This study reports growth from birth to 2 years in a cohort of children diagnosed with CF by NBS. Classification modelling is also used to identify the variables affecting infant growth, to our knowledge this it is the first time this methodology has been used in this group.
Previous cohort studies show CF babies have a lower birth weight than healthy children although it is usually still within the normal range [16, 17]. Our cohort follows this pattern with a mean birth weight z scores of − 0.32. The lower birth weight may relate to gestational age as this was on average 38.9 weeks. Although the WHO-UK anthropometric calculator corrects the birth weight z scores for gestational age, it only does this for those < 37 weeks. CFTR may have a role in prenatal growth. As children with PS CF have higher residual CFTR function than PI CF infants, this would be consistent with the observation of lower birth weights in PI infants. This hypothesis requires replication in a larger cohort as the difference in birth weight between PI and PS infants was not statistically significant. Interestingly the gestation age was very similar for PI and PS infants (38.5 versus 38.8 weeks). Infants with CF have been shown to have reduced levels of insulin like growth factor [18]. This may explain the difference in birth weight between CF and non-CF babies and why some children with well managed CF still fail to reach their growth potential.
Postnatally, pancreatic function has a clear effect with the weight difference between the PS and PI infants becoming statistically significant at the first clinic visit when the child had ‘untreated CF’ for an average of 22 days. The degree of faltering growth observed in this short period was one of the most important variables identified by the classification model in predicting infant growth. Therefore, infants who experience the most severe nutritional consequences before treatment, continue to do so after this is started. These infants are likely to be those with mutations associated with the most severe loss of CFTR function. Despite treatment with pancreatic enzyme replacement therapy, PI infants had a significantly lower height and weight in the first year of life than PS infants. This difference reduced in the second year showing catch-up growth can be achieved with prolonged treatment pancreatic enzyme replacement therapy and appropriate nutritional support.
Infants with CF who are PI are more likely to have lower weight and height z scores than those who are PS [16]. It is therefore unsurprising that faecal elastase is one of the variables used by the classification models to predict future growth. PI infants usually have at least one class I, II or III mutation which are associated with higher sweat chloride which explains its inclusion in some of the models. Chronic infection with PA has an adverse effect on nutritional parameters in children with CF [17]. In our study, a single isolation of PA was linked with reduced infant weight and height. It is possible this was a direct effect of the PA infection or more likely that children who isolate PA have more significant lung disease which affects growth. The effects of acute and chronic SA infection on the growth of children in CF is not well known but early infection, especially occurring as a co-infection with other organisms, may be associated with severe lung disease which would affect growth [19, 20].
The importance of birth weight in predicting future growth is well established in the healthy children. The GECKO Drenthe Birth Cohort included 2447 healthy infants and identified birth weight and mode of feeding as the most important factors at predicting growth in the first 6 months of life [18]. The classification modelling in our study did not identify mode of feeding as a factor predictive of future growth although the sample size may have been too small to identify this. Early nutritional status is a key predictor of future health in children with CF [20]. It is therefore unsurprising that CF children with low birth weight have increased pulmonary disease in later childhood [17]. Increasing the birth weight of children with CF would therefore have long term health benefits. This could only be achieved through general public health measures targeting all pregnant mothers as it is unusual for the diagnosis of CF to be made prenatally.
Our study has several limitations. As we did not have a matched control group of non-CF infants from the same area we relied on the WHO-UK anthropometric calculator to generate z scores but accept this may miss local variations. There are potentially a huge number of variables that could affect infant growth. Due to the retrospective nature of this study we were limited as to which factors we could collect data on. Relevant variables which we were unable to collect data on included: parental height and weight, maternal smoking status, maternal diet during pregnancy, pulmonary exacerbations, treatment regimen, nutritional support, adherence with treatment and socioeconomic status. All of these may affect infant growth [9]. We used mean z scores over the first and second years of life for height and weight as our outcome for the statistical modelling. We accept this approach lacks granularity but the wide variation seen in the individual measurements it gave us the most useful summary outcome. We considered using alternative growth indices calculated from the weight and height measurements. However, the WHO does not recommend using BMI for age in children under 2 years and as percentage weight-for-height is not independent of the raw data it would have made the modelling results difficult to interpret.