In This article

• A large claims-based study examined 24,200 pregnancies with prescription stimulant exposure.
• First-trimester stimulant exposure alone was not associated with increased risk for most adverse pregnancy outcomes and was associated with lower rates of some outcomes, including preterm birth and small-for-gestational-age infants.
• Continued stimulant exposure into the second and third trimesters was associated with higher rates of pre-eclampsia, placental abruption, preterm birth, stillbirth, and small-for-gestational-age infants.
• Because this was an observational study, the findings do not establish that stimulant treatment causes these adverse outcomes. Differences in ADHD severity, psychiatric comorbidity, stimulant dose, health behaviors, and other factors may contribute to the observed associations.
• Decisions about stimulant treatment during pregnancy should be individualized, balancing potential medication-related risks against the potential consequences of untreated ADHD.

Several recent articles have raised concerns about the safety of ADHD medications during pregnancy. In our clinic, we are seeing more women with ADHD who are planning pregnancy.  While they have ADHD, they are typically a more complex population, with high rates of co-occurring mood and anxiety disorders. In this setting, ADHD medications may do more than support executive functioning; they may be essential to mood stability and overall functioning.  

Medical news outlets are quick to report new findings but rarely place them within the context of the broader research literature. Over the coming weeks, we will publish a three-part series reviewing recent studies on ADHD medications and pregnancy outcomes, aiming to give patients and providers the fuller picture needed to make informed decisions.

This is the first of a 3-part series on pregnancy outcomes in women using ADHD medications during pregnancy.  A large new claims-based study by Hasan and colleagues offers additional information on the impact of the use of prescription stimulants during pregnancy and maternal and fetal outcomes.

Study Design and Results

Using MarketScan Commercial Claims and Encounters data (2013–2021) — covering more than 30 million lives across over 100 health plans — the researchers identified 24,200 pregnancies with stimulant exposure (amphetamine- or methylphenidate-containing medications) at some point from the pre-pregnancy period through delivery. Within this group:

• 6,113 pregnancies (25.3%) had exposure only before conception
• 18,087 (74.7%) had exposure during pregnancy itself
• Of those exposed during pregnancy, 10,266 (56.8%) discontinued treatment in the first trimester, while 7,821 (43.2%) continued into the second or third trimester

Each exposure group was compared against a matched cohort of pregnancies with no stimulant exposure. 

Outcomes assessed included spontaneous abortion, ectopic pregnancy, and stillbirth, along with obstetric complications such as placental abruption, pre-eclampsia, gestational hypertension, small-for-gestational-age infants, and preterm birth.

Stimulant exposure limited to the first trimester:

• Stimulant use during the first trimester was not associated with an increased risk of most adverse outcomes compared with unexposed pregnancies
• First-trimester stimulant use associated with reduced risks of spontaneous abortion, preterm birth, and small-for-gestational-age infants

Explaining the lower risk of some adverse outcomes, the authors suggest that ADHD symptom control in early pregnancy may support better engagement with prenatal care and healthier maternal behaviors, indirectly benefiting pregnancy outcomes.

Continued exposure into the second or third trimester:

• Use of stimulants throughout pregnancy was associated with increased risk of hypertensive disorders of pregnancy, placental abruption, preterm birth, stillbirth, and small-for-gestational-age infants
• Increased risk was observed when stimulant-exposed pregnancies were compared to unexposed pregnancies and when compared to pregnancies with early (first-trimester-only) exposure

In comparing pregnancies with continued (trimester 2 and 3) exposure against those with early, first-trimester-only exposure, continuation carries higher risk of some adverse outcomes:

• Gestational hypertension: No significant difference between groups
• Pre-eclampsia: Higher in the continued-exposure group (RR = 1.33, 95% CI [1.12, 1.59])
• Placental abruption: Higher in the continued-exposure group (RR = 1.78, 95% CI [1.11, 2.84])
• Stillbirth: Higher in the continued-exposure group (RR = 3.54, 95% CI [1.48, 8.44])
• Preterm birth (RR = 1.86, 95% CI [1.51, 2.28])
• Small for gestational age (RR = 1.47, 95% CI [1.12, 1.92])

Possible Explanations for the Findings

The findings are biologically plausible. Prescription stimulants can increase blood pressure and cause blood vessel constriction, which could potentially reduce blood flow to the placenta. This may help explain the higher rates of hypertensive disorders, placental abruption, fetal growth restriction, and preterm birth observed with continued stimulant exposure.

However, there is another important possibility: confounding by indication. In this naturalistic study, women who continue stimulant treatment throughout pregnancy may differ in important ways from those who discontinue treatment. They may have more severe ADHD or higher levels of psychiatric comorbidity, including anxiety or depression, as well as differences in health behaviors or engagement with prenatal care. These factors may themselves be associated with adverse pregnancy outcomes.

Notably, previous studies have linked depression and anxiety with adverse outcomes, including preterm birth, hypertension during pregnancy, and pre-eclampsia. Thus, while stimulant medications may contribute to increased vulnerability to these outcomes, it is also possible that women who elect to continue stimulants during pregnancy have underlying psychiatric or behavioral characteristics that independently increase risk.

The researchers used propensity-score matching to account for differences between the groups, but this approach cannot eliminate confounding from factors that were not measured or adequately captured in the claims data. In particular, the study cannot fully account for differences in ADHD severity, stimulant dose, clinical decision-making, or other behavioral and social factors.

This is an important limitation when interpreting the findings. The study shows an association between continued stimulant exposure and certain adverse pregnancy outcomes; it does not establish that stimulant treatment caused these outcomes. The fact that risks were higher among women who continued treatment raises concerns and warrants attention, but further research is needed to determine how much of this increased risk is attributable to the medication itself and how much reflects differences in the women who continue treatment during pregnancy.

Stimulant Use During Pregnancy: What This Study Means

This study adds to a growing body of literature regarding the use of ADHD medications during pregnancy.  Continued treatment with stimulants throughout the pregnancy was associated with a small increase in risk for several complications, including pre-eclampsia, placental abruption, preterm birth, stillbirth, and small-for-gestational-age infants; however, because these findings come from an observational study, one cannot establish that stimulants cause these outcomes. 

Decisions about continuing or discontinuing stimulant treatment during pregnancy should therefore be individualized, weighing the potential risks of medication exposure against the consequences of untreated ADHD, including impaired functioning, increased risk of accidents, difficulty maintaining healthy behaviors and prenatal care, and increased vulnerability to perinatal mood and anxiety disorders.

—Ruta Nonacs, MD PhD