A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate.

BACKGROUND: Bartter syndrome (BS) is a rare congenital salt-losing renal tubular transport disorder, characterized by salt wasting, polyuria, biochemical abnormalities, and acid-base homeostasis imbalance. The syndrome has five different genetic forms, and novel mutations of CLCNKB gene lead to type 3 BS also known as classic BS. In this case, we report clinical and molecular findings from a newborn baby with BS. CASE: A 10-day-old male infant born at 37 weeks of gestation by cesarean section following a pregnancy complicated with polyhydramnios, and fetal distress to a 30-year-old gravida 3, para 3 mother, with a 2500 g birth weight was brought to the pediatric emergency department due to weight loss and jaundice. The neonate was referred to the neonatal intensive care unit (NICU) with a preliminary diagnosis of hyponatremic dehydration (Na: 122 mmol/L, 10% dehydration) and hypokalemic hypochloremic metabolic alkalosis (K: 2.13 mmol/L, Cl: 63 mmol/L, pH: 7.62, pCO2 : 39 mmHg, HCO3 : 40.8 mmol/L, BE: 16.9 mmol/L), and hypocalcemia (ionized Ca: 0.72 mmol/L). On arrival to the NICU, symptomatic focal seizures, and polyuria complicated his course. Spot urine biochemistry revealed a renal salt wasting and hypercalciuria: Creatine 11.4 mg/dL Na: 51 mmol/L (54-150), K: 26 mmol/L (20-80), Cl: 164 mmol/L, fractional excretion of sodium (FENa): 3% (0.9-1.6), fractional excretion of chloride (FECl): 17% (<0.5%) and Ca/Cr: 0.33 (<0.2). Biochemical abnormalities disappeared through intravenous fluid and electrolyte therapy, but he could not achieve adequate weight gain, and polyuric urine output (6.5 cc/kg/h), and metabolic alkalosis continued as the enteral feedings advance. Patient's serum renin: 184 pg/mL (5-27 pg/mL) and aldosterone: 1670 pg/mL (1-180 ng/dL) were elevated. Polyuria, renal salt wasting, electrolyte and acid-base disturbances, and hyperreninemic hyperaldosteronism established the diagnosis as Bartter syndrome. An oral indomethacin (1 mg/kg/day) treatment, on the 8th day. ensured the weight gain, and normalized daily urine output. He achieved the goal of birth weight on the 30th day and he was 3520 g weight at discharge on day 42. The genetic tests of the patient as KCNJ1 SLC12A1 gene sequence analysis revealed a novel homozygous mutation in the 14th exon of the CLCNKB gene, the c.1334_1338del CTTTT (p. Ser445fs*4) variant was identified. DISCUSSION: The diagnosis of BS should be considered in the presence of a medical history of severe polyhydramnios of fetal origin. Postnatally, polyuria, signs of dehydration, renal salt wasting, and hypokalemic-metabolic alkalosis should prompt the clinician to request genetic testing for BS in the neonatal period. This case is presented to emphasize that early diagnosis of BS should be considered in newborns presenting with electrolyte abnormalities and metabolic alkalosis accompanying dehydration and favorable growth results can be achieved by starting indomethacin treatment in the early neonatal period. The clinical exome sequencing illustrated a novel missense variant in the CLCNKB gene leading to the molecular diagnosis of BS type 3.

Transient Neonatal Diabetes Mellitus and Seizure with an Unknown Etiology.

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes, usually occurring in the first 6 months of life. Here, we present a newborn, which was admitted with epileptic seizure on the postnatal second day of life. Sepsis and meningitis were ruled out. Cranial imaging and electroencephalography revealed normal. She developed transient NDM on the follow-up and was diagnosed to carry an ABCC8 mutation. Although the neurological features are more common in patients with KCJN11 mutations, patients with ABCC8 mutations could also represent with subtle neurodevelopmental changes or even with epileptic seizures. The genetic testing and appropriate therapy is important in this patient group for predicting clinical course and possible additional features.

The impact of initial hematocrit values after birth on peri-/intraventricular hemorrhage in extremely low birth weight neonates.

AIM: Peri-/intaventricular hemorrhage (P/IVH) is a common condition in preterm neonates and is responsible for substantial adverse neurological outcome especially in extremely low birth weight infants. As hematocrit after birth is a surrogate marker for blood volume, this study aimed to evaluate the effect of initial hematocrit values after birth on P/IVH development in extreme low birth weight (ELBW) neonates. PATIENTS AND METHODS: A prospective cohort analysis of 92 eligible ELBW neonates was performed. The relationship between initial hematocrit values in ELBW neonates after birth and subsequent development of P/IVH was examined. RESULTS: Twenty-nine of 92 infants developed P/IVH. There were significant differences in initial Hct and maximum carbon dioxide (max PCO2) in the first 3 days levels in the P/IVH group compared with no P/IVH group. Initial Hct level at birth in the P/IVH group were significantly lower than the no P/IVH group while max PCO2 in the first 3 days were found to be significantly high in the P/IVH group. There were no significant differences in other baseline demographic, perinatal, and neonatal characteristics while in univariate analysis, higher gestational age and initial Hct were associated with decreased likelihood of P/IVH. In multiple regression analysis after adjustment, only initial Hct remained significantly associated with P/IVH. There was no difference between the population by subgroups of IVH (IVH I-II and IVH III-IV) according to hematocrit and the severity of IVH. CONCLUSION: Higher initial Hct at birth is associated with decreased P/IVH in ELBW infants. We hypothesized the argument that ELBW infants who have lower initial Hct at birth have less suboptimal volume status that predisposing lower cerebral blood flow and the resultant decrease in cerebral blood flow precede the development of P/IVH.

Tolvaptan Response in a Hyponatremic Newborn with Syndrome of Inappropriate Secretion of Antidiuretic Hormone.

The use of tolvaptan to treat both euvolemic and hypervolemic hyponatremia has rapidly increased in recent years. However, data on its effects on children, especially newborns and infants, are limited. Here, we present a newborn who developed syndrome of inappropriate secretion of antidiuretic hormone following an intracranial hematoma drainage operation who was unresponsive to conventional treatments. The infant was successfully treated with tolvaptan, a competitive inhibitor of the vasopressin V2 receptor.

Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage.

OBJECTIVE: Our objective was to determine the neurodevelopmental outcome at 18-24 months' of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH). METHODS: This was a retrospective cohort study of all preterm infants who were <37 weeks' gestation, had Grade 3-4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. Severe IVH was defined as the presence of grade 3-4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18-24 months' CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness. RESULTS: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3-4). Of them, 74 (71.1%) infants (group 1 = 31, group 2 = 29 and group 3 = 14 infants) completed the follow-up visit and evaluated at 18-24 months' CA. Median Apgar score (p < 0.01) and resuscitation at birth (p < 0.01) were significantly different for groups 1-3. The use of catheterization, need for mechanical ventilation, need for phototherapy, retinopathy of premature and bronchopulmonary dysplasia were significantly higher in group 1 compared to groups 2 and 3 (p < 0.001, p < 0.001, p < 0.01, p < 0.01 and p = 0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p = 0.03 and p = 0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p = 0.68 and p = 0.068). CONCLUSION: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.

Transient ileus associated with the use of mydriatics after screening for retinopathy of prematurity in a very low birth weight infant.

Very low birth weight (VLBW) infants have ophthalmologic examinations for retinopathy of prematurity (ROP) prior to discharge, with appropriate follow-up and intervention where appropriate. Eye drops such as cylopentolate, tropicamide, and phenylephrine are used at different concentrations to provide proper pupil dilation for screening ROP. Topical instillation of eye drops may cause mild or severe ocular or systemic adverse effects. Early recognition of systemic toxicity after eye drop instillation is important. The authors present a case of a VLBW infant who developed significant abdominal symptoms (mimicking ileus) that were significant enough to discontinue oral feeding after ocular instillation of 0.5% tropicamide and 2.5% phenylephrine eye drops for routine examination of ROP. After structural and functional gastrointestinal disorders and sepsis were excluded, symptoms resolved completely after discontinuation of the drug. This report is thought to be the first in the medical literature to address 5% tropicamide and 2.5% phenylephrine eye drops, and the combination that may lead to serious complication after ROP examinations.

Is folic acid supplementation really necessary in preterm infants ≤ 32 weeks of gestation?

OBJECTIVES: The aim of this study was to define whether there was folate deficiency in hospitalized preterm infants, and, second, to define the effect of feeding modalities on serum folate levels. METHODS: Infants born ≤ 32 weeks of gestation were included in the study. Blood samples for the determination of serum folate levels were obtained on days 14 and 28 postnatally, as well as 36 weeks postconceptionally (or just before discharge if patients are discharged <36 weeks)--samples A, B, and C, respectively. Infants were divided into 3 groups based on mode of feeding; human breast milk (HBM), fortified HBM (fHBM), or preterm formula (PF). RESULTS: A total of 162 preterm infants were enrolled: 17 (10.5%) of whom received HBM alone, 94 (58%) received fHBM, and 51 (31.5%) were fed with PF. None of the preterm infants developed folate deficiency during the study period. Preterm infants in the fHBM and PF groups had significant higher serum folate levels in samples C when compared with those receiving HBM alone (P < 0.001 for both). Multivariate analysis to evaluate the effects of maternal supplementation, smoking habit, gestational age, birth weight, and cumulative folic acid intake in samples A, B, and C suggested that maternal smoking and maternal folic acid supplementation had significant effects on serum folate levels in sample A and B. CONCLUSIONS: Preterm infants receiving parenteral nutrition with high folic acid content have no risk of folate deficiency during the 2 months of age; however, preterm infants fed orally from birth with HBM or PF with a low folic acid content could be at risk for folate deficiency, especially when mothers are smokers and/or do not receive folic acid supplementation during pregnancy.

A neonate with subcutaneous fat necrosis after passive cooling: does polycythemia have an effect?

Subcutaneous fat necrosis (SCFN) is an inflammatory disorder of adipose tissue. The main risk factors for the development of SCFN are perinatal asphyxia and hypothermia. Presented here is a case of a newborn who developed SCFN in association with polycythemia and hypocalcemia following treatment by passive cooling. Neonates who undergo passive or whole body cooling therapy should be closely monitored for any signs of SCFN.

The effect of whole-body cooling on hematological and coagulation parameters in asphyxic newborns.

Although moderate therapeutic hypothermia is the only proven neuroprotective therapy in neonatal hypoxic ischemic encephalopathy secondary to perinatal asphyxia (PA), there is lack of data for its effect on hemostasis. To investigate the effect of neonatal asphyxia on hemostasis and to evaluate the effect of whole body cooling on hematological parameters. Hematological parameters evaluated on the first day of patients with PA before start of hypothermia were compared with those of healthy controls. The effects of whole body cooling on the same parameters were also evaluated on the fourth day. A total of 17 neonates with PA and 15 healthy controls were included. Mean values for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and d-dimer obtained on the first day were significantly higher in the PA group compared to healthy controls (P ≤ .001 for all comparisons), whereas platelet count, levels of fibrinogen, factors II, V, VII, IX, X, and XI were significantly lower (P ≤ .005 for all comparisons). Levels of factor XIII were normal in both groups. In the study group, mean values for PT, INR, aPTT, and d-dimer evaluated on postnatal day 4 were significantly lower compared to values obtained on the first day of birth in PA group (P < .05 for all comparisons), with statistically significant increases in mean levels of fibrinogen, factor II, V, VII, IX, X, and XII (P < .05 for all comparisons). PA results in significant reductions in levels of factors of the extrinsic pathway and has been associated with thrombocytopenia and disseminated intravascular coagulation. Hypothermia may actually improve the clinical picture in such patients rather than aggravating the hemostatic disturbance, particularly with the implementation of supportive treatment.

A comparison of different methods of temperature measurement by mothers and physicians in healthy newborns.

OBJECTIVE: To compare the accuracy of digital axillary thermometer (DAT), rectal glass mercury thermometer (RGMT) and infrared forehead skin thermometer (IFST) measurements made by mothers and physicians in healthy newborns. METHODS: The body temperature measurements of 120 healthy newborns were made on their 2nd day of life using DAT, RGMT and IFST, first by mothers followed by a designated physician. Correlation analysis was performed for the measurements obtained by mothers and the physician. The presence of a former child or children at home, the educational level of the mother and maternal age were also recorded. RESULTS: No correlation was observed between the measurements made by mothers and the physician using RGMT (R(2) = 0.096). The temperatures measured by mothers and the physician showed a significant correlation when a DAT and IFST were used (R(2) = 0.923, p < 0.001; R(2) = 0.916, p < 0.001, respectively). CONCLUSIONS: Difficulty of use and interpretation make RGMTs less practical than DATs and IFST for use by mothers. Measurements with an IFST are obtained from a newborn's forehead in a shorter length of time compared to DATs, which makes it a more practical option.

Risk Factors for Hospitalization due to Lower Respiratory Tract Infection in Preterm Infants on Palivizumab Prophylaxis.

OBJECTIVE: To determine the risk factors associated with lower respiratory tract infections (LRTI) related hospitalizations in preterm infants receiving palivizumab throughout the high season for respiratory syncytial virus (RSV) infection. METHODS: Premature infants who were commenced on palivizumab prophylaxis during the RSV season were included in the study following parental consent. Information on demographic, social, prenatal and postnatal clinical characteristics was recorded and risk factors associated with hospitalization were evaluated for each patient. FINDINGS: While 234 participants (Group 1, 92.8%) did not require hospitalization during the study period, 18 patients (Group 2, 7.2%) were hospitalized at least once for LRTI during the RSV season. The rate of moderate-severe bronchopulmonary dysplasia (BPD) was significantly higher in group 2 compared to group 1 (38.9% vs 16.2%; P=0.016). Of the 18 infants who were hospitalized, 6 (33.3%) tested positive for RSV while the remaining 12 patients (66.7%) were negative for RSV. Odds ratio (OR) analysis of several risk factors revealed the presence of BPD (OR: 3.28; 95%CI: 1.19-9), being from a family with low socioeconomic status (OR: 3.64; 95%CI 1.08-12.3) to be associated with a higher likelihood of LRTI-related hospitalization. CONCLUSION: Our data demonstrated that RSV is an important LRTI agent and cause of hospitalization especially in preterm infants with additional risks such as BPD, gestational age of <28 weeks and low socioeconomic status. We suggest that improving care conditions and decreased BPD with prematurity would help in prevention of LRTI hospitalization.

Proadrenomedullin as a prognostic marker in neonatal sepsis.

BACKGROUND: Proadrenomedullin (pro-ADM) for the diagnosis of proven and clinical sepsis in a newborn cohort including preterm newborns has not been investigated. We aimed to investigate the value of pro-ADM as a new marker by comparing it with conventional markers in neonatal sepsis (NS). METHODS: Participants were stratified into three groups; proven sepsis (Group 1a), clinical sepsis (Group 1b), and the control group (Group 2), which consisted of newborns of matched gestational age and birth weight. Sequential measurements of white blood cell count, C-reactive protein (CRP), interleukin-6 (IL-6), and pro-ADM were compared. RESULTS: A total of 76 patients with NS (31 with proven sepsis and 45 with clinical sepsis) and 52 healthy controls were enrolled. Mean baseline serum levels of CRP, IL-6, and pro-ADM were significantly higher in both Group 1a and Group 1b as compared with healthy controls (P < 0.001 for both). Although mean baseline CRP and IL-6 levels were similar between groups, mean baseline pro-ADM level was higher in the proven sepsis group than in the clinical sepsis group (P < 0.001). CONCLUSION: The use of pro-ADM in combination with other acute-phase reactants such as CRP and IL-6 for the diagnosis and follow-up of patients with NS has high sensitivity and specificity.

Intrauterine upper extremity thrombosis successfully treated with recombinant tissue plasminogen activator, enoxaparin and collagenase.

Intrauterine ischemia of the limbs is a rare condition involving thrombosis and ischemia of the extremities before birth. The clinical presentation depends on the extremity affected as well as the timing of thrombosis. Very few cases with extremity hypoperfusion and gangrene due to intrauterine thrombosis have been reported in the literature, and therefore there is no consensus on the optimal therapeutic strategy for such cases. Presented here is a case of a newborn with intrauterine brachial arterial thrombosis of the right upper extremity who was successfully treated by a combination of recombinant tissue plasminogen activator, enoxaparin and collagenase application followed by surgery.