Understanding the Heart Risks: Antidepressant Use During Pregnancy and Congenital Heart Disease in Newborns

Table of Contents

• Key Points
• Why This Research Matters
• Background: Depression and Antidepressant Use in Pregnancy
• How the Study Was Conducted
• Key Findings: Heart Abnormalities Detected
• What These Findings Mean for Patients
• Study Limitations
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In 40 pregnancies with antidepressant exposure, fetal echocardiography found congenital heart disease in 18%, versus about 1% in the general population.
• Specific heart defects were linked to fluoxetine, citalopram, escitalopram, and venlafaxine; sertraline, paroxetine, bupropion, and duloxetine had no observed defects.
• All fetal echocardiogram findings were confirmed by postnatal echocardiograms, and two independent cardiologists agreed on every case.
• The study was retrospective, single-center, and small, so it cannot prove cause and effect or give definitive risk rates.
• Women taking SSRIs or SNRIs during pregnancy should have a careful risk-benefit discussion with their healthcare provider and consider fetal echocardiography monitoring.

Why This Research Matters

Depression during pregnancy is a major health care problem. Approximately 10 to 20 percent of women experience depression during their pregnancy. Untreated depression can harm both mother and baby, which is why many doctors prescribe antidepressant medications to pregnant women.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have become the mainstay of drug treatment for maternal depression during pregnancy. However, whether these medications pose risks to the developing fetus has remained an open question.

Previous research has shown that antidepressants can cross the placenta from mother to baby. Fluoxetine (Prozac) and citalopram (Celexa) have the highest ratio of umbilical vein-to-maternal serum concentration, meaning they pass most easily from mother to fetus. Sertraline (Zoloft) and paroxetine (Paxil) have the lowest ratio.

This study addresses an important question that has not been well studied: is prenatal exposure to antidepressants associated with congenital heart disease (CHD)—structural heart problems present at birth? Prior studies have documented various adverse outcomes in babies exposed to antidepressants, including gestational hypertension, reduced birth weight, altered neonatal pain responses, and persistent pulmonary hypertension of the newborn. But few longitudinal studies have specifically examined the link between antidepressants and heart defects.

The researchers set out to examine the risk for congenital heart disease in fetuses exposed to SSRIs and SNRIs, using fetal echocardiography (ultrasound imaging of the baby's heart) to look for abnormalities before birth—and then verifying those findings after birth.

Background: Depression and Antidepressant Use in Pregnancy

The use of antidepressant medications during pregnancy has increased steadily over the years, with a reported prevalence of 8 to 13% in the United States. The U.S. Food and Drug Administration (FDA) classifies most SSRIs and SNRIs as class C, meaning animal studies have shown a potential risk to the fetus and there are no adequate human studies. Paroxetine (Paxil) is classified as class D, indicating evidence of human fetal risk.

The official report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists states that serotonin reuptake inhibitor use during pregnancy has been associated with miscarriages, premature and/or low birth weight infants, and fetal malformations.

Known risks of SSRI exposure for newborns include:

• Prematurity (babies born too early)
• Low birth weight
• Persistent pulmonary hypertension of the newborn (a serious condition where a newborn's circulation does not adapt to breathing after birth)
• Decreased Apgar scores (a quick assessment of a newborn's health taken shortly after birth)
• Increased admissions to neonatal intensive care or special care nurseries

Third-trimester exposure specifically increases the risk of:

• Respiratory distress syndrome (difficulty breathing)
• Feeding difficulties
• Hyperbilirubinemia (jaundice, or yellowing of the skin and eyes)
• Neonatal convulsions (seizures in newborns)

Additionally, women with depression who take SSRIs have a higher incidence of preterm birth compared to women with depression who do not take SSRIs. Several studies have reported that paroxetine exposure during the first trimester is associated with fetal cardiac abnormalities, including septal defects (holes in the walls between the heart's chambers), right ventricular outflow tract obstruction defects, left ventricular outflow tract obstruction defects, and conotruncal abnormalities (defects affecting the large blood vessels leaving the heart). These findings, however, have not been reproduced in larger prospective trials. Another report has indicated that using SSRIs together with benzodiazepines during pregnancy may increase the risk of cardiac maldevelopment compared to SSRIs alone. Other studies suggest an increased risk of pulmonary hypertension in newborns when SSRIs are used during the third trimester.

How the Study Was Conducted

The research team conducted a retrospective review of medical records at Children's Hospital of New Orleans. They identified all pregnant women who underwent fetal echocardiography between January 1, 2009, and December 31, 2014, because of in-utero exposure to either SSRIs or SNRIs—a total of 40 women.

Women were excluded from the study if:

• They themselves had a known congenital heart defect or a genetic abnormality
• They were taking benzodiazepines or tricyclic antidepressant medications

For each woman included, the researchers recorded the mother's age, the specific antidepressant medication(s) being used, the gestational age at the time of the fetal echocardiogram, and the echocardiographic findings. Two experienced fetal cardiologists independently reviewed each echocardiogram, and each was blinded to the other's findings—meaning neither doctor knew what the other had concluded, which reduces the chance of bias. The study was approved by the institutional review board of Louisiana State University Health Science Center in New Orleans.

After the babies were born, the cardiac abnormalities that had been diagnosed in utero were confirmed with postnatal transthoracic echocardiograms (ultrasound studies of the heart performed through the chest wall). This confirmation step is a major strength of the study design.

Key Findings: Heart Abnormalities Detected

A total of 40 pregnant women with prenatal exposure to SSRIs or SNRIs were identified. The breakdown of their medications was as follows:

• 31 women (77.5%) were taking SSRIs
• 6 women (15%) were taking SNRIs
• 3 women (7.5%) were taking a combination of drugs

Among the 31 women on SSRIs:

• 5 were on citalopram (Celexa)
• 9 were on escitalopram (Lexapro)
• 9 were on fluoxetine (Prozac)
• 7 were on sertraline (Zoloft)
• 1 was on paroxetine (Paxil)

Among the 6 women on SNRIs:

• 2 were on venlafaxine (Effexor)
• 3 were on bupropion (Wellbutrin)
• 1 was on duloxetine (Cymbalta)

The 3 women on combination therapy were taking: fluoxetine plus bupropion, sertraline plus paroxetine, and venlafaxine plus bupropion.

Of the 40 fetuses, 7 (18%) were found to have congenital heart disease. For context, the incidence of CHD in the general population is about 1%.

Broken down by medication class:

• 5 out of 31 women (16%) on SSRIs had fetuses with cardiac abnormalities
• 2 out of 6 women (33%) on SNRIs had fetuses with cardiac abnormalities
• None of the 3 women on combination drugs had a fetus with CHD

The specific heart defects found, arranged by medication, were:

1. Fluoxetine (2 cases): Two fetuses, at 19 and 19.5 weeks of gestation, were found to have a large posteriorly malaligned ventricular septal defect (VSD—a hole in the wall between the heart's lower chambers), sub-aortic stenosis (narrowing below the aortic valve), and critical coarctation of the aorta (a severe narrowing of the main artery leaving the heart). These are major heart defects that require cardiac surgery.
2. Citalopram (2 cases): One fetus at 25 weeks of gestation had a moderate-size mid-muscular VSD. Another fetus at 23.5 weeks had a moderate-size secundum atrial septal defect (ASD—a hole in the wall between the heart's upper chambers).
3. Venlafaxine (2 cases): One fetus at 33.5 weeks had constriction of the ductus arteriosus (a blood vessel that normally closes shortly after birth), with a ductal Doppler flow velocity of 2.38 m/sec (about 2.4 m/sec)—indicating increased blood flow speed through the narrowed vessel. Another fetus at 27 weeks was found to have two mid-muscular VSDs.
4. Escitalopram (1 case): One fetus at 28.3 weeks had a large membranous VSD, a secundum ASD, and a left superior vena cava (an anatomical variant involving an extra vein in the chest).

Both fetal cardiologists independently reviewed the studies and arrived at the same conclusions in every case. Moreover, all cardiac abnormalities diagnosed before birth were confirmed after birth by postnatal transthoracic echocardiogram.

Looking at the severity of the findings: two fetuses were diagnosed with major congenital heart defects that required cardiac surgery during the newborn period. Four other fetuses were diagnosed with septal defects (ASDs and VSDs). One fetus was diagnosed with ductal constriction secondary to venlafaxine—an SNRI not previously known to have direct cardiac effects. Importantly, this fetus had not been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), which are a known cause of ductal constriction.

To put these numbers in perspective, according to data from the Centers for Disease Control and Prevention (CDC), the general population occurrence of these defects is:

• Atrial septal defect: 13 per 10,000 children
• Ventricular septal defect: 42 per 10,000 children
• Coarctation of the aorta: 4 per 10,000 children

The authors also compared their findings with earlier research. A meta-analysis conducted by Myles and colleagues did not find any congenital malformations in mothers who took citalopram during pregnancy—yet in this study, citalopram was associated with septal defects in two cases. This discrepancy is worth noting. The study did not find any CHD in the single woman taking paroxetine, but with only one woman exposed to the drug, no meaningful conclusion can be drawn. In several other studies, paroxetine has been consistently associated with CHD—a concern that led the FDA to issue a public health advisory about its use in the first trimester in 2005. Fluoxetine was associated with cardiac malformations in this study, which is consistent with previous research findings.

What These Findings Mean for Patients

This is one of the first studies to provide detailed echocardiographic evidence of heart abnormalities in fetuses exposed to specific antidepressants, verified after birth. The rate of CHD in the study group (18%) is strikingly higher than the general population rate (1%). However, because of the small sample size, these numbers should be interpreted with caution.

The findings highlight several important points:

• The risk of CHD is not identical across all antidepressants. Fluoxetine and escitalopram were associated with more severe defects, while citalopram-associated defects were moderate in size.
• Even medications not previously linked to direct cardiac effects, such as venlafaxine, can cause complications like ductal constriction.
• The comparison group here is the general population, not women with untreated depression. Depression itself can affect pregnancy outcomes, so it remains unclear whether the risk comes from the medication, the depression itself, or a combination of both.
• In every case, the fetal echocardiogram findings matched what was confirmed after birth—which strengthens confidence in fetal echocardiography as a diagnostic tool for detecting these conditions during pregnancy.

For women who are pregnant or planning to become pregnant and are taking antidepressants, these findings reinforce the need for a thorough, informed discussion with their healthcare providers about the risks and benefits of continuing or changing treatment.

Study Limitations

Like most other epidemiological studies, this one had both strengths and limitations. The authors were transparent about these.

Limitations included:

• Retrospective design: The study looked back at medical records rather than following patients forward in time, which means it cannot establish cause and effect.
• Single-center study: All patients came from one institution (Children's Hospital of New Orleans), which may limit how well the findings apply to other populations.
• Small sample size: With only 40 women, and even smaller numbers taking each individual medication, the results are not statistically definitive.
• No accounting for other medications: The study did not consider maternal use of other medications, such as anti-seizure medications or oral hypoglycemics (diabetes medications), which could independently affect the risk of CHD.
• No family history review: The researchers did not review whether the mothers had other children with congenital heart disease, which is relevant since CHD can run in families.

Strengths of the study included:

• Confirmed medication use: Antidepressant use was confirmed through chart reviews rather than self-reported telephone interviews, reducing the risk of inaccurate reporting.
• Postnatal confirmation: Every fetal echocardiographic finding was verified after birth with a postnatal echocardiogram.
• Independent review: All echocardiographic findings were read by two independent fetal cardiologists blinded to each other's assessments, reducing interpretation bias.

Recommendations for Patients

The study authors emphasize that this research does not mean antidepressants should never be used during pregnancy. Untreated depression carries serious risks for both mother and baby, and abruptly stopping medication can also be harmful. Instead, they recommend the following:

1. Have a careful risk-benefit discussion: Talk openly with your healthcare provider about the risks of the medication versus the risks of untreated depression in your specific situation.
2. Ask about monitoring: If you are taking an SSRI or SNRI during pregnancy, ask your obstetrician whether a fetal echocardiogram should be considered to check on the baby's heart development.
3. Seek coordinated care: Involve your obstetrician, psychiatrist, and—if needed—a pediatric cardiologist in your care plan so that all aspects of your health and your baby's health are addressed together.
4. Do not stop medications without medical advice: Suddenly stopping antidepressants can lead to withdrawal symptoms and worsening depression. Any changes to medication should be made in consultation with your healthcare team.
5. Stay informed: The authors call for prospective, long-term safety studies—research that follows women and their children over many years—before firm conclusions can be drawn about the safety of individual antidepressants in pregnancy.

The authors' final takeaway: there is a possible association between congenital heart disease and prenatal exposure to SSRIs or SNRIs. Until we have prospective long-term safety studies, careful risk-benefit analysis needs to be applied when considering the use of SSRIs or SNRIs during pregnancy.

Frequently Asked Questions

What did the study find about antidepressant use during pregnancy and heart defects?

In a study of 40 pregnant women taking SSRIs or SNRIs, fetal echocardiography found congenital heart disease in 18% of fetuses, much higher than the 1% rate in the general population. Specific defects were linked to fluoxetine, citalopram, escitalopram, and venlafaxine. Because the group was small, the findings need cautious interpretation.

How was the study conducted?

Researchers reviewed medical records of 40 pregnant women who took SSRIs or SNRIs and had fetal echocardiograms between 2009 and 2014 at one hospital. Two fetal cardiologists independently reviewed each echocardiogram, and all abnormalities found before birth were confirmed with postnatal echocardiograms after delivery.

What were the limitations of this study?

The study was retrospective, single-center, and had a small sample size of only 40 women. It did not account for other medications or family history of heart defects. Because of these limitations, the findings cannot prove cause and effect, and results may not apply to all populations.

Should I stop taking my antidepressant if I'm pregnant or planning to become pregnant?

No. The study authors emphasize that untreated depression carries serious risks for both mother and baby, and abruptly stopping medication can be harmful. They recommend a careful risk-benefit discussion with your healthcare provider about your specific situation, and never stopping medication without medical advice.

What should I do if I take an SSRI or SNRI during pregnancy?

The study authors suggest asking your obstetrician whether a fetal echocardiogram should be considered to check the baby's heart development. Involve your obstetrician, psychiatrist, and if needed, a pediatric cardiologist in coordinated care. Stay informed and discuss all risks and benefits with your healthcare team.

I'm pregnant and taking an antidepressant. Should I get a second opinion about the risk of heart defects in my baby?

Pregnant women taking SSRIs or SNRIs, especially fluoxetine, citalopram, escitalopram, or venlafaxine, may face a meaningful decision about fetal heart risks. In a group of 40 exposed pregnancies, congenital heart disease appeared in 18% of fetuses, compared to a 1% baseline in the general population. Specific defects were linked to these medications. A second opinion can help you weigh whether fetal echocardiography is advisable and how to balance treatment of depression against potential risks. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Risk of Congenital Heart Disease in Newborns with Prenatal Exposure to Anti-depressant Medications

Authors: Pooja H. Desai, Priyank J. Yagnik, Nancy Ross Ascuitto, Parna Prajapati, Steffan Sernich

Journal: Cureus, May 15, 2019, Volume 11, Issue 5, e4673. DOI: 10.7759/cureus.4673

Categories: Cardiology, Obstetrics/Gynecology, Psychiatry

This patient-friendly article is based on peer-reviewed research published in an open-access format under the Creative Commons Attribution License (CC-BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.