Vasileios Giapros

Morbidity and mortality patterns in small-for-gestational age infants born preterm

Objective. Small-for-gestational age (SGA) neonates born prematurely may be at higher risk for adverse effects during the early postnatal period than premature neonates born appropriate for gestational age (AGA).This study aims to study comparatively morbidity and mortality in SGA and AGA neonates born with low gestational age (GA). Methods. The study population included all preterm infants born alive with GA 24–31 weeks in Northwestern Greece during a 9-year period and hospitalized in the regional neonatal intensive care unit (NICU). The association of SGA status with neonatal death, and with chronic lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), and sepsis was assessed, using multiple logistic regression analysis. Results. Of 210 infants without congenital anomalies born at GA 24–31 weeks, 51 were SGA and 159 were AGA. CLD was more common in SGA than in AGA neonates (57.1% vs 29.3%, p < 0.05), but no differences were found in the rates of IVH, NEC, ROP, RDS, and sepsis. The mortality rate in the SGA group was 33.3% vs 17% in the AGA group (p < 0.01), and in the subgroups 28–31 weeks 24.1% vs 6.3%, respectively, (p < 0.01). In logistic regression analysis, SGA status was strongly associated with increased mortality and CLD, independent of confounding factors [odd ratios and confidence intervals: 3.4 (CI: 1.8–10.6) p = 0.03 and 3.9 (CI: 1.7–11.5) p < 0.01, respectively. Conclusions. SGA neonates with GA 24–31 weeks were at increased risk of development of CLD and of neonatal death compared with AGA neonates of the same GA.

Implications of 99mTc-DMSA Scintigraphy Performed During Urinary Tract Infection in Neonates

OBJECTIVE: To evaluate prospectively whether normal scintigraphic results during urinary tract infections (UTIs) in neonates were predictive of the absence of dilating vesicoureteral reflux (VUR) (grade ≥III) and permanent renal damage (PRD). METHODS: Term neonates with a first symptomatic, community-acquired UTI participated in the study. Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months. DMSA scintigraphy, to determine the development of PRD, was repeated 6 months after UTI. RESULTS: Seventy-two neonates (144 renal units) were enrolled. Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19% of renal units, VUR in 22%, and grade ≥III VUR in 13%. The majority (71%) of renal units with grade ≥III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade ≥III VUR were 29% (95% confidence interval: 11%–55%) and 82% (95% confidence interval: 74%–88%), respectively. PRD was found in 7% of renal units, all of which had abnormal early DMSA scintigraphic results. PRD was significantly more frequent among renal units with grade ≥III VUR than among nonrefluxing renal units (P < .05). CONCLUSIONS: Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR. To rule out dilating VUR, voiding cystourethrography may be required.

The effects of gestational age and growth restriction on compensatory kidney growth

BACKGROUND Low birth weight is associated with altered renal development, adult onset hypertension and renal disease. The aim of this prospective longitudinal study was to estimate the renal growth during the first 2 years of life in small-for-gestational age (SGA) infants of varied gestational age (GA) and with differing degrees of growth retardation (GR) at birth. Material and methods. The study included 466 children: SGA, n = 243, and appropriate-for-gestational age (AGA), n = 223, classified according to GA into three groups (28-34, 34-36 and >36 weeks, respectively). The SGA children were also classified according to the degree of GR: birth weight <3rd percentile, and birth weight 3-10th percentiles. Serial renal ultrasonography (US) for kidney length (KL) measurement was performed at the ages of 36 and 40 weeks corrected age and 3, 6, 12 and 24 months of chronological age. The ratios of KL(3) to crown to heel length (CHL), body weight (BW) and body surface area (BSA) were used as estimators of relative kidney length (RKL). RESULTS A total of 1898 measurements were performed. In the full-term and near-term SGA infants (GA >36 weeks), RKL was similar to or even higher than that in AGA controls (P < 0.05 at 12 and 24 months). In two groups of preterm infants (GA 34-36, 28-34 weeks), RKL was lower than in AGA controls either after the first 6 months (GA 34-36 group, P < 0.05) or throughout the study period (GA 28-34 group, P < 0.05). The absolute KL was more severely affected in the preterm babies (GA <36 weeks) with BW <3rd percentile than in those of GA 3rd-10th percentile. CONCLUSION While in full-term and near-term SGA infants RKL is similar to or even higher than that of AGA infants, in smaller preterm babies (<36 weeks of GA) the RKL is impaired up to the second year of life.

Prothrombotic State, Cardiovascular, and Metabolic Syndrome Risk Factors in Prepubertal Children Born Large for Gestational Age

OBJECTIVE To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS At 6–7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS LGA children had higher levels of leptin (P < 0.01), fasting insulin (P < 0.01), and HOMA-IR (P < 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P < 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016). CONCLUSIONS Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3–4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3–4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = −0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.

Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance.

OBJECTIVE The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction. RESEARCH DESIGN AND METHODS Serum levels of adiponectin, leptin, fasting glucose, fasting insulin (IF), the homeostasis model assessment insulin resistance index (HOMA-IR), IGF-1, free IGF-1, IGF-binding protein (IGFBP)-1 and -3, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaluated in 57 children at age 4–10 years. Of these, 32 had been born appropriate size for gestational age (AGA) and 25 SGA (14 in the <3rd percentile and 11 in the 3rd–10th percentile). RESULTS The SGA 3rd–10th percentile children were already insulin resistant at prepubertal age (IF 39.6 ± 16.8 vs. 27 ± 12 pmol/l, P < 0.01, and HOMA-IR 1.4 ± 0.6 vs. 0.95 ± 0.42 in SGA vs. AGA children, P < 0.05). Their IGF-1 and IGFBP-3 concentrations were significantly lower than those in AGA children (160.4 ± 66.2 vs. 207 ± 66.8 μg/l, P < 0.05 and 2.3 ± 0.4 vs. 3.51 ± 1.21 mg/l in SGA vs. AGA children, P < 0.01). The SGA <3rd percentile children had higher adiponectin (15.6 ± 5.7 mg/l, P < 0.05) and IGFBP-1 levels (113.5 ± 33.9 μg/l, P < 0.05) than AGA children (11.3 ± 6.6 mg/l and 90.8 ± 24.2 μg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 ± 68.4 μg/l, P < 0.05 and 2.4 ± 0.7 mg/l, P < 0.01). They also had significantly lower waist circumference (P < 0.05). Leptin levels did not differ among groups, but an inverse correlation with IGFBP-1 (r = −0.55, P < 0.01) was found in the pooled SGA group. CONCLUSIONS Intrauterine growth restriction appears to affect the IGF axis at prepubertal age, and its severity plays a role in insulin sensitivity.

Low gestational age and chronic lung disease are synergistic risk factors for retinopathy of prematurity

AIMS This retrospective, population based study was designed to investigate risk factors for development of retinopathy of prematurity (ROP) and their possible interrelationships, in neonates of gestational age (GA) <32 weeks born in a well-defined geographical region. STUDY DESIGN-SUBJECTS: The study population included all preterm infants born alive with GA 24-32 weeks in Northwestern Greece during a 9-year period and hospitalised in the regional neonatal intensive care unit (NICU). OUTCOME MEASUREMENTS The association was assessed of the presence of ROP with maternal factors: age, pathology of pregnancy, in-vitro fertilisation, multiple gestation, mode of delivery, perinatal factors: gender, antenatal steroids, transportation, resuscitation, GA, birth weight (BW), small for GA status and postnatal morbidity: chronic lung disease (CLD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), maximum O(2) needs, hypoxic/hyperoxic episodes, patent ductus arteriosus (PDA), sepsis, using multiple logistic regression analysis. RESULTS Of 189 infants without congenital anomalies born at GA 24-32 weeks ROP was diagnosed in 24 (12.7%) (>grade 2: 6). Logistic regression analysis showed ROP to be strongly associated with GA, odds ratio (OR) 2.1, confidence interval (CI) 1.3-3.3, p<0.01 and CLD, OR 10.2, CI 2.3-44, p<0.01, respectively, independent of confounding factors. By estimating interaction on an additive scale it was shown that the combined risk effect of GA and CLD was larger than the sum of the individual risk effects, implying synergistic effect. CONCLUSIONS ROP was closely and independently related to both low GA and the diagnosis of CLD, which were interrelated in the development of ROP.

Serum transferrin receptor, ferritin, and reticulocyte maturity indices during the first year of life in 'large' preterm infants.

Background:  Preterm infants are at risk of developing iron deficiency; among the iron status and hemopoiesis indices the serum transferrin receptor (sTfr) has been shown to be a useful indicator in assessing iron status, while immature reticulocyte production is regarded as an estimator of erythropoiesis.

Growth Restriction at Birth and Kidney Function During Childhood

BACKGROUND Individuals born small for gestational age (SGA) are at risk of developing hypertension and kidney disease later in life. The time that this may occur is unknown. This study aims to examine kidney function in preschool children who were SGA. STUDY DESIGN A case-control study. SETTINGS & PARTICIPANTS The study included 100 children, 60 SGA and 40 appropriate-for-gestational-age (AGA) controls matched with the SGA children according to birth characteristics (gestational age and sex) and characteristics at the time of the study (body weight, body height, body mass index, and age). SGA children were classified according to severity of growth restriction into 2 groups: birth weight less than the 3rd percentile (n = 25) and birth weight from the 3rd to 10th percentile (n = 35). PREDICTORS Being SGA and severity of growth restriction at birth. OUTCOMES & MEASUREMENTS Kidney function was estimated at a mean age of 5 years by using serum creatinine level; estimated glomerular filtration rate; urinary albumin excretion; fractional excretion of sodium, potassium, phosphate, magnesium, and uric acid; transtubular potassium gradient; and urinary calcium-creatinine ratio calculated from 3-hour urine collections. Blood pressure and kidney length also were measured. RESULTS Kidney length, serum creatinine level, and estimated glomerular filtration rate did not differ among the 3 groups. Systolic and diastolic blood pressures were greater in SGA children with birth weight less than the third centile versus controls (107.5 +/- 11 versus 102 +/- 10 mm Hg [P = 0.03] and 69 +/- 7.5 versus 65 +/- 8.6 mm Hg [P = 0.02] for systolic and diastolic blood pressure, respectively). Both groups of SGA children had greater urinary calcium excretion than AGA children (urinary calcium-creatinine ratio, 0.16 +/- 0.08 and 0.16 +/- 0.10 in SGA with birth weight < 3rd and 3rd to 10th percentiles versus 0.10 +/- 0.09 in AGA; P = 0.04 and P = 0.03, respectively). SGA children also had lower uric acid excretion despite greater serum uric acid levels (fractional excretion of uric acid, 7.4% +/- 4% and 6.9% +/- 5% versus 10.5% +/- 5.9%; P = 0.02 and P = 0.003, respectively). LIMITATIONS Relatively small sample size, blood pressure was measured on a single visit. CONCLUSIONS Children born SGA showed alterations in calcium and uric acid urinary excretion at preschool age, and blood pressure was related to the severity of growth restriction.

Vitamin D and parathormone levels of late-preterm formula fed infants during the first year of life

Background/Objectives:Preterm infants are at risk for low vitamin D but documentation on late-preterm infants is sparse. This prospective study monitored longitudinally vitamin D and parathormone (PTH) levels in late-preterm formula fed infants during the first year of life, taking into consideration in utero and postnatal growth, and season and diet.Subjects/Methods:The study population comprised 128 infants of gestational age (GA) 32–36 weeks, of which 102 were appropriate (AGA) and the remaining 26 were small for GA (SGA). Serum levels of vitamin D (25(OH)D), PTH calcium, phosphate (P) and alkaline phosphate were estimated at 2 and 6 weeks, and at 3, 6, 9 and 12 months of age.Results:The 25(OH)D levels were relatively low at 2 and 6 weeks in both AGA and SGA infants (21±11, 20±7 ng/ml and 25±16, 23±8 ng/ml, respectively), but increased at 6 months (45±14, 47±10 ng/ml) and remained stable thereafter. SGA infants had lower 25(OH)D levels at 9 and 12 months (AGA 45±14, 47±18 ng/ml vs SGA 38±13, 37±13 ng/ml, P<0.05). Deficiency of 25(OH)D (<20 ng/ml) was found in 18.5% of measurements in 92 (72%) infants, and its insufficiency (20–32 ng/ml) was found in 29.2% of measurements in 99 (77.3%) infants. Most measurements with vitamin D <32 ng/ml were observed at the first three study points, where PTH showed an inverse association with 25(OH)D, reaching a plateau thereafter.Conclusions:Late-preterm, formula fed infants may have suboptimal vitamin D levels and elevated PTH, especially, during the first 3 months. Those born SGA may have lower vitamin D levels up to the end of the first year of life.