Abstract
Purpose
To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations.
Methods
A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register.
Results
There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92–3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02–3.02), again without any clear drug specificity.
Conclusions
There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.
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References
Rey E, Couturier A (1994) The prognosis of pregnancy in women with chronic hypertension. Am J Obst Gynecol 181:410–416
McCowan LM, Buist RG, North RA et al (1996) Perinatal morbidity in chronic hypertension. Br J Obstet Gynecol 103:123–129
Sibal BM, Caritis SN, Hauth JC et al (2000) Preterm delivery in women with pregestational diabetes or chronic hypertension relative to women with uncomplicated pregnancies. The National Institute of Child Health and Human Development – Fetal Medicine Units Network. Am J Obst Gynecol 183:1520–1524
Ray JG, Burrows RF, Burrows E et al (2001) McMaster outcome study of hypertension in pregnancy. Early Hum Dev 64:129–143
Abalos E, Duley L, Steyn DW et al (2007) Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews 1: CD002252. doi:10.1002/14651858.CD002252.pub2.
Heinonen OP, Slone D, Shapiro S (1977) Birth defects and drugs in pregnancy. Publishing Sciences Group, Littleton, MA
Källén B, Otterblad Olausson P (2003) Maternal drug use in early pregnancy and infant cardiovascular defect. Reprod Toxicol 17:255–261
Cooper WO, Hernandez-Diaz S, Arbogast P et al (2006) Major congenital malformations after first-trimester exposure to ACE inhibitors. New Engl J Med 354:2443–2451
National Board of Health and Welfare, Centre for Epidemiology (2003) The Swedish Medical Birth Register – a summary of content and quality. http://www.sos.se/FULLTEXT/112/2003-112-3/2003-112-3.pdf. Accessed May 12, 2008
Källén B (1995) A birth weight for gestational age standard based on data in the Swedish Medical Birth Registry 1985-1989. Eur J Epidemiol 11:601–606
National Board of Health and Welfare, Centre for Epidemiology (2004) Registration of congenital malformations in Swedish health registers. http://www.socialstyrelsen.se/Publicerat/2004/5120/2004-112-1.htm. Accessed May 12, 2008
Källén B, Otterblad Olausson P (2001) Monitoring of maternal drug use and infant congenital malformations. Does loratadine cause hypospadias? Int J Risk Safety Med 14:115–119
Åberg A, Westbom L, Källén B (2001) Congenital malformations among infants whose mothers had gestational or preexisting diabetes. Early Hum Develop 61:85–95
Scialli AR, Lione A (2006) ACE inhibitors and major congenital malformations (letter). New Engl J Med 355:1280
Briggs GG, Freeman RK, Yaffe SJ (2005) Drugs in pregnancy and lactation, 7th edn. Lippincott Williams and Wilkins, Philadelphia
Barr M Jr (1994) Teratogen update: angiotensin-converting enzyme inhibitors. Teratology 50:399–409
Harewood WJ, Phippard AF, Duggin G et al (1994) Fetotoxicity of angiotensin-converting enzyme inhibition in primate pregnancy: a prospective, placebo-controlled study in baboons (Papio hamadryas). Am J Obstet Gynecol 171:633–642
Buttar HS (1997) An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem 176:61–71
Tabacova S (2005) Mode of action: angiotensin-converting enzyme inhibition—developmental effects associated with exposure to ACE inhibitors. Crit Rev Toxicol 35:747–755
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Lennestål, R., Otterblad Olausson, P. & Källén, B. Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants. Eur J Clin Pharmacol 65, 615–625 (2009). https://doi.org/10.1007/s00228-009-0620-0
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DOI: https://doi.org/10.1007/s00228-009-0620-0