Primary Pulmonary Hypertension (PPH) in Newborns

Common drugs used to treat depression (including Zoloft, Prozac, Celexa, and Paxil) have recently come under fire in the pediatric community.

A case-control study found that infants of women who took an SSRI (an anti-depressant drug that acts by blocking the reuptake of serotonin so that more serotonin is available to act on receptors in the brain) after 20 weeks of gestation had six times the risk of a lung disorder compared with babies born of drug-free women, reported Christina D. Chambers, Ph.D., M.P.H., of the University of California and colleagues in the Feb. 9, 2006 issue of the New England Journal of Medicine.

Researchers recruited 377 women whose babies had Persistent Pulmonary Hypertension of the Newborn (PPHN) and compared them with 836 matched controls.

At the end of the 20th week of gestation, 14 infants with the lung disorder had been exposed to an SSRI compared with only six control infants (adjusted odds ratio 6.1, 95% CI, 2.2-16.8), the team reported.

Timing and drug type were specific. Neither the use of an SSRI before the 20th week of gestation nor use of non-SSRI anti-depressants at any time during pregnancy was associated with an increased risk of the infant lung disorder.

The report comes on the heels of two earlier anti-depressant studies with troubling news for pregnant women with major depression. Israeli researchers found SSRI use linked to neonatal withdrawal syndrome, while Massachusetts General researchers reported a greater risk of relapse for severely depressed women who stopped using the drugs during pregnancy.

Describing the possible biological mechanisms for the effect, the authors wrote that the lung acts as a reservoir for anti-depressants. They suggest that serotonin may increase pulmonary vascular resistance or disrupt normal pulmonary vasodilation after birth by blocking the action of nitric oxide.

Further research to replicate these findings is needed to assess different drugs and dosages, Dr. Chambers said.

In an accompanying editorial, James L. Mills, M.D., of the National Institute of Child Health and Human Development in Bethesda, MD., wrote that the lung disorder is uncommon, so even a sixfold increased risk would not result in a large number of cases. Referring to the earlier Israeli report of neonatal withdrawal syndrome in infants of mothers treated with SSRIs, he said there is pressing need to compare SSRIs with other forms of treatment for depression. Data are lacking, he wrote, on the best way to manage depression in pregnant women.

Meanwhile, he said, clinicians will need to consider the findings of Dr. Chambers and colleagues in dealing with the risk-benefit ratio of drug use.

Primary source: New England Journal of Medicine, February 9, 2006 Source reference: Chambers, Christina D., Ph.D, M.P.H, et al. "Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn," 354; 6: 579-587
 

What is Persistent Pulmonary Hypertension Of The Newborn (PPHN)?

Normally, when a baby is born and begins to breathe air, his circulatory system quickly adapts to the outside world. The pressure in the lungs changes as air enters and inflates the lungs. As a result, the ductus arteriosus, which previously supplied the fetal heart with blood, permanently closes. Blood returning to the heart from the body can now be pumped into the lungs, where oxygen and carbon dioxide are exchanged. The blood is then returned to the heart and pumped back out to the body in an oxygen-rich state.

In a baby with PPHN, however, the fetal circulatory system doesn't "switch over." The ductus arteriosus remains open, and the baby's blood flow continues to bypass the lungs. Even though the baby is breathing, oxygen in the breathed air will not reach the bloodstream. Because the blood returning from the body is unable to enter the lungs properly - and instead flows through the still-open ductus arteriosus - it returns to the heart in an oxygen-poor state. This condition is known as persistent fetal circulation, or PFC.

In the womb, the pathway of your baby's blood circulation is different than it is after birth. In the uterus, a baby's circulation bypasses the lungs. The lungs are not needed to exchange oxygen because the placenta (the organ that nourishes and protects your developing baby) supplies the baby with oxygen through the umbilical cord. The pulmonary artery - which, after birth, will carry blood from the heart to the lungs - instead sends blood directly back to the heart through a fetal blood vessel called the ductus arteriosus.

Depending on the degree of PPHN causing the persistent fetal circulation, the oxygen in the air your baby breathes into his lungs is not adequately picked up and carried by the blood to other areas of the body that need it (such as the brain, kidneys, liver, and other organs). These organs soon become stressed from lack of oxygen.

PPHN sometimes develops as the result of another event during delivery or from a disease or congenital condition affecting the newborn (usually one that either directly affects the lungs or oxygen supply to the baby before or during birth). Often, however, PPHN occurs as an isolated condition. It is usually seen within 12 hours after birth. PPHN occurs in approximately one in 700 births.
 

Other Resources

University of Washington Pediatrics
Newborn Services Clinical Guideline