Severe Neonatal Jaundice Research Articles

Predictors of early-onset permanent hearing loss in malnourished infants in Sub-Saharan Africa

The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the criteria for undernutrition by the Growth Standards of the World Health Organization (WHO) based on weight-for-age, weight-for-length and body-mass-index-for-age were enlisted. EPHL was determined after two-stage screening with transient-evoked otoacoustic emissions, automated auditory brainstem response and diagnostic evaluation. Factors predictive of EPHL were explored with multivariable logistic regression analysis. Some 39 (1.7%) infants from 2254 undernourished infants were confirmed with hearing loss (>30 dB HL). Bilateral EPHL was mild in 7 (17.9%) and moderate-to-profound in 26 (66.7%). EPHL was unilateral in 6 (15.4%). Multiparity, chronological age of more than 30 days, the absence of skilled attendant at birth and severe neonatal jaundice were associated with an increased risk of EPHL while having a Christian mother and exclusive breast feeding had protective effect against EPHL. EPHL is highly prevalent among undernourished infants and associated with modifiable risk factors that can be addressed at the community-level and used as a basis for targeted intervention in resource-poor countries.

Preliminary Evaluation of Six Current Bilirubin Adsorbents on Potential Application for the Hemoperfusion of Severe Neonatal Jaundice

Background: Now hemoperfusion has not been used for the treatment of severe neonatal jaundice, and bilirubin adsorbent with high adsorption and safety should be the prerequisite for the use.

Incidence of neonatal hyperbilirubinemia: a population-based prospective study in Pakistan

To estimate the incidence of neonatal jaundice and hyperbilirubinemia in a poor urban community in Karachi, where 70% of births occur at home. Home-based pregnancy and newborn surveillance were conducted from September 2004 to July 2006 in a multi-ethnic population by trained community health workers. Newborns were visited several times at scheduled intervals until 59 days of life; any baby with jaundice was referred to the local clinic. Clinical assessments of jaundice were assigned by a physician and recorded using an adapted Kramer scale. Blood for plasma bilirubin was obtained if parents consented. Of a birth cohort of 1690 young infants during the study period, 466 infants (27.6%) were referred to our centre with jaundice. Of these, 64% were 0-6 days old. Bilirubin was measured in 125 of 466 (27%) jaundiced newborns. Overall detected rate of hyperbilirubinemia (bilirubin >5 mg/dl) among 1690 newborns was 39.7/1000 live births (95% CI 29.3-47.6). Rate of plasma bilirubin levels in the range of 15-20 mg/dl was 13/1000 live births (95% CI 7.6-18.4); levels >20 mg/dl were observed in 3.5/1000 live births (95% CI 0.4-5.5). The proportion of newborns with bilirubin > or =15 mg/dl was significantly higher among those assigned a Kramer score of 4-5 compared to those receiving a score of 1-3 (P-value 0.00004). A significant burden of untreated severe neonatal jaundice, causing potential neurological sequelae, exists in developing countries such as Pakistan. WHO guidelines are needed for screening and appropriate management of neonatal jaundice in developing countries.

Reducing the burden of severe neonatal jaundice in G6PD-deficient populations in low-income countries: are we doing enough?

Severe neonatal jaundice (NNJ) remains an important cause of hospitalisation in the first week of life particularly in developing countries where glucose-6-phosphate-dehydrogenase (G6PD) deficiency is prevalent. NNJ is seldom associated with mortality when closely monitored but portends significant long-term risks in settings where hospitals are ill-equipped to provide phototherapy or exchange blood transfusion. Early detection in high-risk populations is an important first step towards redressing the current lack of global initiatives on NNJ. Investment in the development of low-cost bilirubin monitoring devices, functional phototherapy units at first-level health facilities and improved care-seeking practices are also essential, particularly in sub-Saharan Africa.

Pre-exchange transfusion administration of albumin: An overlooked adjunct in the treatment of severe neonatal jaundice?

In this issue of Indian Pediatrics, Shahian and Moslehi(1) report that albumin given prior to exchange transfusion in jaundiced but healthy term newborns is associated with significantly lower post-procedure total serum unconjugated bilirubin levels (TSB) and a reduced need for further treatment. Unfortunately, the evidence presented does not support routine administration of albumin prior to exchange transfusion because the actual amounts of bilirubin removed by the procedure are not documented. The bilirubin removed by the procedure is readily obtained by measuring the volume and bilirubin content of the blood discarded during the procedure(2-4). Without these critical data, the study does not prove causation (i.e. that albumin administration was the cause of the difference in outcome).

Perinatal Outcome of Babies Delivered to Eclamptic Mothers: A Prospective Study from a Nigerian Tertiary Hospital

Background: Eclampsia is a leading cause of maternal and perinatal mortality in Nigeria. Preventive and interventional measures have been shown to reduce maternal mortality and morbidity with no significant beneficial effect on neonatal outcomes. The aim of this study is to assess the perinatal outcome of eclampsia at the University of Port-Harcourt Teaching Hospital (UPTH). Materials and methods: This prospective, cross-sectional study was conducted on 88 consecutive patients presenting with antepartum eclampsia at the UPTH between 1st January 2007 and 31st December 2008. A protocol was developed and used to collect information about socio-demographic characteristics, mode of delivery, perinatal complications and outcome. Data collected was entered into a spread sheet using SPSS 15.0 for Windows® statistical software which was also used for analysis. Chi square was used to test relationship between variables. P value<0.05 was considered statistically significant. Results: There were a total of 5488 deliveries at the University of Port-Harcourt Teaching Hospital from January 2007 to December 2008. Of these, 5,310 were live births while 404 were perinatal deaths giving perinatal mortality rate of 73.6 per 1000 live births. Eighty eight (1.6%) of the mothers were eclamptic. Eight (9.1%) were booked, 80 (90.1%) were unbooked. The mean gestational age at delivery was 35.1 ± 4.2 weeks. The main mode of delivery was by emergency caesarian section in 49 (55.7%) of the patients. Others were spontaneous vertex delivery (34.1%), assisted vaginal breech delivery (6.8%) and instrumental vaginal delivery (3.4%). Fifty four babies (61.4%) were admitted into the Special Care Baby Unit. Indications for admission include prematurity (n=23), low birth weight (n=10), severe birth asphyxia (n=12), neonatal jaundice (n=4) and neonatal sepsis (n=5). There were 37 perinatal deaths giving a perinatal mortality rate of 411 per 1000 live births. Of the mortalities, 19 were intrauterine foetal deaths, while 18 were early neonatal deaths. Causes of death include severe birth asphyxia (n=6), respiratory distress syndrome (n=4), prematurity (n=4), neonatal jaundice (n=1) and sepsis (n=3). Conclusion: Eclampsia is a major contributor of perinatal mortality and morbidity in Nigeria. Detection and appropriate management of preeclampsia is critical to reduce the risk of eclampsia.

Growth without Growth Hormone and Similar Dysmorphic Features in Three Patients with Sporadic Combined Pituitary Hormone Deficiencies

Background/Aims: Mutations in the HESX1 gene are associated with a broad spectrum of phenotypes: septo-optic dysplasia, midline defects, pituitary abnormalities with consequent hypopituitarism, isolated growth hormone (GH) deficiency or combined pituitary hormone deficiencies (CPHD). This study examined the prevalence of mutations in the HESX1 gene in patients with CPHD. Patients/Methods: Sixty patients with sporadic CPHD without septo-optic dysplasia were screened for mutations in HESX1. Results: Three patients were found to be heterozygous for the same Asn125Ser variant in the HESX1 gene. In all 3, panhypopituitarism was presented in the neonatal period, manifested by severe hypoglycemia and neonatal jaundice in 2 patients and respiratory distress in 1. Remarkable findings from physical examination included coarse face; prominent, large, low-set ears; and skeletal abnormalities. Magnetic resonance imaging, performed in 2 patients, revealed a hypoplastic anterior and ectopic posterior pituitary without other midline anomalies. Despite persistent GH deficiency and undetectable levels of insulin-like growth factor 1, all patients had normal linear growth along the 10–25th percentile without GH therapy. Conclusion: The present study expands the clinical picture of HESX1 mutations by demonstrating that patients heterozygous for Asn125Ser may have a severe endocrinologic and neuroradiologic phenotype and similar dysmorphic features appearing very early in life.

Sensorineural hearing loss in infants with neonatal jaundice in Lagos: a community-based study

To establish the incidence and predictors of sensorineural hearing loss (SNHL) in infants with neonatal jaundice (NNJ) in an inner-city setting with predominantly non-hospital births. A community-based study in Lagos, Nigeria in which infants with SNHL attending well-child clinics for routine immunisation were detected by two-stage universal hearing screening with transient evoked oto-acoustic emissions and automated auditory brainstem response from July 2005 to December 2006. Predictors of SNHL among infants with a history of NNJ were determined with multivariate logistic regression based on adjusted odds ratio (OR) at 95% confidence intervals (CI). Of the 3676 infants enrolled, 52.4% were not born in hospital and 71 (2.1%) were confirmed to have SNHL. Fourteen (6.0%) of the 234 infants with NNJ had SNHL. Bilateral hearing loss was moderate (41-70 dB) in three (21.4%), severe (71-90 dB) in eight (57.1%) and profound (>90 dB) in two (14.3%) infants. One infant (7.1%) had unilateral SNHL. Six (42.9%) of the infants with SNHL had a profile suggestive of auditory neuropathy/dyssynchrony. Christianity (OR 0.15, CI 0.03-0.93), multiparity (OR 7.33, CI 1.17-45.99), low social class (OR 6.04, CI 1.33-27.48), infant's age (OR 10.17, CI 1.91-54.05), multiple gestations (OR 10.55, CI 1.98-56.11) and exchange blood transfusion (OR 7.74, CI 1.66-36.2) were predictive of SNHL. This model has a sensitivity of 85.7%, a specificity of 83.6%, a negative predictive value of 98.9% but a positive predictive value of only 25.0% for identifying SNHL among infants with severe NNJ. SNHL is prevalent among infants with NNJ and community-orientated early detection to curtail the associated long-term developmental consequences is feasible in resource-poor settings where facilities for clinical monitoring are limited. Hearing evaluation of infants treated for severe NNJ should be incorporated into the management and follow-up of these patients.

Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis

Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life.

Universal infant hearing screening programme in a community with predominant non-hospital births: a three-year experience

Background:To evaluate three-year outcomes of a pilot community-based universal newborn/infant hearing screening programme (UNHS) and the associated factors in a low-income country where a high proportion of births occur outside...

Infants with severe neonatal jaundice in Lagos, Nigeria: incidence, correlates and hearing screening outcomes

To establish the incidence, correlates and hearing screening outcomes of infants with severe neonatal jaundice in Nigeria. Community-based study in which all infants attending Bacille Calmette-Guérin immunisation clinics in inner-city Lagos were enrolled into a universal hearing screening programme during which correlates of severe neonatal jaundice (requiring phototherapy and/or exchange blood transfusion) were explored with multivariable logistic regression. Of the 5262 infants enrolled, only 48.7% were born in hospitals although almost all mothers (97.9%) attended antenatal clinics. 6.7% had a history of neonatal jaundice of whom 5.5% (95% CI:4.9-6.2) received phototherapy and 1.9% (95% CI:1.5-2.3) had an exchange blood transfusion. Factors independently associated with severe neonatal jaundice were maternal religion, occupation, use of herbal preparations during pregnancy, infant's gender, weight at screening, multiple gestation and place of birth. All but two infants with severe neonatal jaundice were exclusively breast-fed. Of those who failed the hearing tests, 17.3% were treated with phototherapy and 11.3% had an exchange blood transfusion. At least 8.9% of infants requiring phototherapy and 17.3% of those requiring exchange blood transfusion were at risk of sensorineural hearing loss. Severe neonatal jaundice is a significant condition associated with modifiable risk factors in this population. Policy initiatives for prevention, early detection followed by appropriate and timely intervention are urgently needed to reduce the disease burden.

Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria

Since exchange blood transfusion (EBT) is associated with serious complications, phototherapy has been made more powerful to reduce the need for EBT in the developed world. This study was undertaken to determine the indications for EBT in neonatal jaundice (NNJ) at our unit and what proportion of EBTs was possibly avoidable. All the babies who had EBT for hyperbilirubinemia over a three-year period were included. Age, sex, weight, place of delivery, blood group of baby and mother, other investigations, management, and the outcome of the babies were recorded. Of the 1686 babies admitted to the neonatal unit, 90 (5.3%) had EBT. Fourteen (15.6%) were inborn while 76 (84.4%) were out-born babies. Fifty-six (62.2%) babies were admitted primarily for NNJ while 34 (37.8%) developed NNJ during admission. Thirty-six (40.0%) of the babies had phototherapy for more than 24 hours prior to EBT either because they were of very low birthweight or NNJ was detected very early and therapy was so commenced. Sixty-eight (75.6%) babies had single EBT while the remaining 22 (24.4%) had two sessions of EBT. Factors associated with severe NNJ in babies requiring EBT included low birthweight (<2500 g, 44.4%), ABO incompatibility (30.0%), glucose-6-phosphate dehydrogenase deficiency (34.4%) and septicemia (26.1%). Twenty-seven (30.0%) of the neonates developed features of kernicterus: 26 before admission while 1 during admission; all except one were delivered outside the hospital. The EBT rate in our center was high. With more effective phototherapy, EBT could be avoided in most of the babies who initially had phototherapy for more than 24 hours before EBT and repeated EBT sessions. Health education of the population at risk, especially pregnant women, and early referral at the primary health care level will reduce the burden of severe NNJ.

Congenital thrombotic thrombocytopenic purpura associated with unilateral moyamoya disease

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy disorder associated with congenital or acquired deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The central nervous system and kidneys are the two major organs of involvement in TTP. Moyamoya (puff of smoke) disease is a cerebral arteriopathy of unknown etiology characterized by narrowing or occlusion of the distal internal carotid or proximal anterior or middle cerebral arteries, which causes the formation of multiple tiny collateral networks. We report here a case of an 11-year-old boy with unilateral moyamoya disease and congenital TTP. The patient had a history of severe neonatal jaundice and thereafter recurrent episodes of hemolytic anemia associated with renal dysfunction and cerebral infarction. The plasma ADAMTS13 activity of the patient <3% of normal, and ADAMTS13 gene analysis revealed an abnormal splicing mutation (c.330+1 G > A) in one allele and a novel missense mutation (p.Ile1217Thr) in the other. This is the first case of a genetically confirmed congenital TTP associated with unilateral moyamoya disease. Although the causal relationship between the two diseases has not been established, TTP may be included as one of the causes of moyamoya syndrome.

Natural History of 33 Patients with Upshaw-Schulman Syndrome Has Revealed That All the Gravida Develop Thrombocytopenia, Often Followed by Thrombotic Microangiopathy with Stillbirth.

Upshaw-Schulman syndrome (USS) is a congenital deficiency of the activity of von Willebrand factor (VWF)-cleaving protease or ADAMTS13 due to its gene mutations. USS is a complex thrombo-hemorrhagic disease, but its hallmark is severe neonatal jaundice soon after birth that often requires for exchange blood transfusion, and subsequently during childhood they have repeated episodes of chronic thrombocytopenia and hemolytic anemia that are reversed by infusions of fresh frozen plasma. However, after a discovery of ADAMTS13, the presence of two phenotype expression on USS-patients was described; one is the early-onset type as abovementioned, and the other is the late-onset type which is asymptomatic during childhood and the first bout develops after adolescent or during adulthood, in association with infections or pregnancy. During the past 8 years, we diagnosed 33 patients with USS. Through analyzing the natural history and the phenotype-genotype expression in these patients, and more specifically to 9 USS-patients who had their first bout at pregnancy, we found that two clinical phenotypes of USS are mostly attributable to misdiagnosis or overlook of thrombocytopenia during childhood, and excluded a possibility of the concern on a trace amount of ADAMTS13 activity which has not been evaluated by the previous methods. Further, in vitro studies we have clearly shown that platelet aggregation or thrombi formation under high shear stress is tremendously up-regulated in the absence of ADAMTS13, that occurs proportionally to the amount of high VWF multimers, that in part is assumed to be an in vitro reflection of the circulation in USS-gravida. [Display omitted]

Coexistence of Congenital Red Cell Pyruvate Kinase Deficiency and Hereditary Stomatocytosis.

We describe a case of chronic hemolytic anemia due to the co-presence of pyruvate kinase (PK) deficiency and Hereditary Stomatocytosis (HSto). The propositus was a 30 years old adopted male with no known family history; he had severe neonatal jaundice requiring exchange transfusion, followed by a life-long history of moderate to severe chronic hemolytic anemia (Hb 7–10 g/dL), with jaundice and splenomegaly. At the age of 6 months hemoglobin screening was made and a beta trait was found. At the age of 20 splenectomy and cholecystectomy were performed. Surgery resulted in an increase of 1.5 g/dL in haemoglobin, and in a conspicuous rise of reticulocytes (from 125×109/L to 562×109/L). Two thrombotic events occurred thereafter, the former 6 days after surgery, and the latter two years later, during a toxoplasmosis infection. At the time of the study Hb was 10.8 g/dL, MCV 82.2 fL, reticulocytes 562×109/L, unconjugated bilirubin 2.19 mg/dL, LDH 335 U/L, haptoglobin <20 mg/dL, serum ferritin 342 ng/mL and transferrin saturation 71%. The peripheral blood smear examination showed the presence of echinocytes (13%), stomatocytes (11%), acantocytes (10%), schistocytes (7%), elliptocytes (6%), spherocytes (4%), target cells (4%) and a few erythroblasts. Erythrocyte osmotic fragility was decreased; screening test for unstable hemoglobins and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of red cell membrane gave normal results. The study of the most important red cell enzymes revealed reduced PK activity (6.0 UI/gHb, normal range 11.1–15.59 UI/gHb) and thermal stability (43%, normal range 57–100%). Direct sequencing of PK-LR gene showed a compound heterozygosity for mutation 1456T (Arg486Trp) and the new variant −73g>c. Mutation −73g>c occurs in the most proximal of the four GATA motifs in the R-type promoter region and possibly result in a decrease of mRNA synthesis, as already reported for the variant −72a>g (Manco et al, 2000). Molecular analysis of HFE gene showed heterozygosity for H63D mutation. The history of post splenectomy thrombosis and the presence of stomatocytes in peripheral blood smear prompted us to investigate for the coexistence of hereditary stomatocytosis. The determination of plasma potassium and sodium concentration revealed an increase in intracellular sodium (16.3 mmol/LRBC, reference range 5.0–12.0) and a decrease in intracellular potassium (74.73 mmol/LRBC, reference range 90–103), suggestive for a diagnosis of dehydrated HSto, or hereditary xerocytosis. This defect likely accounts for the thrombophilic state in this case, since HSto is known to be associated with hypercoagulability, particulary after splenectomy.

Bilirubin encephalopathy: A study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases

Bilirubin encephalopathy (BE), which includes acute (kernicterus) and chronic (postkernicteric) forms, results from severe neonatal jaundice. In order to investigate neurodegenerative mechanisms in autopsy cases of BE, we immunohistochemically examined expressions of neurotransmitters, neuropeptides, and calcium-binding proteins in the basal ganglia; and deposition of oxidative products. Expression of tyrosine hydroxylase was reduced in the putamen in cases of acute BE, and in the globus pallidus in cases of acute and chronic postkernicteric BE. Methionine–enkephalin expression was reduced in the external segment of the globus pallidus in cases of acute and chronic postkernicteric BE, and immunoreactivity for substance P was severely altered in both internal and external segments in cases of chronic postkernicteric BE. A decrease in the number of parvalbumin-immunoreactive interneurons in the external segment of the globus pallidus was observed predominantly in cases of acute BE, whereas the number of interneurons immunoreactive for calbindin-D28K was reduced in the putamen in cases of chronic postkernicteric BE. Nuclear immunoreactivity for 8-hydroxy-2′-deoxyguanosine was seen in the putamen in half of the BE cases. These findings indicated that the putamen was impaired in BE and the pallidal external segment was also damaged in the acute form of BE, suggesting that oxidative damage to DNA is implicated in lesions of the basal ganglia.

Blood transfusion therapy in neonates admitted into the Special Care Baby Unit (SCBU) of University of Port Harcourt Teaching Hospital, Port Harcourt

Blood transfusion is associated with potential risks and adverse effects; it is therefore pertinent to ensure that it is given only when it is indicated. The objective of this study is to determine the rate and the indications of blood transfusion in neonates admitted into the Special Care Baby Unit (SCBU) of University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt. A prospective study of Neonates admitted into SCBU between January 1st 2003 and December 31st 2004 and who had blood transfusion during their hospitalization was carried out. Preterm babies are more likely to be transfused and are also more likely to receive multiple blood transfusions. Severe neonatal jaundice and severe anaemia are the commonest indication for blood transfusions in the neonates. Exchange blood transfusions (EBTs) were utilized more often than top up transfusions even among preterms. Adverse events were seen more in those that had EBT CONCLUSION: The rate of blood transfusion is still very high among neonates. Concerted efforts should be made to prevent severe neonatal jaundice and severe anaemia and thus reduce the rate of blood transfusion.

Molecular basis of glutathione reductase deficiency in human blood cells

AbstractHereditary glutathione reductase (GR) deficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red blood cells and leukocytes of the patients in family 1 did not contain any GR activity, and the GR protein was undetectable by Western blotting. Owing to a 2246-bp deletion in the patients' DNA, translated GR is expected to lack almost the complete dimerization domain, which results in unstable and inactive enzyme. The red blood cells from patient 2 did not exhibit GR activity either, but the patient's leukocytes contained some residual activity that correlated with a weak protein expression. Patient 2 was found to be a compound heterozygote, with a premature stop codon on one allele and a substitution of glycine 330, a highly conserved residue in the superfamily of NAD(P)H-dependent disulfide reductases, into alanine on the other allele. Studies on recombinant GR G330A revealed a drastically impaired thermostability of the protein. This is the first identification of mutations in the GR gene causing clinical GR deficiency.

Rapid detection of the UGT1A1 single nucleotide polymorphism G211A using real‐time PCR with Taqman minor groove binder probes

The UGT1A1 Taqman MGB probe single nucleotide polymorphism (SNP) genotyping assay was developed to detect nucleotide 211 of the UDP-glucoronocyltransferase 1A1 (UGT1A1) gene. Defects in this enzyme interfere with process of conjugation of bilirubin and cause unconjugated hyperbilirubinemia. Variation at nucleotide 211 in the coding region of the UGT1A1 gene has been shown to be prevalent in Japanese and Chinese. Using an ABI sequence detection system (SDS) 7000, an allele-specific real-time PCR-based genotyping method was established to detect nucleotide G211A. Cord blood from 125 infants without hyperbilirubinemia (controls) were compared with cord blood from 74 infants (cases) with severe hyperbilirubinemia (total serum bilirubin > 300 micromol/L). Homozygous variation of the UGT1A1 gene at nucleotide 211(A/A) is significantly more common in cases (14.9%) than in controls (0.8%) (P<0.001). Direct sequencing from 20 randomly selected samples showed eight samples with homozygous wild type, seven with homozygous variant, and five samples were heterozygous. The result from this assay was in complete concordance with the DNA sequencing result and clearly discriminate wild-type (G/G), homozygous variant (A/A), and heterozygous (G/A). This assay is rapid and robust for screening of SNP G211A to determine if this polymorphism plays a role in causing severe neonatal jaundice in the local context.

The Frequency of UDP-Glucuronosyltransferase 1A1 Promoter Region (TA)7 Polymorphism in Newborns and it's Relation with Jaundice

Increased bilirubin formation and decreased bilirubin conjugation play an important role in the pathogenesis of the newborn jaundice. Although physiologic jaundice is seen in most of the newborns, there are many risk factors that affect the severity and duration of hyperbilirubinemia. The latest studies showed that the frequency and severity of neonatal jaundice have been increased when mutations of the gene coding UDP-glucuronosyltransferase(UGT)1A1 coexist with other risk factors. Healthy term newborns weighing over 2500 g. were included in this study. The patient group consisted of 107 newborns either with total bilirubin level over 15 mg dl(-1) within 7 days or 5 mg dl(-1) after 15 days of age. The control group consisted of 55 newborns with bilirubin levels in physiological ranges. We investigated the frequency of promoter region [thymine-adenine(TA)]7 polymorphism in UGT1A1 gene. Factors which might cause pathologic and prolonged jaundice with coexisting polymorphism were also investigated. UGT1A1 6/7 genotype was found to be 11% in patient group and 13% in the control group. The difference between patient and control groups was not statistically significant. (TA)7 allele frequency was 0.069 and it is concluded that UGT1A1 promoter region polymorphism was not a risk factor for neonatal jaundice.