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Fruit of the Womb
Fruit of the Womb

SSRIs and Persistent Pulmonary Hypertension

Freshly oxygenated blood from the placenta enters the baby through the umbilical vein. Some of this blood is diverted into the liver before traveling to the heart and the rest goes directly to the heart through a blood vessel, called the ductus venosus. The ductus venosus is oriented in such a way that the highly oxygenated blood carried in this vessel, preferentially, shoots through a hole (the foramen ovale) between the upper chambers of the heart (the atria), is pumped into the left ventricle and then into the ascending aorta through which it is distributed, largely, to the organs above the diaphragm, especially the brain.

The less oxygenated blood that enters the fetal heart, preferentially, ends up in the right ventricle and is pumped out through the pulmonary artery. However, instead of going into the lungs, as will be the case after the baby is born, most of this blood bypasses the lungs through an extension of the pulmonary artery, called the ductus arteriosus, that plugs directly into the descending aorta, providing oxygen to organs below the diaphragm and returning blood back to the placenta through the umbilical arteries so that it can get more oxygen.

The ductus venosus, the foramen ovale, and the ductus arteriosus, comprise what is known as the ‘fetal circulation’ that helps distribute the most oxygen to the most important organs while conserving oxygen by diverting blood flow away from the lungs while the baby is in the womb. When the baby is born and takes its first breath, the lungs fill with air, resistance to blood flow through the lungs goes down, and all of these ‘shunts’ begin to close, generally, completing that process within minutes to hours after birth. When conversion to the normal extrauterine circulation is complete, poorly oxygenated blood enters only the right side of the heart, is pumped from the right ventricle into the pulmonary artery, then into the lungs where it picks up oxygen, and returns to the left side of the heart and into the circulation.

So, now what does all of this have to do with SSRI antidepressant drugs like paroxetine (Paxil), fluoxitene (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro)? Dr. SW Wen and colleagues at the University of Ottawa reported last year (Am J Obstet Gynecol 2006;194:161-6)that women on SSRIs later in pregnancy were at increased risk for preterm delivery (19.3% vs. 12.0%), low birth weight babies (9.0% vs. 5.3%), unexplained fetal death (1.1% vs. 0.4%), and babies who had seizures in the neonatal period (0.4% vs. 0.1%). Babies exposed to SSRIs late in pregnancy also may be at risk for withdrawal symptoms such as jitteriness, irritability, high-pitched crying, increased muscle tone, and difficulties eating and sleeping. Indeed, one study reported that as many as one-third of babies exposed to SSRIs late in pregnancy will suffer some degree of withdrawal symptoms (Levinson-Castiel R, et al., Arch Pediatr Adolesc Med 2006;160:173-6)

However, a far greater problem was reported by Dr. Christina Chambers and colleagues in the New England Journal of Medicine (2006;354:579-87) and relates to our discussion on fetal circulation. These investigators found a six-fold greater risk for persistent pulmonary hypertension (PPHN) in babies whose mothers took an SSRI drug after 20 weeks’ gestation compared to babies whose mothers did not. PPHN is a serious problem that can result in respiratory failure with short- and long-term morbidity and mortality of 10-20%. PPHN is accompanied by increased resistance to blood flowing through the lungs and, if present, can result in persistence of the fetal circulation described above where blood continues to bypass the lungs through the foramen ovale and the ductus arteriosus. That may be hunky-dory for a fetus, but it is very bad news for a newborn baby who has no other source of oxygen than its own lungs. The mechanism by which SSRIs contribute to PPHN is currently unknown, but the seriousness of this complication warrants honest assessment of the risks and benefits of continuing these drugs during pregnancy.

To put this into perspective, PPHN was found in about 1% of babies exposed to SSRIs late in pregnancy and this risk must always be weighed against the maternal risks of complications related to discontinuing SSRI antidepressant therapy. Indeed, LS Cohen and colleagues reported in the Journal of the American Medical Association (JAMA. 2006;295:499-507) last year that women who discontinued their antidepressant therapy during pregnancy were five times more likely to suffer a relapse of depression than those who did not. If a woman suffers from a serious depressive condition, and is either pregnant or considering a pregnancy, she should not discontinue her therapy on her own without consultation with her physician.
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