Running head: AN INTEGRATIVE REVIEW 1

Psychotropic Medication Use During Pregnancy

Chelsea Lawson

Bon Secours Memorial College of Nursing

Arlene Holowaychuk, MSN

Nursing Research NUR 4122

November 12, 2017

I Pledge the Honor Code

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Abstract

The purpose of this paper is to analyze the literature on the effects of psychotropic medication on

neonates exposed in utero. The design of this paper is an integrative review. Using PubMed and

the words “psychotropic medications” and “pregnancy”, five articles were selected for this

integrative review. The articles were narrowed to peer-reviewed academic articles published

within the last five years and written in English. The results of these five studies are diverse and

non-conclusive as to whether there was increased risk of adverse effects on the neonate exposed

in utero. The limitations of this study include the retrospective nature of the studies chosen and

the inexperience of the researcher. Implications for changes in practice include teaching healthy

coping skills to pregnant women with mental illness and decreasing the number of psychotropic

drugs prescribed during pregnancy. Future research is needed specifically on the effects of

psychotropic medication use during pregnancy on the neonate compared with the effects of the

poor maternal coping skills developed to endure the mental illness.

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Psychotropic Medication Use During Pregnancy

The purpose of this integrative review is to explore the effects of psychotropic

medication on neonates exposed during gestation compared with neonates not exposed to

psychotropic medication during gestation. The incidence of mental illness is rising which in turn

causes the use of psychotropic medications to rise. From 2001 to 2008 there was an increase in

the use of psychotropic medication during pregnancy. In 2001 three women per one thousand

pregnancies were taking psychotropic medications, and in 2008 eight women per one thousand

pregnancies were taking psychotropic medications (Vigod, Gomes, Wilton, Taylor, & Ray,

2015). There is not much known on the effects of psychotropic medication on the neonate. More

research is needed because there could potentially be an ethical dilemma in providing

psychotropic medications compared with not providing psychotropic medication. Providing

psychotropic medication can put the neonate at an increased risk for complications from

exposure to the medication in utero, but not providing psychotropic medications can put the

neonate at an increased risk for complications from exposure to maternal mental illness and poor

maternal coping skills. The researcher chose the following PICO question due to her immense

passion for the mentally ill population: In pregnant women with mental illness, what is the effect

of psychotropic drug therapy on the neonate when compared to pregnant women not on

psychotropic drug therapy?

Design/Research Methods

The research design is an integrative review. The search engine, PubMed, was used to

gather articles relevant to the PICO question. The search terms “psychotropic medication” and

“pregnancy” were utilized to generate results. The search resulted in 811 articles. To ensure

article credibility, the search criteria was narrowed to peer-reviewed academic journals,

qualitative and quantitative research, published within the last five years, and written in English.
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All five articles chosen related to the PICO question. The articles chosen were published

between 2012 and 2017 with all five being quantitative research articles. (Cantarutti, Merlino,

Monzani, Giaquinto, & Corrao, 2016; Huybrechts et al., 2015; Huybrechts et al., 2016;

Sadowski, Todorow, Yazdani Brojeni, Koren, & Nulman, 2013; Vigod et al., 2015).

Findings/Results

The results of the five articles provide conflicting evidence on whether psychotropic

medications cause significant adverse effects in the neonate. Three articles concluded that there

were significant risks of adverse neonatal outcomes (Huybrechts et al., 2015; Huybrechts et al.,

2016; Sadowski et al., 2013) while two articles concluded that there was no way to determine if

the adverse effects were experienced because of medication or because of exposure to poor

maternal coping skills and the maternal mental illness (Cantarutti et al., 2016; Vigod et al.,

2015). A summary of the research is provided in Table 1. There was much diversity in the study

findings. This review structure is based on the following themes: preterm birth, low birth weight,

and adaptation.

Preterm Birth

Neonates born to mentally ill women taking psychotropic medications have an increased

risk of being born at less than thirty-seven weeks’ gestational age (Cantarutti et al., 2016). In a

quantitative study Cantarutti, Merlino, Monzani, Giaquinto, and Corrao (2016), focused on

women using antidepressants in pregnancy. This study was conducted by using data provided

from the healthcare database in Lombardy, Italy. Cantarutti et al., researched 385,673 births over

a five-year span. The authors used chi-squared and the log-binomial regression model to validate

data collected and used statistical analysis to analyze the data. Cantarutti et al., reports that while

psychotropic medication could be the cause of the preterm birth, poor coping skills developed to
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manage the mental illness could contribute to the preterm birth as well. Therefore, pregnant

women with mental illness should be taught positive coping skills.

Vigod, Gomes, Wilton, Taylor and Ray (2015), used a quantitative, retrospective study to

analyze antipsychotic use in pregnancy. This study was conducted using a high dimensional

propensity score. The participants were women from Ontario, Canada that had delivered a single

baby between 2003 and 2012. Each of the 1,021 mothers that had used psychotropic medication

during pregnancy was paired with a control that had not used psychotropic medication during

pregnancy. The authors used a high dimensional propensity score to create cohorts in the

population. The authors found that there were no significantly increased risks for preterm birth in

neonates exposed to antipsychotics compared to neonates not exposed to antipsychotics.

Low Birth Weight

Neonates exposed to psychotropic medication in utero have an increased risk of low birth

weight (Cantarutti et al., 2016). There ae differences in defining what is considered low birth

weight. In the study by Vigod et al., (2015), low birth weight is considered “<3rd centile or >97th

centile” (Vigod et al., p. 1) while Cantarutti et al., (2016), defined low birth weight as “less than

2,500 grams” (Cantarutti et al., p. 4). Cantarutti et al., found that neonates exposed to

psychotropic medications in utero had a 20% increased chance of low birth weight. While

Cantarutti et al., found that neonates exposed to psychotropic medication in utero had an

increased risk of low birth weight, the authors found that poor maternal coping skills could

contribute to neonatal low birth weight. Vigod et al., reported that there was low birth weight in

neonates exposed to psychotropic medication, but the incidence was not significantly elevated

when compared to neonates not exposed to psychotropic medications.

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Adaptation

Neonates exposed to psychotropic medication in utero have an increased risk of

adaptation problems such as respiratory or gastrointestinal issues (Huybrechts et al., 2015;

Huybrechts et al., 2016; Sadowski et al., 2013). In the article by Huybrechts et al., (2015), the

authors used a cohort, retrospective, quantitative study. Medicaid Analytic Extract was used to

gather information on pregnant women enrolled in Medicaid from the date of the last menstrual

period through one month postpartum. There were 3,789,330 women studied that were enrolled

in Medicaid within the specified time frame. The sample was narrowed to only include women

with a psychiatric diagnosis that included depression. The authors analyzed the data collected via

a logistic regression analysis. The results identified that while there is an increased risk of

persistent pulmonary hypertension in neonates exposed to psychotropic medication, the

increased risk is small.

In the study by Huybrechts et al., (2016), the authors used a quantitative study to gather

information on the increased risk of congenital malformations in the neonate exposed to

psychotropic medication during gestation. The 1,360,101 participants were chosen based on their

enrollment in Medicaid. Each participant had to be enrolled in Medicaid three months before the

last menstrual period and at least one month after delivery of the neonate. Authors pulled data

from the pregnancy cohort of the Medicaid Analytic Extract. The authors used statistical,

sensitivity, and exploratory analysis to analyze the data collected. Based on this study, there is a

slight increased risk for congenital malformations in neonates exposed to psychotropic

medications in utero. However, the benefits of the psychotropic medication in the mother

outweigh weigh the risk of congenital malformation in the neonate.

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Sadowski, Todorow, Yazdani Brojeni, Koren, and Nulman, (2013), used a retrospective,

quantitative study to research the effects of exposure in utero to no psychotropic therapy,

psychotropic monotherapy, and psychotropic polytherapy on the neonate. Sadowski et al.,

selected participants who called the Motherisk Program at the Hospital for Sick Children in

Toronto, Canada. Inclusion criteria included taking a second-generation antipsychotic for a

minimum of four weeks. Exclusion criteria included taking a second-generation antipsychotic for

less than four weeks and ingesting illicit drugs. Each of the 133 participants was matched with a

healthy control. The authors used a triangulation method with a series of statistical tests to

validate data. The results showed that there was an increased risk of poor neonatal adaption

(PNA) in neonates exposed to psychotropic monotherapy in utero. When considering

psychotropic polytherapy, the results showed a significantly increased risk for admission into the

NICU and significantly increased risk for PNA for neonates exposed in utero.

Discussion/Implication

The results and conclusions from the articles chosen for this integrative review showed a

diversity in results regarding adverse effects in neonates exposed to psychotropic medications.

Cantarutti et al., (2016) found that while there was an increased risk for preterm birth and low

birth weight in neonates exposed to psychotropic medications in utero, those complications could

also be caused by poor coping skills developed by the mother to manage her mental illness.

Huybrechts et al., (2015), found that there was a slightly increased risk of neonates developing

persistent pulmonary hypertension if exposed to psychotropic medications. Sadowski et al.,

(2013), found that neonates exposed to psychotropic medications had an increased risk of poor

neonatal adaption signs such as respiratory and gastrointestinal problems. Because all five

articles had diverse results with no conclusive result, there is ample room for future research.
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Based on the information in these articles, changes in practice can be implemented.

Pregnant women with mental illness should be taught healthy coping skills to manage the illness.

Cantarutti et al., 2016, found that poor coping skills could contribute to preterm birth and low

birth weight in neonates. Sadowski et al., (2013), found that psychotropic polytherapy

significantly increased the risk for marked neonatal adverse effects when compared with

psychotropic monotherapy. Therefore, providers should decrease the number of psychotropic

medications prescribed during pregnancy.

Future research should focus on the effects of psychotropic therapy on the neonate

compared with the effects of the pregnant woman’s mental illness and poor coping skills on the

neonate. By doing this, future researchers can determine whether the adverse effects in the

newborn that have previously been found are related to exposure to psychotropic medication in

utero or exposure to mental illness and poor maternal coping skills in utero. The incidence of

mental illness is rising, and the ideal would be conclusive results on the effects of psychotropic

medication on the neonate.

Limitations/Conclusion

There are limitations that should be noted regarding the studies chosen for this integrative

review. The biggest limitation of this study is the researcher’s lack of knowledge with the

integrative review process. Other limitations include: gaps in the literature, limited relevant

literature, and the strength of the studies chosen in this review. The researcher’s limited

knowledge on researching articles, analyzing data, recommending change in practice should also

be noted. Delimitations of this study include being limited to five articles written in English and

published within the past five years.

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The authors of the studies chosen for this integrative review agreed that there should be

further research on of the effects psychotropic medications taken during pregnancy on neonates.

Psychotropic medications can cause adverse effects in the neonate, but a pregnant woman’s poor

coping skills can also cause adverse effects in the neonate. Having an increased knowledge of the

effects of exposure to medication compared with exposure to the mother’s mental illness will

help to treat pregnant women with a mental illness in the future. While all five articles chosen for

this study are relevant to the PICO question chosen, the five articles lack the strength that is

needed to be considered solid studies. More research is needed to understand the effects of

maternal use of psychotropic drugs during pregnancy on the neonate.

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References

Cantarutti, A., Merlino, L., Monzani, E., Giaquinto, C., & Corrao, G. (2016). Is the risk of

preterm birth and low birth weight affected by the use of antidepressant agents during

pregnancy? A population-based investigation. PLOS ONE, 11(12), 1-10.

doi:10.1371/journal.pone.0168115

Huybrechts, K. F., Bateman, B. T., Palmsten, K., Desai, R. J., Patorno, E., Gopalakrishnan, C.,

… Hernandez-Diaz, S. (2015). Antidepressant use late in pregnancy and risk of

persistent pulmonary hypertension of the newborn. Obstetrical & Gynecological

Survey, 70(10), 2142-2151. doi:10.1097/01.ogx.0000472158.66771.3e

Huybrechts, K. F., Hernández-Díaz, S., Patorno, E., Desai, R. J., Mogun, H., Dejene, S. Z., …

Bateman, B. T. (2016). Antipsychotic use in pregnancy and the risk for congenital

malformations. JAMA Psychiatry, 73(9), 938-946.

doi:10.1001/jamapsychiatry.2016.1520

Sadowski, A., Todorow, M., Yazdani Brojeni, P., Koren, G., & Nulman, I. (2013). Pregnancy

outcomes following maternal exposure to second-generation antipsychotics given with

other psychotropic drugs: A cohort study. BMJ Open, 3(7), 1-10. doi:10.1136/bmjopen-

2013-003062

Vigod, S. N., Gomes, T., Wilton, A. S., Taylor, V. H., & Ray, J. G. (2015). Antipsychotic drug

use in pregnancy: High dimensional, propensity matched, population based cohort

study. BMJ, 350(11), 1-9. doi:10.1136/bmj.h2298

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Table 1 – Quantitative and Qualitative Article Summaries

Table 1

Article 1

Author Department of Statistics and Quantitative Methods, Division of

(Year)/Qualifications Biostatistics, University of Milano-Biocca

Operative Unit of Territorial Health Services Region of Lombardy:

Milan, Italy

Department of Mental Health, Ca Granda Niguarda Hospital: Milan,

Italy

Department of Women’s and Children’s Health, University of

Padova: Padova, Italy

Abstract/ Abstract includes background, objective, methods, results, and

Introduction/ conclusions

Background/Problem Introduction is clear and concise with the problem statement clearly

Statement stated as the effects of antidepressants of the unborn fetus. The

purpose of this article was to investigate the effects of

antidepressants in regard to the risk of preterm birth and low birth

weight.

Conceptual/ No conceptual or theoretical framework

Theoretical

Framework

Design/Research Quantitative

Methods/Sample/ Researchers collected data from healthcare utilization databases of

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Setting/Ethical Lombardy.

Considerations/ The sample size was 384,673 mother-newborn couplets

Major Variable No mention of ethical considerations

Studied/ Studied use of antidepressants in pregnancy related to preterm birth

Measurement and low birth weight

Tool/Data Collection Chi-squared, the log-binomial regression model

Tool/Data Analysis Statistical Analysis System Software

Findings/Results Participants who used antidepressants during pregnancy had a higher

prevalence of preterm birth and low birth weight compared to

participants who had never used antidepressants.

Discussion/ While prenatal exposure to antidepressants puts the fetus at risk for

Implications preterm birth and low birth weight, the unhealthy coping mechanisms

that the mother’s form to cope with depression could also cause

preterm birth and low birth weight.

Limitations/ Exclusion of mother-new-born pairs lacking identification codes

Conclusions could affect less healthy women

Exclusion of mother’s who spontaneously aborted or electively

aborted

No information on whether the medication was consumed as directed

Not being able to assess the validity of data collected due to privacy

concerns

Not assessing when (trimester/gestational weeks) the antidepressants

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were used during pregnancy

Women who take antidepressants during pregnancy have higher rates

of preterm birth and low birth weight. However; these complications

may be because of depression and unhealthy habits formed to cope

with the depression during pregnancy. More research is needed on

the risks versus benefits of antidepressant therapy during pregnancy

Appraisal/Worth to Relevant to my PICO

practice

Article 2

Author PhD

(Year)/Qualifications MD

ScD

MS

DrPH

Abstract/ Abstract includes importance, objective, design and setting,

Introduction/ participants, exposures for observational studies, main outcomes and

Background/Problem measures, results, and conclusions and relevance.

Statement The introduction is not clearly identified, but the problem statement

is the effect of antidepressants on the newborn. The purpose of this

study is to research the correspondence between antidepressant use in

pregnancy and persistent pulmonary hypertension in the newborn.

Conceptual/ None discussed

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Theoretical

Framework

Design/Research Quantitative study

Methods/Sample/ Data was extracted from the Medicaid Analytic eXtract for 46 states

Setting/Ethical and Washington D.C.

Considerations/ 3,789,330 pregnant women enrolled in Medicaid no greater than 2

Major Variable months past their last menstrual period through at least 1 month after

Studied/ delivery.

Measurement Studied antidepressant use and the persistent pulmonary hypertension

Tool/Data Collection of the newborn

Tool/Data Analysis Researchers compared sociodemographic, clinical, and health care

use characteristics between exposure groups and determined the

frequency of PPHN in exposed and unexposed women. Results were

presented in 4 adjusted levels.

Findings/Results Participants that took antidepressants had an increased risk of

delivering a baby with PPHN. The risk is lower than once thought.

Discussion/ That women can continue to take antidepressants during pregnancy

Implications without the fear of higher risk for PPHN.

Limitations/ There is no guarantee that participants are taking the medications as

Conclusions prescribed.
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Appraisal/Worth to Relevant to my PICO.

practice

Article 3

Author PhD

(Year)/Qualifications MD

BS

Abstract/ Abstract includes importance, objective, design,

Introduction/ setting, and participants, exposures, main outcomes and

Background/Problem measure, results, and conclusions and relevance. The

Statement background is clear and concise with the problem statement being

that there is little known about the side effects of antipsychotics on

the unborn fetus, but the use of antipsychotics is increasing rapidly.

Conceptual/ No mention of a conceptual or theoretical framework

Theoretical

Framework

Design/Research Researchers used the pregnancy cohort in the Medicaid Analytic

Methods/Sample/ Extract Database

Setting/Ethical Researchers used statistical, sensitivity, and exploratory analyses to

Considerations/ analyze the data

Major Variable 1,314,715 participants

Studied/ Studied the use of antipsychotics on congenital malformations in the

newborn
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Measurement

Tool/Data Collection

Tool/Data Analysis

Findings/Results The risk for congenital malformations was higher in those women

treated with antipsychotics

Discussion/ There is an increased risk for congenital malformations in the women

Implications treated with antipsychotics

More research needs to be done with a way to ensure that the

medication is being taken like it should be

Limitations/ Possible selection bias

Conclusions Possible miscoding of information in the database where data was

collected

No guarantee that medication was taken the way it was prescribed

Absence of a validation test for non-cardiac malformations

Appraisal/Worth to Relevant to my PICO.

practice

Article 4

Author Qualifications are not easy to find. After searching the internet at

(Year)/Qualifications least one author has a PhD

Abstract/ Abstract includes objectives, design, setting, participants, main

Introduction/ outcome measures, results, and conclusions.

Background/Problem The problem statement in this study is the lack of information

Statement regarding the effects of second-generation antipsychotics (SGAs) and

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the concomitant use of other psychotropic drugs with SGAs on both

the mother and the fetus.

Conceptual/ No conceptual or theoretical framework

Theoretical

Framework

Design/Research Descriptive cohort study

Methods/Sample/ 370 participants

Setting/Ethical Ethical considerations clearly shown

Considerations/ Used triangulation to validate data

Major Variable Series of statistical tests for data validation

Studied/

Measurement

Tool/Data Collection

Tool/Data Analysis

Findings/Results Significant adverse effects on neonates

Discussion/ There are clear implications for practice. Decrease the number of

Implications psychotropic medications taken during pregnancy.

Limitations/ Limitations in the retrospective aspect of the study

Conclusions Not able to distinguish between the effects of the mental illness on

the neonate versus the medication effects on the neonate

Well written without jargon, but full of abbreviations

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As there are more psychotropic drugs used there are more severe

neonatal outcomes

Appraisal/Worth to Relevant to my PICO

practice

Article 5

Author MD

(Year)/Qualifications PhD

University of Toronto

Abstract/ Abstract included objective, design, setting, participants, main

Introduction/ outcome measures, results, and conclusions

Background/Problem Background in clear with the problem statement clearly stated as the

Statement dearth of knowledge on the outcomes of antipsychotics in the unborn

fetus.

Conceptual/ No conceptual or theoretical framework mentioned

Theoretical

Framework

Design/Research Population based cohort study using health data for women with

Methods/Sample/ public medicine coverage that delivered a baby.

Setting/Ethical All participants had to fill a prescription 180 days before and 180

Considerations/ days after pregnancy

Major Variable 52, 615 participants

Studied/ HDPS algorithm

Statistical and sensitivity analysis

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Measurement Studied the effects of antipsychotics on short term perinatal outcomes

Tool/Data Collection

Tool/Data Analysis

Findings/Results Antipsychotics do not pose an increased worsening of perinatal

outcomes.

Discussion/ Large population based study

Implications It is safe to use antipsychotics in pregnancy with no significant

increased risk for poor neonatal outcomes

Limitations/ Because the participants were women that were eligible for public

Conclusions drug assistance, the participants were mainly of a lower

socioeconomic status leaving the results of the study less

generalizable.

Did not assess for previous cardiac function on the mother or cardiac

function in the newborn

Appraisal/Worth to Relevant to my PICO

practice