Women with AHP at higher pregnancy complication risk: Study
Babies born of women with the disease were more likely to be small
Women with acute hepatic porphyria (AHP) were at a higher risk of developing high blood pressure and diabetes during pregnancy than their healthy counterparts, and their babies were more likely to be born small, according to a Swedish study.
Those with acute intermittent porphyria (AIP) — the most common AHP type — who had high levels of porphobilinogen (PBG), a heme precursor that builds up to toxic levels in the disease, were also at a higher risk for adverse pregnancy outcomes.
The findings reflect an increased risk for pregnancy and birth-related outcomes “despite an increased disease awareness and better overall care for patients with AHP,” the researchers wrote, noting a need for a “multidisciplinary model of care for pregnant women with AHP.”
The study, “Maternal and fetal outcomes in acute hepatic porphyria: A Swedish National Cohort Study,” was published in the Journal of Inherited Metabolic Disease.
AHP is group of porphyrias wherein heme precursors accumulate to toxic levels in the liver, driving sudden and severe pain attacks and neurological symptoms. Heme is a molecule that helps transport oxygen throughout the body.
Types of AHP include AIP, ALAD porphyria, hereditary coproporphyria, and variegate porphyria, which, while they feature similar symptoms, are each caused by a distinct genetic mutation.
The onset of AHP typically occurs after puberty and its symptoms are more common in women of reproductive age than in men, indicating reproductive hormones may play a role in its expression.
Some reports suggest women with AHP may be at a higher risk of certain pregnancy-associated complications, but such studies “are often limited to case reports and case series,” the researchers wrote.
Scientists in Sweden previously found that most AHP pregnancies were uncomplicated and that elevations in heme precursors during pregnancy didn’t raise risks.
Complications with AHP, lower birth weight babies
The same research team has now examined a larger set of pregnancy and birth data from all 214 adult women with AHP included in the Swedish Porphyria Register between 1987 and 2015, as well as 2,174 healthy adult women from the general population who had at least one registered birth in the Swedish Medical Birth Register.
A total of 382 deliveries were recorded among women with AHP and 4,143 among those in the healthy group.
A significantly higher proportion of women with AHP (6.3%) developed high blood pressure, or hypertension, during pregnancy relative to the healthy group (3.6%), a finding researchers noted was “consistent with some previous reports.”
Women with AHP were also more likely to develop diabetes during pregnancy (2.6%) than healthy women (0.8%), a new finding that “merits further study,” they said.
Babies born to women with AHP were more likely to have a low birth weight and have an Apgar score of 7 or less immediately after birth compared with babies born to healthy women. Apgar scores are an indicator of a newborn’s health, with lower scores reflecting worse health.
For women with AIP, the most common type of AHP, higher maximal lifetime urine levels of PBG were associated with certain pregnancy risks. Specifically, women with high lifetime PBG were at an increased risk of developing high blood pressure and gestational diabetes during pregnancy relative to women with normal or moderate PBG levels.
“This aligns with emerging knowledge that biochemical activity in AIP over time correlates to disease complications and manifestations,” the researchers wrote.
Women with normal or moderate PBG levels were more likely to have a newborn with an Apgar score of 7 or less.
Addressing pregnancy-associated risks
Given the increased pregnancy-associated risks among women with AHP, “we suggest that all women with AHP should receive preconception counseling to be made aware of the clinical manifestations of porphyria and to be advised about self-care and preventative measures to avoid exacerbation,” wrote the researchers, who noted such measures may include adequate nutrition, avoiding disease triggers, and rest.
The researchers emphasized that a woman’s physician should make an individualized care plan for their patient based on her disease manifestations and heme precursor levels. Women with more active disease might need specialized care or more frequent monitoring, they noted.
“Although our observations reflect Swedish maternal health care, we think that our results may be generally applicable,” the scientists wrote.
The study was supported by grants from Alnylam Pharmaceuticals, which markets the approved AHP therapy Givlaari (givosiran).