CRD summary

This review assessed the adverse effects on infants of in utero exposure to serotonin re-uptake inhibitors (SRIs) during the last trimester of pregnancy. The authors concluded that SRI exposure may result in a mild, self-limited neonatal behavioural syndrome. The conclusions are reasonable, although there were some methodological weaknesses in the conduct of the review.

Authors' objectives

To review the evidence relating to serotonin re-uptake inhibitor (SRI) neonatal syndrome and to help clinicians guide their patients in a risk-benefit decision-making process.

Searching

MEDLINE (from 1966 to February 2005) and PsycINFO (from 1974 to February 2005) were searched; the search terms were reported. In addition, reference lists were checked for further articles. There were no language restrictions.

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.

If not reported in the article, the relative risks and corresponding 95% confidence intervals (CIs) were calculated using exact methods.

Methods of synthesis

Results of the review

The review includes 9 cohort studies, of which eight had a control group that was either not exposed or had early exposure (before 26 weeks of pregnancy) to an SRI (exposed n=992, controls n=4,462,180). An additional 18 case reports (reported by 13 papers) and 2 case series were included.

Five of the 9 cohort studies (4 prospective and 1 retrospective) defined a neonatal behavioural syndrome which included signs of poor neonatal adaption (such as jitteriness, problems with breathing or feeding, and hypothermia). In the pooled analysis of these studies, there was an increased risk of an SRI-related neonatal behavioural syndrome for late SRI exposure compared with no or early exposure, with a relative risk (RR) of 3.0 (95% CI: 2.0, 4.4). Most reports of a behavioural syndrome in the case reports and cohort studies were related to exposure to paroxetine and fluoxetine.

There were also increased risks of admission to a special care nursery (RR 2.6, 95% CI: 1.4, 4.7) and respiratory difficulties (RR 2.3, 95% CI: 1.6, 3.2) for infants with late SRI exposure compared with no or early exposure. There were no occurrences of a 'severe' syndrome (seizures, dehydration, excessive weight loss and hyperpyrexia) in 313 full-term infants where sufficient details were reported for this to be assessed. No neonatal deaths attributable to late pregnancy SRI exposure were reported.

Authors' conclusions

The neonatal behavioural syndrome associated with in utero exposure to SRIs during the last trimester of pregnancy is usually mild, self-limited, similar to familiar syndromes such as infantile colic, and can be managed with supportive care.

CRD commentary

This review had broad inclusion criteria, specifying eligible participants and outcomes, but not eligible study designs. Two relevant databases were searched with no language restrictions but, since no efforts were made to locate unpublished data, some research might have been missed. The authors did not state how papers were selected for the review or how relevant data were extracted, so it was not possible to assess whether steps were taken to minimise bias during the review process. The limitations of case reports and cohort studies as sources of evidence were discussed. However, the quality of the cohort studies and differences between them were not assessed.

Owing to differences in the study designs, outcome definitions and length of SRI exposure between comparator groups in the individual studies, the pooling of individual study results might not have been appropriate and, therefore, should be treated with some caution. The authors' conclusions and recommendations for practice and further research seem reasonable given the evidence presented in the review.

Implications of the review for practice and research

Practice: The authors stated that the risks and benefits of discontinuing an SRI during pregnancy need to be carefully balanced on an individual patient basis.

Research: The authors stated that further research should develop a definition and instrument for the diagnosis of neonatal behavioural syndrome. In addition, the incidence, severity spectrum, and preventive and therapeutic interventions for this syndrome need to be established.

Bibliographic details

Moses-Kolko E L, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner K L. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 2005; 293(19): 2372-2383. [PubMed: 15900008]

Original Paper URL

http://jama.ama-assn.org/

Indexing Status

Subject indexing assigned by NLM

MeSH

Female; Gestational Age; Humans; Infant Behavior /drug effects; Infant, Newborn; Infant, Newborn, Diseases /chemically induced /prevention & control; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Risk Assessment; Serotonin Uptake Inhibitors /adverse effects; Syndrome

AccessionNumber

12005008241

Database entry date

31/12/2005

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.