CRD summary

This review of individual patient data evaluated the effect of prenatal treatment for congenital toxoplasmosis on mother-to-child transmission and infants' clinical manifestations. Treatment was associated with a lower rate of mother-to-child transmission, but did not change the risk of clinical manifestations. The authors stated that randomised clinical trials are needed to confirm these findings. These conclusions are likely to be reliable.

Authors' objectives

To estimate the effects of prenatal treatment for congenital toxoplasmosis on the risk of mother-to-child transmission of infection and clinical manifestations during infancy, with an individual patient data (IPD) meta-analysis.

Searching

MEDLINE, EMBASE and Pascal were searched from 1980 to 2002. The search was updated through Current Contents in November 2005. The reference lists of identified papers were checked and experts in the field were contacted for additional studies. No language restrictions were applied.

Study selection

Assessment of study quality

The authors did not state how and whether any inconsistency or missing data were verified with the trial investigators. Four reviewers examined the IPD before deciding whether to include a trial.

Data extraction

The authors did not state whether trial investigators were contacted to verify the finalised data.

Methods of synthesis

Results of the review

The IPD from 14 studies (including IPD for 20 cohorts of 1,721 women and 26 cohorts of 550 infants) were included in the review. The authors stated that other eligible trials were identified, but one trialist refused to participate and the investigators of 4 studies did not respond.

Mother-to-child transmission.

The risk of mother-to-child transmission increased with gestational age at seroconversion (OR 1.15 per week, 95% CI: 1.12, 1.17). Prenatal treatment was associated with a lower risk of transmission (OR 0.94 per week, 95% CI: 0.90, 0.98), especially when treatment was started early after the mother's seroconversion. The odds of transmission also decreased significantly with higher (5 degrees) latitude (OR 0.71, 95% CI: 0.53, 0.96). Rates of mother-to-child transmission were not significantly different when patients were treated with spiramycin compared with pyrimethamine-sulphonamide (OR 0.79, 95% CI: 0.55, 1.13). Clinical manifestations.

Higher gestational age at seroconversion was associated with a lower risk of overall clinical manifestations (OR 0.96 per week, 95% CI: 0.93, 0.99, p=0.01), intracranial lesions (OR 0.91 per week, 95% CI: 0.87, 0.95) and ocular lesions (OR 0.97 per week, 95% CI: 0.93, 1.00, p=0.04) in infancy. The risk of any clinical manifestations was comparable between infants of treated and untreated mothers (OR 1.11, 95% CI: 0.61, 2.02). Correcting for the type of treatment, period of the study, or the latitude of the centre did not modify these findings. The combination of spiramycin and pyrimethamine-sulphonamide carried a higher risk of any clinical manifestations than pyrimethamine-sulphonamide alone (OR 1.29, 95% CI: 1.42, 9.34).

Authors' conclusions

Prenatal treatment appears to carry a lower risk of mother-to-child transmission, but does not seem to decrease the risk of clinical manifestations in infected liveborn infants. A large randomised controlled trial would be needed to confirm these findings.

CRD commentary

This meta-analysis of IPD addressed a well-defined question in terms of the participants, outcomes and study design, while it used a broad definition for the intervention. The authors searched several bibliographic databases without language restrictions and made efforts to identify additional unpublished trials, although they did not assess publication bias. It is unclear whether trialists were contacted to check each trial's eligibility and whether checking, validation and reanalysis of raw data from the included clinical trials were conducted. The number of excluded studies, as well as the number of participants in trials for which data could not be retrieved, were specified. At least two reviewers made decisions about inclusion and exclusion and the criteria used for study selection were reported. It is not clear whether statistical heterogeneity was assessed. The data appear to have been analysed using appropriate techniques for the meta-analysis of IPD. Although the reporting of the methods of this review is lacking in some areas, the authors' conclusions appear appropriate and, based on the evidence presented, are likely to be reliable.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that large randomised clinical trials are needed to clarify the real benefit of prenatal treatment, both within and outside Europe.

Funding

Part of the Eurotoxo project, which is funded by the European Commission, contract number QLG4-CT-2002-30262.

Bibliographic details

Thiebaut R, Leproust S, Chene G, Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data. Lancet 2007; 369: 115-122. [PubMed: 17223474]

Other publications of related interest

1. Wallon M, Liou C, Garner P, Peyron F. Congenital toxoplasmosis: systematic review of evidence of efficacy of treatment in pregnancy. BMJ 1999;318:1511-4. 2. Eskild A, Oxman A, Magnus P, Bjorndal A, Bakketeig LS. Screening for toxoplasmosis in pregnancy: what is the evidence of reducing a health problem? J Med Screen 1996;3:188-94.

Indexing Status

Subject indexing assigned by NLM

MeSH

Coccidiostats /therapeutic use; Europe; Female; Gestational Age; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Logistic Models; Pregnancy; Pregnancy Complications, Parasitic /diagnosis /drug therapy /physiopathology; Prenatal Diagnosis /economics /methods; Spiramycin /therapeutic use; Toxoplasmosis, Congenital /diagnosis /drug therapy /transmission; Treatment Outcome

AccessionNumber

12007000587

Database entry date

31/01/2008

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.