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1.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of Disease in Childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
doi:10.1136/adc.2010.186049
PMCID: PMC3081806  PMID: 21220263
2.  Why do Families of Sick Newborns Accept Hospital Care? A Community-Based Cohort Study in Karachi, Pakistan 
Objective
Sick young infants are at high risk of mortality in developing countries but families often decline hospital referral. Our objective was to identify the predictors of acceptance of referral for hospital care among families of severely ill newborns and infants <59 days old in three low-income communities of Karachi, Pakistan.
Study design
A cohort of 541 newborns and infants referred from home by community health workers doing household surveillance, and diagnosed with a serious illness at local community clinics between January 1 and December 31, 2007, was followed-up within 1 month of referral to the public hospital.
Results
Only 24% of families accepted hospital referral. Major reasons for refusal were financial difficulties (67%) and father/elder denying permission (65%). Religious/cultural beliefs were cited by 20% of families. Referral acceptance was higher with recognition of severity of the illness by mother (OR=12.7; 95% CI=4.6–35.2), family’s ability to speak the dominant language at hospital (OR=2.0; 95% CI=1.3–3.1), presence of grunting in the infant (OR=3.3; 95% CI=1.2–9.0), and infant temperature <35.5°C (OR=4.1; 95% CI=2.3–7.4). No gender differential was observed.
Conclusion
Refusal of hospital referral for sick young infants is very common. Interventions that encourage appropriate care seeking, as well as community-based management of young infant illnesses when referral is not feasible are needed to improve neonatal survival in low-income countries.
doi:10.1038/jp.2010.191
PMCID: PMC3152606  PMID: 21273989
newborn health; care-seeking; Pakistan
3.  Young infant sepsis: aetiology, antibiotic susceptibility and clinical signs 
Summary
Globally, young infant mortality comprises 40% of the estimated 10.8 million child deaths annually. Almost all (99%) of these deaths arise in low- and middle-income countries (LMICs). Achievement of the Millennium Development Goal for child survival, however, requires a significant improvement in the management of infections in young infants. We have reviewed current evidence from LMICs on one major cause of young infant mortality, severe infection, and have described the range of pathogens, reported antibiotic susceptibility and value of clinical signs in identifying severe bacterial illness. Evidence from the reviewed studies appears to show that common pathogens in young infant infections change over time and vary within and across settings. However, there are few good, large studies outside major urban settings and many reports describe infections of babies born in hospital when most young infant infections probably occur in the majority born at home. Yet what knowledge there is can aid in instituting prompt and appropriate therapy, and perhaps thus minimize the emergence of multidrug-resistant bacteraemia, a major threat at least in hospital settings. Improved country level data on pattern of microorganisms, resistance and antibiotic use are required to help reduce mortality through development of local, evidence-based clinical guidelines.
doi:10.1016/j.trstmh.2007.05.005
PMCID: PMC2673057  PMID: 17658566
Sepsis; Aetiology; Antibiotics; Signs; Bacterial infection; Infant
4.  Young infant sepsis: aetiology, antibiotic susceptibility and clinical signs 
Summary
Globally, young infant mortality comprises 40% of the estimated 10.8 million child deaths annually. Almost all (99%) of these deaths arise in low- and middle-income countries (LMICs). Achievement of the Millennium Development Goal for child survival, however, requires a significant improvement in the management of infections in young infants. We have reviewed current evidence from LMICs on one major cause of young infant mortality, severe infection, and have described the range of pathogens, reported antibiotic susceptibility and value of clinical signs in identifying severe bacterial illness. Evidence from the reviewed studies appears to show that common pathogens in young infant infections change over time and vary within and across settings. However, there are few good, large studies outside major urban settings and many reports describe infections of babies born in hospital when most young infant infections probably occur in the majority born at home. Yet what knowledge there is can aid in instituting prompt and appropriate therapy, and perhaps thus minimize the emergence of multidrug-resistant bacteraemia, a major threat at least in hospital settings. Improved country level data on pattern of microorganisms, resistance and antibiotic use are required to help reduce mortality through development of local, evidence-based clinical guidelines.
doi:10.1016/j.trstmh.2007.05.005
PMCID: PMC2673057  PMID: 17658566
5.  The management of sick young infants at primary health centres in a rural developing country 
Archives of Disease in Childhood  2005;90(2):200-205.
Aims: To investigate the epidemiology of illness among young infants at remote health clinics in a rural developing country, and to determine risk factors for mortality that might be used as triggers for emergency treatment or referral.
Methods: Multi-site 12 month observational study of consecutive presentations of infants less than 2 months, and an investigation of neonates who died in one district without accessing health care.
Results: Forty per cent of 511 young infant presentations occurred in the first week of life and most of these in the first 24 hours. Twenty five deaths were recorded: 18 in the health facilities and seven in villages. In addition there were eight stillbirths. Clinical signs predicting death were: not able to feed, fast respiratory rate, apnoea, cyanosis, "too small", "skin-cold", and severe abdominal distension. Signs indicating severe respiratory compromise were present in 25% of young infants; failure to give oxygen therapy was a modifiable factor in 27% of deaths within health facilities. A high proportion of seriously ill young infants were discharged from health facilities early without adequate follow up. A common reason for not seeking care for fatally ill neonates was the perception by parents that health staff would respond negatively to their social circumstances.
Conclusions: Clinical signs with moderate positive predictive value for death may be useful triggers for emergency treatment and longer observation or urgent referral. The results of this study may be useful in planning strategies to address high neonatal mortality rates in developing countries.
doi:10.1136/adc.2003.047951
PMCID: PMC1720244  PMID: 15665182
6.  Development and technical basis of simplified guidelines for emergency triage assessment and treatment in developing countries 
Archives of Disease in Childhood  1999;81(6):473-477.
Simplified guidelines for the emergency care of children have been developed to improve the triage and rapid initiation of appropriate emergency treatments for children presenting to hospitals in developing countries. The guidelines are part of the effort to improve referral level paediatric care within the World Health Organisation/Unicef strategy integrated management of childhood illness (IMCI), based on evidence of significant deficiencies in triage and emergency care. Existing emergency guidelines have been modified according to resource limitations and significant differences in the epidemiology of severe paediatric illness and preventable death in developing countries with raised infant and child mortality rates. In these settings, it is important to address the emergency management of diarrhoea with severe dehydration, severe malaria, severe malnutrition, and severe bacterial pneumonia, and to focus attention on sick infants younger than 2 months of age. The triage assessment relies on a few clinical signs, which can be readily taught so that it can be used by health workers with limited clinical background. The assessment has been designed so that it can be carried out quickly if negative, making it functional for triaging children in queues.


PMCID: PMC1718149  PMID: 10569960
7.  Paediatric referrals in rural Tanzania: the Kilombero District Study – a case series 
Background
Referral is a critical part of appropriate primary care and of the Integrated Management of Childhood Illness (IMCI) strategy. We set out to study referrals from the aspect both of primary level facilities and the referral hospital in Kilombero District, southern Tanzania. Through record review and a separate prospective study we estimate referral rates, report on delays in reaching referral care and summarise the appropriateness of pediatric referral cases in terms of admission to the pediatric ward at a district hospital
Methods
A sample of patient records from primary level government health facilities throughout 1993 were summarised by age, diagnosis, whether a new case or a reattendance, and whether or not they were referred. From August 1994 to July 1995, mothers or carers of all sick children less than five years old attending the Maternal and Child Health (MCH) clinic or outpatient department (OPD) of SFDDH were interviewed using a standard questionnaire recording age, sex, diagnosis, place of residence, whether the child was admitted to the paediatric ward, and whether the child was referred.
Results
From record review, only 0.6% of children from primary level government facilities were referred to a higher level of care. At the referral hospital, 7.8 cases per thousand under five catchment population had been referred annually. The hospital MCH clinic and OPD were generally used by children who lived nearby: 91% (n = 7,166) of sick children and 75% (n = 607) of admissions came from within 10 km. Of 235 referred children, the majority (62%) had come from dispensaries. Almost half of the referrals (48%) took 2 or more days to arrive at the hospital. Severe malaria and anaemia were the leading diagnoses in referred children, together accounting for a total of 70% of all the referrals. Most referred children (167/235, 71%) were admitted to the hospital paediatric ward.
Conclusions
The high admission rate among referrals suggests that the decision to refer is generally appropriate, but the low referral rate suggests that too few children are referred. Our findings suggest that the IMCI strategy may need to be adapted in sparsely-populated areas with limited transport, so that more children may be managed at peripheral level and fewer children need referral.
doi:10.1186/1472-698X-2-4
PMCID: PMC111197  PMID: 11983024
8.  Causes and outcome of young infant admissions to a Kenyan district hospital 
Archives of Disease in Childhood  2003;88(5):438-443.
Aims: To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya. These data, currently lacking, are important given present efforts to standardise their care through the integrated management of childhood illness (IMCI) and for prioritising both health care provision and disease prevention strategies.
Methods: Prospective, 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward.
Results: A total of 1080 infants were studied. Mortality was 18% overall, though in those aged 0–7 days it was 34%. Within two months of discharge a further 5% of infants aged <60 days on admission had died. Severe infection and prematurity together accounted for 57% of inpatient deaths in those aged <60 days, while jaundice and tetanus accounted for another 27%. S pneumoniae, group B streptococcus, E coli, and Klebsiella spp. were the most common causes of invasive bacterial disease. Hypoxaemia, hypoglycaemia, and an inability to feed were each present in more than 20% of infants aged 0–7 days. Both hypoxaemia and the inability to feed were associated with inpatient death (OR 3.8 (95% CI 2.5 to 5.8) and 7.4 (95% CI 4.8 to 11.2) respectively).
Conclusions: Young infants contribute substantially to paediatric inpatient mortality at the first referral level, highlighting the need both for basic supportive care facilities and improved disease prevention strategies.
doi:10.1136/adc.88.5.438
PMCID: PMC1719579  PMID: 12716721
9.  Community Health Workers Can Identify and Manage Possible Infections in Neonates and Young Infants: MINI—A Model from Nepal 
The mortality rates of infants and children aged less than five years are declining globally and in Nepal but less among neonates. Most deliveries occur at home without skilled attendants, and most neonates may not receive appropriate care through the existing medical systems. So, a community-based pilot programme—Morang Innovative Neonatal Intervention (MINI) programme—was implemented in Morang district of Nepal to see the feasibility of bringing the management of sick neonates closer to home. The objective of this model was to answer the question: “Can a team of female community health volunteers and paid facility-based community health workers (collectively called CHWs) within the existing heath system correctly follow a set of guidelines to identify possible severe bacterial infection in neonates and young infants and successfully deliver their treatment?” In the MINI model, the CHWs followed an algorithm to classify sick young infants with possible severe bacterial infection (PSBI). Female Community Health Volunteers (FCHVS) were trained to visit homes soon after delivery, record the birth, counsel mothers onessential newborn care, and assess the newborns for danger-signs. Infants classified as having PSBI, during this or subsequent contacts, were treated with co-trimoxazole and referred to facility-based CHWs for seven-day treatment with injection gentamicin. Additional supervisory support was provided for quality of care and intensified monitoring. Of 11,457 livebirths recorded during May 2005–April 2007, 1,526 (13.3%) episodes of PSBI were identified in young infants. Assessment of signs by the FCHVs matched that of more highly-trained facility-based CHWs in over 90% of episodes. Treatment was initiated in 90% of the PSBI episodes; 93% completed a full course of gentamicin. Case fatality in those who received treatment with gentamicin was 1.5% [95% confidence interval (CI) 1.0-2.3] compared to 5.3% (95% CI 2.6-9.7) in episodes that did not receive any treatment. Within the existing government health infrastructure, the CHWs can assess and identify possible infections in neonates and young infants and deliver appropriate treatment with antibiotics. This will result in improvement in the likelihood of survival and address one of the main causes of neonatal mortality.
PMCID: PMC3131126  PMID: 21766561
Antibiotic use; Bacterial infections; Drug therapy; Health workers; Infant, Newborn; Neonatal mortality; Sepsis; Nepal
10.  THE VALIDITY OF CLINICAL CRITERIA IN PREDICTING PNEUMONIA AMONG CHILDREN UNDER FIVE YEARS OF AGE 
Background:
Pneumonia is a major cause of morbidity and mortality, especially among infant and young children. Early diagnosis and treatment is essential to reduce the risk. To achieve this, physicians require high quality diagnostic indicators. The aim of the present study is to assess the validity of clinical symptoms and signs in predicting pneumonia among children below the age of 5 years.
Patients and Methods:
This is a case series study for a sample of 103 children aged 4 days-59 months who were admitted to Al-Khanssa Teaching Hospital, Mosul, Iraq, suffering from respiratory symptoms and for whom a chest x-ray was requested. Sensitivity, specificity, predictive values and likelihood ratios were estimated for each clinical criterion.
Results:
Pneumonia was diagnosed on radiological bases in about 70% of the patients. All symptoms had high sensitivity with very low specificity. The best positive predictive values for symptoms were for fast and difficult breathing. However, the signs of Crackle, Tachypnoea, nasal flarring and chest indrawing yielded the best sensitivity estimates. Moreover, a body temperature of ≥38 °C was the best single predictor of pneumonia with a sensitivity of 67% and specificity of 75.8%. The absence of the 3 signs (nasal flaring, chest indrawing and crackles) ruled out pneumonia effectively. The sensitivity of this combination of signs was 98.6%. Detecting a body temperature ≥38 °C and grunting simultaneously was adequate to confirm the disease.
Conclusions:
The study suggests that using clinical criteria in combination could improve physicians′ prediction of pneumonia among children.
PMCID: PMC3410098  PMID: 23012040
Validity; Pneumonia; Epidemiology
11.  Kangaroo care for the preterm infant and family 
Paediatrics & Child Health  2012;17(3):141-143.
Kangaroo care (KC) is the practice of skin-to-skin contact between infant and parent. In developing countries, KC for low-birthweight infants has been shown to reduce mortality, severe illness, infection and length of hospital stay. KC is also beneficial for preterm infants in high-income countries. Cardiorespiratory and temperature stability, sleep organization and duration of quiet sleep, neurodevelopmental outcomes, breastfeeding and modulation of pain responses appear to be improved for preterm infants who have received KC during their hospital stay. No detrimental effects on physiological stability have been demonstrated for infants as young as 26 weeks’ gestational age, including those on assisted ventilation. Mothers show enhanced attachment behaviours and describe an increased sense of their role as a mother. The practice of KC should be encouraged in nurseries that care for preterm infants. Information is available to assist in developing guidelines and protocols.
PMCID: PMC3287094  PMID: 23449885
Family-centred care; Kangaroo care; Preterm infant; Skin-to-skin care
12.  Markers of serious illness in infants under 6 months old presenting to a children's hospital. 
Archives of Disease in Childhood  1990;65(7):750-756.
Six hundred and eighty two assessments were performed on 641 babies under 6 months of age who presented to the emergency department of the Royal Children's Hospital, Melbourne, to try and determine the best markers of serious illness in young infants. Detailed, specific questions that quantified a baby's functional response to illness gave the most useful information. As a group, the six most common predictive symptoms of serious illness were: taking less than half the normal amount of feed over the preceding 24 hours, breathing difficulty, having less than four wet nappies in the preceding 24 hours, decreased activity, drowsiness, and a history of being both pale and hot. The presence of the corresponding sign on examination increased the predictive value of the symptom by 10-20%. Specific, highly predictive (though less common) signs included moderate to severe chest wall recession, respiratory grunt, cold calves, and a tender abdomen. A list of low, medium, and high risk symptoms has been constructed and the five measurements that were most useful in predicting serious illness in young infants have been detailed.
PMCID: PMC1792442  PMID: 2201263
13.  Transportation of sick neonates, 1972: an unsatisfactory aspect of medical care 
An analysis of personnel and facilities used for transfer of sick newborn infants to the Neonatal Intensive Care Unit of The Hospital for Sick Children, Toronto during the months November 1971 and February to April 1972 showed many deficiencies. In many instances severely ill patients were accompanied by inadequately trained staff, transport incubators were either inadequate to maintain the babies' temperatures or were used inappropriately, resuscitation facilities were not available and oxygen concentrations could neither be measured nor varied as desired.
Infants who weighed less than 1500 g. at birth and who died following transfer had significantly lower mean body temperatures on arrival at the referral hospital than those who survived. Mean transport incubator temperatures were too low in all groups of infants but were lower in those who died, although the difference was not statistically significant.
PMCID: PMC1946984  PMID: 4750297
14.  Effect of intrauterine cocaine exposure on respiratory distress syndrome in very low birthweight infants. 
To evaluate the effect of intrauterine cocaine exposure on lung maturity of very low birthweight infants, the medical records of all infants with birthweight < 1500 g born between January 1989 and December 1990 at DC General Hospital were reviewed. Infants with conditions known to cause lung maturity, severe congenital anomalies, proven early sepsis, and birthweight > or = 500 g were excluded. A total of 69 infants were included in the study. Chest roentgenograms of these infants were evaluated by a pediatric radiologist, who was unaware of the infant's medical course, for evidence of respiratory distress syndrome (RDS), and radiological findings were correlated with clinical signs. Forty infants were exposed to cocaine in utero (cocaine group) and 29 were not exposed (noncocaine group). African-American ethnicity, pregnancy-induced hypertension, prolonged rupture of membranes, and alcohol use were similar in both groups. Tobacco use among cocaine group mothers was higher (42.5% versus 13.8%; P = .01). Gestational age (28.3 +/- 2.8 versus 28.3 +/- 3 weeks), birthweight (966 +/- 282 versus 1059 +/- 295 g), male gender, and Apgar scores were similar in both groups. Thirty (75%) infants in the cocaine group developed RDS compared with 19 (66%) in the noncocaine group (P > .05). Using multiple logistic regression analysis and controlling for smoking, alcohol use, and prolonged rupture of membranes (24 to 72 hours), the incidence of RDS between the groups remained statistically insignificant. We conclude that intrauterine cocaine exposure does not alter the incidence of RDS in very low birthweight infants.
PMCID: PMC2607679  PMID: 8046765
15.  Clinical indicators of bacterial meningitis among neonates and young infants in rural Kenya 
BMC Infectious Diseases  2011;11:301.
Background
Meningitis is notoriously difficult to diagnose in infancy because its clinical features are non-specific. World Health Organization (WHO) guidelines suggest several indicative signs, based on limited data. We aimed to identify indicators of bacterial meningitis in young infants in Kenya, and compared their performance to the WHO guidelines. We also examined the feasibility of developing a scoring system for meningitis.
Methods
We studied all admissions aged < 60 days to Kilifi District Hospital, 2001 through 2005. We evaluated clinical indicators against microbiological findings using likelihood ratios. We prospectively validated our findings 2006 through 2007.
Results
We studied 2,411 and 1,512 young infants during the derivation and validation periods respectively. During derivation, 31/1,031 (3.0%) neonates aged < 7 days and 67/1,380 (4.8%) young infants aged 7-59 days (p < 0.001) had meningitis. 90% of cases could be diagnosed macroscopically (turbidity) or by microscopic leukocyte counting. Independent indicators of meningitis were: fever, convulsions, irritability, bulging fontanel and temperature ≥ 39°C. Areas under the receiver operating characteristic curve in the validation period were 0.62 [95%CI: 0.49-0.75] age < 7 days and 0.76 [95%CI: 0.68-0.85] thereafter (P = 0.07), and using the WHO signs, 0.50 [95%CI 0.35-0.65] age < 7 days and 0.82 [95%CI: 0.75-0.89] thereafter (P = 0.0001). The number needed to LP to identify one case was 21 [95%CI: 15-35] for our signs, and 28 [95%CI: 18-61] for WHO signs. With a scoring system, a cut-off of ≥ 1 sign offered the best compromise on sensitivity and specificity.
Conclusion
Simple clinical signs at admission identify two thirds of meningitis cases in neonates and young infants. Lumbar puncture is essential to diagnosis and avoidance of unnecessary treatment, and is worthwhile without CSF biochemistry or bacterial culture. The signs of Meningitis suggested by the WHO perform poorly in the first week of life. A scoring system for meningitis in this age group is not helpful.
doi:10.1186/1471-2334-11-301
PMCID: PMC3217941  PMID: 22044635
meningitis; "young infants"; neonates; "lumbar puncture"; "clinical signs"; "resource-poor"
16.  Modelling consultation rates in infancy: influence of maternal and infant characteristics, feeding type and consultation history 
Background: Severity of illness, sociodemographic factors, and breastfeeding have been identified as predictors of consultation rates in infants, and prescriptions for antibiotics have been found to increase future consultation rates in older children. The Baby Check trial (1996–1998) provided detailed information about consultations for 935 babies during their first 6 months.
Aims: To investigate potential predictors of consultation rates in babies.
Design of study: A 6-month cohort study of newborn babies originally enrolled into a randomised controlled trial. Maternal and infant characteristics were collected from hospital discharge records. Primary care consultation data for each baby were collected by case note review.
Setting: Thirteen general practices in Glasgow.
Method: Multilevel models were used to analyse the number of consultations for each baby during its first 26 weeks, dependent upon the baby's age, the calendar month, maternal and infant characteristics, and previous consultations.
Results: The strongest predictors of consultation rates were previous consultations, particularly during the preceding week. Breastfed babies and those with older mothers consulted less often. A multilevel model was better than a fixed effects model, with considerable variation in consultation rates between babies.
Conclusion: Infants' consultation rates over time can be analysed using multilevel models, if details of primary care consultations are available. These models can incorporate the effects of fixed variables and those that change during the follow-up period. Our findings add to previous research linking breastfeeding with reduced morbidity in infancy, and for that reason breastfeeding should continue to be promoted in primary care.
PMCID: PMC1324840  PMID: 15296559
breastfeeding; consultation; infants; primary health care; statistical models
17.  Predicting the duration of symptoms in lower respiratory tract infection 
Background
Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration.
Aim
To determine predictors of illness duration in acute LRTI in primary care.
Design of study
Secondary analysis of trial data to identify independent predictors of illness severity and duration.
Setting
Primary care.
Method
Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad).
Results
The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration −1.72 days; 95% confidence interval [CI] = −3.02 to −0.41) or in individuals with a history of fever (−1.22 days; 95% CI = −0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor.
Conclusion
Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.
doi:10.3399/bjgp08X264045
PMCID: PMC2233957  PMID: 18307851
bronchitis; cough; prognosis; respiratory tract infections
18.  Pulmonary Hypertension in Preterm Infants With Bronchopulmonary Dysplasia 
Korean Circulation Journal  2010;40(3):131-136.
Background and Objectives
With the increasing survival of preterm infants, pulmonary hypertension (PH) related to bronchopulmonary dysplasia (BPD) has become an important complication. The aim of this study was to investigate the characteristics and outcome of PH in preterm infants with BPD and to identify the risk factors for PH.
Subjects and Methods
We reviewed the records of 116 preterm infants with BPD cared for at a single tertiary center between 2004 and 2008.
Results
Twenty-nine (25%) infants had PH >2 months after birth. PH occurred initially at a median age of 65 days (range, 7-232 days). Severe BPD, a birth weight <800 g, long-term ventilator care and oxygen supplementation, a high ventilator setting, infection, and a patent ductus arteriosus (PDA) were related to PH based on univariate analysis (p<0.05). The infants who had longer oxygen supplementation were significantly more likely to have PH (odds ratio, 18.5; 95% confidence interval, 4.1-84.6; p<0.001). PH was improved in 76% of infants after a median of 85 days (range, 20-765 days). Four infants (14%) died. The death of 3 infants was attributed to PH.
Conclusion
BPD was frequently complicated by PH. Although PH resolved in the majority of infants, PH in preterm infants with BPD can be fatal. Regular screening for PH and adequate management are required.
doi:10.4070/kcj.2010.40.3.131
PMCID: PMC2844979  PMID: 20339498
Hypertension, pulmonary; Infant, premature; Bronchopulmonary dysplasia
19.  Cost-effectiveness of Essential Newborn Care Training in Urban First-Level Facilities 
Pediatrics  2011;127(5):e1176-e1181.
OBJECTIVE:
To determine the cost-effectiveness of the World Health Organization (WHO) Essential Newborn Care (ENC) training of health care providers in first-level facilities in the 2 largest cities in Zambia.
METHODS:
Data were extracted from a study in which the effectiveness of the ENC training was evaluated (including universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, skin-to-skin care, care of the small infant, danger signs, and common illnesses). The costs to train an ENC instructor for each first-level delivery facility and the costs of salary/benefits for 2 coordinators responsible for maintenance of the program were recorded in 2005 US dollars. The incremental costs per life gained and per disability-adjusted life-year averted were calculated.
SETTING:
A 5-day ENC training-of-trainers was conducted in Lusaka, Zambia, to certify 18 college-trained midwives as ENC instructors. The instructors trained all clinic midwives working in their first-level facilities as part of a before-and-after study of the effect of ENC training on early neonatal mortality conducted from Oct 2004 to Nov 2006.
RESULTS:
All-cause 7-day (early) neonatal mortality decreased from 11.5 per 1000 to 6.8 per 1000 live births after ENC training of the clinic midwives (relative risk: 0.59; 95% confidence interval: 0.48–0.77; P < .001; 40 615 births). The intervention costs were $208 per life saved and $5.24 per disability-adjusted life-year averted.
CONCLUSIONS:
ENC training of clinic midwives who provide care in low-risk facilities is a low-cost intervention that can reduce early neonatal mortality in these settings.
doi:10.1542/peds.2010-2158
PMCID: PMC3387868  PMID: 21502223
developing countries; low-middle income countries; neonatal mortality; perinatal mortality; midwives
20.  Diagnosis and management of pertussis 
PERTUSSIS IS INCREASING IN FREQUENCY among children too young to be vaccinated and among adolescents and adults. This increase is due mainly to waning immunity among vaccinated individuals, who become susceptible during adolescence and adulthood and maintain the circulation of Bordetella pertussis. Infants are at highest risk of severe illness requiring hospital admission, complications and death. The clinical presentation in adolescents, adults and vaccinated individuals may be atypical, with paroxysmal cough of short duration or simply a persistent cough. Culture and polymerase chain reaction may be used to identify B. pertussis infection, but their sensitivity is high only in the early phase of the disease. Serologic tests are not standardized for the diagnosis of pertussis, and their clinical application is limited. Erythromycin is still considered in some countries to be the “gold standard” for therapy and prophylaxis; however, azithromycin and clarithromycin seem equally efficacious and are associated with fewer side effects.
doi:10.1503/cmaj.1040766
PMCID: PMC548414  PMID: 15710944
21.  Neonatal respiratory distress: potential for prevention. 
Canadian Medical Association Journal  1979;120(9):1076-1080.
A prospective study was conducted of 100 consecutive admissions to the neonatal intensive care unit of the Hospital for Sick Children, Toronto, of infants with respiratory distress syndrome or transient tachypnea of the newborn. It was found that in 15% of cases the illness was completely preventable, being the result of unintentionally premature termination of pregnancy. Significant intrapartum asphyxia occurred in 44% of the infants in whom respiratory distress syndrome developed. Factors placing the pregnancy at high risk were present antenatally in most cases, and most of the deliveries took place in hospitals without adequate facilities or staff, or both, for the requirements of the infant at and following birth.
PMCID: PMC1819281  PMID: 445301
22.  Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational study 
BMJ : British Medical Journal  2005;330(7498):995.
Objectives To determine how well antibiotic treatment is targeted by simple clinical syndromes and to what extent drug resistance threatens affordable antibiotics.
Design Observational study involving a priori definition of a hierarchy of syndromic indications for antibiotic therapy derived from World Health Organization integrated management of childhood illness and inpatient guidelines and application of these rules to a prospectively collected dataset.
Setting Kilifi District Hospital, Kenya.
Participants 11 847 acute paediatric admissions.
Main outcome measures Presence of invasive bacterial infection (bacteraemia or meningitis) or Plasmodium falciparum parasitaemia; antimicrobial sensitivities of isolated bacteria.
Results 6254 (53%) admissions met criteria for syndromes requiring antibiotics (sick young infants; meningitis/encephalopathy; severe malnutrition; very severe, severe, or mild pneumonia; skin or soft tissue infection): 672 (11%) had an invasive bacterial infection (80% of all invasive bacterial infections identified), and 753 (12%) died (93% of all inpatient deaths). Among P falciparum infected children with a syndromic indication for parenteral antibiotics, an invasive bacterial infection was detected in 4.0-8.8%. For the syndrome of meningitis/encephalopathy, 96/123 (76%) isolates were fully sensitive in vitro to penicillin or chloramphenicol.
Conclusions Simple clinical syndromes effectively target children admitted with invasive bacterial infection and those at risk of death. Malaria parasitaemia does not justify withholding empirical parenteral antibiotics. Lumbar puncture is critical to the rational use of antibiotics.
doi:10.1136/bmj.38408.471991.8F
PMCID: PMC557145  PMID: 15797893
23.  Prospective Analysis of Pulmonary Hypertension in Extremely Low Birth Weight Infants 
Pediatrics  2012;129(3):e682-e689.
OBJECTIVES:
Pulmonary hypertension is associated with bronchopulmonary dysplasia in extremely low birth weight (ELBW) infants and contributes to morbidity and mortality. The objective was to determine the prevalence of pulmonary hypertension among ELBW infants by screening echocardiography and evaluate subsequent outcomes.
METHODS:
All ELBW infants admitted to a regional perinatal center were evaluated for pulmonary hypertension with echocardiography at 4 weeks of age and subsequently if clinical signs suggestive of right-sided heart failure or severe lung disease were evident. Management was at discretion of the clinician, and infants were evaluated until discharge from the hospital or pre-discharge death occurred.
RESULTS:
One hundred forty-five ELBW infants (birth weight: 755 ± 144 g; median gestational age: 26 weeks [interquartile range: 24–27]) were screened from December 2008 to February 2011. Overall, 26 (17.9%) were diagnosed with pulmonary hypertension at any time during hospitalization (birth weight: 665 ± 140 g; median gestational age: 26 weeks [interquartile range: 24–27]): 9 (6.2%) by initial screening (early pulmonary hypertension) and 17 (11.7%) who were identified later (late pulmonary hypertension). Infants with pulmonary hypertension were more likely to receive oxygen treatment on day 28 compared with those without pulmonary hypertension (96% vs 75%, P < .05). Of the 26 infants, 3 died (all in the late group because of cor pulmonale) before being discharged from the hospital.
CONCLUSIONS:
Pulmonary hypertension is relatively common, affecting at least 1 in 6 ELBW infants, and persists to discharge in most survivors. Routine screening of ELBW infants with echocardiography at 4 weeks of age identifies only one-third of the infants diagnosed with pulmonary hypertension. Further research is required to determine optimal detection and intervention strategies.
doi:10.1542/peds.2011-1827
PMCID: PMC3289526  PMID: 22311993
premature infant; bronchopulmonary dysplasia; pulmonary hypertension
24.  Poverty, user fees and ability to pay for health care for children with suspected dengue in rural Cambodia 
User fees were introduced in public health facilities in Cambodia in 1997 in order to inject funds into the health system to enhance the quality of services. Because of inadequate health insurance, a social safety net scheme was introduced to ensure that all people were able to attend the health facilities. However, continuing high rates of hospitalization and mortality from dengue fever among infants and children reflect the difficulties that women continue to face in finding sufficient cash in cases of medical emergency, resulting in delays in diagnosis and treatment. In this article, drawing on in-depth interviews conducted with mothers of children infected with dengue in eastern Cambodia, we illustrate the profound economic consequences for households when a child is ill. The direct costs for health care and medical services, and added indirect costs, deterred poor women from presenting with sick children. Those who eventually sought care often had to finance health spending through out-of-pocket payments and loans, or sold property, goods or labour to meet the costs. Costs were often catastrophic, exacerbating the extreme poverty of those least able to afford it.
doi:10.1186/1475-9276-7-10
PMCID: PMC2386469  PMID: 18439268
25.  Referral of mothers and infants for intensive care. 
British Medical Journal  1979;2(6187):414-416.
During 1975-7, 96 mothers were referred to University College Hospital for delivery from 39 other hospitals because their pregnancies were considered to be at very high risk. One hundred of the 111 infants born to the 96 mothers weighed 2500 g or less and 60 weighed 1500 g or less. A high proportion of the infants developed serious illnesses necessitating intensive care. The birth-weight-specific neonatal mortality rates of the infants were much lower than those of infants born in England and Wales as a whole and were also lower than those of the 370 infants transported to this hospital for intensive care after delivery elsewhere. Whenever possible mothers with very high-risk pregnancies should be referred for delivery to centres with full facilities for the intensive care of the mother, fetus, and newborn infant.
PMCID: PMC1595657  PMID: 486967

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