Somatic development and some indices of lipid metabolism in 11-year-old children born with extremely low birth weight (<1000 G) (long-term cohort study)

In recent years the survival rate of high-risk infants, especially those born prematurely with ELBW (extremely low birth weight) has increased due to extremely great progress in technological and medical sciences [1, 2, 3] but their mortality is still very high. In comparison to full-term infants, newborns with ELBW need much more multidisciplinary medical care [4, 5].

To continue the prospective follow-up cohort study on the somatic development and lipid metabolic parameters of 11-year-old children born with extremely low birth weight and to compare them with the results obtained in the study of 7-year-old children from the same group.

The characteristics of 204 children included in our long-term study are shown in Figure 1. They were born with ELBW (≤1000 g) in the Malopolska voivodeship between September 2002 and August 2004. The patients were assessed twice: first between September 2009 and December 2010 at the age of 7 years (13), and the second time between December 2013 and March 2015 at the age of 11 years (fig. 1). The control group consisted of 36 children born at term that were chosen randomly from the general population and matched with regard to age and gender, and also assessed longitudinally at 7 and 11 years old. The characteristics of the subjects are listed in table I.

Fig. 1

Anthropometric examination included the following parameters: weight (g), length/height (cm), head circumference (cm), arm circumference (cm), waist circumference (cm), and skinfold thickness at the triceps (mm); all expressed as absolute values and z-scores. We calculated the body mass index (BMI) and determined blood lipid levels for each of the study participants.

Our patients underwent all the physical measurements barefoot while wearing underclothes. Weight was taken on a medical scale to the nearest 100g. Height was measured with either a fixed stadiometer with the head set in a Frankfurt plane, or a standard medical tape to determine crown-heel length, in non-walking children to the nearest millimeter. BMI was expressed as weight in kilograms per height in meters squared. All the circumference measurements were taken by a standard medical tape to the nearest millimeter. The occipitofrontal circumference was measured over the most prominent part of the occiput and above the supraorbital ridges, the waist circumference was set at the level of the umbilicus, the arm circumference was specified at the mid-point between the olecranon process and the acromion. The skinfold thickness was evaluated with a calibrated skinfold caliper over the triceps at the midpoint between the tip of the shoulder and the tip of the elbow.

Laboratory evaluation: After the physical examination, a venous blood sample (3 ml) was taken for the assessment of serum total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG) level. Total cholesterol, HDL, LDL and TG were measured by a colorimetric method, using the VITROS Integrated System (Ortho Clinical Diagnostics, New Jersey, USA). Age-adjusted normal reference ranges were used to assess the accurate level of the lipid profile. Normal values [mmol/l] were as follows: total cholesterol 2.95-5.57, HDL 0.69-1.81, LDL 1.51-3.34 TG 0.57-2.36 for girls, and total cholesterol 2.82-5.27, HDL 0.65-1.81, LDL 1.27-3.35 TG 0.51-2.12 for boys.

Statistical analysis was conducted using JMP 9.0.0, 2010 SAS Institute Inc. The detected differences were considered to be statistically significant in case of p<0.05. Demographic and clinical data comparisons between the study and control groups were performed using Student’s t-test, Mann-Whitney U-test, chi-square test. The comparisons between the measurements acquired at 7 and at 11 years were performed using the paired t-test.

The protocol of the study was approved by the Jagiellonian University Medical College Ethics Committee. The parents of all the participants provided written informed consents.

A total of 89 children born with ELBW were enrolled in the study, 81 were evaluated in their 7^th year of life, and 62 children − in their 11^th year of life (Fig. 1). The control group consisted of 36 children born at term that were chosen randomly from the general population and matched with regard to age and gender, and also assessed longitudinally. Characteristics of the subjects are listed in Table I.

At 7 years, children (13) who were born as ELBW preemies were shorter (113.75 cm (-0.72) vs.124.52 cm(0.53)), lighter (19.47 kg (-1.12) vs. 25.23kg (0.39)), had smaller head circumference (49.81 cm (-2.19) vs. 52.5cm (-0.377)), reduced waist circumference (50.14 cm (-0.83) vs. 55.45 cm (0.34)), reduced middle upper arm circumference, MUAC (17.51 cm, v. 19.29 cm), reduced skinfold thickness (0.76 cm (-0.817) vs. 0.92 cm (-0.19)) and smaller BMI (14.5 (-0.99) vs. 16.16 (0.12)) expressed both as absolute values and z-score values compared to the control group (tab. II).

At 11 years old, the ELBW children were still smaller than their born-at-term peers as demonstrated by the anthropometric parameters such as height (141.7 cm (-0.368) vs. 146.26 cm (0.65)), weight (33.88 kg (-0.59) vs. 40.45 kg (0.66)), head circumference (51.37 cm (-2.05) vs. 54.02 cm (-0.33)), waist circumference (61.7 cm (0.26) vs. 67.84 cm (1.06), MUAC (20.95 cm, vs. 22.85 cm), skinfold thickness (1.17 cm (-0.25) vs. 1.68 cm (0.78)) and BMI (16.74 (-0.62) vs. 18.72 (0.36)) expressed both as absolute values and z-score values (tabl. III).

The anthropometric parameters analyzed in the study and control groups increased at comparable rates along their estimated channels of the growth chart, with exception of height, which was significantly faster among the ELBW children (tab. IV).

We noted that ELBW male subjects were significantly smaller, as shown in all the recorded physical growth parameters, compared to their matched controls at 11 years, while ELBW females demonstrated physical growth (such as height, weight, MUAC, waist circumference and BMI) comparable to their controls at 11 years (data not shown). There was no statistically significant difference with regard to lipid profile between the two investigated groups (tab. V).

We present the results of a longitudinal prospective cohort study that explores potential correlations between birth weight, postnatal weight gain and anthropometric variables of very preterm-born children once they reach the age of 11 years. The study showed that ELBW preterm children demonstrated much poorer growth than full-term children at 11 years. The stature of our controls very closely matched that of the normal population, unlike the ELBW children whose mean height was significantly lower. The mean deficit in stature in the ELBW group was around 4.6 cm, and it was comparable to the height difference found by Peralta- Carcelen and colleagues in their study of 14-year-old VLBW (very low birth weight) children [8]. Saigal et al. [9] showed that children born ELBW were at an increased risk for short stature in adolescence. Not only were the preterm children shorter and lighter, but they also had relatively smaller head circumferences. We presented similar results, our ELBW children’s head circumferences were significantly smaller (-2 SD) compared to the reference values. We hypothesized that those children might eventually develop lower IQ, since there were reports of a correlation between head circumference and IQ (10). We used Z-scores in our study to monitor changes during the development of our ELBW children. We believe that the results reported in such a way added more strength to our longitudinal study, since according to Shann, the use of Z-scores comparable across ages provided a more sensitive assessment of deviations of growth than the use of percentiles [11].

We examined some indices of lipid metabolism since preterm infants might have an increased risk of adverse metabolic outcomes in later life. We also checked the metabolic status of our subjects by analysis of their fat mass and lipid profile. We measured their mid-upper arm circumference, skinfold thickness and waist circumference, although we did not assess the amount of fat mass directly using the DXA method, which is known to be a gold standard. Anthropometric parameters were significantly lower in comparison to the control group both at 7 and 11 years of age. Our results were similar to the findings of Gianni et al. [12], who examined children with birth weight <1800 g and gestational age <34 weeks at the age of 4.8-6.6 years using dual energy x-ray absorptiometry (DXA).They found a significantly lower amount of adipose tissue in the group of preterm infants in comparison with the full-term infants’ group. Moreover, they noted aberrant fat distribution with reduced subcutaneous and increased intra-abdominal amount of adipose tissue. However, we observed a “catch-up” period in our ELBW children during the time-span of our study. When we analyzed the z-score values, their skinfold thickness and waist circumference were both at -0.8SD at 7 years, and increased to -0.2 and +0.2 at 11 years, respectively. It was in agreement with the work by Hack M. et al., who carried out a prospective cohort study of VLBW infants.They noted that the catch-up growth in weight, height, and BMI occurred between 8 and 20 years among VLBW females, in contrast to the VLBW males who remained significantly smaller than their controls at 20 years old [6, 7]. In another study, Peralta-Carcelen et al. compared the growth parameters between a group of almost 15-year-old ELBW adolescents and their sex and age matched controls born at normal birth weight (NBW). On average, ELBW adolescents were shorter and lighter than their normal-birth-weight NBW counterparts. Just as in all the other studies, the ELBW adolescents had lower mean z-scores for height, weight, and head circumference than NBW adolescents. However, in agreement with our findings, their body composition was similar between groups [8].

We believe that our study further emphasizes the need for a careful follow-up through the adolescent years of ELBW children. Further research is needed to fully understand long-term metabolic and psychosomatic developmental implications with a holistic [14] approach to the therapy.

Preterm extremely low birth weight (<1000 g) children are at an increased risk of growth failure. Once they reach teenage years, they are shorter and lighter than their age- and sex-matched peers born-at-term. They also have smaller heads. The indices of lipid metabolism we selected did not show statistically evident differences between groups. There is a need for longitudinal studies to further monitor the development of children born with extremely low birth weight in order to organize proper interdisciplinary medical care with a holistic approach to the therapy [14].