Specific Birth Defects Following Antiseizure Medications Used By Pregnant Women With Epilepsy.

Background and Objectives: Previous research has been limited in the comprehensive study of associations between the use of individual antiseizure medications (ASMs) in pregnancy and specific groups of birth defects, and systematic reviews and meta-analyses on the topic are limited by pooled samples and study designs. This study investigated birth defects related to ASM use in pregnancy in children born to women with epilepsy in Sweden over 20 years. Methods: We used data from Swedish national registers to follow a cohort of 17,996 children born to women diagnosed with epilepsy any time before conception in Sweden from 1996 to 2016, following them through 2017. We examined maternal-reported use of the 4 most commonly reported ASMs: lamotrigine (n = 2,148, 11.9%), carbamazepine (n = 1,940, 10.8%), valproic acid (n = 1,043, 5.80%), and levetiracetam (n = 587, 3.26%). We identified birth defects using diagnoses recorded at the time of discharge from the hospital and inpatient and outpatient diagnoses recorded in the first year of life. Models were estimated in a stepped fashion: unadjusted, adjusted for covariates, among a subcohort born to women diagnosed 10 years before conception (n = 14,586), and restricted to monotherapy. Results: Valproic acid use in pregnancy had the strongest and most widespread associations with birth defects in children, with carbamazepine also having links to several birth defects, including respiratory system and genital organ defects. Lamotrigine use in pregnancy was associated with cleft lip/palate and chromosomal abnormalities. Levetiracetam was most often used with other ASMs and preliminarily associated with many birth defects. Discussion: Our findings support avoidance of valproic acid use in pregnancy whenever possible. Lamotrigine and carbamazepine may be safer alternatives. However, these medications were also associated with certain birth defects, including some not reported previously. We are among the first to examine the possible effects of levetiracetam use in pregnancy, though more research is needed to investigate this further.

Preliminary examination of ADHD inattentive and cognitive disengagement syndrome symptoms in relation to probe-caught mind-wandering during a sustained attention to response task.

OBJECTIVE: The role of mind-wandering- periods of internally-directed distractibility - among patients with attention-deficit/hyperactivity disorder (ADHD) has recently garnered attention, though few studies have assessed mind-wandering using thought probes during a sustained attention to response task (SART) or examined the possible role of cognitive disengagement syndrome (CDS) symptoms. We examined whether parent- and/or teacher-reported ADHD-inattentive (ADHD-IN) or CDS symptoms were independently associated with probe-caught mind-wandering. METHODS: Fifty-four children (ages 9-12; 35.2% female) completed a SART with thought probes inquiring about various on- and off-task thoughts, including mind-wandering and distraction. Questionnaires provided information on demographics, medication treatment, and parent- and teacher-reported ADHD-IN and CDS symptoms. Regression models were estimated separately by informant to examine whether ADHD-IN or CDS symptoms were uniquely associated with mind-wandering or distraction frequency during the SART. RESULTS: Higher teacher-reported CDS ratings, but not ADHD-IN ratings, were uniquely associated with more probe-caught mind-wandering. No significant findings related to parent-reported symptoms or probe-caught distraction were observed. CONCLUSIONS: These preliminary findings add to an emerging body of work pointing to CDS as more consistently or strongly associated than ADHD-IN with mind-wandering. Theoretical and clinical implications are discussed.

Examining daily stimulant medication use and sleep in adolescents with ADHD.

Research has been inconclusive as to whether stimulant treatment causes or exacerbates sleep problems in adolescents with ADHD. This study examined sleep differences in adolescents with ADHD as a function of stimulant use. Participants were adolescents with ADHD (N = 159, ages 12-14). Parents reported on receipt of stimulant treatment (n = 92, 57.86%; n = 47 amphetamines, n = 45 methylphenidate). Adolescents wore actigraphs and completed daily diaries assessing sleep and daily use of stimulants for 2 weeks. Sleep parameters included daily-reported bedtime, sleep onset latency (SOL), sleep duration, daytime sleepiness, and difficulty waking the following morning; and actigraphy-measured sleep onset time, total time in bed, and sleep efficiency. We estimated between- and within-individual associations between stimulant medication use and sleep indices with all stimulants, after removing adolescents using sleep aids and weekend days, and as a function of stimulant type. Adolescent sleep did not differ between those receiving and not receiving stimulant treatment. Within individuals using stimulants, we largely observed no significant differences between medicated and unmedicated days, though findings were most often significant for school days only. Small effects were found indicating longer SOL, later sleep onset time, and more daytime sleepiness related to medication use. In contrast, there were slight improvements to sleep duration and sleep efficiency related to methylphenidate use, though methylphenidate was also associated with later sleep onset time and more daytime sleepiness. Given the inconsistent and small effects, findings suggest that stimulant medication may impact sleep, but does not appear to be a primary contributor to sleep problems in adolescents with ADHD.

Multi-method examination of cognitive disengagement syndrome and ADHD inattentive symptoms in relation to early adolescents' academic functioning.

Cognitive disengagement syndrome (CDS), previously referred to as sluggish cognitive tempo, is a set of symptoms characterized by excessive daydreaming, mental fogginess, and slowed behavior/thinking. Studies examining the association between CDS and academic functioning have reported mixed findings and have relied upon limited measures of CDS, broad ratings of academic impairment, and/or focused only on elementary-aged children. The current study examined the relationship between CDS and academic functioning in adolescents using a comprehensive, multi-informant, multi-method design. Participants were 302 adolescents (Mage = 13.17 years; 44.7% female; 81.8% White; 52% with ADHD) recruited in the fall of their 8th grade. Above and beyond ADHD inattentive symptoms, CDS symptoms were related to poorer homework performance, lower math fluency, and lower daily academic motivation across multiple informants, and teacher-reported CDS symptoms were related to lower grades. Findings were not moderated by ADHD diagnosis, suggesting that associations between CDS and academic outcomes do not differ for adolescents with and without ADHD. Findings demonstrate that CDS symptoms are uniquely associated with daily academic difficulties as well as global indices of academic performance. These findings have implications for assessing and monitoring CDS symptoms in interventions aiming to improve the academic functioning in adolescents with and without ADHD.

Pharmacologic Management of Cognitive Disengagement Syndrome (CDS) and Implications for Attention-Deficit/Hyperactivity Disorder (ADHD) Treatment: Emerging Treatments and Recommendations for Future Research.

Although the study of cognitive disengagement syndrome (CDS; previously called sluggish cognitive tempo) first emerged in the 1980s, very little is known about treating CDS or its impact on evidence-based interventions for attention-deficit/hyperactivity disorder (ADHD) with which it frequently co-occurs. The objective of this leading article was to investigate the existing evidence on medication treatment and CDS, including studies that have examined CDS response to medication and CDS as a moderator of ADHD treatment response. A total of seven studies were identified. At present, the limited existing literature suggests that psychostimulants such as methylphenidate and lisdexamfetamine, as well as atomoxetine, may improve CDS symptoms, although replication and research on related medications is needed. However, there are indications that CDS symptoms may predict a reduced response to methylphenidate in children with ADHD. Although untested, research on the neurobiological, neuropsychological, and behavioral correlates of CDS point to a possible benefit of other ADHD medications (e.g., guanfacine), medications that treat narcolepsy (e.g., modafinil), and medications traditionally used to treat depression and anxiety (e.g., viloxazine, bupropion, fluvoxamine), some of which have also recently been used in ADHD management. The article concludes with recommendations for future research on pharmacologic treatment and CDS.

A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures.

OBJECTIVE: The present study aimed to examine whether antidepressant initiation increases the risk of hospitalizations and unplanned outpatient visits for seizures. Research has provided conflicting evidence as to whether antidepressant initiation causes seizures. Because epilepsy and depression are comorbid, this remains an important question, particularly in the care of those already at-risk for seizures. METHODS: We used Swedish-register data, including 658,766 antidepressant initiators and 1:1 age-, region-, and sex-matched non-initiators, ages 12-65. We used filled prescriptions to identify any antidepressant and serotonergic antidepressant and inpatient hospitalizations and unplanned outpatient (to avoid coding routine epilepsy maintenance as a seizure) visits to identify seizures, respectively. We first compared seizure visit incidence between antidepressant-initiators and matched non-users in the year following initiation from 2006 to 2013. To examine seizure risk over months pre- and post-initiation, within-individual analyses compared risk during the month one year prior to initiation with all subsequent months. We examined associations for any antidepressant and serotonergic antidepressants, as well as for any initiator and initiators with a history of seizures. RESULTS: Our matched-cohort results showed higher incidence of seizure visits among antidepressant users compared with non-users (e.g., adjusted incidence rate ratio [IRR]=3.14, 95% confidence interval [CI]=2.83-3.49). In within-individual analyses, the months after initiation were associated with higher incidence of seizure visits when compared with the month one year prior to initiation (e.g., one month after initiation IRR=1.96, 95%CI=1.64-2.34), but in individuals with a seizure history we observed weaker or no associations in the months after initiation (e.g., two months after initiation IRR=1.12, 95%CI=0.87-1.45). Notably, irrespective of potential seizure history, the months preceding initiation were associated with the greatest risk (e.g., one month before initiation IRR=2.86, 95% CI=2.42-3.38). CONCLUSIONS: Our findings suggest that there may be an elevated risk of seizures during antidepressant treatment, though the period of highest risk was before the initiation of antidepressants. Risk for seizure visits was lower among individuals with a history of prior seizures, which may be reassuring for the clinical care of these patients or indicate lack of treatment seeking following seizures. This study highlights the need to consider seizure risk across time; the failure to account for these dynamics may help account for discrepant findings in previous studies.

Physical and Extracurricular Activity in Adolescents With and Without ADHD: Examining Group Differences and the Role of Cognitive Disengagement Syndrome Symptoms.

OBJECTIVE: This study examined extracurricular and physical activity related to ADHD (diagnosis and symptoms) and cognitive disengagement syndrome (CDS) symptoms. METHODS: Participants were 302 adolescents (ages 12-14) with and without ADHD and primary caregivers. ADHD diagnosis was determined with parent interview. Questionnaires provided information on parent-reported demographic characteristics, ADHD symptoms, and extracurricular activity involvement; and adolescent-reported ADHD and CDS symptoms and indices of physical activity. RESULTS: Although ADHD diagnosis and symptom dimensions were correlated with less extracurricular and physical activity involvement, CDS symptoms were most often independently associated with these outcomes. Females and adolescents from lower income homes also often had less involvement in extracurricular and physical activity. CONCLUSIONS: Findings point to the need for more research in this area, careful assessment of risk factors (i.e., CDS symptoms, economic burden), and interventions that address inactivity in adolescents with ADHD, including those that address inequity related to income and sex.

Suicide Risk Before Mental Health Treatment Initiation: Implications for Screening and Access to Care.

With rising suicide rates in the United States over the past two decades, a critical need has emerged to improve interventions to prevent suicide. Previous research has indicated that the period before initiation of mental health treatment may be a particularly vulnerable time for individuals with suicidal behavior. Presence of suicide risk before treatment initiation highlights the need to improve suicide screening and access to care. The authors propose various care and policy considerations to increase, support, and maintain suicide prevention efforts.

A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions.

INTRODUCTION: Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women. STUDY DESIGN: We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications. RESULTS: The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions-from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics-38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of preexisting mental health diagnoses (e.g. anxiety disorder odds ratio [OR] = 3.13, 95% confidence interval [CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g. benzodiazepines OR = 4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids. CONCLUSIONS: These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.

A population-based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes.

BACKGROUND: Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood. OBJECTIVES: We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes. METHODS: We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights. RESULTS: After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52). CONCLUSIONS: Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.

Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.

OBJECTIVE: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors. METHODS: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication. RESULTS: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53). CONCLUSIONS: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.

Maternal prescribed opioid analgesic use during pregnancy and associations with adverse birth outcomes: A population-based study.

BACKGROUND: Published research on prescribed opioid analgesic (POA) use during pregnancy and birth outcomes is limited in scope and has not adequately adjusted for potential confounding factors. To help address these gaps, we estimated associations between maternal POAs during pregnancy and two adverse birth outcomes using a large population-based dataset, multiple definitions of POA exposure, and several methods to evaluate the influence of both measured and unmeasured confounding factors. METHODS AND FINDINGS: We obtained data by linking information from several Swedish registers and conducted a retrospective cohort study on a population-based sample of 620,458 Swedish births occurring between 2007 and 2013 (48.6% female; 44.4% firstborn). We evaluated associations between prenatal POA exposure and risk for preterm birth (PTB; <37 gestational weeks) and small for gestational age (SGA; birth weight 2 standard deviations below the expected weight for gestational age or lower). We evaluated the influence of confounding by adjusting for a wide range of measured covariates while comparing exposed and unexposed infants. Additionally, we adjusted for unmeasured confounding factors by using several advanced epidemiological designs. Infants exposed to POAs anytime during pregnancy were at increased risk for PTB compared with unexposed infants (6.4% exposed versus 4.4% unexposed; adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.31-1.45, p < 0.001). This association was attenuated when we compared POA-exposed infants with acetaminophen-exposed infants (OR = 1.18, 95% CI 1.07-1.30, p < 0.001), infants born to women who used POAs before pregnancy only (OR = 1.05, 95% CI 0.96-1.14, p = 0.27), and unexposed siblings (OR = 0.99, 95% CI 0.85-1.14, p = 0.92). We also evaluated associations with short-term versus persistent POA use during pregnancy and observed a similar pattern of results, although the magnitudes of associations with persistent exposure were larger than associations with any use or short-term use. Although short-term use was not associated with SGA (adjusted ORsingle-trimester = 0.95, 95% CI 0.87-1.04, p = 0.29), persistent use was associated with increased risk for SGA (adjusted ORmultiple-trimester = 1.40, 95% CI 1.17-1.67, p < 0.001) compared with unexposed infants. The association with persistent exposure was attenuated when we used alternative comparison groups (e.g., sibling comparison OR = 1.22, 95% CI 0.60-2.48, p = 0.58). Of note, our study had limitations, including potential bias from exposure misclassification, an inability to adjust for all sources of confounding, and uncertainty regarding generalizability to countries outside of Sweden. CONCLUSIONS: Our results suggested that observed associations between POA use during pregnancy and risk of PTB and SGA were largely due to unmeasured confounding factors, although we could not rule out small independent associations, particularly for persistent POA use during pregnancy.

Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy. METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within-individual to adjust for unmeasured, time?constant confounding. RESULTS: Among 995 individuals who initiated ADHD medication during follow-up, within-individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person-years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57-0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders. SIGNIFICANCE: We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.

Symbolic flexibility during unsupervised word learning in children and adults.

Considerable debate in language acquisition concerns whether word learning is driven by domain-general (symbolically flexible) or domain-specific learning mechanisms. Prior work has shown that very young children can map objects to either words or nonlinguistic sounds, but by 20 months of age this ability narrows to only words. This suggests that although symbolically flexible mechanisms are operative early, they become more specified over development. However, such research has been conducted only with young children in ostensive teaching contexts. Thus, we investigated symbolic flexibility at later ages in more referentially ambiguous learning situations. In Experiment 1, 47 6- to 8-year-olds acquired eight symbol-object mappings in a cross-situational word learning paradigm where multiple mappings are learned based only on co-occurrence. In the word condition participants learned with novel pseudowords, whereas in the sound condition participants learned with nonlinguistic sounds (e.g., beeps). Children acquired the mappings, but performance did not differ across conditions, suggesting broad symbolic flexibility. In Experiment 2, 41 adults learned 16 mappings in a comparable design. They learned with ease in both conditions but showed a significant advantage for words. Thus, symbolic flexibility decreases with age, potentially due to repeated experiences with linguistic materials. Moreover, trial-by-trial analyses of the microstructure of both children's and adults' performance did not reveal any substantial differences due to condition, consistent with the hypothesis that learning mechanisms are generally employed similarly with both words and nonlinguistic sounds.

Attention-deficit/hyperactivity disorder medication and seizures.

OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures. METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication. RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history. CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.

A Family-Based Study of the Association Between Labor Induction and Offspring Attention-Deficit Hyperactivity Disorder and Low Academic Achievement.

The current study examined associations between labor induction and both (1) offspring attention-deficit hyperactivity disorder (ADHD) diagnosis in a Swedish birth cohort born 1992-2005 (n = 1,085,008) and (2) indices of offspring low academic achievement in a sub-cohort born 1992-1997 (n = 489,196). Associations were examined in the entire sample (i.e., related and unrelated individuals) with adjustment for measured covariates and, in order to account for unmeasured confounders shared within families, within differentially exposed cousins and siblings. We observed an association between labor induction and offspring ADHD diagnosis and low academic achievement in the population. However, these associations were fully attenuated after adjusting for measured covariates and unmeasured factors that cousins and siblings share. The results suggest that observed associations between labor induction and ADHD and low academic achievement may be due to genetic and/or shared environmental factors that influence both mothers' risk of labor induction and offspring neurodevelopment.