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Introduction Caffeine is commonly consumed during pregnancy, but elimination from the blood is slowed.' Fetal concentrations are believed to be in equilibrium with maternal concentrations.[1] Although it is biologically plausible [...]

Abstract Objective - To examine the relation between preterm birth and socioeconomic and psychological factors, smoking, and alcohol and caffeine consumption. Design - Prospective study of outcome of pregnancy. Setting [...]

While it has been established that women who smoke during pregnancy give birth to smaller babies, it is not clear whether smokers eat less food, or less nutritious food, or perhaps there is another explanation for the lower birth weights entirely. In Britain, social class is strongly related to both smoking and nutrient intake; women in professional careers smoke less and eat more nutritious diets than women in manual labor occupations. Ninety-four women who smoked at least 15 cigarettes per day and 206 nonsmokers kept a record of all foods eaten over seven days at 28 weeks' gestation. Most of the subjects (178) repeated the seven-day food records at 36 weeks. They were given detailed instructions on how to weigh foods on a scale so that portion sizes would be correct; in almost all cases subjects were able to weigh their food. The data showed that as a group the nonsmokers ate a more nutritious diet than the smokers; while total energy intake was equivalent in the two groups, nonsmokers ate foods that contained more nutrients per calorie. Smoking appeared to have a significant adverse effect on the consumption of many nutrients, after corrections were made for the influence of social factors. In both groups, food intake was reduced during late pregnancy, but the reduction was more pronounced among smokers. The authors conclude that smokers from all socioeconomic classes had diets of lower quality than nonsmokers. Poor nutrition, particularly inadequate vitamin intakes, may contribute to the lower birth weights of infants born to mothers who smoke. (Consumer Summary produced by Reliance Medical Information, Inc.)

Selective dorsal rhizotomy (SDR) is an irreversible surgical procedure involving the division of selected sensory nerve roots, followed by intensive physiotherapy. The aim is to improve function and quality of life in children with cerebral palsy and a Gross Motor Function Classification System (GMFCS) level of II or III (walks with or without assistive devices, respectively). We assessed gross motor function before and after SDR and postoperative quality of life in a study commissioned by NHS England.

Intrapancreatic lipid (IPL) has been linked to β-cell dysfunction. Black populations disproportionately develop type 2 diabetes (T2D) and show distinctions in β-cell function compared with white populations.

IMPORTANCE: Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial. OBJECTIVE: To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. DESIGN, SETTING, AND PARTICIPANTS: We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study’s treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016. INTERVENTIONS: Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. MAIN OUTCOMES AND MEASURES: The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing. RESULTS: Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D′ = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation. CONCLUSIONS AND RELEVANCE: Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00153816

ImportanceSurgical treatment can bring seizure remission in people with focal epilepsy but requires careful selection of candidates.ObjectivesTo determine which preoperative factors are associated with postoperative seizure outcome.DesignWe audited seizure outcome of 693 adults who had resective epilepsy surgery between 1990 and 2010 and used survival analysis to detect preoperatively identifiable risk factors of poor seizure outcome.ResultsSeven factors were significantly associated with increased probability of recurrence of seizures with impaired awareness postsurgery: MRI findings (eg, HR adjusted for other variables in the model 2.5; 95% CI 1.6 to 3.8 for normal MRI compared with hippocampal sclerosis), a history of secondarily generalised convulsive seizures (2.3; 95% CI 1.7 to 3.0 for these seizures in the previous year vs never), psychiatric history (1.3; 95% CI 1.1 to 1.7), learning disability (1.8; 95% CI 1.2 to 2.6) and extratemporal (vs temporal) surgery (1.4; 95% CI 1.02, 2.04). People with an older onset of epilepsy had a higher probability of seizure recurrence (1.01; 95% CI 1.00, 1.02) as did those who had used more antiepileptic drugs (1.05; 95% CI 1.01 to 1.09). Combinations of variables associated with seizure recurrence gave overall low probabilities of 5-year seizure freedom (eg, a normal MRI and convulsive seizures in the previous year has a probability of seizure freedom at 5 years of approximately 0.19).Conclusions and relevanceReadily identified clinical features and investigations are associated with reduced probability of good outcome and need consideration when planning presurgical evaluation.

AbstractBackground:Children with chronic kidney disease (CKD) are at increased risk of future cardiovascular (CV) events. Our aim in this prospective single-centre cross-sectional analysis was to assess the relationship of a novel panel of CV biomarkers with left ventricular hypertrophy (LVH). Methods:A panel of five CV biomarkers (asymmetric dimethyl arginine, high sensitivity C-reactive protein, homocysteine, N-terminal pro-B type natriuretic peptide and uric acid) were measured on the same day as an echocardiogram assessment, in paediatric patients with pre-dialysis stages 3-5 of CKD. Results:Of 73 children aged 5-18 years, LVH, all eccentric, was identified in 38. Systolic blood pressure (BP), glomerular filtration rate (GFR) and higher intake of calcium-based phosphate binders were significantly worse in children with LVH. In multivariate models analysing each biomarker one at a time with confounders [GFR, systolic BP z-score, anti-hypertensive medication (yes/no) and elemental calcium intake], clinic systolic BP z-score and elemental calcium intake consistently displayed a significant relationship with indexed left ventricular mass (LVMI). None of the evaluated CV biomarkers displayed a significant relationship with LVMI. Conclusions:In our cohort of children with moderately severe pre-dialysis CKD we have identified no suitable biomarkers to detect LVH. We would therefore recommend that echocardiographic determination of LVMI remains the technique of choice for detection of LVH in children with CKD.© 2014 S. Karger AG, Basel

Background:The aim of this study was to determine whether small-for-gestational-age (SGA) infants born very prematurely had increased respiratory morbidity in the neonatal period and at follow-up.Methods:Data were examined from infants recruited into the United Kingdom Oscillation Study (UKOS). Of the 797 infants who were born at <29?wk of gestational age, 174 infants were SGA. Overall, 92% were exposed to antenatal corticosteroids and 97% received surfactant; follow-up data at 22–28 mo were available for 367 infants.Results:After adjustment for gestational age and sex, SGA infants had higher rates of supplementary oxygen dependency at 36?wk postmenstrual age (odds ratio (OR): 3.23; 95% confidence interval: 2.03, 5.13), pulmonary hemorrhage (OR: 3.07; 95% CI: 1.82, 5.18), death (OR: 3.32; 95% CI: 2.13, 5.17), and postnatal corticosteroid requirement (OR: 2.09; 95% CI: 1.35, 3.23). After adjustment for infant and respiratory morbidity risk factors, a lower mean birth weight z-score was associated with a higher prevalence of respiratory admissions (OR: 1.40; 95% CI: 1.03, 1.88 for 1 SD change in z-score), cough (OR: 1.28; 95% CI: 1.00, 1.65), and use of chest medicines (OR: 1.32; 95% CI: 1.01, 1.73).Conclusion:SGA infants who were born very prematurely, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity at follow-up, which was not due to poor neonatal outcome.

There is considerable heterogeneity in the myocardial substrate of patients undergoing cardiac resynchronization therapy (CRT), in particular in the etiology of heart failure and in the location of conduction block within the heart. This may account for variability in response to CRT. New approaches, including endocardial and multisite left ventricular (LV) stimulation, may improve CRT response. We sought to evaluate these approaches using noncontact mapping to understand the underlying mechanisms.

Introduction:Although important new strategies have improved outcomes for very preterm infants, males have greater mortality/morbidity than females. We investigated whether the excess of adverse later effects in males operated through poorer neonatal profile or if there was an intrinsic male effect.Results:Male sex was significantly associated with higher birth weight, death or oxygen dependency (72% vs. 61%, boys vs. girls), hospital stay (97 vs. 86 days), pulmonary hemorrhage (15% vs. 10%), postnatal steroids (37% vs. 21%), and major cranial ultrasound abnormality (20% vs. 12%). Differences remained significant after adjusting for birth weight and gestation. At follow-up, disability, cognitive delay, and use of inhalers remained significant after further adjustment.Discussion:We conclude that in very preterm infants, male sex is an important risk factor for poor neonatal outcome and poor neurological and respiratory outcome at follow-up. The increased risks at follow-up are not explained by neonatal factors and lend support to the concept of male vulnerability following preterm birth.Methods:Data came from the United Kingdom Oscillation Study, with 797 infants (428 boys) born at 23–28 wk gestational age. Thirteen maternal factors, 8 infant factors, 11 acute outcomes, and neurological and respiratory outcomes at follow-up were analyzed. Follow-up outcomes were adjusted for birth and neonatal factors sequentially to explore mechanisms for differences by sex.

Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery.

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group.

The role of infection in bronchopulmonary dysplasia (BPD) is unknown. We present an observational study of 55 premature infants born weighing less than 1.3 kg within two level III neonatal intensive care units. Endotracheal aspirates (ETA) and nasogastric aspirates (NGA) were studied with denaturing gradient gel electrophoresis (DGGE) profiling to elucidate the total bacterial community, and species-specific PCR was used to detect the presence of Mycoplasmahominis, Ureaplasma urealyticum, and Ureaplasma parvum. DGGE identified bacterial species in 59% of NGA and ETA samples combined. A diverse range of species were identified including several implicated in preterm labor. Species-specific PCR identified M.hominisin 25% of NGA and 11% of ETA samples. Among the 48 infants surviving up to 36 wk-postconceptual age, ordinal logistic regression showed the odds ratio for BPD or death where Ureaplasmawas present/absent as 4.80 (95% CI 1.15–20.13). After adjusting for number of days ventilated, this was reduced to 2.04 (0.41–10.25). These data demonstrate how the combined use of DGGE and species-specific PCR identifies a high exposure in uteroand around the time of birth to bacteria that might be causally related to preterm delivery and subsequent lung injury.

Time-series studies have shown short-term temporal associations between low levels of ambient particulate air pollution and adverse health effects. It is not known whether or to what extent this literature is affected by publication bias.

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded. Following successful treatment with a high-pressure balloon, 212 patients were randomized. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon. The primary endpoint was time to loss of clinically driven target lesion primary patency. Primary analysis showed no significant evidence for a difference in time to end of target lesion primary patency between groups: hazard ratio 1.18 with a 95% confidence interval of 0.78 to 1.79. There were no significant differences for any secondary outcomes, including patency outcomes and adverse events. Thus, our study demonstrated no evidence that paclitaxel-coated balloons provide benefit, following standard care high-pressure balloon angioplasty, in the treatment of arteriovenous fistulas. Hence, in view of the benefit suggested by other trials, the role of paclitaxel-coated angioplasty balloons remains uncertain.

Background We identified child-related determinants of health-related quality of life (HRQoL) in children aged 8–14 years who were treated for 2 common types of pediatric brain tumors. Methods Questionnaire measures of HRQoL and psychometric assessments were completed by 110 children on 3 occasions over 24 months. Of these 110, 72 were within 3 years of diagnosis of a cerebellar tumor (37 standard-risk medulloblastoma, 35 low-grade cerebellar astrocytoma), and 38 were in a nontumor group. HRQoL, executive function, health status, and behavioral difficulties were also assessed by parents and teachers as appropriate. Regression modeling was used to relate HRQoL z scores to age, sex, socioeconomic status, and 5 domains of functioning: Cognition, Emotion, Social, Motor and Sensory, and Behavior. Results HRQoL z scores were significantly lower after astrocytoma than those in the nontumor group and significantly lower again in the medulloblastoma group, both by self-report and by parent-report. In regression modeling, significant child-related predictors of poorer HRQoL z scores by self-report were poorer cognitive and emotional function (both z scores) and greater age (years) at enrollment (B = 0.038, 0.098, 0.136, respectively). By parent-report, poorer cognitive, emotional and motor or sensory function (z score) were predictive of lower subsequent HRQoL of the child (B = 0.043, 0.112, 0.019, respectively), while age at enrollment was not. Conclusions Early screening of cognitive and emotional function in this age group, which are potentially amenable to change, could identify those at risk of poor HRQoL and provide a rational basis for interventions to improve HRQoL.

The effects on birthweight of the number of cigarettes smoked and their tar, nicotine and carbon monoxide yields were investigated prospectively in 1309 pregnant women of whom 414 were smokers. Several approaches to modelling the effect of smoking were tried. These suggested that while both yield and quantity smoked were important, yield had the greatest effect. This led to an empirical approach whereby consistent smokers were divided into four categories according to whether they smoked a low or high quantity of cigarettes per day and whether they smoked low or high yield cigarettes. Using these four groups it emerged that women smoking a low quantity of low yield cigarettes had babies of a similar mean birthweight to those of non-smokers whereas those smoking a low quantity of high yield cigarettes had babies whose birthweight was reduced to the same degree (6% or more) as those of mothers who smoked higher quantities. This apparent threshold was estimated as 13 cigarettes/day and 15 mg/cigarette carbon monoxide. We conclude that brand smoked is at least as important as quantity and that in this population there is evidence for threshold for tobacco smoke intake below which to discernible effect on birthweight is seen.