Implementation and evaluation of a quality improvement initiative to reduce late gestation stillbirths in Australia: Safer Baby Bundle study protocol.

BACKGROUND: In 2015, the stillbirth rate after 28 weeks (late gestation) in Australia was 35% higher than countries with the lowest rates globally. Reductions in late gestation stillbirth rates have steadily improved in Australia. However, to amplify and sustain reductions, more needs to be done to reduce practice variation and address sub-optimal care. Implementing bundles for maternity care improvement in the UK have been associated with a 20% reduction in stillbirth rates. A similar approach is underway in Australia; the Safer Baby Bundle (SBB) with five elements: 1) supporting women to stop smoking in pregnancy, 2) improving detection and management of fetal growth restriction, 3) raising awareness and improving care for women with decreased fetal movements, 4) improving awareness of maternal safe going-to-sleep position in late pregnancy, 5) improving decision making about the timing of birth for women with risk factors for stillbirth. METHODS: This is a mixed-methods study of maternity services across three Australian states; Queensland, Victoria and New South Wales. The study includes evaluation of 'targeted' implementer sites (combined total approximately 113,000 births annually, 50% of births in these states) and monitoring of key outcomes state-wide across all maternity services. Progressive implementation over 2.5 years, managed by state Departments of Health, commenced from mid-2019. This study will determine the impact of implementing the SBB on maternity services and perinatal outcomes, specifically for reducing late gestation stillbirth. Comprehensive process, impact, and outcome evaluations will be conducted using routinely collected perinatal data, pre- and post- implementation surveys, clinical audits, focus group discussions and interviews. Evaluations explore the views and experiences of clinicians embedding the SBB into routine practice as well as women's experience with care and the acceptability of the initiative. DISCUSSION: This protocol describes the evaluation of the SBB initiative and will provide evidence for the value of a systematic, but pragmatic, approach to strategies to reduce the evidence-practice gaps across maternity services. We hypothesise successful implementation and uptake across three Australian states (amplified nationally) will be effective in reducing late gestation stillbirths to that of the best performing countries globally, equating to at least 150 lives saved annually. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the ACTRN12619001777189 database, date assigned 16/12/2019.

The WHO application of ICD-10 to deaths during the perinatal period (ICD-PM): results from pilot database testing in South Africa and United Kingdom.

OBJECTIVE: To apply the World Health Organization (WHO) Application of the International Classification of Diseases, tenth revision (ICD-10) to deaths during the perinatal period: ICD-Perinatal Mortality (ICD-PM) to existing perinatal death databases. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, UK. POPULATION: Perinatal death databases. METHODS: Deaths were grouped according to timing of death and then by the ICD-PM cause of death. The main maternal condition at the time of perinatal death was assigned to each case. MAIN OUTCOME MEASURES: Causes of perinatal mortality, associated maternal conditions. RESULTS: In South Africa 344/689 (50%) deaths occurred antepartum, 11% (n = 74) intrapartum and 39% (n = 271) in the early neonatal period. In the UK 4377/9067 (48.3%) deaths occurred antepartum, with 457 (5%) intrapartum and 4233 (46.7%) in the neonatal period. Antepartum deaths were due to unspecified causes (59%), chromosomal abnormalities (21%) or problems related to fetal growth (14%). Intrapartum deaths followed acute intrapartum events (69%); neonatal deaths followed consequences of low birthweight/ prematurity (31%), chromosomal abnormalities (26%), or unspecified causes in healthy mothers (25%). Mothers were often healthy; 53%, 38% and 45% in the antepartum, intrapartum and neonatal death groups, respectively. Where there was a maternal condition, it was most often maternal medical conditions, and complications of placenta, cord and membranes. CONCLUSIONS: The ICD-PM can be a globally applicable perinatal death classification system that emphasises the need for a focus on the mother-baby dyad as we move beyond 2015. TWEETABLE ABSTRACT: ICD-PM is a global system that classifies perinatal deaths and links them to maternal conditions.

Application of ICD-PM to preterm-related neonatal deaths in South Africa and United Kingdom.

OBJECTIVE: We explore preterm-related neonatal deaths using the WHO application of the International Classification of Disease (ICD-10) to deaths during the perinatal period: ICD-PM as an informative case study, where ICD-PM can improve data use to guide clinical practice and programmatic decision-making. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, and the UK. POPULATION: Perinatal death databases. METHODS: Descriptive analysis of neonatal deaths and maternal conditions present. MAIN OUTCOME MEASURES: Causes of preterm neonatal mortality and associated maternal conditions. RESULTS: We included 98 term and 173 preterm early neonatal deaths from South Africa, and 956 term and 3248 preterm neonatal deaths from the UK. In the South African data set, the main causes of death were respiratory/cardiovascular disorders (34.7%), low birthweight/prematurity (29.2%), and disorders of cerebral status (25.5%). Amongst preterm deaths, low birthweight/prematurity (43.9%) and respiratory/cardiovascular disorders (32.4%) were the leading causes. In the data set from the UK, the leading causes of death were low birthweight/prematurity (31.6%), congenital abnormalities (27.4%), and deaths of unspecified cause (26.1%). In the preterm deaths, the leading causes were low birthweight/prematurity (40.9%) and deaths of unspecified cause (29.6%). In South Africa, 61% of preterm deaths resulted from the maternal condition of preterm spontaneous labour. Among the preterm deaths in the data set from the UK, no maternal condition was present in 36%, followed by complications of placenta, cord, and membranes (23%), and other complications of labour and delivery (22%). CONCLUSIONS: ICD-PM can be used to appraise the maternal and newborn conditions contributing to preterm deaths, and can inform practice. TWEETABLE ABSTRACT: ICD-PM can be used to appraise maternal and newborn contributors to preterm deaths to improve quality of care.

Optimising the International Classification of Diseases to identify the maternal condition in the case of perinatal death.

OBJECTIVE: The WHO application of the tenth edition of the International Classification of Diseases (ICD-10) to deaths during the perinatal period (ICD Perinatal Mortality, ICD-PM) captures the essential characteristics of the mother-baby dyad that contribute to perinatal deaths. We compare the capture of maternal conditions in the existing ICD-PM with the maternal codes from the WHO application of ICD-10 to deaths during pregnancy, childbirth, and the puerperium (ICD Maternal Mortality, ICD-MM) to explore potential benefits in the quality of data received. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa and the UK. POPULATION: Perinatal death databases. METHODS: The maternal conditions were classified using the ICD-PM groupings for maternal condition in perinatal death, and then mapped to the ICD-MM groupings of maternal conditions. MAIN OUTCOME MEASURES: Main maternal conditions in perinatal deaths. RESULTS: We reviewed 9661 perinatal deaths. The largest group (4766 cases, 49.3%) in both classifications captures deaths where there was no contributing maternal condition. Each of the other ICD-PM groups map to between three and six ICD-MM groups. If the cases in each ICD-PM group are re-coded using ICD-MM, each group becomes multiple, more specific groups. For example, the 712 cases in group M4 in ICD-PM become 14 different and more specific main disease categories when the ICD-MM is applied instead. CONCLUSIONS: As we move towards ICD-11, the use of the more specific, applicable, and relevant codes outlined in ICD-MM for both maternal deaths and the maternal condition at the time of a perinatal death would be preferable, and would provide important additional information about perinatal deaths. TWEETABLE ABSTRACT: Improving the capture of maternal conditions in perinatal deaths provides important actionable information.

Australian women's perceptions and practice of sleep position in late pregnancy: An online survey.

BACKGROUND: Going-to-sleep in the supine position in later pregnancy (≥28 weeks) has been identified as a risk factor for stillbirth. Internationally, public awareness campaigns have been undertaken encouraging women to sleep on their side during late pregnancy. AIM: This study aimed to identify sleep practices, attitudes and knowledge in pregnant women, to inform an Australian safe sleeping campaign. METHODS: A web-based survey of pregnant women ≥28 weeks' gestation conducted from November 2017 to January 2018. The survey was adapted from international sleep surveys and disseminated via pregnancy websites and social media platforms. FINDINGS: Three hundred and fifty-two women participated. Five (1.6%) reported going to sleep in the supine position. Most (87.8%) had received information on the importance of side-sleeping in pregnancy. Information was received from a variety of sources including maternity care providers (186; 66.2%) and the internet (177; 63.0%). Women were more likely to report going to sleep on their side if they had received advice to do so (OR 2.3; 95% CI 1.0-5.1). Thirteen (10.8%) reported receiving unsafe advice, including changing their going-to-sleep position to the supine position. DISCUSSION: This indicates high level awareness and practice of safe late-pregnancy going-to-sleep position in participants. Opportunities remain for improvement in the information provided, and understanding needs of specific groups including Aboriginal and Torres Strait Islander women. CONCLUSION: Findings suggest Australian women understand the importance of sleeping position in late pregnancy. Inconsistencies in information provided remain and may be addressed through public awareness campaigns targeting women and their care providers.

Survey of Australian maternity hospitals to inform development and implementation of a stillbirth prevention 'bundle of care'.

BACKGROUND: 'Bundles of care' are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers. OBJECTIVE: To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention. METHODS: A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued; best practice frequency; and, barriers and enablers to implementation. RESULTS: 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations "all the time" for smoking cessation support (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices. CONCLUSIONS: Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth.

Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more).

BACKGROUND: Prelabour rupture of membranes at term is managed expectantly or by elective birth, but it is not clear if waiting for birth to occur spontaneously is better than intervening. OBJECTIVES: To assess the effects of planned early birth versus expectant management for women with term prelabour rupture of membranes on fetal, infant and maternal wellbeing. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (November 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004), MEDLINE (1966 to November 2004) and EMBASE (1974 to November 2004). SELECTION CRITERIA: Randomised or quasi-randomised trials of planned early birth compared with expectant management in women with prelabour rupture of membranes at 37 weeks' gestation or more. DATA COLLECTION AND ANALYSIS: Two review authors independently applied eligibility criteria, assessed trial quality and extracted data. A random-effects model was used. MAIN RESULTS: Twelve trials (total of 6814 women) were included. Planned management was generally induction with oxytocin or prostaglandin, with one trial using homoeopathic caulophyllum. Overall, no differences were detected for mode of birth between planned and expectant groups: relative risk (RR) of caesarean section 0.94, 95% confidence interval (CI) 0.82 to 1.08 (12 trials, 6814 women); RR of operative vaginal birth 0.98, 95% 0.84 to 1.16 (7 trials, 5511 women). Significantly fewer women in the planned compared with expectant management groups had chorioamnionitis (RR 0.74, 95% CI 0.56 to 0.97; 9 trials, 6611 women) or endometritis (RR 0.30, 95% CI 0.12 to 0.74; 4 trials, 445 women). No difference was seen for neonatal infection (RR 0.83, 95% CI 0.61 to 1.12; 9 trials, 6406 infants). However, fewer infants under planned management went to neonatal intensive or special care compared with expectant management (RR 0.72, 95% CI 0.57 to 0.92, number needed to treat 20; 5 trials, 5679 infants). In a single trial, significantly more women with planned management viewed their care more positively than those expectantly managed (RR of "nothing liked" 0.45, 95% CI 0.37 to 0.54; 5031 women). AUTHORS' CONCLUSIONS: Planned management (with methods such as oxytocin or prostaglandin) reduces the risk of some maternal infectious morbidity without increasing caesarean sections and operative vaginal births. Fewer infants went to neonatal intensive care under planned management although no differences were seen in neonatal infection rates. Since planned and expectant management may not be very different, women need to have appropriate information to make informed choices.

Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants.

The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.

Chest physiotherapy for preventing morbidity in babies being extubated from mechanical ventilation.

BACKGROUND: Chest physiotherapy has been used to clear secretions and help lung ventilation in newborns who have needed mechanical ventilation for respiratory problems. However concerns about the safety of some forms of chest physiotherapy have been expressed. OBJECTIVES: To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials; Cochrane Controlled Trials Register (Cochrane Library Issue 4 2001); MEDLINE (1966-2001); and CINAHL (1982-2001), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period. DATA COLLECTION AND ANALYSIS: Assessment of methodological quality and extraction of data for each included trial was undertaken independently by the authors. Data were extracted for the primary outcomes of postextubation lobar collapse, use of reintubation, duration of oxygen therapy, intracranial haemorrhage, cerebral cystic lesions, long term neurosensory impairment and death. Subgroup analysis was performed on different treatment frequencies and gestational age less than 32 weeks. Meta-analysis was conducted using a fixed effects model. Results are presented as relative risk (RR), risk difference (RD) and number needed to treat (NNT) for categorical data and mean difference (MD) for data measured on a continuous scale. All outcomes are reported with the use of 95% confidence intervals. MAIN RESULTS: In this review of four trials, two of which were carried out 15 & 23 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse [RR 0.80 (95% CI 0.49,1.29)], though a reduction in the use of reintubation was shown in the overall analysis: RR 0.32 (95% CI 0.13,0.82); RD -7% (95% CI-13, -2); NNT 14 (95% CI 8, 50). There is insufficient information to adequately assess important short and longer term outcomes, including adverse effects. REVIEWER'S CONCLUSIONS: The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited. Further randomised controlled trials addressing the role of prophylactic active chest physiotherapy for neonates in the postextubation period may be unwarranted.

Radiant warmers versus incubators for regulating body temperature in newborn infants.

BACKGROUND: The provision of a thermoneutral environment is an essential component of the immediate and longer term care of newborn infants. A variety of methods are currently employed including incubators and open-care systems, with or without modifications such as heat shields and plastic wrap. The system used must allow ready access to the infant but should also minimise alterations in the immediate environment. OBJECTIVES: To assess the effects of radiant warmers versus incubators on neonatal fluid and electrolyte balance, morbidity and mortality. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register (Cochrane Library Issue 4 2001), MEDLINE (1966 -2001), and CINAHL (1982-2001). SELECTION CRITERIA: Randomised or quasi-randomised trials in which radiant warmers were compared to incubators in a neonatal population. DATA COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of included trials was conducted by the authors. Data were analysed using relative risk (RR) and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta-analysis was undertaken using a fixed effect model. MAIN RESULTS: Eight studies are included in this review; six employed a crossover design. In the overall comparison of radiant warmers vs incubators, radiant warmers caused a statistically significant increase in insensible water loss (IWL) [WMD 0.94g/Kg/day (95% CI 0.47, 1.41)] and a trend towards increased oxygen consumption which was not statistically significant [WMD 0.27mL/kg/min (95% CI -0.09, 0.63)]. Due to small numbers, effects on important clinical outcomes could not be adequately assessed. A comparison of radiant warmers with heat shields vs incubators without heat shields showed a trend for increased IWL in the radiant warmer group, which was not statistically significant. No difference was shown in oxygen consumption. REVIEWER'S CONCLUSIONS: Radiant warmers result in increased IWL compared to incubators. This needs to be taken into account when calculating daily fluid requirements. The results of this review do not provide sufficient evidence concerning effects on important outcomes to guide clinical practice. Further randomised controlled trials are required to assess the effects of radiant warmers versus incubators in neonatal care on important short and long term outcomes, with particular attention to extremely low birthweight infants in the early neonatal period.

Radiant warmers versus incubators for regulating body temperature in newborn infants.

BACKGROUND: The provision of a thermoneutral environment is an essential component of the immediate and longer term care of newborn infants. A variety of methods are currently employed including incubators and open-care systems, with or without modifications such as heat shields and plastic wrap. The system used must allow ready access to the infant but should also minimise alterations in the immediate environment. OBJECTIVES: To assess the effects of radiant warmers versus incubators on neonatal fluid and electrolyte balance, morbidity and mortality. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2003), MEDLINE (1966 -2003), and CINAHL (1982-2003), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language. SELECTION CRITERIA: Randomised or quasi-randomised trials in which radiant warmers were compared to incubators in a neonatal population. DATA COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of included trials was conducted by the authors. Data were analysed using relative risk (RR) and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta-analysis was undertaken using a fixed effect model. MAIN RESULTS: Eight studies are included in this review; six employed a crossover design. In the overall comparison of radiant warmers vs incubators, radiant warmers caused a statistically significant increase in insensible water loss (IWL) [WMD 0.94g/Kg/day (95% CI 0.47, 1.41)] and a trend towards increased oxygen consumption which was not statistically significant [WMD 0.27mL/kg/min (95% CI -0.09, 0.63)]. Due to small numbers, effects on important clinical outcomes could not be adequately assessed. A comparison of radiant warmers with heat shields vs incubators without heat shields showed a trend for increased IWL in the radiant warmer group, which was not statistically significant. No difference was shown in oxygen consumption. REVIEWER'S CONCLUSIONS: Radiant warmers result in increased IWL compared to incubators. This needs to be taken into account when calculating daily fluid requirements. The results of this review do not provide sufficient evidence concerning effects on important outcomes to guide clinical practice. Further randomised controlled trials are required to assess the effects of radiant warmers versus incubators in neonatal care on important short and long term outcomes, with particular attention to extremely low birthweight infants in the early neonatal period.

Chest physiotherapy for preventing morbidity in babies being extubated from mechanical ventilation.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure. SEARCH STRATEGY: The standard search strategy for the Neonatal Review Group was used as outlined in the Cochrane Handbook in the Cochrane Library. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period. The methodological quality of each trial was assessed by two independent authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The data were analysed from 3 trials. Subgroup analysis was performed on different treatment frequencies. MAIN RESULTS: In this review of 3 small trials, 2 of which were carried out 10 & 20 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse (RR 0.69;0.33,1.45), though a reduction in the use of reintubation was shown in the overall analysis (RR 0.24;0.08,0.75). Subgroup analysis of different treatment frequencies showed the same effect with more frequent treatment (1 & 2 hourly) but showed a trend to increased lobar collapse, and no reduction in the use of reintubation, with less frequent treatment (4 hourly). There is insufficient information to assess other important short and long term outcomes, including adverse effects. REVIEWER'S CONCLUSIONS: The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited.

Radiant warmers versus incubators for regulating body temperature in newborn infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To assess the effects of radiant warmers versus incubators (in the neonatal period) on fluid and electrolyte balance, neonatal morbidity and mortality. SEARCH STRATEGY: The standard strategy of the Cochrane Neonatal Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, Medline, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal handsearching mainly in the English language. SELECTION CRITERIA: All randomised or quasi-randomised trials in which radiant warmers are compared to incubators in a neonatal population. DATA COLLECTION AND ANALYSIS: Methods used to collect data from the included studies: Each author extracted data separately, then compared and resolved differences. A referee was sought for unresolved differences. Methods used to synthesise the data : Standard method of Neonatal Review Group with the use of weighted mean difference for outcome data measured on a continuous scale. MAIN RESULTS: A statistically significant increase in insensible water loss (IWL) was shown in neonates nursed under radiant warmers (WMD 0.94g/Kg/day, 95% CI 0.48, 1.41). A trend towards increased oxygen consumption which was not statistically significant was shown for the radiant warmer group (WMD 0. 27mL/kg/min, 95% CI -0.10, 0.63). A comparison of the radiant warmers with heat shields vs incubator without heat shields showed a similar trend for increased IWL in the radiant warmer group which was not statistically significant (WMD 1.00g/kg/day, 95% CI -0.10, 2. 10). No difference was shown in the rate of oxygen consumption when radiant warmers with heat shields were compared to incubators (WMD -0.05, 95% CI -0.84, 0.74). REVIEWER'S CONCLUSIONS: Radiant warmers result in increased IWL compared to incubators which needs to be taken into account when calculating daily fluid requirements.The results of this review do not provide sufficient evidence on important outcomes with the use of radiant warmers vs incubators to guide clinical practice. Further randomised controlled trials are required to assess the role of radiant warmers in neonatal care with particular attention to the extremely low birthweight population.

Calcium channel blockers for inhibiting preterm labour.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials (June 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002), MEDLINE (1965 to June 2002), EMBASE (1988 to June 2002), and Current Contents (1997 to June 2002). We also contacted recognised experts and cross referenced relevant material. SELECTION CRITERIA: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks' gestation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Twelve randomised controlled trials involving 1029 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within seven days of receiving treatment (relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.97) and prior to 34 weeks' gestation (RR 0.83; 95% CI 0.69 to 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.14; 95% CI 0.05 to 0.36), the frequency of neonatal respiratory distress syndrome (RR 0.63; 95% CI 0.46 to 0.88), necrotising enterocolitis (RR 0.21; 95% CI 0.05 to 0.96), intraventricular haemorrhage (RR 0.59 95% CI 0.36 to 0.98) and neonatal jaundice (RR 0.73; 95% CI 0.57 to 0.93). REVIEWER'S CONCLUSIONS: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to other tocolytic agents compared, mainly betamimetics. Further research should address the effects of different dosage regimens and formulations of calcium channel blockers on maternal and neonatal outcomes.

Calcium channel blockers for inhibiting preterm labour.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials, the Cochrane Controlled Trials Register (February 2002), MEDLINE, EMBASE, and Current Contents. We also contacted recognised experts and cross referenced relevant material. SELECTION CRITERIA: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks gestation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Eleven randomised controlled trials involving 870 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within 48 hours (relative risk (RR) 0.73; 95% confidence interval (CI) 0.54, 0.98) and within seven days (RR 0.76; 95% CI 0.59, 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.15; 95% CI 0.06, 0.43), the frequency of neonatal respiratory distress syndrome (RR 0.64; 95% CI 0.45, 0.91) and neonatal jaundice (RR 0.73; 95% CI 0.57, 0.93). REVIEWER'S CONCLUSIONS: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to betamimetic agents. Further research should address the effects of different dosage regimens and formulations of nifedipine on maternal and neonatal outcomes.

Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity.

Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. Monitoring of salivary caffeine concentrations is less invasive than blood sampling, especially in very sick premature neonates. Caffeine citrate-3 mg/kg, 15 mg/kg, or 30 mg/kg-was administered once daily for 7 days in a randomized, parallel design to 59 newborn, premature infants with an initial loading dose of twice the maintenance dose. Serum and saliva samples (131 pairs) were collected and assayed by high-performance liquid chromatography (HPLC) for caffeine content. Measurable caffeine concentrations in serum ranged from 0.28 to 93.3 mg/L and in saliva from 0.35 to 91.5 mg/L. The mean ratio of the saliva-to-serum concentrations was 0.924. There was no significant difference in precision between the serum and salivary data. The mean serum caffeine concentration was 29.9 mg/L, and the mean salivary concentration was 27.7 mg/L, indicating a small negative bias for saliva versus serum monitoring. Salivary caffeine concentration monitoring is a satisfactory alternative to blood sampling across a wide range of caffeine doses used to treat apnea.

Theophylline population pharmacokinetics from routine monitoring data in very premature infants with apnoea.

1. Theophylline is commonly used in neonatology for the treatment and prophylaxis of apnoea of prematurity, and during ventilator weaning. 2. NONMEM was used to study the population pharmacokinetics of intravenous and oral theophylline from retrospective drug monitoring data in 82 premature neonates, weighing < 1500 g at birth, and < or = 32 weeks gestational age. 3. Clearance (CL), volume of distribution (V), and oral bioavailability (F1) from liquid preparations were modelled alone, and under the influence of demographic and clinical covariates, assuming a 1-compartment model with first-order elimination. 4. The final population models with influential co-variates were as follows: CL (1h-1) = 0.0000123 *body weight (g) + 0.000377 *postnatal age (days); V (1) = 0.000937 *body weight (g); F = 0.918. 5. The CL was lower and V was higher than previously reported for less premature neonates, term babies, and older children. 6. Predictive performance of the population models was evaluated by Bayesian forecasting in a similar, but independent cohort of 30 infants. There was statistically insignificant bias and imprecision between measured and predicted serum theophylline concentrations. 7. Based on the validated population models, recommended maintenance theophylline dosages are provided for infants aged between 2 and 50 days, and weighing 700 to 2000 g.

Periextubation caffeine in preterm neonates: a randomized dose response trial.

OBJECTIVE: To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period. METHODS: A randomized double-blind clinical trial of three dosing regimens of caffeine citrate (3, 15 and 30 mg/kg) for periextubation management of ventilated preterm infants was undertaken. Infants born <32 weeks gestation who were ventilated for>48 h were eligible for the study. Caffeine citrate was given as a once daily dose for a period of 6 days commencing 24 h prior to a planned extubation, or within 6 h of an unplanned extubation. The primary outcome measure was extubation failure, defined as neonates who were unable to be extubated within 48 h of caffeine loading or who required reventilation or doxapram dose within 7 days of caffeine loading. Continuous recordings of oxygen saturation and heart rate were undertaken in a subgroup of enrolled infants. RESULTS: A total of 127 babies were enrolled into the study (42, 40, 45, in the 3, 15, and 30 mg/kg groups, respectively). No statistically significant difference was demonstrated in the incidence of extubation failure between dosing groups (19, 10, and 11 infants in the 3, 15, and 30 mg/kg groups, respectively), however, infants in the two higher dose groups had statistically significantly less documented apnoea than the lowest dose group. Of the 37 neonates with continuous pulse oximetry recordings, those on higher doses of caffeine recorded a statistically significantly higher mean heart rate, oxygen saturations and less time with oxygen saturations <85%. CONCLUSIONS: This trial indicated there were short-term benefits of decreased apnoea in the immediate periextubation period for ventilated infants born <32 weeks gestation receiving higher doses of caffeine. Further studies with larger numbers of infants assessing longer-term outcomes are necessary to determine the optimal dosing regimen of caffeine in preterm infants.