Zhumin Zhang

Growth and pulmonary outcomes during the first 2 y of life of breastfed and formula-fed infants diagnosed with cystic fibrosis through the Wisconsin Routine Newborn Screening Program

BACKGROUND The optimal feeding (breast milk, formula, or a combination) for infants with cystic fibrosis (CF) is unknown. Recommendations from the CF Foundation are based on limited data. OBJECTIVE We compared growth and pulmonary outcomes between breastfed and formula-fed infants through the age of 2 y. DESIGN A total of 103 CF infants born in 1994-2006 and diagnosed through newborn screening in Wisconsin were studied. Breastfed infants were classified by the duration of exclusive breastfeeding (ExBF). Exclusive formula-feeding (ExFM) was classified by the formulas caloric density (ie, standard [0.67 kcal/mL (20 kcal/oz) (ExFM20)] throughout infancy or high density [≥0.74 kcal/mL (22 kcal/oz) (ExFM22+)] for some duration of infancy). RESULTS Fifty-three infants (51% of infants) were breastfed and 50 infants (49% of infants) were ExFM. In breastfed infants, the duration of ExBF was <1 mo (53% of infants), 1-1.9 mo (21% of infants), 2-3 mo (17% of infants), and 4-9 mo (9% of infants). In ExFM infants, 23 infants (46%) received a formula with a high caloric density; approximately half (n = 13) of the ExFM infants received the formula by 6 mo of age. Proportionately more infants with pancreatic sufficiency (n = 9) were ExBF ≥1 mo (44% of infants), and none of the infants were ExFM22+, compared with infants with meconium ileus (n = 24; 13% of infants were ExBF ≥1 mo, and 38% of infants were ExFM22+) or pancreatic insufficiency (n = 70; 25% of infants were ExBF ≥1 mo, and 20% of infants were ExFM22+) (P = 0.02). In infants with pancreatic insufficiency, weight z scores declined from birth to 6 mo (P < 0.0001) in infants who were ExBF ≥2 mo, and the number of Pseudomonas aeruginosa infections through the age of 2 y was fewer in breastfed than in ExFM infants (P = 0.003) but did not differ by the duration of ExBF. CONCLUSION For infants with CF, ExBF <2 mo does not compromise growth and is associated with a respiratory benefit.

Comparing the Use of Centers for Disease Control and Prevention and World Health Organization Growth Charts in Children with Cystic Fibrosis through 2 Years of Age

OBJECTIVE To examine differences between use of World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) growth reference in children with cystic fibrosis (CF) up to 2 years of age. STUDY DESIGN Growth from 1-24 months in 2587 children, born 2003-2006 and recorded in the US CF Foundation Registry, was evaluated using WHO and CDC references. RESULTS In both boys and girls with CF aged 1-24 months, use of WHO charts resulted in ∼8 percentile lower length-for-age and ∼13% higher short stature rate (length-for-age <5th percentile). WHO weight-for-age was ∼9 percentile lower prior to age 6 months, crossed at 6-7 months, and remained ∼14 percentile higher at 8-24 months. WHO weight-for-length (WFL) percentile (WFLp) was similar before 12 months but ∼10 percentile higher at 12-24 months compared with CDC. When using WHO charts, 9% of children had underweight (WFLp <50th) classified differently and this rate varied with age: 4% in the first year, 7% at 12, 13% at 15, and 16% at 18 months, respectively. Weight status assessed by WHO body mass index (BMI) charts was different from WHO WFL charts. At 24 months when switching back to CDC, 26% of children with normal WFLp on WHO charts appeared underweight on CDC charts. A 70th percentile of WHO BMI percentile was equivalent to the 50th percentile CDC BMI percentile. CONCLUSIONS Growth status in children with CF differed when using WHO and CDC references, particularly during the second year of life. These differences need to be considered for all uses of growth assessment in CF.

Effect of smoking status on total energy expenditure.

Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.

Pubertal Height Growth and Adult Height in Cystic Fibrosis After Newborn Screening

BACKGROUND: To examine long-term growth benefit of newborn screening (NBS), adolescent peak height velocity (PHV), and adult height were compared between the screened (diagnosed early via NBS) and the control (identified generally by symptoms) in the Wisconsin Randomized Clinical Trial. METHODS: Data from 107 children born in 1985–1994 and followed through 2012 were analyzed. PHV was estimated by a semiparametric growth curve model and compared with Tanner reference. RESULTS: Meconium ileus (MI; n = 25) was associated with the worst pubertal growth and adult height, including 1 child who did not experience apparent PHV; children with pancreatic sufficiency (n = 18) achieved the best growth (normal PHV and adult height). In children with pancreatic insufficiency without meconium ileus (n = 64), the subgroup most likely to benefit from NBS, screened children had similar PHV but better adult height compared with controls. Specifically, in boys, the screened group (n = 22) achieved normal PHV (9.5 cm at 13.5 years); the control group (n = 19) had similar onset age (13.6 years) but 0.6-cm lower magnitude (P = .08). In girls, the screened group (n = 10) had somewhat later (12.5 years vs 11.7 years, P = .12) and lower PHV (7.3 cm vs 7.9 cm, P = .33) than the controls (n = 13), coinciding with later menarche (13.6 years vs 12.2 years, P = .10). Adult height was taller in the screened than the control (50th vs 29th percentile, P = .02), even after adjusted for genetic potential (32nd vs15th percentile, P = .006). Differences in adult height were primarily attributable to NBS and better prepubertal growth. CONCLUSIONS: Early linear growth benefits of NBS were sustained through puberty, leading to better adult height in cystic fibrosis.

Early life growth patterns persist for 12 years and impact pulmonary outcomes in cystic fibrosis

BACKGROUND In children with cystic fibrosis (CF), recovery from growth faltering within 2 years of diagnosis (Responders) is associated with better growth and less lung disease at age 6 years. This study examined whether these benefits are sustained through 12 years of age. METHODS Longitudinal growth from 76 children with CF enrolled in the Wisconsin CF Neonatal Screening Project was examined and categorized into 5 groups: R12, R6, and R2, representing Responders who maintained growth improvement to age 12, 6, and 2 years, respectively, and I6 and N6, representing Non-responders whose growth did and did not improve during ages 2-6 years, respectively. Lung disease was evaluated by % predicted forced expiratory volume in one second (FEV1) and chest radiograph (CXR) scores. RESULTS Sixty-two percent were Responders. Within this group, 47% were R12, 28% were R6, and 25% were R2. Among Non-responders, 76% were N6. CF children with meconium ileus (MI) had worse lung function and CXR scores compared to other CF children. Among 53 children with pancreatic insufficiency without MI, R12 had significantly better FEV1 (97-99% predicted) and CXR scores during ages 6-12 years than N6 (89-93% predicted). Both R6 and R2 experienced a decline in FEV1 by ages 10-12 years. CONCLUSIONS Early growth recovery in CF is critical, as malnutrition during infancy tends to persist and catch-up growth after age 2 years is difficult. The longer adequate growth was maintained after early growth recovery, the better the pulmonary outcomes at age 12 years.

WS11.8 Early diagnosis through newborn screening (NBS) improved long-term growth and adult height at age 18 years in CF patients with pancreatic insufficiency

Objectives To determine if early growth benefit of NBS sustains to adulthood, we compared adolescent peak height velocity (PHV) between screened (diagnosed early via NBS) and control (identified by symptoms) groups in the Wisconsin RCT. Methods Data from 106 patients born in 1985–94 and followed through 2012 with the same care protocol were analyzed. Results Pancreatic sufficient patients (n = 18) achieved normal pubertal PHV and adult height at age 18 y ( th %tile). Meconium ileus patients (MI, n=25) had reduced PHV and shorter adult height at age 18 y (males: 34 th %tile; females: 17 th %tile). In non-MI patients who had pancreatic insufficiency (n = 64), boys in the screened group (n = 22) had normal and slightly higher PHV (9.5 cm/y at 13.5 y) than the control group (n = 29, 8.9 cm/y at 13.6 y), girls in the screened group (n = 13) had later and slightly lower PHV (7.3 cm/y at 12.5 y) compared to control group (n = 11, 7.9 cm/y at 11.7 y), but the lower PHV in screened girls coincided with later menarche (13.6 y vs. 12.2 y) and was compensated by longer duration of pre-pubertal growth. Thus, adult heights at age 18 y in both sexes were taller in screened compared to control (50 th vs. 29 th %tile, p=0.025), which remained significant after adjusting for parental height (32 nd vs 15 th %tile, p=0.003). Multiple regression analysis revealed that the taller adult height in the screened group was primarily due to achievement of better pre-pubertal height (e.g., 47 th vs. 27 th percentile at age 7 y) rather than greater adolescent PHV. Conclusion This longest duration cohort study shows that early diagnosis/care can promote better long term growth and is a sustained benefit of NBS.

WS11.7 Feeding, growth and nutritional status of infants with CF diagnosed through newborn screening (NBS): Findings from a new multi-center study in the USA

Objective NBS for CF became universal in the USA in 2010. To identify optimal feeding for CF infants, a multi-center prospective study known as FIRST (Feeding Infants Right … from the STart) was initiated in 2012 to enroll 160 infants by 2016 at 5 CF Centers (Madison and Milwaukee, WI; Indianapolis, IN; Salt Lake City, UT; and Boston, MA). Method Nutritional status in the first year of life from 91 infants (52% boys) enrolled at 1.4±0.6 mo to FIRST was assessed biochemically and anthropometrically. By 31/12/14, 80 infants were 6 mo and 60 infants were 12 mo old. Result Growth was normal at birth [3210±505 g (41 st %tile) and 50.1±2.8 cm (63 rd %tile)] but declined to the 18 th %tile at age 2 mo. Catch-up growth was observed; weight increased to 33 rd %tile at 6 mo and 64 th %tile at 12 mo, but length did not fully recover at 12 mo (44 th %tile). At birth, 73% were breastfed: 65% exclusive (exB) and 8% combined with formula (B&F). The rate of exB decreased to 41% by 1 mo and 16% by 6 mo, while B&F and exF increased to 27% and 57%, respectively, at 6 mo. In the first 6 mo of life, 60% of infants received fortified breast milk or high caloric density formula (22–30 kcal/oz). Abnormal essential fatty acid status was common before age 3 mo with 18% deficient [triene-tetraene (T/T) ratio >0.02] and another 18% insufficient (T/T ratio >0.01). Low vitamin D [25(OH)D Conclusion This new infant study shows that early diagnosis/care leads to substantial catch-up growth but biochemical nutritional status remains suboptimal. (Funded by NIH/CFF).

WS16.6 Newborn screening and early life weight recovery are associated with better adolescent growth in children with CF

WS16.5 Comparison of cystic fibrosis adolescents with normal and low bone mineral density M. Mielus1, D. Sands1, B. Oralewska2, M. Oltarzewski3, J. Walkowiak4. 1Institute of Mother and Child, CF Centre, Warsaw, Poland; 2Child Memorial Health Institute, Department of Pediatric Gastroenterology and Hepathology, Warsaw, Poland; 3Institute of Mother and Child, Screening Department, Warsaw, Poland; 4Poznan University of Medical Sciences, Department of Gastroenterology and Metabolic Diseases, Poznan, Poland