Three or four doses of intravenous immunoglobulin G treatment for isoimmune hemolytic disease: A case series and literature review.

BACKGROUND: Neonates affected by isoimmune hemolytic disease (HDN) are at risk of developing severe hyperbilirubinemia. Studies show that increasing levels of bilirubin impact neonatal neurodevelopment. To avoid complications associated with exchange transfusion, intravenous immunoglobulin G (IVIG) is used to treat hyperbilirubinemia. We included all infants who received more than two doses of IVIG treatment for isoimmune hemolytic disease. We analyzed the incidence of side effects associated with IVIG treatment and the rate of exchange transfusion. METHODS: A retrospective chart review performed between October 2011-October 2022 at East Carolina University Health identified neonates who received more than two doses IVIG for HDN. Neonates of postmenstrual age greater than 28 days old, receiving less than three doses of IVIG or received IVIG for other indications were excluded. The occurrences of adverse events, demographics and use of other medical therapies were reviewed. RESULTS: Eleven neonates were included in the case series. Most common cause of severe hyperbilirubinemia was attributed to ABO incompatibility. Six patients (54%) received three doses of IVIG, and five patients (45%) received four doses of IVIG with bilirubin levels decreasing below exchange transfusion. No treatment exceeding four doses of IVIG was reported, nor adverse events during treatment. CONCLUSIONS: In this cohort of neonates with HDN, bilirubin levels decreased after treatment with multiple doses of IVIG. Future research on recommendations of optimal total number doses of IVIG to reduce the risk for exchange transfusion.

Doxorubicin and zoledronate treatment in a dog with hemophagocytic histiocytic sarcoma.

A 6-year-old castrated male greyhound dog was referred for hemophagocytic histiocytic sarcoma (HHS) diagnosed following splenectomy. Severe thrombocytopenia, mild hypoalbuminemia, mild hypocholesterolemia, and mild hyperbilirubinemia were present. Abdominal ultrasound findings were concerning for hepatic metastasis. Doxorubicin and zoledronate combination therapy was initiated. The dog improved clinically and its thrombocytopenia, hypoalbuminemia, and hyperbilirubinemia resolved. The dog appeared well for 147 d before tumor progression was noted. The dog was treated with lomustine as a final measure, with no response. The dog survived for 6 mo with chemotherapy. To the authors' knowledge, this is the first report of clinical benefit of chemotherapy for HHS. Key clinical message: Doxorubicin should be considered for treating canine HHS since this variant of the disease is historically refractory to lomustine. Further research regarding efficacy of doxorubicin and zoledronate should be pursued.

Traitement à la doxorubicine et au zolédronate chez un chien atteint de sarcome histiocytaire hémophagocytaire. Un lévrier mâle castré de 6 ans a été vu pour un sarcome histiocytaire hémophagocytaire (HHS) diagnostiqué à la suite d'une splénectomie. Une thrombopénie sévère, une hypoalbuminémie légère, une hypocholestérolémie légère et une hyperbilirubinémie légère étaient présentes. Les résultats de l'échographie abdominale étaient préoccupants quant aux métastases hépatiques. Un traitement associant doxorubicine et zolédronate a été instauré. Le chien s'est amélioré cliniquement et sa thrombocytopénie, son hypoalbuminémie et son hyperbilirubinémie ont disparu. Le chien semblait en bonne santé pendant 147 jours avant de constater une progression tumorale. Le chien a été traité avec de la lomustine comme mesure finale, sans réponse. Le chien a survécu 6 mois grâce à la chimiothérapie. À la connaissance des auteurs, il s'agit du premier rapport faisant état d'un bénéfice clinique de la chimiothérapie pour le HHS.Message clinique clé :La doxorubicine doit être envisagée pour traiter le HHS canin puisque cette variante de la maladie est historiquement réfractaire à la lomustine. Des recherches plus approfondies concernant l'efficacité de la doxorubicine et du zolédronate devraient être poursuivies.(Traduit par Dr Serge Messier).

An evaluation of ursodeoxycholic acid treatment in prolonged unconjugated hyperbilirubinemia due to breast milk.

Background/Aim: Prolonged jaundice is one of the most common problems during neonatal period. The aim of this study was to evaluate the efficiency of ursodeoxycholic acid (UDCA) treatment in newborn infants with prolonged unconjugated hyperbilirubinemia. Materials and Methods: The present study included 27 patients who were fed by breast milk and followed up in the outpatient clinic due to prolonged jaundice without any underlying etiological factor; 10 mg/kg/day UDCA was administrated in two doses for 7 days. Furthermore, 20 newborns diagnosed with prolonged jaundice with same characteristics were enrolled as the control group. The control group was also given a placebo; demographic characteristics, liver functions tests before and after the treatment, bilirubin decrease rates, and hemogram parameters of groups were compared. Results: Total bilirubin levels in the study and control groups before the treatment were 16.02 ± 1.41 mg/dL and 15.93 ± 1.66 mg/dL, respectively (P = 0.84). Total bilirubin levels in the study and control groups at day 7 after UDCA treatment were detected 8.18 ± 2.31 mg/dL and 13.92 ± 2.66 mg/dL, respectively (P < 0.001), and at day 14 after the treatment were 5.45 ± 2.59 mg/dL and 11.91 ± 2.83 mg/dL, respectively (P < 0.001). Furthermore, serum aspartate aminotransferase (AST) was detected <21 U/L in the ROC analysis after UDCA treatment (P = 0.04). Conclusion: The study outcomes indicated that an efficient reduction in total bilirubin levels may be achieved, and outpatient clinic follow-up period may be reduced in patients whom UDCA was administrated. Moreover, it may be speculated that AST can be used to evaluate the efficacy after treatment. However, studies with larger sample sizes are needed for the routine use of UDCA in the treatment of prolonged jaundice.

Atazanavir-induced unconjugated hyperbilirubinemia prevents vascular hyporeactivity during experimental human endotoxemia.

Objective: Inflammation-induced free radical release is important in the pathogenesis of several diseases, including atherosclerosis and sepsis. Heme oxygenase (HO) breaks down heme into carbon monoxide, iron, and biliverdin. Biliverdin IXα is directly converted to bilirubin by biliverdin reductase. Unconjugated bilirubin is a powerful antioxidant, and elevated levels have beneficial effects in preclinical models and human cardiovascular disease. However, its impact during acute inflammation in humans is unknown. In the present study, we investigated the impact of atazanavir-induced (unconjugated) hyperbilirubinemia on antioxidant capacity, inflammation, and vascular dysfunction in human experimental endotoxemia. Approach and results: Following double-blinded four-day treatment with atazanavir 2dd300 mg (or placebo), twenty healthy male volunteers received 2 ng/kg Escherichia coli lipopolysaccharide intravenously. Blood was drawn to determine the bilirubin levels, antioxidant capacity, and cytokine response. It was demonstrated that following atazanavir treatment, total bilirubin concentrations increased to maximum values of 4.67 (95%CI 3.91-5.59) compared to 0.82 (95%CI 0.64-1.07) mg/dL in the control group (p<0.01). Furthermore, the anti-oxidant capacity, as measured by the ferric-reducing ability of plasma (FRAP), was significantly increased with 36% in hyperbilirubinemia subjects (p<0.0001), and FRAP concentrations correlated strongly to bilirubin concentrations (R2 = 0.77, p<0.001). Hyperbilirubinemia attenuated the release of interleukin-10 from 377 (95%CI 233-609) to 219 (95%CI 152-318) pg/mL (p=0.01), whereas the release of pro-inflammatory cytokines remained unaltered. In vitro, in the absence of hyperbilirubinemia, atazanavir did not influence lipopolysaccharide-induced cytokine release in a whole blood assay. Vascular function was assessed using forearm venous occlusion plethysmography after intra-arterial infusion of acetylcholine and nitroglycerin. Hyperbilirubinemia completely prevented the LPS-associated blunted vascular response to acetylcholine and nitroglycerin. Conclusions: Atazanavir-induced hyperbilirubinemia increases antioxidant capacity, attenuates interleukin-10 release, and prevents vascular hyporesponsiveness during human systemic inflammation elicited by experimental endotoxemia. Clinical trial registration: http://clinicaltrials.gov, identifier NCT00916448.

A possible case of bictegravir-associated severe unconjugated hyperbilirubinemia.

BACKGROUND: Bictegravir (BIC) co-formulated with emtricitabine (FTC) and tenofovir alafenamide (TAF) is approved by Federal Food and Drug Administration in 2018 for both treatment-naïve and experienced persons living with HIV (PLWH). CASE PRESENTATION: A young man with recently diagnosed human immunodeficiency virus (HIV) infection presented with jaundice. Blood work was significant for mild anemia and grade 4 unconjugated hyperbilirubinemia. A comprehensive evaluation for hemolytic anemia failed to reveal any etiology. Other causes of hyperbilirubinemia were negative. Four months prior, patient was started on antiretroviral therapy with a single tablet regimen containing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), brand name Biktarvy®, and the medication was suspected to be the cause. The medication was held, and the hyperbilirubinemia improved. CONCLUSION: Severe hyperbilirubinemia can be found in the patient using BIC/FTC/TAF. The data for this adverse reaction is scarce, and more studies are needed on this possible side effect. The mechanism of unconjugated hyperbilirubinemia by INSTI remains undefined.

Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term.

OBJECTIVE: To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. STUDY DESIGN: A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. RESULTS: In total, 27 infants were studied. The mean free bilirubin (µg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. CONCLUSIONS: Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.

Indirect hyperbilirubinemia and jaundice during chronic hepatitis C in an HIV-infected patient treated with glecaprevir/pibrentasvir (GLE/PIB) and antiretroviral therapy (ART). The first reported case in Italy.

Glecaprevir (GLE)/pibrentasvir (PIB) is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Primary treatment and re-treatment with GLE/PIB are effective and safe for patients without decompensated liver cirrhosis and chronic hepatitis C in a real-world clinical setting. However, in the context of compensated cirrhosis and concomitant administration of inhibitors of cytochromes, a careful monitoring of liver biomarkers, as well as therapeutic drug monitoring (TDM), may be advisable during GLE/PIB therapy. The GLE / PIB combination is very effective and safe in achieving a sustained virological response, but it can be associated with the development of severe hepatic adverse events, which require virological and serum concentration monitoring of the two drugs to prevent a serious liver damage. The possible onset of hyperbilirubinemia must not necessarily lead to the suspension of therapy, because the phenomenon may be transient. We report what is likely the first known case of severe jaundice after treatment with GLE/PIB in Italy in a patient with compensated chronic hepatitis in the context of HIV disease.

Slow increase of bilirubin concentration during administration of lenalidomide, bortezomib and dexamethasone for multiple myeloma (unmasking previously undiagnosed Gilbert syndrome) and disappearance of necrobiotic xanthogranuloma after complete remission of multiple myeloma.

BACKGROUND: Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. CASE DESCRIPTION: We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. CONCLUSION: NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

Clinical and demographic factors contributing to asparaginase-associated toxicities in children with acute lymphoblastic leukemia.

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; 95% CI: 1.96-11.02), and cumulative toxicity burden (OR = 3.28, 95% CI: 1.97-5.47); high-risk therapy with hypersensitivity (OR 2.25; 95% CI 1.25-4.05); and overweight with cumulative toxicity burden (OR = 1.76, 95% CI: 1.20-2.57). Eight unique toxicity profiles were identified. Older age, overweight, and treatment intensity contribute to pegaspargase-associated toxicities.

A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study.

PURPOSE: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. METHODS: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. RESULTS: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). CONCLUSION: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD. TRIAL REGISTRATION NUMBER: NCT03295006.

Oridonin alleviates hyperbilirubinemia through activating LXRα-UGT1A1 axis.

Hyperbilirubinemia is a serious hazard to human health due to its neurotoxicity and lethality. So far, successful therapy for hyperbilirubinemia with fewer side effects is still lacking. In this study, we aimed to clarify the effects of oridonin (Ori), an active diterpenoid extracted from Rabdosia rubescens, on hyperbilirubinemia and revealed the underlying molecular mechanism in vivo and in vitro. Here, we showed that liver X receptor alpha (LXRα) deletion eliminated the protective effect of Ori on phenylhydrazine hydrochloride-induced hyperbilirubinemia mice, indicating that LXRα acted as a key target for Ori treatment of hyperbilirubinemia. Ori significantly increased the expression of LXRα and UDP-glucuronosyltransferase 1A1 (UGT1A1) in the liver of wild-type (WT) mice, which were lost in LXRα-/- mice. Ori or LXR agonist GW3965 also reduced lipopolysaccharide/D-galactosamine-induced hyperbilirubinemia via activating LXRα/UGT1A1 in WT mice. Liver UGT1A1 enzyme activity was elevated by Ori or GW3965 in WT mice. Further, Ori up-regulated LXRα gene expression, increased its nuclear translocation and stimulated UGT1A1 promoter activity in HepG2 cells. After silencing LXRα by siRNA, Ori-induced UGT1A1 expression was markedly reduced in HepG2 cells and primary mouse hepatocytes. Taken together, Ori stimulated the transcriptional activity of LXRα, resulting in the up-regulation of UGT1A1. Therefore, Ori or its analogs might have the potential to treat hyperbilirubinemia-related diseases through modulating LXRα-UGT1A1 signaling.

Yinzhihuang Oral Liquid Ameliorates Hyperbilirubinemia Induced by δ-Aminolevulinic Acid and Novobiocin in Neonatal Rats.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.

Optimization of zinc oxide nanoparticle-catalyzed in vitro bilirubin photolysis and in vivo treatment of hyperbilirubinemia.

Aim: To optimize the Zinc oxide nanoparticles (ZnONPs)-catalyzed in vitro photolysis of bilirubin and to test their effect on bilirubin clearance in vivo. Materials & methods: ZnONPs, synthesized in an alkaline medium, were characterized. Response surface methodology was used to optimize the in vitro photolysis catalyzed by the nanoparticles (NPs). Blood samples from phenylhydrazine-induced hyperbilirubinemic rabbits which had been administered ZnONPs and UV light were analyzed to assess in vivo clearance of bilirubin. Results: The ZnONP-assisted UV treatment showed the linear and quadratic positive effects on the in vitro bilirubin photolysis with an optimal photolysis of bilirubin at 225 mg dl-1 concentration of ZnONPs and a UV exposure of 1.80 h. The ZnONP-assisted phototherapy of hyperbilirubinemic animals was also found to be more effective for in vivo clearance of bilirubin than phototherapy alone. Conclusion: After further trials, ZnONP-assisted phototherapy could be a potential treatment for hyperbilirubinemia in humans.

Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia.

AIM: This study aimed to investigate the effect of adding ursodeoxycholic acid (UDCA) to phototherapy in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency and hyperbilirubinaemia. G6PD deficiency is a common cause of severe hyperbilirubinaemia in neonates. METHODS: This study was a triple blind, clinical trial study of 40 neonates with G6PD deficiency and hyperbilirubinaemia who admitted for phototherapy in hospitals affiliated to the University of Medical Sciences. The treatment group (n = 20) received UDCA 10 mg/kg (2 cc/kg) daily divided into 2 doses every 12 h. The control group (n = 20) received the same volume of placebo syrup. The drug and placebo treatments were continued until the bilirubin level dropped below 171 µmol/L. Both the control and treatment group received continuous phototherapy. Independent sample t-test, survival analysis and logrank test were used to statistically analyse the results. RESULTS: The mean total bilirubin level was 231.9 ± 18.8 µmol/L and 184.3 ± 18.6 µmol/L in the control and intervention group respectively, 24 h after drug administration and 209.7 ± 19.3 µmol/L and 157.4 ± 16.4 µmol/L, respectively, 48 h after intervention (P < 0.05). The median length of hospitalisation in the treatment group was approximately 1 day lower than the control group (logrank test P value: <0.001). CONCLUSION: The study showed that the addition of UDCA to phototherapy accelerates the reduction of total bilirubin level in neonates with G6PD deficiency and can reduce the duration of hospitalisation.

An unusual cause of fever and jaundice.

A 52 year old previously healthy woman from Mumbai presented with fever and jaundice of 10 days duration. At admission, she was jaundiced with tachycardia, tachypnea, hypoxia, hypotension, conjunctival congestion and mild erythematous flush over the skin. She had very high WBC counts and CRP's with direct hyperbilirubinemia and azotemia. Investigations for infectious causes of fever were negative. RT-PCR for SARS-CoV-2 in the nasopharynx was negative. However her SARS-CoV-2 antibodies were reactive. She also had echocardiographic and biochemical evidence of cardiac dysfunction. The diagnosis of Multisystem inflammatory syndrome-Adult (MIS-A) was thus established. She rapidly improved with intravenous immunoglobulin (2 gm/kg) and high dose steroids.

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid Metabolism, and Pregnancy Outcomes in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial.

This study was performed to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid metabolism, and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). The current randomized, double-blind, placebo-controlled clinical trial was conducted in 36 patients with GDM. Participants were randomly divided into two groups to intake either 200 µg/day selenium supplements as selenium yeast or placebo (n = 18 each group) for 6 weeks. Selenium supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.03) and glucose transporter 1 (GLUT-1) (P = 0.01) in lymphocytes of subjects with GDM compared with the placebo. Selenium supplementation did not affect gene expression of low-density lipoprotein receptor (LDLR) and lipoprotein(a) [Lp(a)]. Supplementation with selenium had a significant decrease in incidence of newborns' hyperbilirubinemia (5.6% vs. 33.3%, P = 0.03) and newborns' hospitalization (5.6% vs. 33.3%, P = 0.03) compared with the placebo. Overall, we found that selenium supplementation for 6 weeks among patients with GDM significantly increased PPAR-γ and GLUT-1 expression, but did not affect gene expression of LDLR and LP(a). It also reduced incidence of newborns' hyperbilirubinemia and newborns' hospitalization. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N35.