The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

Neonatal Resuscitation Practices in Turkey: A Survey of the Turkish Neonatal Society and the Union of European Neonatal and Perinatal Societies.

OBJECTIVE: Optimal care in the delivery room is important to decrease neonatal morbidity and mortality. We aimed to evaluate neonatal resuscitation practices in Turkish centers. MATERIALS AND METHODS: A cross-sectional survey consisted of a 91-item questionnaire focused on delivery room practices in neonatal resuscitation and was sent to 50 Turkish centers. Hospitals with <2500 and those with ≥2500 births/year were compared. RESULTS: In 2018, approximately 240 000 births occurred at participating hospitals with a median of 2630 births/year. Participating hospitals were able to provide nasal continuous-positiveairway-pressure/high-flow nasal cannula, mechanical ventilation, high-frequency oscillatory ventilation, inhaled nitric oxide, and therapeutic hypothermia similarly. Antenatal counseling was routinely performed on parents at 56% of all centers. A resuscitation team was present at 72% of deliveries. Umbilical cord management for both term and preterm infants was similar between centers. The rate of delayed cord clamping was approximately 60% in term and late preterm infants. Thermal management for preterm infants (<32 weeks) was similar. Hospitals had appropriate equipment with similar rates of interventions and management, except conti nuous-positive-airway-pressure and positive-end-expiratory-pressure levels (cmH2O) used in preterm infants (P = .021, and P = .032). Ethical and educational aspects were also similar. CONCLUSIONS: This survey provided information on neonatal resuscitation practices in a sample of hospitals from all regions of Turkey and allowed us to see weaknesses in some fields. Although adherence to the guidelines was high among centers, further implementations are required in the areas of antenatal counseling, cord management, and circulation assessment in the delivery room.

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.

Is Cord Blood Bilirubin Level a Reliable Predictor for Developing Significant Hyperbilirubinemia?

OBJECTIVE: We aimed to investigate whether cord blood bilirubin (CBB) level could be used to identify the newborns at a high risk of developing hyperbilirubinemia. STUDY DESIGN: Total and direct serum bilirubin level were evaluated from umbilical cord blood of newborns. We checked blood groups and Rh status of all mothers and determined blood groups and direct Coombs test (DC) of newborns born to mothers whose blood group was O type or Rh negative to determine the maternal-fetal blood group or Rh incompatibility. RESULTS: A total of 418 newborns were included, and phototherapy (PT) was required in 17 newborns. The cutoff value of CBB for predicting the occurrence of significant hyperbilirubinemia requiring PT was 1.67 mg/dL, with a sensitivity of 82% and specificity of 99%. The mean CBB level in babies receiving PT was 2.4 ± 0.9 mg/dL. When blood group, CBB level, DC, gender, and mode of delivery were assigned as possible risk factors, multivariate analysis showed ABO, Rh incompatibility, and CBB level increased the risk of PT requirement. CONCLUSION: CBB could be useful to determine newborns at a risk of developing hyperbilirubinemia and prevent developing severe complications due to delay in diagnosis.

The follow-up results of newborn hearing screening of Gaziosmanpasa Taksim Research and Training Hospital.

AIM: This study aimed to present the results of newborns who were referred to advanced audiology centers after newborn hearing screening, and to determine concordance of our results with the American Academy of Pediatrics guidelines about the ages of hearing loss, aid fitting, and cochlear implantation. MATERIALS AND METHODS: A total of 7502 newborns were screened in Gaziosmanpasa Taksim Research and Training Hospital between March 2014 and June 2016 using the transient otoacustic emissions test as the first two steps and automated auditory brainstem response test for the third step. Newborns who had risk factors were screened using the automated auditory brainstem response only. Newborns who failed the screening tests were referred to advanced audiology centers. RESULTS: Of the 7502 newborns, 6736 (90%) completed the screening. The ratio of hearing loss was 0.08%. Six of 62 newborns who failed auditory brainstem response test and were referred to advanced audiology centers had severe bilateral hearing loss. One of the patients was not fitted with a hearing aid because the family refused it. The other one was not fitted an aid and did not undergo cochlear implantation because of severe and treatment-resistant acute otitis media. The age of diagnosis for the rest was before three months, and except for one patient, hearing aid fitting was before six months. The age of cochlear implantation was 12 months for two patients and 14 months for two patients. CONCLUSION: Ninety percent of patients completed the screening, the age of diagnosis for hearing loss was before three months and aid fitting was before six months, except for one patient. The results of the study were compatible with the diagnosis and treatment guidelines of the American Academy of Pediatrics.

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.

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.

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.

Impact of mode of delivery on skin microcirculation in term healthy newborns within the first day of life.

BACKGROUND: Microcirculation is an important component of hemodynamic physiology. It can be assessed simply by clinical scores or by a variety of techniques including sidestream dark field (SDF) imaging and peripheral perfusion index (PI) measurements. Mode of delivery may have affects on microcirculation during transitional period. The aim of this study was to compare skin microcirculation in newborns born via vaginal delivery (VD) or cesarian section (C/S). METHODS: Term healthy newborns not requiring NICU admission were included. Vital signs were recorded. Skin microcirculation was determined by clinical scoring including capillary refill time, skin color, warmth of extremities, by SDF imaging where capillary density and microvascular flow is determined and by PI measurements where pulsatile and nonpulsatile capillary flow is measured. Assessments were done at 30 min and 24 h of life. Results were compared between VD and C/S groups and overtime. RESULTS: There were 12 newborns in VD group and 25 newborns in C/S group. No difference was observed in microcirculation assessments between groups. However VD group had increased hyperdynamic flow overtime. CONCLUSION: In healthy term newborns microcirculation does not seem to be affected by mode of delivery, however results may differ in sick or preterm newborns.

Perfusion index assessment during transition period of newborns: an observational study.

BACKGROUND: Perfusion index (PI) is becoming a part of clinical practice in neonatology to monitor peripheral perfusion noninvasively. Hemodynamic and respiratory changes occur in newborns during the transition period after birth in which peripheral perfusion may be affected. Tachypnea is a frequent symptom during this period. While some tachypneic newborns get well in less than 6 h and diagnosed as "delayed transition", others get admitted to intensive care unit which transient tachypnea of newborn (TTN) being the most common diagnosis among them. We aimed to compare PI of neonates with TTN and delayed transition with controls, and assess its value on discrimination of delayed transition and TTN. METHODS: Neonates with gestational age between 37 and 40 weeks who were born with elective caesarian section were included. Eligible neonates were monitored with Masimo Set Radical7 pulse-oximeter (Masimo Corp., Irvine, CA, USA). Postductal PI, oxygen saturation and heart rate were manually recorded every 10 s for 3 min for two defined time periods as 10th minute and 1st hour. Axillary temperature were also recorded. Newborn infants were grouped as control, delayed transition, and TTN. RESULTS: Forty-nine tachypneic (TTN; 21, delayed transition; 28) and 30 healthy neonates completed the study. PI values were similar between three groups at both periods. There were no correlation between PI and respiratory rate, heart rate, and temperature. CONCLUSION: PI assessment in maternity unit does not discriminate TTN from delayed transitional period in newborns which may indicate that peripheral perfusion is not severely affected in either condition.

Mass Effect of Pulmonary Sequestration: Multiloculated-Multiseptated Pneumomediastinum.

Pulmonary sequestration (PS) and pneumomediastinum are two rare clinical diseases. Pneumomediastinum was generally observed in infants either with diseased lungs or who were performed assisted ventilation or resuscitation following birth. It was reported in patients with existing ectopic thoracic kidney and laryngeal cysts however, no coexisting congenital lung anomalies were reported. Here, we report the pneumomediastinum occurred due the extralobar PS because of the mass effect of the lesion.

Nasal HFOV with Binasal Cannula Appears Effective and Feasible in ELBW Newborns.

Non-invasive ventilation has been used increasingly in recent years to reduce the duration of endotracheal ventilation and its complications, especially bronchopulmonary dysplasia. Nasal continuous positive airway pressure and nasal intermittent positive pressure ventilation are the most common non-invasive modalities, and nasal high-frequency oscillatory ventilation (n-HFOV) is relatively new but it seems effective and feasible. We present three premature cases who were ventilated with n-HFOV with Neotech RAM Cannula as interphase. In two cases, we used n-HFOV with good results to prevent extubation failure, and in one case, we used it to avoid intubation with success. n-HFOV may be useful both in early times of respiratory failure and also to facilitate extubation particularly in patients with prolonged intubation.

Functional brain maturation of prematurely born, growth discordant monochorionic twins assessed by aEEG.

The amplitude-integrated electroencephalogram (aEEG) is a simple and convenient tool for brain function monitoring. It is being more widely used in monitoring high risk neonates in neonatal intensive care units. Normal values and patterns for aEEG activity in preterm infants are still being developing. Here we report the functional brain maturation of preterm twin siblings with aEEG who were severely affected by fetal growth discordance. The aEEG records of growth retarded twin was compared with her appropriate for gestational age sibling in order to see if there is also a developmental discordance in the functional brain maturation of these twins.

Skinfold thickness of preterm newborns when they become late preterm infants.

BACKGROUND: Nutrition of very low-birth-weight newborns is important for a good physical and neurologic outcome. Body composition assessment, together with anthropometric measurements, is considered necessary to monitor adequate nutrition and growth. Objectives of this study were to assess body fat changes in newborns ≤32 weeks gestation by weekly skinfold thickness (SFT) measurements and to compare them with those of late preterm infants born at 34, 35, and 36 weeks once they reached 34, 35, and 36 weeks corrected age (CA). MATERIALS AND METHODS: Preterm infants ≤32 weeks gestation had SFT measured from 4 body sites, including biceps, triceps, and subscapulary and suprailiac regions, by a Holtain caliper starting from 48 hours of age at weekly intervals until 34, 35, and 36 weeks CA. The measurements were compared with those of late preterm controls born at 34, 35, and 36 weeks gestation. RESULTS: There were 37 preterm infants in the patient group. When reaching 34, 35, and 36 weeks CA, preterm infants had higher SFT values compared with controls in all body sites. Median and range of total SFT were 14.6 mm (9.6-18.9 mm) in patients and 11 mm (7.8-16.4 mm) in controls at 34 weeks CA, 15.5 mm (10.7-21.8 mm) in patients and 12.3 mm (7-17 mm) in controls at 35 weeks CA, and 16.4 mm (11.8-23.7 mm) in patients and 12.9 mm (7-17.8 mm) in controls at 36 weeks CA (P = .001 in all). No sex difference was observed at 34 and 35 weeks. CONCLUSION: These results show that preterm infants start accumulating excess fat even from early weeks of life. Careful assessment of growth by tools other than simple anthropometric measurements is essential to avoid future complications.

The risk assessment study for hemolytic disease of the fetus and newborn in a University Hospital in Turkey.

Maternal red-cell alloimmunization occurs when a woman's immune system is sensitized to foreign red-blood cell surface antigens, leading to the production of alloantibodies. The resulting antibodies often cross the placenta during pregnancies in sensitized women and, if the fetus is positive for red-blood-cell surface antigens, this will lead to hemolysis of fetal red-blood cells and anemia. The most severe cases of hemolytic disease in the fetus and newborn baby are caused by anti-D, anti-c, anti-E and anti-K antibodies. There are limited data available on immunization rates in pregnant women from Turkey. The aim of the present study was to provide data on the frequency and nature of maternal RBC alloimmunization in pregnant women in a tertiary care hospital. In this study, we retrospectively evaluated the indirect antiglobulin test results of Rh-negative pregnant women performed in our Blood Bank between 2006 and 2012. Indirect antiglobulin test positive women also underwent confirmatory antibody screening and identification. During the study period, 4840 women admitted to our antenatal clinics. With regards to the major blood group systems (ABO and Rh), the most common phenotype was O positive (38.67%). There were 4097 D-antigen-positive women (84.65%) and 743 women with D-antigen-negative phenotype (15.35%). The prevalence of alloimmunization was found to be 8.74% in D-antigen negative group. Despite prophylactic use of Rh immunglobulins, anti-D is still a common antibody identified as the major cause of alloimmunization in our study (anti-D antibody 68.57%, non-D antibody 31.42%). While alloimmunization rate to D antigen was 6.46%, non-D alloimmunization rate was 2.69% among Rh-negative pregnant women. Moreover, detailed identification facilities for antibodies other than anti-D are not available in most of centers across Turkey. However, large-scale studies on pregnant women need to be done in order to collect sufficient evidence to formulate guidelines and to define indications for alloantibody screening and identification.