Anti-hypertensive drugs in pregnancy and fetal growth: Evidence for "pharmacological programming" in the first trimester?

Objectives: To determine the timing and exact nature of the effect of the drug atenolol upon fetal growth. Also to discover if the reduction in fetal growth is due to superimposed pre-eclampsia or any other confounding variable. Design: A retrospective cohort study of prospectively collected data in a hypertensive pregnancy database. Setting: Two district general hospitals in the midlands of England. Both hospitals have specialised medical antenatal clinics for pregnant women with chronic hypertension. Participants: 491 pregnancies in 380 women with essential or secondary hypertension. Outcome measures: The outcome measures used were the infant birth weight, birth weight standardized for gestational age, and the ponderal index at birth, a surrogate measure for in utero growth restriction. Results: The babies of women taking atenolol at conception or during the first trimester had significantly lower birth weights (by 139-512 g, p<0.01) than women on calcium channel blockers or no medication. Likewise the ponderal index was also significantly reduced, p<0.01. In addition most of these babies were small for gestational age (SGA) with 70% on or below the 10th centile and 40% below the third centile. No such independent association was seen with anti-hypertensives taken in the second trimester. Conclusions: Atenolol taken at the time of conception and/or during the first trimester of pregnancy was associated with low birth weight. This finding was independent of the development of superimposed pre-eclampsia. Other anti-hypertensives were not found to be associated with low birth weight. Use of atenolol in the second trimester of pregnancy did not produce the same effect and was not materially different in its effects from the other anti-hypertensive drugs. In the second trimester, the development of superimposed pre-eclampsia is the over-riding effect in the reduction of infant birth weight. Atenolol used in the first trimester could be pharmacologically programming these infants to restricted growth patterns.