Do Gene Polymorphisms Play a Role in Newborn Hyperbilirubinemia?

Objectives: Polymorphisms of the uridine-diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, hepatic solute carrier organic anion transporter 1B1/B3 (SLCO1B1/3) gene, and glutathione S-transferase (GST) gene have been associated with significant hyperbilirubinemia in some populations. This study aims to determine whether the variation of UGT1A1, SLCO1B1/3 and GST genes play an important role in neonatal hyperbilirubinemia in Turkish newborn infants. Methods: The study included 61 idiopathic hyperbilirubinemia cases, 28 prolonged jaundice cases, and 41 controls. Ten common polymorphisms in four genes involved in bilirubin metabolism were examined. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect variants of those genes. Results: No association was found between the variants of UGT1A1 at nt 211, the SLCO1B1 gene at nt 388, 463, 521, 1463, the SLCO1B3 gene at nt 334, 727+118, 1865+19721, and the GST gene at nt 313, 341, and neonatal hyperbilirubinemia. There was no difference between the case and control groups in terms of allele frequencies of these genes (except SLCO1B3 at nt 334) (p>0.05 in all comparisons). The presence of the G allele of the SLCO1B3 at nt 334 variant gene seemed to protect from jaundice in infants with idiopathic hyperbilirubinemia. Conclusion: These gene polymorphisms currently studied do not seem to modulate the risk of hyperbilirubinemia in Turkish newborn infants.

Treacher Collins syndrome with multiple congenital heart defects after paroxetine exposure: case report.

Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development with an incidence of I in 40,000 to in 70,000 live births. It is characterized by abnormalities of the pinnae which are frequently associated with atresia of the external auditory canals and anomalies of the middle ear ossicles. Rarely congenital heart defects can be present. Prenatal paroxetine exposure may enhance the risks of major malformation, particularly cardiac defects. This article reports a newborn, whose mother used paroxetine during pregnancy, presenting with multiple congenital heart defects associated to typical physical characteristics of Treacher Collins syndrome.

Crisponi syndrome: a new mutation in CRLF1 gene associated with moderate outcome.

SUMMARY: Crisponi syndrome (CS) is a rare, autosomal recessive disorder, characterized by hyperthermia, extensive muscular contractions in the face after even minimal stimuli or crying, hypertonia, opisthotonus, camptodactyly, and typical facial features. Recently, it has been demonstrated that CRLF1 (cytokine receptor-like factor 1) gene mutation is associated with CS. Here we report a case of CS with a new mutation in the CRLF1 gene associated with moderate clinical phenotype.

Papillorenal syndrome with de novo reciprocal translocation t(2;15) (q31; q26).

Renal hypoplasia is a congenital anomaly, the etiology of which is not yet fully known. Genetic studies have shown that certain genes, in utero environmental factors and molecular mechanisms have a role in the identification ofnephron formation and kidney size. The coexistence of bilateral renal hypoplasia and optic disc coloboma is observed in papillorenal syndrome, which caused by the mutation of the PAX2 gene. In the case presented in this article, bilateral renal hypoplasia and optic disc coloboma have been detected to coexist. The analysis of the PAX2 gene, which was carried out with an eye to the papillorenal syndrome, did not reveal any mutations. However, de novo t(2;15) (q31; q26) (reciprocal translocation) was detected in chromosome analysis. As far as we know, there are not any publications focusing on the clinical importance of this type of translocation. In cases with renal hypoplasia and optic disc coloboma, the possibility of a de novo translocation between chromosomes 2 and 15 should be considered.

A novel mutation of laminin ß-2 gene in Pierson syndrome manifested with nephrotic syndrome in the early neonatal period.

Pierson syndrome is a rare autosomal recessive disorder which is mainly characterized by congenital nephrotic syndrome (CNS), diffuse mesangial sclerosis (DMS) and distinct ocular abnormalities, including microcoria. Most affected children exhibit early onset of chronic renal failure, neurodevelopmental deficits, and blindness. It is caused by a homozygous or compound heterozygous mutation in the gene encoding laminin beta2 (LAMB2) on chromosome 3p21. In this article, we report on a patient with CNS, bilateral megalocornea and microcoria. The patient had developed renal failure at very early postnatal period and died of septic shock. A novel homozygous donor splice mutation (IVS4 + 2T > C) in LAMB2 gene was identified in the patient.

Spectrum of Brevundimonas vesicularis infections in neonatal period: a case series at a tertiary referral center.

OBJECTIVES: To report infections caused by Brevundimonas vesicularis and the treatment regimens administered based on antibiotic studies of this Gram-negative bacterium in the neonatal period. PATIENTS AND METHODS: Eight hospitalized neonates with positive blood cultures for Brevundimonas spp. were studied. Demographic data, clinical and laboratory findings, nutritional regimens, presence of primary disease, and the antibiotic regimens administered during the treatment of these neonates were noted. Antimicrobial susceptibility tests were performed on isolates of the positive cultures. RESULT: Four neonates were preterm, and four were full-term infants. The underlying diseases--with the exception of being a neonate--were congenital heart disease (4 patients), respiratory distress syndrome (2), multiple congenital cerebral anomalies (1), and meconium aspiration syndrome (1). Septicemia was observed in all eight patients, while three also had concurrent meningitis. Multidrug resistance to the antimicrobials, including piperacillin-tazobactam, ceftazidime, and aztreonam, were identified in all eight infants; however, susceptibility to amikacin and imipenem was retained. All study patients responded to the antibiotic treatments and subsequent cultures were sterile. One patient died due to other causes. CONCLUSIONS: We consider that until larger series are available, B. vesicularis should be regarded as virulent. Consequently, in this era of multi-resistant Gram-negative bacteria, serious B. vesicularis infections in neonates should be treated with a broad-spectrum agent, such as third-generation cephalosporin until the results of susceptibility testing are available. Our case reports demonstrate that the susceptibility of this organism to all aminoglycosides and third-generation cephalosporin is not uniform, but that most of the isolates are susceptible to imipenem. More treatment experience and more exact results from antimicrobial susceptibility testing are required to improve on present treatment regimens for invasive B. vesicularis infections.

A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome.

Denys-Drash syndrome (DDS) is a rare disorder characterized by glomerulopathy, genital abnormalities and predisposition to Wilms' tumor. It is associated with constitutional Wilms'tumor suppressor 1 (WT1) gene mutations, in which the majority being missense mutations in the zinc-finger region. Here, we present a newborn with DDS, associated with a novel heterozygous missense mutation, p.Asp396His, on exon 9 of WT1.

A linear fracture and meningitis associated with non-infected cephalohematoma in a neonate.

We present a neonate with cephalohematoma complicated by a linear skull fracture and Staphylococcus epidermidis meningitis. Clinicians, especially neonatologists, should be aware that a cephalohematoma in the newborn infant with a history of vacuum-assisted delivery could be the origin or trigger point of the infection either as sepsis, meningitis or osteomyelitis. The utmost importance of screening studies should be emphasized in order to be aware of the pathogenic potential of cephalohematomas.

An uncommon association of vacterl complex with hypertrophic pyloric stenosis and horseshoe lung.

We report a case of VACTERL complex which had concomitant horseshoe lung, laryngeal cleft, and hypertrophic pyloric stenosis, which has not been previously reported.

Neonatal thrombo-embolism: risk factors, clinical features and outcome.

BACKGROUND: There are few data with respect to prothrombotic risk factors in neonates. AIM: To determine the associated risk factors, clinical features and outcome in newborn infants diagnosed with thrombo-embolism. METHODS: Case records of 25 infants (17 full-term and eight preterm) diagnosed with thrombo-embolism between January 2005 and April 2008 in a neonatal intensive care unit were reviewed. RESULTS: Of the 25 infants, 18 cases of venous (72%) and seven of arterial (28%) thrombo-embolism were recorded; in 18 it was associated with central catheterisation. The sites of thrombosis were portal vein (15), right renal vein (one), right femoral vein (one), multiple veins (one), right femoral artery (3), right iliac artery (2), bilateral iliac and renal arteries (one) and left renal artery (one). Hereditary thrombotic mutations were detected in three patients and anticardiolipin antibody was detected in one, none of whom had been catheterised. The remaining three non-catheterised patients had perinatal risk factors. Venous catheter placement was undertaken in 12 patients (48%), eleven of whom had: umbilical venous catheterisation for exchange transfusion (9), partial exchange transfusion (one) and venous access (one), and one had femoral venous catheterisation for an angiographic study. Arterial catheterisation was undertaken in seven patients (28%) (one infant had both umbilical venous and arterial catheters) for angiographic studies (5) and blood sampling (2). Of the 18 catheterised patients (72%), thrombophilic studies were undertaken in 13 and none had abnormal results. Additional perinatal risk factors were present in 18 patients (72%) and included prematurity (8), congenital heart disease (8), septicaemia (5), dehydration (3), respiratory distress syndrome (3), polycythemia (2), meconium aspiration syndrome (one), pneumonia (one), maternal diabetes (one), necrotising enterocolitis (one) and perinatal asphyxia (one). Although most of the patients recovered after anticoagulant or fibrinolytic therapy, the five (20%) deaths were associated mainly with underlying diseases. CONCLUSION: The most important risk factor for thrombo-embolic events in neonates is placement of central catheters and some perinatal prothrombotic conditions. Nevertheless, hereditary or acquired thrombophilic risk factors may also be a cause of thrombo-embolism.

Hyperparathyroidism secondary to maternal hypoparathyroidism and vitamin D deficiency: an uncommon cause of neonatal respiratory distress.

A 4-day-old neonate presented with respiratory distress owing to chest wall deformity associated with metabolic bone disease. He was found to have congenital hyperparathyroidism and his mother was suffering from post-surgical hypoparathyroidism and vitamin D deficiency. The patient was given calcium lactate and maintenance doses of vitamin D. The respiratory distress subsided, the parathyroid hormone level returned to normal and by 4 weeks of age bone mineral content had improved. Congenital hyperparathyroidism should be considered in neonates presenting with respiratory distress and chest deformity.

Apparent Lenz microphthalmia syndrome: a patient with unusual manifestations.

Lenz microphthalmia syndrome was first described by Lenz et al. in 1955 (9). The cardinal features of the syndrome are microphthalmia or anophthalmia, microcephaly, mental retardation, external ear, digital, cardiac, skeletal, dental and genitourinary anomalies. Here we present a case of Lenz microphthalmia syndrome that shows the typical characteristics and, additionally, macrophallus, a broad chest with widely spaced nipples, wide gap between first and second toes, which are unusual manifestations in Lenz Microphthalmia Syndrome.

Outcome of primary peritoneal drainage for perforated necrotizing enterocolitis: comparison between laparotomy and drainage.

Perforation of the gastrointestinal tract in neonates is still associated with high mortality rates. Laparotomy is usually required to treat gastrointestinal perforation, however peritoneal drainage under local anesthesia has been also described as an alternative mode of treatment. In our institute, laparotomy was the first choice for the management of gastrointestinal perforation in neonates until 1999. Because of the high mortality rates in this group of patients, our policy has since changed to the use of primary peritoneal drainage instead. The aim of this study is to compare the effectiveness of primary peritoneal drainage (PPD) and primary laparotomy (PL) procedures in the management of gastrointestinal perforation due to necrotizing enterocolitis in neonates. Between 1994 - 1998, ten babies with intestinal perforation underwent PL, whereas fifteen newborns with similar findings were treated with PPD between 1999 and 2003. Eight (80 %) of the patients died in the PL group prior to 1999. In the PPD group 8 (53.3 %) of babies required no further treatment and were discharged without any complications. Four (26.7 %) patients in this group needed laparotomy later, and three (75 %) of them survived. In conclusion, we believe that PPD is more effective than PL for the management of perforated necrotizing enterocolitis in neonates. Laparotomy can be used in particularly unresponsive cases after primary peritoneal drainage.

D2 receptor imaging with iodine-123-iodobenzamide brain SPECT in infants with hypoxic-ischemic brain injury.

UNLABELLED: The purpose of this study was to evaluate the striatal dopamine D2 receptor density in infants with perinatal hypoxic-ischemic brain injury (HIBI) using 123I-iodobenzamide (IBZM) brain SPECT and to correlate the findings with the severity of HIBI and neurologic outcome. METHODS: Twenty infants who were diagnosed to have perinatal HIBI were included in this study. They were classified as having mild (n = 6), moderate (n = 10) or severe (n = 4) HIBI according to their neurologic findings at birth using the criteria of Sarnat and Sarnat. Neurologic outcome of these infants was determined by serial neurologic examinations and the Denver developmental screening test; 10 infants recovered without any deficit and the remaining 10 were affected to a degree varying from motor impairment to cerebral palsy. All 20 infants were examined using 123I-IBZM brain SPECT at age 7.8 +/- 2.3 mo. Transaxial slices were obtained 2 hr after intravenous injection of 300 micro ci (11.1 MBq) 123I-IBZM and the activity ratios of striatal to occipital cortex (ST/OC) were calculated. RESULTS: The mean ST/OC ratios in patients with mild, moderate and severe HIBI (1.219 +/- 0.078, 1.097 +/- 0.069 and 0.813 +/- 0.140, respectively) were significantly different from each other (p = 0.001). The infants who recovered from HIBI without any neurologic sequelae had higher mean ST/OC ratios than the others (1.184 +/- 0.010 versus 0.969 +/- 0.160, p = 0.002). CONCLUSION: The results of this study show that in infants with HIBI, striatal D2 receptor density decreases as the severity of injury increases. The D2 receptor density is higher in infants who recover without neurologic deficits compared to those who are affected neurologically. Dopamine D2 receptor imaging can be used to assess the severity of HIBI in children.

Level of conus medullaris in term and preterm neonates.

AIMS: To compare the levels of conus medullaris in preterm and term neonates; to show the time of ascent to normal; and to evaluate the babies with low conus medullaris levels for tethered cord syndrome. METHODS: Levels were assessed using ultrasonography in 41 preterm and 64 term neonates. RESULTS: In the preterm group the conus medullaris level in one infant (2.4%) was below L4. In three infants (7.2%) it was between L2 and L3 and in 37 infants (90.4%) it was above L2. In the term group it was below L4 in one baby (1.6%), between L2 and L3 in four (6.3%), and above L2 in 57 babies (92.1%). The difference in the conus medullaris levels between term and preterm neonates and genders was not significant. Two patients, one with a conus medullaris level at L4-L5, and the other at L2-L3, had Down's syndrome. CONCLUSION: The ascent of conus medullaris seems to occur early in life. It is important to follow up patients with conus medullaris levels at or below the 4th lumbar vertebra for the development of tethered cord syndrome.

The effect of asphyxia on gut blood flow in term neonates.

Transcutaneous Doppler ultrasound measurements were made of the superior mesenteric artery of 25 term infants to correlate the intestinal blood flow with neonatal acid-base status as measured in umbilical artery blood and newborn condition as reflected by Apgar score. Compared with the babies whose umbilical artery pH was higher than 7.20 (peak systolic velocity: 84.1 cn/sn, mean velocity 48.6 cm/sn), the blood flow of superior mesenteric artery was significantly decreased in the newborn babies whose umbilical artery pH was less than 7.20 (peak systolic velocity 48.8 cm/sn, mean velocity = 32.6 cm/sn). Although no such relationship existed between Apgar scores and superior mesenteric artery blood flow indices, a significant linear correlation between superior mesenteric artery blood flow and umbilical artery pH was noted. A reduction of intestinal circulation was observed during umbilical cord blood acidemia and hypoxemia.