Recovery of Birth Weight z Score Within 2 Years of Diagnosis Is Positively Associated With Pulmonary Status at 6 Years of Age in Children With Cystic Fibrosis
OBJECTIVE. We recently reported that 60% of children newly diagnosed with cystic fibrosis who had pancreatic insufficiency responded to treatment initiation and achieved catch-up weight gain to a level comparable with their birth weight z score within 2 years of diagnosis (“responders”), whereas the remaining 40% failed to do so (“nonresponders”). The present study examined the impact of this early weight recovery on subsequent growth pattern and pulmonary status at 6 years of age.
PATIENTS AND METHODS. Sixty-three children with cystic fibrosis who had pancreatic insufficiency but no meconium ileus, and were enrolled in the Wisconsin Cystic Fibrosis Neonatal Screening Project, were studied. Responders were defined by a recovery of weight z score comparable with that at birth within 2 years of diagnosis. From ages 2 to 6, growth was measured by both height and BMI. Pulmonary status was evaluated by symptoms, spirometry, quantitative chest radiography, and respiratory microbiology.
RESULTS. The majority (71%) of the responders maintained their early weight recovery through 6 years of age, whereas only 32% of the nonresponders achieved substantial growth improvement from 2 to 6 years of age. Proportionately fewer responders reported cough symptoms (10% daytime cough; 22% nighttime cough) compared with nonresponders (41% daytime cough; 45% nighttime cough) at age 6. The percentage of predicted forced expiratory volume in 1 second at age 6 was 11% higher in responders (99.5% ± 13.9%) compared with nonresponders (88.3% ± 18.5%). Responders had significantly better Brasfield (20.1 ± 1.4) and Wisconsin chest radiograph (8.3 ± 3.3) scores compared with nonresponders (Brasfield: 18.9 ± 1.8; Wisconsin: 12.3 ± 8.3). Respiratory microbiology results were not significantly different. Multiple regression analyses indicated that the positive association between responder and percent predicted forced expiratory volume in 1 second at 6 years of age remained statistically significant after controlling for infections with Pseudomonas aeruginosa and Staphylococcus aureus and chest radiograph scores. Growth patterns from 2 to 6 years of age were not associated with pulmonary measures at age 6.
CONCLUSIONS. Patients with cystic fibrosis with pancreatic insufficiency who achieved early growth recovery within 2 years of diagnosis had fewer cough symptoms, higher lung function, and better chest radiograph scores at 6 years of age.
Cystic fibrosis (CF) is a life-threatening genetic disorder that is generally characterized by intestinal malabsorption, impaired growth, and lung disease. Malnutrition is prevalent,1–5 as indicated by the observation that nearly half of children newly diagnosed with CF have a height or weight below the fifth percentile,3 and is associated with poor clinical outcomes.1,6–10 Therefore, optimizing nutritional status is critical for patients with CF. However, it is unclear why some patients with CF respond to treatment initiation and succeed in recovering from malnutrition and growth faltering/failure experienced before diagnosis, whereas others fail to do so. In a recent study,11 we reported that ∼60% of children with CF who had pancreatic insufficiency (PI) but no meconium ileus (MI) responded to treatment initiation and achieved catch-up weight gain to a level comparable with their birth weight z score within 2 years of CF diagnosis (“responders”), whereas the remaining 40% did not achieve it (“nonresponders”). Diagnosis through newborn screening, less severe malnutrition, and pulmonary disease at the time of diagnosis, sustained high energy intake at >120% of estimated energy requirement (EER),12 and sustained normal plasma linoleic acid level were found to be significant determinants of this early treatment response.11
In the present study, we hypothesized that the early weight recovery experienced by the responders leads to better pulmonary status at 6 years of age, when reliable pulmonary function data can be obtained for the majority of children with CF.13 Specifically, we examined whether (1) responders maintained their early weight recovery beyond 2 years after diagnosis up to 6 years of age, (2) nonresponders achieved substantial growth improvement from 2 to 6 years of age, (3) high energy intake contributed to growth maintenance in responders and growth improvement in nonresponders from 2 to 6 years of age, and (4) responders experienced better pulmonary status compared with nonresponders at 6 years of age. Data from children with CF enrolled in the Wisconsin Cystic Fibrosis Neonatal Screening Project14,15 were used to address these questions.
SUBJECTS AND METHODS
The study population eligible for the present study consisted of 80 children with CF who have PI but not MI and were enrolled in the Wisconsin Cystic Fibrosis Neonatal Screening Project, which is a prospective longitudinal investigation initiated in 1985 to assess the benefits and risks of newborn screening for CF.14,15 The design and purpose of the Wisconsin Cystic Fibrosis Neonatal Screening Project have been described in detail elsewhere.14,15 Briefly, for half of the randomly assigned newborns, early diagnosis of CF was established through neonatal screening, whereas the diagnosis of CF in newborns randomly assigned to the control arm was generally established by traditional methods (ie, through signs and symptoms of CF). The study protocol was approved by the Human Subjects Committee at the University of Wisconsin and the Research and Publications Committee/Human Rights Board at Children's Hospital of Wisconsin.
Of the 80 eligible patients, 9 were excluded from our first study of treatment responsiveness11 for various reasons stated in detail in that report (eg, false-negative screening result, lack of birth weight data, or low birth weight). Another 8 patients were lost to follow-up before 6 years of age; the remaining 63 patients were included in the present study. No significant differences on baseline characteristics (ie, gender, responder status, age of diagnosis, height and weight z scores at diagnosis) were found between the 63 patients included in the present study and the 80 eligible patients.
Measurements of Nutritional Status
Birth weight was obtained from medical charts or newborn screening records. Anthropometric measurements were obtained according to a standardized protocol and performed by trained research nurses and dietitians. Recumbent length (before 2 years of age), standing height (after 2 years of age), and weight were measured at diagnosis, every 6 weeks for the first year of life, and every 3 months thereafter.14,16 Recumbent length was measured with the use of a calibrated wooden board, and standing height was measured with a stadiometer to the nearest 0.5 cm. Weight of unclothed infants <2 years of age was measured on a springless infant scale, and older children were weighed without shoes and outer clothing on a springless adult scale, both to the nearest 0.1 kg. Age- and gender-specific z scores for weight (WTz), length/height (HTz), and BMI (BMIz) were computed by using the 2000 Centers for Disease Control and Prevention growth charts (available at www.cdc.gov/growthcharts).17
Three-day food records were distributed to the family at diagnosis and every 6 months thereafter to assess dietary intake, as described in detail elsewhere.11,14,18,19 Computerized nutrient-analysis programs, Nutritionist III, IV, and V (N-Squared Computing, Silverton, OR), were used to calculate daily energy intake.11,14,19,20 Energy intake was expressed as a percentage of the EER on the basis of the dietary reference intakes released in 200212 and used an “active” physical activity factor.21
Definition of Responders Within 2 Years of Diagnosis
As described in detail previously,11 we evaluated early treatment response on the basis of recovery from malnutrition and growth faltering, which is a common presentation for children with newly diagnosed, untreated CF.2,3,25,26 Children with CF were referred to as responders if their catch-up weight gain within 2 years of diagnosis resulted in achieving a WTz similar to their WTz at birth. Children with CF who did not gain sufficient weight to achieve a WTz comparable with their birth WTz within 2 years of diagnosis were referred to as nonresponders. The rationale of using birth WTz to define adequate weight gain is based on the observation that birth weights of children with CF tend to be similar25,26 or only slightly lower18,26 compared with those of healthy children, but a large percentage of children with CF fall below the fifth percentile by the time of diagnosis.3,25,26 In addition, physical growth of infants and young children varies greatly because of intrauterine, genetic, and nutritional influences.27 Therefore, recovery of weight to a level comparable with one's birth WTz represents a more individualized indicator of treatment responsiveness than using a common reference level (such as weight >5th or 10th percentile) for all children with CF.
Classification of Growth Patterns Beyond 2 Years After Diagnosis up to 6 Years of Age
Growth beyond 2 years after diagnosis up to 6 years of age was evaluated on the basis of the combination of changes in HTz and BMIz. WTz was not used in combination with HTz to define growth pattern between 2 and 6 years of age, because WTz is influenced by both age and height and, thus, is highly correlated with HTz. For example, a child may have a low WTz simply because of being short for age and not because of a low weight for height. On the other hand, BMIz is an independent indicator of weight-for-height proportion, thus providing a complementary measure to HTz.
Specifically, the cumulative changes in HTz and BMIz from ages 2 to 6 (ie, ΔHTz and ΔBMIz) were estimated by using linear regression technique for each individual child with CF (ie, slope multiplied by the 4-year interval). Thereafter, ΔHTz and ΔBMIz were evaluated relative to a 1-channel difference (equivalent to an ∼0.67 z score) on the respective Centers for Disease Control and Prevention growth charts (Fig 1). For responders, those whose ΔHTz and/or ΔBMIz increased or remained stable were classified as “maintained” (Fig 1, gray boxes) because their responder status was maintained over the period of ages 2 to 6. On the other hand, responders whose ΔHTz and/or ΔBMIz declined were classified as “lessened” (Fig 1, clear boxes). For nonresponders, those whose ΔHTz and/or ΔBMIz increased were classified as “improved” (Fig 1, gray boxes), whereas those whose ΔHTz and ΔBMIz remained stable or declined were classified as “unchanged” (Fig 1, clear boxes) because their nonresponder status did not change from the ages of 2 to 6.
Pulmonary and Clinical Outcome Measures
Measures of pulmonary status included parent-reported respiratory symptoms (cough and wheezing),28 lung function by spirometry,13,29 lung image by quantitative chest radiology,30–32 and pulmonary infection by respiratory microbiology.33,34
Respiratory symptoms (cough and wheezing) were reported by the parents/caregivers at each protocol visit (at diagnosis, every 6 weeks during the first year of life, and every 3 months thereafter). The frequency of cough was recorded as 0 = none, 1 = rare/occasional, 2 = mild dry cough, 3 = mild productive cough, and 4 = frequent/severe. Wheezing experiences were recorded as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. We considered cough to be present if the score was ≥2 and wheezing to be present if the score was ≥1, as reported previously.28
Pulmonary function tests (PFTs) were obtained every 6 months beginning when the children reached age 4 (to allow for a training period between ages 4 and 6 years), as described in detail previously.13 The quality of data were ensured by using the pediatric alternate spirometry system we developed and validated previously.13,29 Only data accepted by at least 2 of the 3 raters were considered valid.13,29 Fifty-five (87%) patients had at least 1 valid PFT measurement between ages 4 and 8 years; the valid PFT measurement that was closest to 6 years of age (mean age at PFT: 6.2 ± 0.9 years [range 4.5–8.7 years]) for each patient was retained for analysis. The remaining 8 patients had PFT measurements between ages 4 and 8 years, but none of the measurements were accepted by the pediatric alternate spirometry system. Percent predicted forced vital capacity (%FVC), forced expiratory volume in 1 second (%FEV1), and FEV1 to FVC ratio were calculated by using equations from Wang et al.35
Chest radiograph (CXR) scores were used to evaluate hyperinflation (“air trapping”) and structural abnormalities of the lungs such as bronchiectasis.30,31 CXRs were obtained every 6 months from diagnosis to 4 years of age and annually thereafter.30,31 The original films obtained at diagnosis, 2 and 4 years of age, and every year thereafter were scored by using the Wisconsin Chest Radiograph scoring system13,30,31 and the Brasfield system.32 Two raters, who were unaware of patient identities and demonstrated previously to score the images similarly with standardized methods,30,31 assigned subscores according to disease categories; the total score was computer generated.30,31
To evaluate pulmonary infections, cultures of respiratory secretions were obtained by vigorous oropharyngeal swabbing during forced coughing at the time of diagnosis, every 6 months thereafter, and at all sick visits as described elsewhere.33 These secretions were cultured to detect the presence of microbial pathogens. The 2 respiratory pathogens that are most likely to infect young children with CF, Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), were analyzed in the present study. PA infection was examined in multiple ways: (1) the traditional approach of “never positive” versus “ever positive”33 at ages 2 and 6 years; and (2) the relatively new approach36–38 of “never,” “transient” (1–2 positive results), “intermittent” (3–4 positive results but no more than 2 consecutive positive results), and “persistent” (5–10 positive results and no more than 2 consecutive negative results) between 2 and 6 years of age.
In addition, Shwachman-Kulczycki39 scores were obtained to indicate the overall clinical severity of CF at each protocol visit. The Shwachman-Kulczycki scoring system includes 4 interrelated components: general activity, physical examination, nutrition, and CXR findings with a scoring range of 5 to 25 points for each component and a total score of 20 to 100 points.39 The 4 components of the score were determined by the managing physician, who was unaware of patient status (ie, responder versus nonresponder).
Analyses focused on comparing clinical characteristics between responders and nonresponders, and among the 4 growth patterns from ages 2 to 6, as illustrated in Fig 1. SAS 8.02 (SAS Institute, Inc, Cary, NC) and R (www.r-project.org)40 were used for data processing and statistical analyses. One-way analysis of variance was used to compare means when the data seemed normally distributed, and the Wilcoxon rank-sum test was used to compare means when the data seemed skewed. Nonparametric analysis of variance was used to compare medians. χ2 (when sample size was >5 in all subgroups), Fisher's exact (when sample size was <5 in a given subgroup), and Mantel-Haenszel χ2 tests were used to compare proportions. Multiple regression analysis was used to evaluate the association between responder status and %FEV1 while adjusting for relevant covariates. When the overall P value from type III analysis indicated statistical significance, multiple comparisons were performed to identify differences between subgroups of interest. All analyses on pulmonary function at age 6 used 55 children with CF who had valid %FEV1 data.
Comparison of Responders and Nonresponders at 2 Years of Age
At 2 years of age, responders had significantly better growth (HTz, WTz, and BMIz) and Shwachman-Kulczycki scores (physical examination subscore, growth subscore, and total score) compared with nonresponders (Table 1). Parent-reported cough symptoms, Brasfield and Wisconsin CXR scores, as well as SA and PA infections at 2 years of age did not differ significantly between responders and nonresponders.
Growth Patterns of Responders and Nonresponders From 2 to 6 Years of Age
As shown in Table 2, the majority (71%) of responders experienced improved or stable growth. On the other hand, less than one third of the nonresponders experienced substantial growth improvement over the subsequent 4 years.
At 6 years of age, responders whose growth was maintained from ages 2 to 6 (Table 2) had the best HTz and BMIz; both were above the 50th percentile (ie, z scores >0). Responders whose growth lessened from ages 2 to 6 had significantly lower BMIz but not HTz compared with responders whose growth was maintained from ages 2 to 6 (Table 2). Nevertheless, HTz, WTz, and BMIz scores of responders whose growth lessened from ages 2 to 6 remained somewhat better compared with nonresponders whose growth was unchanged from ages 2 to 6 (Table 2). Nonresponders whose growth improved from ages 2 to 6 had the lowest HTz, but BMIz was better than nonresponders whose growth remained unchanged from ages 2 to 6 (Table 2).
Additional analysis was performed to examine whether energy intake and plasma linoleic acid concentrations from ages 2 to 6 years differed between responders and nonresponders. On average, nonresponders consumed more calories (%EER: 141 ± 25) than responders (%EER: 119 ± 26) from ages 2 to 6 years (P = .005). Energy intake did not differ significantly in responders whose growth was maintained compared with those whose growth lessened, nor in nonresponders whose growth improved compared with those whose growth was unchanged (Table 2). Average plasma linoleic acid concentrations did not differ significantly among the 4 growth categories (Table 2).
Pulmonary Status of Responders and Nonresponders at 6 Years of Age
As shown in Fig 2, responders had significantly higher %FEV1 (99.5% ± 13.9%) compared with nonresponders (88.3% ± 18.5%) (P = .015). Percent predicted FVC (responders: 103.1% ± 11.2%; nonresponders: 97.6% ± 16.1%) and percent predicted FEV1/FVC ratio (responders: 96.4% ± 10.2%; nonresponders: 93.5% ± 14.5%) did not differ significantly in responders compared with nonresponders. No significant differences were found in %FEV1 (Fig 2), %FVC, or percent predicted FEV1/FVC ratio at 6 years of age between responders whose growth was maintained or lessened, and between nonresponders whose growth was improved or unchanged, from 2 to 6 years of age.
Consistent with pulmonary function data, CXR scores were better in responders than in nonresponders. As shown in Fig 3, responders had higher Brasfield CXR scores (20.1 ± 1.4 [normal score: 25]; P = .010) and lower Wisconsin CXR scores (8.3 ± 3.3 [normal score: 0]; P = .042) compared with nonresponders (Brasfield CXR score: 18.9 ± 1.8; Wisconsin CXR score: 12.3 ± 8.3) at 6 years of age. The average CXR scores from 2 to 6 years of age were also significantly better in responders (Brasfield CXR score: 20.7 ± 1.1; Wisconsin CXR score: 6.7 ± 2.1) than in nonresponders (Brasfield CXR score: 19.8 ± 2.0; Wisconsin CXR score: 9.2 ± 5.5) (P = .030 and .009 for Brasfield and Wisconsin scores, respectively). No significant differences were found in either CXR score at 6 years of age between responders whose growth was maintained or lessened and between nonresponders whose growth improved or was unchanged from 2 to 6 years of age (Fig 3).
With regard to pulmonary infections, no significant differences were found in the rates of ever-positive for PA and SA at age 6 between responders (PA: 37%; SA: 29%) and nonresponders (PA: 27%; SA: 41%). Additional analysis showed that the percentage of patients with never (responders: 37%; nonresponders: 32%), transient (responders: 39%; nonresponders: 36%), intermittent (responders: 7%; nonresponders: 14%), and persistent (responders: 17%; nonresponders: 18%) PA colonization from ages 2 to 6 years also did not differ significantly between responders and nonresponders. Lastly, no significant differences were found in the rate of ever-positive for PA and SA at 6 years of age between responders whose growth was maintained or lessened and between nonresponders whose growth improved or unchanged from 2 to 6 years of age.
In addition to the objective measures of lung function and CXR scores, proportionately fewer responders reported experiencing less daytime cough (10%; P = .02) and nighttime cough (22%; P = .05) at 6 years of age compared with nonresponders (41% daytime cough and 45% nighttime cough). Total Shwachman-Kulczycki score at age 6 was significantly higher in responders (94 ± 5) than nonresponders (89 ± 6) (P = .002).
Factors Associated With %FEV1 at 6 Years of Age
Regression analyses were performed to identify significant predictors of pulmonary function at age 6. Univariate analysis demonstrated that responder status (ie, achieving a catch-up weight gain within 2 years of diagnosis) is the single strongest predictor of %FEV1 at age 6 (Table 3). Of the 3 variables indicative of PA status, PA infection at age 6 had a stronger association with %FEV1 at age 6 than PA infection at age 2 or from ages 2 to 6. On the other hand, SA infection at age 2 had a stronger association with %FEV1 at age 6 than SA infection at age 6. Regarding CXR scores, mean CXR score from ages 2 to 6 had a stronger association with %FEV1 at age 6 than CXR score at age 2 or at age 6. Brasfield and Wisconsin CXR scores had a similar strength of associations with %FEV1 at age 6.
On the basis of observations from the univariate analyses, SA infection at age 2, PA infection at age 6, and mean Brasfield CXR score were included as covariates in multiple regression analyses to examine their influences on the association between responder status and %FEV1 at age 6. All multivariate models in Table 3 showed that responder status remained a significant and the strongest predictor of %FEV1 at age 6. This association did not change when other PA, SA, or CXR variables were adjusted for in the multivariate models.
This study used a prospective cohort to investigate the impact of early recovery of birth weight z score within 2 years of diagnosis of CF on pulmonary status at age 6. Our results demonstrate that, for children with CF who have PI but no MI, early attainment of birth weight status after CF diagnosis is associated with significantly better pulmonary outcomes at 6 years of age, which are consistently reflected in the symptoms (cough scores), function (%FEV1), and structural appearance (CXR scores) of the lungs. The difference in pulmonary function (ie, ∼10% in %FEV1 between responders and nonresponders) is large enough to be clinically significant, especially in view of the average annual decline of %FEV1 typically estimated at 2% to 3%.5 In addition, compared with nonresponders, these early responders required lower caloric intake to maintain adequate growth and achieve better pulmonary function, which may be associated with lower work of breathing (ie, less energy expenditure for respiration). The third novel finding from the present study is that this early weight recovery had a stronger effect on pulmonary status at 6 years of age than subsequent maintenance or improvement of growth experienced from 2 to 6 years of age.
Results from the present and our previous11work advance our knowledge in understanding the patterns of growth experienced by children with CF who have PI but no MI during the first 6 years of life. Specifically, we showed that 60% of these children responded to treatment initiation and achieved catch-up weight gain to a level similar to their birth weight z score within 2 years of diagnosis11; the majority (∼70%) of these responders maintained this growth recovery through 6 years of age, but the remaining ∼30% exhibited a decline in growth from 2 to 6 years of age. Conversely, 40% of children with CF who had PI but not MI did not achieve early weight recovery,11 and only few of these nonresponders (∼30%) experienced substantial growth improvement from 2 to 6 years of age. Our data suggest that high caloric intake contributed to growth maintenance within responders (average intake of >120% of estimated requirement) and growth improvement within nonresponders (average intake of >140% of estimated requirement) from ages 2 to 6 years (Table 2).
The temporal relationships between energy intake and growth patterns observed in our studies demonstrate the complex interactions between treatment and response that change over time for a chronic disease such as CF. First, we observed that sustained high energy intake after diagnosis contributed to initial treatment response.11 However, average caloric intake from ages 2 to 6 was significantly lower in responders than in nonresponders (Table 2). The latter observation should not be interpreted as a negative association between energy intake and growth from ages 2 to 6. Instead, it is an example of reverse causality in that poor growth in nonresponders leads to the recommendation of and adherence to a higher caloric intake during this period. However, it may also be possible that nonresponders' dietary intakes were overreported because the CF care team was likely to be closely monitoring food intake to ensure adherence to high caloric intake.
The complex interactions between treatment and response also make the search for factors determining treatment responsiveness difficult. One major challenge is to define what constitutes treatment and response. In our studies, we developed a novel approach that uses individualized growth parameters to define nutritional response, that is, catch-up weight gain with birth weight as the reference point to define initial treatment response and changes in height and BMI patterns within 1 growth channel as the reference point to define subsequent response. However, we are not able to quantify treatment received by individual patients. Although therapeutic protocols are well defined for our study population, the amount of treatment received is likely to be continuously influenced, and adjusted, by the subject's response. An example to support this argument is the observation by Konstan et al41 that children with CF with the best %FEV1 at age 6 had the most rapid decline of %FEV1 during the subsequent 3 years, which the authors attributed to less comprehensive therapy. Delineating the impact of therapeutic variation on treatment response will require the development of new research methods.
In the present study, neither PA nor SA infection explained the difference in pulmonary outcomes between responders and nonresponders. One possible explanation is that, in this young population, the prevalence of PA and SA infection was relatively low, with most infections being transient. A longer evaluation period is likely needed to assess the impact of respiratory infections on pulmonary function in responders and nonresponders.
Although we showed that children with CF diagnosed by newborn screening were more likely to be responders compared with those diagnosed by conventional methods,11 and responders had better pulmonary status at age 6 compared with nonresponders, our previous results did not reveal significantly better pulmonary function in screened patients compared with those diagnosed by traditional methods.29 Several possibilities may contribute to these findings. First, the benefit of newborn screening on pulmonary status at 6 years of age may depend on early nutritional response. This is supported by our observations that screened responders have better %FEV1 and CXR scores than screened nonresponders (data not presented). Second, only 77% (55 of 71) of the study population was included in pulmonary analyses at age 6 because of loss to follow-up or invalid %FEV1 data. Reduction in sample size as well as the somewhat imbalanced sample attrition between screened responders (75% retention) and control nonresponders (92% retention), although not statistically significant (P = .25), may have affected comparisons between screened and conventional diagnosis groups.
Results from this study provide clear evidence that in children with CF with PI but without MI, response to treatment initiation as indicated by achieving an early weight status recovery within 2 years of diagnosis is associated with better pulmonary status at 6 years of age. In addition, these early responders require lower energy intake to maintain adequate growth compared with that required for promoting further growth improvement in nonresponders. The indication that the benefit of newborn screening on pulmonary status at 6 years of age may depend on early nutritional response emphasizes the need for comprehensive therapy after screening. Additional research is needed to determine if the nutritional and pulmonary benefits experienced by these early responders persist throughout childhood.
This study was supported by National Institutes of Health grants 1R01DK072126, 2R01 DK34108, 1ULRR025011, and M01RR00058.
The following faculty members participated in this project: Jeff Douglas, PhD, Norman Fost, MD, MPH, Christopher Green, MD, Ronald Gregg, PhD, Michael Kosorok, PhD, Ronald Laessig, PhD, HuiChuan Lai, PhD, Mari Palta, PhD, Michael Rock, MD, Margie Rosenberg, PhD, Audrey Tluezek, PhD, L.J. Wei, PhD, Susan West, PhD, and Benjamin Wilfond, MD (University of Wisconsin Medical School, Madison); and W. Theodore Bruns, MD, William Gershan, MD, Elaine Mischler, MD, Mark Splaingard, MD, and Lee Rusakow (Medical College of Wisconsin, Milwaukee). The study was coordinated and managed superbly on a day-to-day basis at both sites by Anita Laxova. In addition, the group includes outstanding teams of biostatisticians (Rebecca Koscik, Sharon Shen, Lan Zeng, and Zhanhai Li), nurses (Karen Moucha, Miriam Block, Holly Colby, Lynn Feenan, Mary Ellen Freeman, Catherine McCarthy, and Darci Pfeil), nutritionists (Lisa Davis, Mary Marcus, and Tami Miller), and superb leaders of the Wisconsin State Laboratory of Hygiene's newborn screening program (David Hassamer and Gary Hoffman).
- Accepted June 4, 2008.
- Address correspondence to HuiChuan J. Lai, PhD, University of Wisconsin, Department of Nutritional Sciences, 1415 Linden Dr, Madison, WI 53706. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject
To our knowledge, there have been no published articles on this topic.
What This Study Adds
Results from this study represent new knowledge regarding how early weight status and subsequent growth impact pulmonary function in early childhood.
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