The role of antibiotics in the prevention of cross infections in newborn infants and mothers during the puerperium]

Epidemiological efficiency of antibiotic prophylaxis of hospital infections (HIs) in maternity homes was analyzed by the materials on the clinical observation of 43995 newborns and their mothers within a period of 1986 to 1989 as well as by the data on the bacteriological examination of 6616 smears from the mucosa of the nose, pharynx, rectum and umbilical wounds of 1890 newborns carried out within the same period. It was shown that the prophylactic use of the antibiotics in the maternity homes led to changes in the microflora colonizing the newborns. The more massive was the use of the antibiotics in the departments of newborns and the postnatal departments, the more intensive was replacement of gram-positive microflora in the newborns by gram-negative organisms among which Klebsiella strains with high antibiotic resistance predominated. This involved an increase in the incidence of pneumonia and sepsis in the newborns and a higher death rate among the newborns due to HIs. In parallel there was observed an increase in the incidence of metro-endometritis in the puerperae++ and a simultaneous decrease in the number of the cases with lactational mastitis as a result of lower numbers of Staphylococcus aureus cultures isolated from various loci of the newborns. It was concluded that antibiotics were not the drugs to be used as prophylactic agents in control of HIs in maternity homes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aspergillus in the Intensive Care Unit

Invasive aspergillosis (IA), the most life-threatening form of aspergillosis, has become a major opportunistic fungal disease in immunocompromised patients. In high-risk patients with hematologic malignancies, IA appears to decline with the use of mold-active antifungal prophylaxis, but the situation is less clear in other patient groups at risk for IA, and precise epidemiologic data from patients treated in intensive care units (ICUs) are lacking. Most Aspergillus culture isolates from nonsterile body sites do not represent disease, but isolation of Aspergillus in critically ill patients is a marker of poor prognosis and is associated with high mortality regardless of invasion or colonization. This review presents current information on epidemiology, risk factors, and diagnosis, and discusses treatment options for patients with IA in the ICU.     

Prophylaxis for Candida in the intensive care unit patient

Candidemia is one of the most frequent causes of bloodstream infections in intensive care units in the United States and the developed world. It involves a substantial morbidity, crude/attributable mortality, and increased health care costs in excess of an average of $40,000 per episode. Prophylaxis is one of many strategies to control this disease; however, the success of this strategy is directly related to the selection of populations at highest risk and the availability of safe, effective, and economical drugs. Current risk assessment strategies based on clinical prediction rules offer the possibility of targeted prophylaxis, making this approach even more attractive.     

Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group.

OBJECTIVE--To determine the clinical benefits of selective decontamination of the digestive tract in patients treated in intensive care units. DESIGN--Meta-analysis of 22 randomised trials that compared different combinations of oral non-absorbable antibiotics, with or without a systemic component, with no treatment in controls. SUBJECTS--4142 patients seen in general and specialised intensive care units around the world. 2047 received some form of antibiotic treatment, the remainder no prophylaxis. DATA ANALYSIS--Each trial was reviewed through direct contact with study investigators. Data collected were: the randomisation procedure, number of patients, number excluded from the analysis, and numbers of respiratory tract infections and deaths. Data were combined according to an intention to treat analysis with the Mantel-Haenszel-Peto method. MAIN OUTCOME MEASURES--Respiratory tract infections and total mortality. RESULTS--Selective decontamination of the digestive tract significantly reduced respiratory tract infections (odds ratio 0.37; 95% confidence interval 0.31 to 0.43). The value of the common odds ratio for total mortality (0.90; 0.79 to 1.04) suggested at best a moderate treatment effect, reaching statistical significance only when the subgroup of trials of topical and systemic treatment combined was considered separately (odds ratio 0.80; 0.67 to 0.97). No firm conclusions could be drawn owing to large variations in patient mix and severity within and between trials. CONCLUSIONS--The findings strongly indicate that selective decontamination significantly reduces infection related morbidity in patients receiving intensive care. They also highlight why definite conclusions about the effect of prophylaxis on mortality cannot be drawn despite the large number of trials available. Based on the most favourable results obtained by pooling data from trials in which combined topical and systemic treatment was used it may be estimated that 6 (range 5-9) and 23 (13-139) patients would need to be treated to prevent one respiratory tract infection and one death respectively.     

Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.     

Leucocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity in G-6-PD deficient Chinese

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied for erythrocyte G-6-PD deficiency using 49 hemizygous males, 16 heterozygous females, and 19 normal controls. The mean G-6-PD activity in leucocytes of the affected neonates (9.2 +/- 5.4 units) and the children (11.2 +/- 5.3 units) were significantly lower than those of normal newborns (22.9 +/- 5.1 units, P less than 0.01). Seventy percent of the effected newborns and 58% of the children with G-6-PD deficiency had the leucocyte enzyme activity of less than 13 IU/10(9)WBC. The leucocyte enzyme activity (14.6 +/- 8.6 units) of 16 heterozygous G-6-PD deficient mothers was also lower than that of normal controls (23.1 +/- 7.0 units). The present study thus concludes that, in G-6-PD deficient Chinese, the enzyme defect is demonstrable not only in erythrocytes but also in leucocytes.     

Reducing the incidence of infection after caesarean section: implications of prophylaxis with antibiotics for hospital resources.

OBJECTIVES--To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section. DESIGN--Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice. SETTING--Trials included in the overview were from obstetric units in several different countries, including the United Kingdom. The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford. SUBJECTS--A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment. Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987. MAIN OUTCOME MEASURE--Cost effectiveness of prophylaxis with antibiotics. RESULTS--The odds of wound infection are likely to be reduced by between about 50 and 70% by giving antibiotics routinely at caesarean section. Forty one (8.4%) women who had caesarean section were coded by the Oxford obstetric data system as having developed wound infection. The additional average cost of hospital postnatal care for women with wound infection (compared with women who had had caesarean section and no wound infection) was estimated to be 716 pounds; introducing routine prophylaxis with antibiotics would reduce average costs of postnatal care by between 1300 pounds and 3900/100 pounds caesarean sections (at 1988 prices), depending on the cost of the antibiotic used and its effectiveness. CONCLUSIONS--The results suggest that giving antibiotics routinely at caesarean section will not only reduce rates of infection after caesarean section but also reduce costs.     

Distance to Care,Facility Delivery and Early Neonatal Mortality in Malawi and Zambia

Background

Globally, approximately 3 million babies die annually within their first month. Access to adequate care at birth is needed to reduce newborn as well as maternal deaths. We explore the influence of distance to delivery care and of level of care on early neonatal mortality in rural Zambia and Malawi, the influence of distance (and level of care) on facility delivery, and the influence of facility delivery on early neonatal mortality.

Methods and Findings

National Health Facility Censuses were used to classify the level of obstetric care for 1131 Zambian and 446 Malawian delivery facilities. Straight-line distances to facilities were calculated for 3771 newborns in the 2007 Zambia DHS and 8842 newborns in the 2004 Malawi DHS. There was no association between distance to care and early neonatal mortality in Malawi (OR 0.97, 95%CI 0.58–1.60), while in Zambia, further distance (per 10 km) was associated with lower mortality (OR 0.55, 95%CI 0.35–0.87). The level of care provided in the closest facility showed no association with early neonatal mortality in either Malawi (OR 1.02, 95%CI 0.90–1.16) or Zambia (OR 1.02, 95%CI 0.82–1.26). In both countries, distance to care was strongly associated with facility use for delivery (Malawi: OR 0.35 per 10km, 95%CI 0.26–0.46). All results are adjusted for available confounders. Early neonatal mortality did not differ by frequency of facility delivery in the community.

Conclusions

While better geographic access and higher level of care were associated with more frequent facility delivery, there was no association with lower early neonatal mortality. This could be due to low quality of care for newborns at health facilities, but differential underreporting of early neonatal deaths in the DHS is an alternative explanation. Improved data sources are needed to monitor progress in the provision of obstetric and newborn care and its impact on mortality.     

Prevalence of severe retinopathy of prematurity in a geographically defined population in Croatia

The aim of this study was to evaluate the prevalence of stage III of retinopathy of prematurity (ROP) among newborns of birth weight < 1500 g and gestational age (GA) < or = 32 weeks, and to compare these prevalences during two time periods (1998-2002 and 2003-2007). The investigation was conducted at the Department of Gynecology and Obstetrics, University Hospital in Rijeka, Croatia. The screening for ROP was performed by an ophthalmologist using a binocular indirect ophthalmoscope. Over a period of 10 years, there were 28,627 liveborn newborns, with 136 (0.48%) premature newborns with a birth weights < 1500 g and 226 (0.79%) newborns with GA at birth < or = 32 weeks. The proportions of survivors among newborns with birth weights < 1500 g (51.1% vs. 70.5%) and among newborns with GA at birth < or = 32 weeks (67.9% vs. 77.0%) were significantly higher in the later period. During the period 2003-2007, the proportion examined for ROP was higher among newborns with birth weight < 1500 g (52.9% vs. 97.1%) and among newborns with GA at birth < or = 32 weeks (46.5% vs. 96.9%). The prevalence of stage III ROP was significantly lower in 2003-2007 compared to that in 1998-2002 among newborns with birth weight < 1500 g (30.6% vs. 14.0%) and newborns with GA at birth < or = 32 weeks (22.4% vs. 8.8%). The prevalence of total ROP among newborns was significantly lower in 2003-2007 compared with 1998-2002. This decrease in prevalence may be explained by advances in neonatal intensive care unit, increased survival of very low birth weight infants and carefully timed retinal examinations.     

Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling Based on Demographics,Excess Mortality,and Interventions

Background

The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.

Methods and Findings

First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400–398,800) in 2010 to 404,200 (CI: 242,500–657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900–106,100]; 2050: 140,800 [CI: 95,500–200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600–48,800]; 2050: 44,700 [CI: 27,100–70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700–59,100]; 2050: 33,900 [CI: 15,900–64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800–6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800–14,232,700) newborns with SCA globally, 85% (CI: 81%–88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.

Conclusions

Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors'' Summary     

High Compliance with Newborn Community-to-Facility Referral in Eastern Uganda:.An Opportunity to Improve Newborn Survival

Background

Seventy-five percent of newborn deaths happen in the first-week of life, with the highest risk of death in the first 24-hours after birth.WHO and UNICEF recommend home-visits for babies in the first-week of life to assess for danger-signs and counsel caretakers for immediate referral of sick newborns. We assessed timely compliance with newborn referrals made by community-health workers (CHWs), and its determinants in Iganga and Mayuge Districts in rural eastern Uganda.

Methods

A historical cohort study design was used to retrospectively follow up newborns referred to health facilities between September 2009 and August 2011. Timely compliance was defined as caretakers of newborns complying with CHWs’ referral advice within 24-hours.

Results

A total of 724 newborns were referred by CHWs of whom 700 were successfully traced. Of the 700 newborns, 373 (53%) were referred for immunization and postnatal-care, and 327 (47%) because of a danger-sign. Overall, 439 (63%) complied, and of the 327 sick newborns, 243 (74%) caretakers complied with the referrals. Predictors of referral compliance were; the newborn being sick at the time of referral- Adjusted Odds Ratio (AOR) = 2.3, and 95% Confidence-Interval (CI) of [1.6 - 3.5]), the CHW making a reminder visit to the referred newborn shortly after referral (AOR =1.7; 95% CI: [1.2 -2.7]); and age of mother (25-29) and (30-34) years, (AOR =0.4; 95% CI: [0.2 - 0.8]) and (AOR = 0.4; 95% CI: [0.2 - 0.8]) respectively.

Conclusion

Caretakers’ newborn referral compliance was high in this setting. The newborn being sick, being born to a younger mother and a reminder visit by the CHW to a referred newborn were predictors of newborn referral compliance. Integration of CHWs into maternal and newborn care programs has the potential to increase care seeking for newborns, which may contribute to reduction of newborn mortality.     

Natural Conception May Be an Acceptable Option in HIV-Serodiscordant Couples in Resource Limited Settings

Many HIV serodiscordant couples have a strong desire to have their own biological children. Natural conception may be the only choice in some resource limited settings but data about natural conception is limited. Here, we reported our findings of natural conception in HIV serodiscordant couples. Between January 2008 and June 2014, we retrospectively collected data on 91 HIV serodiscordant couples presenting to Beijing Youan Hospital with childbearing desires. HIV counseling, effective ART on HIV infected partners, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in negative female partners and timed intercourse were used to maximally reduce the risk of HIV transmission. Of the 91 HIV serodiscordant couples, 43 were positive in male partners and 48 were positive in female partners. There were 196 unprotected vaginal intercourses, 100 natural conception and 97 newborns. There were no cases of HIV seroconversion in uninfected sexual partners. Natural conception may be an acceptable option in HIV-serodiscordant couples in resource limited settings if HIV-positive individuals have undetectable viremia on HAART, combined with HIV counseling, PrEP, PEP and timed intercourse.     

Facilitators and barriers in implementing units for short term terminal care in nursing homes

Minimal care requirements were drafted for units for short-term palliative care for terminally ill patients in nursing homes in The Netherlands. The requirements were evaluated by (a) determining to what extent ten units were able to meet these requirements and (b) which facilitators and barriers influenced the implementation of the units. Staff members of the ten units were interviewed using a semi-structured interview protocol six months after the units were established. The results show that on average 69 percent of the requirements were met. Requirements for expertise development were best met (77 percent), and requirements for personnel and team were met least (58 percent). Facilitators for meeting the requirements included development of new housing or renovation, being part of a care provider network, and onetime subsidies. Barriers included lack of funds and shortage of staff. Further development of the requirements based on the results of this study by a committee of experts was advised.     

Crimean-Congo haemorrhagic fever in southern Russia

At the end of the 20th--the beginning of the 21st century activation of a natural focus of Crimean-Congo haemorrhagic fever (CCHF) in southern Russia was noted. As a consequence, in 2002 outbreaks and sporadic cases of this disease were registered on the territory of 6 out of 13 administrative units of the Southern Federal District. To minimize the epidemiological consequences of the aggravating epidemiological situation considerable efforts and means were required from health care organs and institutions of the state sanitary and epidemiological service, including essential financial expenditures. The results of natural foci of CCHF survey, obtained by 2002, as well as main trends of prophylactic and antiepidemic interventions are presented. Scientific research and practical observations made it possible to work out a number of methodological regulations concerning the diagnostics, treatment and prophylaxis of CCHF.     

Phototherapy increases DNA damage in lymphocytes of hyperbilirubinemic neonates

Phototherapy is commonly used in the treatment of hyperbilirubinemia in newborns. No serious side effects related to phototherapy have been observed, but concerns regarding its potential to damage DNA have been expressed, based on animal or cell-culture studies. The aim of this study was to investigate, in neonates with hyperbilirubinemia, the possible relation between phototherapy and DNA damage. The study included 33 full-term newborns with non-physiological jaundice and 14 healthy newborns with physiological jaundice as controls. Phototherapy was performed with an array of six fluorescent lamps producing radiation with wavelengths of 480-520 nm at 12 microW/cm(2)/nm. DNA damage in lymphocytes was determined by use of the alkaline comet assay. The DNA damage increased significantly with the duration of phototherapy, as shown by measurements at 24, 48, and 72 h (P<0.001). These findings indicate that phototherapy, widely used in neonatology units, increases DNA damage in newborns. It remains to be seen whether the genotoxic effect observed in the present study can cause any long-term health effect in phototherapy-treated infants in later life.     

Prevalence and structure of acute respiratory virus infections

Information on epidemiology of acute respiratory virus infections (ARVI) is reviewed and analyzed. In addition to influenza viruses, the role of respiratory syncytial viruses (RSV), rhino- and adenoviruses, as well as other viruses, in the development of respiratory diseases, especially in newborns, young children and elderly persons, is emphasized. A high proportion of RSV in the etiology the severe forms of ARVI and in the development of intrauterine infection is pointed out. The conclusion has been made that the identification of the causative agents of ARVI with the use of modern methods makes it possible to determine the real role of each of the pathogens in the formation of the severe forms of diseases, as well as the expediency of vaccinal prophylaxis.     

Adherence to Hypothermia Guidelines: A French Multicenter Study of Fullterm Neonates

Aim

The objective of this study was to describe the French practice of hypothermia treatment (HT) in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to analyze the deviations from the guidelines of the French Society of Neonatology.

Materials and Methods

From May 2010 to March 2012 we recorded all cases of HIE treated by HT in a French national database. The population was divided into three groups, "optimal HT" (OHT), “late HT” (LHT) and “non-indicated” HT (NIHT), according to the guidelines.

Results

Of the 311 newborns registered in the database and having HT, 65% were classified in the OHT group, 22% and 13% in the LHT and NIHT groups respectively. The severity of asphyxia and HIE were comparable between newborns with OHT and LHT, apart from EEG. HT was initiated at a mean time of 12 hours of life in the LHT group. An acute obstetrical event was more likely to be identified among newborns with LHT (46%), compared to OHT (34%) and NIHT (22%). There was a gradation in the rate of complications from the NIHT group (29%) to the LHT (38%) group and the OHT group (52%). Despite an insignificant difference in the rates of death or abnormal neurological examination at discharge, nearly 60% of newborns in the OHT group had an MRI showing abnormalities, compared to 44% and 49% in the LHT and NIHT groups respectively.

Conclusion

The conduct of the HT for HIE newborns is not consistent with French guidelines for 35% of newborns, 22% being explained by an excessive delay in the start of HT, 13% by the lack of adherence to the clinical indications. This first report illustrates the difficulties in implementing guidelines for HT and should argue for an optimization of perinatal care for HIE.     

Organ donation from intensive care units in England.

OBJECTIVE--To audit all deaths in intensive care units (excepting coronary care only and neonatal intensive care units) in England to assess potential for organ procurement. DESIGN--An audit in which 14 regional health authorities and London special health authorities each designated a regional liaison officer to identify intensive care units and liaise with Department of Health and the Medical Research Council''s biostatistics unit in distribution, return, and checking of audit forms. Audit took place from 1 January to 31 March 1989 and will continue to 31 December 1990. SETTING--278 Intensive care units in England. PARTICIPANTS--Colleagues in intensive care units (doctors, nurses, coordinators, and others), who completed serially numbered audit forms for all patients who died in intensive care. RESULTS--The estimated number of deaths in intensive care units was 3085, and validated audit forms were received for 2853 deaths (92%). Brain stem death was a possible diagnosis in only 407 (14%) patients (about 1700 cases a year) and was confirmed in 282 (10%) patients (an estimated 1200 cases a year). Half the patients (95% confidence interval 45% to 57%) in whom brain stem death was confirmed became actual donors of solid organs. Tests for brain stem death were not performed in 106 (26%) of 407 patients with brain stem death as a possible diagnosis, and general medical contraindication to organ donation was recorded for 48 (17%) of 282 patients who fulfilled brain stem death criteria before cessation of heart beat. The criteria were fulfilled before cessation of heart beat and in the absence of any general medical contraindication to organ donation in 234 patients, 8% of those dying in intensive care (an estimated 1000 cases a year). Consent for organ donation was given in 152 (70%) of 218 cases (64% to 76%) when the possibility of organ donation was suggested to relatives. In only 14 out of 232 families (6%; 3% to 9%) was there no discussion of organ donation with relatives. Corneal suitability was recorded as "not known" in a high proportion (1271; 45%) of all deaths and intensive care units reported only 123 corneal donors (4% of all audited deaths). CONCLUSION--When brain stem death is a possible diagnosis tests should always be carried out for confirmation. Early referral to the transplant team or coordinator should occur in all cases of brain stem death to check contraindications to organ donation. There should be increased use of asystolic kidney donation, and patients should be routinely assessed for suitability for corneal donation. Finally, more publicity and education are necessary to promote consent.     

Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

BackgroundNeonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns.ObjectiveThis study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns.Design/MethodsTwelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns.ResultsCompared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns.ConclusionsThese findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.