Novel Compound Heterozygous Mutations of TGM1 Gene Identified in a Turkish Collodion Baby Diagnosed with Non-Bullous Congenital Ichthyosiform Erythroderma.

Autosomal recessive congenital ichthyosis (ARCI) is a group of diseases presenting as collodion baby at birth. ARCI is categorized as Harlequin ichthyosis, lamellar ichthyosis, and non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit icthyosis (BSI) and others. We describe the case of a male newborn with NBCIE whose whole exome sequencing revealed two variants of TGM1 gene (NM_000359.3) in a compound heterozygous state: c.790C>T (p.Arg264Trp) in exon 5 and c.2060G>A (p.Arg687His) in exon 13. In the literature, the Arg264Trp variant has been reported as homozygous or compound heterozygous with other variants in patients with BSI. In contrast, the Arg687His variant has been reported only as homozygous in patients with BSI. To the best of our knowledge, this is the first case whose two compound heterozygous variants, exhibiting the NBCIE phenotype, instead of the BSI.

Pitt-Hopkins syndrome accompanying hypoxic ischemic encephalopathy in a newborn.

Hypoxic-ischemic encephalopathy (HIE) is one of the substantial causes of developmental-cognitive disability in neonates. In this early period, it is difficult to diagnose accompanying or predisposing genetic diseases in HIE patients. Herein, we present a patient with HIE who was diagnosed with Pitt-Hopkins syndrome in the newborn period.

Breast Milk Protein Percentiles According to Gestational and Postnatal Age: Could It Be Used as a New Alternative in Guided Fortification?

Human milk is the first choice for infant nutrition but it must be multinutrient fortified for optimum growth and neurodevelopment in preterm infants. However, there is no consensus on ideal fortification method. The authors aimed to generate the human-milk protein content percentiles during the first five postnatal weeks in four preterm groups (n = 108) with median gestational age of 32 (23-36) wk, who were fed adjustably fortified breast milk in the NICU between October 2011 and June 2013. Total 540 breast milk samples of mothers of 108 infants were weekly analyzed for protein intake. It was observed that the median human-milk protein levels decreased throughout the five postnatal weeks in all groups. None of the preterm infants was able to take the recommended daily protein intake with the fortification protocol of the authors' unit. Preterm human-milk protein charts can be used as a new practical individualized fortification guiding method instead of laborious targeted or adjustable approaches currently in use.

Neonatal Seizures and Future Epilepsy: Predictive Value of Perinatal Risk Factors, Electroencephalography, and Imaging.

CONTEXT: There are limited data in the literature about the relationship between neonatal seizures and subsequent epilepsy. AIMS: This study aimed to identify the predictive value of perinatal factors, etiologies, electroencephalography (EEG), and cranial ultrasonography (USG) for future epilepsy after neonatal seizures. MATERIALS AND METHODS: A total of 92 children with epilepsy who had seizures during their neonatal period were retrospectively evaluated whether the contribution of perinatal, natal, and postnatal risk factors confining clinical, laboratory, EEG, and imaging to subsequent epilepsy. Chi-square, uni, and multivariate logistic regression were applied to find out predictive factors for subsequent epilepsy. RESULTS: The rate of epilepsy was 57.6 % during 1-6 years follow-up. Birth weight, Apgar scores at first and fifth minutes, resuscitation history, abnormal neurological examination, etiology, response to the treatment, abnormal EEG, or USG findings were the most important risk factors for future epilepsy in univariate analysis (P < 0.05). Furthermore, asphyxia, fifth minute Apgar scores, response to the treatment, USG, and EEG were independent predictors (P < 0.05) for subsequent epilepsy in multivariate logistic regression. No relationship was found between subsequent epilepsy and mode of delivery, seizure onset time, and seizure types (P > 0.05). CONCLUSION: Although there are recent promising and advanced techniques in neonatal intensive care units, asphyxia is still one of the most important risk factors for not only poor neurological conditions but also for future epilepsy after neonatal seizures. Apgar scores, treatment with multiple antiepileptic drugs, poor background EEG activity, and abnormal neuroimaging seem to have strong predictive values for developing subsequent epilepsy. Therefore, patients with a history of neonatal seizures should be closely followed up to decrease the risk of long-term outcomes and early detection of epilepsy.

Neuroprotective effect of L-arginine in a neonatal rat model of hypoxic-ischemia.

Aim: The aim of the present study is to investigate the neuroprotective effects of l-Arginine (l-arg) in the seven-day-old rat hypoxia-ischemia model. Materials and methods: L-Arginine (n = 10) or saline (n = 8) was administered intraperitoneally to seven-day-old rats before hypoxia-ischemia. In addition, 18 seven-day-old rats were given l-Arginine (n = 10) or saline (n = 8) after hypoxic-ischemic insult. Neuronal apoptosis was investigated by terminal dUDP-biotin nick end-labeling (TUNEL) following three days of recovery. The ratios of right side numerical density to the sum of right and left sides' numerical densities (right apoptosis index) were calculated for every brain region in rats receiving l-arginine and they were compared with the vehicle groups. Results: Right side apoptosis indexes of the hippocampus (mean ± SD; 35.0 ± 16.1) and striatum (41.9 ± 16.0) were significantly decreased in the l-Arginine post-treatment groups when compared to vehicles (61.0 ± 17.0 and 62.4 ± 27.0 respectively) (p < 0.05). There was no significant difference in the right apoptosis indexes of the cortex between l-Arginine post-treated group and the vehicle group. There were also no significant differences between the right side apoptosis indexes of the l-Arginine pretreatment groups and those of the vehicle group in any of the three regions (p > 0.05). Conclusions: It is concluded that neuronal apoptosis due to hypoxic-ischemic injury may likely to be reduced by post-treatment of l-Arginine in the neonatal rat model and l-Arginine provides a new possibility for neuroprotective strategies based on NO production.

Effects of blood transfusion on regional tissue oxygenation in preterm newborns are dependent on the degree of anaemia.

AIM: Most of the preterm infants are transfused at least once during their stay in the neonatal intensive care unit (NICU). The aims of this study were to demonstrate if packed red blood cell (pRBC) transfusion modulates regional (cerebral, abdominal, renal) tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) and to demonstrate if we can use NIRS to guide transfusion decisions in neonates. METHODS: A multi-probe NIRS device was applied to anaemic preterm infants of gestational age <33 weeks for 30-60 min before and 24 h after pRBC transfusion. We evaluated the results separately in the subgroup with a pre-transfusion haemoglobin (Hb) < 8 g/dL. Cerebral, abdominal and renal tissue oxygen saturation (rSO2 ) and abdominal/cerebral, abdominal/renal and renal/cerebral rSO2 ratios before and 24 h after transfusion were compared. RESULTS: There was no significant difference in cerebral rSO2 and abdominal/renal rSO2 ratios before and 24 h after transfusion, but abdominal and renal rSO2 and abdominal/cerebral and renal/cerebral rSO2 ratios at the 24th h following transfusion increased significantly. This increase was observed in the subgroup with pre-transfusion Hb < 8 g/dL. Although statistically significant, the increase in renal oxygenation was within the limits of variability. CONCLUSIONS: The increase in tissue oxygenation in abdominal region after pRBC transfusion suggests decreased tissue oxygenation of intestines during severe anaemia despite cerebral oxygenation being maintained at that particular Hb level. The impact of the increase on renal oxygenation with pRBC transfusion is unclear and might need further investigation. Increase in abdominal rSO2 may cause reperfusion injury, oxidative damage and trigger necrotising enterocolitis.

Do the adiponectin and leptin levels in preterm and term breast milk samples relate to infants' short-term growth?

Adiponectin and leptin are involved in appetite control and body weight regulation. We aimed to evaluate the relationship between breast milk adipokine levels and short-term growth of preterm and term infants. Thirty-one preterm (median=35.3 weeks) and 34 term (median=38.7 weeks) infants were enrolled. Enzyme-linked immunosorbent assay was used to detect adipokines in mature milk. Infant growth was followed during the first 3 months. Although weight gain in the first month was insufficient, positive linear growth was observed in the following months for preterm infants, while term infants had positive steady linear growth. The median level of adipokines was found to be higher in preterm infants (P>0.05). Adiponectin showed significant negative correlations with some anthropometric measurements of term infants. However, in preterm infants, adiponectin was negatively correlated with length increment and positively correlated with body mass index (BMI) increment in the second-third month. In addition, leptin was negatively associated with the head circumference at birth in preterm infants and the triceps skinfold thickness increment in the first-second month term infants (P<0.05). In linear regression models, while gestational age, adiponectin and leptin were not related, maternal age and pre-pregnancy BMI had effects on body weight increment in 0-1 months (P<0.05). In conclusion, adiponectin may affect short-term growth, while leptin has no important effect. It would be beneficial to carry out longitudinal studies to evaluate the effects of these adipokines on the growth of infants.

Are breast milk adipokines affected by maternal dietary factors?

Background Maternal diet and gestational age of infant may affect the composition of breast milk. The aim of this study was to evaluate the relationship between breast milk adiponectin and leptin levels of mothers delivering preterm and term infants and maternal diet. Methods Sixty-five mothers (31 preterm, 34 term) were included in the study. General information about parents and infants and food consumption of mothers were determined through a questionnaire. Milk samples were taken from mothers during the period between the 15th and 30th day after birth (mature milk). For the evaluation of maternal diet, the nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were used. Results According to MAR, 71.0% of preterm mothers' and 79.4% of term mothers' dietary adequacy was categorized as "good", and none of the mothers fell into the "insufficient" category (p>0.05). The median (interquartile range [IQR]) level of adipokines was found to be higher in preterm than in term mothers (24.6 [14.3] ng/mL; 22.9 [9.7] ng/mL for adiponectin and 2.0 [2.5] ng/mL; 0.0 [2.3] ng/mL for leptin, respectively) (p>0.05). A negative correlation was found between the leptin level and intake of unsaturated fatty acids, protein NAR and meat, poultry and fish consumption in preterm mothers (p<0.05). A positive correlation was found between leptin concentration and MAR, protein, calcium, potassium NAR and consumption of dairy products in term mothers (p<0.05). In the regression model, gestational age and MAR are important predictors of leptin. Conclusions These results show that maternal diet is related to the leptin content in breast milk.

Hepatic Complications of Umbilical Venous Catheters in the Neonatal Period: The Ultrasound Spectrum.

OBJECTIVES: Umbilical venous catheterization is commonly used in the neonatal period; however, it has some complications. In this study, we evaluated neonates who underwent umbilical venous catheterization and developed hepatic complications. Furthermore, we aimed to define all of the possible lesions and to clarify the imaging findings of umbilical venous catheter-induced hepatic injury. METHODS: Two hundred forty-four neonates who underwent umbilical venous catheterization between March 2013 and September 2015 in a single tertiary care referral center were included in this study. To determine whether they had any hepatic complications, all patients underwent abdominal grayscale and Doppler ultrasound examinations, and their clinical data were recorded. RESULTS: The frequency of liver-related complications from umbilical venous catheterization was 33.6% (82 of 244). Air in the portal venous system was the most frequent complication (20.1% [49 of 244]). Left portal venous thrombosis was noted in 6.1% (15 of 244). Parenchymal lesions in the liver related to umbilical venous catheterization were seen in 7.4% of patients (18 of 244) as follows: single nodular echogenic lesions (4.1% [10 of 244]), branching small nodular echogenic lesions (2.1% [5 of 244]), and large irregular heterogeneous lesions with laceration and perihepatic fluid (1.2% [3 of 244]). There was no statistical significance for any type of complication according to the gestational age (P > .05). CONCLUSIONS: Hepatic complications due to umbilical venous catheters are not uncommon in the neonatal period. Ultrasound is the best imaging modality for confirming the diagnosis and for follow-up.

Echocardiography may cause significant pain response in preterm infants.

OBJECTIVE: The objective of this study is to evaluate if echocardiographic examination causes any pain response in term and preterm infants. METHODS: Term and preterm neonates who admitted to Neonatal Intensive Care Unit at Gazi University Hospital and Etlik Zubeyde Hanim Training and Research Hospital and were performed echocardiography for any reason were included into the study. Neonates were evaluated before, during and 10 minutes after the examination. Vital signs (heart rate, respiratory rate, blood pressure, transcutaneous oxygen saturation) were recorded. All subjects were also evaluated with Neonatal Infant Pain Scale during the examination. RESULTS: In this study, we evaluated 99 newborn infants. Five infants who received fentanyl treatment were excluded. The heart rate (p = 0.000), respiratory rate (p = 0.000), diastolic blood pressure (p = 0.001) and oxygen saturation (p = 0.000) during the examination were significantly different than the values before and 10 minutes after the examination. Infants whose gestational age ≤32 weeks (n:20) have significantly higher NIPS scores (mean ± SEM = 3.3 ± 0.4) than the infants whose gestational age is greater than 32 weeks (n:71) (mean ± SEM = 2.4 ± 0.2). CONCLUSIONS: Echocardiographic examination which is known as noninvasive and painless causes significant pain in preterm infants.

Turkish Neonatal Society guideline on enteral feeding of the preterm infant.

Early initiation of enteral feeding with the own mother's milk and prevention of postnatal growth failure is the target of nutrition in preterm infants. Together with total parenteral nutrition, mouth care and minimal enteral nutrition is started with colostrum in the very early hours of life in small preterm infants. Expressed mother's milk is given via a gastric tube and gradually increased in accordance with the gestational age/birth weight and the risk factors. For infants born heavier than 1 000 grams, the aim is to reach total enteral feeding at the end of first week, and at the end of the second week for infants weighing less than 1000 grams. Supporting mothers in milk expression and kangaroo mother care, promoting non-nutritive feeding, appropriate fortification of mother' milk, and initiating and advancing breastfeeding as soon as the infant is ready are all crucial. Donor mother milk, and as a second choice, preterm formula is advised if the mother's milk is not available. Individualized post-discharge nutrition decisions can be taken in accordance with the actual growth at the time of discharge. The goal is optimal neurodevelopmental achievement together with the prevention of long-term metabolic problems. Late preterm infants, which constitute the majority of preterm infants, also need close nutritional attention and follow-up.

Turkish Neonatal Society guideline on parenteral nutrition in preterm infants.

Postnatal growth failure due to inappropriate and insufficient nutrition is a risk for preterm infants, especially for very-low-birth-weight or extremely-low-birth-weight infants. This extrauterine growth failure causes negative effects on long-term neurodevelopment. Early initiation of intensive parenteral nutrition with appropriate protein and energy supply is a nutritional emergency when enteral feeding cannot be achieved. This approach prevents protein catabolism and helps achievement of positive protein balance and postnatal growth. Protein, lipid, and glucose initiation with appropriate doses that reach timely goals constitute the major elements of parenteral nutrition. The transition to enteral nutrition with the mother's milk at the earliest convenience must be targeted in parenteral nutrition.

Turkish Neonatal Society guideline on nutrition of the healthy term newborn.

Research shows strong evidence that breastfeeding offers many health benefits for infants and mothers, as well as potential economic and environmental benefits for communities. The World Health Organization recommends breastfeeding exclusively for up to 6 months of age, with continued breastfeeding along with appropriate complementary foods up to two years of age or beyond.

Effects of Volume Guaranteed Ventilation Combined with Two Different Modes in Preterm Infants.

BACKGROUND: Volume-controlled ventilation modes have been shown to reduce duration of mechanical ventilation, incidence of chronic lung disease, failure of primary mode of ventilation, hypocarbia, severe intraventricular hemorrhage, pneumothorax, and periventricular leukomalacia in preterm infants when compared with pressure limited ventilation modes. Volume-guarantee (VG) ventilation is the most commonly used mode for volume-controlled ventilation. Assist control, pressure-support ventilation (PSV), and synchronized intermittent mandatory ventilation (SIMV) can be combined with VG; however, there is a lack of knowledge on the superiority of each regarding clinical outcomes. Therefore, we investigated the effects of SIMV+VG and PSV+VG on ventilatory parameters, pulmonary inflammation, morbidity, and mortality in preterm infants. METHODS: Preterm infants who were born in our hospital between 24-32 weeks gestation and needed mechanical ventilation for respiratory distress syndrome were considered eligible. Patients requiring high-frequency oscillatory ventilation for primary treatment were excluded. Subjects were randomized to either SIMV+VG or PSV+VG. Continuously recorded ventilatory parameters, clinical data, blood gas values, and tracheal aspirate cytokine levels were analyzed. RESULTS: The study enrolled 42 subjects. Clinical data were similar between groups. PSV+VG delivered closer tidal volumes to set tidal volumes (60% vs 49%, P = .02). Clinical data, including days on ventilation, morbidity, and mortality, were similar between groups. Chronic lung disease occurred less often and heart rate was lower in subjects who were ventilated with PSV+VG. The incidence of hypocarbia and hypercarbia were similar. Interleukin-1ß in the tracheal aspirates increased during both modes. CONCLUSION: PSV+VG provided closer tidal volumes to the set value in ventilated preterm infants with respiratory distress syndrome and was not associated with overventilation or a difference in mortality or morbidity when compared to SIMV+VG. Therefore, PSV+VG is a safe mode of mechanical ventilation to be used for respiratory distress syndrome.

Effects of a closed system suction connector on airway resistance in ventilated neonates.

BACKGROUND/AIM: Increased airway resistance reduces the effectiveness of ventilation treatment. Endotracheal tubes (ETTs) and connectors contribute to resistance. However, the effect of a closed system suction (CSS) connector is not well known. We compared the in vivo resistance occurring with a CSS connector with that of the standard connector. MATERIALS AND METHODS: This prospective study was conducted at Gazi University Hospital's neonatal intensive care unit. Intubated neonates were studied for two cycles; each cycle contained two periods of ETT + connector pairs (15 min/period) as follows: cycle 1 [A: long ETT + standard connector; B: long ETT + CSS connector] and cycle 2 [C: shortened ETT + standard connector; D: shortened ETT + CSS connector]. Resistance of 40 breaths/period was averaged for each case, and the means were analyzed by Wilcoxon test for pairwise comparisons between standard and CSS connectors. As each case provided two cycle data, 16 cycle data were compared. RESULTS: The CSS connector increased resistance by 13.8% (range: 3.0%-22.1%) compared to the standard connector; P < 0.001. The resistance increase was similar between long [17.3% (range: 3.0%-17.7%)] and shortened ETTs [15.3% (range: 5.0%-29.6%)]; P = 0.834. CONCLUSION: CSS connectors were found to increase airway resistance in ventilated neonates. The contribution of CSS should be considered during ventilation, particularly in the presence of difficulty in providing sufficient tidal volume.

Iloprost Instillation in Two Neonates with Pulmonary Hypertension.

Pulmonary hypertension may coexist with certain diseases in neonates. Iloprost inhalation is one of the treatments which cause selective pulmonary vasodilatation. Inhalation is not an easy way of drug administration in mechanically ventilated infants; as some exhibit desaturations during inhalation. Moreover, inhalation of drug requires cessation of mechanical ventilation, if patient is on high frequency oscillatory ventilation. We presented two patients with pulmonary hypertension; term baby with congenital diaphragmatic hernia and preterm baby with respiratory distress syndrome; who had iloprost instillation during mechanical ventilation treatment. Iloprost instillation was well tolerated with no side effects in the term patient with diaphragmatic hernia; whereas severe blood pressure fluctuations were observed in the preterm infant. This report may courage administration of iloprost in term neonates with resistant pulmonary hypertension.

Regional brain volume reduction and cognitive outcomes in preterm children at low risk at 9 years of age.

OBJECTIVE: More information is needed on "low-risk" preterm infants' neurological outcome so that they can be included in follow-up programs. A prospective study was performed to examine the regional brain volume changes compared to term children and to assess the relationship between the regional brain volumes to cognitive outcome of the low-risk preterm children at 9 years of age. PATIENTS: Subjects comprised 22 preterm children who were determined to be at low risk for neurodevelopmental deficits with a gestational age between 28 and 33 weeks without a major neonatal morbidity in the neonatal period and 24 age-matched term control children term and matched for age, sex, and parental educational and occupational status. METHODS: Regional volumetric analysis was performed for cerebellum, hippocampus, and corpus callosum area. Cognitive outcomes of both preterm and control subjects were assessed by Weschler Intelligence Scale for Children Revised (Turkish version), and attention and executive functions were assessed by Wisconsin Card Sorting Test and Stroop Test TBAG version. RESULTS: Low-risk preterm children showed regional brain volume reduction in cerebellum, hippocampus, and corpus callosum area and achieved statistical significance when compared with term control. When the groups were compared for all WISC-R subscale scores, preterm children at low risk had significantly lower scores on information, vocabulary, similarities, arithmetics, picture completion, block design, object assembly, and coding compared to children born at term. Preterm and term groups were compared on the Stroop Test for mistakes and corrections made on each card, the time spent for completing each card, and total mistakes and corrections. In the preterm group, we found a positive correlation between regional volumes with IQ, attention, and executive function scores. Additionally, a significant correlation was found between cerebellar volume and attention and executive function scores in the preterm group. CONCLUSION: Low-risk preterm children achieve lower scores in neurophysiological tests than children born at term. Preterm birth itself has a significant impact on regional brain volumes and cognitive outcome of children at 9 years of age. It is a risk factor for regional brain volume reductions in preterm children with low risk for neurodevelopmental deficits. The significant interaction between cerebellar volume reduction and executive function and attention may suggest that even in preterm children at low risk can have different trajectories in the growth and development of overall brain structure.

Our experience in two cases of type IV laryngotracheoesophageal cleft (LTEC) with a diagnosis of antenatal esophageal atresia.

Laryngotracheoesophageal clefts (LTECs) are rare congenital defects that are often accompanied by additional anomalies. The major issues in the treatment of these patients are intraoperative exposure insufficiency, technical difficulty of the operation, and anesthesia problems originating from the respiratory tract. Problems originating from mechanical ventilation and respiratory tract, eating disorders and relapse of fistula are among the problems encountered following surgery. Most of the time, concomitant additional anomalies also worsen the clinical picture. It was our aim with these case reports to report our experience in two cases with Type IV LTEC ranging from the inoperable type IV LTEC due to additional anomalies mounted up to severe respiratory distress to the carina that we operated on with a single stage anterior cervicothoracic approach on its fifth day on life.

Different presentations of cow`s milk protein allergy during neonatal period.

Aktas S, Ergenekon E, Ünal S, Türkyilmaz C, Hirfanoglu IM, Atalay Y. Different presentations of Cow's milk protein allergy during neonatal period. Turk J Pediatr 2017; 59: 322-328. Cow`s milk protein allergy (CMPA) is the most common cause of allergy occurring in the first year of life due to infant formula or breast-milk of mothers who are drinking cow`s milk or eating cow's milk products. Most children with allergic colitis are symptomatic in the first months, usually by 4 weeks. There are rare cases whom were sensitized prenatally and demonstrated symptoms in the first week, even in the first 2 days of life. The most common clinical sign of CMPA is bloody stool in a well-appearing infant. Gross bloody stool or fecal occult blood are also the common signs of necrotizing enterocolitis (NEC), especially in preterm infants with systemic instability. The treatment options are totally different so the clinician has to be very careful evaluating the patient. We report 5 preterm cases of CMPA, two of whom were siblings. Two of them presented with massive bloody stools and 3 of them presented with abdominal distension and fecal occult blood all of which were initially considered as NEC. Literature review of 20 cases with similar history is summarized as well.