BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has recently been associated with an increased risk for certain malformations. METHODS: Using the Swedish Medical Birth Register, we identified women who had reported the use of SSRIs in early pregnancy and studied their infants, born between July 1, 1995 and the end of 2004. Congenital malformations were identified from that register, from the Register of Congenital Malformations, and from the Hospital Discharge Register. The effect of drug exposure was studied after adjustment for a number of identified maternal characteristics that could act as confounders. RESULTS: We identified 6,481 women who reported the use of SSRIs in early pregnancy and their 6,555 infants. There was no general increase in malformation risk. An increased risk for cystic kidneys was seen, but this was based on only nine malformed infants, and the pathology varied between these cases. An in-depth study of cardiovascular defects identified an association between such defects and notably ventricular and atrial septum defects and maternal use of paroxetine but not other SSRls. No support for a postulated association between SSRI use and infant craniostenosis or omphalocele was found. CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk factor for infant malformations. The association between paroxetine use and infant cardiovascular defects may be a result of multiple testing, but is supported by other studies.