Anti-hypertensive drugs in pregnancy and fetal growth: evidence for "pharmacological programming" in the first trimester? 2002

Helen Bayliss, and D Churchill, and Michele Beevers, and D G Beevers
Department of Obstetrics, Good Hope Hospital, NHS Trust, Rectory Road, Sutton Coldfield, B75 7RR, UK.

OBJECTIVE 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. METHODS A retrospective cohort study of prospectively collected data in a hypertensive pregnancy database. METHODS Two district general hospitals in the midlands of England. Both hospitals have specialised medical antenatal clinics for pregnant women with chronic hypertension. METHODS 491 pregnancies in 380 women with essential or secondary hypertension. METHODS 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.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007236 Infant, Small for Gestational Age An infant having a birth weight lower than expected for its gestational age.
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011249 Pregnancy Complications, Cardiovascular The co-occurrence of pregnancy and a cardiovascular disease. The disease may precede or follow FERTILIZATION and it may or may not have a deleterious effect on the pregnant woman or FETUS. Cardiovascular Pregnancy Complications,Complications, Cardiovascular Pregnancy,Pregnancy, Cardiovascular Complications,Cardiovascular Pregnancy Complication,Complication, Cardiovascular Pregnancy,Pregnancies, Cardiovascular Complications,Pregnancy Complication, Cardiovascular
D011256 Pregnancy Outcome Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; or SPONTANEOUS ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO. Outcome, Pregnancy,Outcomes, Pregnancy,Pregnancy Outcomes
D011261 Pregnancy Trimester, First The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation. Early Placental Phase,Pregnancy, First Trimester,Trimester, First,Early Placental Phases,First Pregnancy Trimester,First Pregnancy Trimesters,First Trimester,First Trimester Pregnancies,First Trimester Pregnancy,First Trimesters,Phase, Early Placental,Phases, Early Placental,Placental Phase, Early,Placental Phases, Early,Pregnancies, First Trimester,Pregnancy Trimesters, First,Trimesters, First
D005260 Female Females
D005314 Embryonic and Fetal Development Morphological and physiological development of EMBRYOS or FETUSES. Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal

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