Use of ACE inhibitors in the second and third trimesters has previously been linked to fetopathy.
This study, however, is the first to show that exposure to the drugs during the first trimester is associated with a 2.7-fold increased risk of teratogenicity.
The research focused on 29,507 infants, 209 of whom were exposed to ACE inhibitors in the first trimester and 202 to other antihypertensives.
Major congenital malformations were diagnosed in 2.9 per cent of the infants overall, and in 7.1 per cent of those exposed to ACE inhibitors.
Use of the drugs in the first trimester was linked to a 3.7-fold higher risk of cardiovascular and a 4.4-fold higher risk of CNS malformations.
No increased risk was observed with other antihypertensive drugs. The researchers concluded that exposure to ACE inhibitors during the first trimester should be avoided.
Professor Morris Brown, president of the British Hypertension Society, said the findings concurred with guidelines being drawn up by the society and NICE, due to be published at the end of this month.
'For women of childbearing age, first-line treatment should always be beta-blockers, unless contraindicated,' he said. 'In black women, calcium-blockers or diuretics are the drugs of choice.'
But he added that no treatment might be best for women with mild hypertension who are planning a pregnancy.
Dr Terry McCormack, chairman of the Primary Care Cardiovascular Society and a GP in Whitby, North Yorkshire, said: 'Anyone who could potentially become pregnant should not use this drug.'
N Eng J Med 2006; 354: 2,443-51
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