Schizophrenia and type 2 diabetes: Perceptions and understandings of illness management in everyday life.

People with schizophrenia and type 2 diabetes face complex challenges in daily life and the management of both illnesses is burdensome. This qualitative interview study aimed to explore perceptions and understandings of the day-to-day management of schizophrenia and type 2 diabetes. Fourteen semi-structured interviews were conducted between January 2020 and October 2021 in the participants' respective mental health clinics, in their homes or by phone. Thematic analysis led to four themes representing participants' self-management strategies and perceived challenges. The first theme showed that participants use self-learned strategies for managing schizophrenia. In contrast, they perceived type 2 diabetes self-management as governed by a set of rules and guidelines given by health professionals. The second theme showed that both psychotic and negative symptoms present challenges to diabetes management. Theme 3 illustrated that participants consider their type 2 diabetes to be a very serious illness. They worried about potential long-term consequences and expressed wishes and motivation to improve their lifestyle. The final theme showed that participants discuss challenges related to their schizophrenia with family and friends but not type 2 diabetes. In conclusion, this study highlights the importance of considering individual challenges and everyday routines when supporting this population. It underlines the need for future research to further explore the complexity of managing the illnesses and to understand the needs for treatment and support.

Strengthening the clinical academic pathway: a systematic review of interventions to support clinical academic careers for doctors and dentists.

OBJECTIVE: Evaluate existing evidence on interventions intended to increase recruitment, retention and career progression within clinical academic (CA) careers, including a focus on addressing inequalities. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane Controlled Register of Trials, PsycINFO and Education Resource Information Center searched October 2019. STUDY SELECTION: Eligible studies included qualified doctors, dentists and/or those with a supervisory role. Outcomes were defined by studies and related to success rates of joining or continuing within a CA career. DATA EXTRACTION AND SYNTHESIS: Abstract screening was supported by machine learning software. Full-text screening was performed in duplicate, and study quality was assessed. Narrative synthesis of quantitative data was performed. Qualitative data were thematically analysed. RESULTS: 148 studies examined interventions; of which 28 were included in the quantitative synthesis, 17 in the qualitative synthesis and 2 in both. Studies lacked methodological rigour and/or were hindered by incomplete reporting. Most were from North America. No study included in the syntheses evaluated interventions aimed at CA dentists.Most quantitative evidence was from multifaceted training programmes. These may increase recruitment, but findings were less clear for retention and other outcomes. Qualitative studies reported benefits of supportive relationships, including peers and senior mentors. Protected time for research helped manage competing demands on CAs. Committed and experienced staff were seen as key facilitators of programme success. Respondents identified several other factors at a programme, organisational or national level which acted as facilitators or barriers to success. Few studies reported on the effects of interventions specific to women or minority groups. CONCLUSIONS: Existing research is limited by rigour and reporting. Better evaluation of future interventions, particularly those intended to address inequalities, is required. Within the limits of the evidence, comprehensive multifaceted programmes of training, including protected time, relational and support aspects, appear most successful in promoting CA careers. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework: https://osf.io/mfy7a.

Antidepressant treatment for postnatal depression.

BACKGROUND: Depression is one of the most common morbidities of the postnatal period. It has been associated with adverse outcomes for women, children, the wider family and society as a whole. Treatment is with psychosocial interventions or antidepressant medication, or both. The aim of this review is to evaluate the effectiveness of different antidepressants and to compare their effectiveness with placebo, treatment as usual or other forms of treatment. This is an update of a review last published in 2014. OBJECTIVES: To assess the effectiveness and safety of antidepressant drugs in comparison with any other treatment (psychological, psychosocial, or pharmacological), placebo, or treatment as usual for postnatal depression. SEARCH METHODS: We searched Cochrane Common Mental Disorders's Specialized Register, CENTRAL, MEDLINE, Embase and PsycINFO in May 2020. We also searched international trials registries and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with depression during the first 12 months postpartum that compared antidepressant treatment (alone or in combination with another treatment) with any other treatment, placebo or treatment as usual. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the study reports. We requested missing information from study authors wherever possible. We sought data to allow an intention-to-treat analysis. Where we identified sufficient comparable studies we pooled data and conducted random-effects meta-analyses. MAIN RESULTS: We identified 11 RCTs (1016 women), the majority of which were from English-speaking, high-income countries; two were from middle-income countries. Women were recruited from a mix of community-based, primary care, maternity and outpatient settings. Most studies used selective serotonin reuptake inhibitors (SSRIs), with treatment duration ranging from 4 to 12 weeks. Meta-analysis showed that there may be a benefit of SSRIs over placebo in response (55% versus 43%; pooled risk ratio (RR) 1.27, 95% confidence interval (CI) 0.97 to 1.66); remission (42% versus 27%; RR 1.54, 95% CI 0.99 to 2.41); and reduced depressive symptoms (standardised mean difference (SMD) -0.30, 95% CI -0.55 to -0.05; 4 studies, 251 women), at 5 to 12 weeks' follow-up. We were unable to conduct meta-analysis for adverse events due to variation in the reporting of this between studies. There was no evidence of a difference between acceptability of SSRI and placebo (27% versus 27%; RR 1.10, 95% CI 0.74 to 1.64; 4 studies; 233 women). The certainty of all the evidence for SSRIs was low or very low due to the small number of included studies and a number of potential sources of bias, including high rates of attrition. There was insufficient evidence to assess the efficacy of SSRIs compared with other classes of antidepressants and of antidepressants compared with other pharmacological interventions, complementary medicines, psychological and psychosocial interventions or treatment as usual. A substantial proportion of women experienced adverse effects but there was no evidence of differences in the number of adverse effects between treatment groups in any of the studies. Data on effects on children, including breastfed infants, parenting, and the wider family were limited, although no adverse effects were noted. AUTHORS' CONCLUSIONS: There remains limited evidence regarding the effectiveness and safety of antidepressants in the management of postnatal depression, particularly for those with more severe depression. We found low-certainty evidence that SSRI antidepressants may be more effective in treating postnatal depression than placebo as measured by response and remission rates. However, the low certainty of the evidence suggests that further research is very likely to have an important impact on our effect estimate. There is a continued imperative to better understand whether, and for whom, antidepressants or other treatments are more effective for postnatal depression, and whether some antidepressants are more effective or better tolerated than others. In clinical practice, the findings of this review need to be contextualised by the extensive broader literature on antidepressants in the general population and perinatal clinical guidance, to inform an individualised risk-benefit clinical decision. Future RCTs should focus on larger samples, longer follow-up, comparisons with alternative treatment modalities and inclusion of child and parenting outcomes.

Early full enteral feeding for preterm or low birth weight infants.

BACKGROUND: The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not be well tolerated or may increase the risk of necrotising enterocolitis. Early full enteral feeding, however, might increase nutrient intake and growth rates; accelerate intestinal physiological, metabolic, and microbiomic postnatal transition; and reduce the risk of complications associated with intravascular devices for fluid administration.  OBJECTIVES: To determine how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth and adverse events such as necrotising enterocolitis, in preterm or low birth weight infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials; MEDLINE Ovid, Embase Ovid, Maternity & Infant Care Database Ovid, the Cumulative Index to Nursing and Allied Health Literature, and clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials to October 2020. SELECTION CRITERIA: Randomised controlled trials that compared early full enteral feeding with delayed or progressive introduction of enteral feeds in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately assessed trial eligibility, evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RR), risk differences, and mean differences (MD) with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included six trials. All were undertaken in the 2010s in neonatal care facilities in India. In total, 526 infants participated. Most were very preterm infants of birth weight between 1000 g and 1500 g. Trials were of good methodological quality, but a potential source of bias was that parents, clinicians, and investigators were not masked. The trials compared early full feeding (60 mL/kg to 80 mL/kg on day one after birth) with minimal enteral feeding (typically 20 mL/kg on day one) supplemented with intravenous fluids. Feed volumes were advanced daily as tolerated by 20 mL/kg to 30 mL/kg body weight to a target steady-state volume of 150 mL/kg to 180 mL/kg/day. All participating infants were fed preferentially with maternal expressed breast milk, with two trials supplementing insufficient volumes with donor breast milk and four supplementing with preterm formula.  Few data were available to assess growth parameters. One trial (64 participants) reported a slower rate of weight gain (median difference -3.0 g/kg/day), and another (180 participants) reported a faster rate of weight gain in the early full enteral feeding group (MD 1.2 g/kg/day). We did not meta-analyse these data (very low-certainty evidence). None of the trials reported rate of head circumference growth. One trial reported that the mean z-score for weight at hospital discharge was higher in the early full enteral feeding group (MD 0.24, 95% CI 0.06 to 0.42; low-certainty evidence). Meta-analyses showed no evidence of an effect on necrotising enterocolitis (RR 0.98, 95% CI 0.38 to 2.54; 6 trials, 522 participants; I² = 51%; very low-certainty evidence). AUTHORS' CONCLUSIONS: Trials provided insufficient data to determine with any certainty how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth in preterm or low birth weight infants. We are uncertain whether early full enteral feeding affects the risk of necrotising enterocolitis because of the risk of bias in the trials (due to lack of masking), inconsistency, and imprecision.

Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis.

Importance: Rapid and accurate diagnosis of late-onset infection in newborn infants could inform treatment decisions and avoid unnecessary administration of antibiotics. Objective: To compare the accuracy of serum C-reactive protein (CRP) with that of microbiological blood culture for diagnosing late-onset infection in newborns. Data Sources: MEDLINE (1946-2019), Embase (1946-2019), and Science Citation Index (1900-2019) databases were searched for references (any language). The MeSH search terms included were "exp infant, newborn/" or "premature birth/" plus free text synonyms; and "C-reactive protein/" plus free text synonyms; and "exp sepsis/" or "exp bacterial infections/" plus free text synonyms. The proceedings from relevant conferences and references of identified papers were scrutinized. Authors were contacted to request missing data. Study Selection: Cohort and cross-sectional studies were included that compared the accuracy of serum CRP levels with microbiological culture results to diagnose late-onset (>72 hours after birth) infection in newborns (any gestational age) hospitalized after birth. Two reviewers assessed study eligibility. Among 10 394 records, 148 studies were assessed as full texts. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline extension for Diagnostic Test Accuracy (DTA) reviews was followed. Two reviewers assessed the method quality of each study using guidance from the Cochrane Screening and Diagnostic Test Methods Group (adapted from the Quality Assessment of Diagnostic Accuracy Studies 2). Main Outcomes and Measures: The primary meta-analysis outcome was diagnostic test accuracy of serum CRP level taken at initial investigation of an infant with suspected late-onset infection. The median specificity (proportion of true-negative results) and calculated pooled sensitivity (proportion of true-positive results) were determined by generating hierarchical summary receiver characteristic operating curves. Results: In total, 22 studies with 2255 infants were included (sample size range, 11-590 infants). Participants in most studies were preterm (<37 weeks) or very low-birth weight (<1500 g) infants. Two studies additionally enrolled infants born at term. Most studies (16) used a prespecified CRP level cutoff for a "positive" index test (5-10 mg/L), and most studies (17) used the culture of a pathogenic microorganism from blood as the reference standard. Risk of bias was low with independent assessment of index and reference tests. At median specificity (0.74), pooled sensitivity was 0.62 (95% CI, 0.50-0.72). Adding serum CRP level to the assessment of an infant with a 40% pretest probability of late-onset infection (the median for the included studies) generated posttest probabilities of 26% for a negative test result and 61% for a positive test result. Conclusions and Relevance: The findings suggest that determination of serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to aid early diagnosis or to select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.

Pharmacy-based management for depression in adults.

BACKGROUND: It is common for peoples not to take antidepressant medication as prescribed, with around 50% of people likely to prematurely discontinue taking their medication after six months. Community pharmacists may be well placed to have a role in antidepressant management because of their unique pharmacotherapeutic knowledge and ease of access for people. Pharmacists are in an ideal position to offer proactive interventions to people with depression or depressive symptoms. However, the effectiveness and acceptability of existing pharmacist-based interventions is not yet well understood. The degree to which a pharmacy-based management approach might be beneficial, acceptable to people, and effective as part of the overall management for those with depression is, to date, unclear. A systematic review of randomised controlled trials (RCTs) will help answer these questions and add important knowledge to the currently sparse evidence base. OBJECTIVES: To examine the effects of pharmacy-based management interventions compared with active control (e.g. patient information materials or any other active intervention delivered by someone other than the pharmacist or the pharmacy team), waiting list, or treatment as usual (e.g. standard pharmacist advice or antidepressant education, signposting to support available in primary care services, brief medication counselling, and/or (self-)monitoring of medication adherence offered by a healthcare professional outside the pharmacy team) at improving depression outcomes in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR) to June 2016; the Cochrane Library (Issue 11, 2018); and Ovid MEDLINE, Embase, and PsycINFO to December 2018. We searched theses and dissertation databases and international trial registers for unpublished/ongoing trials. We applied no restrictions on date, language, or publication status to the searches.  SELECTION CRITERIA: We included all RCTs and cluster-RCTs where a pharmacy-based intervention was compared with treatment as usual, waiting list, or an alternative intervention in the management of depression in adults over 16 years of age. Eligible studies had to report at least one of the following outcomes at any time point: depression symptom change, acceptability of the intervention, diagnosis of depression, non-adherence to medication, frequency of primary care appointments, quality of life, social functioning, or adverse events.  DATA COLLECTION AND ANALYSIS: Two authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment (including GRADE). We discussed disagreements within the team until we reached consensus. Where data did not allow meta-analyses, we synthesised results narratively.  MAIN RESULTS: Twelve studies (2215 participants) met the inclusion criteria and compared pharmacy-based management with treatment as usual. Two studies (291 participants) also included an active control (both used patient information leaflets providing information about the prescribed antidepressant). Neither of these studies reported depression symptom change. A narrative synthesis of results on acceptability of the intervention was inconclusive, with one study reporting better acceptability of pharmacy-based management and the other better acceptability of the active control. One study reported that participants in the pharmacy-based management group had better medication adherence than the control participants. One study reported adverse events with no difference between groups. The studies reported no other outcomes. Meta-analyses comparing pharmacy-based management with treatment as usual showed no evidence of a difference in the effect of the intervention on depression symptom change (dichotomous data; improvement in symptoms yes/no: risk ratio (RR), 0.95, 95% confidence interval (CI) 0.86 to 1.05; 4 RCTs, 475 participants; moderate-quality evidence; continuous data: standard mean difference (SMD) -0.04, 95% CI -0.19 to 0.10; 5 RCTs, 718 participants; high-certainty evidence), or acceptability of the intervention (RR 1.09, 95% CI 0.81 to 1.45; 12 RCTs, 2072 participants; moderate-certainty evidence). The risk of non-adherence was reduced in participants receiving pharmacy-based management (RR 0.73, 95% CI 0.61 to 0.87; 6 RCTs, 911 participants; high-certainty evidence). We were unable to meta-analyse data on diagnosis of depression, frequency of primary care appointments, quality of life, or social functioning. AUTHORS' CONCLUSIONS: We found no evidence of a difference between pharmacy-based management for depression in adults compared with treatment as usual in facilitating depression symptom change. Based on numbers of participants leaving the trials early, there may be no difference in acceptability between pharmacy-based management and controls. However, there was uncertainty due to the low-certainty evidence.

Formula versus maternal breast milk for feeding preterm or low birth weight infants.

BACKGROUND: Artificial formula can be manipulated to contain higher amounts of macro-nutrients than maternal breast milk but breast milk confers important immuno-nutritional advantages for preterm or low birth weight (LBW) infants. OBJECTIVES: To determine the effect of feeding preterm or LBW infants with formula compared with maternal breast milk on growth and developmental outcomes. SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), and Ovid MEDLINE, Ovid Embase, Ovid Maternity & Infant Care Database, and CINAHL to October 2018. We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared feeding preterm or low birth weight infants with formula versus maternal breast milk. DATA COLLECTION AND ANALYSIS: Two review authors planned independently to assess trial eligibility and risk of bias, and extract data. We planned to analyse treatment effects as described in the individual trials and report risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with 95% confidence intervals. We planned to use a fixed-effect model in meta-analyses and to explore potential causes of heterogeneity in subgroup analyses. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We did not identify any eligible trials. AUTHORS' CONCLUSIONS: There are no trials of formula versus maternal breast milk for feeding preterm or low birth weight infants. Such trials are unlikely to be conducted because of the difficulty of allocating an alternative form of nutrition to an infant whose mother wishes to feed with her own breast milk. Maternal breast milk remains the default choice of enteral nutrition because observational studies, and meta-analyses of trials comparing feeding with formula versus donor breast milk, suggest that feeding with breast milk has major immuno-nutritional advantages for preterm or low birth weight infants.

Nutrient-enriched formula versus standard formula for preterm infants.

BACKGROUND: Preterm infants may accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with nutrient-enriched rather than standard formula might increase nutrient accretion and growth rates and might improve neurodevelopmental outcomes. OBJECTIVES: To compare the effects of feeding with nutrient-enriched formula versus standard formula on growth and development of preterm infants. SEARCH METHODS: We used the Cochrane Neonatal standard search strategy. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (until November 2018), as well as conference proceedings, previous reviews, and clinical trials databases. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared feeding preterm infants with nutrient-enriched formula (protein and energy plus minerals, vitamins, or other nutrients) versus standard formula. DATA COLLECTION AND ANALYSIS: We extracted data using the Cochrane Neonatal standard methods. Two review authors separately evaluated trial quality and extracted and synthesised data using risk ratios (RRs), risk differences, and mean differences (MDs). We assessed certainty of evidence at the outcome level using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We identified seven trials in which a total of 590 preterm infants participated. Most participants were clinically stable preterm infants of birth weight less than 1850 g. Few participants were extremely preterm, extremely low birth weight, or growth restricted at birth. Trials were conducted more than 30 years ago, were formula industry funded, and were small with methodological weaknesses (including lack of masking) that might bias effect estimates. Meta-analyses of in-hospital growth parameters were limited by statistical heterogeneity. There is no evidence of an effect on time to regain birth weight (MD -1.48 days, 95% confidence interval (CI) -4.73 to 1.77) and low-certainty evidence suggests that feeding with nutrient-enriched formula increases in-hospital rates of weight gain (MD 2.43 g/kg/d, 95% CI 1.60 to 3.26) and head circumference growth (MD 1.04 mm/week, 95% CI 0.18 to 1.89). Meta-analysis did not show an effect on the average rate of length gain (MD 0.22 mm/week, 95% CI -0.70 to 1.13). Fewer data are available for growth and developmental outcomes assessed beyond infancy, and these do not show consistent effects of nutrient-enriched formula feeding. Data from two trials did not show an effect on Bayley Mental Development Index scores at 18 months post term (MD 2.87, 95% CI -1.38 to 7.12; moderate-certainty evidence). Infants who received nutrient-enriched formula had higher Bayley Psychomotor Development Index scores at 18 months post term (MD 6.56. 95% CI 2.87 to 10.26; low-certainty evidence), but no evidence suggested an effect on cerebral palsy (typical RR 0.79, 95% CI 0.30 to 2.07; 2 studies, 377 infants). Available data did not indicate any other benefits or harms and provided low-certainty evidence about the effect of nutrient-enriched formula feeding on the risk of necrotising enterocolitis in preterm infants (typical RR 0.72, 95% CI 0.41 to 1.25; 3 studies, 489 infants). AUTHORS' CONCLUSIONS: Available trial data show that feeding preterm infants nutrient-enriched (compared with standard) formulas has only modest effects on growth rates during their initial hospital admission. No evidence suggests effects on long-term growth or development. The GRADE assessment indicates that the certainty of this evidence is low, and that these findings should be interpreted and applied with caution. Further randomised trials would be needed to resolve this uncertainty.

Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants.

BACKGROUND: Parenteral nutrition solutions, artificial formulas, and human breast milk contain insufficient iodine to meet recommended intakes for preterm infants. Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants and this may be associated with adverse neonatal and longer-term outcomes. OBJECTIVES: To assess the evidence from randomised controlled trials that dietary supplementation with iodine reduces mortality and morbidity in preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 1), Ovid MEDLINE, Ovid Embase, Ovid Maternity & Infant Care Database, and CINAHL to February 2018. We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared supplementing enteral or parenteral feeds with iodine (as iodide salt) versus placebo or no supplementation in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. We analysed treatment effects as described in the individual trials and reported risk ratios (RR) and risk differences for dichotomous data, and mean differences (MD) for continuous data, with 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and planned to explore potential causes of heterogeneity in sensitivity analyses. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Two randomised controlled trials fulfilled the eligibility criteria. Both trials used methods to limit bias including allocation concealment and blinding of clinicians and investigators to the allocated intervention. The trials enrolled 1394 infants. One trial recruited 1273 participants. Most participants were born very preterm (less than 32 weeks' gestation) and about one-third were extremely preterm (less than 28 weeks' gestation). Analyses found no effect of iodine supplementation on mortality before hospital discharge (typical RR 1.01, 95% CI 0.72 to 1.42; 2 studies, 1380 infants) or on neurodevelopmental assessments at two years post-term (Bayley Scales of Infant and Toddler Development, Third Edition main domain composite scores: cognitive: MD -0.30, 95% CI -2.44 to 1.84; motor: MD 0.20, 95% CI -2.15 to 2.55; language: MD -0.10, 95% CI -2.50 to 2.30; 1 study, 1259 infants). There were no differences in the proportion of infants who died or had a composite score less than 85 in any main Bayley domain (RR 1.05, 95% CI 0.94 to 1.17; 1 study, 1259 infants), or had visual impairment (RR 0.63, 95% CI 0.28 to 1.45; 1 study, 1092 infants) or auditory impairment (RR 1.05, 95% CI 0.51 to 2.16; 1 study, 1093 infants). Using GRADE methods, we assessed the evidence for the effects on mortality and neurodevelopment outcomes as high-certainty. AUTHORS' CONCLUSIONS: The available trial data, predominantly from one large, high-quality multicentre study published in 2017, do not show any evidence of beneficial effects of iodine supplementation for preterm infants. Given the high certainty of these estimates of effect, further trials of this intervention in this population are unlikely to be considered research priorities.

C-reactive protein for diagnosing late-onset infection in newborn infants.

BACKGROUND: Late-onset infection is the most common serious complication associated with hospital care for newborn infants. Because confirming the diagnosis by microbiological culture typically takes 24 to 48 hours, the serum level of the inflammatory marker C-reactive protein (CRP) measured as part of the initial investigation is used as an adjunctive rapid test to guide management in infants with suspected late-onset infection. OBJECTIVES: To determine the diagnostic accuracy of serum CRP measurement in detecting late-onset infection in newborn infants. SEARCH METHODS: We searched electronic databases (MEDLINE, Embase, and Science Citation Index to September 2017), conference proceedings, previous reviews, and the reference lists of retrieved articles. SELECTION CRITERIA: We included cohort and cross-sectional studies evaluating the diagnostic accuracy of serum CRP levels for the detection of late-onset infection (occurring more than 72 hours after birth) in newborn infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility for inclusion, evaluated the methodological quality of included studies, and extracted data to estimate diagnostic accuracy using hierarchical summary receiver operating characteristic (SROC) models. We assessed heterogeneity by examining variability of study estimates and overlap of the 95% confidence interval (CI) in forest plots of sensitivity and specificity. MAIN RESULTS: The search identified 20 studies (1615 infants). Most were small, single-centre, prospective cohort studies conducted in neonatal units in high- or middle-income countries since the late 1990s. Risk of bias in the included studies was generally low with independent assessment of index and reference tests. Most studies used a prespecified serum CRP threshold level as the definition of a 'positive' index test (typical cut-off level between 5 mg/L and 10 mg/L) and the culture of a pathogenic micro-organism from blood as the reference standard.At median specificity (0.74), sensitivity was 0.62 (95% CI 0.50 to 0.73). Heterogeneity was evident in the forest plots but it was not possible to conduct subgroup or meta-regression analyses by gestational ages, types of infection, or types of infecting micro-organism. Covariates for whether studies used a predefined threshold or not, and whether studies used a standard threshold of between 5 mg/L and 10 mg/L, were not statistically significant. AUTHORS' CONCLUSIONS: The serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to be considered sufficiently accurate to aid early diagnosis or select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.

Naloxone for opioid-exposed newborn infants.

BACKGROUND: Naloxone, a specific opioid antagonist, is available for the treatment of newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. It is unclear whether newborn infants may benefit from this therapy and whether naloxone has any harmful effects. OBJECTIVES: To determine the effect of naloxone on the need for and duration of neonatal unit stay in infants of mothers who received opioid analgesia prior to delivery or of mothers who have used a prescribed or non-prescribed opioid during pregnancy. SEARCH METHODS: We searched the following databases in February 2018: the Cochrane Central Register of Controlled Trials (the Cochrane Library 2018, Issue 1), MEDLINE (OvidSP), MEDLINE In process & Other Non-Indexed Citations (OvidSP), Embase (OvidSP), CINAHL (EBSCO), Maternity and Infant Care (OvidSP), and PubMed. We searched for ongoing and completed trials in the WHO International Clinical Trials Registry Platform and the EU Clinical Trials Register. We checked the reference lists of relevant articles to identify further potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials comparing the administration of naloxone versus placebo, or no drug, or another dose of naloxone to newborn infants with suspected or confirmed in utero exposure to opioid. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Neonatal with separate evaluation of trial quality and data extraction by two review authors and synthesis of data using risk ratio, risk difference, and mean difference. MAIN RESULTS: We included nine trials, with 316 participants in total, that compared the effects of naloxone versus placebo or no drug in newborn infants exposed to maternal opioid analgesia prior to delivery. None of the included trials investigated infants born to mothers who had used a prescribed or non-prescribed opioid during pregnancy. None of these trials specifically recruited infants with cardiorespiratory or neurological depression. The main outcomes reported were measures of respiratory function in the first six hours after birth. There is some evidence that naloxone increases alveolar ventilation. The trials did not assess the effect on the primary outcomes of this review (admission to a neonatal unit and failure to establish breastfeeding). AUTHORS' CONCLUSIONS: The existing evidence from randomised controlled trials is insufficient to determine whether naloxone confers any important benefits to newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. Given concerns about the safety of naloxone in this context, it may be appropriate to limit its use to randomised controlled trials that aim to resolve these uncertainties.