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  • Journal article
    Mitra S, Whitehead L, Smith K, MacLean B, Nixon R, Veysey A, Campbell-Yeo M, Kuhle S, Gale C, Soll R, Dorling J, Johnston BCet al., 2024,

    Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences

    , Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 109, Pages: 232-238, ISSN: 1359-2998

    Importance: Prophylactic cyclooxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks’ gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Objective: To develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants.Methods: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence-to-Decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including five experienced neonatal care providers, two methods experts, one pharmacist, two parents of former extremely preterm infants and two adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis, and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. Recommendations: The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants [conditional recommendation, moderate certainty in estimate of effects]. Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group [conditional recommendation, low certainty in the estimate of effects]. The panel strongly recommended against use of prophylactic acetaminophen [strong recommendation, very low certainty in estimate of effects] until further research evidence is available.

  • Journal article
    Rees P, Callan C, Chadda KR, Vaal M, Diviney J, Sabti S, Harnden F, Gardiner J, Battersby C, Gale C, Sutcliffe Aet al., 2024,

    Childhood outcomes after low-grade Intraventricular Haemorrhage: a systematic review and meta-analysis

    , Developmental Medicine and Child Neurology, Vol: 66, Pages: 282-289, ISSN: 0012-1622

    Aim:To undertake a systematic review and meta-analysis exploring school-aged neurodevelopmental outcomes of children after low-grade intraventricular haemorrhage (IVH).Methods:The published and grey literature was extensively searched to identify observational comparative studies exploring neurodevelopmental outcomes after IVH grade 1-2. Our primary outcome was neurodevelopmental impairment after 5 years of age, which included cognitive, motor, speech and language, behavioural, hearing or visual impairments.Results:This review included 12 studies and over 2,036 preterm infants with low grade IVH. Studies used 30 different neurodevelopmental tools to determine outcomes. There was conflicting evidence of the composite risk of neurodevelopmental impairment after low-grade IVH. There was evidence of an association between low-grade IVH and lower IQ at school age -4.23 95% CI (-7.53, -0.92) I2=0% but impact on school performance was unclear. Studies reported an increased crude risk of cerebral palsy after low-grade IVH OR 2.92 95%CI (1.95, 4.37) I2=41%. No increased risk of speech and language impairment or behavioural impairment was found. Few studies addressed hearing and visual impairment.Interpretation:This review presents evidence that low-grade IVH is associated with specific neurodevelopmental impairments at school age, lending support to the theory that low-grade IVH is not a benign condition.

  • Journal article
    Daskalakis G, Pergialiotis V, Domelloef M, Ehrhardt H, Di Renzo GC, Koc E, Malamitsi-Puchner A, Kacerovsky M, Modi N, Shennan A, Ayres-de-Campos D, Gliozheni E, Rull K, Braun T, Beke A, Kosinska-Kaczynska K, Areia AL, Vladareanu S, Srsen TP, Schmitz T, Jacobsson Bet al., 2023,

    European guidelines on perinatal care: corticosteroids for women at risk of preterm birth

    , JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, Vol: 36, ISSN: 1476-7058
  • Journal article
    Molloy EJ, Branagan A, Hurley T, Quirke F, Devane D, Taneri PE, El-Dib M, Bloomfield F, Maeso R, Pilon B, Bonifacio SL, Wusthoff CJ, Chalak L, Bearer C, Murray DM, Badwani N, Campbell SK, Mulkey S, Gressens P, Ferriero DM, de Vries LS, Walker K, Kay S, Boylan GB, Gale C, Robertson NJ, D'Alton M, Gunn AJ, Nelson KBet al., 2023,

    Neonatal Encephalopathy and Hypoxic-Ischemic Encephalopathy: moving from controversy to consensus definitions

    , Pediatric Research, Vol: 94, Pages: 1860-1863, ISSN: 0031-3998

    Neonatal encephalopathy (NE) is a “clinical syndrome of disturbed neurologic function in the first week after birth in an infant born at or beyond 35 weeks of gestation, manifest by a subnormal level of consciousness or seizures, often accompanied by difficulty with initiating and maintaining respiration, and depression of tone and reflexes.”1,2 This broad clinical definition does not specify subgroups, etiology, or guide management.3,4,5 This editorial aims to describe variations in the definition of neonatal encephalopathy and etiological subgroups of NE used in research and clinical practice. Our group aims to develop consensus definitions to improve understanding of diagnosis and treatment and to help improve how families are informed about these conditions.

  • Journal article
    Ramanan A, Modi N, de Wildt S, 2023,

    Improving clinical paediatric research and learning from COVID-19: recommendations by the Conect4Children expert advice group (vol 91, pg 1069, 2021)

    , PEDIATRIC RESEARCH, Vol: 94, Pages: 2121-2121, ISSN: 0031-3998
  • Journal article
    Evans K, Battersby C, Boardman JP, Boyle E, Carroll W, Dinwiddy K, Dorling J, Gallagher K, Hardy P, Johnston E, Mactier H, Marcroft C, Webbe JWH, Gale Cet al., 2023,

    National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the UK

    , Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 108, Pages: 569-574, ISSN: 1359-2998

    BACKGROUND: The provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials. OBJECTIVE: To involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK. DESIGN: Research questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups. PARTICIPANTS: One hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds. RESULTS: Two hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support. CONCLUSIONS: We have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care.

  • Journal article
    Venkatesan T, Rees P, Gardiner J, Battersby C, Purkayastha M, Gale C, Sutcliffe Aet al., 2023,

    National trends in preterm infant mortality in the United States by race and socioeconomic status, 1995-2020

    , JAMA Pediatrics, Vol: 177, Pages: 1085-1095, ISSN: 1072-4710

    Importance Inequalities in preterm infant mortality exist between population subgroups within the United States.Objective To characterize trends in preterm infant mortality by maternal race and socioeconomic status to assess how inequalities in preterm mortality rates have changed over time.Design, Setting, and Participants This was a retrospective longitudinal descriptive study using the US National Center for Health Statistics birth infant/death data set for 12 256 303 preterm infant births over 26 years, between 1995 and 2020. Data were analyzed from December 2022 to March 2023.Exposures Maternal characteristics including race, smoking status, educational attainment, antenatal care, and insurance status were used as reported on an infant’s US birth certificate.Main Outcomes and Measures Preterm infant mortality rate was calculated for each year from 1995 to 2020 for all subgroups, with a trend regression coefficient calculated to describe the rate of change in preterm mortality.Results The average US preterm infant mortality rate (IMR) decreased from 33.71 (95% CI, 33.71 to 34.04) per 1000 preterm births per year between 1995-1997, to 23.32 (95% CI, 23.05 to 23.58) between 2018-2020. Black non-Hispanic infants were more likely to die following preterm births than White non-Hispanic infants (IMR, 31.09; 95% CI, 30.44 to 31.74, vs 21.81; 95% CI, 21.43 to 22.18, in 2018-2020); however, once born, extremely prematurely Black and Hispanic infants had a narrow survival advantage (IMR rate ratio, 0.87; 95% CI, 0.84 to 0.91, in 2018-2020). The rate of decrease in preterm IMR was higher in Black infants (−0.015) than in White (−0.013) and Hispanic infants (−0.010); however, the relative risk of preterm IMR among Black infants compared with White infants remained the same between 1995-1997 vs 2018-2020 (relative risk, 1.40; 95% CI, 1.38 to 1.44, vs 1.43; 95% CI, 1.39 to 1.46). The rate of decrease in preterm IMR was higher in nonsmokers compar

  • Journal article
    Harnden F, Lanoue J, Modi N, Uthaya S, Battersby Cet al., 2023,

    A data-driven approach to understanding neonatal palliative care needs in England and Wales: a population based study 2015-2020

    , Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 108, Pages: 540-544, ISSN: 1359-2998

    ObjectiveTo quantify admissions to neonatal units in England and Wales with potential need for palliative care. Design, setting, and patientsDiagnoses and clinical attributes indicating a high likelihood of requiring palliative care were mapped to categories within the British Association of Perinatal Medicine’s (BAPM) framework on palliative care. We extracted data from the National Neonatal Research Database on all babies born and admitted to neonatal units in England and Wales 2015-2020.OutcomesThe number and proportion of babies meeting BAPM categories, their discharge outcomes, and the characteristics of babies who died during neonatal care but did not fulfil any BAPM category.Results12,123/574,954 (2.1%) babies met one or more BAPM category: 6,239/12,123 (51%) conformed to BAPM category 4 (postnatal conditions with high risk of severe impairment), 3,796 (31%) to category 2 (antenatal/postnatal diagnosis with high risk of significant morbidity or death), 1,399 (12%) to category 3 (born at margin of viability), and 288 (2%) to category 1 (antenatal/postnatal diagnosis not compatible with long-term survival); 401 babies (3%) met criteria for multiple categories. 6,814/12,123 (56%) were discharged home, 2,385 (20%) were discharged to other settings and 2,914 (24%) died before neonatal discharge. 3,000/5,914 (51%) babies who died during neonatal care did not conform to any BAPM category. Of these, 2,630/3,000 (88%) were born preterm.ConclusionsAt least 2% of babies admitted to neonatal units had palliative care needs according to existing BAPM categories; most survived to discharge. Of deaths, 51% were not captured by the BAPM categories; most were extremely preterm.

  • Journal article
    Ali S, Mactier H, Morelli A, Hurd M, Placzek A, Knight M, Ladhani S, Draper E, Sharkey D, Doherty C, Kurinczuk J, Quigley M, Gale Cet al., 2023,

    Neonatal outcomes of maternal SARS-CoV-2 infection in the UK: a prospective cohort study using active surveillance

    , Pediatric Research, Vol: 94, Pages: 1203-1208, ISSN: 0031-3998

    Background:Newborns may be affected by maternal SARS-CoV-2 infection during pregnancy. We aimed to describe the epidemiology, clinical course and short-term outcomes of babies admitted to a neonatal unit (NNU) following birth to a mother with confirmed SARS-CoV-2 infection within 7 days of birth.Methods:This is a UK prospective cohort study; all NHS NNUs, 1 March 2020 to 31 August 2020. Cases were identified via British Paediatric Surveillance Unit with linkage to national obstetric surveillance data. Reporting clinicians completed data forms. Population data were extracted from the National Neonatal Research Database.Results:A total of 111 NNU admissions (1.98 per 1000 of all NNU admissions) involved 2456 days of neonatal care (median 13 [IQR 5, 34] care days per admission). A total of 74 (67%) babies were preterm. In all, 76 (68%) received respiratory support; 30 were mechanically ventilated. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy. Twenty-eight mothers received intensive care, with four dying of COVID-19. Eleven (10%) babies were SARS-CoV-2 positive. A total of 105 (95%) babies were discharged home; none of the three deaths before discharge was attributed to SARS-CoV-2.Conclusion:Babies born to mothers with SARS-CoV-2 infection around the time of birth accounted for a low proportion of total NNU admissions over the first 6 months of the UK pandemic. Neonatal SARS-CoV-2 was uncommon.Study registration:ISRCTN60033461; protocol available at http://www.npeu.ox.ac.uk/pru-mnhc/research-themes/theme-4/covid-19.

  • Journal article
    Nezafat Maldonado B, Singhal G, Chow LY, Hargreaves D, Gale C, Battersby Cet al., 2023,

    Association between birth location and short-term outcomes for babies with gastroschisis, congenital diaphragmatic hernia and oesophageal fistula: a systematic review

    , BMJ Paediatrics Open, Vol: 7, Pages: 1-14, ISSN: 2399-9772

    Background Neonatal care is commonly regionalised, meaning specialist services are only available at certain units. Consequently, infants with surgical conditions needing specialist care who are born in non-surgical centres require postnatal transfer. Best practice models advocate for colocated maternity and surgical services as the place of birth for infants with antenatally diagnosed congenital conditions to avoid postnatal transfers. We conducted a systematic review to explore the association between location of birth and short-term outcomes of babies with gastroschisis, congenital diaphragmatic hernia (CDH) and oesophageal atresia with or without tracheo-oesophageal fistula (TOF/OA).Methods We searched MEDLINE, CINAHL, Web of Science and SCOPUS databases for studies from high income countries comparing outcomes for infants with gastroschisis, CDH or TOF/OA based on their place of delivery. Outcomes of interest included mortality, length of stay, age at first feed, comorbidities and duration of parenteral nutrition. We assessed study quality using the Newcastle-Ottawa Scale. We present a narrative synthesis of our findings.Results Nineteen cohort studies compared outcomes of babies with one of gastroschisis, CDH or TOF/OA. Heterogeneity across the studies precluded meta-analysis. Eight studies carried out case-mix adjustments. Overall, we found conflicting evidence. There is limited evidence to suggest that birth in a maternity unit with a colocated surgical centre was associated with a reduction in mortality for CDH and decreased length of stay for gastroschisis.Conclusions There is little evidence to suggest that delivery in colocated maternity-surgical services may be associated with shortened length of stay and reduced mortality. Our findings are limited by significant heterogeneity, potential for bias and paucity of strong evidence. This supports the need for further research to investigate the impact of birth location on outcomes for babies with congenital

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