José Quero

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism

OBJECTIVEnTo determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism.nnnSTUDY DESIGNnOne hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA).nnnMETHODSnVenous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-alpha, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined.nnnRESULTSnPreterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones.nnnCONCLUSIONSnOur findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.

Intussusception in a preterm neonate; a very rare, major intestinal problem--systematic review of cases.

Abstract Intussusception is an extremely rare disorder in preterm infants and it is often misdiagnosed as necrotizing enterocolitis. We report a case of intussusception in a 30-day-old preterm infant of 26 weeks of gestational age and a birthweight of 610 g who was diagnosed via abdominal ultra sonography. A systematic review of the literature was performed and reports on 23 previous cases were found. The presence of recognizable causes of intussusception in preterms, such as Meckels diverticulum, bowel polypus, etc. was very infrequent. Comorbidity before and after intussusception is heterogeneous and related to prematurity. The intussusception is predominantly located in the small bowel (91,6%)–ileal or jejunal. The condition is misdiagnosed as NEC and managed conservatively until clinical deterioration occurs. A definitive diagnosis is thus established during abdominal surgery, which is usually delayed an average of 9.5 days from the onset of symptoms. Our case illustrates the capability of abdominal ultrasonography to establish early diagnosis of intussusception in the premature newborn.

Higher frequency of uncommon 1.5–2 Mb deletions found in familial cases of 22q11.2 deletion syndrome

Familial 22q11.2 deletions have been reported as a 6%–28% of the total affected cases of 22q11.2 microdeletion syndrome (del22q11.2). Different deletion genotypes have been described for this disorder, with a predominant 3 Mb deletion present in 90% of the cases, a less common 1.5–2 Mb deletion in 8%, and atypical smaller deletions in 2%. We have studied 15 cases of del22q11.2 from 6 families (two of them three‐generation families) that were previously diagnosed through FISH. We have sized the deleted region by allele genotyping of 12–16 polymorphic markers in all cases, and we have found three families affected with the 1.5–2 Mb deletion, two affected with the 3 Mb deletion, and one in which the deletion size could not be determined. This predominance of the smaller 1.5–2 Mb deletions in our familial cases differs from the minor frequency observed in sporadic cases of del22q11.2. This finding suggests that small deletions are more linked to familial inheritance than large ones, possibly due to psychosocial or biological factors associated with differences in the phenotype. Deletion sizing on routine diagnosis may help characterizing the inheritability of 22q11.2 microdeletion syndrome.

Incidencia y prevalencia de la encefalopatía hipoxico-isquémica en la primera década del siglo xxi

AIMnTo examine the incidence and the prevalence of neonatal hypoxic-ischemic encephalopathy (HIE) in a tertiary Spanish center over a 9-year period, before the implementation of a hypothermia program.nnnMETHODSnAll infants > or =34 weeks gestation, born between 2000 and 2008 with evidence of perinatal asphyxia and neonatal encephalopathy were identified. HIE was classified as mild, moderate or severe. Joinpoint regression model was used to identify changes in the trends of HIE incidences.nnnRESULTSnA total of 90,963 live infants were born in La Paz Hospital between 2000 and 2008, and 23.3% of them (21.228) were admitted to the Neonatal Unit. In addition, 200 infants were referred from other centers. A total of 110 infants had HIE, of which 90% were inborn. The overall incidence of HIE was 1.088 per 1,000 live births, and the incidence of clinically significant HIE (moderate and severe grades) was 0.49 per 1,000 live births. The incidence of HIE showed a linear downward trend throughout the study period (slope=-5.37; P<0.05). Fifty-two neonates had moderate or severe HIE, this represents a prevalence of 2.42 per 1,000 infants admitted to the Neonatal Unit and means that 5-6 infants a year would have been candidates for therapeutic hypothermia.nnnCONCLUSIONSnNeonatal HIE, and in particular significant HIE, is an infrequent condition. The low prevalence of HIE requires that these infants are referred to regional centers with sufficient experience in the use of therapeutic hypothermia, and in the management of all the medical problems associated with HIE.

Effect of dexamethasone therapy on cerebral and ocular blood flow velocity in premature infants studied by colour Doppler flow imaging

Abstract Although dexamethasone (DEX) is used widely in neonates with chronic, and even recently with acute respiratory disease, its potential side-effects on human cerebral and ocular haemodynamics remain unknown. The effects of DEX on cerebral and ocular blood flow velocities were assessed in preterm infants with lung disease and mechanical ventilation. Ten ventilated preterm infants received DEX (0.25 mg/kg/12 h) for ongoing chronic lung disease or extubation failure. Colour Doppler flow imaging studies of the internal carotid, anterior cerebral and ophthalmic arteries were made before and 10, 30, 60, 120 and 240 min after the 1st, 3rd, and 5th doses of DEX. Peak systolic, temporal mean, and end-diastolic flow velocities and the resistence index (RI) of Pourcelot were determined. The brain was examined by ultrasonography before and at the end of each Doppler study. All patients were continuously monitored for transcutaneous blood gases and blood pressure. All flow velocities and the RI of the internal carotid, anterior cerebral and ophthalmic arteries showed a similar trend throughout the study. The means of the values averaged for the 240 min of cerebral and ocular blood flow velocity with each dose were progressively higher and the values of the RI progressively lower up to the 5th dose. The most significant changes occurred in end-diastolic flow velocity and consisted of a percentage increase between the 1st and 5th dose of 72% in the internal carotid artery, 102% in the anterior cerebral artery and 84% in the ophthalmic artery. Changes in arterial blood pressure followed a pattern similar to that of changes in blood flow velocity.n Conclusions Dexamethasone increments cerebral and ocular blood flow velocity. We speculate that this finding may be relevant to the development of brain and retinal injury.

Unrelated chromosomal anomalies found in patients with suspected 22q11.2 deletion.

Screening for 22q11.2 deletions has not an easy approach due to the wide variability of their associated phenotype. Many clinical features overlap with those of other known syndromes and reported loci. Patients referred to exclude a 22q11.2 deletion are usually tested with a locus‐specific FISH probe, with 10% positive cases depending on the selection criteria, but patients testing negative for FISH at 22q11.2 may have other chromosomal aberrations in routine cytogenetic analysis. We tested 819 patients suspected of having a 22q11.2 deletion. Eighty‐eight patients (10.7%) were positive for 22q11.2 deletion, whereas 30 patients (3.7%) showed other chromosomal abnormalities involving deletions and duplications, derivative chromosomes, marker chromosomes, apparently balanced and unbalanced translocations and sex chromosome aneuploidies. Of these alterations, 28 did not involve region 22q11 and most had not been associated with 22q11.2 deletion phenotype before. We discuss the similarity of DiGeorge/velocardiofacial syndrome with other known clinical entities and suggest correlations between the new loci and the observed clinical features. The frequency of unrelated chromosomal anomalies reported in this study and in other previous reports highlights the importance of conventional cytogenetic analysis as an initial genome‐wide screening tool in all referred patients, and provides useful data to optimize diagnostic and screening protocols according to the most frequent chromosomal findings.

Growth in Preterm Infants until 36 Weeks' Postmenstrual Age Is Close to Target Recommendations

Objective: To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants. Subjects/Methods: A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks PMA. Results: Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 ± 0.66 at birth to -1.89 ± 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 ± 0.64 at 36 weeks PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks. Conclusion: Despite achieving a protein and energy intake close to the described target intake, the rate of growth in our infants was lower than indicated by the intrauterine growth curve. Lower gestational age, lower birth weight and severe illness had a negative effect on growth.

Cerebrospinal fluid 309-1309-1309-1in neonates with central nervous system infections

Beta2-microglobulin (β2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. β2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T=toxoplasmosis, O=others, R=rubella, C=cytomegalovirus and H=herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF β2m levels compared to neonates with sterile culture (6.24±2.66 vs 1.74±0.5 mg/l;P<0.0001). CSF β2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF β2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98±2.5 vs 3.2±0.25 mg/l;P<0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF β2m was accurate in distinguishing between neonates with and without CNS infection.ConclusionCSF β2m may be a useful ancillary tool in neonates when CNS infection is suspected.

Management of Patent Ductus Arteriosus in Preterm Babies

There is a higher incidence of delayed closure of the patent ductus arteriosus in premature babies with respiratory distress syndrome. From July, 1975, to December, 1977, 57 small, preterm infants with patent ductus arteriosus were diagnosed at our neonatal intensive care unit. From July, 1975, until September, 1976 (first period), 23 patients were diagnosed, and 11 underwent surgical ligation of a patent ductus arteriosus. There were 3 early deaths. From October, 1976, until December, 1977, out of a total of 34 patients with diagnosed patent ductus, 18 were treated with indomethacin, and only 3 required ligation. Our present policy for patent ductus arteriosus with respiratory distress syndrome in the premature baby is to initiate early treatment with indomethacin. If this treatment fails and the infants status deteriorates, we perform early surgical ligation of the ductus in order to minimize the time on mechanical ventilation and lessen the chances of the development of bronchopulmonary dysplasia.

Effects of the cyclooxygenase inhibitor ibuprofen on retinal and choroidal blood flow during hyperoxia in newborn piglets.

PURPOSEnThe effect of the cyclooxygenase inhibitor ibuprofen (IB) on choroidal (ChBF) and retinal (RBF) blood flow during hyperoxia was examined in 21 spontaneously breathing newborn piglets.nnnMETHODSnChBF and RBF were measured using radiolabelled microspheres before and 30 min after either saline or IB (30 mg/kg, i.v.) infusion in room air and subsequently, after 90 min of hyperoxia (O2).nnnRESULTSnThe basal RBF and ChBF did not change after IB infusion. However, during hyperoxia a significant decrease in RBF was observed in the IB group (54 +/- 5 to 37 +/- 3 ml/min/100 g, p < 0.02) and in the control group (54 +/- 3 to 37 +/- 5 ml/min/100 g, p < 0.02). Also, ChBF decreased in the IB group (2,635 +/- 446 to 1,670 +/- 199 ml/min/100 g, p < 0.02) and in the control group, (2,997 +/- 346 to 2,014 +/- 246 ml/min/100 g,p < 0.02) during hyperoxia.nnnCONCLUSIONSnDespite cyclooxygenase inhibition with IB, RBF and ChBF decreased to the same extent as in the control group following exposure to O2. These data suggest that hyperoxia decrease RBF and ChBF through mechanisms and/or mediators other than the cyclooxygenase by-products of arachidonic acid metabolism.