Mortality and morbidity of extremely low birth weight infants in Hong Kong, 2010-2017: a single-centre review.

BACKGROUND: Extremely low birth weight (ELBW) infants exhibit high rates of mortality and morbidity. We retrospectively assessed factors associated with mortality and morbidity among ELBW infants. METHODS: Perinatal demographic data were reviewed for all ELBW infants born between 2010 and 2017 at a tertiary neonatal unit. RESULTS: For non-survivors (21% of ELBW infants) and survivors, the median gestational ages were 24.1 and 26.2 weeks, respectively, and median birth weights were 650 g and 780 g, respectively (all P<0.001). Regression analyses showed that non-survival was positively associated with lower gestational age (adjusted odds ratio [aOR]=6.71 for every 1-week decrease; 95% confidence interval [CI]=1.73-26.00; P=0.006) and grade 3 or 4 intraventricular haemorrhage (aOR=29.23; 95% CI=1.39-613.84; P=0.030); non-survival was negatively associated with the presence of bronchopulmonary dysplasia (aOR=0.01; 95% CI= <0.001-0.23; P=0.005); length of neonatal intensive care unit stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=89.60; 95% CI=43.86-135.34; P<0.001); and length of hospital stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=2.08; 95% CI=0.43-3.73; P=0.015) and a low Apgar score at 1 minute (B-coefficient=-0.63; 95% CI=-1.04 to -0.22; P=0.003). CONCLUSION: Extremely low birth weight infants exhibited significant mortality and morbidity; there was no survival prior to 23.6 weeks' gestation or below 550 g birth weight. The presence of grade 3 or 4 intraventricular haemorrhage was independently associated with non-survival. Survivors were significantly more likely to exhibit bronchopulmonary dysplasia; survivors with necrotising enterocolitis were more likely to require longer stays in the neonatal intensive care unit and in hospital.

Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants.

OBJECTIVE: To assess the incidence of late onset (> 72 hours) infection and necrotising enterocolitis (NEC) in very low birthweight (VLBW) infants in two 36 month periods using two hand hygiene protocols: conventional handwashing (HW; first 36 month period); an alcohol hand rub and gloves technique (HR; second 36 month period). METHOD: VLBW infants admitted to the neonatal intensive care unit during the period December 1993-November 1999 were eligible. A new hand hygiene protocol using alcohol handrub and gloves was introduced in December 1996. Each patient's case record was reviewed retrospectively by two independent investigators using a standard data collection form. The incidence of NEC and systemic infections, including bacterial or fungal septicaemia, meningitis, and peritonitis, in the two periods were compared. RESULTS: The HW and HR groups contained 161 and 176 VLBW infants respectively. The incidence of late onset systemic infection decreased from 13.5 to 4.8 episodes (including NEC)/1000 patient days after introduction of the HR regimen, representing a 2.8-fold reduction. Similarly, the incidence of Gram positive, Gram negative, and fungal infections decreased 2.5-fold, 2.6-fold, and 7-fold respectively. There was also a significant reduction in the incidence of NEC in the HR group (p < 0.0001). Subgroup analysis revealed that the incidence of methicillin resistant Staphylococcus aureus (MRSA) septicaemia was significantly decreased in the second 36 month period (p = 0.048). The clinical data suggest that infants in the HW group had significantly earlier onset of sepsis (p < 0.05) and required oxygen supplementation for longer (p < 0.05) than those in the HR group. Significantly more VLBW infants were discharged from the neonatal intensive care unit without ever being infected (p < 0.0001), and also significantly fewer infants had more than one episode of infection in the HR group (p < 0.0001). CONCLUSION: The introduction of the HR protocol was associated with a 2.8-fold reduction in the incidence of late onset systemic infection, and also a significant decrease in the incidence of MRSA septicaemia and NEC in VLBW infants. This decrease in infection rate was maintained throughout the second 36 month period.

Infection control for SARS in a tertiary paediatric centre in Hong Kong.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease. After the appearance of an index patient in Hong Kong in February 2003, SARS outbreaks occurred rapidly in hospitals and spread to the community. The aim of this retrospective study is to evaluate the effectiveness of a triage policy and risk-stratified infection control measures in preventing nosocomial SARS infection among paediatric healthcare workers (HCWs) at the Prince of Wales Hospital, a general hospital to which children with SARS are referred in Hong Kong. The acute paediatric wards were stratified into three areas: (1) ultra high-risk area, (2) high-risk area and (3) moderate-risk area according to different risk levels of nosocomial SARS transmission. The implementation of different levels of infection control precautions was guided by this risk stratification strategy. Between 13 March and 23 June, 38 patients with probable and suspected SARS, 90 patients with non-SARS pneumonia, and 510 patients without pneumonia were admitted into our unit. All probable SARS cases were isolated in negative-pressure rooms. Twenty-six HCWs worked in the ultra high-risk area caring for SARS patients and 88 HCWs managed non-SARS patients in other ward areas. None of the HCWs developed clinical features suggestive of SARS. In addition, there was no nosocomial spread of SARS-associated coronavirus to other patients or visitors during this period. In conclusion, stringent infection control precautions, appropriate triage and prompt isolation of potential SARS patients may have contributed to a lack of nosocomial spread and HCW acquisition of SARS in our unit.

Pertussis--a re-emerging infection?

Seven cases of pertussis in patients aged between 1 and 6 months detected over 3 months were reported. Paroxysmal cough (six cases), post-tussive vomiting (three cases) and poor feeding (three cases) were the most common presenting symptoms. Bordetella pertussis was isolated from six patients. The total leucocyte counts were mildly increased (10.8-15.6x10(9)/L). The lymphocyte counts were markly raised (59-73%) and appear to be useful indicators of pertussis. It appears that herd immunity does not offer adequate protection to the vulnerable group even in well-vaccinated populations. High vaccination coverage should be maintained, and vaccination should be given as early an age as possible. Aggressive efforts to identify cases and contacts are essential. Health care workers should have a high index of suspicion for pertussis, in particular for those with paroxysmal cough and high lymphocyte counts so as to give timely diagnosis and treatment.

Infection control for SARS in a tertiary neonatal centre.

The Severe Acute Respiratory Syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus, which can readily spread in the healthcare setting. A recent community outbreak in Hong Kong infected a significant number of pregnant women who subsequently required emergency caesarean section for deteriorating maternal condition and respiratory failure. As no neonatal clinician has any experience in looking after these high risk infants, stringent infection control measures for prevention of cross infection between patients and staff are important to safeguard the wellbeing of the work force and to avoid nosocomial spread of SARS within the neonatal unit. This article describes the infection control and patient triage policy of the neonatal unit at the Prince of Wales Hospital, Hong Kong. We hope this information is useful in helping other units to formulate their own infection control plans according to their own unit configuration and clinical needs.

Haematopoietic stem and progenitor cells in human term and preterm neonatal blood.

BACKGROUND AND OBJECTIVES: Whilst cord blood (CB) contains a significant number of haematopoietic stem and progenitor cells suitable for bone marrow transplantation, levels of these cells are very low in the adult circulation. In previous studies, we demonstrated that stem and progenitor cells are present in neonatal blood (NB) and reported the first sibling transplant using a combination of CB and NB for a patient with beta-thalassaemia major. However, our preliminary data showed that the number of CD34+ cells decreased rapidly in the peripheral blood of neonates soon after birth. To further investigate the mechanism of the change of stem and progenitor cells in NB, we measured the steady-state levels of CD34+ cells, early progenitor subsets and the expression of adhesion molecules, in term and preterm neonates. MATERIALS AND METHODS: NB was collected serially from infants at 2, 4, 6, 8, 24 and 48 h after birth and was analysed by three-colour flow cytometry. RESULTS: Our results demonstrated that the number of CD34+ cells rapidly decreased in term NB, particularly during the first 2-6 h of life, by 29.2 +/- 5.55% (P = 0.0003) in absolute counts/ml. A decrease was observed in all subsets of CD34+ cells studied, including the CD33+, CD71+, CD62L+ and CD49d+ populations. In contrast, the CD34+ cell number increased in preterm infants in the first 8 h of life, before starting to decrease. Significant inverse correlations were observed between gestational age and levels of CD34+ cells (P = 0.0065, 4-h collection time-point). CONCLUSION: Our study suggests that changes in the levels of CD34+ stem and progenitor cells in NB might be triggered by parturition and affected by the gestational age. Our findings confirmed that if targeted as a supplementary source of stem and progenitor cells to CB for transplantation, NB should be collected as soon as possible after birth.

Oxygen consumption and resting energy expenditure during phototherapy in full term and preterm newborn infants.

OBJECTIVES: To determine the effect of phototherapy on the oxygen consumption and resting energy expenditure of term and preterm newborn infants. METHODS: A total of 202 infants (gestation 30-42 weeks; body weight 1270-4100 g) requiring phototherapy for the treatment of neonatal hyperbilirubinaemia were enrolled in a randomised crossover study. In random sequence, the oxygen consumption and resting energy expenditure were measured twice in each infant by indirect calorimetry, once at the end of six hours of continuous phototherapy and once after a control period of at least six hours without phototherapy. Anterior abdominal wall temperature was servocontrolled at 36.5 degrees C throughout the study. RESULTS: At the end of six hours of continuous phototherapy, oxygen consumption (mean (SD): 6.21 (1.35) v 6.26 (1.51) ml/kg, p = 0.555) and resting energy expenditure (178.11 (37.62) v 180.37 (43.14) kJ/kg/24 h, p = 0.382) did not differ significantly from those measured after the control period. There were also no significant differences in heart rate, respiratory rate, or rectal temperature. Subgroup analysis of those of gestation < 37 weeks or < 34 weeks also showed no effect of phototherapy on either oxygen consumption or resting energy expenditure. CONCLUSION: Phototherapy has no effect on the metabolic rate of thermally stable term or preterm infants.

Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants.

AIM: To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes. RESULTS: Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10 v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms. CONCLUSIONS: Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.

Central nervous system candidiasis in preterm infants: limited value of biochemical markers for diagnosis.

Two rare cases of isolated central nervous system (CNS) candidiasis in preterm infants have been diagnosed in a tertiary neonatal centre over the past 6 years. Despite the life-threatening nature of the disease, biochemical infection markers were not useful for the early identification of localized fungal infection. Because the infection was likely to have been blood borne, we postulated that the initial fungal load was probably low and that the organisms were rapidly eliminated from the circulation after a few had been deposited in the CNS. Hence, the absence of fungaemia or systemic involvement precluded the activation of cytokines and cellular markers. Clinicians should be aware of the limitation of biochemical infection markers so that diagnosis and treatment of fungal infection will not be delayed.

Pneumocystis carinii pneumonia in an immunocompetent infant with congenital cytomegalovirus infection.

The case of a term infant with congenital cytomegalovirus (CMV) infection who developed Pneumocystis carinii pneumonia (PCP) at 4 months of age is reported. Our patient suffered from severe malnutrition and zinc deficiency secondary to necrotizing enterocolitis since the age of 2 months. There was no evidence of human immunodeficiency virus infection. Qualitative and quantitative in vitro leukocyte functions were also normal. This case highlights the fact that PCP can occur in apparently immunocompetent term infants. Malnourished infants with zinc deficiency or congenital CMV infection are at increased risk of developing PCP.

Severe congenital absence of skin in a preterm infant.

A severe case of aplasia cutis congenita in a preterm infant is described. Although major problems with thermoregulation and fluid balance were anticipated, these parameters were relatively easy to control once the patient was stabilized. Meticulous skin care and rapid formation of a membranous-like fibrous tissue layer covering the denuded areas probably played an important role in minimizing excessive fluid and heat loss. The prognosis in aplasia cutis congenita is determined by the underlying associated anomalies, the severity of skin lesions and, in our case, the maturity of the infant who died from complications of prematurity.

Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.

AIM: To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome. METHODS: Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications. RESULTS: More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects. CONCLUSION: These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.

Human neonatal blood: stem cell content, kinetics of CD34+ cell decline and ex vivo expansion capacity.

Haemopoietic stem cells are present in fetal blood but their levels decline rapidly in the peripheral circulation of the infant after birth. We previously reported a case of stem cell transplant in a beta-thalassaemia boy using a combination of the cord blood (CB) and neonatal blood (NB) of his sister. This transplant resulted in a successful engraftment. To investigate the possibility of using NB to supplement CB for related transplants, we further characterized stem and progenitor cells and lymphocyte subsets in 20 NB samples, comparing the findings with those in 20 CB samples. Our data showed that NB contained substantial levels of CD34+ cells, CD34+CD38- cells, colony-forming units-granulocyte macrophage (CFU-GM), colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E) and long-term culture initiating cells (LTCIC). NB was similar to CB in the levels of T lymphocytes, but the amounts of B lymphocytes and natural killer cells were higher in CB (P = 0.033, P= 0.001, respectively). The kinetics of CD34+ cells in NB was investigated in serial blood samples obtained from 10 full-term infants at 2, 4, 6, 8, 24 and 48h after birth. CD34+ cells decreased rapidly after birth, declining to only 30% of the 2h level at 48h (P<0012). The rate of decline was greatest in the first 4 h of life. NB from four infants was expanded by culturing the blood samples in the presence of thrombopoietin (Tpo), interleukin 1beta (IL1beta), IL-3, IL-6, flt-3 ligand and stem cell factor (SCF) for 7 d. This resulted in the increase of CD34+ cells, CFU-GM and CFU-MK by 271+/-179, 556+/-385 and 113+/-75 fold respectively. Three of the five samples expanded for 7 d contained LTCIC. These findings suggest that NB might be a supplementary or alternative source of stem cells to CB for transplant. The ethics and practicality of this approach deserve further exploration.

Is homozygous alpha-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous alpha-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous alpha-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease.

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.

Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants.

AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit. The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution. Prophylaxis was started 24 hours before the start of oral feeds. All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs. Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria. RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035). Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002). CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence. However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms. Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients.

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants.

OBJECTIVES: A prospective study comparing the efficacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (< 1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus. METHODOLOGY: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (+/-1 week) and birthweight (+/-100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group. RESULTS: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment (P > 0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups (P < 0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group. CONCLUSIONS: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.