In Utero Antihypertensive Medication Exposure and Neonatal Outcomes: A Data Linkage Cohort Study

Hypertension. 2020 Mar;75(3):628-633. doi: 10.1161/HYPERTENSIONAHA.119.13802. Epub 2019 Dec 30.

Abstract

Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in utero exposure to antihypertensive treatment is conflicting, with many studies suffering from significant methodological issues, such as inappropriate study design, small sample sizes, and no untreated control group. We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010-2014 in Scotland to assess outcomes following in utero exposure to antihypertensive medication. We identified a cohort of 265 488 eligible children born over the study period; of which, 2350 were exposed to in utero antihypertensive medication, 4391 exposed to treated late-onset hypertension, and 7971 exposed to untreated hypertension during pregnancy. Untreated hypertension was associated with increased risk of preterm birth (adjusted risk ratio [aRR], 1.15 [99% CI, 1.01-1.30]), low birth weight (aRR, 2.01 [99% CI, 1.72-2.36]) and being small for gestational age (aRR, 1.50 [99% CI, 1.35-1.66]), while in utero antihypertensive exposure was also associated with preterm birth (aRR, 3.12 [99% CI, 2.68-3.64]), low birth weight (aRR, 2.23 [99% CI, 1.79-2.78]), and being small for gestational age (aRR, 2.13 [99% CI, 1.81-2.52]). Late-onset hypertension was also associated with preterm birth (aRR, 2.21 [99% CI, 1.86-2.62]), low birth weight (aRR, 2.06 [99% CI, 1.74-2.43]), and being small for gestational age (aRR, 1.90 [99% CI, 1.68-2.16]). Our results suggest that hypertension is a key risk factor for low birth weight and preterm birth. Although preterm birth may be associated with antihypertensive medication exposure during pregnancy, these associations may reflect increasing hypertension severity necessitating treatment.

Keywords: antihypertensive agents; child; gestational age; hypertension; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / therapeutic use
  • Cesarean Section / statistics & numerical data
  • Emergencies
  • Female
  • Fetal Growth Retardation / epidemiology
  • Humans
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Hypertension, Pregnancy-Induced / drug therapy
  • Infant, Extremely Low Birth Weight
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature
  • Infant, Small for Gestational Age
  • Middle Aged
  • Pre-Eclampsia / etiology
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / drug therapy
  • Pregnancy Complications, Cardiovascular / physiopathology
  • Pregnancy Outcome*
  • Premature Birth / epidemiology
  • Premature Birth / physiopathology
  • Prenatal Exposure Delayed Effects*
  • Retrospective Studies
  • Risk Factors
  • Scotland / epidemiology
  • Young Adult

Substances

  • Antihypertensive Agents