Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life

Abstract

for the Baby Observational and Nutrition Study (BONUS) Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network IMPORTANCE Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described.OBJECTIVE To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. DESIGN, SETTING, AND PARTICIPANTSThe Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015. Participants included 231 infants younger than 3.5 months who underwent NBS and had confirmed CF, with a gestational age of at least 35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%) completed 12 months of follow-up. EXPOSURE Cystic fibrosis.MAIN OUTCOME AND MEASURES Attained weight and length for age and World Health Organization normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori). RESULTSOf the 231 infants enrolled, 110 infants (47.6%) were female and 121 (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had lower than mean birth weights (mean z score, −0.15; 95% CI, −0.27 to −0.04) and higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved normal weight by 12 months, a significant improvement over a prescreening cohort of newborns with CF from 20 years before the contemporary cohort (mean z score increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12 months (mean z score, −0.56; 95% CI, −0.70 to −0.42). Only 30 infants (13.6%) were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were at less than the 10th percentile of length for age at more than half their visits. Male sex, pancreatic insufficiency, meconium ileus, histamine blocker use, and respiratory Pseudomonas aeruginosa infection were associated with lower weight or length during the first year. Insulinlike growth factor 1 levels were significantly lower among low-length infants. Persistently low-weight infants consumed significantly more calories, and weight and length z scores were negatively correlated with caloric intake.CONCLUSIONS AND RELEVANCE Since initiation of universal NBS for CF, significant improvement has occurred in nutritional status, with normalization of weight in the first year of life. However, length stunting remains common.

Pulmonary findings in infants with cystic fibrosis during the first year of life: Results from the Baby Observational and Nutrition Study (BONUS) cohort study

“…The mean length of respiratory hospitalization was 11.3 ± 9.23 days and the median length of respiratory hospitalization was 9.5 days (3.5, 15). As previously reported, there was no association between respiratory hospitalization and growth parameters 2 . Hospitalized infants were more likely to have crackles and/or wheezes (p=0.009) and abnormal CXR score (p=0.0008), however there was no association between respiratory hospitalization and growth of Pa on OP culture.…”

“…The Baby Observational and Nutrition Study (BONUS) was a prospective cohort study conducted at 28 US Cystic Fibrosis Foundation (CFF) accredited care centers within the CFF Therapeutic Development Network, with methods previously described 2 . Length, weight, and occipital frontal circumference (OFC) were performed at each visit by trained and certified staff 6,1 .…”

“…9, 10 Infants were denoted as having a severe phenotype if both CFTR alleles were classes I-III 11 . Infants were categorized as being Pseudomonas aeruginosa ( Pa ) positive if Pa was recovered on at least one oropharyngeal (OP) swab, collected clinically, during the year of observation 2 . We used the Wisconsin score to assess chest radiographs (CXR).…”

“…Newborn screening for cystic fibrosis (CF) over the last 20 years has contributed to improved weight and stature in children with CF in the United States, particularly in the first year of life 1,2 . CF pulmonary disease begins early, with inflammation and infection leading to bronchiectasis in up to 80% of children age 5 years and above 1 .…”

“…Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. Previous publications have reported on the correlations of clinical parameters such as Pseudomonas aeruginosa ( Pa ), pancreatic insufficiency and growth factor levels with weight and length in the first year of life 2 , as well as the lack of pancreatic enzyme dose effect on growth 5 . This current clinical report summarizes the pulmonary findings in the BONUS CF infants, including symptoms of cough, wheeze, crackles and chest x-ray (CXR) abnormalities, frequency of cultures for CF specific organisms, as well as the relationship of pulmonary findings to acid suppression medications.…”