Cystic fibrosis signs in newborns may not predict poorer long-term outcomes

Study: Lung function in these patients tended to decline more during adolescence

Written by Michela Luciano, PhD

Developing cystic fibrosis (CF) during the first month of life may no longer necessarily predict poorer long-term outcomes, a new study from Portugal suggests.

Despite experiencing substantial disease burden early in life, people whose signs of CF first manifested during the neonatal period had similar long-term nutritional outcomes and survival as those who did not have symptoms as newborns. Their lung function, however, tended to decline more during adolescence, although the difference between the groups was not statistically significant.

“Neonatal presentation in CF no longer confers a uniformly adverse long-term prognosis under contemporary care,” researchers wrote. “However, the observed trend toward greater [lung] decline during adolescence suggests persistent respiratory vulnerability requiring long-term surveillance.”

The study, “Long-term clinical outcomes of neonatal cystic fibrosis presentation: a single-center retrospective study,” was published in the European Journal of Pediatrics.

CFTR modulators have improved outcomes for many CF patients

CF is caused by mutations that disrupt the production or function of the CFTR protein, which helps regulate the movement of salt and water in and out of cells. This leads to the buildup of thick, sticky mucus in several organs, particularly the lungs and digestive system, driving CF symptoms.

In some babies, signs of CF can develop during the first weeks of life. These can include meconium ileus — an intestinal blockage caused by unusually thick first stool — pancreatic insufficiency, in which the pancreas does not make or release enough enzymes to properly digest food and absorb nutrients, poor weight gain, liver problems, and respiratory symptoms.

Such neonatal manifestations have historically been associated with a more severe clinical course. However, newborn screening for CF, which was incorporated into the Portuguese National Newborn Screening Program in 2018, enables earlier diagnosis. Meanwhile, the introduction of CFTR modulators, a class of medications for the treatment of CF, has dramatically improved outcomes for many people with CF.

Digestive manifestations common among neonatal patients

Against this changing treatment landscape, researchers in Portugal sought to determine whether neonatal CF presentation remains associated with poorer long-term outcomes.

They retrospectively analyzed data from 61 people with CF who were followed at a reference center in Lisbon between 2013 and March 2025. Neonatal presentation was defined as having at least one CF-related manifestation during the first 28 days of life.

Based on this definition, 16 patients (26.2%) had presented with CF during the neonatal period, while the remaining 45 (73.8%) had not. By the end of the study, 24 participants were younger than 18 and 37 were adults.

Screening data were unavailable for 72.6% of participants, mostly because they were born before Portugal’s newborn screening program was implemented. Overall, 39 patients (63.9%) were receiving CFTR modulator therapy.

Among those with neonatal presentation, digestive manifestations were particularly common. Fifteen of the 16 had meconium ileus, all of whom required surgery, while 15 had pancreatic insufficiency and 12 had poor weight gain. Four had neonatal cholestasis, a liver condition that can cause bile to build up, while none had respiratory symptoms during the neonatal period.

Despite this substantial early disease burden, long-term nutritional outcomes were similar between the groups. Body mass index (BMI), a measure of weight relative to height, followed broadly similar patterns from infancy through age 18, with no significant differences at any of the ages assessed.

A persistent trend toward greater decline in pulmonary function during adolescence suggests that early severe disease expression may still confer a degree of long-term respiratory vulnerability.

Lung function showed a somewhat different pattern. At age 10, forced expiratory volume in one second (FEV1) — a standard measure of how much air a person can forcibly breathe out in one second — was similar between the groups, averaging about 87% of predicted in the neonatal group and 89% in the non-neonatal group.

By age 18, however, average FEV1 had declined in the neonatal group, while remaining relatively stable among those without neonatal presentation. Although the difference was not statistically significant, the researchers said the trend may point to persistent respiratory vulnerability among people whose disease manifested very early in life.

CF-related complications developed at similar overall rates in the neonatal and non-neonatal groups (81.2% vs. 77.8%), although the pattern of complications suggested greater disease burden and more advanced clinical progression in the non-neonatal group. The median number of hospitalizations was also similar between the groups (2.5 vs. 2), as were death rates during follow-up (6.2% vs. 8.9%).

The study was limited by its small size, retrospective single-center design, and differences in participants’ exposure to CFTR modulators and newborn screening. Still, the findings suggest that neonatal CF “no longer defines a uniformly adverse long-term prognosis in the era of newborn screening and CFTR modulator therapy,” the researchers wrote.

Yet “a persistent trend toward greater decline in pulmonary function during adolescence suggests that early severe disease expression may still confer a degree of long-term respiratory vulnerability,” the team added.

The prognostic meaning of neonatal CF may continue to change as CFTR modulators are started earlier in life, the researchers noted.

“Larger prospective studies are needed to clarify long-term impact of severe neonatal disease manifestations in this rapidly changing therapeutic landscape,” they concluded.

Source:https://cysticfibrosisnewstoday.com/news/cystic-fibrosis-signs-newborns-predict-poorer-outcomes/