PEDIATRICS Vol. 117 No. 2 February 2006, pp. 391-400 (doi:10.1542/peds.2004-2832)
Temporal Associations Among Energy Intake, Plasma Linoleic Acid, and Growth Improvement in Response to Treatment Initiation After Diagnosis of Cystic Fibrosis
a Nutritional Sciences
b Biostatistics and Medical Informatics
c General Clinical Research Center
d Department of Pediatrics and the State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin
e Department of Pediatrics at the Medical College of Wisconsin, Milwaukee, Wisconsin
f Department of Statistics, Dongguk University, Seoul, Korea
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
OBJECTIVE. It is unclear why some patients with cystic fibrosis (CF) succeed ("responders") in recovering from malnutrition and growth faltering after treatment initiation whereas others fail to do so ("nonresponders"). We conducted a study to test the hypothesis that sustained high energy intake (
EN) and normal plasma essential fatty acid status are critical determinants of treatment responsiveness within 2 years after diagnosis of CF.
METHODS. A total of 71 CF children who had pancreatic insufficiency but not meconium ileus and were enrolled in the Wisconsin CF Neonatal Screening Project were studied. Responders were defined by having achieved adequate weight gain, as indicated by a recovery of weight z score (Wtz) comparable to Wtz at birth (WtzBR) within 2 years of diagnosis. EN and sustained normal plasma linoleic acid level (pLA) were defined by achieving energy intake 
120% of estimated requirement for 75% of the time and maintaining plasma LA 26% of total fatty acids for 75% of the time, respectively.
RESULTS. Thirty-two (68%) screened patients and 13 (54%) patients whose CF was diagnosed conventionally recovered WtzBR within 2 years of diagnosis. Screened patients responded at significantly younger ages (mean/median: 6.3/4.3 months) than patients whose CF was diagnosed conventionally (mean/median: 15.8/11.8 months). Proportionately fewer screened patients (33%) achieved EN compared with patients whose CF was diagnosed conventionally (73%). However, more screened patients responded to EN and recovered WtzBR (91%) than patients whose CF was diagnosed conventionally (56%), although this difference was of borderline significance. Compared with having neither EN nor pLA, the likelihood of being a responder was greatest with combined EN and pLA, followed by EN only. The positive associations between EN and pLA to treatment responsiveness remained significant after adjustment for neonatal screening status, baseline height and weight status, and indices of pulmonary disease severity.
CONCLUSION. EN and pLA are critical in promoting adequate weight gain in children with newly diagnosed CF.
Key Words: cystic fibrosis • diet • energy intake • growth • height • linoleic acid • malnutrition • neonatal screening • prospective study • weight
Abbreviations: CF—cystic fibrosis • RDA—recommended dietary allowance • LA—linoleic acid • EN—sustained high energy intake • PI—pancreatic insufficiency • MI—meconium ileus • WtzBR—weight z score at birth • Wtz—weight z score • Htz—height z score • EER—estimated energy requirement • DRI—Dietary Reference Intakes • pLA—sustained normal plasma linoleic acid • dLA—sustained adequate dietary linoleic acid intake • WtzDX—weight z score at diagnosis • HtzDX—height z score at diagnosis • 
WtzDX-BR—change in weight z score from birth to diagnosis
CYSTIC FIBROSIS (CF) is a life-threatening, genetic disorder that is characterized by intestinal malabsorption, impaired growth, and lung disease.1,2 Malnutrition is prevalent,3–6 as indicated by the observation that among children with newly diagnosed CF, nearly half have a height or weight below the fifth percentile,3 and is associated with poor clinical outcomes.7–11 Therefore, optimizing nutritional status is critical for patients with CF. Achieving a daily energy intake at or above 120% of the recommended dietary allowance (RDA)12 is a widely accepted guideline for nutrition management in patients with CF.13–17 However, few prospective studies have evaluated the validity of this energy recommendation.18–21
It is unclear why some patients with CF respond to treatment initiation and succeed ("responders") in recovering from malnutrition and growth faltering/failure experienced before diagnosis, whereas others fail to do so ("nonresponders"). Among the few longitudinal studies that showed trends between energy intake and growth, relevant parameters are presented in the traditional format, as group mean values, with little or no information on the proportion of children who did or did not respond to treatment initiation. Furthermore, interstudy results are inconsistent. For example, in a 3-year study of CF by Kawchak et al,21 mean calorie intake at 108% to 122% of the recommended level seemed to be insufficient to prevent declines in height and weight percentiles in children who were aged 5 to 10 years and were pancreatic insufficient (PI). In contrast, our previous studies,18,20 using the cohort of children who were enrolled in the Wisconsin CF Neonatal Screening Project, showed that children who were PI, but without meconium ileus (MI), when diagnosed via neonatal screening, were able to achieve near-normal weight (ie, average weight of 40th–50th percentiles) from 2 to 10 years of age when mean energy intake was at 118% of RDA.20,22 Nevertheless, large variations in growth and energy intake were observed during the first 2 years of life in our studies,21,22 suggesting differential responses among individual patients after treatment was initiated. Even in studies of intensive oral energy supplementation in children with CF who had growth failure, variation in responsiveness is evident, as reported in a meta-analysis.23
In addition to optimizing energy intake, normalizing plasma essential fatty acid status was reported to be associated with better growth in children with CF.19,24–26 Low plasma linoleic acid (LA) concentrations and essential fatty acid deficiency are evident even among infants whose CF is diagnosed before 6 weeks of age via neonatal screening, with 54% having low plasma LA and 27% having abnormal triene/tetraene ratio.18 Plasma LA concentration was shown to be correlated positively with growth in children whose CF was diagnosed before 3 months and followed up to 12 years of age.19 Another study by van Egmond et al25 showed better growth among infants who had CF and consumed a predigested formula that contained high LA (12% of energy) compared with those who consumed a comparable formula with lower LA (7% of energy), despite a lower intake of total energy in the former group. In support of these findings, studies of oral supplementation by Mischler et al24 and Steinkamp et al26 also demonstrated increased plasma LA concentrations and growth improvements in malnourished children with CF.
In view of the findings described above, we hypothesized that sustained high energy intake (EN) and normal plasma essential fatty acid status are critical determinants of treatment responsiveness. Data from children who have CF and are enrolled in the Wisconsin CF Neonatal Screening Project20,27 were used to examine this hypothesis for the period of 2 years after CF diagnosis.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Study Population
The study population included in this report consists of a subgroup of children who have CF and are enrolled in the Wisconsin CF Neonatal Screening Project, which is a prospective longitudinal investigation that was initiated in 1985 to assess the benefits and risks of newborn screening for CF.20,27 The design and purpose of the Wisconsin CF Neonatal Screening Project has been described in detail elsewhere.20,27 Briefly, for half of the randomly assigned newborns, early diagnosis of CF was established through neonatal screening, whereas the diagnosis of CF in newborns who were randomly assigned to the control arm was established by conventional 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.
A total of 80 children who have CF with PI but without MI were identified22 from the Wisconsin CF Neonatal Screening Project database. Patients with pancreatic sufficiency were excluded because they are at lower risk for malnutrition,28 as indicated by our previous study showing normal growth (ie, mean height-for-age at 
50th percentile) with mean energy intake at 99% RDA.20 Patients with MI were also excluded because they were shown to have poor growth and plasma essential fatty acid status19,29 despite higher energy intake than patients without MI with similar age of diagnosis and treatment protocol. Of the 80 patients, 1 in the screened group had delayed, symptomatic diagnosis at age 5.4 years as a result of a false-negative screening test and 2 patients in the conventional diagnosis group were identified through the unblinding process20 instead of by conventional methods as a result of signs and symptoms. These 3 patients were excluded because the first patient was in fact not identified through neonatal screening and the other 2 patients' CF would not have been diagnosed by the conventional methods. In addition, 3 patients did not have birth weight data, and another 3 had low birth weight (<2500 g). These 6 patients were also excluded because adequate weight gain could not be defined according to our method described below. The remaining 71 patients constitute the study population in the present study, and their data from diagnosis up to 2 years after diagnosis were analyzed.
Assessment of Growth, Essential Fatty Acid Status, and Dietary Intake
Growth
Birth weight was obtained from medical records. Standardized measurement of recumbent length (before 2 years of age), height (after 2 years of age), and weight were obtained at diagnosis, every 6 weeks for the first year of life, and every 3 months thereafter.20,30 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 was measured in unclothed infants who were younger than 2 years, and older children were weighed without shoes and outer clothing, to the nearest 0.1 kg. Sixty-eight (96%) patients had all anthropometric measurements obtained; the remaining 3 patients had at least 82% of measurements obtained. Age- and gender-specific z scores for birth weight (WtzBR), weight (Wtz), and height (Htz) were computed by using the 2000 growth reference (www.cdc.gov/growthcharts).31
Essential Fatty Acid Status
Essential fatty acid status was assessed at diagnosis and every 6 months thereafter.24,30 Plasma fatty acid composition was measured in total lipid extracts by using the gas-chromatography methods described by Farrell et al.25,32 Sixty-nine (97%) patients had all plasma fatty acid measurements obtained. The remaining 2 patients had 50% to 75% of measurements obtained.
Dietary Intake
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.18–20 Additional 3-day food records were collected when a patient completed a 72-hour fat absorption study. Forty-two (59%) patients completed all food records, 13 (18%) patients completed 75% of food records, 11 (15%) patients completed 25% to 50% of food records, and 5 did not complete any food records. Computerized nutrient analysis programs, Nutritionist III, IV, and V (N-Squared Computing, Silverton, OR) were used to calculate daily energy intake.19,20,22 LA intake was also estimated by using published values of human milk and formula composition, manufacturer's data when available, and food composition tables.33
Average daily energy intake was expressed as a percentage of the estimated energy requirement (EER) based on the new Dietary Reference Intakes (DRI) released in 2002.34 The DRI's EER equations for children who are younger than 3 years incorporate age, body weight, and the energy cost for growth. For older children, EER equations are age- and gender-specific and incorporate an additional physical activity factor. Of the 260 food records analyzed in the present study, only 1 was obtained at more than 3 years of age. For this record, an "active" physical activity factor was assumed in calculating EER.
Definition of Adequate Weight Gain
Patients were classified as responders, ie, those who attained adequate weight gain, and nonresponders, ie, those who failed to attain adequate weight gain. Adequate weight gain was defined as having recovered WtzBR and maintaining this improvement for 2 consecutive visits (equivalent to 6 months of time). Although birth weight is influenced by the intrauterine environment and may not truly reflect the genetic potential of a child, using birth weight status to define adequate weight gain is preferred over the commonly used indicator of Wtz greater than the 5th or 10th percentile for the following reasons: (1) physical growth varies among individuals as a result of genetic influences,35 and (2) birth weights of children with CF tend to be similar36,37 or slightly lower18,37 than healthy children, but a large percentage (50%) fall below the 5th percentile by the time of diagnosis.3,36,37 Therefore, recovery of weight to a level comparable to birth in response to treatment initiation may provide a more appropriate indicator of treatment responsiveness. To allow for normal variation in catch-up and catch-down growth, Wtz within 0.25 SD of WtzBR was used as the criterion for growth recovery. This cut point was selected on the basis of common clinical perception of a meaningful change in growth percentile, whereby a 0.25-SD change corresponds to 10 percentile points' deviation near the middle of the growth channels and 5 percentile points' deviation near the top/bottom of the growth channels.
Definition of EN
The duration of high energy intake was estimated according to the following sequence: (1) for a given visit, high energy intake was defined by an intake 120% of EER; (2) a high energy intake for a given visit was assumed to be representative of energy intake for the length of time between that visit and the previous visit; and (3) the duration of high energy intake was equal to sum of the length of time estimated from (2) above.
Because the timing of recovering WtzBR differed greatly among individual patients, the duration of high energy intake was expressed as a percentage of the total length of time. For the responders, the total length of time corresponded to the interval from diagnosis to the first Wtz that reached WtzBR. For the nonresponders, the total length of time corresponded to the interval from diagnosis to 2 years after diagnosis. EN was defined as having achieved energy intake 120% EER for 75% of the time.
Definition of Sustained Normal Plasma LA Status and Sustained Adequate Dietary LA Intake
Normal plasma LA status was defined by plasma LA 26% of total plasma fatty acids.32 Dietary LA intake was considered adequate at 5% of total energy intake.34 The duration of normal plasma LA status and adequate dietary LA intake were estimated by the same method used to calculate the duration of high energy intake, described above. Similarly, the duration of normal plasma LA status and adequate dietary LA intake were expressed as percentages of the total length of time. Sustained normal plasma LA status (pLA) and sustained adequate dietary LA intake (dLA) were defined as having maintained these conditions for 75% of the time.
Statistical Analysis
Analyses focused on comparing the characteristics between responders and nonresponders and were stratified by neonatal screening status. SAS 8.02 (SAS Institute, Inc, Cary NC) and R (www.r-project.org)38 were used for data processing and statistical analyses. One-way analysis of variance was used to compare means when the data appeared normally distributed, and the Wilcoxon rank sum test was used to compare means when the data appeared skewed. Nonparametric analysis of variance was used to compare medians. 
2 (when sample size was >5 in all subgroups), Fisher's exact (when sample size was <5 in a given subgroup), and Mantel-Haenszel 2 tests were used to compare proportions. Additional analysis using logistic regression was performed to evaluate the likelihood of being a responder (recovering WtzBR) given EN or pLA and, while adjusting for relevant covariates, such as Wtz at diagnosis (WtzDX), Htz at diagnosis (HtzDX), change in Wtz from birth to diagnosis (WtzDX-BR), essential fatty acid status at diagnosis, neonatal screening status, gender, and/or F508 status. When the overall P value for EN and pLA status from type III analysis indicated statistical significance, pair-wise comparisons were performed to identify differences between subgroups of interest. For these analyses, 11 responders in the screened group recovered WtzBR before their first documented food record and, therefore, could not be included in these analyses.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Growth Improvement After CF Diagnosis and Treatment Initiation
Among the 71 children who had CF with PI but without MI, 32 (68%) screened patients and 13 (54%) conventionally diagnosed patients responded to treatment and recovered their WtzBR within 2 years of CF diagnosis (Table 1). WtzBR differed significantly between nonresponders in the screened group and responders in the conventional diagnosis group but did not differ among the other groups. Screened patients had a smaller decline in Wtz from birth to diagnosis compared with patients diagnosed by conventional methods (Table 1). Nevertheless, the majority of patients in both groups (77% overall) experienced decline in Wtz between birth and diagnosis (Table 1).
|
At the time of diagnosis,
20% of the patients had essential fatty acid deficiency, as indicated by plasma LA <26% and triene/tetraene ratio >0.2. Only 50% of the patients had normal essential fatty acid status (Table 1). These proportions did not differ significantly by neonatal screening status or between responders and nonresponders (Table 1). Last, it should be mentioned that the distributions of gender and F508 status did not differ significantly among the 4 groups compared in Table 1 (P > .59 for all comparisons, data not presented).
Table 2 compares the characteristics of the responders whose CF was diagnosed through neonatal screening with those whose CF was diagnosed conventionally. The amount of time taken to recover WtzBR was not statistically different between the 2 groups; 70% of patients recovered WtzBR within 6 months of treatment initiation. However, screened patients recovered WtzBR at a significantly earlier age (two thirds by 6 months of age) compared with conventionally diagnosed patients (16% by 6 months of age). In addition, almost half of the patients whose CF was diagnosed conventionally did not recover WtzBR until after 1 year of age, as compared with 16% in screened patients.
|
At the time of recovering WtzBR, responders in the screened group tended to have better Htz and Wtz than responders in the conventional diagnosis group, although these differences were not significant (Table 2). Patients whose CF was diagnosed conventionally had greater improvement in Htz (P = .02) and to a lesser extent Wtz (P = .09), compared with screened patients (Table 2).
Association Between EN, pLA, and Growth Improvement
Table 3 shows that 70% of the patients who had EN were responders, whereas only 46% of the patients who did not achieve EN were responders (P = .02). A similar but not significant trend was observed with pLA. When EN and pLA were examined simultaneously, the proportion of responders was highest among patients who achieved EN + pLA (89%), followed by those with EN but without pLA (61%) and those with pLA but without EN (57%), and lowest among those with neither EN nor pLA (43%). This trend was statistically significant after adjustment for mode of diagnosis (P = .04).
|
Table 4 presents additional comparisons between responders and nonresponders according to the mode of diagnosis. Our results show that proportionately more patients whose CF was diagnosed conventionally (73%) received
EN than screened patients (33%; P = .01). However, more screened patients responded to EN and recovered WtzBR (91%) than patients whose CF was diagnosed conventionally (56%), although this difference was borderline (P = .09). This differential response to EN between screened patients and patients whose CF was diagnosed conventionally seemed to be explained by pLA status, that is, among patients with EN and pLA, screened patients and patients whose CF was diagnosed conventionally had similar response rates (100% vs 83%). However, among patients with EN but without pLA, screened patients were found to have higher response rate (88%) than patients whose CF was diagnosed conventionally (40%; P = .07). These observations most likely reflect the need for more extensive nutrition therapy in patients whose CF was diagnosed conventionally, as their HtzDX and WtzDX worsened to a greater extent as a result of delayed diagnosis.
|
Table 5 presents results from logistic-regression analyses that assessed the contributions of
EN and pLA, as well as other baseline factors that may influence treatment response. Among the baseline factors examined, neonatal screening, lower WtzBR, smaller decline in Wtz from birth to diagnosis, and higher HtzDX increased the likelihood of being a responder. In the presence of these baseline factors summarized in Table 5, EN and pLA status remained a significant predictor of responder status (P = .019). Pair-wise comparisons demonstrated that achieving the combination of EN and pLA was associated with the greatest likelihood of being a responder, followed by EN alone, when compared with failure to achieve either EN or pLA. Achieving both EN and pLA was also associated with an increased likelihood of being a responder compared with pLA alone (P = .04).
|
Finally, it should be mentioned that the exclusion of 11 responders who regained WtzBR before the first dietary assessment, from the results presented in Tables 3 to 5, may have introduced selection bias. Because nearly all of them (10 of 11) responded by the second clinic visit, we performed a subgroup analysis to minimize this potential bias by excluding all responders (n = 13) who recovered WtzBR by the second clinic visit after diagnosis. Results remained essentially the same: combined
EN and pLA was positively and significantly associated with responder status (P = .002), the effect of EN was positive but borderline significant (P = .099), and the effect of pLA was not significant.
Association Between dLA and pLA
To answer the question of whether achieving pLA depends on adequate dietary intake of LA, we examined the contribution of dLA to pLA. Table 6 shows that proportionately more patients with dLA achieved pLA in both screened and conventional diagnosis groups; this trend was significant after adjustment for mode of diagnosis (P = .002). Additional analysis by logistic regression supports this trend, that is, dLA was positively associated with pLA (P = .01) after adjustment for plasma LA status at the time of diagnosis (Table 7). These results indicate that sustained adequate dietary intake of LA supports the achievement of normal plasma LA levels.
|
|
Influence of the Severity of CF on Growth Improvement
To investigate whether the severity of CF also affects treatment responsiveness, we examined the associations of several clinical indices to responder status. These indices included self-reported cough and wheezing experiences, Pseudomonas aeruginosa colonization status, and Shwachman-Kulczycki score. As reported in detail elsewhere,39–41 these parameters were collected every 3 to 6 months. Our results showed that, in addition to
EN and the baseline factors presented in Table 5, the Shwachman-Kulczycki chest radiographic score (P = .001), the combined Shwachman-Kulczycki activity and physical examination scores (P = .003), P aeruginosa colonization status (P < .001), but not cough and wheezing scores (P > .10) were significantly associated with the likelihood of being a responder. It should also be noted that the positive associations between EN and pLA to responder status remained significant in the presence of these clinical parameters. |
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
To our knowledge, this is the first study using a prospective cohort to examine the relative contributions of
EN and pLA to achieving adequate weight gain during the critical period of growth in young children with newly diagnosed CF. In our study population, ie, CF children who had varying severity of malnutrition as a result of PI but not MI, nearly 80% experienced declines in their weight status at the time of CF diagnosis compared with their birth status. Among these children, 60% were able to recover their weights to a level comparable to birth within 2 years after treatment was initiated, whereas the remaining 40% failed to do so. Among the responders, 70% accomplished it within 6 months after diagnosis, but 20% took 1 to 2 years. Results from this study enabled us to identify important factors that determine responsiveness to treatment initiation in achieving a goal of recovering weight status at birth in young children with newly diagnosed CF.
First of all, our results provide clear evidence that receiving caloric intake >120% of estimated requirement for a prolonged period (ie, EN) is critical in promoting adequate weight gain. The association between EN and recovery of WtzBR was observed in both screened patients and patients whose CF was diagnosed conventionally but was stronger in screened patients. This is evidenced by the observation that a lower proportion (56%) of patients whose CF was diagnosed conventionally and who received EN responded to EN, whereas the majority (91%) of screened patients who received EN were responders.
Second, our results suggest that pLA, in the absence of EN, is insufficient to promote adequate weight gain. Nevertheless, the importance of achieving and maintaining normal plasma LA levels should be emphasized, because the subgroup of patients who achieved combined EN and pLA had the highest response rate (89%; Table 3) of recovering WtzBR. In addition, the response rate in the subgroup of patients who received EN alone was approximately half of those who received combined EN and pLA (40% vs 83%) in the conventional diagnosis group (Table 4). These findings raise the possibility that pLA may be a limiting factor in promoting adequate weight gain in children with prolonged or more severe malnutrition as a result of delayed diagnosis. However, additional research is needed to elucidate the underlying mechanisms by which LA affects growth of children with CF.
Third, in addition to energy intake and plasma LA, our results suggest that the severity of malnutrition manifested at the time of diagnosis has a significant, negative impact on attaining adequate weight gain. Patients whose CF was diagnosed through neonatal screening, characterized by smaller declines in WtzDX-BR and better Htz at the time of diagnosis, were associated with a greater likelihood of being responders. In addition, among patients who recovered WtzBR, the length of time taken to recover was substantially shorter in those with <2-SD decline in WtzDX-BR compared with those with >2-SD decline in WtzDX-BR. These findings led us to speculate that some threshold effects may exist regarding the impact of malnutrition on the recovery of WtzBR.
Despite our findings above, it should be noted that approximately half of screened patients and 25% of patients conventionally diagnosed who did not achieve EN or pLA were able to recover WtzBR. These patients may have milder CF, such as less severe PI (thus better digestion and absorption of nutrients and not requiring EN) and/or less severe pulmonary disease. Variations in the severity of CF lung disease and other clinical manifestations of CF are likely to influence individual responsiveness to treatment initiation. This speculation is supported by our supplemental analyses demonstrating significant associations between Shwachman-Kulczycki clinical scores and P aeruginosa colonization status to the likelihood of recovering WtzBR.
In our study, the level of energy intake equivalent to 120% of estimated requirement was calculated on the basis of the new EER equations released from the DRI in 2002.34 This approach differs from previous dietary intake studies21,42,43 in which the 1989 RDA12 was used as the reference for expressing energy intake levels. According to calculations from our data, energy requirement estimated by the 1989 RDA are 12% to 22% (depending on the specific gender and age groups) higher than that estimated by using DRI's EER equations.34 Thus, our definition of 120% EER34 is equivalent to 100% of the 1989 RDA.12 Another unique approach in our study is that our analyses focused on examining the period of time whereby EN was maintained, instead of examining energy intake obtained at a single time point, with regard to its impact on treatment response. To our knowledge, this approach is novel and has not been reported previously.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Results from this study provide clear evidence that achieving and maintaining high energy intake at a level equal or >120% of the requirement, estimated on the basis of the new DRI, is a critical determinant of treatment responsiveness as defined by a successful recovery of weight status at birth. In children who are identified early through neonatal screening,
EN seems to be sufficient and effective in facilitating the recovery of the decline in weight experienced before diagnosis. However, in children whose CF was diagnosed conventionally, who experienced longer and more severe malnutrition before diagnosis, maintaining normal plasma LA for a prolonged period in addition to sustaining a high energy intake may be important in facilitating adequate weight gain. These findings suggest that frequent monitoring of plasma LA (through assessment of plasma fatty acid profile) is necessary and should be implemented in routine clinical care for patients with newly diagnosed CF. This study also provides additional evidence to support routine implementation of newborn screening programs, because children who have CF and are identified through neonatal screening not only require less extensive nutrition intervention but also respond to it at younger ages than children whose CF is diagnosed conventionally. Future research is needed to determine whether EN and pLA status are necessary to maintain adequate growth beyond 2 years after CF diagnosis.
|
ACKNOWLEDGMENTS |
|---|
This work was supported by National Institutes of Health grants DK 02891, 2R01 DK34108, and M01RR03186 and Cystic Fibrosis Foundation grant A001-5-01.
We thank Dr Philip Farrell for reviewing the manuscript and providing suggestions related to linoleic acid and growth in CF.
The Wisconsin Cystic Fibrosis Neonatal Screening Project is led by Dr Philip Farrell, MD, PhD. The following faculty members have 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; W. Theodore Bruns, MD, William Gershan, MD, Elaine Mischler, MD, Mark Splaingard, MD, and Lee Rusakow, Medical College of Wisconsin, Milwaukee. The investigation has been 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).
|
FOOTNOTES |
|---|
Accepted May 31, 2005.
Address correspondence to HuiChuan J. Lai, PhD, RD, Department of Nutrition Sciences, 1415 Linden Dr, Madison, WI 53706. E-mail: lai{at}nutrisci.wisc.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
- Kraemer R, Rudeberg A, Hadorn B, Rossie E. Relative underweight in cystic fibrosis and its prognostic value. Acta Paediatr Scand. 1978;67 :33 –37[Web of Science][Medline]
- Wood RE, Boat TF, Doershuk CF. State of the art: cystic fibrosis. Am Rev Respir Dis. 1976;113 :833 –878[Web of Science][Medline]
- Lai HC, Kosorok MR, Sondel SA, et al. Growth status in children with cystic fibrosis based on the National Cystic Fibrosis Patient Registry data: evaluation of various criteria used to identify malnutrition. J Pediatr. 1998;132 :478 –485[CrossRef][Web of Science][Medline]
- Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry Annual Data Report 2002. Bethesda, MD: Cystic Fibrosis Foundation;2003
- Giglio L, Candusso M, D'Orazio C, Mastella G, Faraguna D. Failure to thrive: the earliest feature of cystic fibrosis in infants diagnosed by neonatal screening. Acta Paediatr. 1997;86 :1162 –1165[Web of Science][Medline]
- McNaughton SA, Stormont DA, Shepherd RW, Francis PW, Dean B. Growth failure in cystic fibrosis. J Paediatr Child Health. 1999;35 :86 –92[CrossRef][Web of Science][Medline]
- Beker LT, Russek-Cohen E, Fink RJ. Stature as a prognostic factor in cystic fibrosis survival. J Am Diet Assoc. 2001;101 :438 –442[CrossRef][Web of Science][Medline]
- Sahebjami H, Doers JT, Render ML, Bond TL. Anthropometric and pulmonary function test profiles of outpatients with stable chronic obstructive pulmonary disease. Am J Med. 1993;94 :469 –474[CrossRef][Web of Science][Medline]
- Zemel BS, Jawad AF, FitzSimmons S, Stallings VA. Longitudinal relationship among growth, nutritional status, and pulmonary function in children with cystic fibrosis: analysis of the Cystic Fibrosis Foundation National CF Patient Registry. J Pediatr. 2000;137 :374 –380[CrossRef][Web of Science][Medline]
- Shwachman H, Redmond A, Khaw KT. Studies in cystic fibrosis. Report of 130 patients diagnosed under 3 months of age over a 20-year period.
Pediatrics. 1970;46
:335
–343
[Abstract/Free Full Text] - Konstan MW, Butler SM, Wohl ME, et al. Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis. J Pediatr. 2003;142 :624 –630[CrossRef][Web of Science][Medline]
- National Research Council. Recommended Dietary Allowances. 10th ed. Washington, DC: National Academy Press;1989
- Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002;35 :246 –259[CrossRef][Web of Science][Medline]
- Daniels L, Davidson GP, Martin AJ. Comparison of the macronutrient intake of healthy controls and children with cystic fibrosis on low fat or nonrestricted fat diets. J Pediatr Gastroenterol Nutr. 1987;6 :381 –386[Web of Science][Medline]
- Cannella PC, Bowser EK, Guyer LK, Borum PR. Feeding practices and nutrition recommendations for infants with cystic fibrosis. J Am Diet Assoc. 1993;93 :297 –300[CrossRef][Web of Science][Medline]
- Roy CC, Darling P, Weber AM. A rational approach to meeting macro- and micronutrient needs in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1984;3 (suppl 1):S154–S162
- Bell L, Durie P, Forstner GG. What do children with cystic fibrosis eat? J Pediatr Gastroenterol Nutr. 1984;3 (suppl 1):S137–S146
- Marcus MS, Sondel SA, Farrell PM, et al. Nutritional status of infants with cystic fibrosis associated with early diagnosis and intervention.
Am J Clin Nutr. 1991;54
:578
–585
[Abstract/Free Full Text] - Lai HC, Kosorok MR, Laxova A, Davis LA, FitzSimmon SC, Farrell PM. Nutritional status of patients with cystic fibrosis with meconium ileus: a comparison with patients without meconium ileus and diagnosed early through neonatal screening.
Pediatr. 2000;105
:53
–61
[Abstract/Free Full Text] - Farrell PM, Kosorok MR, Rock MJ, et al. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.
Pediatrics. 2001;107
:1
–13
[Abstract/Free Full Text] - Kawchak DA, Zhao H, Scanlin TF, Tomezsko JL, Cnaan A, Stallings VA. Longitudinal, prospective analysis of dietary intake in children with cystic fibrosis. J Pediatr. 1996;129 :119 –129[CrossRef][Web of Science][Medline]
- Farrell PM, Lai HC, Li Z, et al. Evidence on improved outcomes with early diagnosis of cystic fibrosis through neonatal screening: enough is enough! J Pediatr. 2005;147 :S30 –S36[CrossRef][Web of Science][Medline]
- Jelalian E, Stark LJ, Reynolds L, Seifer R. Nutrition intervention for weight gain in cystic fibrosis: a meta analysis. J Pediatr. 1998;132 :486 –492[CrossRef][Web of Science][Medline]
- Mischler EH, Parrell SW, Farrell PM, Raynor WJ, Lemen RJ. Correction of linoleic acid deficiency in cystic fibrosis. Pediatr Res. 1986;20 :36 –41[Web of Science][Medline]
- van Egmond AW, Kosorok MR, Koscik R, Laxova A, Farrell PM. Effect of linoleic acid intake on growth of infants with cystic fibrosis.
Am J Clin Nutr. 1996;63
:746
–752
[Abstract/Free Full Text] - Steinkamp G, Demmelmair G, Ruhl-Bagheri I, von der Hardt H, Koletzko B. Energy supplements rich in linoleic acid improve body weight ad essential fatty acid status of cystic fibrosis patients. J Pedatr Gastroenterol Nutr. 2000;31 :418 –423[CrossRef][Web of Science][Medline]
- Fost N, Farrell PM. A prospective randomized trial of early diagnosis and treatment of cystic fibrosis: a unique ethical dilemma. Clin Res. 1989;37 :495 –500[Web of Science][Medline]
- Couper RT, Corey M, Moore DJ, Fisher LJ, Forstner GG, Durie PR. Decline of exocrine pancreatic function in cystic fibrosis patients with pancreatic sufficiency. Pediatr Res. 1992;32 :179 –182[Web of Science][Medline]
- Lloyd-Still JD, Bibus DM, Powers CA, Johnson SB, Holman RT. Essential fatty acid deficiency and predisposition to lung disease in cystic fibrosis. Acta Paediatr. 1996;85 :1426 –1432[Web of Science][Medline]
- Farrell PM, Kosorok MR, Laxova A, et al. Nutritional benefits of neonatal screening for cystic fibrosis.
N Engl J Med. 1997;337
:963
–969
[Abstract/Free Full Text] - Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC growth charts for the United States: methods and development. Vital Health Stat 11. 2000;iii–x:1–190
- Farrell PM, Mischler EH, Engle MJ, Brown DJ, Lau SM. Fatty acid abnormalities in cystic fibrosis. Pediatr Res. 1985;19 :104 –109[Web of Science][Medline]
- Pennington JAT, Church HN, eds. Bowes and Church's Food Values of Portions Commonly Used. 14th–17th eds. New York, NY: Harper & Row;1985 –1998
- National Academy of Sciences. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, DC: National Academies Press;2002
- Greco L, Santamaria F, Salvatore D, de Ritis G. Growth dynamics in cystic fibrosis. Acta Paediatr. 1993;82 :254 –260[Web of Science][Medline]
- Pederzini F, D'Orazio C, Tamiazzo G, Faraguna D, Giglio L, Mastella G. Growth evaluation at one year of life in infants with cystic fibrosis diagnosed by neonatal screening. Pediatr Pulmonol. 1991;7 (suppl):64 –68
- Bronstein MN, Sokol RJ, Abman SH, et al. Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis. J Pediatr. 1992;120 :533 –540[CrossRef][Web of Science][Medline]
- Ihaka R, Gentleman RR: A language for data analysis and graphics. J Computat Graphic Stat. 1996;5 :299 –314[CrossRef]
- Kosorok MR, Jalaluddin M, Farrell PM, et al. Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis. Pediatr Pulmonol. 1998;26 :81 –88[CrossRef][Web of Science][Medline]
- Lai HC, Kosorok MR, Laxova A, Makholm LM, Farrell PM. Delayed diagnosis of US females with cystic fibrosis.
Am J Epidemiol. 2002;156
:165
–173
[Abstract/Free Full Text] - Farrell PM, Li Z, Kosorok MR, et al. Bronchopulmonary disease in children with cystic fibrosis after early or delayed diagnosis.
Am J Respir Crit Care Med. 2003;168
:1100
–1108
[Abstract/Free Full Text] - Stark LJ, Mulvihill MM, Jelalian E, et al. Descriptive analysis of eating behavior in school-age children with cystic fibrosis and healthy control children.
Pediatrics. 1997;99
:665
–671
[Abstract/Free Full Text] - Tomezsko JL, Stallings VA, Scanlin TF. Dietary intake of healthy children with cystic fibrosis compared with normal control children.
Pediatrics. 1992;90
:547
–553
[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  H. J. Lai, S. M. Shoff, P. M. Farrell, and with the Wisconsin Cystic Fibrosis Neonatal Screen 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 Pediatrics, February 1, 2009; 123(2): 714 - 722. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
