Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations.

BACKGROUND: Celiac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied. AIM: We aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices. METHOD: We conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran. RESULTS: We included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing. CONCLUSION: This study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies.

Delayed cord clamping for prevention of intraventricular hemorrhage in preterm neonates: a randomized control trial.

BACKGROUND: Intraventricular hemorrhage (IVH) is a common condition in preterm neonates and is responsible for substantial adverse neurodevelopmental outcome in preterm neonates. Prevention of IVH is an important intervention for better neurological outcome in these preterm neonates. AIMS AND OBJECTIVE: This study aimed to determine whether delayed cord clamping (DCC) was superior to immediate cord clamping (ICC) for the prevention of IVH in preterm neonates. PATIENTS AND METHODS: In this two centered prospective double-blind randomized controlled trial, eligible neonates with gestational age from 26 to 34 weeks were randomized to receive either ICC (cord clamped in 10-15 s) or DCC (cord clamped in 30-45 s) groups. The grading and severity of IVH were evaluated by cranial ultrasound scan done on the 3-4th and 7-10th days after birth. RESULTS: Among the 148 enrolled neonates, 79 were in the ICC group and 69 were in the DCC group. There was no difference in maternal and neonatal baseline characteristics except the neonates in the DCC group weighed more (ICC 1528.77 ± 365.5 g vs. DCC 1658.11 ± 419.52 g; p = .047) at birth. There was no significant difference in the incidence of any grade of IVH in both groups (ICC 12.8% vs. DCC 14.5%; p = .745). There was a significantly higher incidence of grade I IVH (ICC 2.5% vs. DCC 13%; p = .024) in the DCC group. The incidence of grade II IVH (ICC 5.1% vs. DCC 0%; p = .123); grade III IVH (ICC 3.8% vs. DCC 1.4%; p = .623); and grade IV IVH (ICC 1.3% vs. DCC 0%; p>.999) were comparable between the two groups. The incidence of a significant IVH (grades II, III, and IV) was significantly less in the DCC group (ICC 10.1% vs. DCC 1.4%, p = .036). The mean initial hemoglobin levels were significantly higher in neonates enrolled in DCC (15.41 ± 2.1 vs. 16.46 ± 2.45 g/dL; p = .007). There was a significant reduction in the number of days of hospital stay (ICC 18.78 ± 15.42 vs. DCC 13.21 ± 16.16; p = .002). There was no difference in initial hematocrit, platelet count, maximum bilirubin level, and Apgar score (p>.05). CONCLUSIONS: Although there was no reduction in any grade of IVH, the incidence of significant IVH (grades II, III, and IV) was significantly decreased with the use of DCC in preterm neonates. Delayed cord clamping also resulted in a significant increase in birth weight, higher hemoglobin levels, and shorter hospital stays without any increase in the risks of hyper-bilirubinemia, low Apgar score, and neonatal mortality. TRIAL REGISTRY: IRCT2014031116936N1, https://www.irct.ir/trial/15707.

Prevalence of Cytomegalovirus in Semen of Male Partners of Infertile Couples and the Virus Impact on Sperm Parameters.

BACKGROUND: Genital tract infection is one of the causes of male infertility. Several studies have shown a role for human cytomegalovirus (CMV) in this context. In the present study, the prevalence of CMV in a population of male partners of infertile couples was estimated and the impact of CMV on sperm parameters was determined. METHODS: In this cross sectional study, CMV DNA and virus copy number were examined in the semen of 150 participants including 80 with normal semen analysis (SA) and 70 with abnormal SA, by quantitative Real-Time PCR. Sperm parameters were compared between CMV positive and negative groups. Comparisons with p- values under 0.05 were considered significant. Logistic regression was performed to control the effect of some variables with p<0.25 on sperm parameters. RESULTS: CMV DNA was detected in the semen of 28 (18.6%) individuals. 21 men (30%) with abnormal SA and 7 (8.8%) with normal SA were positive for CMV DNA (p=0.001). The mean virus copy number was 883.1±4662.01 for the men with abnormal SA and 2525.7±12680.9 for those with normal SA (p=0.001). Sperm count was (32.1±23.5) ×106 in CMV positive and (44.2±24.1) ×106 in CMV negative groups (p=0.022). Normal sperm morphology was 2.73±2.83% and 5.99±5.44% in CMV positive and negative groups, respectively (p<0.001). After controlling some variables, the sperm morphology remains the only statistically significant sperm parameter that was reduced by CMV. CONCLUSION: The higher CMV prevalence in the semen of males with abnormal SA compared to normal SA and significant reduction of sperm morphology in the presence of CMV, are in favor of the negative impact of CMV on male fertility.

Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene.

BACKGROUND: Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. CASE PRESENTATION: The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. CONCLUSIONS: Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

Sublingual versus Vaginal Misoprostol for the Induction of Labor at Term: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: We sought to compare the effectiveness and safety of sublingual versus vaginal misoprostol for the termination of pregnancy with a live full-term fetus. METHODS: This randomized, triple-blind, placebo-controlled clinical trial was performed on 200 primiparous women with normal, singleton, full-term pregnancies candidated for the induction of labor. Sublingual and vaginal tablets containing misoprostol (25 mcg) or placebo in similar shapes were administered every 4 hours until the Bishop score reached above 8. Maternal and neonatal complications and outcomes were compared. RESULTS: There were 100 parturient women in each group. The mean maternal age, gestational age, and Bishop score at the commencement of misoprostol had no statistical differences between the sublingual and vaginal groups. The mean time interval between misoprostol commencement and delivery was 497.10±291.49 and 511.67±08.46 minutes for the sublingual and vaginal groups, correspondingly. Twenty-two women had Cesarean deliveries in the sublingual group versus 14 in the vaginal group. Meconium-stained amniotic fluid was seen in 12 women in the sublingual group and 4 in the vaginal group (P=0.03). Late fetal heart rate deceleration was observed in 8 women in the sublingual group and 4 in the vaginal group (P=0.22). The mean neonatal birth weight, blood gas value at birth, Apgar score, and length of admission time in the neonatal intensive care unit were not different between the 2 groups. CONCLUSION: Sublingual and vaginal misoprostol had similar effectiveness; however, meconium-stained liquor was observed considerably more frequently with sublingual misoprostol than with vaginal misoprostol. TRIAL REGISTRATION NUMBER: IRCT201402096541N3.

Surgical management of a rare form of cervical dysgenesis with normal vagina, normal vaginal portion of the cervix and obstructed uterus.

This case was an extremely rare form of cervical dysgenesis that presented with cyclic pain. Diagnostic laparoscopy and vaginoscopy showed the presence of a blind uterus at the level of the internal cervical os with a normal vagina and exocervix. Müllerian ducts are the embryologic origin for the uterus, cervix and upper part of the vagina. Müllerian duct migration initiates from the upper part of the Müllerian system. Therefore an obstructed uterus is usually associated with cervical and upper vaginal anomalies. This case was unusual because of the presence of an isolated segmental atresia at the level of the internal cervical os. However the vaginal portion of the cervix, vagina and urinary system were normal. We theorized that the absence of an appropriate fusion between the Müllerian duct and its underlying mesoderm, loss of cell-to-cell communication and special gene expression during a critical time period or a vascular accident between 12-22 weeks of gestation might have caused this anomaly. The patient underwent a laparotomy to create a utero-cervical canal using a peritoneal graft.