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

Abstract

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 participants: The 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).

Results: Of 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.

Figure 1. Distribution of Baby Observational and Nutritional Study (BONUS) Infant z Scores for Growth at 3, 6, and 12 Months of Age

Curves indicate World Health Organization (WHO) standard growth curves for healthy infants; we calculated z scores for attained weight, length, and occipital frontal circumference (OFC) for age of infants in the BONUS cohort using the WHO standard growth curves.

Figure 2. Baby Observational and Nutritional Study (BONUS) Cohort and Historic Infant Cohort z Scores for Growth During the First Year of Life

We calculated z scores for mean attained weight and length for age of infants using the World Health Organization standard growth curves. The historic cohort includes infants in the 1994–1995 Cystic Fibrosis Foundation Patient Registry (Registry) birth cohort. Error bars indicate 95% CIs. Percentages indicate the percentages of the cohort undergoing newborn or prenatal screening.

Figure 3. Feeding Type and Caloric Intake in the Growth of Baby Observational and Nutritional Study (BONUS) Cohort During the First Year of Life

We calculated z scores for mean attained weight and length for age of infants using the the World Health Organization (WHO) standard growth curves and plotted these by breastfed (BF) only, formula fed (FF) only, and both. Caloric intake by weight categorization and length categorization was calculated among exclusively FF or solid food–fed BONUS infants. Low categorization indicates that more than 50% of measurements are less than the 10th percentile of the WHO standard curve, with at least 1 such measurement occurring after 6 months of age. Error bars indicate 95% CIs.

Figure 4. Plasma Hormonal Growth Factors by Weight and Length at Enrollment and 6 and 12 Months of Age in the Baby Observational and Nutritional Study (BONUS) Cohort

Distributions of insulinlike growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are shown by normal vs low weight and length categorizations. Boxes indicate 25th, 50th, and 75th percentiles; dashed horizontal lines, reference level; open circles, outliers; and whiskers, 1.5 times the 25th to 75th percentile. Low categorization indicates that more than 50% of measurements are less than the 10th percentile of the World Health Organization standard curve, with at least 1 measurement occurring after 6 months of age. To convert IGF to nanomoles per liter, multiply by 0.131. ^aCalculated as comparison of plasma hormonal levels between low and normal growth categorizations across all 3 points.