Should we be afraid of long-term cardiac consequences in children with multisystem inflammatory syndrome? Experience from subsequent waves of COVID-19.

The purpose of the study was to assess and compare short- and long-term cardiac complications of the multisystem inflammatory syndrome in children (MIS-C) by predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants throughout the pandemic. The analysis of prospectively collected data comparing cardiac complications of MIS-C during and after hospitalization across the original/alpha, delta, and omicron waves. Cardiac complications were defined as cardiac failure with systolic function impairment or hypotension or abnormalities in echocardiographic findings (decrease in LVEF, FS, valvular insufficiency, pericardial effusion, or coronary artery abnormalities). A total of 120 patients with MIS-C admitted to the Children's Hospital of Krakow between November 1, 2020, and May 5, 2023, were included in the study (74 during original/alpha dominance, 31 delta, and 15 omicron). Patients in the omicron group were found to be younger than those in the alpha and delta groups (37 vs. 75 vs. 80 months, p = 0.03). The frequency of cardiac failure with systolic function impairment or hypotension was diagnosed more frequently in the original/alpha and delta groups than in the omicron group (44.59% vs. 41.94% vs. 13.33%, p = 0.08) also echocardiographic abnormalities changed, with rates of 60.8%, 35.5%, and 13.3% (p < 0.001) accordingly. The multivariable regression revealed an older age (OR = 1.19, 95% CI = 1.07-1.33, p = 0.002) as the only independent factors of cardiac failure with systolic function impairment or hypotension. In all patients, signs of cardiac failure resolved during the hospitalization. Moreover, in 98.3% of patients, all echocardiagraphic abnormalities resolved completely during the observation period.    Conclusion: The cardiac complications of MIS-C appeared to advance less severely in younger children during the Omicron outbreak. In long-term observation, symptoms of cardiac failure resolve completely. Similarly, also echocardiographic abnormalities normalize in the vast majority of patients. What is Known: • Knowledge about the long-term cardiac complications of MIS-C is still evolving and uncertain. • The greatest concern of MIS-C is cardiac complications, including cardiac failure and coronary artery dilatation. What is New: • Long-term observations revealed complete resolution of cardiac complications in the vast majority of patients with MIS-C, irrespective of the dominant variant. • Cardiac complications of MIS-C were less common in younger children during subsequent pandemic waves in our patient population.

Nutritional status and feeding difficulties in children up to 2 years of age with cow's milk allergy.

BACKGROUND/OBJECTIVES: To assess the nutritional status and incidence of feeding difficulties in Polish children up to 2 years of age with cow's milk allergy (CMA) on cow's milk proteins-free diet. METHODS: A cross-sectional, multi-center study included children aged 6 months to 2 years with confirmed or suspected (without oral food challenge) diagnosis of CMA on the elimination diet for at least 1 month. The primary outcomes were an assessment of proportion of children with impaired nutritional status (with the weight for length and body mass index (BMI) z-score > 1 and <-1), and feeding difficulties according to the Montreal Children's Hospital Feeding Scale. Children with confirmed and suspected CMA were assessed separately. RESULTS: A 144 children with confirmed CMA and 88 with suspected CMA were included (57 and 78% with multiple food allergies, respectively). Among children with confirmed CMA, one-third (35.5%) of participants had any nutritional status impairment regardless of definition. Among those, most of children had mild malnutrition (10.4 vs. 9%) and possible risk of overweight (11.1 vs. 9.7%; following respectively BMI for age and weight for length z-scores). Only 16.0% of children had feeding difficulties. Feeding difficulties was identified to be a risk factor for moderate malnutrition compared to children without feeding difficulties (odds ratio 10, 95% confidence interval: 4-27). CONCLUSIONS: Mild malnutrition and possible risk of overweight are concern in children up to 2 years of age on cow's milk proteins-free diet. Feeding difficulties are less common, however, may affect the nutritional status.

Skin prick tests are not useful for the qualification for venom immunotherapy in children.

Background: The basis for qualification for venom immunotherapy (VIT) is the fulfilment of both the clinical and immunological criteria. Diagnostic tests that confirm the immunological criterion of an IgE-mediated sensitization include skin prick tests (SPT), intradermal tests (IDT), and serum specific IgE (sIgE) for the culprit venom. Objective: This study aimed to assess the usefulness of SPT as the immunological marker in the diagnosis of insect venom sensitization in children with history of systemic reaction (SR) to insect sting evaluated by means of I-IV-grades Mueller's scale. There are no such studies in children. Methods: This cross-sectional study sample consisted of 416 children aged 3-18 years (mean age 10.6 ± 3.8), 76% males, all with the history of a systemic reaction (SR) after a Hymenoptera sting (48% of grade III/IV according to Mueller scale), diagnosed between 1999 and 2019 in the tertiary referral centre. The standard diagnostic tests were used. Specificity, sensitivity, and positive and negative predictive values were computed to assess the diagnostic properties of the clinical tests to distinguish between mild and severe SR. To assess the relative value of an individual test in predicting the qualification to VIT we incorporated the Shapley value (SV). Results: Positive SPT results were found in up to no more than 3% of children; among them less than 1% had only positive SPT and were negative for sIgE and IDT. Approximately 85% of the children had detectable venom sIgE, followed by positive IDT (75%). Almost 70% of children had positive both sIgE and IDT results. In children with grade III/IV reaction, about 80% of children had positive results of both of these tests. sIgE and IDT had sensitivity >0.80, whereas SPT had high specificity (>0.97) in differentiating between mild and severe SR. Relative value of diagnostic tests in predicting qualification to VIT varied between venoms. Bee venom IDT had higher SV (0.052) than sIgE (0.041). In contrast, wasp venom sIgE had higher SV (0.075) than IDT (0.035). Conclusion: SPTs are not an useful immunological marker of venom sensitization in children, and eliminating SPT does not result in a loss of diagnostic accuracy. Limiting diagnostics to venom sIgE and IDT would shorten the procedure and reduce costs. Future studies are needed to determine if venom sIgE as the first line diagnostic test, with IDT added only if the venom sIgE is undetectable, is an optimal diagnostic process.

Inflammasome function in monocyte subsets and a risk of late-onset sepsis in preterm very low birth weight neonates.

BACKGROUND: Immature immune systems predispose very low birth weight (VLBW) neonates to systemic infections in early life. Defective inflammasome function may increase a neonate's susceptibility to late-onset sepsis (LOS). METHODS: Blood samples were taken on the 5th day of life (DOL) for all VLBW neonates (non-LOS and before-LOS groups; N.=76), and within 24 hours of sepsis onset (LOS group; N.=39). Monocyte (MO) subsets and intracellular interleukin-1ß (IL-1ß) expression were analyzed using flow cytometry. Inflammasome function, defined as level of IL-1ß and interleukin-18 (IL-18) was measured with enzyme-linked immunosorbent assay. IRA B cells were reported as a fraction of all B cells. RESULTS: Stimulation of classical MO in non-LOS cells demonstrated a higher expression of intracellular IL-1ß in comparison to MO from before LOS group. Serum from the LOS group revealed a higher level of IL-18. Stimulation of mononuclear cultures from samples taken during LOS resulted in significantly increased supernatant level of IL-1ß and IL-18 in comparison to samples taken on 5th DOL. No changes in the levels of IRA B cells were detected with the onset of sepsis. CONCLUSIONS: We did not observe a difference in the functioning of the inflammasome within monocytes taken on 5th DOL from premature VLBW neonates. Furthermore, there was no observable change in the IRA B cells of the septic and non-septic groups. The decreased expression of intracellular IL-1ß within classical MO of the before-LOS group may be an independent risk factor for LOS development.

Irisin concentration in infant formulas and breast milk.

BACKGROUND: Irisin is a newly discovered myokine with antiobesity properties. The delivery of irisin with the breast milk or formula is an emerging concept that myokine present at human milk influences postnatal energy balance and developmental parameters. The aim of the study was to evaluate irisin concentration in breast milk of mothers with term and preterm babies and in infant formulas. METHODS: A total of 49 lactating mothers were enrolled in the study: 31 mothers of very low birth weight preterm infants and 18 mothers of term infants. Milk samples were collected twice: during the first week after delivery and after 4 weeks of delivery. Irisin concentration was determined using ELISA kits both in human milk and in samples of 14 different infant formulas. RESULTS: There were no differences in milk irisin levels between preterm and full-term milk samples during both the 1st and the 4th week after delivery. There were also no differences in irisin concentration between transitional milk and mature milk in both tested groups. Irisin concentrations in preterm and full-term milk were significantly higher than in formulas for 30 days period after delivery. A significant increase of irisin concentration in natural milk 4 weeks postdelivery in comparison to 1st week after delivery was observed (mean difference 0.362 µg/mL; P=0.0063). CONCLUSIONS: This study provides evidence that irisin is present in infant formulas, although in less amount than in human milk. Further research is needed to assess, if children fed with infant formulas may disadvantage from lower irisin supply.

Over-the-counter antipyretics use among children from Southeastern Poland.

BACKGROUND: Over-the-counter (OTC) drugs are becoming increasingly popular. However, little is known about parents' practices concerning the use of OTC antipyretics in children. This paper aimed to study the habits and knowledge of parents regarding the use of OTC antipyretics in their offspring, considering the demographic and socioeconomic characteristics of the families. MATERIAL AND METHODS: A multiple-purpose survey was conducted anonymously among 229 parents of patients hospitalised in the Department of Paediatrics, University Children's Hospital, Krakow. Each parent answered 23 questions regarding OTC antipyretics use in his/her hospitalised child throughout the whole child's life. The data was statistically analysed. RESULTS: OTC antipyretics are administered to their children by 92% of parents. In the vast majority (87%), health care professionals or a leaflet were the sources of information on the drug and its dosage. Parents also used information from TV or the Internet (27%) and friends and family (30%), especially those in the younger age group. Families with high socioeconomic status were more likely to use health care professionals' advice for drug knowledge. Parents of children with allergic diseases made less use of nonmedical sources of knowledge. CONCLUSIONS: The majority of parents use OTC antipyretic drugs in their children. However, a high percentage of people using nonmedical sources of information is of concern. It is necessary to educate caregivers and to build the parents' awareness that they take an active role in their child's treatment. It would be useful to create generally available recommendations for home treatment.

Hymenoptera sting in the head and neck region is not a risk factor for grade IV systemic reactions in patients with venom allergy.

INTRODUCTION Hymenoptera insect stings (ISs) in the head and neck (H&N) region are commonly considered to be a risk factor for grade IV systemic reactions (SRs) in patients with Hymenoptera venom allergy (HVA). However, clinical data addressing this issue are scarce. OBJECTIVES The aim of our study was to verify whether ISs in the H&N region were related to a higher risk of grade IV SRs in patients with HVA. PATIENTS AND METHODS This retrospective cross­sectional study included 195 patients aged 2 to 74 years and treated with venom immunotherapy due to at least a grade II SR to ISs. The study sample comprised 109 adults (56%; mean [SD] age, 41.08 [14.62] years; male, 50.5%) and 86 children (mean [SD] age, 9.53 [4.37] years; male, 72.1%; P <0.001 for age and P = 0.002 for sex). The IS site was divided into 7 categories. RESULTS The H&N region was the most common site for the IS (one­third of the study group). In the entire study population, the risk of grade IV SRs was numerically, though insignificantly higher for ISs in the trunk (odds ratio [OR], 1.58; 95% CI, 0.42-5.92; P = 0.50) and legs (OR, 1.56; 95% CI, 0.49-5.10; P = 0.45), as compared with the H&N region. The H&N region showed a similar risk of grade IV SRs when compared with all the other IS sites combined into a single category (OR, 0.87; 95% CI, 0.43-1.75, P = 0.7). CONCLUSIONS ISs in the H&N region were not confirmed to be a risk factor for grade IV SRs in patients with HVA, regardless of age and sex.

Does type of feeding affect body composition in very low birth weight infants? - A prospective cohort study.

BACKGROUND: The aim of the study was to analyse body composition of preterm infants fed with either breast milk or formula compared to a control group of full-term newborns. METHODS: Fifty-three newborns were enrolled: a group of 34 very low birth weight (VLBW) preterm newborns subdivided into a formula-fed (n = 23; group A) and breast milk-fed (n = 11; group B) group, and a control group of 19 full-term infants (group C). Their body composition was assessed by a bioelectrical impedance analysis (BIA) either at the estimated time of birth in the VLBW group or during the 1st week of life in the full-term group. RESULTS: There was no difference in body weight or length between any of the three studied groups. However, we discovered that fat free mass (% FFM) was lower (83.5% vs. 85.5%; p < 0.01), while fat mass (% FM) was higher (16.4% vs.14.5%; p < 0.01) in group A compared to full-term newborns. There were no such differences in FFM (84.3% vs. 85.5%; p = 0.13) or FM (15.7% vs. 14.5%; p = 0.13) between group B and control. CONCLUSION: To sum up, the VLBW infants fed with breast milk shared similar body composition with the full-term infants, while the formula-fed VLBW developed higher amounts of adipose tissue and lower amounts of fat-free mass. This is the first study to expose differences in fat tissue content attributed to type of provided nutrition, which has become significant as early as estimated time of birth despite the comparable weight.

Evaluation of irisin and visfatin levels in very low birth weight preterm newborns compared to full term newborns-A prospective cohort study.

Premature infants represent one of the groups with increased risk for metabolic syndrome. Our study is the first one to evaluate irisin and visfatin levels, associated with the metabolic syndrome, both in blood of preterm and full-term infants, as well as in the breastmilk of their mothers. A total of 72 newborns was enrolled in the study, including 53 very low birth weight preterm infants and a control group of 19 term infants. The levels of irisin and visfatin were determined by a commercial enzyme-linked immunoabsorbent assay both in the baby serum and maternal milk twice, first during the 1st week of life and then 4 weeks later. Preterm infants had significantly lower serum irisin levels compared to the term infants. Overall, serum irisin level during the 1st week of life was positively correlated with several anthropometric measurements at birth, as well as during 5th weeks of age. In contrast, serum visfatin levels during 5th week of life were negatively correlated with z-scores of birth weight, weight and head circumference during 5th week of age. We found a strong negative correlation between serum irisin and serum visfatin levels at both analyzed time points. The level of milk visfatin was significantly higher in the mothers of the preterm group during 5th week of life. In conclusion, our results provide further evidence that irisin and visfatin may play physiologic roles in development of both preterm and full-term newborns during their first month after birth. Observed differences in irisin and visfatin serum and breastmilk concentrations during the earliest stages of life may contribute to development of catch up growth, but also, they might eventually lead to a higher risk for metabolic syndrome in prematurely born children in later years.

Plasma Free Fatty Acids and their Binding Proteins in Preterm Infants.

BACKGROUND/AIMS: The objective of the study was to evaluate the circulating concentrations of plasma free fatty acids (FFA), fatty acid binding proteins: FABP-1 and FABP-4 in preterm infants depending on different feeding protocol. METHODS: A total of 43 premature infants (≤34 weeks) were enrolled in the study, and divided into 3 subgroups: nursed while staying in the department (53%), breast-fed only during the first 24 h (16%), and formulafed from the beginning (31%). The control group consisted of 12 healthy, full-term, breast-fed newborns. Blood samples were collected after delivery and 1 month later. We measured plasma concentrations of FFA, FABP-1, and FABP-4. RESULTS: FFA plasma concentrations were significantly lower in preterm babies when compared to control group (p = 0.003) in the prenatal period. After 1 month, a significant decrease in FFA concentration was noted in all groups of preterm babies independently from feeding protocol. After a month, breast-fed preterm infants and controls had significantly lower FABP-1 levels than preterm formula-fed infants (all p < 0.05), while the highest concentrations of FABP-4 were noted in formula-fed preterm infants when compared to breast-fed preterm infants and the control group (all p < 0.05). CONCLUSIONS: Prematurity is connected with disturbances in plasma FFA concentrations. FABP-1, as well as FABP-4, plasma levels in preterm infants depend on feeding protocol.

Analysis of selected aspects of inflammasome function in the monocytes from neonates born extremely and very prematurely.

BACKGROUND: Inflammasomes regulate activation of caspase-1, which cleaves and activates interleukin (IL)-1ß and IL-18, the cytokines that trigger pro-inflammatory and antimicrobial responses. There is very little known about inflammasome function in the subsets of monocytes (MO) isolated from preterm neonates born extremely and very prematurely. METHODS: A group of 76 very low birth weight patients without early-onset sepsis was divided into extremely preterm (<28 gestational week) or very preterm (28-32 gestational week) neonates. The first blood sample was collected on the 5th day of life (5th DOL) to analyse MO subsets as well as the intracellular IL-1ß expression and supernatant concentration of IL-1ß and IL-18. Secondary blood samples were collected within 24h of late-onset sepsis (LOS) development and analysed as above. RESULTS: On the 5th DOL, the extremely preterm neonates were characterized by a significantly higher absolute count of MO, in particular in the classical and intermediate subsets, as compared to the very preterm group. The counts of the intermediate and non-classical MO subsets increased during LOS in all neonates. We did not observe significant differences in the intracellular IL-1ß expression between the analysed groups. Furthermore, the levels of the analysed cytokines in the MO supernatants were comparable between the extremely and very preterm neonates on the 5th DOL. Finally, a higher level of IL-18 was observed in the supernatant of the extremely preterm group during LOS. CONCLUSIONS: During LOS, extremely preterm neonates excrete a higher level of IL-18 cytokines compared to very preterm neonates. Further studies are required to determine whether this observation is a result of a higher count of the circulating MO or is a true reflection of increased inflammasome function in this particular group of newborns.

Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates.

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome.

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).

AIM: 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. MATERIAL AND METHODS: 204 newborns with birth weight ≤1000 g were born in the Malopolska voivodship between 1.09.2002 and 31.08.2004. From this group 115 (56%) children died during infancy and 89 (44%) infants survived. At the age of 7 years 81 (91%) of the children from this group were examined. At the age of 11 years investigations were carried out in 62 (75%) of the children, while 19 (26%) were lost to follow-up. All the children underwent anthropometric measurements. Moreover, the lipid profile (serum total cholesterol, triglycerides, HDL-cholesterol, LDL cholesterol) was evaluated. The control group consisted of 36 children born at term chosen randomly from the general population and matched with regard to age and sex. RESULTS: Children born with extremely low birth weight were generally smaller than their peers. At 7 years, they were shorter (113.75 cm(-0.72) vs.124.52 cm(0.53)), lighter (19.47 kg(-1.12)vs.25.23 kg(0.39)), had a smaller head circumference (49.81 cm(-2.19) vs.52.5 cm(-0.377)), waist circumference (50.14 cm(-0.83) vs.55.45 cm (0.34)), mid-upper arm circumference (17.51 cm vs. 19.29 cm), skinfold thickness (0.76cm(-0.817) vs.0.92cm (-0.19)) and body mass index (14.5 kg/m2 (-0.99)vs.16.16 kg/m2 (0.12)) expressed both as absolute values and z-score values compared to the control group. At 11 years old, the 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)), mid-upper arm circumference (20.95 cm vs. 22.85 cm), skinfold thickness (1.17 cm(-0.25)vs.1.68 cm(0.78)) and body mass index (16.74 kg/m2 (-0.62) vs.18.72 kg/m2 (0.36)) expressed both as absolute values and z-score values were still lower in children born with extremely low birthweight than in the control group. However, their gains over the time period between 7 and 11 years were comparable to their born-at-term peers in all the measured anthropometric parameters. There were no statistically evident differences in the indices of lipid metabolism. CONCLUSIONS: Preterm children with extremely low birth weight (<1000 g) are at an increased risk of growth failure. Once they reach teenage years they are shorter and lighter than their age- and sexmatched born-at-term peers. They also have smaller heads. In our study we did not find statistically evident differences between the investigated and control group in lipid indices. There is a need for longitudinal studies to observe somatic, mental and metabolic development in order to organize multidisciplinary holistic medical care for them.

ASSESSMENT OF BODY COMPOSITION USING BIOELECTRICAL IMPEDANCE ANALYSIS IN PRETERM NEONATES RECEIVING INTENSIVE CARE.

AIM: Evaluation of bioelectrical impedance values and body composition during early infancy in groups of preterm newborns and full-term newborns. MATERIAL AND METHODS: A total of 38 newborns was enrolled in the study: 26 very low birth weight preterm newborns with the mean birth weight of 1236 g (SD: 161) as the study group and 12 term newborns with birth weight of 2500-4000 g as the control group. Anthropometric measurements and body composition using bioimpedance analysis at the age of 1 week and at the age of 3 months were assessed. RESULTS: At the age of 1 week we noted higher resistance with the impedance variables R5, R50 R100 in the group of preterm newborns compared to the full-term newborns' group (923(144) vs. 647(78) p < 0.01; 870 (140) vs. 615 (73) p < 0.01; 844 (141) vs. 599 (72) p < 0.01). Moreover, the bioimpedance index and fat mass (%) were significantly lower in the group of preterm infants at the age of 3 months (3.81 (0.9) vs. 5.72 (1.1) p < 0.01; 16.1% (1.7) vs. 18.9% (2.7) p = 0.006). We observed a decreased amount of the percentage of total body water (TBW%) in both of the analyzed infant groups throughout the observational period. At the age of 3 months the amount of TBW % was similar in both groups (71.5% (7.03) vs. 70.8% (8.8) p = 0.8). CONCLUSIONS: Bioimpedance analysis is a simple, non-invasive, repeatable method to estimate total body water, fat-free mass, and fat mass, both in term and preterm newborns. The study confirms differences in body composition between preterm newborns and full-term newborns. Moreover, we have shown that the differences are present until the end of the 3rd month of life, with the exception of the amount of water percentage (TBW %), which are similar in both groups.

HOW TO DETERMINE THE NUTRITIONAL STATUS OF PRETERM BABIES?--REVIEW OF THE LITERATURE.

Prematurity is a high risk factor threatening the well-being of newborns and their somatic and psychological development in the future. Preterm babies need special medical care in which proper nutrition and metabolic control play an evident role. Our review presents the current knowledge concerning the clinical value of different methods investigated in the neonatal unit setting, including: protein markers of nutritional status (albumin,prealbumin, transferrin, and Retinol Binding Protein (RBP) and hormonal markers of nutritional status (somatomedin C, visfatin and ghrelin). Moreover, there is a discussion of the methods used for evaluating body composition. A variety of different techniques based on the physical properties of organisms was tested on neonates, e.g. the Dual Energy X-ray Absorptiometry (DEXA) method and Bioelectrical Impedance Analysis (BIA). Based on the review of the literature, we can speculate that none of the above methods represents a good single marker of the babies' nutritional status, or a prognostic factor for the future development of premature infants and infants born with IUGR. A combination of several methods from different groups seems to be a promising possibility. It is critical to continue looking for markers that will in a simple and efficient way help to optimize the correct nutritional therapy in infants with IUGR and those who were born prematurely.