Neonatal acute kidney injury following Valsartan exposure in utero: report of two cases.

BACKGROUND: Maternal sartan intake during pregnancy has been associated with several fetal/neonatal complications related to disturbed renal development. Description of cases: We present two cases of neonatal acute kidney injury (AKI) following valsartan administration during pregnancy and provide evidence for the use of novel AKI biomarkers in these neonates. The first case was a female neonate, delivered at 32+4 weeks of gestation after maternal valsartan intake from 24 to 32 gestational weeks. In the second case, ultrasound examination revealed a growth-restricted fetus with severe oligohydramnios following maternal valsartan intake during the first 29 gestational weeks. In the absence of any improvement in amniotic fluid, the neonate was born at 31+5 weeks. In both cases, AKI was documented after birth, but renal function progressively recovered. Urine cystatin-C and neutrophil gelatinase-associated lipocalin were found abnormally increased during the first week of life. CONCLUSION: Sartan use during pregnancy is associated with the development of neonatal AKI. Novel urine biomarkers may be used to document renal injury. Hippokratia 2016, 20(1): 73-75.

Therapeutic hypothermia in asphyxiated neonates with hypoxic-ischemic encephalopathy: A single-center experience from its first application in Greece.

BACKGROUND/AIM: Therapeutic hypothermia has become an established therapy in asphyxiated neonates with evidence of moderate/severe hypoxic-ischemic encephalopathy. Herein, we describe our recent experience with total body cooling in asphyxiated neonates, which is the first relevant report in Greece. PATIENTS AND METHODS: The medical records of all asphyxiated newborns treated with therapeutic hypothermia in our center between September 2010 and October 2013 were retrospectively reviewed. We recorded data related to neonatal-perinatal characteristics, whole body cooling and outcome. RESULTS: Twelve asphyxiated neonates [median gestational age 38 weeks (36-40)] received whole body cooling (rectal temperature 33.5 ± 0.5 (o)C for 72 hours) during the study period for moderate (n=3) and severe (n=9) hypoxic-ischemic encephalopathy. Cooling was passive in 4 and active in 8 (66.7%) cases. Therapeutic hypothermia was initiated at the median age of 5 hours (0.5-11) after birth. Seven neonates survived (58.3%) to hospital discharge. On follow-up (7-35 months), neurodevelopment outcome was normal in 1 case, while 3, 1 and 2 subjects had mild, moderate and severe impairment, respectively. CONCLUSIONS: Our initial experience with whole body cooling supports its beneficial effect in asphyxiated neonates. This treatment should be offered in all centers involved in the care of such neonates using either simple means (passive cooling) or automated cooling devices. Hippokratia 2014; 18 (3): 226-230.

Neonatal outcomes of late preterm deliveries with pre-eclampsia.

AIM: The aim of the study was to examine the impact of pre-eclampsia on neonatal outcomes of late preterm deliveries. METHODS: A retrospective study was conducted, enrolling pregnancies delivered between 34 0/7 and 36 6/7 weeks of gestation during the period 2004-2007 in a large tertiary center. Pregnancies were divided in group 1, including those complicated with pre-eclampsia and group 2, including normotensive cases. Epidemiological characteristics, mode of delivery and complications contributing in late preterm delivery were initially studied. Neonatal morbidity parameters of our interest included mean Apgar score in the 1st and 5th minute, admission to Neonatal Intensive Care Unit (NICU) and need for emergency intubation. Intrauterine growth retardation (IUGR), low birth weight (LBW) and very LBW (VLBW), respiratory distress syndrome (RDS), hypoglycemia, NICU infection, abnormal cerebral ultrasonographic findings and duration of NICU residence were also compared between the two groups. RESULTS: Out of 363 late preterm pregnancies, 29 (8%) were delivered because of pre-eclampsia. Mean gestational week and birth weight were significantly lower in group 1. The rate of elective caesarean section was also significantly higher in this group. The same observation was made concerning rates of IUGR, LBW and VLBW neonates. Furthermore, incidence of NICU admission and hypoglycemia were significantly higher in the group of infants born by pre-eclamptic mothers. Incidence of RDS and cerebral echo pathology were also higher, but without significant difference when compared to group 2. CONCLUSION: Neonatal adverse outcomes were increased in late preterm infants of pre-eclamptic women in comparison with those of normotensive women.

Serum levels of daptomycin in pediatric patients.

BACKGROUND: Limited data are available on the pharmacokinetics and optimal dosage of daptomycin, a lipopeptide compound possessing activity against Gram-positive bacteria, in the pediatric population, particularly in neonates and infants. We determined serum levels of daptomycin in hospitalized pediatric patients treated with various dosages of this agent. METHODS: Blood samples were obtained from pediatric patients of all ages with normal renal function who had received daptomycin between May 2009 and December 2010. Serum levels prior ("trough") and 30 min after end of the infusion ("peak") were determined using an ultra-performance liquid chromatography-UV detection method. RESULTS: A total of four daptomycin dosages and four patients were studied. Three patients were infants (gestational age: 29-38 weeks, age at sampling 26-65 days) and the fourth was a 7-year-old boy. A dosage of 6 mg/kg/12 h of daptomycin to the infants resulted in trough concentrations of <4-8.4 mg/l and peak concentrations of 10.9-17.7 mg/l. Comparable levels were observed after one of the infants received a dosage of 11 mg/kg/12 h, while a further dosage increase to 15 mg/kg/12 h yielded peak concentrations of 35.5 mg/l. The 7-year-old child received a daptomycin dosage of 12 mg/kg once daily; trough and peak levels were 4.2 and 103.4 mg/l, respectively. CONCLUSIONS: A dosage of daptomycin 6 mg/kg/12 h in small infants results in lower peak and similar trough concentrations compared with a dosage of 4 mg/kg/day administered to adults. This results suggests that daptomycin dosages of more than 6 mg/kg/12 h may be needed for this pediatric age group to achieve a similar drug exposure as adults.

Association of increased maternal ferritin levels with gestational diabetes and intra-uterine growth retardation.

AIM: The objectives of the present study were to determine whether or not increased serum ferritin in women with premature labour is associated with gestational diabetes mellitus (GDM) and intra-uterine growth retardation (IUGR) and, if so, whether or not such increased levels reflect excess maternal iron stores, and have an effect on neonatal iron status and outcome. METHODS: This prospective, single-hospital, observational study involved 63 mothers and their 90 preterm neonates. Full blood counts as well as serum ferritin, soluble transferrin receptor (sTfR) and erythropoietin concentrations were compared across the three study groups based on maternal ferritin levels at the time of delivery. Perinatal history, neonatal morbidity and early outcomes were also assessed. RESULTS: High maternal ferritin levels were significantly associated with higher rates of GDM and IUGR. However, there was no correlation between maternal ferritin and sTfR levels or between maternal and neonatal iron status. CONCLUSION: Elevated maternal ferritin is not a reflection of excess iron stores, but is related to an increased risk of GDM or IUGR. Also, maternal ferritin levels are not associated with either neonatal iron status or neonatal outcomes.

Hydrothorax as a sole manifestation of congenital parvovirus B19 infection.

We present a case of congenital parvovirus B19 infection in a term neonate manifested with isolated massive hydrothorax and mild anemia. Parvovirus B19 DNA was detected in maternal and neonatal blood as well as in pleural fluid despite lack of suggestive serology.

Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection.

UNLABELLED: The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19--PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling METHOD: Healthy neonates had significantly lower percentages of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+) monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.

Evidence of early systemic activation and transendothelial migration of neutrophils in neonates with severe respiratory distress syndrome.

Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and sL-selectin using an enzyme-linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G-CSF and IL-6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL-selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS.

Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial.

The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the neutrophil count and function of preterm neonates with documented sepsis. For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied. Of the 62 patients, 27 septic neonates had an absolute neutrophil count (ANC) > 5000/mm3 (group A) and were scheduled not to receive rhG-CSF and 35/62 had an ANC < 5000/mm3 (n=35) and were randomly assigned either to receive rhG-CSF (group B) or not to receive it (group C). rhG-CSF (10 microg/kg) was administered for 3 consecutive days (0, 1, 2). The ANC, plasma levels of G-CSF (ELISA), neutrophil respiratory burst activity (NRBA) and neutrophil expression of CD11a, CD11b and CD11c (flow cytometry) were measured in all septic neonates on days 0 (onset of sepsis), 1, 3 and 5 and in the healthy neonates once within the first 2 days of life. We found that on day 0, G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones. The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates. Administration of rhG-CSF resulted in a rapid and significant increase in ANC, NRBA and CD11a, CD11b and CD11c expression that persisted throughout the follow up. CONCLUSION; The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and beta2 integrin expression.

Cerebrocostomandibular syndrome in four sibs, two pairs of twins.

We report four sibs, two pairs of twins, with cerebrocostomandibular syndrome (CCMS). The family history was negative. All four babies had the characteristic features of CCMS, including Pierre-Robin anomalad and rib dysplasia. Cerebral involvement was evident in two of the patients who had suffered perinatal asphyxia. The presence of the syndrome in all four sibs together with the negative family history in previous generations is consistent with Mendelian autosomal recessive inheritance with high penetrance.

Prophylactic intravenous administration of immune globulin in preterm infants: effect on serum immunoglobulin concentrations during the first year of life.

In a prospective study, serum IgG, IgA, IgM, and IgG subclass levels of 66 preterm infants (gestational age less than or equal to 34 weeks) were measured sequentially from birth to 12 months of life. Infants were divided into two groups, comparable for gestational age, birth weight, sex, and intensive care, on the basis of admission order: the treatment group, consisting of 33 infants who received intravenous immune globulin therapy (0.5 gm/kg at 10-day intervals) prophylactically, and the control group, consisting of 33 infants who did not receive. Twenty of the 33 treated infants received only one infusion and the remaining 13 received two to five infusions. The mean number of infusions per neonate was 1.96. Immunoglobulin measurements showed that the proportion of infants with an IgG level of greater than or equal to 7 gm/L on the tenth and thirtieth days of life was significantly higher in the treatment than in the control group (p less than 0.01). At the same ages, mean serum IgG, IgG1, and IgG2 concentrations were significantly higher in the treatment group (p less than 0.001). Thereafter levels in both groups fell progressively, reaching their lowest point between 3 and 5 months of age. During this period, profound hypogammaglobulinemia (IgG less than 2 gm/L) was observed in 3 of 33 treated and 11 of 33 untreated infants (p less than 0.05). By 3 months of age, mean serum total IgG concentrations were still significantly higher in treated than in untreated infants (p less than 0.05), but the IgG subclass concentrations were not. After the third month, no significant differences between the two groups were observed. Moreover, the sequentially measured serum IgA and IgM levels in the two groups remained comparable from birth to age 12 months. The IgG level at different ages from 3 to 12 months was not correlated with either birth weight or the number of infusions performed during the neonatal period (p greater than 0.1). We conclude that prophylactic intravenous administration of immune globulin to preterm infants with a birth weight of 1000 to 2000 gm, at a dose of 0.5 gm/kg every 10 days, results in maintenance of a satisfactory serum IgG level throughout the high-risk period for infections. Such treatment does not have a suppressive effect on subsequent serum immunoglobulin concentrations.