excerpt :Rubella vaccine is a highly effective live attenuated vaccine used to prevent foetal death or congenital rubella syndrome (CRS) which can occur when a susceptible (non-immune) pregnant woman is infected with the rubella wild virus. This risk of transmission of rubella infection to the foetus during the first 10 weeks of pregnancy is as high as 90% and declines thereafter [2,3]. CRS is classically defined as one or more of deafness, heart defects, or cataracts with evidence of rubella infection.
Maternal infections
2020, Handbook of Clinical NeurologyCitation Excerpt :Therefore, CRS should always be considered in a fetus or neonate with ultrasound findings or clinical picture suggestive of congenital infection regardless of maternal serostatus. When suspected, rubella congenital infection should be confirmed antenatally by PCR, culture, and fetal IgM performed on chorionic villus sampling, fetal blood sampling, or amniotic fluid (Ho-Terry et al., 1990; Bosma et al., 1995; Tanemura et al., 1996; Mace et al., 2004; Andrade et al., 2006; Best, 2007; Pham et al., 2013). Laboratory diagnosis of CRS can be confirmed by isolation of the virus or positive result for rubella RT-PCR from a clinical specimen including pharyngeal swab, conjunctivae, cerebrospinal fluid (CSF), or urine.
The fetal origins of mental illness
2019, American Journal of Obstetrics and GynecologyNo. 368-RUBELLA IN PREGNANCY
2018, Journal of Obstetrics and Gynaecology CanadaCitation Excerpt :There is no gold standard for antenatal diagnosis of rubella congenital infection. Rubella PCR, rubella culture, and fetal IgM can be performed following CVS, fetal blood sampling, or amniocentesis.22,44-49 Amniocentesis is recommended at least 6 weeks after known maternal infection and after the 20th week of gestation.