Pregnancy May Contribute to PAH Onset in Women with BMPR2 Gene Mutations

Pregnancy can be a trigger for pulmonary arterial hypertension (PAH) in women with a genetic predisposition to the disease, according to a case study published in the journal Pulmonary Circulation.

In the study, “Pregnancy As A Possible Trigger For Heritable Pulmonary Arterial Hypertension,” researchers detail the development of aggressive PAH during a second pregnancy.

The patient, a 33-year old woman, had a family history of PAH and a mutation in the BMPR2 gene (the gene whose mutations are associated with PAH onset), but no PAH symptoms or heart abnormalities. At the time of her first pregnancy, several analyses showed normal blood pressure and heart function. She delivered a healthy baby after 40 gestation weeks and, although the delivery was complicated by a mild postpartum hemorrhage, one month later her exams were normal.

The woman refused to undergo a cardiac catheterization, and doctors counseled her about her BMPR2 mutation and advised her to use contraception.

Three years later, she again became pregnant. At six weeks of gestation, the woman had normal heart function, but doctors detected a shift in the heart septum, suggestive of increased pressure in the right ventricle. Right ventricle dilation and blood pressure increased in the following weeks, although heart function was preserved.

A few days before delivery, the patient initiated intravenous Flolan (epoprostenol; a vasodilator taken to reduce blood pressure), starting at 2 ng/kg/min daily andincreasing up to 8 ng/kg/min. One day before delivery, the patient initiated treatment with intravenous adrenaline (2.5 μg/kg/min).

“Her second pregnancy was typical of patients with PAH, with worsening right heart strain and dysfunction, and current data suggest that her mortality risk during that pregnancy was high,” the researchers wrote. “She has now developed overt heritable PAH and is being treated with PAH-specific therapy.”

The baby was born healthy by cesarean delivery (with adrenaline support at 5 μg/kg/min), although the mother had high pulmonary artery pressure (64/31 mmHg; mean 42 mmHg). But the postpartum period was uneventful. Adrenaline treatment was stopped one day after the delivery and Flolan dosage decreased, and stopped in the following week. Eight months later, her right ventricle size and function were normal again.

Genetic counseling was offered to the patient and her family, with options including genetic testing of her children or periodic clinical and heart evaluations as they grow.

“In women, the years of fertility coincide with the years of highest risk of developing idiopathic pulmonary arterial hypertension (PAH),” the authors wrote. “Indeed, it has long been noted that idiopathic PAH may first be noticed during pregnancy or postpartum.” Despite this observation, pregnancy is currently not considered a risk factor for idiopathic PAH.

Carriers of BMPR2 gene mutations who are asymptomatic for PAH may experience increased pulmonary arterial pressure when their blood flow increases, such as during exercise. According to the researchers, pregnancy should represent an even greater stress in patients at risk of developing PAH.

“Certainly, once pulmonary hypertension is established, the hemodynamic abnormalities worsen during pregnancy,” they wrote.

The team believes that increased heart function, hormonal influences, and metabolic changes associated with pregnancy (in this case, more than one) contribute to the onset of PAH in women with BMPR2 gene mutations. Although symptoms may improve after delivery, these women are at high risk of dying.

Such patients should be followed up over time to confirm whether pregnancy promotes PAH onset in a population at risk.