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.
Highlights
Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment
Hypertension during pregnancy can fall into several categories: chronic hypertension, indicated by a diagnosis of hypertension or antihypertensive use before 20 weeks, or if unresolved following birth; gestational hypertension, indicated by new onset diagnosis of hypertension after 20 weeks gestation, without proteinuria; preeclampsia, indicated by hypertension occurring after 20 weeks gestation, with or without proteinuria; and preeclampsia superimposed on chronic hypertension, indicated by preeclampsia in the presence of previously diagnosed hypertension.[20]
While there is previous literature reporting an increased risk of adverse outcomes, such as preterm birth and low birth weight following in utero antihypertensive exposure,[2,4,5,6,17,23] the majority of these studies were of small size, had a poor study design, such as inappropriate control groups, methodologies with residual confounding, and lacked an untreated hypertensive group, leading to further possible confounding
Summary
Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. With some reporting an increased incidence of preterm birth[1,2,3,4,5,6] and low birth weight,[1,3,4,5] while others report no increased risk.[7,8,9] We recently reviewed antihypertensive use during pregnancy and child outcomes[10] and identified a lack of good quality studies, with many limited by self-reported medication use,[1,6,11,12] small study size,[13,14,15] and a lack of an untreated comparison group.[1,6,11,12,13,16,17,18] An updated Cochrane review[19] assessed trials investigating antihypertensive medication in mild to moderate hypertension during pregnancy and concluded that there was no association between preterm birth or being small for gestational age following medication exposure. The aim of this study was to assess the immediate birth outcomes for mother and child after in utero exposure to antihypertensive medication
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