Prenatal CF treatment for intestinal blockage shows varying results
Trikafta has different outcomes for 3 infants, per case series
Prenatal Trikafta treatment of three fetuses with cystic fibrosis (CF) for an intestinal blockage called meconium ileus resulted in different outcomes, potentially due to treatment duration, according to a case series.
One infant showed a complete resolution of meconium ileus at birth, one had persistent signs that were cleared with minimally invasive treatment, and a third, the one with the shortest Trikafta exposure, had persistent blockages that required surgery.
“These cases highlight the potentially life-altering effects of prenatal [Trikafta] use and the need for awareness of this clinical situation among fetal care providers,” the researchers wrote.
The case series, “Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis,” was published in the Journal of Cystic Fibrosis.
CF is a genetic disease marked by the accumulation of abnormally thick mucus in various organs, including the lungs and digestive tract. It’s inherited in a recessive manner, meaning a person will develop CF if the person inherits two copies of the defective gene, one from each biological parent, who are referred to as carriers.
Condition seen in CF babies
Up to 20% of babies with CF are born with meconium ileus, when a newborn’s first stool, called meconium, is abnormally thick and sticky, blocking the small intestine. It’s one of the earliest and most severe manifestations of CF, and it often requires surgical intervention and can lead to digestive complications and poor growth.
In isolated cases, mothers who are CF carriers or patients have received treatment with Trikafta, an approved CFTR modulator, to prevent meconium ileus in their unborn infants. While preventing the intestinal condition may have substantial, lifelong benefits for CF infants, Trikafta use in CF carriers during pregnancy is off label and considered controversial.
Researchers at Children’s Hospital of Colorado said questions remain about the ideal timing of prenatal Trikafta treatment and the ethics of treating pregnant CF carriers to benefit unborn children. They described three cases of infants with CF and meconium ileus who were treated prenatally with Trikafta.
In the first case, ultrasound screening at a gestational age of 17 weeks (about 4 months) detected signs of meconium ileus. Prenatal genetic testing of the amniotic fluid around the fetus in the womb revealed two identical mutations called F508del, the most common CF-causing genetic defect.
Trikafta treatment began at 31 weeks (about 7 months) gestational age. Ten days later, an ultrasound showed a slightly reduced meconium ileus compared with one week before treatment. The condition continued to ease until scans showed normal intestinal dimensions before delivery.
The baby girl was born at 39 weeks (9 months) and passed two large meconium stools within a day without medical intervention. Four days after delivery, Trikafta was stopped, and abdominal X-rays showed no signs of meconium ileus. By 8 months, the infant was growing well and on pancreatic enzyme replacement therapy (PERT).
Prenatal treatment important
In the second case, an ultrasound at 20 weeks gestational age found signs of meconium ileus in a female fetus, and testing confirmed CF with two F508del mutations. A repeat ultrasound at 28 weeks confirmed these findings but with a widening and thickening of the bowel. Prenatal Trikafta was started at 30 weeks gestational age.
However, follow-up ultrasounds up to 36 weeks showed multiple areas of bowel dilation. Labor was induced soon after. Rectal irrigations helped clear the meconium and the passage of stools after the newborn failed to pass the meconium and showed signs of meconium plugs.
The infant had continued Trikafta exposure through breastmilk from birth to 5 months. Although the newborn was hospitalized for a lung infection that required oxygen supplementation, she was growing well on PERT with no signs of treatment-related toxicity in liver function tests.
The third case of prenatal meconium ileus was also detected via fetal ultrasound at 28 weeks of gestational age in a female fetus. Seven weeks later, CF was confirmed at 35 weeks gestational age with two F508del variants, and Trikafta treatment was initiated.
Trikafta was stopped after the infant was delivered at 38 weeks. The baby required surgery to remove meconium plugs and remained in the intensive care unit for six weeks. She was treated for cholestasis, a condition in which the flow of the digestive fluid bile from the liver to the intestines is blocked or reduced. Despite starting PERT, her body weight at 3 months was lower than normal, and she was at risk of malnutrition.
“The infant with the most severe outcome had the shortest duration of [Trikafta] exposure and may have been able to receive this medication sooner had a referral to a CF center been made,” the researchers wrote.
The cases show that “as data emerge about the potentially life-altering effects of prenatal [Trikafta] use, provider advocacy will become increasingly important in caring for infants with CF, even before they are born,” they wrote.
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