No abstract

Aspartylglucosaminuria is a rare autosomal recessive lysosomal storage disorder leading early to a progressive intellectual disability. Monozygous Qatari twins presented with an unusual perinatal manifestation characterized by severe muscular hypotonia, scarce spontaneous movements, multiple contractures, and respiratory insufficiency. Biochemical investigations suggested aspartylglucosaminuria, and a novel homozygous mutation c.439T>C (p.S147P) was found in the aspartylglucosaminidase gene. However, it cannot be excluded that the unusual neonatal presentation is due to an additional autosomal recessive disease in this multiply consanguineous family. The classical aspartylglucosaminuria phenotype (progressive speech delay, psychomotor retardation, and behavioral abnormalities) was observed in 3 Turkish siblings. Although aspartylglucosaminuria was suspected early, the definite diagnosis was not confirmed until the age of 18 years. A novel homozygous mutation c.346C>T (p.R116W) was found. These 5 cases emphasize that aspartylglucosaminuria is panethnic and may possibly present with prenatal manifestation. Screening for aspartylglucosaminuria should be done in all patients with unexplained psychomotor retardation.

Background Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. Objective To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. Methods This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women's Wellness and Research Center, Doha, Qatar during 2012-2014. Infants of 24 0/7-29 6/7 weeks' gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. Results No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. Conclusions While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD.

Introduction: The aim of this study to review the socioeconomic determinants of neonatal death compared to living infants in a multinational’s population. Methods: A retrospective data analysis of 58,990 births. Population-based Cohort study retrieved from the perinatal registry for the 4 years period. We compared socio-economic factors in cases of neonatal death [NND] who died in the hospital with infants who have discharged alive from the hospital [AL]. Socioeconomic factors including nationality, religion, marital status, level of education, parents’ occupation, family income, consanguinity, early childbearing, smoking, assisted conception, antenatal care, and place of delivery. Results: There were 336 cases of ND and 58,654 of AL. The prevalence of NND was 5.7/1000 births. There were more neonatal deaths among uneducated mothers with P-value < 0.0003, and OR=2.0, mothers with low income (P=0.0008, CI=1.34-3.16, OR=2.07), families living in a shared houses (P=0.008, CI=1.23-3.19, OR=1.34), consanguinity (P=0.005, CI=1.13-2.0, OR=1.5), unemployed father (P=0.027, CI=1.24-4.28, OR=2.4), father’s education (P=0.017, CI=1.065-1.92, OR=1.4), assisted conception (P= 0.0001, CI=2.99-5.46, OR=4.04) and those mothers with no antenatal care (P=0.0001, CI=2.54-4.48, OR=3.37). Preterm birth in a referral/tertiary hospital was significantly high. There was no negative impact of nationality, mother’s occupation, maternal age, gravidity, or smoking. Comparing means among maternal and neonatal outcome categories showed no negative impact of crowding index (family members/number of rooms), number of rooms, number of family members, number of children in the house, or number of parties. Conclusion: In this study, antenatal care, parent’s education, father’s unemployment, low income of the mother, poor housing, consanguinity, assisted conception, and preterm birth were all associated with in-hospital neonatal death.