Failure to thrive: the earliest feature of cystic fibrosis in infants diagnosed by neonatal screening

Abstract

The benefits of early treatment of nutritional and respiratory problems in the CF infant and of genetic counselling for the parents are widely recognized. However, clinical diagnosis of CF is often delayed despite early onset of symptoms and the usefulness of neonatal population screening as a preventive measure is still under debate. This study analyses the clinical history of CF patients diagnosed exclusively on the basis of positive neonatal screening tests with the aim of identifying the earliest markers of the disease. We studied 103 CF infants born in north-east Italy, diagnosed following neonatal screening: assay of immunoreactive trypsin (IRT) from a heel-prick blood sample followed by a measurement of meconium lactase in cases with raised IRT. Diagnosis was confirmed by sweat test at an average age of 39 days. Eighty-one patients (79%) had symptoms strongly suggestive of CF at diagnosis, and signs and/or symptoms of pancreatic insufficiency were present in 16 of the remaining 22 cases. The most frequent symptom was growth failure (69% of infants) and of these, 44% weighed the same as at birth or less. Pancreatic insufficiency was confirmed by the low level of faecal chymotrypsin found in 85% of cases. IRT was elevated in all cases. CF had not been suspected in any symptomatic infant, although most of the infants had been monitored by a paediatrician. In conclusion, most infants with CF diagnosed by neonatal screening are already symptomatic in the first six weeks of life and the most frequent symptom is failure to thrive; pancreatic insufficiency was already present in most cases. In areas without CF neonatal screening programs, the disease should be excluded by differential diagnosis in all cases with growth failure notwithstanding adequate caloric intake in the first months of life. The high sensitivity, low cost and simple execution of IRT and fecal chymotrypsin tests make them an ideal first step in suspect cases before proceeding to the sweat test, often performed late because of limited availability.

Inflammation of the cystic fibrosis mouse small intestine

“…A major phenotype of the CF mouse is low body weight that is ϳ30% less than controls at 4 -8 wk of age for mice maintained on the liquid Peptamen diet (9). Low body weight is also a condition of human CF patients (16), but the cause of this failure to thrive is not fully understood. It partially reflects inadequate digestion and nutrient absorption, but may also be contributed to by the abnormal energy expenditure consumed by inflammation in affected organs.…”

Newborn Screening for Cystic Fibrosis

“…Half of infants with CF identified through the NBS program in Colorado showed decreased weight percentile [44], a lower rate of weight gain and decreased triceps skin-fold thickness at diagnosis [45] despite consuming above the recommended caloric intake. In a cohort of infants diagnosed by NBS in Northeast Italy, 69% exhibited growth failure and 44% of the group had not had any weight gain since birth [46]. Initial and prolonged stunting of head growth as manifested by head circumference z-scores was also seen in the Wisconsin control (conventionally diagnosed) group [47].…”

“…Studies from regions performing NBS for CF have consistently shown indices of poor nutrition at the time of diagnosis [45,46]. These deficiencies occur in both breastand bottle-fed infants.…”

Growth Monitoring to Detect Children with Cystic Fibrosis

“…In Caucasian European newborns the incidence is about 1:2,500, whereas in Caucasian North American newborns the incidence is approximately 1:3,500 [1,2]. The symptoms of CF usually start at an early age and include meconium ileus, recurrent respiratory symptoms (cough, wheeze, pneumonia), steatorrhea, diarrhea, abdominal distension and failure to thrive (FTT) (slowed growth) [3,4]. Newborn screening programs for CF have been introduced in several countries.…”