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AIM: To develop a trigger tool for parents and lay caregivers of children with medical complexity (CMC) at home and to validate its content. DESIGN: This was a multi-method study, using qualitative data, a Delphi method and a concept mapping approach. METHODS: A three-round electronic Delphi was performed from December 2021 to April 2022 with a panel of 23 expert parents and 30 healthcare providers, supplemented by a preliminary qualitative exploration of children's signs of deterioration and three consensus meetings to develop the PArents' Trigger Tool for Children with Medical Complexity (PAT-CMC). Cognitive interviews with parents were performed to assess the comprehensiveness and comprehensibility of the tool. The COREQ checklist, the COSMIN guidelines and the CREDES guidelines guided the reporting respectively of the qualitative study, the development and content validity of the trigger tool and the Delphi study. RESULTS: The PAT-CMC was developed and its content validated to recognize clinical deterioration at home. The tool consists of 7 main clusters of items: Breathing, Heart, Devices, Behaviour, Neuro-Muscular, Nutrition/Hydration and Other Concerns. A total of 23 triggers of deterioration were included and related to two recommendations for escalation of care, using a traffic light coding system. CONCLUSION: Priority indicators of clinical deterioration of CMC were identified and integrated into a validated trigger tool designed for parents or other lay caregivers at home, to recognize signs of acute severe illness and initiate healthcare interventions. IMPACT: The PAT-CMC was developed to guide families in recognizing signs of deterioration in CMC and has potential for initiating an early escalation of care. This tool may also be useful to support education provided by healthcare providers to families before hospital discharge. PATIENT OR PUBLIC CONTRIBUTION: Parents of CMC were directly involved in the selection of relevant indicators of children's clinical deterioration and the development of the trigger tool. They were not involved in the design, conducting, reporting or dissemination plans of this research.
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AIM: To explore the process of recognition and response to clinical deterioration of children with medical complexity at home by their parents. BACKGROUND: Children with medical complexity are characterised by known chronic conditions associated with frailty and functional limitations, dependence on healthcare services and high use of technology and resources. Their medical complexity often leads to the onset of complications. Targeted care ensures timely recognition and response to clinical deterioration at home, thus avoiding serious sequelae, inappropriate hospitalisations and improving quality of life. Evidence on parents' process of the recognition and response to clinical deterioration at home is limited. DESIGN: Qualitative study using a Grounded Theory methodology. METHOD: Seven online focus groups were conducted with parents and healthcare providers experienced in their care. The interviews were transcribed verbatim and analysed through open, axial and selective coding, using a constant comparative iterative method. The COREQ guidelines guided the reporting of this work. RESULTS: Four categories and one core category were identified: (1) Awareness of the unique and shared characteristics of children with medical complexity; (2) Parents' care maintenance and management; (3) Parents' care monitoring; (4) Parents' response to clinical deterioration and (5) Seeking the Shift of Agency, the core category as the foundation of the Process of Recognition and rEsponse of PAREnts to Deterioration (PRE-PARE-D) theory. CONCLUSION: The role of parents of children with medical complexity is evolving into active care leaders, by developing care management and care monitoring competences and negotiating care with healthcare providers. RELEVANCE TO CLINICAL PRACTICE: The shift of agency from healthcare providers to parents requires education and counselling pathways to promote the development of parent's self-efficacy, competencies and empowerment in the care management of their children. Home care delivery for children with medical complexity should aim at sustaining this partnership between healthcare providers and parents.
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Deterioro Clínico , Servicios de Atención de Salud a Domicilio , Humanos , Niño , Teoría Fundamentada , Calidad de Vida , Padres , Investigación CualitativaRESUMEN
BACKGROUND: Central line-associated bloodstream infections (CLABSI) are significant cause of complications in pediatric intensive care units (PICUs). An emerging challenge are CLABSIs in children with medical complexity (CMC) admitted to PICU. CMC are patients with chronic conditions with or without neurological impairment needing for tracheostomy and/or home mechanical or non-invasive ventilation and/or gastrostomy/jejunostomy. We evaluate CLABSI incidence in a PICU with high prevalence of CMC. METHODS: This was a retrospective study in the PICU of the Bambino Gesù Children Hospital from January 2017 to December 2020. The medical records were reviewed and demographic, clinical and microbiological data were extracted. CLABSI were defined according to the Center for Disease Control and Prevention's National Healthcare Safety Networks (NHSN) surveillance. RESULTS: A total of 101 children with 125 central lines (CLs) were included; 79/101 (78%) patients were CMC and 50/101 (50%) had a thracheostomy. CLABSI incidence was 2.75/1000 CL-days (9 cases/3269 CL-days); incidence was 0 in patients without underling conditions and 3.14/1000 in CMC (p < 0.001). CLABSI were due to gram negative bacteria in five patients, Candida spp in three and Staphylococcus hominis in one. CLs were removed in eight cases while in the later one, with CLABSI due to Pseudomonas aeruginosa, a conservative strategy was adopted cause of unavailable alternative venous access and removed at discharge with negative culture. All patients recovered. CONCLUSIONS: A target 0% CLABSI was possible in critically ill children without underling condition while a high incidence was reported in CMC and sustained by a peculiar CLABSI ecology. This ecology should be considered when a CLABSI was suspected in CMC for prompt antibiotics stewardship.
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Bacteriemia , Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Sepsis , Humanos , Niño , Estudios Retrospectivos , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Bacteriemia/diagnóstico , Bacteriemia/epidemiología , Bacteriemia/microbiologíaRESUMEN
BACKGROUND: The aim of the study is to determine that Glycopirrolate is safe and effective in decreasing drooling in children with medical complexity under 3 years of age. Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY. GLY (Glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood-brain barrier penetration and consequently has limited central effects. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3-16 years. Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies while one a retrospective review. METHODS: this is a case report of eighteen children (sex ratio 11/8, median age 17 months, range 2-36 months) under three years of age, followed by a multidisciplinary team at the Bambino Gesù Children Hospital. The median follow-up was of 31.5 months (range 1-69 months). Response to treatment was assessed according to the Drooling Impact Scale administered at time 0 and after 1 month. All patients have an important neurological impairment: nine patients have a cerebral palsy (Gross Motor Function Classification System class V) and nine a genetic/malformative syndrome. Twelve patients have a tracheostomy and two need mechanical ventilation. Gastrostomy is present in 16 out of 18 patients. All patients received Glycopirrolate. The median starting daily dose was 0.065 mg/kg/die (range 0.02-0.21 mg/kg/die) three times a day. The drooling impact scale was administered at time O and after 1 month. RESULTS: Four out 18 patients stopped treatment for adverse event, lack of efficacy or parental decision. The mean Drooling Impact Scale at time 0 was 89 (range 81-100) and after 1 month 61(range 43-78); the difference was statistically significant (P < 0.001). The overall response to treatment was 94%. CONCLUSIONS: This is the first study to determine the safety and effectiveness of Glycopyrrolate in decreasing drooling in a specific subset of patients. No major side effects were observed. Further comparative studies are needed to confirm our results.
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Glicopirrolato/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Sialorrea/tratamiento farmacológico , Preescolar , Niños con Discapacidad , Femenino , Humanos , Lactante , MasculinoRESUMEN
Children with medical complexity (CMC) are a high priority population with chronic illnesses dependent on the use of health services, on technological systems to support their vital functions and characterized by multiple health needs. One of the main challenges linked to chronic conditions is finding solutions to monitor CMC at home, avoiding re-hospitalization and the onset of complications. Telemedicine enables to remotely follow up patients and families. An integrative review was performed to assess whether telemedicine improves health outcomes for CMC. Medline/PubMed, CINAHL, Cochrane Library, Web of Science, and Scopus were searched to identify studies describing the effect of using telemedicine systems on health outcomes for CMC. The PRISMA guidelines were used to select the papers. The methodological quality of the studies was evaluated through the Johanna Briggs Institute critical appraisal tools and the Cochrane Collaboration ROB 2.0. A total of 17 papers met the quality criteria and were included. Specialized telemedicine systems (tele-visits), telehealth, and tele-monitoring have been reported to reduce unplanned hospitalizations and visits, decrease total costs for healthcare services and families, and increase satisfaction for family members. No effect was found on the quality of life in children and their families.Conclusion: Available evidence supporting the use of telemedicine in CMC is favorable but limited. High-quality methodological studies including other unexplored health outcomes such as mental health, hospital readmissions, mortality, caregiver competences, and self-efficacy are needed to confirm the effectiveness of telemedicine systems in improving health outcomes for CMC. What is Known: ⢠CMC are an extremely fragile patient population with frequent access to healthcare services compared with other chronic conditions. ⢠There is conflicting evidence of the effectiveness of telemedicine clinical outcomes, healthcare utilization, and costs in pediatrics. What is New: ⢠There is some evidence that for CMC, telemedicine reduces unplanned hospitalizations, healthcare service costs, and financial burden for families, while increasing caregivers' satisfaction with care. ⢠Further research is needed to confirm the effectiveness of telemedicine systems in improving health for CMC.
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Calidad de Vida , Telemedicina , Cuidadores , Niño , Enfermedad Crónica , Humanos , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management. METHODS: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values. RESULTS: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred. CONCLUSIONS: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.
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COVID-19/terapia , COVID-19/transmisión , Transmisión de Enfermedad Infecciosa , Madres , Atención Posnatal , Adulto , COVID-19/epidemiología , Prueba de COVID-19 , Femenino , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
We evaluated severe acute respiratory syndrome coronavirus 2 RNA clearance in 22 children. The estimation of positivity at day 14 was 52% for nasopharyngeal swab and 31% for stool samples. These data underline the significance of nasopharyngeal and stoolsample for detecting infected children. Additional studies are needed for transmissibility.
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Betacoronavirus , Infecciones por Coronavirus/virología , Neumonía Viral/virología , Esparcimiento de Virus , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/transmisión , Heces/virología , Femenino , Humanos , Lactante , Recién Nacido , Italia/epidemiología , Masculino , Nasofaringe/virología , Pandemias , Neumonía Viral/transmisión , ARN Viral/metabolismo , SARS-CoV-2 , Factores de TiempoRESUMEN
INTRODUCTION: Children with special health-care needs are an emerging and consistent population. In a subset of children with medical complexity (CMC) a continuous access to the central vascular system is advisable to eliminate unnecessary pain and stress and to improve home management and palliative care. METHODS: The surgical registry of a tertiary hospital was checked in order to identify CMC who underwent totally implantable venous access device (VAD) placement. Medical records were reviewed. RESULTS: From October 2009 to August 2014, a totally implantable VAD was placed in 10 children. Seven out of 10 patients were affected by cerebral palsy while 3 presented a genetic syndrome. The median duration of the indwelling catheter was 31 months (range 5 to 77 months). Six catheters are still in place since the first placement. Infectious complications were observed in two patients, respectively, a Candida albicans and a Staphylococcus aureus colonization; in both cases the VAD was removed. In another two cases, removal was planned for reservoir dislodgment within the subcutaneous tissue. No other major complications were observed during the procedure and the follow-up period. Emergency admissions decreased from a median value of 0.4/month (range 0-1.5/month) to 0.2/month (range 0-0.6/month) after the VAD placement. CONCLUSIONS: A totally implanted VAD in CMC is safe and manageable. As expected, infection seems to be the major complication with no infection-related death. Malnutrition and musculoskeletal deformities, which are frequent comorbidities in CMC, should be considered to reduce the risk of dislodgment/migration.
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Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/terapia , Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Preescolar , Remoción de Dispositivos , Diseño de Equipo , Femenino , Humanos , Lactante , Masculino , Registros Médicos , Cuidados Paliativos , Datos Preliminares , Sistema de Registros , Estudios Retrospectivos , Centros de Atención Terciaria , Factores de Tiempo , Resultado del TratamientoRESUMEN
The biologic effects of insulin-like growth factor-1 (IGF-1) are mediated by specific cell surface receptors. IGF-1 binding to the extracellular alpha-subunits activates the tyrosine kinase intrinsic to the cytoplasmic portion of the IGF-1 receptor, leading to autophosphorylation of specific tyrosine residues in the receptor beta-subunit. One early molecular event that links the receptor kinase to the biologic actions of IGF-1 is tyrosine phosphorylation of the insulin receptor substrate family (IRS-1 to -4). IRS acts as a multisite 'docking' protein by binding to downstream signal-transducing molecules. Phosphorylation of multiple tyrosine residues results in the association of IRS-1 with the Src homology 2 (SH2) domains of other cytoplasmic signaling proteins, including phosphatidylinositol 3' kinase, Syp, Grb2 and Nck. By binding to Grb2, IRS proteins couple the IGF-1 receptor to the Ras/mitogenactivated protein kinase pathway. This pathway regulates cell growth, differentiation and proliferation. Severe pre- and postnatal growth retardation may arise from abnormalities of IGF-1 signaling such as IGF-1-binding alterations and IGF-1 receptor mutations. Knockout studies have shown severe growth impairment in mice lacking IRS family components or Akt. Finally, in human placentas from pregnancies complicated by intrauterine growth retardation, multiple alterations of IGF-1-signaling molecules have recently been described.
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Enfermedades del Sistema Endocrino/congénito , Enfermedades del Sistema Endocrino/genética , Somatomedinas/genética , Femenino , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/genética , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Modelos Biológicos , Mutación , Enfermedades Placentarias/genética , Embarazo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Transducción de Señal , Somatomedinas/fisiología , Factores de TiempoRESUMEN
BACKGROUND/AIMS: Our aim was to investigate glucose homeostasis, insulin sensitivity and insulin-like growth factor (IGF) system status in children born small for gestational age (SGA). METHODS: A case-control study was carried out at birth, infancy and childhood, comparing SGA with children appropriate for gestational age strictly matched for age, gender, pubertal status and body mass index. Ninety newborns, 52 infants, and 68 children were studied. Fasting insulin (I(F)), fasting glucose (G(F)) to I(F) ratio (G(F)/I(F)), the homeostasis model assessment of insulin sensitivity, the quantitative insulin sensitivity check index, insulinogenic index and the triglyceride/high-density lipoprotein-cholesterol ratio were measured. IGF-I, IGF-binding protein-3 and the IGF-I/IGF-binding protein-3 molar ratio were assessed. RESULTS: Glucose concentrations were lower in SGA newborns (p < 0.0001), infants (p = 0.01), and children (p = 0.001). Birth weight correlated with glucose levels at birth (r = 0.59, p < 0.0001), 12 months (r = 0.29, p = 0.04) and childhood (r = 0.44, p < 0.0001). CONCLUSION: Our results provide evidence for a developmental adaptation of glucose metabolism in SGA children leading to reduced glucose concentrations.
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Glucemia/análisis , Recién Nacido de Bajo Peso/sangre , Recién Nacido Pequeño para la Edad Gestacional/sangre , Parto/sangre , Peso al Nacer , Tamaño Corporal , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Children born small for gestational age are at high risk of developing insulin resistance, type 2 diabetes, hyperlipidemia, hypertension and cardiovascular disease in adulthood. In addition, approximately 10% of SGA children do not achieve a normal adult height. Studies performed in SGA children to evaluate markers of metabolic disease in prepubertal, pubertal and adolescent subjects, indicate a higher prevalence of subtle endocrine and metabolic abnormalities that may precede the onset of overt disease in adulthood. At present, however, there are no conclusive data supporting the need of systematic close monitoring of GH-IGF, hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes, as well as insulin sensitivity, glucose homeostasis, and lipid metabolism. Monitoring of metabolic parameters should probably be reserved to SGA children with genetic predisposition to type 2 diabetes and hyperlipidemia, as early identification of metabolic alterations might prompt effective preventive interventions and, ultimately, reduce cardiovascular risk.
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Biomarcadores/sangre , Recién Nacido Pequeño para la Edad Gestacional/sangre , Glucemia/metabolismo , Niño , Preescolar , Hormona de Crecimiento Humana/sangre , Humanos , Recién Nacido , Insulina/sangre , Leptina/sangre , Lípidos/sangreRESUMEN
In the past decade, several epidemiological studies have shown a relationship between intrauterine growth retardation and insulin resistance, type 2 diabetes and cardiovascular disease in adulthood. Although the biological mechanisms underlying this association are still largely unknown, different explanatory hypotheses have been proposed. It seems likely that the various pathways may interact with each other, all contributing at different degrees to the development of the metabolic disturbances.
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Fetal growth restriction is associated with an increased risk of developing insulin resistance and type 2 diabetes in adulthood. In addition, 10-20% of children born small for gestational age (SGA) do not achieve a normal final height. The purpose of this study was to investigate insulin sensitivity and endocrine status in SGA children, compared with that in children born appropriate for gestational age (AGA). Furthermore, within the SGA group, we aimed to relate postnatal growth to anthropometric, biochemical, and endocrine parameters. Eighty-two SGA children (with a mean age of 8.6 +/- 3.5 yr) and 53 short-AGA children (with a mean age of 9.3 +/- 3.3 yr) were studied. A case-control study was carried out in 26 SGA and 26 short-AGA subjects. For each SGA subject, we selected a short-AGA child matched for sex, age (within 1 yr), pubertal status, body mass index (within 0.5 kg/m(2)), and height (within 0.25 z-score). Children's statures were corrected for their midparental height, and SGA children were subdivided into 2 groups: catch-up growth (CG) group (children with corrected height with at least 0 z-score); and non-CG (NCG) group (subjects with corrected height with less than 0 z-score). Comparing SGA with short-AGA subjects, no significant differences in fasting insulin, fasting glucose/insulin ratio, homeostasis assessment model for insulin resistance, and homeostasis assessment model-beta-cell values were observed. SGA children showed significantly reduced levels of glucose (4.4 +/- 0.6 vs. 4.9 +/- 0.6 mM, P < 0.0001), total cholesterol (160.1 +/- 28.8 vs. 171.8 +/- 28.5 mg/dl, P = 0.02), and high-density-lipoprotein cholesterol (53.3 +/- 12.1 vs. 58 +/- 11.4 mg/dl, P = 0.02). The analysis of the subjects selected for the case-control study confirmed that SGA children did not have significant differences in the indices of insulin sensitivity but showed significantly lower glucose levels (4.4 +/- 0.7 vs. 4.9 +/- 0.4 mM, P < 0.005). Subdividing the SGA group into CG (n = 25) and NCG (n = 57) children, we found that NCG children showed significantly higher levels of TSH (2.5 +/- 1.3 vs. 1.9 +/- 0.6 mU/liter, P = 0.002). Our data indicate that SGA children do not have altered insulin sensitivity when compared with auxologically identical AGA subjects but show a significant reduction of glucose concentrations. Whether the lower glucose levels are attributable to an early phase of augmented insulin sensitivity, as previously reported in animal models, has to be established. The finding of higher TSH concentrations in SGA children with blunted CG suggests that intrauterine reprogramming might involve thyroid function, which, in turn, might affect postnatal growth and cholesterol metabolism, eventually increasing the risk of cardiovascular disease.
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Glucemia/análisis , Recién Nacido/crecimiento & desarrollo , Recién Nacido Pequeño para la Edad Gestacional/sangre , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Tirotropina/sangre , Estatura , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Concentración OsmolarRESUMEN
Intrauterine growth retardation (IUGR) is one of the major causes of short stature in childhood. Although postnatal catch-up growth occurs in the majority of IUGR children, approximately 20% of them remain permanently short. The mechanisms that allow catch-up growth or, on the contrary, prevent IUGR children from achieving a normal height are still unknown. Our aim was to investigate whether intrauterine reprogramming of hypothalamic-pituitary-adrenal axis may be involved in postnatal growth retardation of IUGR children through a modulation of the function of the IGF system. Anthropometry, IGF system assessment, cortisol measurement, and lipid profile evaluation were performed in 49 IUGR children. Children were subdivided into two groups according to their actual height corrected for midparental height: CG (catch-up growth) group, 19 children with corrected height >or=0 z-score; and NCG (noncatch-up growth) group, 30 subjects with corrected height <0 z-score. CG children showed significantly higher birth weight (p < 0.005) and body mass index (p < 0.05). No significant differences in IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, soluble IGF-II receptor levels (IGF2R), IGF-II/IGF2R ratio, and relative amounts of IGFBP-3 circulating forms were found between CG and NCG children. None of the IGF system-related variables correlated with anthropometric indices. NCG children showed significantly higher concentrations of cortisol (p < 0.005) and cortisol levels resulted inversely to birth weigh (r = -0.34, p < 0.05), birth length (r = -0.36, p < 0.05), and corrected height (r = -0.44, p < 0.01). Whereas total and HDL cholesterol concentrations were not significantly different in the two groups, LDL cholesterol levels were significantly higher in NCG children (p < 0.05), and five of 49 showed LDL cholesterol concentrations >3.4 mM (130 mg/dL). LDL cholesterol was inversely related to birth weight (r = -0.31, p < 0.05), corrected stature (r = -0.32, p < 0.05), and actual height (r = -0.31, p < 0.05) and directly related to the levels of IGF2R (r = 0.44, p < 0.01). Reanalysis of 15 of 30 IUGR newborns in whom we previously reported an inverse relationship between cord blood cortisol levels and first trimester length gain (r = -0.54, p < 0.005) showed that the relative amount of the IGFBP-3 18-kD fragment was related inversely to cortisol (r = -0.67, p < 0.01) and directly to early postnatal growth (r = 0.65, p < 0.05). Our results suggest that catch-up growth in IUGR children might be affected by intrauterine reprogramming of hypothalamic-pituitary-adrenal axis, which may result in a permanent modification of the neuroendocrine response to stress: children with increased cortisol secretion may be at higher risk of growth failure. During the neonatal period cortisol might act by limiting IGFBP-3 proteolysis and, therefore, reducing IGF bioavailability.