Support for healthy breastfeeding mothers with healthy term babies.

BACKGROUND: There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended that infants be breastfed exclusively until six months of age, with breastfeeding continuing as an important part of the infant's diet until at least two years of age. However, current breastfeeding rates in many countries do not reflect this recommendation. OBJECTIVES: 1. To describe types of breastfeeding support for healthy breastfeeding mothers with healthy term babies. 2. To examine the effectiveness of different types of breastfeeding support interventions in terms of whether they offered only breastfeeding support or breastfeeding support in combination with a wider maternal and child health intervention ('breastfeeding plus' support).  3. To examine the effectiveness of the following intervention characteristics on breastfeeding support:      a. type of support (e.g. face-to-face, telephone, digital technologies, group or individual support, proactive or reactive);      b. intensity of support (i.e. number of postnatal contacts);      c. person delivering the intervention (e.g. healthcare professional, lay person);     d. to examine whether the impact of support varied between high- and low-and middle-income countries. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (which includes results of searches of CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP)) (11 May 2021) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. Support could be provided face-to-face, over the phone or via digital technologies. All studies had to meet the trustworthiness criteria.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods. Two review authors independently selected trials, extracted data, and assessed risk of bias and study trustworthiness.  The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: This updated review includes 116 trials of which 103 contribute data to the analyses. In total more than 98,816 mother-infant pairs were included.  Moderate-certainty evidence indicated that 'breastfeeding only' support probably reduced the number of women stopping breastfeeding for all primary outcomes: stopping any breastfeeding at six months (Risk Ratio (RR) 0.93, 95% Confidence Interval (CI) 0.89 to 0.97); stopping exclusive breastfeeding at six months (RR 0.90, 95% CI 0.88 to 0.93); stopping any breastfeeding at 4-6 weeks (RR 0.88, 95% CI 0.79 to 0.97); and stopping exclusive breastfeeding at 4-6 (RR 0.83 95% CI 0.76 to 0.90). Similar findings were reported for the secondary breastfeeding outcomes except for any breastfeeding at two months and 12 months when the evidence was uncertain if 'breastfeeding only' support helped reduce the number of women stopping breastfeeding.  The evidence for 'breastfeeding plus' was less consistent. For primary outcomes there was some evidence that 'breastfeeding plus' support probably reduced the number of women stopping any breastfeeding (RR 0.94, 95% CI 0.91 to 0.97, moderate-certainty evidence) or exclusive breastfeeding at six months (RR 0.79, 95% CI 0.70 to 0.90).  'Breastfeeding plus' interventions may have a beneficial effect on reducing the number of women stopping exclusive breastfeeding at 4-6 weeks, but the evidence is very uncertain (RR 0.73, 95% CI 0.57 to 0.95). The evidence suggests that 'breastfeeding plus' support probably results in little to no difference in the number of women stopping any breastfeeding at 4-6 weeks (RR 0.94, 95% CI 0.82 to 1.08, moderate-certainty evidence). For the secondary outcomes, it was uncertain if 'breastfeeding plus' support helped reduce the number of women stopping any or exclusive breastfeeding at any time points.  There were no consistent findings emerging from the narrative synthesis of the non-breastfeeding outcomes (maternal satisfaction with care, maternal satisfaction with feeding method, infant morbidity, and maternal mental health), except for a possible reduction of diarrhoea in intervention infants.  We considered the overall risk of bias of trials included in the review was mixed. Blinding of participants and personnel is not feasible in such interventions and as studies utilised self-report breastfeeding data, there is also a risk of bias in outcome assessment.   We conducted meta-regression to explore substantial heterogeneity for the primary outcomes using the following categories: person providing care; mode of delivery; intensity of support; and income status of country.  It is possible that moderate levels (defined as 4-8 visits) of 'breastfeeding only' support may be associated with a more beneficial effect on exclusive breastfeeding at 4-6 weeks and six months. 'Breastfeeding only' support may also be more effective in reducing women in low- and middle-income countries (LMICs) stopping exclusive breastfeeding at six months compared to women in high-income countries (HICs). However, no other differential effects were found and thus heterogeneity remains largely unexplained. The meta-regression suggested that there were no differential effects regarding person providing support or mode of delivery, however, power was limited.  AUTHORS' CONCLUSIONS: When 'breastfeeding only' support is offered to women, the duration and in particular, the exclusivity of breastfeeding is likely to be increased. Support may also be more effective in reducing the number of women stopping breastfeeding at three to four months compared to later time points.  For 'breastfeeding plus' interventions the evidence is less certain. Support may be offered either by professional or lay/peer supporters, or a combination of both. Support can also be offered face-to-face, via telephone or digital technologies, or a combination and may be more effective when delivered on a schedule of four to eight visits. Further work is needed to identify components of the effective interventions and to deliver interventions on a larger scale.

Prevention of Morbidity in Sickle Cell Disease (POMS2a)-overnight auto-adjusting continuous positive airway pressure compared with nocturnal oxygen therapy: a randomised crossover pilot study examining patient preference and safety in adults and children.

DESIGN: This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology. METHODS: Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation. RESULTS: Ten adults (three female, median age 30.2 years, range 18-51.5 years) and eleven children (five female, median age 12 years, range 8.7-16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6-81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference -3.2 g/L (95% CI -6.0 to -0.2 g/L) and -2.5 g/L (95% CI -4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (-1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI -0.116 to 0.401) days additional pain with APAP compared with NOT. CONCLUSION: In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain. TRIAL REGISTRATION: ISRCTN46078697 . Registered on 18 July 2014.

Chest radiographs versus CT for the detection of rib fractures in children (DRIFT): a diagnostic accuracy observational study.

BACKGROUND: Internationally, chest radiography is the standard investigation for identifying rib fractures in suspected physical abuse in infants. Several small observation studies in children have found that chest CT can provide greater accuracy than radiography for fracture detection, potentially aiding medicolegal proceedings in abuse cases; however, to our knowledge, this greater accuracy has not been comprehensively evaluated. We aimed to determine differences in rib fracture detection rates between post-mortem chest radiographs and chest CT images, using forensic autopsy as the reference standard. METHODS: In this retrospective diagnostic accuracy study, we searched the Great Ormond Street Hospital (London, UK) radiology information system for all children aged 0-16 years who had a post-mortem skeletal survey (ie, full-body radiography), CT, and full autopsy between Jan 1, 2012, and Jan 1, 2017, for a purpose of death investigation. Cases were excluded if the imaging was done for a reason other than a forensic investigation or if image quality was suboptimal. Radiologists were recruited as reporters on a voluntary basis via membership databases from international radiology and post-mortem imaging societies with no specific inclusion or exclusion criteria. Reporters were sent a set of chest radiographs on a password protected and encrypted USB flash drive or via a secure filesharing website and independently reported on the presence of rib fractures, fracture location, and the confidence level of their interpretation. They were masked to the clinical information of the images. 1 month later, the same reporters were sent CTs for the same cases in a random order and asked to report on the same features. The primary objective was to compare the accuracy of detection of rib fractures by use of post-mortem chest radiographs and CTs, with autopsy data as reference standard. Accuracy was assessed by comparison of diagnostic statistics, calculated using random-intercept multilevel logistic models with reporter and patient included as cross-classified random-effects. FINDINGS: 25 cases of children (aged 1 month to 7 years), with 136 rib fractures at autopsy with paired post-mortem chest radiographs and CTs, were selected for analysis. 38 radiologists were recruited as reporters from 23 international centres; 12 (32%) were consultants, median experience of 14·5 years (range 6-27), and 26 (68%) were registrars, median experience of 4 years (range 2-9). Across all radiologists, three times as many rib fractures were correctly detected by use of chest CTs compared with chest radiography (sensitivity 44·9% [95% CI 31·7-58·9] vs 13·5% [8·1-21·5]; difference 31·4% [23·3-37·8; p<0·001]). Sensitivity for detection on the correct rib was higher by use of CT than by use of radiography (62·4% [95% CI 44·9-77·1] vs 23·1% [12·9-37·8]; difference 39·3% [31·9-42·2; p<0·001]), as was diagnosis of a patient with any rib fracture or fractures (81·5% [75·8-86·0] vs 64·7% [57·3-71·4]; difference 16·7% [11·5-22·2; p<0·001]). Radiologist confidence was higher when using CT images than radiographs (highest confidence rating given on 3317 [63·6%] of 5218 fractures for CT vs 1518 [46·6%] of 3303 on radiographs) and was a predictor for accurate fracture detection. INTERPRETATION: Chest CT provides greater accuracy than conventional chest radiography for post-mortem rib fracture detection, irrespective of radiologist experience or fracture location, although both methods detected a substantial number of false positives. The diagnostic accuracy of CT should be studied further in live children ideally in a multicentre trial to assess the applicability of our results. FUNDING: Great Ormond Street Children's Charity, Medical Research Council, Royal College of Radiologists, Research Councils UK, National Institute for Health Research.

Support for healthy breastfeeding mothers with healthy term babies.

BACKGROUND: There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended that infants be breastfed exclusively until six months of age, with breastfeeding continuing as an important part of the infant's diet until at least two years of age. However, current breastfeeding rates in many countries do not reflect this recommendation. OBJECTIVES: To describe forms of breastfeeding support which have been evaluated in controlled studies, the timing of the interventions and the settings in which they have been used.To examine the effectiveness of different modes of offering similar supportive interventions (for example, whether the support offered was proactive or reactive, face-to-face or over the telephone), and whether interventions containing both antenatal and postnatal elements were more effective than those taking place in the postnatal period alone.To examine the effectiveness of different care providers and (where information was available) training.To explore the interaction between background breastfeeding rates and effectiveness of support. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (29 February 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: This updated review includes 100 trials involving more than 83,246 mother-infant pairs of which 73 studies contribute data (58 individually-randomised trials and 15 cluster-randomised trials). We considered that the overall risk of bias of trials included in the review was mixed. Of the 31 new studies included in this update, 21 provided data for one or more of the primary outcomes. The total number of mother-infant pairs in the 73 studies that contributed data to this review is 74,656 (this total was 56,451 in the previous version of this review). The 73 studies were conducted in 29 countries. Results of the analyses continue to confirm that all forms of extra support analyzed together showed a decrease in cessation of 'any breastfeeding', which includes partial and exclusive breastfeeding (average risk ratio (RR) for stopping any breastfeeding before six months 0.91, 95% confidence interval (CI) 0.88 to 0.95; moderate-quality evidence, 51 studies) and for stopping breastfeeding before four to six weeks (average RR 0.87, 95% CI 0.80 to 0.95; moderate-quality evidence, 33 studies). All forms of extra support together also showed a decrease in cessation of exclusive breastfeeding at six months (average RR 0.88, 95% CI 0.85 to 0.92; moderate-quality evidence, 46 studies) and at four to six weeks (average RR 0.79, 95% CI 0.71 to 0.89; moderate quality, 32 studies). We downgraded evidence to moderate-quality due to very high heterogeneity.We investigated substantial heterogeneity for all four outcomes with subgroup analyses for the following covariates: who delivered care, type of support, timing of support, background breastfeeding rate and number of postnatal contacts. Covariates were not able to explain heterogeneity in general. Though the interaction tests were significant for some analyses, we advise caution in the interpretation of results for subgroups due to the heterogeneity. Extra support by both lay and professionals had a positive impact on breastfeeding outcomes. Several factors may have also improved results for women practising exclusive breastfeeding, such as interventions delivered with a face-to-face component, high background initiation rates of breastfeeding, lay support, and a specific schedule of four to eight contacts. However, because within-group heterogeneity remained high for all of these analyses, we advise caution when making specific conclusions based on subgroup results. We noted no evidence for subgroup differences for the any breastfeeding outcomes. AUTHORS' CONCLUSIONS: When breastfeeding support is offered to women, the duration and exclusivity of breastfeeding is increased. Characteristics of effective support include: that it is offered as standard by trained personnel during antenatal or postnatal care, that it includes ongoing scheduled visits so that women can predict when support will be available, and that it is tailored to the setting and the needs of the population group. Support is likely to be more effective in settings with high initiation rates. Support may be offered either by professional or lay/peer supporters, or a combination of both. Strategies that rely mainly on face-to-face support are more likely to succeed with women practising exclusive breastfeeding.

Challenges in Collating Spirometry Reference Data for South-Asian Children: An Observational Study.

METHODS: Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110). RESULTS: Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The 'GLI-Other' equation fitted data from North India reasonably well while 'GLI-Black' equations provided a better approximation for South-Asian data than the 'GLI-White' equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. CONCLUSION: Until improved and more robust prediction equations can be derived, we recommend the use of 'GLI-Black' equations for interpreting most South-Asian data, although 'GLI-Other' may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration.

UNLABELLED: The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices. AIM: To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation. METHOD: RVRTC data from healthy subjects using Jaeger BabyBody or the 'Respiratory Analysis Software Program, RASP' systems were collated from four centres internationally. Data were excluded if gestational age <37 weeks or birth weight <2.5 kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda-mu-sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF). RESULTS: RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4-118 weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV0.5, compared with only 10% when using the new equations. CONCLUSIONS: Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up.

Birth data accessibility via primary care health records to classify health status in a multi-ethnic population of children: an observational study.

BACKGROUND: Access to reliable birth data (birthweight (BW) and gestational age (GA)) is essential for the identification of individuals who are at subsequent health risk. AIMS: This study aimed to explore the feasibility of retrospectively collecting birth data for schoolchildren from parental questionnaires (PQ) and general practitioners (GPs) in primary care clinics, in inner city neighbourhoods with high density of ethnic minority and disadvantaged populations. METHODS: Attempts were made to obtain birth data from parents and GPs for 2,171 London primary schoolchildren (34% White, 29% Black African origin, 25% South Asians, 12% Other) as part of a larger study of respiratory health. RESULTS: Information on BW and/or GA were obtained from parents for 2,052 (95%) children. Almost all parents (2,045) gave consent to access their children's health records held by GPs. On the basis of parental information, GPs of 1,785 children were successfully contacted, and GPs of 1,202 children responded. Birth data were retrieved for only 482 children (22% of 2,052). Missing birth data from GPs were associated with non-white ethnicity, non-UK born, English not the dominant language at home or socioeconomic disadvantage. Paired data were available in 376 children for BW and in 407 children for GA. No significant difference in BW or GA was observed between PQ and GP data, with <5% difference between sources regardless of normal or low birth weight, or term or preterm status. CONCLUSIONS: Parental recall of birth data for primary schoolchildren yields high quality and rapid return of data, and it should be considered as a viable alternative in which there is limited access to birth records. It provides the potential to include children with an increased risk of health problems within epidemiological studies.

Disparities in pulmonary function in healthy children across the Indian urban-rural continuum.

RATIONALE: Marked socioeconomic health-care disparities are recognized in India, but lung health inequalities between urban and rural children have not been studied. OBJECTIVES: We investigated whether differences exist in spirometric pulmonary function in healthy children across the Indian urban-rural continuum and compared results with those from Indian children living in the UK. METHODS: Indian children aged 5 to 12 years were recruited from Indian urban, semiurban, and rural schools, and as part of the Size and Lung Function in Children study, London. Anthropometric and spirometric assessments were undertaken. MEASUREMENTS AND MAIN RESULTS: Acceptable spirometric data were obtained from 728 (58% boys) children in India and 311 (50% boys) UK-Indian children. As an entire group, the India-resident children had significantly lower z FEV1 and z FVC than UK-Indian children (P < 0.0005), when expressed using Global Lung Function Initiative-2012 equations. However, when India-resident children were categorized according to residence, there were no differences in z FEV1 and z FVC between Indian-urban and UK-Indian children. There were, however, significant reductions of ∼ 0.5 z scores and 0.9 z scores in both FEV1 and FVC (with no difference in FEV1/FVC) in Indian-semiurban and Indian-rural children, respectively, when compared with Indian-urban children (P < 0.0005). z Body mass index, socioeconomic circumstances, tobacco, and biomass exposure were individually significantly associated with z FEV1 and z FVC (P < 0.0005). CONCLUSIONS: The presence of an urban-rural continuum of lung function within a specific ethnic group emphasizes the impact of environmental factors on lung growth in emerging nations such as India, which must be taken into account when developing ethnic-specific reference values or designing studies to optimize lung health.

Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study.

OBJECTIVES: To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages. DESIGN: A prospective multicentre cohort study. SETTING: Seven maternity units in England. PARTICIPANTS: RhD negative pregnant women who booked for antenatal care before 24 weeks' gestation. INTERVENTIONS: Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down's syndrome screening between 11 and 21 weeks' gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. MAIN OUTCOME MEASURES: The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology. RESULTS: Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks' gestation, respectively. Before 11 weeks' gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative. CONCLUSIONS: Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks' gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.

Modelling survival and mortality risk to 15 years of age for a national cohort of children with serious congenital heart defects diagnosed in infancy.

BACKGROUND: Congenital heart defects (CHDs) are a significant cause of death in infancy. Although contemporary management ensures that 80% of affected children reach adulthood, post-infant mortality and factors associated with death during childhood are not well-characterised. Using data from a UK-wide multicentre birth cohort of children with serious CHDs, we observed survival and investigated independent predictors of mortality up to age 15 years. METHODS: Data were extracted retrospectively from hospital records and death certificates of 3,897 children (57% boys) in a prospectively identified cohort, born 1992-1995 with CHDs requiring intervention or resulting in death before age one year. A discrete-time survival model accounted for time-varying predictors; hazards ratios were estimated for mortality. Incomplete data were addressed through multilevel multiple imputation. FINDINGS: By age 15 years, 932 children had died; 144 died without any procedure. Survival to one year was 79.8% (95% confidence intervals [CI] 78.5, 81.1%) and to 15 years was 71.7% (63.9, 73.4%), with variation by cardiac diagnosis. Importantly, 20% of cohort deaths occurred after age one year. Models using imputed data (including all children from birth) demonstrated higher mortality risk as independently associated with cardiac diagnosis, female sex, preterm birth, having additional cardiac defects or non-cardiac malformations. In models excluding children who had no procedure, additional predictors of higher mortality were younger age at first procedure, lower weight or height, longer cardiopulmonary bypass or circulatory arrest duration, and peri-procedural complications; non-cardiac malformations were no longer significant. INTERPRETATION: We confirm the high mortality risk associated with CHDs in the first year of life and demonstrate an important persisting risk of death throughout childhood. Late mortality may be underestimated by procedure-based audit focusing on shorter-term surgical outcomes. National monitoring systems should emphasise the importance of routinely capturing longer-term survival and exploring the mechanisms of mortality risk in children with serious CHDs.

Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening.

BACKGROUND: Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear. HYPOTHESIS: With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF. METHODS: Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months. RESULTS: Compared with controls, and after adjustment for body size and age, LCI, FRC(MBW) and FRC(pleth) were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p<0.001, z-scores, respectively), while forced expiratory volume (FEV(0.5)) and flows (FEF(25-75)) were significantly lower (-0.9 (-1.3 to -0.6), p<0.001 and -0.7 (-1.1 to -0.2), p=0.004, z-scores, respectively). 21% (15/70) of infants with CF had an elevated LCI (>1.96 z-scores) and 25% (17/68) an abnormally low FEV(0.5) (below -1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV(0.5), using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRC(pleth) >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF(25-75) (r=-0.43, p<0.001) but not with LCI or FEV(0.5). CONCLUSION: Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.

Support for healthy breastfeeding mothers with healthy term babies.

BACKGROUND: There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended infants be exclusively breastfed until six months of age, with breastfeeding continuing as an important part of the infant's diet till at least two years of age. However, breastfeeding rates in many countries currently do not reflect this recommendation. OBJECTIVES: To assess the effectiveness of support for breastfeeding mothers. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 October 2011). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Of the 67 studies that we assessed as eligible for inclusion, 52 contributed outcome data to the review (56,451 mother-infant pairs) from 21 countries. All forms of extra support analysed together showed an increase in duration of 'any breastfeeding' (includes partial and exclusive breastfeeding) (risk ratio (RR) for stopping any breastfeeding before six months 0.91, 95% confidence interval (CI) 0.88 to 0.96). All forms of extra support together also had a positive effect on duration of exclusive breastfeeding (RR at six months 0.86, 95% CI 0.82 to 0.91; RR at four to six weeks 0.74, 95% CI 0.61 to 0.89). Extra support by both lay and professionals had a positive impact on breastfeeding outcomes. Maternal satisfaction was poorly reported. AUTHORS' CONCLUSIONS: All women should be offered support to breastfeed their babies to increase the duration and exclusivity of breastfeeding. Support is likely to be more effective in settings with high initiation rates, so efforts to increase the uptake of breastfeeding should be in place. Support may be offered either by professional or lay/peer supporters, or a combination of both. Strategies that rely mainly on face-to-face support are more likely to succeed. Support that is only offered reactively, in which women are expected to initiate the contact, is unlikely to be effective; women should be offered ongoing visits on a scheduled basis so they can predict that support will be available. Support should be tailored to the needs of the setting and the population group.

Seizures in 204 comatose children: incidence and outcome.

PURPOSE: Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain. METHODS: cEEG (one to three channels) was performed for a median 42 h (range 2-630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state). RESULTS: Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36%, 95% confidence interval, 95% CI, 32-41%) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46%) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95% CI 1.012-1.042; p < 0.0005), Adelaide coma score (aOR 0.813, 95% CI 0.700-0.943; p = 0.006), and EEG grade on admission (excess slow with >3% fast, aOR 5.43, 95% CI 1.90-15.6; excess slow with <3% fast, aOR 8.71, 95% CI 2.58-29.4; low amplitude, 10th centile <9 µV, aOR 3.78, 95% CI 1.23-11.7; and burst suppression, aOR 10.68, 95% CI 2.31-49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95% CI 1.18-4.81). Unfavourable outcome (29/111 survivors; 26%) was independently predicted by the presence of ES (aOR 15.4, 95% CI 4.7-49.7) and PIM (aOR 1.036, 95% CI 1.013-1.059). CONCLUSION: Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool.

Symptom-pattern phenotype and pulmonary function in preschool wheezers.

BACKGROUND: Pulmonary function in preschool wheezing phenotypes based on wheeze onset and duration and atopic status has been extensively described but has not been studied in symptom-pattern phenotypes of episodic (viral) and multiple-trigger wheeze. OBJECTIVE: We investigated whether multiple-trigger wheezers were more likely to have abnormal pulmonary function and increased fraction of exhaled nitric oxide (FeNO) than episodic (viral) wheezers and whether multiple-breath wash-out was more sensitive at detecting abnormal pulmonary function than specific airways resistance (sR(aw)) in preschool wheezers. METHODS: FeNO, multiple-breath wash-out indices (lung clearance index [LCI] and conductive airways ventilation inhomogeneity [S(cond)]) and sR(aw) were measured in healthy children and those with recurrent wheeze aged 4 to 6 years. Subgroup analysis was performed according to current symptom-pattern (multiple-trigger vs episodic [viral]), atopic status (atopic vs nonatopic), and wheeze status (currently symptomatic vs asymptomatic). RESULTS: Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in S(cond), and 15% (95% CI, 3% to 28%; P = .01) in sR(aw) compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P = .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), S(cond) was abnormal in 68% (95% CI, 61% to 74%), and sR(aw) was abnormal in 26% (95% CI, 16% to 35%) of multiple-trigger wheezers. CONCLUSIONS: Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. S(cond) is the most sensitive indicator of abnormal pulmonary function in preschool wheezers.

Creating unbiased cross-sectional covariate-related reference ranges from serial correlated measurements.

Cross-sectional covariate-related reference ranges are widely used in clinical medicine to put individual observations in the context of population values. Usually, such reference ranges are created from data sets of independent observations. If multiple measurements per individual are available, then ignoring the within-person correlation between repeats will lead to overestimation of centile precision. Furthermore, if abnormal measurements have triggered more frequent assessment, the data set will be biased thus producing biased centiles. Where multiple measures per individual exist, the methods commonly used are either randomly or systematically to select one observation per individual or to model individual trajectories and combine these. The first of these approaches may result in discarding a large proportion of the available data and may itself cause bias and the latter requires the form of the changes within individuals to be characterized. We have developed an approach to the modeling of the median, spread, and skew across individuals using maximum likelihood, which can incorporate correlations between dependent observations. Heavily biased data sets are simulated to illustrate how the methodology can eliminate the biases inherent in the data collection process and produce valid centiles plus estimates of the within-person correlations. The "select one per individual" approach is shown to be liable to bias and to produce less precise centiles. We recommend that the maximum likelihood method incorporating correlations be used with existing data sets. Furthermore, this is a potentially more efficient approach to be considered when planning the future collection of data solely for the purposes of creating cross-sectional covariate-related reference ranges.

Fgf2 is expressed in human and murine embryonic choroid plexus and affects choroid plexus epithelial cell behaviour.

BACKGROUND: Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using in vitro models. The application of Fgf2 to brain in vivo can affect the whole tissue, making it difficult to assess specific responses of the CPe. METHODS: Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties in vivo, and rodent CPe monolayer cultures. RESULTS: Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation in vivo. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment. CONCLUSION: Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans.

Lung function from infancy to the preschool years after clinical diagnosis of cystic fibrosis.

RATIONALE: After recent standardization of forced expiratory maneuvers for both infants and preschool children, longitudinal measurements are now possible from birth. OBJECTIVES: The aim of this study was to investigate the evolution of lung function during the first 6 years of life after a clinical diagnosis of cystic fibrosis (CF) in infancy in children with CF and in healthy control subjects. METHODS: The raised volume technique was used during infancy and incentive spirometry during the preschool years. MEASUREMENTS AND MAIN RESULTS: Forty-eight children with CF and 33 healthy control subjects had up to seven (median, 3) measurements. Over these early years, the diagnosis of CF itself accounted for a significant mean reduction of 7.5% (95% confidence interval, 0.9 - 13.6%) in FEV(0.75) and 15.1% (95% confidence interval, 3.6 - 25.3%) in FEF(25-75). Wheeze on auscultation, recent cough, and Pseudomonas aeruginosa (PsA) infection (even if apparently effectively treated) were all independently associated with further reductions in lung function. Premorbid lung function did not predict infection with PsA. CONCLUSIONS: This is the first study to describe physiologic measurements from infancy through the preschool years in subjects with CF and healthy control subjects, the understanding of which is critical for future intervention trials. Airflow obstruction in uncomplicated CF persists through the preschool years despite treatment, with PsA acquisition being associated with further deterioration in lung function, even when apparently eradicated. This suggests that new therapies are needed to treat the airflow obstruction of uncomplicated CF, and rigorous strategies to prevent PsA acquisition.

Clinical and radiological recurrence after childhood arterial ischemic stroke.

BACKGROUND: Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies. METHODS AND RESULTS: Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978-1990) and prospectively (1990-2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction. CONCLUSIONS: Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection.

Long-term visual acuity and its predictors after surgery for congenital cataract: findings of the British congenital cataract study.

PURPOSE: To report long-term postoperative visual acuity in a nationally representative group of children with congenital/infantile cataract and to investigate the factors associated with poor vision. METHODS: All children aged less than 16 years in the United Kingdom who had newly diagnosed congenital/infantile cataract in a 12-month period during 1995-1996 (the British Congenital/infantile Cataract Study) were traced through their managing ophthalmologists. Outcome data were collected at least 6 years after diagnosis, by using specifically designed questionnaires. Ordinal regression analysis identified factors associated with postoperative acuity. RESULTS: Of 153 children who had surgery, complete data were available in 122 (85%). Median age at follow-up was 7 and 6.91 years, respectively, for bilateral and unilateral disease. Median age at surgery was 4.57 months in bilateral and 2.99 months in unilateral cases, with 40% and 45%, respectively, of children operated on by 3 months. Median (range) postoperative acuity was 6/18 (6/5, no perception of light) in bilateral and 6/60 (6/5, no perception of light) in unilateral disease. Poor compliance with occlusion was the factor most strongly associated with poorer acuity in both unilateral and bilateral disease: the odds of worse vision in unilateral cataract were 7.92 times greater with <50% versus 100% compliance (95% CI 1.68-37.26). In bilateral disease, odds of worse vision were reduced with each month of decreasing age at surgery (0.98, 95% CI 0.94-0.99), but increased by the presence of additional medical conditions (3.53, 95% CI 1.08-11.44) and the presence of postoperative ocular complications (2.94, 95% CI 1.38-6.51). CONCLUSIONS: These findings support a secular improvement in postoperative acuity in bilateral, and to a lesser extent, unilateral disease. Nevertheless early detection of congenital cataract through effective newborn screening and improving concordance with occlusion both remain priorities. Further improvements in outcomes in unilateral disease are necessary before parents can be advised universally that treatment will achieve a functionally useful "spare" eye.

Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study.

BACKGROUND: Convulsive status epilepticus is the most common childhood medical neurological emergency, and is associated with significant morbidity and mortality. Most data for this disorder are from mainly adult populations and might not be relevant to childhood. Thus we undertook the North London Status Epilepticus in Childhood Surveillance Study (NLSTEPSS): a prospective, population-based study of convulsive status epilepticus in childhood, to obtain a uniquely paediatric perspective. METHODS: Clinical and demographic data for episodes of childhood convulsive status epilepticus that took place in north London were obtained through a clinical network that covered the target population. We obtained these data from anonymised copies of a standardised admission proforma; accident and emergency, nursing, ambulance, and intensive-care unit notes; and interviews with parents, medical, nursing, and paramedic staff. We investigated ascertainment using capture-recapture modelling. FINDINGS: Of 226 children enrolled, 176 had a first ever episode of convulsive status epilepticus. We estimated that ascertainment was between 62% and 84%. The ascertainment-adjusted incidence was between 17 and 23 episodes per 100,000 per year. 98 (56%, 95% CI 48-63) children were neurologically healthy before their first ever episode and 56 (57%, 47-66) of those children had a prolonged febrile seizure. 11 (12%, 6-18) of children with first ever febrile convulsive status epilepticus had acute bacterial meningitis. Conservative estimation of 1-year recurrence of convulsive status epilepticus was 16% (10-24%). Case fatality was 3% (2-7%). INTERPRETATION: Convulsive status epilepticus in childhood is more common, has a different range of causes, and a lower risk of death than that in adults. These paediatric data will help inform management of convulsive status epilepticus and appropriate allocation of resources to reduce the effects of this disorder in childhood.