The risk - six to 10 per cent - is high enough to merit caution in their use, especially since they are only marginally effective in most cases, researchers said.
"In pregnancy, you're treating the mother but you're worried about the unborn child, and the benefit needs to outweigh the risk," said Anick Berard, professor at Universite de Montreal (UdeM) in Canada.
The study is among the first to examine the link to birth defects among depressed women.
Of the women studied, 3,640 - about 20 per cent - took antidepressants in the first three months.
"We only looked at the first trimester, because this is where all the organ systems are developing. At 12 weeks of gestation, the baby is formed," said Berard.
Antidepressant use during this critical time-window has the potential to interfere with serotonin intake by the foetus, which can result in malformations.
"Serotonin during early pregnancy is essential for the development of all embryonic cells, and thus any insult that disturbs the serotonin signalling process has the potential to result in a wide variety of malformations," researchers said.
Similarly, use of Paxil (paroxetine) was associated with an increased risk of heart defects; venlafaxine (Effexor), with lung defects; and tricyclic antidepressants (such as Elavil), with increased eye, ear, face and neck defects.
Depression is on the rise across the globe and is a leading cause of death, according to the World Health Organisation (WHO).
Depression is particularly serious during pregnancy, and doctors - especially psychiatrists, obstetricians and other specialists - are prescribing more antidepressants than ever to expectant mothers.
"There are a multitude of ways to get mild to moderate depression treated, but you need to have the time and money and also the encouragement to take advantage of them," Berard said.
"Given that an increasing number of women are diagnosed with depression during pregnancy, the new results have direct implications on their clinical management," researchers said.
The study was published in the British Medical Journal.
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