Paracetamol therapy for patent ductus arteriosus in premature infants: a chance before surgical ligation.

Patent ductus arteriosus (PDA) remains a common problem in premature infants. Treatment options include pharmacologic therapy and surgical ligation, but these are associated with potentially significant adverse effects. This report describes the effect of administering oral paracetamol to premature neonates with PDA. The study enrolled seven premature neonates followed up with the diagnosis of hemodynamically significant PDA (hsPDA) between February and December 2012 and treated with oral paracetamol. Patients with hsPDA were given at least two or more courses of ibuprofen treatment. If this therapy failed to promote ductal closure, the patients with clinical symptoms who had hsPDA defined by echocardiography were treated with oral paracetamol (15 mg/kg every 6 h). If these patients did not respond to paracetamol therapy, the PDA was closed by surgical ligation. The mean gestational age of the seven patients in this study was 26.1 weeks, and their mean birth weight was 936 g. Paracetamol treatment was started at 36.2 ± 11.6 days. The mean internal ductal diameter was 2.0 ± 0.2 mm, and the left atrium-to-aorta ratio was 1.5 ± 0.2. All the patients were administered oral paracetamol because of no response to ibuprofen treatment. The hsPDA was successfully closed with oral paracetamol in five (71.4 %) of the seven patients. The remaining two patients had surgical ligation performed, but one of them died. No side effects related to paracetamol were observed. Oral paracetamol may be used as an alternative drug for the management of hsPDA in premature neonates when ibuprofen treatment is unsuccessful and the only other therapeutic option is surgery.

Delayed postmortem cesarean section due to trauma.

Cardiopulmonary arrest is an occasional occurrence during pregnancy. As soon as maternal arrest is noticed in a woman in the second half of her pregnancy, medical teams should be called for perimortem cesarean (C/S). A 31-week-pregnant female patient was brought to our emergency department by the emergency medical service team with cardiopulmonary resuscitation (CPR) after a traffic accident. The patient, with no pulse or spontaneous breathing, was recognized as exitus. However, CPR was sustained to maintain fetal well-being. Before the arrival of the on-call gynecologist, we as emergency physicians initiated C/S both for fetal well-being and to avoid heighten-ing the risk of fetal mortality and morbidity. The Apgar scores were 0/3/4 and oxygen saturation values were 35/65/75% at 1/5/10 min, respectively. On the postnatal 11th day, the patient did not respond despite the advanced cardiac life support (ACLS) and thus was con-sidered exitus. The ACLS team should be knowledgeable and well-equipped to perform C/S, to do aftercare, to watch for related risks in the infant. In our case, it took 40 min for the fetus to be removed from the mother's womb, starting from the estimated time of exitus.

Primary hypogonadism in a case with XLAG syndrome.

Patients with X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, microcephaly, and male genotype with ambiguous genitalia. The basis of the ambiguous genitalia in XLAG syndrome is not well-known. We report a case of the fourth child of healthy consanguineous parents who was presented to the hospital because of non-febrile seizures at 2 months of life. On physical examination, microcephaly, some dysmorphic face features, and ambiguous genitalia were determined. The cranial magnetic resonance imaging of the patient showed lissencephaly, agenesis of the corpus callosum, and enlarged ventricles. His karyotype was 46, XY. He had undetectable testosterone levels and elevated gonadotropins. Neither testicular tissue nor any testosterone response to human chorionic gonadotropin stimulation test was observed. These findings suggest that the hypogonadism in this patient with XLAG syndrome is primary hypogonadism due to gonadal agenesis or dysgenesis.

Cord Blood Levels of Spexin, Leptin, and Visfatin in Term Infants Born Small, Appropriate, and Large for Gestational Age and Their Association with Newborn Anthropometric Measurements

Objective: Children born small for gestational age (SGA) are at risk of future obesity and associated comorbidities. Therefore the identification of risk factors and novel biomarkers which are associated with this risk are needed for early detection and to improve preventive strategies. Spexin (SPX), a novel neuropeptide that is involved in the regulation of obesity and fat metabolism, is a candidate biomarker for predicting obesity and related comorbidities at an early age. The aim of this study was to investigate serum levels of SPX in term infants born small, appropriate, and large for gestational age (LGA) and its association with newborn anthropometric measurements. Methods: One hundred and twenty term newborn babies classified as SGA, appropriate for gestational age (AGA), or LGA and their mothers were included. SPX, leptin and visfatin were measured in cord blood and maternal serum by enzyme-linked immunosorbent assay. Results: Fifty-six (46.7%) neonates were girls and 64 (53.3%) were boys. The mean birth weight was 3170.70±663 g, birth length was 48.9±2.79 cm, and head circumference was 34.5±1.67 cm. Birth weights, lengths, and head circumferences of the neonates in the SGA, AGA, and LGA groups were significantly different. Cord blood SPX and leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups. Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups. Maternal SPX levels of SGA babies were significantly lower than those of the mothers in both the LGA and AGA groups, but no significant difference was observed between the SGA and LGA groups. Maternal visfatin levels of the AGA babies were significantly higher than the maternal levels of SGA and LGA groups. There was no difference in terms of maternal leptin levels. Cord blood SPX and leptin levels were positively correlated with birth weight, length and head circumference. Birth weight increased significantly in line with maternal pregestational body mass index. Conclusion: The lowest SPX levels were found in the SGA babies and cord SPX level was significantly correlated with newborn length, weight, and head circumference.

Comparison of cut and intact cord milking regarding cerebral oxygenation, hemodynamic and hematological adaptation of term infants.

OBJECTIVE: Although both delayed umbilical cord clamping and intact umbilical cord milking (I-UCM) provide the effective placental transfusion at birth, these procedures may not be used in neonates needing resuscitation. The aim of this study is to investigate the effect of cut umbilical cord milking (C-UCM), which permits resuscitation during an immediate transition period (ITP). METHODS: Sixty-two healthy term infants were randomly divided into C-UCM and I-UCM groups at birth. Approximately 30-cm length of cord was milked towards the baby 2-4 times within 20 seconds after birth in both C-UCM and I-UCM groups while the umbilical cord was cut in the former, and intact in the latter. Heart rate, arterial oxygen saturation (SpO2), cerebral regional oxygen saturation (crSO2) (2nd-15th min), blood pressure (BP) (within 15-30 min), residual placental blood volume (RPBV), and hemoglobin levels (at the sixth hour) were monitored during ITP. RESULTS: There were no significant differences in terms of mean gestational age (w) [(39.0 ± 1.2) versus (38.8 ± 1.1)], birth weight (g) [(3351.45 ± 254.30) versus (3256.94 ± 285.52)], Apgar scores at the 5th min (10 ± 0 versus 10 ± 0), first breathing time (sec) (5.4 ± 3.8 versus 5.7 ± 4.1), SpO2, crSO2, BP (mmHg) [(52.9 ± 6.9) versus (51.8 ± 5.7)], hemoglobin levels (g/dl) [(17.7 ± 1.8) versus (18.4 ± 1.4)], and RPBV (ml/kg) [(23.9 ± 4.7) versus (22.9 ± 5.4)] between C-UCM and I-UCM groups (p > .05). CONCLUSION: This study showed that C-UCM is as effective as I-UCM on cerebral oxygenation, hemodynamic and hematological adaptation of term infants in ITP. We suggest that C-UCM can provide additional placental transfusion in term neonates exposed to early cord clamping.

Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients. Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Acquired lung cysts in a premature neonate with congenital cytomegalovirus infection.

We report a preterm newborn diagnosed as having congenital cytomegalovirus infection who developed lung cysts during her clinical follow-up. The lung cysts were shown in chest X-ray, and confirmed by thoracic computed tomography. A few weeks after starting ganciclovir therapy, we observed that the cystic lung changes of the patient were completely improved. No adverse effects of antiviral therapy were observed. Based on this presented patient, it should be kept in mind that congenital cytomegalovirus infection may cause lung cysts.

Fetal sodium valproate exposure causes Baller-Gerold syndrome phenotype: both phenotypes in the same family.

Baller-Gerold syndrome (BGS) is characterized by craniosynostosis and preaxial upper-limb malformations, and it has an autosomal recessive inheritance. Valproate syndrome occurs after exposure to valproic acid in utero, and is characterized by trigonocephaly. Both syndromes can also present with other malformations. Herein, we report a female newborn and her brother who both had a history of fetal exposure to maternal anti-epileptic drugs, especially sodium valproate. On physical examination of the female patient, craniosynostosis, trigonocephaly, right radius aplasia and hypoplastic thumb, and cardiac and renal malformations were determined, and she was diagnosed with BGS phenotype. The brother's examination revealed trigonocephaly, polymastia and hypospadias, and he was diagnosed with valproate syndrome. Based on these patients, we aimed to add further evidence in the literature indicating that the use of sodium valproate alone and in combination with other anti-epileptic drugs throughout pregnancy can increase the risk of serious fetal congenital malformations depending on the doses.

Caffeine prevents bilirubin-induced cytotoxicity in cultured newborn rat astrocytes.

OBJECTIVE: Unconjugated bilirubin (UCB) may cause neurotoxicity in preterm neonates due to immaturity of UGT1A1 leading to bilirubin accumulation in the brain. Caffeine used in the treatment of apnea of prematurity was reported to decrease mechanical ventilation requirement, the frequencies of bronchopulmonary dysplasia, patent ductus arteriosus, cerebral palsy and neurodevelopmental disorders in very low birth weight infants. However, the effect of caffeine on hyperbilirubinemia was not yet clarified. METHODS: We used astrocyte cell cultures obtained from 2-day-old Wistar albino rats via modified Cole and de Vellis method. UCB concentration toxic to 50% of astrocytes, and caffeine concentration increasing cell viability 100% were used in experiments. While no medication was applied to the control group, UCB (50 µM) and caffeine (100 µM) were applied to the bilirubin and caffeine groups for 24 h. Prophylactic and therapeutic caffeine groups were treated with caffeine 4 h before and after UCB exposure. The effects of caffeine were investigated in rat astrocytes exposed to UCB in terms of cell viability, apoptosis, antioxidant defense, proinflammatory cytokines, and Toll-like receptor (TLR)s. RESULTS: Compared to the control group, UCB increased apoptosis, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, total nitrate/nitrite, and TLR4 levels, and decreased cell viability, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione, and TLR9 levels (for all p < .001). Conversely, prophylactic and therapeutic caffeine improved the detrimental effects of UCB. CONCLUSIONS: Caffeine seems encouraging for the prevention and treatment of bilirubin neurotoxicity in rats by means of its antiapoptotic, antioxidant, anti-inflammatory, anti-nitrosative, and anti-TLR-4 properties.

A newborn with positive antiglobulin test whose mother took methyldopa in pregnancy.

Methyldopa is known to cause the production of autoantibodies against red blood cells (RBCs), leading to a positive direct antiglobulin test (DAT) and hemolytic anemia. In about 20% of patients taking methyldopa, IgG autoantibodies develop against RBCs. However, most of the patients do not have hemolysis. A small percentage of such DAT-positive patients, about 2% of those taking methyldopa, develop an autoimmune hemolytic anemia (AIHA). The fact that the DAT is positive in the newborn with unconjugated hyperbilirubinemia is considered as an isoimmune hemolytic disease caused by blood group incompatibility. In this article, a newborn with jaundice and positive DAT without hemolysis is reported. Her mother had the history of taking methyldopa in her pregnancy. Thus, when newborns are detected with positive DAT and jaundice, without blood group incompatibility, mothers should be questioned regarding drugs used in their pregnancy.

An unusual complication of endotracheal intubation: ingestion of a bulb in a premature neonate.

Endotracheal intubation is a common daily procedure used for sustaining life in premature and term neonates in the neonatal intensive care unit. This procedure can be associated with some iatrogenic complications. One of these complications is ingesting a laryngoscope light bulb, and it is an extremely rare complication in neonates. The consequences of ingestion or aspiration may be serious and life-threatening. Herein, a male premature neonate, ingested a laryngoscope light bulb during endotracheal intubation because of surfactant replacement therapy, is reported. This case re-affirms the importance of checking the integrity of equipment before intubation effort.

A Neonatal Septic Arthritis Case Caused by Klebsiella pneumoniae: A Case Report.

Septic arthritis is encountered very rarely during the neonatal period and its diagnosis can delay because of atypical symptoms, thus it may lead to serious sequelae. The sequale can be prevented by early diagnosis and concomitant treatment. In neonates, pain can be experienced as a result of pseudoparalysis and of movement of the effected joints. A 17-day-old neonatal patient was brought to our hospital with complaint of unrest and then diagnosed with septic arthritis due to propagation of Klebsiella pneumoniae in joint fluid culture was represented because of the rarity of such a case.

Familial mutation in Caffey disease with reduced penetrance: A case report.

Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C > T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members.

A Newborn with Congenital Mixed Phenotype Acute Leukemia After In Vitro Fertilization.

Congenital leukemia is a rare disease. The majority of cases of this disease are acute myelogenous leukemia (AML). Congenital acute lymphoblastic leukemia (ALL) is rare and most often is of B cell lineage. Rarely, some cases have been designated biphenotypic or mixed phenotype acute leukemia (MPAL). Herein, we report a preterm newborn referred to us as a result of the appearance of blue-violaceous dermal nodules on her body at birth. She was a twin and the product of an in vitro fertilization (IVF) pregnancy. Physical examination showed jaundice, hepatosplenomegaly, and peripheral facial nerve palsy in addition to dermal nodules. Bone marrow aspiration showed 40% blasts of lymphoid lineage; skin biopsy and its immunohistochemistry revealed myeloblastic infiltration of the dermis. Cytogenetic analysis (46,XX), fluorescence in situ hybridization (FISH) analysis, and cranial magnetic resonance were normal. The patient was diagnosed with congenital MPAL, and an association between IVF and congenital leukemia was suggested.

The effects of resveratrol on hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that causes significant morbidity and mortality in premature infants. Inflammation and oxidative injury play an important role in the pathogenesis of BPD. Resveratrol is an antioxidant and anti-inflammatory agent. In this study, the histopathological and biochemical effects of resveratrol on a hyperoxia-induced lung injury model in newborn rats were investigated. METHODS: The experiment was performed on newborn rat pups from the 3(rd) to 13(th) postnatal day and they were randomly divided into four groups: Group 1 (air-exposed + saline, n = 10), Group 2 (air-exposed + resveratrol, n = 11), Group 3 (hyperoxia-exposed + saline, n = 6) and Group 4 (hyperoxia-exposed + resveratrol, n = 7). Resveratrol was administered (30 mg/kg/day) intraperitoneally. The histopathological effects of resveratrol on lung tissue were assessed by alveolar surface area, fibrosis, and smooth muscle actin (SMA) score, and the biochemical effects on lung tissue were assessed by glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB) levels. RESULTS: The alveolar surface area, fibrosis, SMA score, and NO levels were found to be significantly higher in Group 3 compared with Group 1 (p < 0.05). In addition, it was found that resveratrol treatment significantly reduced the SMA score and the NO and TNF-α levels, and increased the GSH and SOD levels in the hyperoxia group (p < 0.05). CONCLUSION: This experimental study showed that oxidative stress and NO contributed to the pathogenesis of hyperoxia-induced lung injury, and that resveratrol had a preventive effect on hyperoxic lung injury through its anti-inflammatory and antioxidant properties.

Protective effects of Ginkgo biloba extract in rats with hypoxia/reoxygenation-induced intestinal injury.

BACKGROUND: The purpose of this study is to investigate the protective effects of Ginkgo biloba extract (EGb 761) in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury. METHODS: One-day-old Wistar albino rat pups (n = 21) were randomly divided into 3 groups: group 1 (control, untreated and not exposed to H/R, n = 7), group 2 (untreated but exposed to H/R, n = 7), and group 3 (EGb 761 + H/R, n = 7). Ginkgo biloba extract was administered (100 mg/kg per day, subcutaneously) to group 3 for 3 days. On the fourth day, all animals except controls were exposed to H/R and were killed 6 hours after H/R. Histopathologic injury scores (HIS), malondialdehyde, glutathione (GSH), GSH-peroxidase (Px) activities, and nitric oxide (NO) levels were measured on intestinal samples. RESULTS: Although the control group had normal HIS, group 2 had grade 3 HIS. In contrast, group 3 had minimal HIS, and these results were significantly better than those of group 2 (P < .001). Malondialdehyde and NO levels of group 3 were significantly lower than those of group 2 (P < .01). Glutathione and GSH-Px activities of group 1 were higher than those of groups 2 and 3 (P < .05). However, there were no significant differences for GSH and GSH-Px activities between groups 2 and 3. CONCLUSIONS: This study showed that hypoxia and NO contributed to the pathogenesis of H/R-induced intestinal injury and that prophylactically administered EGb 761 had a protective effect on bowel injury.

Protective effects of clarithromycin in rats with hypoxia/reoxygenation-induced intestinal injury.

BACKGROUND: This study was designed to determine the role of oxidative stress, nitric oxide (NO), and glutathione-related antioxidant enzymes in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury and to evaluate the potential benefits of prophylactic clarithromycin. METHODS: One-day-old Wistar albino rat pups (N = 21) were randomly divided into 3 groups: group I (control), group II (exposed to H/R), and group III (clarithromycin + H/R). Clarithromycin was administered (40 mg/kg) subcutaneously to group III for 3 days. On the fourth day, all rats except controls were exposed to H/R and were killed at 6 hours after H/R. Histopathologic injury scores (HIS), malonyldialdehyde, glutathione (GSH), glutathione-peroxidase (GSH-Px) activities, and NO levels were measured on intestinal samples. RESULTS: Whereas there was no difference for malonyldialdehyde levels among groups, HIS and NO levels were higher in group II than groups I and III (P < .05). However, GSH and GSH-Px activities were lower in group II than groups I and III (P < .05). Clarithromycin significantly increased GSH and GSH-Px activities and reduced HIS and NO levels in group III. CONCLUSION: This study showed that oxidative stress and NO contributed to the pathogenesis of H/R-induced bowel injury and that clarithromycin had a protective effect on bowel injury owing to anti-inflammatory and antioxidant effects.

Electrophysiological assessment of the brain function in term SGA infants.

Small for gestational age (SGA) infants are defined as babies having a birth weight below the 10th percentile for gestational age. A great number of studies have shown that children with SGA have an increased risk of impaired neurodevelopment. Electroencephalography (EEG) is an excellent method for measuring brain maturation in newborns. In this study, the effect of SGA on the maturation of cerebrocortical electrographic activity was investigated by the EEG and also analyzed with power spectral analysis. Serial EEGs were performed in 40 term SGAs, and 20 term appropriate for gestational age (AGA) infants in 1st week, 1st and 3rd month. Power spectral analysis was performed quantitatively in five channels (Fp1-C3, C3-O1, Fp2-C4, C4-O2, and Cz-C4 channels). Amplitude levels of the SGA group were significantly lower than the AGA group in all records. Delta frequency was the major frequency component in the groups. Delta frequency activities in the midline vertex region were decreased in the AGA group with increasing postconceptual age while the activities of the SGA group were increased. Contrarily, beta frequency activities in the midline vertex region were increased in the AGA group with increasing postconceptual age while these activities of the SGA group were decreased. Theta frequency activities in the fronto-central regions were lower in the SGA group. In terms of the vertex, k-complex, and sleep spindle, there was no difference between the two groups. We conclude that cerebrocortical electrophysiological maturation has been delayed in term SGA infants during the first three months of postnatal life.