UGT1A1 sequence variants and bilirubin levels in early postnatal life: a quantitative approach

<p>Abstract</p> <p>Background</p> <p>Fundamental to definitively identifying neonates at risk of developing significant hyperbilirubinemia is a better understanding of the genetic factors associated with early bilirubin rise. Previous genetic studies have focused on the UGT1A1 gene, associating common variation in the coding or promoter regions with qualitative assessments of bilirubin (i.e. significantly elevated or not). These studies have had conflicting results and limited success. We chose to approach the problem by focusing on the quantitative (absolute) change in bilirubin levels early in post-natal life. We apply this approach to the UGT1A1 gene - exploring the contribution of both rare and common variants to early bilirubin changes.</p> <p>Methods</p> <p>We sequenced the exons, PBREM, 5'-, and 3'- regions of the UGT1A1 gene in 80 otherwise healthy term neonates who had repeat bilirubin levels measured within the first five days of life.</p> <p>Results</p> <p>Three novel coding variants were observed, but there was no clear relationship between rare coding variants and bilirubin rise. Adjusted linear regression models fit to evaluate the relationship between changing bilirubin levels and common UGT1A1variants found that among 39 neonates whose bilirubin was resampled within 33 hours, individuals homozygous for the mutant allele of a 3'UTR SNP had significantly smaller changes in bilirubin (P = 0.003) than individuals carrying the wild-type allele.</p> <p>Conclusions</p> <p>Collectively, rare UGT1A1 coding variants do not appear to play a prominent role in determining early bilirubin levels; however common variants in the 3' UTR of UGT1A1 may modulate the early bilirubin rise. A quantitative approach to evaluating early bilirubin kinetics provides a more robust framework in which to better understand the genetics of neonatal hyperbilirubinemia.</p

Neonatal jaundice and stool production in breast- or formula-fed term infants

It has remained unclear whether the amount of fecal fat excreted in the stool and stool production influences the severity of neonatal jaundice. We determined the relationship between stool production, fecal fat excretion and jaundice in healthy breast-fed (BF) or formula-fed (FF) (near-)term neonates. From postnatal day 1–4, we quantitatively collected stools from 27 FF and 33 BF infants in daily fractions. Stool production and fecal fat contents were related to unconjugated bilirubin (UCB) levels, as determined by transcutaneous bilirubinometry (TcB). Bilirubin concentrations and stool production did not differ between FF and BF neonates during the study period. Neonatal bilirubin levels were not inversely correlated with stool production. FF and BF infants had similar fecal fat excretion rates. The stool production of FF infants was profoundly lower in the present study than in a 1985 study by De Carvalho et al. [J Pediatr (1985) 107:786–790]. We conclude that increased jaundice during the first postnatal days in healthy term neonates can no longer be attributed to breast-feeding and speculate that improved absorbability of formulas since 1985 has contributed to similar fat excretion and stool production in FF and BF neonates in 2007

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Neonatal hypokalemia

Dilek Sarici1, S Umit Sarici21Kecioren Research and Education Hospital, Kecioren, Ankara, 2Chief of Division of Neonatology, Division of Neonatology, Department of Pediatrics, Gulhane Military Medical Academy, Ankara, TurkeyAbstract: In this article, distribution of potassium (K+) in body fluids, pathophysiology, causes, clinical signs and symptoms, and the evaluation and treatment of neonatal hypokalemia are reviewed. K+ is the most important intracellular cation and normal serum K+ is stabilized between 3.5 and 5.5 mEq/L. Hypokalemia may be caused by increased renal losses, increased extrarenal (gastrointestinal) losses, redistribution or prolonged insufficient K+ intake. Clinical signs and symptoms occur as the result of functional changes in striated muscle, smooth muscle, and the heart. Hypokalemia is usually asymptomatic when K+ levels are between 3.0 and 3.5 mEq/L; however, there may sometimes be slight muscle weakness. Moderate hypokalemia is observed when serum K+ is between 2.5 and 3.0 mEq/L. Proximal muscle weakness is observed most commonly in lower extremities; cranial muscles are normal, but constipation and distention are prominent. Severe hypokalemia develops when serum K+ falls below 2.5 mEq/L. Rhabdomyolysis, myoglobinuria, severe muscle weakness, paralysis, respiratory distress, and respiratory arrest are observed. The clinical signs and symptoms may be unremarkable in cases of chronically developing hypokalemia; however, appropriate treatment is essential when serum K+ level falls below 2.5 mEq/L as the most dangerous complication of hypokalemia is fatal cardiac arrythmia, and changes visible with electrocardiography may not always correlate with the level of hypokalemia. Sodium (Na+), K+, chloride (Cl-), bicarbonate, creatinine, blood sugar, magnesium (Mg), plasma renin activity, aldosterone, and blood gases should be investigated by laboratory testing. Aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine kinase isoenzyme MB should be studied if rhabdomyolysis is suspected. In urine sample density, pH, Na+, K+, Cl-, Mg, creatinine, and myoglobinuria (blood reaction is positive in the absence of erythrocytes on microscopic examination of urine) should be investigated. The primary aim of therapy is to prevent and treat life-threatening cardiac and muscular complications. However, in the presence of severe symptomatic hypokalemia and gastrointestinal problems such as ileus, the intravenous route may be used in cases where serum K+ level is usually below 2.6 mEq/L. K+ given in intravenous fluids should not exceed 40 mEq/L. In case of emergency, 0.3&amp;ndash;1 mEq/kg of K+ may be given intravenously over 1 hour. When higher concentrations (60&amp;ndash;80 mEq/L) are needed, infusion through a central vein under electrocardiography monitoring may be used.Keywords: neonatal, hypokalemia, newborn&amp;nbsp

Blood lead levels in glue sniffers

The aim of this study was to investigate blood levels of lead (Pb) among adolescents with glue sniffing in Turkey. Blood Pb levels were measured in 30 adolescent glue sniffers by atomic absorption spectrophotometry and compared with those of the 30 healthy adolescents. The Pb contents of various glue preparations marketed in Turkey and used by the abusers were also measured. Blood Pb levels were significantly higher in the study group when compared to the control group. Pb was detected at considerably high levels in the contents of all the various glue preparations most commonly used by the cases in the study group. The increased blood Pb levels in glue sniffers may be related to the high lead contents of glues marketed in Turkey. The blood Pb levels and signs of Pb toxicity should be investigated in examination of glue sniffers

The Effect of Probiotics on Reducing Hospitalization Duration in Infants With Hyperbilirubinemia

peer reviewedBackground: Approximately 60% of term and 80% of premature infants are hospitalized for hyperbilirubinemia in the first week of life. Hyperbilirubinemia is the most common cause of infant hospitalization and readmission. Due to the high frequency of hyperbilirubinemia in infants and the high costs of treatment, it is necessary to find a way to decrease hospitalization duration. Objectives: The aim of this study is to assess the adjunctive effect of probiotics on decreasing hospitalization time for infants with hyperbilirubinemia. Methods: In this randomized, controlled clinical trial, 92 term infants with hyperbilirubinemia who met the inclusion criteria were randomly assigned to either the probiotic or control group. Patients in both groups underwent common phototherapy. Once a day, those in the probiotic group were also given half of a capsule of Prokid probiotic, while those in the control group received half of a placebo capsule. The duration of phototherapy and hospitalization, the blood groups of mothers and infants, and each patient’s bilirubin levels before and after phototherapy, direct Coombs test results, and levels of hemoglobin, G6PD, and reticulocytes were recorded. Results: Data from 92 patients with a mean age of 5.25 ± 2.35 days underwent analysis. The control group had 47 (51.1%) patients with a mean age of 5.19 ± 2.51 days and the probiotic group had 45 (48.9%) patients with a mean age of 5.31 ± 2.19 days (P = 0.81). The 92 patients had a mean bilirubin level of 16.70 ± 3.07 mg/dL, with a mean of 16.42 ± 3.53 mg/dL in the control group and 17.00 2.49 mg/dL in the probiotic group (P = 0.37). The duration of hospitalization averaged 3.34 ± 0.70 days overall, with an average of 3.55 ± 0.74 days for the control group and 3.13 ± 0.70 days for the probiotic group. The probiotic group had a significantly lower hospitalization stay in comparison to the control group (P = 0.004). Conclusions: Our findings suggest that probiotics may be beneficial as an adjunct treatment for infants with hyperbilirubinemia by reducing the duration of hospitalization