Timothy J. Watts

Neonatal infections in England: the NeonIN surveillance network.

Introduction Neonatal infection is an important cause of morbidity and mortality. Neonatal infection surveillance networks are necessary for defining the epidemiology of infections and monitoring changes over time. Design Prospective multicentre surveillance using a web-based database. Setting 12 English neonatal units. Participants Newborns admitted in 2006–2008, with positive blood, cerebrospinal fluid or urine culture and treated with antibiotics for at least 5 days. Outcome measure Incidence, age at infection, pathogens and antibiotic resistance profiles. Results With the inclusion of coagulase negative Staphylococci (CoNS), the incidence of all neonatal infection was 8/1000 live births and 71/1000 neonatal admissions (2007–2008). The majority of infections occurred in premature (<37 weeks) and low birthweight (<2500 g) infants (82% and 81%, respectively). The incidence of early onset sepsis (EOS; ≤48 h of age) was 0.9/1000 live births and 9/1000 neonatal admissions, and group B Streptococcus (58%) and Escherichia coli (18%) were the most common organisms. The incidence of late onset sepsis (LOS; >48 h of age) was 3/1000 live births and 29/1000 neonatal admissions (7/1000 live births and 61/1000 admissions including CoNS) and the most common organisms were CoNS (54%), Enterobacteriaceae (21%) and Staphylococcus aureus (18%, 11% of which were methicillin resistant S aureus). Fungi accounted for 9% of LOS (72% Candida albicans). The majority of pathogens causing EOS (95%) and LOS (84%) were susceptible to commonly used empiric first line antibiotic combinations of penicillin/gentamicin and flucloxacillin/gentamicin, respectively (excluding CoNS). Conclusions The authors have established NeonIN in England and defined the current epidemiology of neonatal infections. These data can be used for benchmarking among units, international comparisons and as a platform for interventional studies.

Prospective, Observational Study of Outcomes in Neonates With Severe Thrombocytopenia

OBJECTIVE: A cross-sectional, observational study of outcomes for neonates with severe neonatal thrombocytopenia (SNT; platelet count of <60 × 109 platelets per L) was performed to examine hemorrhage and use of platelet transfusions. METHODS: Neonates who were admitted to 7 NICUs and developed SNT were enrolled for daily data collection. RESULTS: Among 3652 neonatal admissions, 194 neonates (5%) developed SNT. The median gestational age of 169 enrolled neonates was 27 weeks (interquartile range [IQR]: 24–32 weeks), and the median birth weight was 822 g (IQR: 670–1300 g). Platelet count nadirs were <20 × 109, 20 to 39 × 109, and 40 to 59 × 109 platelets per L for 58 (34%), 64 (39%), and 47 (28%) of all enrolled infants, respectively. During the study, 31 infants (18%) had no recorded hemorrhage, 123 (73%) developed minor hemorrhage, and 15 (9%) developed major hemorrhage. Thirteen (87%) of 15 episodes of major hemorrhage occurred in neonates with gestational ages of <28 weeks. Platelet transfusions (n = 415) were administered to 116 infants (69%); for 338 (81%) transfusions, the main recorded reason was low platelet count. Transfusions increased the platelet count from a median of 27 × 109 platelets per L (IQR: 19–36 × 109 platelets per L) to 79 × 109 platelets per L (IQR: 47.5–127 × 109 platelets per L). CONCLUSIONS: Although one third of neonates enrolled in this study developed thrombocytopenia of <20 × 109 platelets per L, 91% did not develop major hemorrhage. Most platelet transfusions were given to neonates with thrombocytopenia with no bleeding or minor bleeding only.

Severe thrombocytopenia and patterns of bleeding in neonates: results from a prospective observational study and implications for use of platelet transfusions

To describe patterns of clinical bleeding in neonates with severe thrombocytopenia (ST and platelet count <60 × 109 L−1), and to investigate the factors related to bleeding.

Neonatal invasive fungal infection in England 2004-2010.

Rates of invasive fungal infection are highest among neonates, especially those of low birthweight. This study aimed to describe the current epidemiology of invasive neonatal fungal infections in a UK neonatal infection surveillance network. From 2004 to 2010 prospective multicentre surveillance was conducted by 14 neonatal units using a web-based database. Clinicians then completed a standardized pro forma for each positive fungal blood and/or cerebrospinal fluid culture. The overall incidence was 2.4/1000 neonatal unit admissions and was highest among babies <1000 g (extreme low birthweight, 18.8/1000). Only five infants (6%) were >1500 g. The majority of infections were caused by Candida albicans (59; 69%) and Candida parapsilosis (17; 20%); 33% of infants had received antifungal prophylaxis. Known risk factors (use of central venous catheter, parenteral nutrition, previous antibiotic use) were common among cases. The attributable case fatality rate was 21% (18/84). Extreme low birthweight infants remain at highest risk of invasive fungal infection and prophylaxis should be particularly considered for this group. The number needing to receive prophylaxis to prevent one case varies significantly among units, hence unit-specific decisions are required. Further research is still needed into the optimal empiric and therapeutic strategies.

Characteristics of Invasive Staphylococcus aureus in United Kingdom Neonatal Units.

Background: In industrialized countries, Staphylococcus aureus (SA) is a leading cause of late-onset neonatal sepsis. Methods: Culture-proven episodes were identified prospectively from neonatal units participating in the neonatal infection surveillance network. Demographic, risk factor, and outcome data were collected. Results: Between 2004 and 2009, there were 117 episodes of SA infections (including 8 methicillin-resistant SA) in 116 infants from 13 units. The median gestational age and birth-weight were 27 weeks (90% ≤37 weeks, 85% ≤32 weeks) and 850 g (90% ≤2500 g), respectively. The overall incidence was 0.6 per 1000 live births and 23/1000 in infants <1500 g. Most episodes (94%) occurred more than 48 hours after birth (late onset). There were 7 early-onset episodes (<48 hours) (median gestational age, 38.5 weeks), all due to methicillin-susceptible SA. At the time of culture, 67 of 95 (71%) infants were receiving respiratory support and 47 of 94 (50%) had a central line in situ. The majority of infants had nonspecific clinical features although evidence of focal infection (skin, soft tissue, bone, joint, or pneumonia) was ultimately seen in 41 of 91 (45%). There were 18 deaths, 4 (all late onset) directly due to methicillin-susceptible SA sepsis (4.4%). Conclusions: SA is the second most common pathogen causing late-onset neonatal infections in this neonatal network. Infants who weigh <1500 g in intensive care settings are the most vulnerable group. Clinical signs are not sufficiently distinctive to allow targeted therapy, suggesting that an antistaphylococcal agent should be part of empiric therapy for late-onset sepsis in premature infants.

Accuracy of the concentration of morphine infusions prepared for patients in a neonatal intensive care unit

Objective To investigate the accuracy of morphine infusions prepared for neonates in relation to the label strength and to identify the differences in deviation between infusions made in neonatal intensive care unit (NICU) and those dispensed ready-to-use from pharmacy. Methods Unused portions of morphine solution for infusion were collected over a 6-weeks period and used to determine the concentration of the drug by high-performance liquid chromatography (HPLC). Results A total of 19.2% of infusions prepared by nurses in the ward and 7.8% prepared in the pharmacy were outside the limit required by the British Pharmacopoeia (±7.5%). Moreover, a deviation in concentration of more than 20% was found in ward-prepared infusions, although this was caused by volume discrepancies of less than 0.2 mL. The frequency and magnitude of deviations found in infusions prepared in pharmacy was lower than in those prepared by NICU. The latter showed significantly higher number of out-of-specification samples (p=0.015); however, deviations from intended concentration occurred in both settings. Significant differences between pharmacy and NICU for volumes of less than 0.5 mL or for less than 1 mL were not identified probably due to small sample size, but statistical data show a trend for differences. Conclusions Current practice of preparation of infusions from strengths intended for older children and adults involves dilution of small volumes in a syringe and leads to inaccuracy in the final concentration of infusions for neonatal use. We propose the implementation of standard concentrations for this patient group to effectively eliminate these errors.

A novel approach to standardised recording of bleeding in a high risk neonatal population

Background Bleeding assessment tools have been developed in other specialties to standardise the recording of bleeding for clinical haemostatic outcomes in transfusion trials, but such tools have not been developed for routine use in neonatology. Aim The objective of this study was to develop, refine and evaluate a neonatal bleeding assessment tool (NeoBAT) to standardise the clinical recording of bleeding in premature and term neonates in an intensive care setting. Methods This prospective neonatal international multicentre study included all episodes of bleeding in infants admitted to the intensive/high dependency care nursery over a 2–4-week period. The NeoBAT was developed to record neonatal bleeding episodes. We tested its reliability and reproducibility with duplicate assessments. Results Duplicate assessments revealed 98% concordance. Bleeding occurred in 25% (37/146) of infants overall and was most common in preterm infants. 11% (16/146) infants had major/severe bleeds, 1% (2/146) moderate and 13% (19/146) minor bleeds. Conclusions Bleeding is common in premature and term neonates admitted to intensive/high dependency care nurseries. This novel bleeding assessment tool facilitates prospective recording of bleeding events in neonatal intensive care settings and may allow standardised bleeding assessments in this high risk population.

Post-vaccination serological test results of infants at risk of perinatal transmission of hepatitis B using an intensified follow-up programme in a London centre.

Immunisation of infants born to hepatitis B virus (HBV) infected mothers is an important public health measure to prevent mother-to-child transmission of HBV. Post-vaccination serological tests (PVST) inform the success of the infant HBV immunisation programme and identify infected infants. Previous studies suggested that the rates of PVST in the UK programme were unsatisfactory. We introduced an intensified local follow-up programme and offered an earlier PVST 2-3 months after the third vaccination at age 4-5 months. Of 219 infants born between 2009 and 2011, 193 infants (88.1%) had at least one PVST: 145 (66.2%) early; 94 (42.9%) standard; 46 (21.0%) both and 26 (11.9%) never tested. Twenty-four infants were identified as high risk for mother-to-child transmission according to national criteria and received both hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine at birth. These infants had a significantly lower hepatitis B surface antibody (anti-HBs) levels at early PVST compared to the lower risk group who received hepatitis B vaccine only (median of 59 vs. 376 mIU/ml, P=0.006). None of the infants tested were infected with hepatitis B. This study illustrates that the rate of PVST can be improved by using an intensified follow-up programme offering an early PVST. The significantly lower anti-HBs levels in the HBIG subgroup is of concern as this group of infants is already at higher risk for acquiring HBV infection. Infants with poor antibody responses can be identified by an early PVST and offered a timely extra booster dose.

Do we know when to treat neonatal thrombocytopaenia

Thrombocytopaenia is highly prevalent in neonatology affecting around 25% (22–35%) of all neonates admitted to neonatal intensive care units.1 Clinical signs of bleeding are also commonly documented in preterm neonates. But the close temporal association commonly noted in sick babies between low platelet counts and the occurrence of bleeding does not establish cause and effect. Thrombocytopaenia is a risk factor for poorer neonatal outcomes, although it is unclear whether it is largely a marker of severity of illness and comorbidity.2 Platelet transfusion remains the only readily available specific treatment for this condition. Decisions about when to treat thrombocytopaenia are therefore linked to defining safe and effective platelet transfusion practices. Policies for neonatal platelet transfusion therapy vary widely between clinicians, institutions and countries, and are inevitably based on specified threshold counts of platelets, although platelet counts provide no information on changes in platelet function. Alternative criterion of the need for platelet transfusions, such as platelet mass (which is based on a sum of platelet count and platelet volume, based on the rationale that larger platelets may be more effective haemostatically), have been proposed, but larger studies to assess clinical outcomes have not been undertaken.3 A large web based survey of neonatologists in Canada and USA reported significant variation between neonates units and indicated that platelet transfusions were frequently administered to non-bleeding neonates with platelet counts >50×109/l.4 In the UK, a telephone survey of all tertiary level neonatal units demonstrated similar variation in practice but with the most common thresholds for transfusion in well or stable term and preterm infants being 25×109 and 30×109/l, respectively.5 It should be stressed that the safety and efficacy of these platelet count thresholds for prophylactic platelet transfusions have never been assessed in randomised trials.6 Murray …

A descriptive single‐centre experience of the management and outcome of maternal alloantibodies in pregnancy

Haemolytic disease of the fetus and newborn (HDFN) occurs when maternal IgG alloantibodies to fetal red blood cell antigens cross the placenta, causing haemolysis in the fetus and/or neonate. After delivery, the main concern is hyperbilirubinaemia, which can cause neurological damage.