Attention deficit hyperactivity disorder (ADHD) is estimated to affect 4.4% of adults in the United States (
1). It is associated with an elevated risk of poorer general and mental health, substance abuse, impaired work performance, and financial distress (
2). Approximately half of adults who had childhood ADHD continue to have the disorder and associated impairments (
1). There is a growing appreciation that girls with ADHD have a substantial likelihood of continuing to have the disorder in adulthood. Biederman et al. (
3) assessed a cohort of girls and demonstrated with longitudinal follow-up that a majority are still affected by ADHD more than a decade later, with approximately one-third continuing to meet full criteria for the disorder, approximately another third meeting partial criteria, and 10% experiencing impaired functioning. A diagnosis of ADHD is also associated with a higher risk of subsequent diagnoses of mood, anxiety, and substance use disorders (
4).
Considerations in Pregnancy
There have been no systematic studies evaluating the course of ADHD across pregnancy and the postpartum period. It is possible that the perinatal period has an impact on the course of ADHD as a result of hormonal changes or other factors. It is plausible that women experience greater distraction from other areas as they focus increasingly on a life transition to motherhood. Treatment decisions are affected by pregnancy, as the wish to avoid medication exposure during pregnancy motivates many women to discontinue stimulants during pregnancy and while breastfeeding. Little is known about the impact of treatment decisions on occupational functioning, interpersonal relationships, course of comorbid illnesses, and quality of life.
Neurocognition, Memory, and Executive Functioning During Pregnancy
It is debatable whether women experience neurocognitive changes across pregnancy. There have been observations that neurocognitive functions, including memory, may be negatively affected by pregnancy, and pregnant women are more likely than nonpregnant women to assess their memory as impaired (
5,
6). Indeed, it is widely believed that there is a syndrome of “pregnancy brain” with memory impairment during pregnancy, the hypothesis being that changes in sex hormone production lead to worsening cognition (
7). We lack studies assessing women with ADHD during pregnancy, but there have been small animal and human studies from which to draw. Some suggest impaired neurocognitive functioning during pregnancy, although these results are inconsistent, and no clear relationships have been elucidated between changes in any one hormone and cognition during pregnancy.
For example, in a study of 19 pregnant women (
8), participants performed better on verbal memory tasks after delivery than they did 2 months before delivery. No associations were found between sex hormones and cognitive performance, although higher levels of progesterone were associated with a higher rate of negative mood states. However, in another study (
9), in which women were assessed in the third trimester and again postpartum (N=55) and compared with nonpregnant comparison women (N=21), investigators found lower verbal memory and processing speed scores for women during pregnancy and the postpartum period relative to the comparison subjects. Prolactin levels were associated with verbal memory and executive functioning scores during pregnancy, while estrogen and cortisol were negatively associated with attention scores in the postpartum period. The timing of such impairments varies among studies (e.g., throughout pregnancy, in late pregnancy only), as does whether such findings extend to the postpartum period (
6,
10,
11). A meta-analysis on this topic (
12) demonstrated that study findings have been inconsistent, and overall there may be impairments among both pregnant and postpartum women on some specific neurocognitive tests of memory, particularly those that draw on executive functioning.
In some animal studies, higher progesterone and estrogen levels have been demonstrated to improve memory. For example, pregnant rats have been reported to outperform nonpregnant female rats on tests of memory and cognition (
13). Other animal studies have shown morphological brain changes during pregnancy in the absence of functional memory impairment (
14).
The inconsistencies in the literature suggest that neurocognitive impairments associated with pregnancy are subtle and unlikely to be experienced universally by pregnant and postpartum women. It is possible that women with preexisting ADHD constitute a vulnerable subgroup for neurocognitive worsening during pregnancy.
Summary and Recommendations
Impairment associated with severe ADHD during pregnancy may have serious consequences, such as psychosocial and financial stressors associated with the untreated disorder when it affects domains such as relationships and occupational functioning. There is also the risk of injury and mortality associated with impaired driving.
Medications may be part of the treatment strategy for women who are trying to conceive or are pregnant or breastfeeding. It is imperative that the benefit of a medication be robust enough to justify any potential exposure during pregnancy. Women approaching childbearing may have had medication-free trials and know in advance how their functioning might be affected if they stop ADHD medications during pregnancy. For women who have not had one, a medication-free trial is warranted, ideally with psychotherapy targeting ADHD symptoms.
For women who have been successfully treated with medications for ADHD and are assessing whether to continue or discontinue medications during pregnancy, key questions in determining the risk of the untreated disorder include:
1.
How have you functioned in the past at work (or school) without the use of medications?
2.
How is your driving when not treated with medications for ADHD? Have you had a history of accidents?
If impairments in work functioning and driving are noted, it is important to explore what accommodations can be made for a pregnancy. For example, can the patient avoid driving? Can the patient implement strategies at work that would minimize the effect of ADHD symptoms, such as changes to her workload or schedule or strategies she might learn through CBT?
A woman who is planning pregnancy might discontinue medication while she is trying to conceive, or might instead wait until she is pregnant to discontinue medications. None of the medications have been demonstrated to have clear risks in very early pregnancy. Women with more severe ADHD may either elect to make major life changes to minimize the impact of ADHD on impairment in their lives or choose to continue using medication. Most available data on stimulant use during pregnancy are derived from use in other contexts, such as substance abuse and weight management during pregnancy, the outcomes of which may not be generalizable to women who use stimulants as prescribed for the treatment of ADHD. The main finding with stimulants is that fetal growth may be reduced when stimulants are used in late pregnancy. Long-term outcomes, including behavioral teratogenicity, have not been adequately studied.
For other non-stimulant medications, such as guanfacine and atomoxetine, even fewer data are available regarding use in pregnancy. More data are available for bupropion, with relatively reassuring information about pregnancy outcomes from prospective studies, except for an inconsistently reported risk of cardiovascular malformation with first-trimester exposure.
Nonpharmacological strategies such as CBT are recommended in order to allow women to function as well as possible during pregnancy either without medication or while using the minimum amount required to maintain functioning. In some cases, such as when a woman has a history of impaired driving when not using medication and there are no alternatives to driving, a stimulant used sparingly on an as-needed basis might be the best and safest option. Since stimulants do have a quick onset, intermittent use is an option, which is not the case with bupropion and atomoxetine, which require daily dosing. Collaborative decision making between patients and their providers is crucial when so many variables and unknowns are involved.