We read with interest the very important and thought-provoking study by Jensen et al.^{Reference Jensen, Grøn, Lidegaard, Pedersen, Andersen and Kessing1} The authors have found an increased rate of low Apgar scores in neonates with prenatal antidepressant exposure, especially with selective serotonin reuptake inhibitors (SSRIs).^{Reference Jensen, Grøn, Lidegaard, Pedersen, Andersen and Kessing1} However, the use of other antidepressants (new or old) and a diagnosis of maternal depression were not associated with low Apgar scores.^{Reference Jensen, Grøn, Lidegaard, Pedersen, Andersen and Kessing1} The study has several merits: nationwide data, large sample size, meticulous record keeping, sound methodology, appropriate use of statistics, controlling confounders to a large extent and, most importantly, having been conducted in a clinically relevant area, where data were limited and there were more questions than answers.

However, there are certain issues with the study. First, the authors have not mentioned which of the SSRIs was implicated in having the greatest or least effect on lowering Apgar score. Second, the dose and duration of antidepressant use were not mentioned and adherence to antidepressants was also not assessed. Third, antidepressant data were collected from psychiatric centres only, perhaps because the authors did not have access to data from general practitioners, which further limits the generalisability of the study findings. Fourth, the authors have not mentioned and not controlled for important confounders such as the presence of a physical disorder in the mother, obstetric complications and nutritional status of mothers, which may also contribute to a low Apgar score. Fifth, there is a possible mistake in tabulating the gestational age of all pregnancies, as the interquartile range is stated as 39-39 weeks (see Table 1). Finally, the authors have themselves mentioned about the significant differences in the antidepressant prescription trends. During the study period, use of antidepressants was very limited in pregnant women, but recently antidepressant use has increased substantially, especially that of SSRIs. This may be an important reason for getting high odds ratios for low Apgar scores with the use of an SSRI. Earlier studies have also reported low Apgar scores with maternal SSRI use.^{Reference Lund, Pedersen and Henriksen2,Reference Oberlander, Bonaguro, Misri, Papsdorf, Ross and Simpson3} Exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes in the fetus^{Reference Oberlander, Bonaguro, Misri, Papsdorf, Ross and Simpson3} and these effects are partly moderated by infant SLC6A4 genotype.^{Reference Maciag, Simpson, Coppinger, Lu, Wang and Lin4}

Today, authors have advised caution and proper monitoring of infants with prenatal antidepressant exposure. This study will definitely provide impetus for future research in this area, and with more robust data, it may also act as a starting point for the modification of existing treatment guidelines.