Strengths and Limitations
One strength is that we quantified the impact of exposure misclassification, applied methods to deal with time-varying exposure and confounders, missing data, and examined ADHD risks from a diagnosis and symptom perspective.7 We attempted to limit confounding by indication by including only women with clinical depression/anxiety during pregnancy, and measured their symptom severity at two time points in pregnancy via a validated instrument.17 We carried out several sensitivity and sub-analyses to explore the robustness of our findings, as well as the role of confounding by maternal psychiatric indicators prior to gestation. In addition, we attempted to overcome the limitation of averaged HRs by estimating period-specific hazards; however, the built-in bias of differential selection on these results cannot be excluded. In addition, we cannot rule out the role of residual confounding by depression severity, genetic, environmental or familial factors, or even chance, on our findings.
Several limitations need mentioning. Symptoms of depressive and anxiety were not measured at baseline, but only at two time points in pregnancy. We relied on maternal self-report of depression/anxiety during or prior to pregnancy, which cannot replace a clinical diagnosis. Information on dosage is not available in MoBa. The ADHD symptom measure was mother-reported. Although the risk of outcome misclassification cannot be ruled out, this was probably non-differential, and the depression-distortion bias had a negligible impact on our effect estimates. Also, the internal consistency of the CPRS-R was high. The MoBa study has a low response rate (41%), with a possible self-selection of the healthiest women into the cohort.10,11 Although association measures have been shown to be valid in MoBa in relation to immediate birth outcomes,34 the impact of selection bias on longer-term outcomes cannot be excluded.35 Our small sample size precluded analyses of SSRI and SNRI as separate groups, or for individual antidepressants, as well as sibling-design analysis. We could, however, take into account familial risk of ADHD using parental ADHD-medications use, as well as parental self-report ADHD symptoms in a subsample.