Acute Kidney Injury in Neonatal Hypoxic-Ischemic Encephalopathy Patients Treated with Therapeutic Hypothermia: Incidence and Risk Factors.

Studies in infants with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia have generally focused on neurological outcomes. Although acute kidney injury (AKI) rate decreased in advent of therapeutic hypothermia (TH), it is still a common and important entity. In this retrospective study, we aimed to investigate the risk factors for AKI in HIE patients treated with hypothermia. Infants treated with TH due to HIE were reviewed retrospectively and infants who developed AKI and not were compared. Ninety-six patients were enrolled in the study. AKI developed in 27 (28%) patients and 4 (14.8%) of them were stage III AKI. In the AKI group, gestational age of the patients was significantly higher (p = 0.035), the 1st minute Apgar score was significantly lower (p = 0.042), and convulsions (p = 0.002), amplitude-integrated electroencephalography disorders (p = 0.025), sepsis (p = 0.017), need for inotropic therapy (p = 0.001), need of invasive mechanical ventilation (p = 0.03), and systolic dysfunction in echocardiography (p = 0.022) were significantly higher. In logistic regression tests, Apgar score at the 1st minute was found to be independent risk factor for developing AKI. AKI has the potential to worsen the neurological damage and correlates with morbidities of perinatal asphyxia. It is important to determine the incidence and risk factors for developing AKI in this delicate group of patients to prevent further renal damage.

The association between NIRS and Doppler ultrasonography in preterm infants with patent ductus arteriosus.

Objective: To determine if near-infrared spectroscopy (NIRS), which is easier to obtain than Doppler ultrasonography (USG), may be used in accordance with Doppler USG to provide additional data for assessment of organ blood flow velocities in preterm infants with hemodynamically significant PDA.Study design: Thirty-one infants who were treated with ibuprofen for closure of PDA were monitored continuously with NIRS. Cerebral, mesenteric, and renal arterial blood flow velocities were measured with Doppler USG before and after the treatment.Results: While cerebral, mesenteric, and renal fractional oxygen extraction (FTOE) measurements decreased significantly (p = .042, p < .001, p < .001, respectively), NIRS measurements (p = .016, p < .001, p < .001, respectively) and mean blood flow velocities (p = .003, p = .011, p = .002, respectively) increased significantly after the treatment. There was a significant correlation between pretreatment cerebral and mesenteric FTOE and resistive index (RI) values (r = 0.45, p = .01, and r = 0.46, p = .01, respectively). However, no correlation was observed between renal FTOE values and renal RI (r = 0.33, p = .06). Posttreatment cerebral, renal, and mesenteric FTOE values correlated positively with corresponding RI (r = 0.41, p = .02; r = 0.39, p = .02; r = 0.65, p < 01; respectively). Pretreatment and posttreatment cerebral, mesenteric, and renal FTOE values and arterial mean velocities were inversely correlated (pretreatment: r = 0.69, p < .01; r = 0.72, p < .01; r = 0.77, p < .01; posttreatment: r = 0.54, p = .01; r = 0.69, p < .01; r = 0.38, p = .01; respectively).Conclusion: As Doppler and NIRS measurements correlated significantly, we concluded that NIRS might be used in monitoring organ blood flow in preterm infants with PDA, which may provide additional data for management of this condition.

THROMBOCYTOPENIA AS A RISK FACTOR FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To study the association between thrombocytopenia and retinopathy of prematurity (ROP). METHODS: The case-control study was conducted on preterm newborns with ROP between January 2011 and January 2014, retrospectively. The patients were assigned into two groups: Cases required intervention and controls developed no or Stage I ROP. RESULTS: Eighty-one premature infants with Type I ROP were enrolled to the study with a mean gestational age of 27.6 ± 2.1 (range: 24-32) weeks and birth weight of 993 ± 292 (range: 560-1,930) g. Mean follow-up time was 38.3 ± 2.7 weeks (min: 32 and max: 46 weeks). Cases were individually matched to a set of controls (1:1 ratio). Thrombocytopenia (<150.000/mm) was seen in 58 (71.6%) of the cases with Type I ROP, whereas only 17 (21%) of the controls had thrombocytopenia (P < 0.001). Logistic regression analysis showed that bronchopulmonary dysplasia and thrombocytopenia were significantly associated with Type I ROP (relative risk [95% confidence interval]: 4.19 [1.47-12] and 6.69 [2.83-15.9], respectively). The thrombocytopenia ratio (P = 0.073), thrombocytopenia 1 week before intervention (P = 0.076) and platelet transfusion ratio (P = 0.062) tended to be higher in Zone I ROP compared with Zone II ROP. CONCLUSION: In our study, there was a significant association between thrombocytopenia and Type I ROP.

Massive pleural effusion on the contralateral side of a venous peripherally inserted central catheter.

A preterm newborn infant, delivered at 30 weeks of gestation and 965 g birth weight, developed respiratory distress with resistant hypoxia after a central catheter line was inserted via the right venae brachialis on postnatal day 21. Left-sided massive pleural effusion, collapsed left lung with air bronchograms, and bidirectional shunting through reopened ductus arteriosus were detected by targeted neonatal echocardiography. Hydrothorax was drained under sonographic guidance, producing a milky-white fluid biochemically compatible with parenteral nutrition. We report this case of hydrothorax secondary to a misplaced central catheter on the contralateral side of its peripheral insertion. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:140-144, 2018.

A pioneering study: oral clarithromycin treatment for feeding intolerance in very low birth weight preterm infants.

PURPOSE: To examine the prokinetic effect of clarithromycin in very low birth weight (VLBW) preterm infants. MATERIALS AND METHODS: VLBW preterm infants who have not achieved half of the full enteral feeding in the second week of life were enrolled in the study. The infants enrolled in the study were randomized. Twenty infants received oral clarithromycin (7.5 mg/kg, twice a day) and 20 control infants did not receive any treatment. RESULTS: Full enteral feeding was attained earlier in the clarithromycin group than in the control group [7 (6-9) versus 9 (9-11) days, respectively; p < .001]. Duration of parenteral nutrition and number of withheld feeds were significantly lower in the clarithromycin group (p = .013 and p < .001, respectively). Parenteral nutrition-associated cholestasis (n = 1 versus 3, p = .1) and length of hospital stay (50 versus 59 median days, p = .1) tend to be lower in the clarithromycin group without any statistical significance. We observed no adverse effect of clarithromycin therapy. CONCLUSIONS: Clarithromycin treatment in VLBW preterm infants resulted in better toleration of enteral feeding. Larger randomized controlled trials are needed to establish routine use of clarithromycin in the treatment of feeding intolerance.

Effect of Intraventricular Hemorrhage on Cerebellar Growth in Preterm Neonates.

The aim of this study is to evaluate cerebellar growth of preterm infants with intraventricular hemorrhage. Vermis height (VH) and transverse cerebellar diameter (TCD) were measured by cranial ultrasound in 18 preterm infants (26-30 weeks) with intraventricular hemorrhage (IVH) at first 3 days of life and at term equivalent age (TEA). IVH was diagnosed by ultrasonography and scaled in accordance with the definitions by Papile et al. Measurements were compared with 18 preterm (26-30 weeks) infants without IVH. Both VH and TCD of preterm infants with IVH were significantly lower than those of preterm ones without IVH at TEA (p < 0.001). No significant difference was found for head circumference (p = 0.158) and weight (p = 0.092). In subgroup analysis, preterm infants with grades 3-4 IVH had significantly lower TCD (p = 0.008) and head circumference (p = 0.033) than the ones with grades 1-2 IVH. However, VH (p = 0.102) and weight (p = 0.480) did not show any difference between these subgroups. IVH may have a significant impact on cerebellar growth on preterm infants at TEA, specially those with a severe IVH. TCD is affected more than VH.

Serum lactate levels and perfusion index: are these prognostic factors on mortality and morbidity in very low-birth weight infants?

AIM: Early hemodynamic assessment of global parameters in critically ill newborns fails and requires mostly invasive measurements in neonatal intensive care unit. Clinical signs are frequently used for assessment of peripheral perfusion. Perfusion index (PI) is a new noninvasive numerical value of peripheral perfusion. Serum lactate levels and PI are the indicators that are important in determining prognosis of preterm infants. In this study, we aimed to investigate the relationship of serum lactate levels and PI with mortality and morbidity in very low-birth weight infants (VLBW). STUDY DESIGN: This study was conducted between July 2014 and July 2015 in a Level III NICU. The study enrolled preterm infants with a gestational age ≤ 32 weeks, birth weight ≤ 1500 g. Serum lactate levels from blood gases and PI, SpO2 measurements were recorded at 1st, 12th and 24th hours by using a new generation pulse-oximeter. Morbidities and mortalities were documented. RESULTS: A total of 60 VLBW infants were enrolled the study. Mean birth weight and gestational age were 991 ± 288 g and 27.5 ± 2.5 w, respectively. Retinopathy of prematurity (ROP) was significantly higher in the patients with high lactate levels (>4 mg/dl) at 1st hour and low-PI levels (<0.5) at 12th hour of life (p = 0.042, p = 0.015), respectively. Bronchopulmonary displasia (BPD) was significantly higher in the patients with low PI (< 0.5) at 1st hour. Lactate and PI values were not significantly correlated with necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, sepsis and mortality. CONCLUSION: High lactate levels (> 4 mg/dl) and low PI (< 0.5) could be used as early parameters for prediction of ROP and BPD. This data suggests that in VLBW infants lactate levels and PI parameters during the first 24 h will be effective in determining the prognosis of the disease. We believe that larger, randomized controlled clinical trials are likely to establish the true benefit.

Effect of Single Intravitreal Bevacizumab on Ophthalmic and Middle Cerebral Arterial Blood Flow in Retinopathy of Prematurity.

PURPOSE: To evaluate the effect of a single intravitreal bevacizumab (IVB) injection on blood flow parameters in the ophthalmic artery (OA) and middle cerebral artery (MCA) in infants with retinopathy of prematurity (ROP). MATERIALS AND METHODS: This prospective and interventional study included 15 infants with ROP who were treated with IVB. Peak systolic velocity (PSV), end-diastolic velocity, mean velocity (MV) and resistivity index were measured using pulse wave Doppler ultrasonography (Philips En Visor C, Amsterdam, The Netherlands) in the OA and MCA, before IVB injection and 1 day, 1 week and 1 month after IVB injection. RESULTS: Measurements of PSV-OA, MV-OA and PSV-MCA showed significant changes after IVB treatment (p = 0.01, p = 0.02, p = 0.02, respectively). The PSV-OA measurements at 1 week and 1 month were significantly lower than the baseline PSV-OA measurement (p = 0.03 and p = 0.01, respectively). The MV-OA measurement was significantly lower at 1 month following IVB as compared to the baseline MV-OA measurement (p = 0.03). The PSV-MCA showed a significant decline 1 day after IVB injection (p = 0.03). CONCLUSIONS: The study demonstrated that IVB causes significant alterations in blood flow parameters in the OA and MCA predicted by Doppler ultrasonography in infants with ROP.

Prenatal diagnosis and outcomes of fetal teratomas.

PURPOSE: Our aim was to evaluate the diagnostic performance of ultrasonography (US) in the prenatal identification of teratomas and the perinatal outcome of the fetuses with those teratomas. METHODS: In this retrospective case series study, we searched the archives using the keywords "fetal mass" or "fetal tumor" or "fetal teratoma" and "sacrococcygeal teratoma," diagnosed between 2009 and 2014, within the US database of our center. RESULTS: One hundred seven fetuses were prenatally diagnosed as having a cystic or solid mass, tumor, or teratoma. Nineteen of those cases were diagnosed prenatally as having fetal teratoma, but that diagnosis could not be verified in three cases. In one fetus, the prenatal diagnosis could not be confirmed. The sensitivity of US in identifying fetal teratoma was 100% and the false-positive rate, 3.3%. Six pregnancies complicated by a fetal teratoma were terminated. A normal karyotype was identified in all fetuses that underwent karyotyping. Among the nine women who continued their pregnancy, polyhydramnios was identified in four fetuses; although high-output heart failure was also identified in two of those fetuses during prenatal follow-up, none developed hydrops. On delivery, nine infants were born alive, but three (33.3%) of them died within the early neonatal period. CONCLUSIONS: US has very high sensitivity and low false-positive rates in identifying fetal teratoma prenatally. The risk of chromosomal abnormalities is very low in fetuses with teratoma, and their prognosis depends on the location and size of the tumor and any associated perinatal complications.

Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants?

OBJECTIVES: To compare the efficacy of oral and intravenous paracetamol for closure of hemodynamically significant patent ductus arteriosus (HSPDA) in very low birth weight (VLBW) preterm infants. METHODS: Eighteen VLBW infants with HSPDA treated with either intravenous (n = 10) or oral (n = 8) paracetamol at 60 mg/kg/d for three consecutive days were analysed retrospectively. Ductal closure rate and evaluation of liver function tests were the major outcomes. RESULTS: After two courses of treatment, HSPDA closure rate was higher in oral paracetamol group than that in the intravenous paracetamol group (88% versus 70%), but it was not statistically significant (p = 0.588). Liver function tests were normal after the treatment. CONCLUSION: Although it was not statistically significant, the cumulative closure rates were higher in oral paracetamol group than those in the intravenous group. Larger trials are needed to confirm these data.

Effect of Prematurity on Cerebellar Growth.

The aim of this study was to evaluate cerebellar growth of preterm infants. Vermis height and transverse cerebellar diameter were measured by cranial ultrasonography in 38 preterm infants (27-32 weeks) at birth and term equivalent age. Measurements were compared with 40 term appropriate-for-gestational-age infants. Preterms at term equivalent age had larger vermis height than term infants (2.39 ± 0.25 cm vs 2.25 ± 0.18 cm, P = .005), whereas no significant difference was found in the transverse cerebellar diameter (5.32 ± 0.38 cm vs 5.44 ± 0.23 cm, P = .13). Vermis height and transverse cerebellar diameter of appropriate-for-gestational-age preterm infants (n = 29) were found larger than small-for-gestational-age ones (n = 9). Vermis height and transverse cerebellar diameter at term equivalent age of appropriate-for-gestational-age preterm infants born before and after 29 weeks of age showed no significant difference. Cerebellar growth is preserved in extreme preterms. However, being small for gestational age may have deleterious effects on cerebellar development.

Intestinal blood flow by Doppler ultrasound: the impact of clarithromycin treatment for feeding intolerance in preterm neonates.

OBJECTIVE: To compare the blood flow velocities of superior mesenteric artery (SMA) before versus after clarithromycin treatment for feeding intolerance in very low-birth weight infants. METHODS: A prospective study was conducted in a group of infant <1500 g with feeding intolerance who received clarithromycin 7.5 mg/kg/dose bid. Before and at the third day of the clarithromycin therapy, SMA blood flow velocity was measured with Doppler ultrasound. RESULTS: SMA peak systolic velocity (PSV) and mean systolic velocity (MV) on the third day of the treatment was found significantly higher than the initial measurement (p = 0.013 and p = 0.027, respectively). End diastolic velocity of the SMA did not change with clarithromycin therapy (p = 0.113). There were no significant changes about pulsatility and resistive index of SMA with regard to clarithromycin therapy. CONCLUSION: Clarithromycin effects the splanchnic circulation. The rise in PSV and MV in SMA is remarkable. These results suggest that the splanchnic blood flow increases significantly after clarithromycin usage.

Does being born small-for-gestational-age affect cerebellar size in neonates?

OBJECTIVE: To investigate how cerebellar vermis height (CVH) and transverse cerebellar diameter (TCD) measurements are affected in SGA neonates. METHODS: A total of 176 [88 SGA and 88 appropriate for gestational age (AGA)] neonates between 26 and 42 weeks of gestation were included. Midsagittal plane through the anterior fontanel and coronal plane through the left mastoid fontanel were used to measure CVH and TCD, respectively. CVH and TCD values were considered normal when they were ≥ 10th percentile, according to nomograms of AGA neonates. RESULTS: Thirty-six asymmetric SGA neonates, 52 symmetric SGA neonates and their 88 gestational age-matched AGA controls were studied. The percentages of neonates with normal CVH and TCD in the symmetric SGA sub-group were significantly lower than those in the AGA and asymmetric SGA sub-groups. The percentages with normal CVH and TCD in the asymmetric SGA sub-group were also found to be low when compared with the AGA sub-group. CONCLUSION: Growth and development of cerebellum may be less spared in SGA neonates. Further studies with larger series are needed in order to evaluate how being born SGA (symmetric and asymmetric) affects cerebellar size and also to see how these findings influence the neurocognitive outcomes of these infants at long-term follow-up.

Can Fecal Calprotectin Level Be Used as a Markers of Inflammation in the Diagnosis and Follow-Up of Cow's Milk Protein Allergy?

PURPOSE: Calprotectin is a cytosolic protein with immunomodulatory, antimicrobial, and antiproliferative actions. The concentration of calprotectin increases in infection, inflammation, and malignancy. We determined if calprotectin can be used as a marker for the diagnosis and follow-up of bowel inflammation in cow's milk protein allergy (CMPA). METHODS: In total, 32 patients newly diagnosed with CMPA were included (24 IgE-mediated, 8 non-IgE-mediated). In all subjects, a complete blood count, total IgE, cow's milk-specific IgE, and fecal calprotectin (FC) were assessed before and after a cow's milk protein (CMP) elimination diet was started. The results were compared with those of 39 healthy children. RESULTS: The mean FC value before the CMP elimination diet was 516±311 µg/g in the 32 patients with CMPA and 296±94 µg/g in the control group (P=0.011). The mean FC value after the diet in these patients was 254±169 µg/g, which was significantly different from the mean value before the CMP elimination diet (P<0.001). When we compared FC levels before the CMP elimination diet in the IgE-mediated group with the control group, we found no significant statistical difference (P=0.142). The mean FC value before the CMP elimination diet was 886±278 µg/g in the non-IgE-mediated group and 296±94 µg/g in the control group; this difference was statistically significant (P<0.001). In the IgE-mediated and non-IgE-mediated groups, FC values after CMP elimination diet were 218±90 µg/g and 359±288 µg/g, respectively, and FC values before CMP elimination diet were 392±209 µg/g and 886±278 µg/g, respectively; these differences were statistically significant (P=0.001 and P=0.025, respectively). CONCLUSIONS: FC levels may be a useful marker for follow-up treatment and recurrence determination in CMPA.

A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects.

Multicentric osteolysis with nodulosis and arthropathy (MONA, NAO (OMIM no. 605156)) is an autosomal recessive member of the 'vanishing bone' syndromes and is notable for the extent of carpal and tarsal osteolysis and interphalangeal joint erosions, facial dysmorphia, and the presence of fibrocollagenous nodules. This rare disorder has been described previously in Saudi Arabian and Indian families. We now report on the first Turkish family with MONA, further confirming the panethnic nature of this disease. Strikingly, and in addition to the previously noted skeletal and joint features, affected members of this family also had congenital heart defects. Molecular analysis identified a novel MMP2 inactivating mutation that deletes the terminal hemopexin domains and thus confirmed the diagnosis of MONA. On the basis of these findings, we suggest that cardiac defects may also represent a component of this syndrome and thus a physiologically relevant target of MMP-2 activity.