Abstract
Introduction
Infection with Toxoplasma gondii is asymptomatic or mild in immunocompetent people and leads to lifelong immunity, but it can have serious consequences in pregnancy. About five per thousand non-immune pregnant women may acquire toxoplasma infection, with a 10-100% risk of transmission to the baby. Risks of transmission to the baby are higher later in pregnancy, but risks of infection causing harm to the baby are greater earlier in pregnancy.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects on mother and baby of treating toxoplasmosis during pregnancy? What are the effects of treating toxoplasmosis in neonates exposed to toxoplasmosis prenatally? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found four systematic reviews, RCTs or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiparasitic drugs in pregnancy, antiparasitic drugs in neonates.
Key Points
Infection with Toxoplasma gondii is asymptomatic or mild in immunocompetent people, and leads to lifelong immunity, but it can have serious consequences in pregnancy.
About five per thousand non-immune pregnant women may acquire toxoplasma infection, with a 10-100% risk of transmission to the baby.
Infection is usually acquired from undercooked meat, or from fruit and vegetables contaminated with cat faeces.
Fetal infection can cause eye and brain damage, growth retardation, and intrauterine death.
Risks of transmission to the baby are higher later in pregnancy, but risks of infection causing harm to the baby are greater earlier in pregnancy.
Children with subclinical infection at birth may have cognitive, motor, or visual defects that may be difficult to diagnose in early childhood.
We don't know whether treating infected pregnant women with spiramycin, pyrimethamine-sulphonamides, or both reduces the risk of fetal infection, as the few studies that have been done have produced conflicting results.
It is possible that treatment of infection in pregnancy may save the pregnancy without preventing infection, which could increase the prevalence of congenital disease.
We don't know whether antiparasitic drugs, given to neonates who have been infected prenatally, are effective, although there is consensus that infected infants should be treated with pyrimethamine and sulfadiazine for 6 to 12 months.
About this condition
Definition
Toxoplasmosis is caused by the parasite Toxoplasma gondii. Infection is asymptomatic or unremarkable in immunocompetent individuals, but leads to a lifelong antibody response. During pregnancy, toxoplasmosis can be transmitted across the placenta and may cause intrauterine death, neonatal growth retardation, mental retardation, ocular defects, and blindness in later life. Congenital toxoplasmosis (confirmed infection of the fetus or newborn) can also present at birth: either as subclinical disease, which may evolve with neurological or ophthalmological disease later in life; or as a disease of varying severity, ranging from mild ocular damage to severe mental retardation.
Incidence/ Prevalence
Reported rates of toxoplasma seroprevalence vary among and within countries, as well as over time. The risk of primary infection is highest in young people, including young women during pregnancy. We found no cohort studies describing annual seroconversion rates in women of childbearing age nor incidence of primary infection. One systematic review (search date 1996) identified 15 studies that reported rates of seroconversion in non-immune pregnant women ranging from 2.4-16/1000 in Europe and from 2-6/1000 in the USA. France began screening for congenital toxoplasmosis in 1978, and during the period 1980-1995 the seroconversion rate during pregnancy in non-immune women was 4-5/1000.
Aetiology/ Risk factors
Toxoplasma infection is usually acquired by ingesting either sporocysts (from unwashed fruit or vegetables contaminated by cat faeces) or tissue cysts (from raw or undercooked meat). The risk of contracting toxoplasma infection varies with eating habits, contact with cats and other pets, and occupational exposure.
Prognosis
One systematic review of studies conducted from 1983-1996 found no population-based prospective studies of the natural history of toxoplasma infection during pregnancy. One systematic review (search date 1997; 9 controlled, non-randomised studies) found that untreated toxoplasmosis acquired during pregnancy was associated with infection rates in children of between 10-100%. We found two European studies that correlated gestation at time of maternal seroconversion with risk of transmission and severity of disease at birth. Risk of transmission increased with gestational age at maternal seroconversion, reaching 70-90% when seroconversion occurred after 30 weeks' gestation. In contrast, the risk of the infant developing clinical disease was highest when maternal seroconversion occurred early in pregnancy. The highest risk of developing early signs of disease (including chorioretinitis and hydrocephaly) was about 10%, recorded when seroconversion occurred between 24 and 30 weeks' gestation. Infants with congenital toxoplasmosis and generalised neurological abnormalities at birth develop mental retardation, growth retardation, blindness or visual defects, seizures, and spasticity. Children with subclinical infection at birth may have cognitive, motor, and visual deficits, which may go undiagnosed for many years. One case-control study (845 school children in Brazil) found mental retardation and retinochoroiditis to be significantly associated with positive toxoplasma serology (population attributable risk 6-9%).
Aims of intervention
To prevent transmission from mother to child, congenital infection, visual impairment, and neurological impairment in neonates and in later life, with minimum adverse effects.
Outcomes
Incidence of spontaneous abortion, fetal infection, and overt neonatal disease (neurological and visual impairment); serological positivity in the newborn; adverse effects of treatment.
Methods
BMJ Clinical Evidence search and appraisal July 2007. The following databases were used to identify studies for this review: Medline 1966 to July 2007, Embase 1980 to July 2007, and the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clincial Trials 2007, Issue 2. Additional searches were carreid out using these websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study-design criteria for inclusion in this review were: published systematic reviews (including RCTs and observational studies) and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the review as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
GRADE evaluation of interventions for congenital toxoplasmosis
| Important outcomes | Incidence of spontaneous abortion, foetal infection, neonatal disease, serological positivity in newborn, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects on mother and baby of treating toxoplasmosis during pregnancy? | |||||||||
| 35 studies (at least 1438 women) | Incidence of infection | Antiparasitic treatment v no treatment | 2 | −2 | −1 | −1 | 0 | Very low | Quality points deducted for incomplete reporting of results and for poor-quality studies. Consistency point deducted for conflicting results. Directness point deducted for differences in gestation periods |
| What are the effects of treating toxoplasmosis in neonates exposed to toxoplasmosis prenatally? | |||||||||
| No studies found |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Kernicterus
Cerebral toxicity caused by high levels of bilirubin in the neonate is known as kernicterus. Clinical effects include vomiting, lethargy, fever, and fits.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
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