Zivanit Ergaz

Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment

Offspring of mothers using ethanol during pregnancy are known to suffer from developmental delays and/or a variety of behavioral changes. Ethanol, may affect the developing fetus in a dose dependent manner. With very high repetitive doses there is a 6–10% chance of the fetus developing the fetal alcoholic syndrome manifested by prenatal and postnatal growth deficiency, specific craniofacial dysmorphic features, mental retardation, behavioral changes and a variety of major anomalies. With lower repetitive doses there is a risk of “alcoholic effects” mainly manifested by slight intellectual impairment, growth disturbances and behavioral changes. Binge drinking may impose some danger of slight intellectual deficiency. It is advised to offer maternal abstinence programs prior to pregnancy, but they may also be initiated during pregnancy with accompanying close medical care. The long term intellectual outcome of children born to ethanol dependent mothers is influenced to a large extent by the environment in which the exposed child is raised.

Prenatal factors associated with autism spectrum disorder (ASD)

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal and postnatal etiologies. We discuss the known associated prenatal factors affecting the fetus throughout pregnancy; whenever relevant, also summarize some animal data. Among the maternal diseases in pregnancy associated with ASD are pregestational and/or gestational diabetes mellitus (PGDM, GDM), maternal infections (i.e. rubella, cytomegalovirus (CMV)), prolonged fever and maternal inflammation, which cause changes in a variety of inflammatory cytokines. Among the drugs are valproic acid, thalidomide, and possibly misoprostol and serotonin reuptake inhibitors (SSRIs). Associations were described with ethanol, and possibly cocaine, heavy metals heavy smoking and Folic acid deficiency. Heavy exposure to pesticides and air pollution during pregnancy was recently associated with ASD. We need more epidemiologic data to establish many of these associations; if proven, they might be promising avenues for prevention.

Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation

Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia. This exceptional outcome may be related to the high residual activity of the mutant protein (32% of wild type) and therapeutic intervention during a critical period of heightened brain exposure and sensitivity to glycine. Ann Neurol 2004;56:139–143

Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

Continuous surveillance to reduce extended-spectrum β-lactamase Klebsiella pneumoniae colonization in the neonatal intensive care unit.

Background: Clinical illness caused by resistant bacteria usually represents a wider problem of asymptomatic colonization. Active surveillance with appropriate institution of isolation precautions represents a potential mechanism to control colonization and reduce infection. The neonatal intensive care unit (NICU) is an environment particularly appropriate for such interventions. Neonates are rarely colonized by resistant bacteria on admission and staff enthusiasm for infection control is high. Objective: To reduce extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) acquisition amongst neonates through a continuous active surveillance intervention. Methods: Fecal ESBL-KP cultures were performed weekly on all neonates over 4 years. Neonates with positive cultures were managed with contact precautions by dedicated nurses separately from other neonates. ESBL-KP acquisition amongst neonates staying >7 days was compared for the consecutive years. A subset of ESBL-KP isolates was typed with pulsed-field gel electrophoresis (PFGE). Results: Surveillance cultures were obtained from 1,482/1,763 (84%) neonates over 4 years. ESBL-KP acquisition decreased continuously from 94/397 (24%) neonates in 2006 to 33/304 (11%) in 2009 (p < 0.001, hazard ratio 0.75, 95% confidence interval 0.66–0.85, p < 0.001 for comparison of years). Hospital-wide ESBL-KP acquisition did not decrease outside the NICU. PFGE identified identical ESBL-KP strains from multiple neonates on six occasions and different strains from single neonates on seven occasions. Conclusions: ESBL-KP is probably both imported into and spread within the NICU. Continuous long-term surveillance with cohorting was associated with a decrease in ESBL-KP acquisition within the NICU. This low-risk intervention should be considered as a means to decrease neonatal acquisition of resistant bacteria.

Congenital chylothorax: Clinical course and prognostic significance

To determine the underlying etiology, associated malformations, clinical course, and prognostic significance of congenital chylothorax.

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan–McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter < 2.5 and 10 μm in diameter (PM2.5 and PM10) during pregnancy is also associated with ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are “clean” of different confounding factors. The associations described in this review emphasize again how little we know about the etiology and pathogenesis of ASD. It is obvious that we need more epidemiologic data to establish many of these associations, but if proven, they might be promising avenues for prevention.

Elimination of vancomycin-resistant enterococci from a neonatal intensive care unit following an outbreak

A policy of weekly faecal cultures for vancomycin-resistant enterococci (VRE) was instituted following the investigation of an outbreak of VRE in our neonatal intensive care unit in 2005. We found that 11 of 18 patients were infected or colonised during the outbreak, including three cases of bloodstream infection and one case of meningitis. This report describes the utility of the surveillance policy in maintaining a VRE-free environment. The outbreak investigation showed that all VRE isolated were Enterococcus faecium of the vanA type. Pulsed-field gel electrophoresis suggested that the outbreak was caused by a single strain. Control of the outbreak was achieved by enhanced contact isolation precautions, cohorting of patients and staff, improved environmental decontamination and closure of the unit to new admissions. The patients with bloodstream infections and meningitis were treated successfully with linezolid. Approximately one year after the outbreak, weekly surveillance detected two patients with faecal carriage of VRE whose periods of admission overlapped. Early intensive intervention was associated with disappearance of the organism from the neonatal intensive care unit. No further cases of colonisation or disease have occurred in the unit in the two and a half years since then.

Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus.

The ductus venosus connects the portal and umbilical veins with the inferior vena cava and acts as a sphincter to protect the fetus from placental overcirculation. Its absence usually causes hydrops fetalis and is associated with high mortality rate, chromosomal anomalies and congenital malformations. In this condition, the umbilical vein almost always drains directly into right-sided structures such as inferior vena cava or right atrium. We reviewed the literature and describe the first case of a fetus with absent ductus venosus and direct connection of the umbilical vein to the coronary sinus.

Diagnosis and management of central-line-associated thrombosis in newborns and infants

Although the use of central lines has many valuable applications in neonates and infants, they may cause serious mechanical, infectious and thrombotic complications. In fact, the use of central lines is the main cause for thrombosis in this age group. The frequency of central-line-related thrombosis in neonates and infants is reported to be as low as 1% when including only symptomatic cases, around 44% when systematically screened for thrombosis, and as high as 65% in autopsy studies. The risk factors for line-related thrombosis in neonates and infants include those associated with the underlying medical conditions, the duration of the line in situ, the placement of the umbilical artery catheter and the therapy used through the line. The contribution of inherited and acquired thrombophilia to central-line-related thrombosis is controversial, and the data are not sufficiently consistent to make a firm recommendation for thrombophilia screening for neonates and infants with central-line-related thrombosis. Most experts will recommend pursuing a thrombophilia work-up in the setting of a significant thrombosis event and will recommend avoiding thrombophilia work-up in subclinical and asymptomatic central-line-related thrombosis. The management of line-related thrombosis is based on expert opinion guidelines and is largely dependent on the type of the catheter and the further requirement of the catheter. Continuous heparin infusion through the central lines prevents catheter occlusion, but has no effect on occurrence of thrombosis. Currently no definitive recommendations exist for thromboprophylaxis in children, infants and neonates with central lines.