Neonatal mortality and morbidity in the post-implementation period of a neonatal teaching program in provincial hospitals in Laos.

OBJECTIVES: Aim of this study was to analyze neonatal mortality and morbidity in the post-implementation period of a neonatal teaching program to examine a possible impact on neonatal outcomes. STUDY DESIGN: This study is a retrospective data analysis of all neonatal patients treated in five provincial hospitals in Laos after implementation of a neonatal teaching program. METHODS: A simulation-based teaching program aims to have positive impact on the theoretical and practical skill of hospital staff in the field of newborn care. A comparison between pre-implementation and post-implementation data of newborns admitted to provincial hospitals in Laos was used to quantify the effect of repetitive teaching on neonatal outcomes. RESULTS: Neonatal mortality and morbidity as well as case fatality rates of infections and asphyxia decreased in the post-implementation period. In contrast, neonatal mortality rate as well as case fatality rate of prematurity increased. The total neonatal mortality rate increased in the post-implementation period. CONCLUSIONS: The pre-implementation and post-implementation data enable longitudinal comparisons between hospitals and highlight the differences between hospitals concerning neonatal mortality and morbidity in provincial hospitals in Laos. These data can serve as a basis for an individual adaption of the teaching program to the unique requirements of each single hospital.

Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

Successful management of neonatal hemochromatosis by exchange transfusion and immunoglobulin: a case report.

Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.

Pandemic A/H1N1(2009) influenza infections in very-low-birth-weight infants--a case series from the German Neonatal Network.

6 cases of clinical influenza A/H1N1(2009) infections were reported within the multi-center German Neonatal Network (GNN) during the primary hospital stay in the pandemic season 2009/2010 and 2010/2011. Clinical symptoms varied from transient hyperthermia to apnea and severe respiratory distress. 1 fatal course with systemic inflammatory response after perinatal transmission of A/H1N1(2009) was observed. Oseltamivir treatment in 3/6 infants was without side effects. The reported cases have major implications for the management of VLBW infants: i) fatal courses after perinatal transmission are possible, ii) postnatal A/H1N1(2009) infection may result in life threatening events at a time when the infant is otherwise stable, iii) vaccination should be recommended for parents and medical staff to avoid nosocomial transmission, iv) more data are needed on the benefit and harm of antiviral drugs in preterm infants, v) neonatologists should suspect A/H1N1(2009) infection when unexplained sepsis-like or respiratory symptoms occur in VLBW infants.

The 2010 Guidelines on Neonatal Resuscitation (AHA, ERC, ILCOR): similarities and differences--what progress has been made since 2005?

In 2010, the American Heart Association (AHA), the European Resuscitation Council (ERC) and the International Liaison Committee on Resuscitation (ILCOR) issued new guidelines on newborn resuscitation. The new recommendations include: (1) pulse-oximetry for patient assessment during newborn resuscitation; (2) to start resuscitation of term infants with an FiO (2) of 0.21; (3) cardio-respiratory resuscitation with a 3:1 chest compression/inflation ratio for a heart rate <60 beats/min; (4) regarding infants born from meconium stained amniotic fluid: no recommendation is given to suction the upper airways at the perineum (when the head is born), but it is recommended to inspect the oropharynx and trachea for obstruction and suction the lower airway before inflations are given when the infant is depressed; (5) for birth asphyxia in term or near term infants, to induce hypothermia (33.5-34.5°C) within 6 h after birth. AHA, ERC and ILCOR used nearly identical literature for their evidence evaluation process. While the AHA and ILCOR guidelines are almost identical, the ERC guidelines differ slightly from the latter with regards to (i) promoting sustained inflations at birth, (ii) promoting a wider range in applied inflations during resuscitation, and (iii) to suction the airways in infants born from meconium stained amniotic fluid, before inflations are given.

Neonatal and childhood mortality rates in Myanmar.

The health system performance in Myanmar was reported by WHO as having the highest childhood mortality numbers in Asia only exceeded by Cambodia and Laos. Previous data reported an infant mortality rate of as high as 105 per 1,000 live births. This review looks at the trend of the mortality rate in neonates and children in Myanmar during the two past decades. Data were retrieved from the Central Statistical Organization (CSO) of Myanmar, from UNICEF and from WHO. Data include the mortality under five years of age (U5MR), infant mortality rate (IMR), neonatal mortality rate (NMR), and maternal mortality rate (MMR). The latest report given by the CSO in 2002/2003 estimates U5MR at 66/1 000, IMR at 50/1,000, and NMR at 16/1 000. Data published by the WHO in 2003 provide a less optimistic perspective: U5MR is reported at 107/1 000, IMR at 76/1,000, and NMR at 35/1 000. 73% of death cases under the age of five years occurred in the age group 0-11 months, 34% of infant death cases happened during the first month of life. The majority of death cases were attributable to acute respiratory infections, diarrhoea, brain infections, or septicaemia. International sources (UNICEF, WHO) indicate a less fortunate situation related to childhood mortality rates in Myanmar as is published by the CSO. Further substantial reductions of mortality rates require structural changes not only in rural areas.

Fatal hypertensive crisis as presentation of mitochondrial complex I deficiency.

Complex I deficiency is a frequent defect of the mitochondrial electron transport chain. We report on a 3-year-old boy, who rapidly deteriorated after sudden flushing and collapse. This fatal and unusual case was characterized by widely uncontrollable arterial hypertension. It might indicate that hypertensive crisis could be a potential manifestation of mitochondrial disorders.

[ILCOR's new resuscitation guidelines in preterm and term infants: critical discussion and suggestions for implementation]. / Neue Reanimationsrichtlinien der ILCOR bei Früh- und Reifgeborenen: Kritische Diskussion und Vorschläge zur praktischen Umsetzung.

Recommendations of the International Liaison Committee on Resuscitation (ILCOR) become updated every five years with changing evidence resulting in revised recommendations for clinical practice. New data exist concerning the adequate oxygen concentration to be used in the delivery room, the management of imminent meconium aspiration, ventilation strategies and the role of body temperature during and after resuscitation of preterm and term newborn infants. Only in some cases new evidence has led to clear-cut recommendations for or against specific interventions. Therefore the present publication cites the original ILCOR-recommendations and discusses these with regard to their practical implementation. The authors of the present work suggest to commence resuscitation independendly of gestational age with room air and adjust the inspiratory oxygen concentration thereafter on clinical grounds. The authors also advocate the retention of the presently performed intranatal suction procedure in cases of meconium-stained amniotic fluid and the use of therapeutic hypothermia following perinatal asphyxia in term newborns according to the protocol of one of the published randomized, controlled trials. Standard equipment for neonatal resuscitation should include pressure gauge for monitoring of inspiratory pressures, oxygen blender, and pulse oxymeter. The predominant majority of ILCOR-recommendations have only been cited and have been commented with respect to their practical implementation within the clinical context.

Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis.

Abnormal growth and development of lymphatic pulmonary structures leads to severe hypoxia in congenital pulmonary lymphangiectasis (CPL). This case study aims to determine the cellular source and topographical distribution of the nitric oxide synthases in CPL. It studies the post mortem tissue of a term newborn with the clinical course and histological findings of CPL and three controls without pulmonary pathology. It was found that endothelial cells of pulmonary arteries and lymphatic structures stained significantly more for endothelial nitric oxide synthase protein in the CPL patient compared to the controls. The authors conclude that synthesis of endothelial nitric oxide synthase is upregulated in vascular and lymphatic endothelial cells in congenital pulmonary lymphangiectasis.

Meta-analysis of inhaled nitric oxide in premature infants: an update.

INTRODUCTION: The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. We performed a meta-analysis of five published randomized controlled trials involving a total of 808 infants below 34 weeks of gestation. RESULTS: The rates of major intracranial hemorrhage (ICH) were similar in both groups (42 of 208 infants receiving iNO vs 52 of 185 controls, relative risk (RR) 0.72, 95 % confidence interval (CI) 0.50-1.02) as was the mortality rate (169 of 415 receiving iNO vs 155 of 393 controls, RR 1.03, 95 % CI 0.87-1.22). Of 415 infants receiving iNO, 188 infants were diagnosed as having chronic lung disease (CLD), compared to 215 of 393 control infants. The RR in favor of iNO was 0.83, 95 % CI 0.72-0.95, p = 0.0092. Treatment failure, defined as death or CLD was significantly reduced in the iNO group (iNO: 126 of 208 infants versus control: 139 of 185, RR in favor of iNO 0.81, 95 % CI 0.70-0.93, p = 0.0025). CONCLUSIONS: We conclude that the use of iNO may decrease the CLD and the combined endpoint CLD and mortality in preterm infants with hypoxemic respiratory failure. However, the most recent and by far largest study was terminated due to an increase in severe ICH. Therefore a cautious use of iNO in preterm infants at risk for ICH is mandatory. Further studies with appropriate neurodevelopmental follow-up need to elucidate if the reduction of CLD in very low birth weight infants is potentially associated with modifications in neurodevelopmental outcome.

Role of erythromycin for treatment of incipient chronic lung disease in preterm infants colonised with Ureaplasma urealyticum.

Ureaplasma urealyticum is frequently isolated from tracheal aspirates of very low birthweight infants who go on to develop chronic lung disease. The use of erythromycin has been advocated in ventilated very low birthweight infants who are colonised with U. urealyticum, although the association between U. urealyticum and chronic lung disease remains controversial. There are only two randomised, controlled trials involving a total of 37 U. urealyticum-positive very low birthweight infants. Both trials failed to demonstrate a reduction in the incidence of chronic lung disease after 7 or 10 days of erythromycin. On the other hand, there are reports of rare but serious adverse effects of erythromycin in newborn infants including sudden cardiovascular compromise and hypertrophic pyloric stenosis. We conclude that, at present, there is insufficient evidence to support the use of erythromycin for the treatment of incipient chronic lung disease in very low birthweight infants colonised with U. urealyticum.

Hyperoxia- and hypoxia-mediated activation of polymorphonuclear leukocytes: a comparison of cord and adult venous blood.

BACKGROUND: Among the most prominent changes occurring in newborn infants is the exposure of tissues and blood cells to increased oxygen tension. This increase is even more pronounced in neonatal resuscitation using 100% oxygen, currently recommended in the published guidelines. OBJECTIVE: To analyse the response of neonatal and adult polymorphonuclear neutrophils (PMN) to high or low oxygen tension in vitro. MATERIALS: Neonatal cord blood and adult venous blood without previous contact to ambient air was exposed to 0, 21, or 100% oxygen for 30 min followed by incubation for up to 24 h. METHODS: Flow cytometry was used to assess PMN activation as indicated by downregulation of L-selectin expression. Cell viability was quantified by the amount of propidium iodide uptake. RESULTS: In adult PMN, L-selectin downregulation was greatly accelerated by hypoxia (PO2=27.2+/-3.4 mmHg) compared with both normoxia (PO2=71.0+/-11.0 mmHg) or hyperoxia (PO2=653.2+/-9.4) (P<0.05). In contrast, hyperoxia was the most potent stimulus for cord blood PMN, compared with both normoxia and hypoxia (P<0.05). Evidence of necrosis as indicated by positive staining for propidium iodide was similar in cord blood (10 h: 5.83% in oxygen) and in adult blood (10 h: 6.45% in oxygen). No differences were found between exposure to hypoxia, normoxia, or hyperoxia. CONCLUSION: Oxygen exposure of neonatal PMN leads to a more pronounced activation as compared with adult cells. Exposure towards high concentrations of oxygen may contribute to inflammatory processes during early neonatal life.

Colonic pneumatosis intestinalis in preterm infants: different to necrotising enterocolitis with a more benign course?

UNLABELLED: Necrotising enterocolitis (NEC) is the predominant immaturity-associated disease of the bowel in the preterm neonate and leads to substantial mortality and long-term morbidity. Diagnostic features of NEC include, apart from the clinical presentation, laboratory and radiological parameters. Pneumatosis intestinalis (PI) on abdominal radiographs is regarded as a criterion of definitive proof for this disease entity. The objective of this presentation is to link the topographic pattern of PI to the clinical course in cases of suspected NEC. We report two cases of radiological appearance of colonic PI indicative of NEC without associated laboratory and/or macroscopic evidence of the disease, and with minor clinical symptoms only. Data from animal studies indicate that decreased blood supply to the small bowel is associated with more extensive bowel damage as compared to impaired colonic perfusion. Therefore the topographical distribution of PI might be a more specific sign as the general presence or absence of PI. CONCLUSION: The topographical pattern of pneumatosis intestinalis may be predictive of the clinical course of inflammatory bowel disease in preterm infants.

Effectiveness of intravaginal progesterone inserts and FSH for inducing synchronized estrus and increasing lambing rate in anestrous ewes.

The objectives of this study were to determine whether a new progesterone (P4)-releasing intravaginal insert would induce fertile estrus and whether FSH combined with the insert would increase prolificacy in anestrous ewes introduced to rams. Ewes of mixed breeding on six farms were assigned to four randomized treatments: control (C), n = 73; 12 d P4 (polycapralactone [PCL] insert with 0.82 g P4), (P12), n = 73; 12 d P4 plus i.m. FSH (Folltropin, 55 mg NIH-FSH-P1 equivalent) in propylene glycol, 24 h before insert removal, (P12F), n = 71; and 5 d P4 plus FSH (P5F), n = 77. Growth and ovulation of follicles were observed ultrasonographically in 20 ewes at four farms (five/treatment) at insert removal and 36, 48, 72, and 96 h later. Intact rams (1:15 ewes in multiple-sire groups) were joined at insert removal, and raddle marks were observed every 12 h for 5 d. On d 26 to 30, rams were removed; ewes were examined for pregnancy then and 20 d later. Percentage of ewes marked by rams was greater in P4-treated (66 to 79%) than in C (12%; P < 0.01) ewes and in P5F (79%) than in P12F (66%; P < 0.05). Diameters of largest follicles at insert removal were greater (P < 0.05) in P4-treated (5.5 +/- 0.2) than in C ewes (4.8 +/- 0.2). Progesterone increased numbers of follicles > 3 mm (P < 0.01) or ovulated (P < 0.05; 2.6 +/- 0.6 vs 1.3 +/- 0.6 in C ewes) and FSH increased number of follicles > 3 mm (P < 0.05). In FSH-treated ewes, ovulation rate tended to be greater after treatment with P4 for 5 than for 12 d (P = 0.09, 3.3 +/- 0.6 and 2.2 +/- 0.4, respectively). More P4-treated than C ewes lambed (P < 0.01) to the first (38 to 45 vs 0%) or both (63 to 66 vs 41%) service periods. Prolificacy (first service) did not differ between FSH-treated ewes (P12F + P5F; 1.8 +/- 0.1) and ewes treated with P4 only (P12; 1.6 +/- 0.1). However, FSH increased prolificacy to first service (1.8 +/- 0.1) over prolificacy to second service (C ewes 1.5 +/- 0.1; P < 0.05, and all ewes 1.4 +/- 0.1; P < 0.01). Pregnancy retention did not differ among treatments but was greater (P < 0.01) in ewes that conceived at the first (90.9 +/- 3.7) than at the second (72.5 +/- 3.3) service period. In conclusion, a PCL insert in combination with ram introduction at insert removal was more effective than ram introduction alone to induce synchronized estrus and ovulation and to yield pregnancy after one or two service periods. Treatment with P4 for 5 d was as effective as for 12 d to induce fertile estrus in FSH-treated anestrous ewes.

In-vitro activation of complement system by lactic acidosis in newborn and adults.

INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates.

Response to inhaled nitric oxide in premature and term neonates.

Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification -- no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right-to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates.

Focal congenital alveolar proteinosis associated with abnormal surfactant protein B messenger RNA.

Two siblings presented with typical clinical features of congenital pulmonary alveolar proteinosis (PAP). Necropsy of one sibling revealed scattered foci of the diagnostic histologic changes in the lung tissue. In contrast to infantile and adult PAP, focal distribution is uncommon in congenital PAP. Defective expression of the granulocyte-macrophage colony-stimulating factor receptor was ruled out. The surfactant protein B (SP-B) content in the lung tissue of the autopsied patient was low, and a deletion in the SP-B messenger RNA was detected. We speculate that the PAP in our patients was related to the reduced quantity and/or to the altered quality of SP-B.

Chest physiotherapy in mechanically ventilated children: a review.

OBJECTIVE: Many physicians, nurses, and respiratory care practitioners consider chest physiotherapy (CP) a standard therapy in mechanically ventilated children beyond the newborn period. CP includes percussion, vibration, postural drainage, assisted coughing, and suctioning via the endotracheal tube. DATA SOURCES: We searched the medical literature by using the key words "chest physiotherapy" and "chest physical therapy" (among others) by means of the MEDLINE and Current Contents databases. STUDY SELECTION: Because of the paucity of objective data, we examined all reports dealing with this topic, including studies on adult patients. For data extraction, not enough material existed to perform a meta-analysis. DATA SYNTHESIS: Despite its widespread use, almost no literature dealing with this treatment modality in pediatric patients exists. Studies with mechanically ventilated pediatric and adult patients have shown that CP is the most irritating routine intensive care procedure to patients. An increase in oxygen consumption often occurs when a patient receives CP accompanied by an elevation in heart rate, blood pressure, and intracranial pressure. CP leads to short-term decreases in oxygen, partial pressure in the blood, and major fluctuations in cardiac output. Changes in these vital signs and other variables may be even more pronounced in pediatric patients because the lung of a child is characterized by a higher closing capacity and the chest walls are characterized by a much higher compliance, thus predisposing the child to the development of atelectasis secondary to percussion and vibration. CONCLUSION: CP in mechanically ventilated children may not be considered a standard therapy. Controlled studies examining the impact of CP on the duration of mechanical ventilatory support, critical illness, and hospital stay are needed.