Common Medications Taken During Pregnancy Not Linked to ASD Risk

Summary: A new study reports prenatal exposure to common antidepressants and antipsychotics does not increase the risk of a child developing autism.

Source: Mount Sinai Hospital.

Babies exposed in the womb to the majority of medications that target neurotransmitter systems, including typical targets of antidepressants and antipsychotic drugs, are not any more likely to develop autism than non-exposed babies, according to research conducted at The Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai and published October 31 in JAMA Psychiatry.

However, the rates of autism were higher among children of mothers with worse general health before pregnancy, suggesting that the mother’s health plays a more critical role in a child’s development than the medications she takes.

While previous research has suggested that children of women who use certain drugs during pregnancy are more likely to be diagnosed with autism those studies only looked at the autism risk in relation to a very small number of drugs. Additionally, the designs of previous studies inherently involved a tight link between offspring exposure and maternal disorder and, therefore, could not fully distinguish between the results of the drug itself and those related to the maternal disorder for which the drug was prescribed.

To overcome such limitations, a multidisciplinary team of researchers at the Icahn School of Medicine at Mount Sinai developed a new method that enabled them to systematically evaluate the effects of a wide range of drugs on the fetus in a sample of nearly 100,000 children born between 1997 and 2007 and followed up for autism until January 2016.

“When we assessed the effects of prenatal exposure to medications that affect major neurotransmitter systems, we found that the most of the associations are substantially modified when accounting for maternal characteristics,” said Magdalena Janecka, PhD, a postdoctoral fellow at The Seaver Center and first author of the paper. “What this suggests is that higher estimates of autism risk among offspring of mothers who take certain medications during pregnancy are most likely not due to pharmacological effects of those drugs.”

Specifically, the study team performed a case-cohort study using data from a large health maintenance organization in Israel. Researchers grouped medications prescribed to pregnant women based on the biological target on which those drugs act, rather than the condition the drug was prescribed to treat. The rationale behind this approach was that if certain types of pharmaceuticals affect the risk of the disorder by interfering with some facet of neurodevelopment, they will exert their effects regardless of maternal indication or of the internal system upon which they were designed to act. This new method allowed the study team to systematically evaluate the actions of more than 180 drugs, sorting them into 55 groups within which the medications were similar in terms of their function but were prescribed for different conditions.

The exposure interval in this study was defined as the pregnancy period (280 days before the child’s birth), and women in the study were considered exposed to a given medication regardless of the number of prescriptions or their redemption rate. Children were classified as exposed to a given group if their mother received a prescription for any medication from that group during pregnancy. Drugs could be classified into multiple groups, reflecting their diverse actions on maternal and fetal systems. Maternal number of diagnoses was defined as the total number of medical/reported health issues between one year prior to pregnancy and the child’s birth.

a pregnant woman
Researchers grouped medications prescribed to pregnant women based on the biological target on which those drugs act, rather than the condition the drug was prescribed to treat. image is in the public domain.

“After adjusting for the child’s year of birth, and a number of maternal factors–including her age at the child’s birth, history of psychiatric and neurological disorders, and number of medical diagnoses around pregnancy–our data indicate that the majority of medications known to affect neurotransmitters, and taken by women during pregnancy, may not themselves influence the estimates of offspring autism risk,” says Dr. Janecka. “In actuality, maternal number of diagnoses can confound associations between prenatal exposures and autism, and therefore should be accounted for in future studies.”

The biology-first method used in this study, in which the shared biological properties of medications are explicitly acknowledged in the analytical procedures, aims to understand the causal mechanisms that underlie the effects of prenatal exposure to medications and, therefore, could be pertinent to studies of other conditions that originate in utero. Researchers at The Seaver Center are currently investigating further how maternal health could affect a child’s risk of autism.

About this neuroscience research article

Funding: This study was funded in part by the Beatrice and Samuel A. Seaver Foundation.

Source: Elizabeth Dowling – Mount Sinai Hospital
Publisher: Organized by
Image Source: image is in the public domain.
Original Research: Open access research for “Association of Autism Spectrum Disorder with Prenatal Exposure to Medication Affecting Neurotransmitter Systems” by Magdalena Janecka, PhD; Arad Kodesh, MD; Stephen Z. Levine, PhD; Shari I. Lusskin, MD; Alexander Viktorin, PhD; Rayees Rahman, BS; Joseph D. Buxbaum, PhD; Avner Schlessinger, PhD; Sven Sandin, PhD; Abraham Reichenberg, PhD in JAMA Psychiatry. Published October 31 2018.

Cite This Article

[cbtabs][cbtab title=”MLA”]Mount Sinai Hospital”Common Medications Taken During Pregnancy Not Linked to ASD Risk.” NeuroscienceNews. NeuroscienceNews, 31 October 2018.
<>.[/cbtab][cbtab title=”APA”]Mount Sinai Hospital(2018, October 31). Common Medications Taken During Pregnancy Not Linked to ASD Risk. NeuroscienceNews. Retrieved October 31, 2018 from[/cbtab][cbtab title=”Chicago”]Mount Sinai Hospital”Common Medications Taken During Pregnancy Not Linked to ASD Risk.” (accessed October 31, 2018).[/cbtab][/cbtabs]


Identification of depression subtypes and relevant brain regions using a data-driven approach

Prenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed.

To investigate the association of early-life interference with different neurotransmitter systems by prenatal medication exposure on the risk of ASD in offspring.

Design, Setting, and Participants
This case-control study included children born from January 1, 1997, through December 31, 2007, and followed up for ASD until January 26, 2015, within a single Israeli health maintenance organization. Using publicly available data, 55 groups of medications affecting neurotransmitter systems and prescribed to pregnant women in this sample were identified. Children prenatally exposed to medications were compared with nonexposed children. Data were analyzed from March 1, 2017, through June 20, 2018.

Main Outcome and Measures
Hazard ratios (HRs) and 95% CIs of ASD risk associated with exposure to medication groups using Cox proportional hazards regression, adjusted for the relevant confounders (eg, birth year, maternal age, maternal history of psychiatric and neurologic disorders, or maternal number of all medical diagnoses 1 year before pregnancy).

The analytic sample consisted of 96 249 individuals (1405 cases; 94 844 controls; mean [SD] age at the end of follow-up, 11.6 [3.1] years; 48.8% female), including 1405 with ASD and 94 844 controls. Of 34 groups of medications, 5 showed nominally statistically significant association with ASD in fully adjusted models. Evidence of confounding effects of the number of maternal diagnoses on the association between offspring exposure to medication and ASD was found. Adjusting for this factor, lower estimates of ASD risk among children exposed to cannabinoid receptor agonists (HR, 0.72; 95% CI, 0.55-0.95; P = .02), muscarinic receptor 2 agonists (HR, 0.49; 95% CI, 0.24-0.98; P = .04), opioid receptor κ and ε agonists (HR, 0.67; 95% CI, 0.45-0.99; P = .045), or α2C-adrenergic receptor agonists (HR, 0.43; 95% CI, 0.19-0.96; P = .04) were observed. Exposure to antagonists of neuronal nicotinic acetylcholine receptor α was associated with higher estimates of ASD risk (HR, 12.94; 95% CI, 1.35-124.25; P = .03).

Conclusions and Relevance
Most of the medications affecting neurotransmitter systems in this sample had no association with the estimates of ASD risk. Replication and/or validation using experimental techniques are required.

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