Low birthweight (LBW) is associated with increased mortality in infancy, but its association with mortality in later childhood and adolescence is less clear. We investigated the association between ...birthweight and all-cause mortality and identified major causes of mortality for different birthweight groups.
We conducted a population study of all live births occurring in England and Wales between 1 January 1993 and 31 December 2011. Following exclusions, the 12,355,251 live births were classified by birthweight: 500-1,499 g (very LBW VLBW, n = 139,608), 1,500-2,499 g (LBW, n = 759,283), 2,500-3,499 g (n = 6,511,411), and ≥3,500 g (n = 4,944,949). The association of birthweight group with mortality in infancy (<1 y of age) and childhood/adolescence (1-18 y of age) was quantified, with and without covariates, through hazard ratios using Cox regression. International Classification of Diseases codes identified causes of death. In all, 74,890 (0.61%) individuals died between birth and 18 y of age, with 23% of deaths occurring after infancy. Adjusted hazard ratios for infant deaths were 145 (95% CI 141, 149) and 9.8 (95% CI 9.5, 10.1) for the VLBW and LBW groups, respectively, compared to the ≥3,500 g group. The respective hazard ratios for death occurring at age 1-18 y were 6.6 (95% CI 6.1, 7.1) and 2.9 (95% CI 2.8, 3.1). Male gender, the youngest and oldest maternal age bands, multiple births, and deprivation (Index of Multiple Deprivation score) also contributed to increased deaths in the VLBW and LBW groups in both age ranges. In infancy, perinatal factors, particularly respiratory issues and infections, explained 84% and 31% of deaths in the VLBW and LBW groups, respectively; congenital malformations explained 36% and 23% in the LBW group and ≥2,500 g groups (2,500-3,499 g and ≥3,500 g groups combined), respectively. Central nervous system conditions explained 20% of deaths in childhood/adolescence in the VLBW group, with deaths from neoplasms and external conditions increasingly prevalent in the 1,500-2,499 g and ≥2,500 g birthweight groups. The study would have benefited had we had access to information on gestational age and maternal smoking, but since the former is highly correlated with birthweight and the latter with deprivation, we believe that our findings remain robust despite these shortcomings.
LBW is associated with infant and later child and adolescent mortality, with perinatal factors and congenital malformations explaining many of the deaths. By understanding and ameliorating the influences of upstream exposures such as maternal smoking and deprivation, later mortality can be decreased by reducing the delivery of vulnerable infants with LBW.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-flow therapy is the most recent, and popular, mode of respiratory support in neonates. However, the evidence supporting its efficacy and safety has not yet been established. We conducted a ...systematic review and meta-analysis of clinical trials comparing efficacy and safety of high-flow therapy compared with other modes of noninvasive ventilation (NIV) in preterm infants.
Articles were indexed by using Medline, Embase, Scopus, OpenSIGLE, Health Management Information Consortium, and Cochrane Central Register of Controlled Trials. Randomized or quasi-randomized clinical trials involving preterm infants, comparing high-flow therapy with other modes of NIV, and reporting extractable data on relevant outcomes, were selected. Data on efficacy, safety, and other common neonatal outcomes were extracted on predesigned forms.
In this analysis, we included 1112 preterm infants, participating in 9 clinical trials. High-flow therapy was similar in efficacy to other modes of NIV in preterm infants when used as primary support (odds ratio of failure of therapy, 1.02 95% confidence interval: 0.55 to 1.88), as well as after extubation (1.09 0.58 to 2.02). There were no significant differences in odds of death (0.48 0.18 to 1.24) between the groups. Preterm infants supported on high-flow had significantly lower odds of nasal trauma (0.13 0.02 to 0.69).
High-flow therapy appears to be similar in efficacy and safety to other conventional modes of NIV in preterm infants. It is associated with significantly lower odds of nasal trauma. Caution needs to be exercised in extreme preterm infants because of the paucity of published data.
Background Early term–born (37-38 weeks' gestation) infants have increased respiratory morbidity during the neonatal period compared with full term–born (39-42 weeks' gestation) infants, but ...longer-term respiratory morbidity remains unclear. Objective We assessed whether early term–born children have greater respiratory symptoms and health care use in childhood compared with full term–born children. Methods We surveyed 1- to 10-year-old term-born children (n = 13,361). Questionnaires assessed respiratory outcomes with additional data gathered from national health databases. Results Of 2,845 eligible participants, 545 were early term–born and 2,300 were full term–born. Early term–born children had higher rates of admission to the neonatal unit (odds ratio OR, 1.7; 95% CI, 1.2-2.5) and admission to the hospital during their first year of life (OR, 1.6; 95% CI, 1.2-2.1). Forty-eight percent of early term–born children less than 5 years old reported wheeze ever compared with 39% of full term–born children (OR, 1.5; 95% CI, 1.1-1.9), and 26% versus 17% reported recent wheezing (OR, 1.7; 95% CI, 1.3-2.4). Early term–born children older than 5 years reported higher rates of wheeze ever (OR, 1.4; 95% CI, 1.05-1.8) and recent wheezing over the last 12 months than full-term control subjects (OR, 1.4; 95% CI, 1.02-2.0). Increased rates of respiratory symptoms in early term–born children persisted when family history of atopy and delivery by means of cesarean sections were included in logistic regression models. Conclusion Early term–born children had significantly increased respiratory morbidity and use of health care services when compared with full term–born children, even when stratified by mode of delivery and family history of atopy.
Previous studies of preterm-born children (<37 weeks' gestation) have demonstrated decrements in lung function, exercise capacity, and increased respiratory symptoms compared to their term-born ...peers. However, it is unclear if these children have decreased levels of physical activity (PA) and increased sedentary behavior as a consequence of this increased respiratory morbidity. We therefore compared objectively measured PA in 7-year old preterm-born children with those born at term.
Children in the Millennium Cohort Study underwent assessment of PA at 7 years of age using accelerometry. 6422/12781 (50%) provided valid accelerometry and had gestational age data. A series of general linear models adjusted for confounders investigated the association between gestational age and levels of Total PA (average accelerometer counts per minute over the period of the recording), Moderate-to-Vigorous PA (MVPA) and sedentary behavior. Mediation analysis was performed to specifically investigate whether the observed association of gestational age on PA was mediated by respiratory symptoms.
PA data were available for 79, 119, 275 and 5949 children born at 25-32, 33-34, 35-36 and 37-43 weeks' gestation respectively. Boys born at ≤32 weeks' gestation had modest but statistically significant reductions in MVPA when compared to term controls. This equated to a reduction of 9 minutes per day. No differences were found for Total PA or sedentary behavior. The association between gestational age and MVPA was not mediated by respiratory symptoms. In females, there was no association between gestational age and any measure of PA or sedentary behavior.
Boys born at ≤32 weeks' gestation took part in less MVPA than their term-born peers at 7 years of age. The differences were modest, but equated to a reduction of over 1 hour per week. Since PA levels have been shown to decline during childhood and adolescence, this vulnerable group deserves further surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing evidence suggests that preterm birth affects later lung function. We systematically reviewed the literature to determine whether percentage predicted forced expiratory volume in 1 s ...(%FEV1) is lower in later life in preterm-born subjects, with or without bronchopulmonary dysplasia (BPD), compared with term-born controls.
Studies reporting %FEV1, with or without a term-born control group, in later life for preterm-born subjects (<37 weeks gestation) were extracted from eight databases. Data were analysed using Review Manager and STATA. The quality of the studies was assessed.
From 8839 titles, 1124 full articles were screened and 59 were included: 28 studied preterm-born children without BPD, 24 with BPD28 (supplemental oxygen dependency at 28 days), 15 with BPD36 (supplemental oxygen dependency 36 weeks postmenstrual age) and 34 born preterm. For the preterm-born group without BPD and for the BPD28 and BPD36 groups the mean differences (and 95% CIs) for %FEV1 compared with term-born controls were -7.2% (-8.7% to -5.6%), -16.2% (-19.9% to -12.4%) and -18.9% (-21.1% to -16.7%), respectively. Pooling all data on preterm-born subjects whether or not there was a control group gave a pooled %FEV1 estimate of 91.0% (88.8% to 93.1%) for the preterm-born cohort without BPD, 83.7% (80.2% to 87.2%) for BPD28 and 79.1% (76.9% to 81.3%) for BPD36. Interestingly, %FEV1 for BPD28 has improved over the years.
%FEV1 is decreased in preterm-born survivors, even those who do not develop BPD. %FEV1 of survivors of BPD28 has improved over recent years. Long-term respiratory follow-up of preterm-born survivors is required as they may be at risk of developing chronic obstructive pulmonary disease.
Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length ...may be altered. We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7-12-year-old children born at less than or equal to34 weeks' gestation and term-born controls. Relative telomere length was measured by qPCR on extracted DNA. Groups were compared using independent t-tests or ANOVA with post-hoc correction. Linear regression analysis was also used. 534 children had satisfactory telomere data including 383 who were preterm-born (mean (SD) birthweight 1732g (558g), gestation 31.1 (2.6) weeks) and 151 term-born (3464g (510g); 39.8 (1.3) weeks). Telomere length was longer in children who had intrauterine growth restriction (IUGR) at birth: mean (SD): 464.6 (166.3) vs. 418.6 (110.7) in the no-IUGR group; in females: 440.2 (130.1) vs. 405.7 (101.5) in males; and in the least deprived group (397.8 (95.0) vs. 437.6 (121.9) most vs least deprivation quintile). Differences were most notable in females with IUGR. However, telomere length was not different between the preterm and term groups; the BPD and no BPD groups nor was it related to lung function or cardiovascular measurements. In multivariable regression analyses, telomere length was associated with sex, IUGR and deprivation with the greatest difference observed in females with IUGR. Telomere length was associated with sex, IUGR and deprivation, especially in females with IUGR, but not with prematurity, BPD, lung function or cardiovascular measurements.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many but not all studies suggest an association between air pollution exposure and infant mortality. We sought to investigate whether pollution exposure is differentially associated with all-cause ...neonatal or postneonatal mortality, or specific causes of infant mortality.
We separately investigated the associations of exposure to particulate matter with aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide (NO2), and sulphur dioxide (SO2) with all-cause infant, neonatal, and postneonatal mortality, and with specific causes of infant deaths in 7,984,366 live births between 2001 and 2012 in England and Wales. Overall, 51.3% of the live births were male, and there were 36,485 infant deaths (25,110 neonatal deaths and 11,375 postneonatal deaths). We adjusted for the following major confounders: deprivation, birthweight, maternal age, sex, and multiple birth. Adjusted odds ratios (95% CI; p-value) for infant deaths were significantly increased for NO2, PM10, and SO2 (1.066 1.027, 1.107; p = 0.001, 1.044 1.007, 1.082; p = 0.017, and 1.190 1.146, 1.235; p < 0.001, respectively) when highest and lowest pollutant quintiles were compared; however, neonatal mortality was significantly associated with SO2 (1.207 1.154, 1.262; p < 0.001) but not significantly associated with NO2 and PM10 (1.044 0.998, 1.092; p = 0.059 and 1.008 0.966, 1.052; p = 0.702, respectively). Postneonatal mortality was significantly associated with all pollutants: NO2, 1.108 (1.038, 1.182; p < 0.001); PM10, 1.117 (1.050, 1.188; p < 0.001); and SO2, 1.147 (1.076, 1.224; p < 0.001). Whilst all were similarly associated with endocrine causes of infant deaths (NO2, 2.167 1.539, 3.052; p < 0.001; PM10, 1.433 1.066, 1.926; p = 0.017; and SO2, 1.558 1.147, 2.116; p = 0.005), they were differentially associated with other specific causes: NO2 and PM10 were associated with an increase in infant deaths from congenital malformations of the nervous (NO2, 1.525 1.179, 1.974; p = 0.001; PM10, 1.457 1.150, 1.846; p = 0.002) and gastrointestinal systems (NO2, 1.214 1.006, 1.466; p = 0.043; PM10, 1.312 1.096, 1.571; p = 0.003), and NO2 was also associated with deaths from malformations of the respiratory system (1.306 1.019, 1.675; p = 0.035). In contrast, SO2 was associated with an increase in infant deaths from perinatal causes (1.214 1.156, 1.275; p < 0.001) and from malformations of the circulatory system (1.172 1.011, 1.358; p = 0.035). A limitation of this study was that we were not able to study associations of air pollution exposure and infant mortality during the different trimesters of pregnancy. In addition, we were not able to control for all confounding factors such as maternal smoking.
In this study, we found that NO2, PM10, and SO2 were differentially associated with all-cause mortality and with specific causes of infant, neonatal, and postneonatal mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop BPD have normal lung function in childhood and many without BPD, including those ...born at 33-34 weeks of gestation, have lung dysfunction in childhood. Since the predictability of BPD for future lung deficits is increasingly doubted, we prospectively recruited preterm-born children to identify early-life factors associated with lung function deficits after preterm birth.
From 767 children aged 7-12 years who had their respiratory symptoms assessed, and had spirometry before and after a bronchodilator in our Respiratory Health Outcomes in Neonates (RHiNO) study, 739 (544 preterm-born at ≤34 weeks of gestation and 195 term-born) had satisfactory lung function. Data were analysed using multivariable logistic regression and mediation.
When preterm-born children were classified according to their lung function, low lung function (prematurity-associated lung disease (PLD)) was associated with BPD, gestation and intra-uterine growth restriction (IUGR) on univariable logistic regression analyses. However, on multivariable logistic regression analyses, gestation (β= -0.153, se 0.051; p=0.003) and IUGR (OR 1.783, 95% CI 1.06-3.00; p=0.029) remained significantly associated with later deficits of lung function, but BPD (OR 0.99, 95% CI 0.52-1.89; p=0.974) did not. Mediation analyses confirmed these results.
Although traditionally BPD has been associated with low lung function in later life, the data show that gestation and IUGR are significantly associated with PLD in childhood, but BPD is not. By identifying children with PLD, we can better understand the underlying mechanisms and develop optimal therapies.
Anastomotic stricture is a common postoperative complication of oesophageal atresia ± tracheoesophageal fistula (OA/TOF) repair. Acid gastro-oesophageal reflux disease (GORD) is considered to be a ...factor in stricture formation and acid suppression medication is recommended post-operatively in consensus guidance. We aimed to investigate whether patients who were treated prophylactically with acid suppression medication had a reduced incidence of strictures compared to those who did not receive it.
A systematic review of studies was performed, searching multiple databases without language or date restrictions. Multiple reviewers independently assessed study eligibility and literature quality. The primary outcome was anastomotic stricture formation, with secondary outcomes of GORD, anastomotic leak, and oesophagitis. Meta-analysis was performed using a random effects model, and the results were expressed as an odds ratio (OR) with 95% confidence intervals (CI).
No randomised studies on the topic were identified. Twelve observational studies were included in the analysis with ten reporting the primary outcome. The quality assessment showed a high risk of bias in several papers, predominantly due to non-objective methods of assessment of oesophageal stricture and the non-prospective, non-randomised nature of the studies. Overall, 1395 patients were evaluated, of which 753 received acid suppression medication. Meta-analysis revealed a trend towards increased odds of anastomotic strictures in infants receiving prophylactic medication, but this was not statistically significant (OR 1.33; 95% CI 0.92, 1.92). No significant differences were found in secondary outcomes.
This meta-analysis found no evidence of a statistically significant link between the prophylactic prescribing of acid suppression medication and the risk of developing anastomotic stricture after OA repair. The literature in this area is limited to observational studies and a randomised controlled trial is recommended to explore this question.
Level III.
Molecular determinants underlying interferon (IFN)-macrophage biology can help delineate enzyme systems, pathways and mechanisms for enabling host-directed therapeutic approaches against infection. ...Notably, while the IFN antiviral response is known to be directly coupled to mevalonate-sterol biosynthesis, mechanistic insight for providing host pathway-therapeutic targets remain incomplete. Here, we show that Nampt and Sirt6 are coordinately regulated upon immune activation of macrophages and contribute to the IFN-sterol antiviral response.
analysis of the
and
promoter regions identified multiple core immune gene-regulatory transcription factor sites, including Stat1, implicating a molecular link to IFN control. Experimentally, we show using a range of genetically IFN-defective macrophages that the expression of
is stringently regulated by the Jak/Stat-pathway while
activation is temporally displaced in a partial IFN-dependent manner. We further show that pharmacological inhibition of Nampt and small interfering RNA (siRNA)-mediated inhibition of Nampt and Sirt6 promotes viral growth of cytomegalovirus in both fibroblasts and macrophages. Our results support the notion of pharmacologically exploiting immune regulated enzyme systems of macrophages for use as an adjuvant-based therapy for augmenting host protective pathway responses to infection.
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