VLBW may be due to prematurity and / or IUGR of different etiologies. Later, growth of these neonates can be influenced by multiple genetic, epigenetic, neonatal (respiratory, cardiac, infectious, nutritional, etc.) and post-neonatal (nutrition, morbidity, culture, etc.) factors. On the other hand, neurodevelopment of these children is also influenced by different factors, coinciding some of them with the above mentioned and being some of them related to other matters (parental intelligence, socio-family level, education, etc.). In published observational studies, it has been analyzed whether growth is related to neurodevelopment in short, medium and long term, although the conclusions are not uniform and debate remains open (2-9).
Beyond neurological alterations diagnosed clinically in follow-up (motor, sensory, cognitive, behavioral, ...), VLBW may present neuropsychological alterations at school age, only detectable by specific tests for this purpose, such RIST test and NEPSY-II battery at 5-7 years (11, 28). For this reason, our study aimed to know relationship between result of these tests and initial growth of VLBW, comparing different definitions of neonatal growth, without entering into the influence of other neonatal factors that are already present in previous publications (11).
Growth.
One of the major problems that arises when assessing relationship between neonatal growth and subsequent neurodevelopment is which growth parameters and somatometry to use. Classically, Fenton´s 10th percentile was cut-off at birth and neonatal discharge for classifying children as IUGR and EUGR, but this classification is now obsolete. First, IGW-21 standards seem much more interesting as basic data, given the way they are obtained (longitudinal with healthy preterm infants), to classify children (21), although it is still not clear whether we should call all those under 10th percentile at discharge or if we should only use this term for those who, born above 10th percentile, go from discharge below it. Other authors go further, proposing that EUGR concept should be based on the reduction of standard deviations, rather than static percentiles, adding a dynamic and critical look to this discussion. This is how the concept of static (or transverse) EUGR and dynamic (or longitudinal) EUGR arose, being this latter the currently preferred (2, 4, 16, 29, 30).
Our small series aimed to evaluate these aspects, analysing static somatometric data (weight, length and HC at birth and discharge), but also some dynamic ones (true EUGR and changes less or greater than -1 and -2 SD between birth and discharge), both for Fenton and IGW-21. Our results support that the percentage of VLBW classified as IUGR and EUGR vary greatly depending on criteria used.
Thus, IGW-21 is slightly less selective at birth in IUGR classification (most cases than Fenton) but, at the same time, stricter at discharge in the static EUGR classification for weight (less cases less than Fenton), which makes some true Fenton-tagged EUGRs slip away (30.4% in our series), while Fenton doesn't miss any of the IGW-21-tagged ones. The same does not happen with length and with CP, which do not present a uniform trend, contrary to what appears in other series (31).
Neuropsychological test
In our 87 VLBW, we found no differences in somatometry at birth and in their growth up to 2 years of age between children with and without neurological alteration clinically diagnosed at 5-7 years, but in neuropsychological tests performed at this age. With RIST index and NEPSY-II battery we have verified that, in addition to static somatometry at birth, certain parameters of neonatal growth and during the first 2 years of life influence the performance of these children at study age.
RIST is a screening test that provides us with a measure of estimated IQ, which, in our series, was correlated with z-score at birth (Fenton´s weight, length and HC, and IGW-21´s length) and at neonatal discharge (Fenton and IGW-21 weight and length), but not with z-score differences between birth and neonatal discharge, nor with the z-score at 2 years. In addition, IUGRs in weight, length and HC, and static EUGRs in length and HC show lower scores, statistically significant, compared to neonates who were not, with differences of 10-20 points between them. Same occurs with neonates who present HC score less than 2SD for WHO at 2 years. These results coincide partially with the previous literature, finding that some neonatal and early postnatal measures which indicated a lower growth status could be related with later and lower IQ achievements (2).
However, it is also worth mentioning major methodological differences of our study with some previous publications, such as the use of different definitions of EUGR, with Fenton and IGW-21 graphs and standars. Therefore, it seems that the use of these new approaches may be of interest, as a possible predictor of subsequent neuropsychological development.
Another issue to consider would be the different importance given to the IQ in these previous publications. As it has been said before, while previous articles are focused on IQ assessment as the only measurement of cognitive development, our aim was to consider a wider neuropsychological profile, and due to that, RIST test was included only as a screening measure of IQ. With these results, we must admit that RIST index is mathematically related with static somatometric values at birth and discharge, but not with dynamic ones. In any case, this relationship, as we discussed previously, can be influenced by many other prior or intermediate factors that surely play important roles.
In NEPSY-II tests, we found some interesting relationships, although we did not find a clear pattern between growth and the different subtasks. It is striking, for example, that Memory for names and Memory for design tasks, related to verbal and visuospatial memory respectively, did not present any type of relationship (neither correlation nor statistically significant differences) with any growth parameter. This may be due to the fact that the memory scores reported in the present study are composite indexes of both short- and long-term memory, which are related but independent cognitive functions and their addition could decrease their ability to differentiate between growth statuses. Besides, it should be noticed that in Memory for designs, any of our participants scored below expected, and then, this can limit the discriminatory capacity of such task.
We also did not find correlations between scalar scores of other studied NEPSY-II subtasks (Inhibition and Route finding subtasks), although we were able to determine some statistically significant differences for some growth items, but without a clear pattern of behavior or clinical differences, important enough to be highlighted. These findings could point to the possibility that slower growth does not affect specific neuropsychological functions, but rather a more global pattern of cognitive development.
In summary, classification IUGR and EUGR (static, dynamic and true) with Fenton and IGW-21 show very varied percentages according to the criteria used in the classification. Besides, growth influence on neuropsychological tests does not seem robust, except for IQ measurement, which is clearly correlated with some static measures and which shows clinically important differences between some groups classified according to these measurements.
New IUGR and EUGR concepts should be evaluated in future studies in this field since, probably, they catalog neuropsychological risk groups differently and modify ideas that were maintained up to that moment. Reviewing growth importance in first weeks of life in later neurodevelopment is a topic of great interest to neonatologists, endocrinologists, neurologists, and psychologists.