CRD summary

This review assessed the effects of selective serotonin re-uptake inhibitors (SSRIs) used during late pregnancy on the foetus and newborn. The authors concluded that SSRIs may have subtle adverse effects. Several limitations were apparent in the reporting of the review process and the methodology used, suggesting that the authors' conclusions cannot be considered reliable.

Authors' objectives

To assess the effects of selective serotonin re-uptake inhibitors (SSRIs) used during late pregnancy on the foetus and newborn.

Searching

MEDLINE, ISI Web of Knowledge, EMBASE and CINAHL were searched using the reported search terms. The University of California - San Diego HealthCare and California Teratogen Information Service and Clinical Research Program website was also searched. The reference lists in relevant studies were screened.

Study selection

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Some authors were contacted to provide additional information. Data were extracted on the absolute numbers of infants with prematurity and/or low birth weight; if unavailable, these values were estimated assuming a normal distribution of data to obtain means and standard deviations.

Methods of synthesis

Results of the review

Nine studies (n=949) were included. Seven studies had control groups (n=699). Two further studies were excluded from the review because of insufficient data available for analysis.

Neonates of women taking SSRIs during the third trimester of pregnancy were significantly more likely than controls to be low birth weight (OR 3.64, 95% CI: 1.01, 13.08, P=0.0481; NNT 31 based on 837 neonates) or to be admitted to an SCN or NICU (OR 3.30, 95% CI: 1.45, 7.54, P=0.0192; NNT 7 based on 549 neonates).

No statistically significantly difference was shown in the likelihood of PNA (OR 4.08, 95% CI: 1.20, 19.93, P=0.0694; NNT 9 based on 483 neonates) or prematurity (OR 1.85, 95% CI: 0.79, 4.29, P=0.1295; NNT 29 based on 909 neonates) with SSRIs.

The authors also reported on effects during lactation, neurodevelopment in the neonatal period, and long-term neurodevelopmental outcomes. However, most of these studies did not meet the inclusion criteria of the review and the methods used to identify them were not reported.

Authors' conclusions

SSRIs given in late pregnancy may have subtle adverse effects on the foetus and newborn.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, study design and intervention; inclusion criteria for the outcomes were broadly defined. Several relevant databases and websites were searched, but the dates searched were not reported. It was not explicitly clear whether unpublished studies were eligible, and their exclusion would raise the possibility of publication bias. It was also not clear whether any language limitations had been applied. The methods used to select studies and extract the data were not described, so it is not known whether any efforts were made to reduce reviewer errors and bias. Study validity was not assessed, thus the results from these studies and any synthesis may not be reliable.

Some relevant information on the included studies was tabulated, but no details of the criteria used to define outcomes or the results of individual studies were given. The authors commented on the heterogeneous populations across the included studies, but did not report any formal assessment of statistical heterogeneity. They also did not present forest plots or discuss clinical heterogeneity, and the designs of the included studies were not reported. The methods used to obtain estimates of outcome data from some individual studies were not reliable, and it appeared that non-controlled studies were included in the meta-analysis. Furthermore, the CIs were wide for most of the pooled outcomes. Collectively, these issues suggested that pooling studies by meta-analysis may not have been appropriate. In addition, the authors reported results from other studies that were not reported as being identified as a result of the systematic literature search. Where studies were not identified using a systematic search, the possibility of selective reporting of studies cannot be excluded.

In summary, the lack of reporting of review methods, the absence of a validity assessment, uncertainty about between-study differences and inappropriate analysis mean that the authors' conclusions cannot be considered reliable.

Implications of the review for practice and research

Practice: The authors stated that until complete data on long-term safety are available, the decision to use SSRIs during pregnancy or lactation needs to take the risks and benefits into account.

Research: The authors did not state any implications for further research but did mention the absence of complete long-term safety data.

Bibliographic details

Lattimore K A, Donn S M, Kaciroti N, Kemper A R, Neal C R, Vazquez D M. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis Journal of Perinatology 2005; 25(9): 595-604. [PubMed: 16015372]

Indexing Status

Subject indexing assigned by NLM

MeSH

Child Development /drug effects; Female; Fetus /drug effects; Humans; Infant, Newborn /physiology; Maternal-Fetal Exchange; Pregnancy; Serotonin Uptake Inhibitors /adverse effects

AccessionNumber

12006003025

Database entry date

31/12/2006

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.