Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system
Open accessAbstract
Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.
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- Findingown data
In this study, no significant association with prior antidepressant use was noted after adjustment for maternal psychopathology.
“However, in the present study, no significant association with prior antidepressant use is noted after adjustment for maternal psychopathology.”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
Analysis of delivery complications did not identify differences between ADHD cases and controls that might mediate the observed risk.
“(Analysis of delivery complications also did not identify differences between ADHD cases and controls that might mediate the observed risk, in contrast to the increased rate of cesarean section for ASD cases versus controls).”
Quote in the paperNot a substantial claim - Findingown data
In adjusted models without maternal diagnosis, antidepressant exposure during pregnancy was associated with ASD risk.
“In adjusted models which did not include maternal diagnosis, antidepressant exposure was associated with ASD risk, as in some prior reports.”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
First-trimester antidepressant exposure had an adjusted odds ratio greater than 2.0 for ADHD.
“Notably, consideration of the first trimester yields adjusted OR >2.0, strongly suggesting that it is the period of greatest risk, although a prior report suggested greatest risk in second trimester12.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Figueroa R . Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31: 641–648. source
Not checked in the free run.
- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
Antidepressant use before pregnancy was associated with increased ASD risk (OR 1.91, 95% CI 1.41-2.58).
“Antidepressant use prior to pregnancy was associated with increase in risk for ASD (OR 1.91 (95% CI 1.41–2.58)).”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
ASD risk was not greater among high-affinity antidepressants.
“Notably, risk was not greater among high-affinity antidepressants, as would be expected under the original biological hypothesis for ASD.”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
After adding maternal depression, the pre-pregnancy antidepressant association with ADHD was no longer statistically significant (OR 1.18, 95% CI 0.86-1.61).
“However, unlike with ASD, the addition of maternal depression to models resulted in this risk no longer remaining statistically significant (OR 1.18 (95% CI 0.86–1.61)).”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
Antidepressant exposure before pregnancy was associated with ADHD risk in offspring in adjusted models (OR 1.69, 95% CI 1.25-2.25).
“As with ASD, antidepressant exposure prior to pregnancy was associated with risk for ADHD in offspring (OR 1.69 (95% CI 1.25–2.25)) in adjusted models.”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
The ASD risk associated with pre-pregnancy antidepressant use remained significant after adjustment for maternal major depressive disorder history.
“Notably, significant ASD risk with pre-pregnancy antidepressant use persisted after adjustment for history of maternal major depressive disorder.”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
For ASD, adding measures of maternal treatment intensity reduced the observed antidepressant effect by more than 10%.
“Notably, inclusion of elements of treatment intensity led to reduction in observed effect by more than 10%, a common rule of thumb for confounding.”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
- Findingown data
Earlier maternal age was associated with ADHD risk in adjusted models.
“Consistent with prior reports, in adjusted models, advanced paternal and maternal age were significantly associated with ASD risk, while earlier maternal age was associated with ADHD risk.”
Quote in the paperNot a substantial claim - Findingown data
Advanced paternal and maternal age were significantly associated with ASD risk in adjusted models.
“Consistent with prior reports, in adjusted models, advanced paternal and maternal age were significantly associated with ASD risk, while earlier maternal age was associated with ADHD risk.”
Quote in the paperNot a substantial claim - Interpretationown data
The first trimester is likely the period of greatest ADHD risk.
“Notably, consideration of the first trimester yields adjusted OR >2.0, strongly suggesting that it is the period of greatest risk, although a prior report suggested greatest risk in second trimester12.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Figueroa R . Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31: 641–648. source
Not checked in the free run.
- Premisecitation
In a prior northern California health plan study of 298 ASD children, antidepressant exposure was associated with adjusted OR 2.2 for ASD.
“In the first study, which included 298 children with ASD in a northern California health plan, antidepressant exposure was associated with adjusted odds ratio of 2.2 for ASD5.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V . Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68: 1104–1112. source
Not checked in the free run.
- Study design and conductreasoning
Clinical markers were likely insufficient to fully capture severity differences between treated and untreated mothers.
“our clinical markers were likely insufficient to fully capture severity differences between treated and untreated mothers.”
Quote in the paperNot a substantial claim - Study design and conductown data
ICD-9 codes for ASD and ADHD had high sensitivity and specificity against blinded neuropsychologist review in the Partners system: ASD sensitivity 1.00 and specificity 0.91; ADHD sensitivity 0.84 and specificity 0.90.
“ICD-9 codes have a high sensitivity and specificity for ASD and ADHD versus healthy control children in the Partners Healthcare system based on blinded review of 60 ASD, ADHD, and healthy control records by an experienced child neuropsychologist (for ASD, sensitivity is 1.00, specificity 0.91; for ADHD, sensitivity is 0.84, specificity 0.90).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V . Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68: 1104–1112. source
Not checked in the free run.
- Interpretationown data
The association between prenatal antidepressant exposure and ASD appeared to result from confounding by maternal psychopathology.
“we identified an association between prenatal antidepressant exposure and risk for ASD which appeared to result from confounding by maternal psychopathology.”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Interpretationown data
The results provide the most direct evidence to date that the ASD risk observed in the two initial reports likely represents confounding by indication.
“First, these results provide the most direct evidence to date that risk for ASD observed in the two initial reports is likely to represent confounding by indication, with antidepressant-treated mothers experiencing greater psychopathology and treatment intensity overall.”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Interpretationown data
Despite a similar pattern of confounding, some ADHD risk appears to persist.
“Third, they indicate that despite a similar pattern of confounding, some risk appears to persist for ADHD, consistent with effects observed in two prior studies, one using claims data, the other a national registry from Denmark12, 13.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [12] Figueroa R . Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31: 641–648. source
Not checked in the free run.
- cites [13] Laugesen K, Olsen MS, Telen Andersen AB, Froslev T, Sorensen HT . In utero exposure to antidepressant drugs and risk of attention deficit hyperactivity disorder: a nationwide Danish cohort study. BMJ Open 2013; 3: e003507. source
Not checked in the free run.
- Study design and conductnone given
Misclassification would tend to bias results toward the null, underestimating rather than inflating true effects.
“Further, with the notable exception of systematic misclassification noted above, misclassification would tend to bias us towards the null hypothesis, underestimating rather than inflating true effects.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
Some control subjects may actually have ASD diagnosed elsewhere because Partners is not a closed system.
“First, there is some risk of misclassification because the Partners healthcare system is not a closed system: some control subjects may actually have ASD diagnosed elsewhere.”
Quote in the paperNot a substantial claim - Interpretationown data
The present study adds to a body of evidence suggesting that the apparent risk of depression treatment during pregnancy may actually reflect maternal psychopathology.
“The present study adds to a body of evidence suggesting that the apparent risk of depression treatment during pregnancy may actually reflect maternal psychopathology;”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Premisecitation
One study found rates of depressive relapse increased 5-fold when antidepressants were discontinued during pregnancy.
“One study found that rates of depressive relapse were increased 5-fold when antidepressants were discontinued during pregnancy8;”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006; 295: 499–507. source
Not checked in the free run.
- May combine two claims. 16
- Classified as probably not a substantial claim. 20
May combine two claims.
Findingown dataFirst pregnancy was associated with risk for both ASD and ADHD.
“Maternal diagnosis of major depressive disorder was associated with risk for both ASD and ADHD, as was first pregnancy.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFor ADHD, adding measures of psychiatric comorbidity and treatment intensity made the antidepressant effect substantially more modest, though adjusted odds ratios with nearly all measures still exceeded 1.7.
“Similar results were observed for ADHD: the effect of antidepressant exposure was substantially more modest when measures of psychiatric comorbidity and treatment intensity were included, although adjusted odds ratios with nearly all measures still exceeded 1.7 (Table 3B)”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
May combine two claims.
Findingown dataMaternal diagnosis of major depressive disorder was associated with risk for both ASD and ADHD.
“Maternal diagnosis of major depressive disorder was associated with risk for both ASD and ADHD, as was first pregnancy.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAntidepressant exposure during pregnancy was associated with ADHD risk, and this association remained significant after adding maternal depression (OR 1.81, 95% CI 1.22-2.70).
“During pregnancy, antidepressant exposure was also associated with ADHD risk; the magnitude of risk was substantially less, but remained significant, after addition of maternal depression to the model. (OR 1.81 (95% CI 1.22–2.70)).”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataCesarean section was associated with autism risk in crude and adjusted models.
“Table 1B depicts details of delivery, with cesarean section associated with autism risk in crude and adjusted models as in prior reports19;”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Schieve LA, Tian LH, Baio J, Rankin K, Rosenberg D, Wiggins L et al. Population attributable fractions for three perinatal risk factors for autism spectrum disorders, 2002 and 2008 autism and developmental disabilities monitoring network. Ann Epidemiol 2014; 24: 260–266. source
Not checked in the free run.
May combine two claims.
Findingown dataThe overall adjusted ASD odds ratio with antidepressants was about 1.1, with a confidence interval that did not exclude 1.
“The magnitude of ASD risk observed with antidepressants overall (adjusted OR ~1.1) is substantially more modest than that observed in two prior studies, with a confidence interval that does not exclude 1.”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
May combine two claims.
Findingown dataAntipsychotic prescription during pregnancy was associated with numerically greater ASD risk than antidepressants, but this risk was not observed for ADHD.
“antipsychotic prescription during pregnancy was associated with numerically greater risk for ASD than antidepressants, although this risk was not observed with ADHD.”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
May combine two claims.
Findingown dataOndansetron exposure during pregnancy showed no evidence of association with ASD or ADHD risk.
“We observed no evidence of association with ASD or ADHD risk.”
Quote in the paperNot a substantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
May combine two claims.
Findingown dataAfter adding maternal major depression, the association between antidepressant exposure during pregnancy and ASD risk was substantially reduced and no longer statistically significant (OR 1.10, 95% CI 0.70-1.70).
“However, with the addition of maternal major depression, this association was substantially reduced and no longer statistically significant (OR 1.10 (95% CI 0.70–1.70)).”
Quote in the paperSubstantial claim- Rests on an assumption: Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
- Rests on an assumption: The matched control children are free of ASD and ADHD.
May combine two claims.
Findingown dataGreater maternal and paternal education had protective effects for ADHD but not ASD in adjusted models.
“For ADHD but not ASD, the protective effects of greater maternal and paternal education were also observed in adjusted models.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationPrevious studies have suggested an independent association between ASD and maternal depression.
“previous studies have suggested an independent association between ASD and maternal depression10, 11.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [10] Daniels JL, Forssen U, Hultman CM, Cnattingius S, Savitz DA, Feychting M et al. Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics 2008; 121: e1357–e1362. source
Not checked in the free run.
- cites [11] Piven J, Palmer P . Psychiatric disorder and the broad autism phenotype: evidence from a family study of multiple-incidence autism families. Am J Psychiatry 1999; 156: 557–563. source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationAntidepressant exposure has been associated with ADHD liability in one cohort.
“given that antidepressant exposure has also been associated with ADHD liability in one cohort12, while a larger one found association with either current or past antidepressant use13.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Figueroa R . Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31: 641–648. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn a Swedish population cohort of 1670 ASD cases, antidepressant exposure was associated with adjusted OR 1.96.
“In the second, for 1670 ASD cases in a Swedish population cohort, antidepressant exposure was associated with adjusted odds ratio of 1.96.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataFor ADHD, a persistent risk was associated with antidepressant exposure, particularly during the first trimester, only partially explained by maternal psychopathology in regression models.
“Conversely, for ADHD, we observed persistent risk associated with antidepressant exposure, particularly during the first trimester, which can only partially be explained in regression models by maternal psychopathology.”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
Classified as probably not a substantial claim.
Study design and conductown dataIn children from a large New England health care system, ASD cases were matched 1:3 with non-ASD controls on birth year, birth hospital, sex, insurance type, race/ethnicity, and preterm status.
“Children with ASD were matched 1:3 with non-ASD control children delivered at MGH, BWH, or NWH with the same year of birth, birth hospital, sex, insurance type as a proxy for socioeconomic status, race/ethnicity, and preterm versus full-term status.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationDiscontinuation of antidepressants during pregnancy can increase risk of relapse five-fold.
“Discontinuation of antidepressants during pregnancy can increase the risk of relapse five-fold8”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006; 295: 499–507. source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductreasoningA third model included maternal major depressive disorder to address confounding by indication.
“Finally, a third model was fit including presence or absence of maternal major depressive disorder (ICD9 codes of 296.2x or 296.3x), to address the possibility of confounding by indication.”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
Classified as probably not a substantial claim.
PremisecitationA health claims-based study and a registry-based study found an association between in utero antidepressant exposure and autism liability in children.
“Subsequently, one health claims-based study5 and one registry-based study6 associated in utero exposure to antidepressants with autism liability in children, while a recent large-scale Danish registry-based study did not replicate this association7.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [5] Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V . Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68: 1104–1112. source
Not checked in the free run.
- cites [6] Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C . Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013; 346: f2059. source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductreasoningADHD cases were frequency-matched with healthy controls using the same matching variables as ASD cases.
“This study group was also frequency-matched with healthy control children as for ASD.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationThe analysis was restricted to one child per mother.
“Consistent with prior reports, we restricted the analysis to 1 child per mother, choosing the child with ASD or ADHD when a mother had both a case and control offspring.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRodent studies suggested prenatal exposure to serotonergic drugs produced autism-like behaviors in offspring.
“Rodent studies nearly a decade ago suggested that prenatal exposure to serotonergic drugs yielded autism-like behaviors in offspring4.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA . Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306: 879–881. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA larger cohort found an association between antidepressant exposure and either current or past antidepressant use.
“given that antidepressant exposure has also been associated with ADHD liability in one cohort12, while a larger one found association with either current or past antidepressant use13.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Laugesen K, Olsen MS, Telen Andersen AB, Froslev T, Sorensen HT . In utero exposure to antidepressant drugs and risk of attention deficit hyperactivity disorder: a nationwide Danish cohort study. BMJ Open 2013; 3: e003507. source
Not checked in the free run.
May combine two claims.
Interpretationown dataASD risk is absent or substantially diminished with highest serotonin-affinity antidepressants and with the serotonergic non-antidepressant ondansetron, while it is present and greater with antipsychotic treatment.
“Second, they suggest the risk is absent or substantially diminished with highest serotonin-affinity antidepressants as well as a serotonergic non-antidepressant, while it is present and of even greater magnitude with antipsychotic treatment.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataConvergent evidence for confounding by indication includes greatest ASD risk with pre-pregnancy exposure, greater risk with less-serotonergic antidepressants and antipsychotics, and reduced effect size with more detailed psychopathology measures.
“Convergent evidence of such confounding includes greatest risk with pre-pregnancy exposure, increased magnitude of risk with less- rather than more-serotonergic antidepressants, as well as with antipsychotics, both categories often used in more severely ill patients, and reduction in effect size with inclusion of more detailed measures of psychopathology or treatment intensity.”
Quote in the paperSubstantial claim- Rests on an assumption: ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
Classified as probably not a substantial claim.
Study design and conductreasoningObstetric and neonatal complications were not included in models of antidepressant exposure and disease outcome because they might lie on the causal pathway.
“However, we did not include complications in models examining antidepressant exposure and disease outcome, because of the possibility that such complications might lie in the causal path (if any) between exposure and disease.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationA recent large-scale Danish registry-based study did not replicate the association between in utero antidepressant exposure and autism.
“Subsequently, one health claims-based study5 and one registry-based study6 associated in utero exposure to antidepressants with autism liability in children, while a recent large-scale Danish registry-based study did not replicate this association7.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Hviid A, Melbye M, Pasternak B . Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013; 369: 2406–2415. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMaternal depression during pregnancy is associated with health complications for both mother and child.
“maternal depression during pregnancy is associated with health complications for both the mother and child9.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Oberlander TF, Warburton W, Misri S, Aghajanian J, Hertzman C . Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 2006; 63: 898–906. source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataLogistic regression models adjusted for gender, race, birth year, insurance type, maternal age, and median income tertile.
“Next, a logistic regression model was fit which included gender, race, birth year, insurance type, maternal age, and median income tertile, yielding an adjusted odds ratio.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe present results are consistent with the most recent and largest registry-based investigation in that both failed to identify risk specifically among SSRI-treated patients.
“Our results are also consistent with the most recent and largest registry-based investigation 7, in that both studies failed to identify risk specifically among SSRI-treated patients.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Hviid A, Melbye M, Pasternak B . Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013; 369: 2406–2415. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSome, but not all, studies suggest maternal psychiatric illness is associated with ASD liability.
“Some, but not all, studies suggest that maternal psychiatric illness is associated with ASD liability6.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C . Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013; 346: f2059. source
Not checked in the free run.
May combine two claims.
PremisecitationA larger Danish registry-based study identified a more modest association with antidepressant exposure, also observed among offspring of mothers with prior, but not current, antidepressant treatment.
“A larger Danish registry-based study identified a more modest association with antidepressant exposure, which was also observed among offspring of mothers with prior, but not current, antidepressant treatment13.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Laugesen K, Olsen MS, Telen Andersen AB, Froslev T, Sorensen HT . In utero exposure to antidepressant drugs and risk of attention deficit hyperactivity disorder: a nationwide Danish cohort study. BMJ Open 2013; 3: e003507. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn the Hviid analysis, as in this study, past but not current antidepressant use represents a risk for ASD.
“In the analysis by Hviid and colleagues, as in this study, past but not current antidepressant use represents a risk for ASD.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn both prior studies, risk was also observed with non-SSRIs, contrary to rodent model predictions.
“In both of these prior studies, contrary to predictions from rodent models 4, risk was also observed with non-SSRIs.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA . Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306: 879–881. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA prior investigation of 431 children with ADHD identified an association with bupropion exposure.
“consistent with a prior investigation of 431 children with ADHD12 which identified association with bupropion exposure.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Figueroa R . Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31: 641–648. source
Not checked in the free run.
The paper relies on this without support.
Prescription records in the electronic health record accurately reflect actual antidepressant exposure during pregnancy.
“Confirmation that agents prescribed were actually dispensed to patients is not available for research purposes.”
The paper relies on this without support.
ICD-9 codes for maternal major depressive disorder adequately capture the severity of maternal psychiatric illness relevant to confounding by indication.
“Finally, a third model was fit including presence or absence of maternal major depressive disorder (ICD9 codes of 296.2x or 296.3x), to address the possibility of confounding by indication.”
The paper relies on this without support.
The matched control children are free of ASD and ADHD.
“These children were defined as not having any prior history of ASD, ADHD, or intellectual disability (ICD9 of 299, 314, or 317–319).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The null result for prenatal SSRIs and ASD agrees with multiple large population studies designed to handle confounding by indication.
“Our findings of no association between prenatal SSRI exposure and ASD are consistent with the conclusions of several large, population-based studies that specifically address confounding by indication (19–26, 42).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [19]
For ASD, seven case-control studies involving 291,468 patients and 13,243 cases and eight cohort studies involving 3,294,218 patients and 27,342 cases were included.
“For ASD as the outcome, seven case–control studies (involving 291,468 patients and 13,243 cases of ASD) [17, 18, 26–29, 32] and eight cohort studies (involving 3,294,218 patients and 27,342 cases of ASD) [16, 19, 25, 30, 31, 33–35] were included.”
A total of 15 observational studies measuring ASD as an outcome were identified.
“there was a total of 15 observational studies measuring ASD as an outcome [16–19, 25–35].”
A total of seven observational studies measuring ADHD as an outcome were identified.
“a total of seven observational studies measuring ADHD as an outcome [17, 18, 31, 34, 36–38] were identified”
For ADHD, three case-control studies involving 51,944 patients and 4,375 cases and four cohort studies involving 2,713,779 patients and 51,938 cases were included.
“For ADHD as the outcome, three case–control studies (involving 51,944 patients and 4,375 cases of ADHD) [17, 18, 36] and four cohort studies (involving 2,713,779 patients and 51,938 cases of ADHD) [31, 33, 37, 38] were included.”
The severity of depression was evaluated in only four studies and was limited either to measures of maternal treatment intensity or to use of a validated self-reported questionnaire, and by applying high-dimensional propensity scores.
“The severity of depression was evaluated in only four studies and was limited either to measures of maternal treatment intensity in terms of number of antidepressant and psychotherapy visits [17, 18] or to use of a validated self-reported questionnaire [19], and by applying high-dimensional propensity scores [25].”
Cites
Autism as a strongly genetic disorder: evidence from a British twin study
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) · Psychological Medicine · doi:10.1017/s0033291700028099 · Cited by 2,461 · see citing works
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Hallmayer, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.76 · Cited by 1,970 · see citing works
Cohen, L. S. (2006) · JAMA · doi:10.1001/jama.295.5.499 · Cited by 1,031 · see citing works
Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2)
Murphy, S. N., Weber, G. M., Mendis, M., Gainer, V. S., Chueh, H. C., Churchill, S. E., & Kohane, I. S. (2010) · Journal of the American Medical Informatics Association · doi:10.1136/jamia.2009.000893 · Cited by 926 · see citing works
Self-citationEarly-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A. (2004) · Science · doi:10.1126/science.1101678 · Cited by 817 · see citing works
Neurotransmitter Receptor and Transporter Binding Profile of Antidepressants and Their Metabolites
Owens, M. J., Morgan, W. N., Plott, S. J., & Nemeroff, C. B. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37161-7 · Cited by 676 · see citing works
(2009) · doi:10.1007/978-0-387-87959-8 · Cited by 554 · see citing works
Oberlander, T. F., Warburton, W., Misri, S., Aghajanian, J., & Hertzman, C. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.898 · Cited by 551 · see citing works
Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders
Croen, L. A. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.73 · Cited by 510 · see citing works
Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013) · BMJ · doi:10.1136/bmj.f2059 · Cited by 365 · see citing works
Piven, J., & Palmer, P. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.4.557 · Cited by 364 · see citing works
Parental psychiatric disorders associated with autism spectrum disorders in the offspring
Daniels, J. L., Forssen, U., Hultman, C. M., Cnattingius, S., Savitz, D. A., Feychting, M., & Sparen, P. (2008) · Pediatrics · doi:10.1542/peds.2007-2296 · Cited by 288 · see citing works
Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism
Hviid, A., Melbye, M., & Pasternak, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301449 · Cited by 195 · see citing works
Murphy, S. N., Mendis, M., Hackett, K. L., Kuttan, R., Pan, W., Phillips, L. C., Gainer, V. S., D, D. A. B. M., GLASER, J. P., Kohane, I. S., et al. (2007) · PubMed Central · Cited by 168 · see citing works
Self-citationInstrumenting the health care enterprise for discovery research in the genomic eraPreprint
Murphy, S. N., Churchill, S. E., Bry, L., Chueh, H. C., Weiss, S. T., Lazarus, R. M., Zeng, Q. T., Dubey, A. K., Gainer, V. S., Mendis, M., et al. (2009) · Genome Research · doi:10.1101/gr.094615.109 · Cited by 126 · see citing works
Self-citationFigueroa, R. (2010) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e3181e5ac93 · Cited by 116 · see citing works
Laugesen, K., Olsen, M. S., Telén Andersen, A. B., Frøslev, T., & Toft Sørensen, H. (2013) · BMJ Open · doi:10.1136/bmjopen-2013-003507 · Cited by 58 · see citing works
Castro, V. M., Gallagher, P., Clements, C. C., Murphy, S. N., Gainer, V. S., D, M. F. M., Weilburg, J. B., Churchill, S. E., Kohane, I. S., Iosifescu, D. V., et al. (2012) · BMJ Open · doi:10.1136/bmjopen-2011-000544 · Cited by 53 · see citing works
Self-citationSchieve, L. A., Tian, L. H., Baio, J., Rankin, K., Rosenberg, D., Wiggins, L., Maenner, M. J., Yeargin-Allsopp, M., Durkin, M., Rice, C., et al. (2014) · Annals of Epidemiology · doi:10.1016/j.annepidem.2013.12.014 · Cited by 50 · see citing works
A Guide to Implementing Quantitative Bias Analysis
Lash, T. L., Fink, A. K., & Fox, M. P. (2009) · Statistics in the health sciences · doi:10.1007/978-0-387-87959-8_2 · Cited by 11 · see citing works
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- Investigators AaDDMNSYP Prevalence of Autism Spectrum Disorders — Autism and Developmental Disabilities Monitoring Network. MMWR Surveill Summ 2012; 61: 1–19.
Cited by
Sorted by citations
Postpartum depression: Etiology, treatment and consequences for maternal care
Brummelte, S., & Galea, L. A. M. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.08.008 · Cited by 567 · see citing works
Predicting suicidal behavior from longitudinal electronic health records.
Barak-Corren, Y., Castro, V. M., Javitt, S., Hoffnagle, A. G., Dai, Y., Perlis, R. H., Nock, M. K., Smoller, J. W., & Reis, B. Y. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16010077 · Cited by 339 · see citing works
Self-citationMcAllister-Williams, R., Baldwin, D. S., Cantwell, R., Easter, A., Gilvarry, E., Glover, V., Green, L., Grégoire, A., Howard, L. M., Jones, I. R., et al. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117699361 · Cited by 219 · see citing works
Brummelte, S., Mc Glanaghy, E., Bonnin, A., & Oberlander, T. F. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.02.037 · Cited by 306 · see citing works
Pregnancy as a period of risk, adaptation, and resilience for mothers and infants
Davis, E. P., & Narayan, A. J. (2020) · Development and Psychopathology · doi:10.1017/s0954579420001121 · Cited by 297 · see citing works
Prenatal Risk Factors and the Etiology of ADHD—Review of Existing Evidence
Sciberras, E., Mulraney, M., Silva, D. T., & Coghill, D. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0753-2 · Cited by 286 · see citing works
Sujan, A. C., Rickert, M. E., Öberg, A. S., Quinn, P. D., Hernández-Díaz, S., Almqvist, C., Lichtenstein, P., Larsson, H., & D’Onofrio, B. M. (2017) · JAMA · doi:10.1001/jama.2017.3413 · Cited by 226 · see citing works
Malm, H., Brown, A. S., Gissler, M., Gyllenberg, D., Hinkka-Yli-Salomäki, S., McKeague, I. W., Weissman, M., Wickramaratne, P., Artama, M., Gingrich, J. A., et al. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.02.013 · Cited by 206 · see citing works
Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., Lau, W. C. Y., Schuemie, M. J., Sturkenboom, M. C. J. M., & Wong, I. C. K. (2017) · BMJ · doi:10.1136/bmj.j2350 · Cited by 135 · see citing works
McCoy, T. H., Castro, V. M., Roberson, A. M., Snapper, L. A., & Perlis, R. H. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.2172 · Cited by 130 · see citing works
Self-citationThe use of electronic health records for psychiatric phenotyping and genomics
Smoller, J. W. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32548 · Cited by 125 · see citing works
Self-citationAssociation of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures
Leppert, B., Havdahl, A., Riglin, L., Jones, H. J., Zheng, J., Smith, G. D., Tilling, K. M., Thapar, A., Reichborn‐Kjennerud, T., & Stergiakouli, E. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.0774 · Cited by 123 · see citing works
Morales, D. R., Slattery, J., Evans, S., & Kurz, X. (2018) · BMC Medicine · doi:10.1186/s12916-017-0993-3 · Cited by 118 · see citing works
Mezzacappa, A., Lasica, P.-A., Gianfagna, F., Cazas, O., Hardy, P., Falissard, B., Sutter-Dallay, A.-L., & Gressier, F. (2017) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2017.0124 · Cited by 108 · see citing works
Validation of Autism Diagnosis and Clinical Data in the SPARK Cohort
Fombonne, E. J., Coppola, L. A., Mastel, S. A., & O’Roak, B. J. (2021) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-021-05218-y · Cited by 106 · see citing works
Optimizing the treatment of mood disorders in the perinatal period
Meltzer-Brody, S. E., & Jones, I. R. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.2/smeltzerbrody · Cited by 102 · see citing works
Glover, M. E., & Clinton, S. M. (2016) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2016.04.008 · Cited by 101 · see citing works
Identification and Management of Peripartum Depression.
Langan, R. C., & Goodbred, A. J. (2016) · PubMed · Cited by 101 · see citing works
Wang, Z., Chan, A. Y. L., Coghill, D., Ip, P., Lau, W. C. Y., Simonoff, E. A., Brauer, R., Wei, L., Wong, I. C. K., & Man, K. K. C. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.4571 · Cited by 97 · see citing works
Suarez, E. A., Bateman, B. T., Hernández–Dı́az, S., Straub, L., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B. M., McDougle, C. J., Zhu, Y., et al. (2022) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2022.4268 · Cited by 95 · see citing works
Antidepressants during pregnancy and autism in offspring: population based cohort study
Rai, D., Lee, B. K., Dalman, C., Newschaffer, C., Lewis, G., & Magnusson, C. (2017) · BMJ · doi:10.1136/bmj.j2811 · Cited by 93 · see citing works
Salari, A., Fatehi-Gharehlar, L., Motayagheni, N., & Homberg, J. R. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.062 · Cited by 93 · see citing works
Liu, X., Agerbo, E., Ingstrup, K. G., Musliner, K., Meltzer-Brody, S., Bergink, V., & Munk-Olsen, T. (2017) · BMJ · doi:10.1136/bmj.j3668 · Cited by 90 · see citing works
Davis, E. P., Hankin, B. L., Swales, D. A., & Hoffman, M. C. (2018) · Development and Psychopathology · doi:10.1017/s0954579418000470 · Cited by 90 · see citing works
Edlow, A. G., Castro, V. M., Shook, L. L., Haneuse, S., Kaimal, A. J., & Perlis, R. H. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.4415 · Cited by 85 · see citing works
Self-citationLebin, L. G., & Novick, A. M. (2022) · Current Psychiatry Reports · doi:10.1007/s11920-022-01372-x · Cited by 84 · see citing works
Garbarino, V. R., Gilman, T. L., Daws, L. C., & Gould, G. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.07.010 · Cited by 83 · see citing works
Castro, V. M., Kong, S. W., Clements, C. C., Brady, R., Kaimal, A. J., Doyle, A. E., Robinson, E. B., Churchill, S. E., Kohane, I. S., & Perlis, R. H. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.190 · Cited by 82 · see citing works
Self-citationKobayashi, T., Matsuyama, T., Takeuchi, M., & Ito, S. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.07.016 · Cited by 82 · see citing works
Millard, S. J., Weston–Green, K., & Newell, K. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.008 · Cited by 81 · see citing works
Prenatal risk factors and genetic causes of ADHD in children
Kian, N., Samieefar, N., & Rezaei, N. (2022) · World Journal of Pediatrics · doi:10.1007/s12519-022-00524-6 · Cited by 75 · see citing works
Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy: A Review of Current Evidence
Alwan, S. S., Friedman, J. M., & Chambers, C. (2016) · CNS Drugs · doi:10.1007/s40263-016-0338-3 · Cited by 75 · see citing works
Prenatal antidepressant exposure associated withCYP2E1DNA methylation change in neonates
Gurnot, C., Martin-Subero, I., Mah, S. M., Weikum, W., Goodman, S. J., Brain, U. M., Werker, J. F., Kobor, M. S., Esteller, M., Oberlander, T. F., et al. (2015) · Epigenetics · doi:10.1080/15592294.2015.1026031 · Cited by 74 · see citing works
Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of discordant siblings
Brandlistuen, R. E., Ystrøm, E., Eberhard‐Gran, M., Nulman, I., Koren, G., & Nordeng, H. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv030 · Cited by 72 · see citing works
Mergy, M. A., Gowrishankar, R., Gresch, P. J., Gantz, S. C., Williams, J. T., Davis, G. L., Wheeler, C. A., Stanwood, G. D., Hahn, M. K., & Blakely, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417294111 · Cited by 69 · see citing works
Robinson, L. R., Bitsko, R. H., O’Masta, B., Holbrook, J. R., Ko, J. Y., Barry, C. M., Maher, B. S., Cerles, A. A., Saadeh, K., MacMillan, L., et al. (2022) · Prevention Science · doi:10.1007/s11121-022-01383-3 · Cited by 68 · see citing works
Gentile, S. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.04.048 · Cited by 67 · see citing works
Kaplan, Y. C., Arslan, E. K., Acar, S., & Sözmen, K. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.09.013 · Cited by 66 · see citing works
Gemmel, M., Bögi, E., Ragan, C. M., Hazlett, M. F., Dubovický, M., van den Hove, D., Oberlander, T. F., Charlier, T. D., & Pawluski, J. L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.023 · Cited by 65 · see citing works
Autism risk following antidepressant medication during pregnancy
Viktorin, A., Uher, R., Reichenberg, A., Levine, S. Z., & Sandin, S. (2017) · Psychological Medicine · doi:10.1017/s0033291717001301 · Cited by 62 · see citing works
Glover, M. E., Pugh, P. C., Jackson, N., Cohen, J. L., Fant, A. D., Akil, H., & Clinton, S. M. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.044 · Cited by 61 · see citing works
Hagberg, K. W., Robijn, A. L., & Jick, S. S. (2018) · Clinical Epidemiology · doi:10.2147/clep.s180618 · Cited by 60 · see citing works
Autism spectrum disorder: Trends in research exploring etiopathogenesis
Gyawali, S., & Patra, B. N. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12860 · Cited by 59 · see citing works
Bitsko, R. H., Holbrook, J. R., O’Masta, B., Maher, B. S., Cerles, A. A., Saadeh, K., Mahmooth, Z., MacMillan, L., Rush, M., & Kaminski, J. W. (2022) · Prevention Science · doi:10.1007/s11121-022-01359-3 · Cited by 58 · see citing works
Gemmel, M., Hazlett, M. F., Bögi, E., Lacalle, S. D., Hill, L. A., Kokras, N., Hammond, G. L., Dalla, C., Charlier, T. D., & Pawluski, J. L. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.07.480 · Cited by 56 · see citing works
Lupattelli, A., Wood, M. E., Ystrøm, E., Skurtveit, S. O., Handal, M., & Nordeng, H. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.12.010 · Cited by 56 · see citing works
Joelsson, P., Chudal, R., Uotila, J., Suominen, A., Sucksdorff, D., Gyllenberg, D., & Sourander, A. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.07.004 · Cited by 55 · see citing works
Ornoy, A., & Koren, G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102370 · Cited by 54 · see citing works
Sujan, A. C., Öberg, A. S., Quinn, P. D., & D'Onofrio, B. M. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13004 · Cited by 52 · see citing works
A systematic review of quantitative bias analysis applied to epidemiological research
Petersen, J. M., Ranker, L. R., Barnard‐Mayers, R., MacLehose, R. F., & Fox, M. P. (2021) · International Journal of Epidemiology · doi:10.1093/ije/dyab061 · Cited by 51 · see citing works
Kaplan, Y. C., Arslan, E. K., Acar, S., & Sözmen, K. (2017) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13382 · Cited by 49 · see citing works
Leshem, R., Bar‐Oz, B., Diav‐Citrin, O., Gbaly, S., Soliman, J., Renoux, C., & Matok, I. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210303121059 · Cited by 48 · see citing works
Variations in Neurodevelopmental Outcomes in Children with Prenatal SSRI Antidepressant Exposure
Rotem‐Kohavi, N., & Oberlander, T. F. (2017) · Birth Defects Research · doi:10.1002/bdr2.1076 · Cited by 47 · see citing works
Viktorin, A., Uher, R., Kolevzon, A., Reichenberg, A., Levine, S. Z., & Sandin, S. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.1727 · Cited by 45 · see citing works
Gondy Leroy, A., Gu, Y., Pettygrove, S. D., Galindo, M. K., Arora, A., & Kurzius‐Spencer, M. (2018) · Journal of Medical Internet Research · doi:10.2196/10497 · Cited by 43 · see citing works
Bashiri, H., Houwing, D. J., Homberg, J. R., & Salari, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-87800-z · Cited by 41 · see citing works
Gemmel, M., Lacalle, S. D., Mort, S. C., Hill, L. A., Charlier, T. D., & Pawluski, J. L. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.10.009 · Cited by 39 · see citing works
Hjorth, S., Bromley, R., Ystrøm, E., Lupattelli, A., Spigset, O., & Nordeng, H. (2019) · PLoS ONE · doi:10.1371/journal.pone.0219778 · Cited by 37 · see citing works
Ames, J. L., Ladd-Acosta, C., Fallin, M. D., Qian, Y., Schieve, L. A., DiGuiseppi, C., Lee, L.-C., Kasten, E. P., Zhou, G., Pinto-Martin, J., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.04.002 · Cited by 36 · see citing works
Zhou, X., Li, Y., Ou, J.-J., & Li, Y. (2018) · Molecular Autism · doi:10.1186/s13229-018-0207-7 · Cited by 36 · see citing works
Millard, S. J., Lum, J. S., Fernandez, F., Weston–Green, K., & Newell, K. A. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881118822141 · Cited by 36 · see citing works
The effects of antenatal depression and antidepressant treatment on placental gene expression
Olivier, J. D. A., Åkerud, H., Skalkidou, A., Kaihola, H., & Poromaa, I. S. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00465 · Cited by 36 · see citing works
Studying the Contribution of Serotonin to Neurodevelopmental Disorders. Can This Fly?
Carvajal-Oliveros, A., & Campusano, J. M. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.601449 · Cited by 34 · see citing works
Boukhris, T., Sheehy, O., & Bérard, A. (2017) · Paediatric and Perinatal Epidemiology · doi:10.1111/ppe.12378 · Cited by 34 · see citing works
Roberts, A. L., Liew, Z., Lyall, K., Ascherio, A., & Weisskopf, M. G. (2018) · American Journal of Epidemiology · doi:10.1093/aje/kwy098 · Cited by 33 · see citing works
Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., Lau, W. C. Y., Schuemie, M. J., Sturkenboom, M. C. J. M., & Wong, I. C. K. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.12.007 · Cited by 32 · see citing works
Frazer, S., Otomo, K., & Dayer, A. G. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.147 · Cited by 32 · see citing works
Selective serotonin reuptake inhibitors for depression in pregnancy
Susser, L. C., Sansone, S. A., & Hermann, A. D. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2016.07.011 · Cited by 31 · see citing works
Sprowles, J. L. N., Wendel, J. R. H., Gutierrez, A., Bailey, R. A., Jablonski, S. A., Williams, M. T., & Vorhees, C. V. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.06.004 · Cited by 31 · see citing works
Mulraney, M., Giallo, R., Efron, D., Brown, S., Nicholson, J. M., & Sciberras, E. (2018) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-018-1254-5 · Cited by 31 · see citing works
Hamad, A. F., Alessi‐Severini, S., Mahmud, S. M., Brownell, M. D., & Kuo, I. F. (2019) · American Journal of Epidemiology · doi:10.1093/aje/kwz178 · Cited by 31 · see citing works
Hamad, A. F., Alessi‐Severini, S., Mahmud, S. M., Brownell, M. D., & Kuo, I. F. (2020) · Canadian Medical Association Journal · doi:10.1503/cmaj.190883 · Cited by 30 · see citing works
Peripartum depression: Early recognition improves outcomes
Howard, M. M., Mehta, N. D., & Powrie, R. O. (2017) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.84a.14060 · Cited by 29 · see citing works
Araújo, J. N. D. M., Delgado, I. F., & Paumgartten, F. J. R. (2020) · Cadernos de Saúde Pública · doi:10.1590/0102-311x00026619 · Cited by 28 · see citing works
Memantine rescues prenatal citalopram exposure-induced striatal and social abnormalities in mice
Zahra, A., Jiang, J., Chen, Y., Long, C., & Yang, L. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.06.003 · Cited by 28 · see citing works
Halvorsen, A., Hesel, B., Østergaard, S. D., & Danielsen, A. A. (2019) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13030 · Cited by 28 · see citing works
Vega, M. L., Newport, G. C., Bozhdaraj, D., Saltz, S. B., Nemeroff, C. B., & Newport, D. J. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.18070766 · Cited by 28 · see citing works
Vuijk, P. J., Martin, J., Braaten, E. B., Genovese, G., Capawana, M. R., O’Keefe, S. M., Lee, B. A., Lind, H. S., Smoller, J. W., Faraone, S. V., et al. (2019) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2019.08.004 · Cited by 26 · see citing works
Self-citationStratification of risk for hospital admissions for injury related to fall: cohort study
Castro, V. M., McCoy, T. H., Cagan, A., Rosenfield, H. R., Murphy, S. N., Churchill, S. E., Kohane, I. S., & Perlis, R. H. (2014) · BMJ · doi:10.1136/bmj.g5863 · Cited by 25 · see citing works
Self-citationShould Antidepressants be Avoided in Pregnancy?
Besag, F., & Vasey, M. J. (2022) · Drug Safety · doi:10.1007/s40264-022-01257-1 · Cited by 25 · see citing works
Disparities in antidepressant use in pregnancy
Yamamoto, A., McCormick, M. C., & Burris, H. H. (2014) · Journal of Perinatology · doi:10.1038/jp.2014.197 · Cited by 25 · see citing works
Yamamoto‐Sasaki, M., Yoshida, S., Takeuchi, M., Tanaka‐Mizuno, S., Ogawa, Y., Furukawa, T. A., & Kawakami, K. (2019) · Maternal Health Neonatology and Perinatology · doi:10.1186/s40748-018-0096-y · Cited by 25 · see citing works
Bond, C. M., Johnson, J. C., Chaudhary, V., McCarthy, E. M., McWhorter, M. L., & Woehrle, N. S. (2019) · Brain Research · doi:10.1016/j.brainres.2019.06.001 · Cited by 25 · see citing works
Ben‐Shlomo, Y., Scharf, J. M., Miller, L. L., & Mathews, C. A. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0742-0 · Cited by 25 · see citing works
Leivonen, S., Scharf, J. M., Mathews, C. A., Chudal, R., Gyllenberg, D., Sucksdorff, D., Suominen, A., Voutilainen, A., Brown, A. S., & Sourander, A. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.01.009 · Cited by 25 · see citing works
Yu, W., Yen, Y.-C., Lee, Y., Tan, S., Xiao, Y., Lokman, H., Ting, A. K. T., Ganegala, H. E. W., Kwon, T., Ho, W., et al. (2019) · Molecular Brain · doi:10.1186/s13041-019-0452-5 · Cited by 24 · see citing works
In Utero Antidepressants and Neurodevelopmental Outcomes in Kindergarteners
Singal, D., Chateau, D. G., Struck, S., Lee, J. B., Dahl, M. E., Derksen, S., Katz, L. Y., Ruth, C., Hanlon‐Dearman, A., & Brownell, M. D. (2020) · PEDIATRICS · doi:10.1542/peds.2019-1157 · Cited by 23 · see citing works
The microbiome as a modulator of neurological health across the maternal-offspring interface
Orchanian, S. B., & Hsiao, E. Y. (2025) · Journal of Clinical Investigation · doi:10.1172/jci184314 · Cited by 22 · see citing works
Yang, F., Chen, J., Miao, M., Yuan, W., Li, L., Liang, H., Ehrenstein, V., & Li, J. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-016368 · Cited by 22 · see citing works
Pawluski, J. L., & Gemmel, M. (2018) · HORMONES · doi:10.1007/s42000-018-0011-y · Cited by 21 · see citing works
Jiang, H., Peng, C., Zhang, X., & Ruan, B. (2017) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.15059 · Cited by 20 · see citing works
Prenatal exposure to antidepressants and risk of epilepsy in childhood
Mao, Y., Pedersen, L. H., Christensen, J., Vestergaard, M., Zhou, W., Olsen, J., & Sun, Y. (2016) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4072 · Cited by 19 · see citing works
Qiu, W., Go, K. A., Wen, Y., Duarte‐Guterman, P., Eid, R. S., & Galea, L. A. M. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.06.012 · Cited by 19 · see citing works
Zucker, I. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.005 · Cited by 19 · see citing works
Uğuz, F. (2018) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000868 · Cited by 19 · see citing works
Ma, S., Zhu, D., Yin, W., Hao, J., Huang, K., Tao, F., Tao, R., & Zhu, P. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.033 · Cited by 19 · see citing works
Brennan, P. A., Dunlop, A. L., Croen, L., Avalos, L. A., Salisbury, A. L., Hipwell, A. E., Nozadi, S. S., Sathyanarayana, S., Crum, R. M., Musci, R. J., et al. (2022) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-022-01000-5 · Cited by 18 · see citing works
Neurobehavioral risks of SSRIs in pregnancy: Comparing human and animal data
Ornoy, A. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2017.05.003 · Cited by 18 · see citing works
Wang, Z., Ho, P. W. H., Choy, M. T. H., Wong, I. C. K., Brauer, R., & Man, K. K. C. (2018) · Drug Safety · doi:10.1007/s40264-018-0755-y · Cited by 18 · see citing works
In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development
Velasquez, J. C., Zhao, Q., Chan, Y., Galindo, L. C. M., Simasotchi, C., Wu, D., Hou, Z., Herod, S. M., Oberlander, T. F., Gil, S., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00180 · Cited by 18 · see citing works
- Authors
- Clements, C. C., Castro, V. M., Blumenthal, S. R., Rosenfield, H. R., Murphy, S. N., Fava, M., Erb, J. L., Churchill, S. E., Kaimal, A. J., Doyle, A. E., Robinson, E. B., Smoller, J. W., Kohane, I. S., & Perlis, R. H.
- Affiliations
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Perlis, R H
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2014-08-26
- Volume
- 20
- Issue
- 6
- Pages
- 727-734
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4427538
- OpenAlex
- W2071055980
- Cited by
- 197
- References
- 21
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 4 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 21 · 2018: 21 · 2017: 38 · 2016: 28 · 2015: 15 · 2014: 7
- FWCI
- 29.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (NIMH R01MH086026)
- National Institute of Mental Health (R01MH100286, R01MH086026)
- U.S. National Library of Medicine (U54LM008748)
- National Center for Research Resources (UL1RR025758)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- prenatal antidepressant exposure, attention deficit hyperactivity disorder, autism spectrum disorder, maternal depression, confounding, pregnancy, maternal mental health, electronic health records, birth cohort
- MeSH terms
- Autism Spectrum Disorder, Antidepressive Agents, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, England, Female, Humans, Male, Mother-Child Relations, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Logistic Models, Case-Control Studies
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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