Impact of NICE clinical guidelines for prevention and treatment of neonatal infections on antibiotic use in very preterm infants in England and Wales: an interrupted time series analysis.

OBJECTIVE: To assess the impact of publication of UK National Institute for Health and Care Excellence (NICE) guidelines on the prevention and treatment of early-onset infections (EOIs) in neonates (clinical guideline 149 (CG149), published in 2012, and its 2021 update (NG195) on antibiotic use in very preterm infants. DESIGN: Interrupted time series analysis using data from the National Neonatal Research Database. SETTING: Neonatal units in England and Wales. PARTICIPANTS: Infants born at 22-31 weeks' gestation from 1 January 2010 to 31 December 2022 and survived to discharge. INTERVENTIONS: Publication of CG149 (August 2012) and NG195 (April 2021). MAIN OUTCOME MEASURES: Measures of antibiotic use, aggregated by month of birth: antibiotic use rate (AUR), the proportion of care days in receipt of at least one antibiotic; percentage of infants who received ≥1 day of antibiotics on days 1-3 for EOI and after day 3 for late-onset infection (LOI); percentage who received ≥1 prolonged antibiotic course ≥5 days for EOI and LOI. RESULTS: 96% of infants received an antibiotic during inpatient stay. AUR declined at publication of CG149, without further impact at NG195 publication. There was no impact of CG149 on the underlying trend in infants receiving ≥1 day antibiotics for EOI or LOI, but post-NG195 the monthly trend began to decline for EOI (-0.20%, -0.26 to -0.14) and LOI (-0.23%, -0.33 to -0.12). Use of prolonged antibiotic courses for EOI and LOI declined at publication of CG149 and for LOI this trend accelerated post-NG195. CONCLUSIONS: Publications of NICE guidance were associated with reductions in antibiotic use; however neonatal antibiotic exposure remains extremely high.

The Relationship Between Reported Daily Nicotine Dose from NRT and Daily Cigarette Consumption in Pregnant Women Who Smoke in an Observational Cohort Study.

INTRODUCTION: For nonpregnant people unable to quit smoking, the NHS recommends nicotine replacement therapy (NRT) for smoking reduction. This is not recommended during pregnancy due to concerns about higher nicotine intake than smoking alone. We investigated the relationship between daily nicotine dose from NRT and cigarette consumption reported by pregnant women receiving smoking cessation support. METHODS: We conducted secondary analysis of data from currently smoking pregnant women, recruited from antenatal clinics (Nottingham University Hospitals, UK) or online between June 2019-September 2020. Participants set a quit date, received a prototype NRT adherence intervention, and reported cigarettes per day (CPD) and daily NRT dose (mg) via smartphone app for 28 days. RESULTS: 388 women were screened, 32 (8%) were eligible and joined the study. 24 (75%) submitted 510 app reports in total. 17 (71%) reported smoking and using NRT concurrently on at least one day, with concurrent use reported on 109 (21%) of app reports.The relationship between daily NRT dose and CPD followed an exponential decay curve of approximately 7%. In multilevel repeated measures modelling using 4 linear splines (knots 17, 40, and 85 mg/NRT), significant fixed effects of daily NRT dose on CPD were observed for splines 1, 3, and 4. The strongest association was spline 1 (0-17 mg/NRT), where each 10 mg NRT increase was associated with a 0.6 CPD reduction (24% on average). CONCLUSIONS: Among women in a cessation study, many smoked and used NRT concurrently; within these women, daily nicotine dose and heaviness of smoking were inversely related. IMPLICATIONS: Findings have implications for the design of future interventions intended to reduce harm associated with smoking in pregnancy. They suggest using NRT alongside smoking in pregnancy could help some women reduce the number of cigarettes they smoke per day.

Association between women's experience of domestic violence and childhood vaccination in West Africa: Cross-sectional analysis of Demographic and Health Survey data.

BACKGROUND: In 2021, 25 million children worldwide did not receive full basic childhood vaccinations, the highest figure in over a decade. There are large variations between countries in vaccination coverage. Globally, the lifetime prevalence of domestic violence among ever-partnered women is 30%. Exposure to domestic violence affects both maternal and child health. However, there is limited contemporary evidence on whether children born to women who are exposed to domestic violence are any more or less likely to be vaccinated. METHODS: We conducted a cross-sectional study using data from the most recent Demographic and Health Surveys (DHS) from 7 West African countries (Benin, Gambia, Liberia, Mali, Nigeria, Senegal, Sierra Leone). We used multivariable logistic regression to examine the association between women's lifetime experience of any emotional, physical and/or sexual domestic violence and whether her most-recent born child aged 12-35 months old had received a full complement of basic childhood vaccinations (covering tuberculosis, diphtheria, tetanus, pertussis, polio and measles). RESULTS: Data from 9,104 mother-child pairs was analysed (range 480 from Senegal to 3,230 from Nigeria). Overall, 47% of children were fully vaccinated (range 31% in Nigeria to 81% in The Gambia). 41% of women reported any experience of domestic violence (range 20% in Senegal to 54% in Sierra Leone). After adjustment for a range of child, maternal, household and partner-level variables, children born to women who reported experience of domestic violence were no more or less likely to be fully vaccinated (adjusted odds ratio = 1.02, 95% confidence interval 0.90-1.17). There was some evidence that the association may vary by country; in Sierra Leone, children born to women who reported experience of domestic violence were significantly less likely to be fully vaccinated (adjusted odds ratio = 0.62, 95%CI 0.44-0.88). CONCLUSIONS: There was no significant association between a woman's exposure to domestic violence and whether her child was fully vaccinated. Further work is needed to understand the contextual factors which may explain potential variations between countries.

Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort study.

Background: Preterm infants often require mechanical ventilation (MV), which can be a painful experience. Opioids (such as morphine) are used to provide analgesia, despite conflicting evidence about their impact on the developing brain. We aimed to quantify the use of opioids during MV in infants born at <32 weeks' gestational age and to investigate the association between opioid use and evidence of brain injury. Methods: In this retrospective propensity score-matched cohort study, we used routinely recorded data from the National Neonatal Research Database to study infants born at 22-31 weeks gestational age who were admitted to neonatal units in England and Wales (between Jan 1, 2012, and Dec 31, 2020) and who were mechanically ventilated on one or more days during their hospital stay. We used propensity score matching to identify pairs of infants (one who received opioids during MV and one who did not) with similar demographic and clinical characteristics. The pre-specified primary outcome was preterm brain injury assessed in all infants who received MV for more than two days and had evidence of preterm brain injury at or before discharge from neonatal care. Adjusted analyses accounted for differences in infants' characteristics, including illness severity and painful/surgical conditions. Findings: Of 67,206 infants included, 45,193 (67%) were mechanically ventilated for one or more days and 26,201 (58% of 45,193) received an opioid whilst ventilated. Opioids were given for a median of 67% of ventilated days (IQR 43-92%) and the median exposure was 4 days (2-11). The percentage of mechanically ventilated infants who received opioids while ventilated increased from 52% in 2012 to 60% in 2020 (morphine, 51%-56%; fentanyl, 6%-18%). In the propensity score-matched cohort of 3608 pairs who were ventilated for >2 consecutive days, the odds of any preterm brain injury (adjusted odds ratio 1.22, 95% CI 1.10-1.35) were higher in those who received opioids compared with those who did not (received opioids, 990/3608 (27.4%) vs. did not receive opioids, 855/3608 (23.7%). The adjusted odds of these adverse outcomes increased with increasing number of days of opioid exposure. Interpretation: Use of opioids during mechanical ventilation of preterm infants increased during the study period (2012-2020). Although causation cannot be determined, among those ventilated for >2 consecutive days, these data suggest that opioid use is associated with an increased risk of preterm brain injury and the risk increases with longer durations of exposure. Funding: University of Nottingham Impact Fund.

Impact of postnatal dexamethasone timing on preterm mortality and bronchopulmonary dysplasia: a propensity score analysis.

BACKGROUND: Postnatal dexamethasone (PND) is used in high-risk preterm infants after the first week of life to facilitate extubation and prevent bronchopulmonary dysplasia (BPD) but the optimal treatment timing remains unclear. Our objective was to explore the association between the timing of PND commencement and mortality and respiratory outcomes. METHODS: This was a retrospective National Neonatal Research Database study of 84 440 premature infants born <32 weeks gestational age from 2010 to 2020 in England and Wales. Propensity score weighting analysis was used to explore the impact of PND commenced at three time-points (2-3 weeks (PND2/3), 4-5 weeks (PND4/5) and after 5 weeks (PND6+) chronological age) on the primary composite outcome of death before neonatal discharge and/or severe BPD (defined as respiratory pressure support at 36 weeks) alongside other secondary respiratory outcomes. RESULTS: 3469 infants received PND. Compared with PND2/3, infants receiving PND6+ were more likely to die and/or develop severe BPD (OR 1.68, 95% CI 1.28-2.21), extubate at later postmenstrual age (mean difference 3.1 weeks, 95% CI 2.9-3.4 weeks), potentially require respiratory support at discharge (OR 1.34, 95% CI 1.06-1.70) but had lower mortality before discharge (OR 0.38, 95% CI 0.29-0.51). PND4/5 was not associated with severe BPD or discharge respiratory support. CONCLUSIONS: PND treatment after 5 weeks of age was associated with worse respiratory outcomes although residual bias cannot be excluded. A definitive clinical trial to determine the optimal PND treatment window, based on early objective measures to identify high-risk infants, is needed.

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population. PURPOSE: Evaluate the temporal trends in the respiratory management and outcomes of preterm infants born below 32 weeks gestational age and develop an individualised dashboard of the incidence of neonatal outcome. METHODS: Using the National Neonatal Research Database, we determined changes in respiratory management, BPD rates, postdischarge respiratory support and mortality in 83 463 preterm infants in England and Wales from 2010 to 2020. RESULTS: Between 2010 and 2020, antenatal corticosteroids use increased (88%-93%, p<0.0001) and neonatal surfactant use decreased (65%-60%, p<0.0001). Postnatal corticosteroid use increased, especially dexamethasone (4%-6%, p<0.0001). More recently, hydrocortisone and budesonide use increased from 2% in 2017 to 4% and 3%, respectively, in 2020 (p<0.0001). Over the study period, mortality decreased (10.1%-8.5%), with increases in BPD (28%-33%), severe BPD (12%-17%), composite BPD/death (35%-39%) and composite severe BPD/death (21%-24%) (all p<0.0001). Overall, 11 684 infants required postdischarge respiratory support, increasing from 13% to 17% (p<0.0001), with 1843 infants requiring respiratory pressure support at discharge. A population dashboard (https://premoutcome.github.io/) depicting the incidence of mortality and respiratory outcomes, based on gestation, sex and birthweight centile, was developed. CONCLUSION: More preterm infants are surviving with worse respiratory outcomes, particularly severe BPD requiring postdischarge respiratory support. Ultimately, these survivors will develop chronic respiratory diseases requiring greater healthcare resources.

How frequent is routine use of probiotics in UK neonatal units?

OBJECTIVE: There is a lack of UK guidance regarding routine use of probiotics in preterm infants to prevent necrotising enterocolitis, late-onset sepsis and death. As practices can vary, we aimed to determine the current usage of probiotics within neonatal units in the UK. DESIGN AND SETTING: Using NeoTRIPS, a trainee-led neonatal research network, an online survey was disseminated to neonatal units of all service levels within England, Scotland, Northern Ireland and Wales in 2022. Trainees were requested to complete one survey per unit regarding routine probiotic administration. RESULTS: 161 of 188 (86%) neonatal units responded to the survey. 70 of 161 (44%) respondents routinely give probiotics to preterm infants. 45 of 70 (64%) use the probiotic product Lactobacillus acidophilus NCFM/Bifidobacterium bifidum Bb-06/B. infantis Bi-26 (Labinic™). 57 of 70 (81%) start probiotics in infants ≤32 weeks' gestation. 33 of 70 (47%) had microbiology departments that were aware of the use of probiotics and 64 of 70 (91%) had a guideline available. Commencing enteral feeds was a prerequisite to starting probiotics in 62 of 70 (89%) units. The majority would stop probiotics if enteral feeds were withheld (59 of 70; 84%) or if the infant was being treated for necrotising enterocolitis (69 of 70; 99%). 24 of 91 (26%) units that did not use probiotics at the time of the survey were planning to introduce them within the next 12 months. CONCLUSIONS: More than 40% of all UK neonatal units that responded are now routinely administering probiotics, with variability in the product used. With increased probiotic usage in recent years, there is a need to establish whether this translates to improved clinical outcomes.

Psychosocial Impacts of Infertility among Omani Women with Polycystic Ovarian Syndrome: A Qualitative Study.

BACKGROUND: To understand the psychosocial experience of infertility among women with polycystic ovarian syndrome in Oman. MATERIALS AND METHODS: In this qualitative study, semi-structured interviews were conducted with 20 Omani women diagnosed with polycystic ovarian syndrome (PCOS) and infertility across two fertility clinics, in Muscat-Oman. Interviews were audio-recorded, transcribed analysed verbatim and qualitatively using the framework approach. RESULTS: Four main themes emerged from participants' interviews related to the cultural aspects around infertility, the impact of infertility on participants' emotions, the effects of infertility on couples' relationship and self-management strategies for dealing with infertility. Culturally, women are expected to conceive soon after marriage, and most participants were blamed for the delay rather than their husbands. Participants experienced psychosocial pressure to bear children, mainly from in laws, where some admitted that their husbands' family suggested they remarried for having children. The majority of women mentioned being emotionally supported by their partners; however marital tensions in the form of negative emotions and threats of divorce were apparent in couples that had been experiencing infertility for longer time. Women were emotionally feeling lonely, jealous and inferior to other women with children and concerned that they would not have children to look after them in older age. Although women who had experienced infertility for a greater duration seemed to become more resilient and cope better, other participants described how they were using different strategies to cope with infertility including taking up new activities; whereas others admitted moving out from their in laws' house or avoiding social gatherings where the topic of children was likely to come up. CONCLUSION: Omani women with PCOS and infertility experience significant psychosocial challenges given the high value placed on fertility within the culture as a result they seem to adapt a variety of coping strategies. Health care providers may consider offering emotional support during consultations.

Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes.

OBJECTIVE: To quantify trends in caffeine use in infants born at <32 weeks' gestational age (GA), and to investigate the effects of early vs late caffeine on neonatal outcomes. STUDY DESIGN: Retrospective propensity score matched cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks' GA admitted to neonatal units in England and Wales (2012-2020). RESULTS: 89% (58 913/66 081) of infants received caffeine. In 70%, caffeine was started early (on the day of birth or the day after), increasing from 55% in 2012 to 83% in 2020. Caffeine was given for a median (IQR) of 28 (17-43) days starting on day 2 (1-3) and continued up to 34 (33-34) weeks postmenstrual age.In the propensity score matched cohort of 13 045 pairs of infants, the odds of preterm brain injury (early caffeine, 2306/13 045 (17.7%) vs late caffeine, 2528/13 045 (19.4%), OR=0.89 (95% CI 0.84 to 0.95)) and bronchopulmonary dysplasia (BPD) (early caffeine, 4020/13 045 (32.8%) vs late caffeine, 4694/13 045 (37.7%), OR=0.81 (95% CI 0.76 to 0.85)) were lower in the group that received early caffeine compared with those who received it later. CONCLUSIONS: Early use of caffeine has increased in England and Wales. This is associated with reduced risks of BPD and preterm brain injury. Randomised trials are needed to find the optimal timing of caffeine use and the groups of infants who will benefit most from early administration of caffeine.

Management of patent ductus arteriosus in very preterm infants in England and Wales: a retrospective cohort study.

OBJECTIVE: To describe the diagnosis and treatment of patent ductus arteriosus (PDA) in infants born at <32 weeks' gestational age (GA) in England and Wales between 2010 and 2017. STUDY DESIGN: Retrospective cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks admitted to neonatal units in England and Wales from 2010 to 2017. RESULTS: Among 58 108 infants born at <32 weeks' GA, 28.3% (n=16 440) had a PDA diagnosed clinically or with echocardiographic confirmation. Of these, 34.8% (n=5721; 9.8% of total <32 weeks' infants included) had PDA treatment including 7.6% (n=1255) with indomethacin, 23.5% (n=3857) with ibuprofen and 5.6% (n=916) with surgical closure. The highest incidence of PDA was among infants born at 24 and 25 weeks' GA (70.2% and 70.8%, respectively), decreasing to 6.1% among infants born at 31 weeks' GA. The percentage of infants with a PDA increased over the study period (25.5% in 2010 to 28.5% in 2017). The percentage of infants who received ibuprofen or indomethacin or had PDA surgery decreased from 41.3% in 2010 to 33.7% in 2017, with an increase in use of ibuprofen from 20.2% to 27.3% while use of indomethacin decreased from 20.0% to 8.8%. Surgical closure of PDA decreased from 9.1% to 3.0%. Indomethacin was used for median (IQR) 3 (2-5) days while ibuprofen was given for 3 (2-4) days, at a median of 8 and 10 days after birth, respectively; surgical treatment was used later at 33 (24-45) days after birth. CONCLUSIONS: Ibuprofen is the preferred drug and surgical interventions are becoming less frequent for PDA closure among very preterm infants in England and Wales. TRIAL REGISTRATION NUMBER: NCT03773289.

Impact of the coronavirus disease 2019 pandemic on breastfeeding during and at discharge from neonatal care: An observational cohort study.

Importance: During the coronavirus disease 2019 (COVID-19) lockdown, changes in the visiting rules in neonatal units might have affected the initiation and continuation of breastfeeding. Objective: To investigate the effects of the implementation of the COVID-19 lockdown in the UK on mother's own milk (MOM) feeding in hospital and at the time of discharge in two UK neonatal units. Methods: Retrospective cohort study using routinely recorded data from electronic patient records. Data were retrieved from two neonatal services in the UK East Midlands region. Adjusted logistic regression was used to compare the odds of MOM feeding before, and after the implementation of the UK lockdown. Results: Among 2073 infants, after adjusting for maternal and infant characteristics and underlying trends over time, there were no differences in the odds of infants receiving any MOM during admission; any MOM at discharge or exclusive MOM at discharge before and after the imposition of the lockdown. Infants with birthweight <1000 g were three times less likely to receive any MOM at discharge compared to those with birthweight >2500 g (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI]: 0.22-0.50). Younger mothers were less likely, and Black British mothers more likely, to be feeding MOM to their infants at discharge, while women in the least deprived Index of Multiple Deprivation (IMD) quintiles were 2-4 times more likely to do so, compared to those in the most deprived IMD quintile (adjusted OR 2.78, 95% CI: 1.97-3.90). Interpretation: Despite the difficulties faced during COVID-19 pandemic-induced restrictions, infants in the participating neonatal units continued to receive MOM in similar proportions as before the pandemic.

Drug utilisation in neonatal units in England and Wales: a national cohort study.

PURPOSE: To describe drug utilisation patterns in neonatal units. METHODS: Retrospective observational cohort study using data held in the National Neonatal Research Database (NNRD) for neonatal units in England and Wales including infants born at 23 to 44 weeks' gestational age (GA) from 01 January 2010 to 31 December 2017. RESULTS: The cohort included 17,501 (3%) extremely preterm infants; 40,607 (7%) very preterm infants; 193,536 (31%) moderate-to-late preterm infants; and 371,606 (59%) term infants. The number of unique drugs received by an infant (median (IQR)) increased with decreasing GA: 17 (11-24) in extremely preterm, 7 (5-11) in very preterm, 3 (0-4) in moderate-to-late preterm, and 3 (0-3) in term infants. The two most frequently prescribed drugs were benzylpenicillin and gentamicin in all GA groups, and caffeine in extremely preterm. Other frequently used drugs among preterm infants were electrolytes, diuretics and anti-reflux medications. Among infants <32 weeks' GA, the largest increase in use was for surfactant (given on the neonatal unit), caffeine and probiotics, while domperidone and ranitidine had the largest decline. CONCLUSION: Antibiotics, for all GAs and caffeine, among preterm infants, are the most frequently used drugs in neonatal medicine. Preterm infants are exposed to a high burden of drugs, particularly antibiotics. Changing patterns in use reflect the emergence of evidence in some areas but several non-evidence-based drugs continue to be used widely. Improvements are needed to ensure rational drug use on neonatal units. REGISTRATION: ClinicalTrials.gov (NCT03773289). Date of registration 21 Dec 2018.

Anti-reflux medication use in preterm infants.

BACKGROUND: Current recommendations do not support the use of anti-reflux medications to treat gastro-oesophageal reflux disease (GORD) among preterm infants. OBJECTIVE: To describe the prevalence of GORD and the use of anti-reflux medications amongst very preterm infants (<32 weeks' gestational age (GA)) in neonatal units in England and Wales. DESIGN: Retrospective cohort study using the National Neonatal Research Database. RESULTS: Among 58,108 infants [median GA (IQR) 29 (27-30) weeks], 15.8% (n = 9191) had a diagnosis of GORD and 36.9% (n = 12,446) received anti-reflux medications. Those who received anti-reflux medications were more preterm [GA, median (IQR): medications, 28 (26-30) vs. no medications, 30 (28-31); p < 0.001] and had lower birth weight [mean (SD): medications, 1124 g (354) vs. no medications, 1265 g (384); p < 0.001]. Most (57%, n = 12,224) received Gaviscon, or Histamine-2 Receptor Antagonist (H2RA) (56%, n = 11,959). Over time, prokinetic use has declined substantially, the use of H2RAs and Gaviscon has reduced although they continue to be used frequently, whilst the use of PPIs has increased. CONCLUSIONS: Anti-reflux medications are frequently prescribed in very preterm infants, despite evidence to suggest that they are not effective and may be harmful. Clear guidelines for diagnosing GORD and the use of anti-reflux medications are required to rationalise the pharmacological management of GORD in preterm infants. IMPACT: Anti-reflux medications are frequently prescribed, often without a diagnosis of gastro-oesophageal reflux disease, to very preterm infants while in the neonatal unit and at discharge. Half of the infants born at <28 weeks' gestational age receive anti-reflux medications in hospital and a quarter are discharged home on them. Although the use of prokinetics declined following alerts of adverse events, histamine2-receptor antagonists and alginates such as Gaviscon continue to be used and the use of proton-pump inhibitors has increased more than 2-fold.

Observational cohort study of changing trends in non-invasive ventilation in very preterm infants and associations with clinical outcomes.

OBJECTIVE: To determine the change in non-invasive ventilation (NIV) use over time in infants born at <32 weeks' gestation and the associated clinical outcomes. STUDY DESIGN: Retrospective cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks admitted to neonatal units in England and Wales from 2010 to 2017. RESULTS: In 56 537 infants, NIV use increased significantly between 2010 and 2017 (continuous positive airway pressure (CPAP) from 68.5% to 80.2% in 2017 and high flow nasal cannula (HFNC) from 14% to 68%, respectively) (p<0.001)). Use of NIV as the initial mode of respiratory support also increased (CPAP, 21.5%-28.0%; HFNC, 1%-7% (p<0.001)).HFNC was used earlier, and for longer, in those who received CPAP or mechanical ventilation. HFNC use was associated with decreased odds of death before discharge (adjusted OR (aOR) 0.19, 95% CI 0.17 to 0.22). Infants receiving CPAP but no HFNC died at an earlier median chronological age: CPAP group, 22 (IQR 10-39) days; HFNC group 40 (20-76) days (p<0.001). Among survivors, HFNC use was associated with increased odds of bronchopulmonary dysplasia (BPD) (aOR 2.98, 95% CI 2.81 to 3.15) and other adverse outcomes. CONCLUSIONS: NIV use is increasing, particularly as initial respiratory support. HFNC use has increased significantly with a sevenfold increase soon after birth which was associated with higher rates of BPD. As more infants survive with BPD, we need robust clinical evidence, to improve outcomes with the use of NIV as initial and ongoing respiratory support.

Nutritional practices and growth of preterm infants in two neonatal units in the UK and Malaysia: a prospective exploratory study.

Objective: To explore differences in nutritional practices and growth outcomes among preterm infants in neonatal units in Malaysia and the UK. Design: Prospective exploratory study of infants born at <34 weeks gestational age (GA). Setting: Two neonatal units, one in Malaysia and one in the UK (May 2019 to March 2020). Methods: Data collected from birth until discharge and compared between units. Results: From 100 infants included, median GA (IQR) was 31 (30-33) and mean±SD birth weight was 1549±444 g. There were more small-for-gestational age infants in Malaysian unit: 12/50 (24%) vs UK: 3/50 (6%), p=0.012 and more morbidities. More Malaysian infants received breast milk (Malaysia: 49 (98%) vs UK: 38 (76%), p=0.001), fortified breast milk (Malaysia: 43 (86%) vs UK: 13 (26%), p<0.001) and exclusive breast milk at discharge (Malaysia: 26 (52%) vs UK: 16 (32%), p=0.043). There was higher parenteral nutrition use among Malaysian infants (40/50 (80%)) vs UK (19/50 (38%)) (p<0.001) with higher protein intake (mean±SD Malaysia: 3.0±0.5 vs UK: 2.7±0.6 g/kg/d, p=0.004) in weeks 1-4 and smaller cumulative protein deficits (mean±SD Malaysia: 11.4±6.1 vs UK: 15.4±8.0 g/kg, p=0.006). There were no significant differences in short-term growth between units and more than half of the infants in both units had ≥1.28 changes in weight-for-age Z-score at discharge (p=0.841). Conclusions: An exploratory comparison of practices showed differences in patient characteristics and nutritional practices which impacted growth. Future studies with larger sample sizes and detailed analysis of maternal characteristics and infants' outcomes are needed for improving care of preterm infants in all settings.

Trends in Prescribing of Nicotine Replacement Therapy to Pregnant Women in Primary Care in England.

INTRODUCTION: Smoking during pregnancy remains common, and the English National Health Service (NHS) has recently been directed to prioritize providing cessation support for pregnant women. We investigated the impact on prescribing of stop smoking treatments to pregnant women of the 2013 transfer of public health budgets from the NHS to administrative authorities responsible for local social care and other nonhealth services (local authorities). METHODS: We used data from the Clinical Practice Research Datalink and Hospital Episode Statistics to determine annual proportions (2005-2017) of women who smoked during pregnancy and who were prescribed, at least once before childbirth, (1) any NRT and (2) long- and short-acting NRT together (dual NRT). Segmented regression was used to quantify the impact of the 2013 transfer of smoking cessation budgets to local authorities, assessing changes in the level and the trend of the proportions post-2013 compared with pre-2013. RESULTS: We identified 84 539 pregnancies in which women were recorded as smoking; any NRT was prescribed in 7.9% (n = 6704) and dual NRT in 1.7% (n = 1466). Prescribing of any NRT was declining prior to 2013 at an absolute decrease of -0.25% per year, but the rate of decline significantly increased from 2013 onwards to -1.37% per year. Prescribing of dual NRT was increasing prior to 2013 but also decreased post-2013. CONCLUSIONS: These findings suggest that transferring responsibility for English Smoking Cessation Services from the NHS to local authorities adversely affected provision of cessation support in pregnancy. Consequently, some women may have been denied access to effective cessation treatments. IMPLICATIONS: Women who smoke during pregnancy may be being denied potentially effective means to help them quit, contrary to NICE guidance, at what can be a teachable moment with substantial immediate and longer-term health benefits for woman and their unborn child, and economic benefits for the NHS. When the organizations responsible for offering smoking cessation support are changed, health systems should consider potential adverse effects on the delivery of support and deploy strategies for mitigating these.

Review of Drug Utilization Studies in Neonatal Units: A Global Perspective.

Rational prescribing is challenging in neonatology. Drug utilization studies help identify and define the problem. We performed a review of the literature on drug use in neonatal units and describe global variations. We searched databases (EMBASE, CINAHL and Medline) from inception to July 2020, screened studies and extracted relevant data (two reviewers). The search revealed 573 studies of which 84 were included. India (n = 14) and the USA (n = 13) reported the most. Data collection was prospective (n = 56) and retrospective (n = 26), mostly (n = 52) from one center only. Sixty studies described general drug use in 34 to 450,386 infants (median (IQR) 190 (91-767)) over a median (IQR) of 6 (3-18) months. Of the participants, 20-87% were preterm. The mean number of drugs per infant (range 11.1 to 1.7, pooled mean (SD) 4 (2.4)) was high with some reporting very high burden (≥30 drugs per infant in 8 studies). This was not associated with the proportion of preterm infants included. Antibiotics were the most frequently used drug. Drug use patterns were generally uniform with some variation in antibiotic use and more use of phenobarbitone in Asia. This study provides a global perspective on drug utilization in neonates and highlights the need for better quality information to assess rational prescribing.

Early childhood respiratory morbidity and antibiotic use in ex-preterm infants: a primary care population-based cohort study.

BACKGROUND: Globally, bronchopulmonary dysplasia (BPD) continues to increase in preterm infants. Recent studies exploring subsequent early childhood respiratory morbidity have been small or focused on hospital admissions. AIMS: To examine early childhood rates of primary care consultations for respiratory tract infections (RTI), lower respiratory tract infections (LRTI), wheeze and antibiotic prescriptions in ex-preterm and term children. A secondary aim was to examine differences between preterm infants discharged home with or without oxygen. METHODS: Retrospective cohort study using linked electronic primary care and hospital databases of children born between 1997 and 2014. We included 253 277 eligible children, with 1666 born preterm at <32 weeks' gestation, followed-up from primary care registration to age 5 years. Adjusted incidence rate ratios (aIRRs) were calculated. RESULTS: Ex-preterm infants had higher rates of morbidity across all respiratory outcomes. After adjusting for confounders, aIRRs for RTI (1.37, 95% CI 1.33-1.42), LRTI (2.79, 95% CI 2.59-3.01), wheeze (3.05, 95% CI 2.64-3.52) and antibiotic prescriptions (1.49, 95% CI 1.44-1.55) were higher for ex-preterm infants. Ex-preterm infants discharged home on oxygen had significantly greater morbidity across all respiratory diagnoses and antibiotic prescriptions compared to those without home oxygen. The highest rates of respiratory morbidity were observed in children from the most deprived socioeconomic groups. CONCLUSION: Ex-preterm infants, particularly those with BPD requiring home oxygen, have significant respiratory morbidity and antibiotic prescriptions in early childhood. With the increasing prevalence of BPD, further research should focus on strategies to reduce the burden of respiratory morbidity in these high-risk infants after hospital discharge.

Rojiroti microfinance and child nutrition: a cluster randomised trial.

OBJECTIVE: To determine whether Rojiroti microfinance, for poor Indian women, improves child nutrition. DESIGN: Cluster randomised trial. SETTING: Tolas (village communities) in Bihar State. PARTICIPANTS: Women and children under 5 years. INTERVENTIONS: With Rojiroti microfinance, women form self-help groups and save their money to provide loans to group members. After 6 months, they receive larger external loans. Tolas were randomised to receive Rojiroti immediately or after 18 months. OUTCOME MEASURES: The primary analysis compared the mean weight for height Z score (WHZ) of children under 5 years in the intervention versus control tolas who attended for weight and height measurement 18 months after randomisation. Secondary outcomes were weight for age Z score (WAZ), height for age Z score, mid-upper arm circumference (MUAC), wasting, underweight and stunting. RESULTS: We randomised 28 tolas to each arm and collected data from 2469 children (1560 mothers) at baseline and 2064 children (1326 mothers) at follow-up. WHZ was calculated for 1718 children at baseline and 1377 (674 intervention and 703 control) at follow-up. At 18 months, mean WHZ was significantly higher for intervention (-1.02) versus controls (-1.37; regression coefficient adjusted for clustering ß=0.38, 95% CI 0.16 to 0.61, p=0.001). Significantly fewer children were wasted in the intervention group (122, 18%) versus control (200, 29%; OR=0.46, 95% CI 0.28 to 0.74, p=0.002). Mean WAZ was better in the intervention group (-2.13 vs -2.37; ß=0.27, 95% CI 0.11 to 0.43, p=0.001) as was MUAC (13.6 cm vs 13.4 cm; ß=0.22, 95% CI 0.03 to 0.40, p=0.02). In an analysis adjusting for baseline nutritional measures (259 intervention children and 300 control), only WAZ and % underweight showed significant differences in favour of the intervention. CONCLUSION: In marginalised communities in rural India, child nutrition was better in those who received Rojiroti microfinance, compared with controls. TRIAL REGISTRATION NUMBER: NCT01845545.