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The article presents the author's response to a commentary by professor Ola Didrik Saugstad on a study that examined the impact of hyperoxia on the cerebral blood flow of children.

Aim Even short periods of hyperoxia may induce prolonged cerebral vasoconstriction in newborn infants, and this could theoretically lead to cerebral ischaemia even once normoxia is re-established. This study aimed to investigate the effect of brief hyperoxic exposures on regional cerebral tissue oxygen saturation (rStO2) and to evaluate whether any observed prolonged cerebral vasoconstriction was related to maturity. Methods The study included 30 infants with a postmenstrual age of more than 32 weeks, who were treated with nasal continuous positive airway pressure and a fraction of inspired oxygen of ≤0.3. The INVOS 5100C oximeter was used to measure rStO2 before, during and after two hyperoxic exposures. If hyperoxia induced a prolonged cerebral vasoconstriction, posthyperoxic rStO2 would be expected to decrease. Results rStO2 increased slightly after the first hyperoxic exposure, with a mean difference of 1.37% (95% CI 0.15, 2.6). After the second oxygen exposure, rStO2 remained unchanged with a mean difference of −0.4% (95% CI −1.6, 0.78). Differences in rStO2 were not related to gestational age in either of the two hyperoxic episodes. Conclusion We found no evidence to support the theory that transient hyperoxia induces prolonged cerebral vasoconstriction in infants with a postmenstrual age above 32 weeks. [ABSTRACT FROM AUTHOR]

Aim: Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature. Methods: In 12 piglets, cerebral perfusion (laser-Doppler flux) and oxygenation [near-infrared spectroscopy (NIRS)] were examined during dopamine (20-50 μg/kg per minute) and nonpharmacologically induced blood pressure (ABP) changes. Effect on cerebral perfusion and oxygenation was quantified as frequency gain between ABP and laser-Doppler flux (gain-LDF) and NIRS [gain-oxygenation index (OI)], respectively. Gain quantifies change in perfusion or oxygenation per ABP-change. CA was estimated as gain-LDF during nonpharmacologically induced ABP changes, that is, as degree of impairment. Dopamine's cerebrovascular effect was estimated by contrasting gain during dopamine- and nonpharmacologically induced ABP changes. Measurements were conducted during both normovolemia- and haemorrhage-induced hypovolemia. Results: Hypovolemia elicited hypotension (p = 0.02) as well as increasing impairment of CA (p = 0.01). However, hypovolemia without hypotension did not affect CA significantly. Dopamine increased perfusion significantly compared to nonpharmacological challenges (mean difference: 1.5%/mmHg, 95% CI: 0.5-2.6, p = 0.007). Oxygenation was, however, similar (mean difference: 0.01 μmol/L per mmHg, 95% CI: −0.03 to 0.05, p = 0.7). Conclusion: Our findings do not support that hypovolemia alone impairs CA. Furthermore, dopamine seems to increase cerebral perfusion but not oxygenation. [ABSTRACT FROM AUTHOR]

Attention-deficit-hyperactivity disorder (ADHD), while largely thought to be a genetic disorder, has environmental factors that appear to contribute significantly to the aetiopathogenesis of the disorder. One such factor is pretern birth with vulnerable cerebrovascular homeostasis. We hypothesised that cerebral ischaemia at birth could contribute to persistent deficient dopaminergic neurotransmission, which is thought to be the pathophysiological basis of the disorder. We examined dopamine D(2/3) receptor binding with positron emission tomography (PET) using [11C] raclopride as a tracer, and continuous reaction times (RT) with a computerized test of variables (TOVA) in six adolescents (12-14 years of age, one female) who had been examined with cerebral blood flow (CBF) measurements at preterm birth and had a subsequent history of attention deficit. We found that high dopamine receptor availability ('empty receptors') was linked with increased RT and RT variability, supporting the concept of a dopaminergic role in symptomatology. High dopamine receptor availability was predicted by low neonatal CBF, supporting the hypothesis of cerebral ischaemia as a contributing factor in infants susceptible to ADHD. [ABSTRACT FROM AUTHOR]

Aim: Exclusive breastfeeding is recommended for the first 6 months of life, but the breastfeeding rate in premature infants is low. We examined the effect of oral stimulation on infant's strength of suction and the relation between this intra-oral vacuum and breastfeeding duration.Method: Between 2016 and 2018, 211 infants in a Danish neonatal unit were randomised 1:1 and of these 108 to oral stimulation intervention and 103 to control. Suction was measured as peak vacuum at enrolment and a corrected age of 6 weeks. Breastfeeding duration was registered.Results: Vacuum increased from enrolment to a corrected age of 6 weeks in all infants, and no effect of oral stimulation intervention was demonstrated P = .08. Infants born ≤32 gestational weeks had lower vacuum compared with infants born after, 350 vs 398 mbar P < .001. For infants born after 32 gestational weeks, the odds ratio for exclusive breastfeeding at 6 months was 1.99 per 100 mbar increase in vacuum P = .01.Conclusion: In our study, infant's intra-oral vacuum increased with age and was not affected by the oral stimulation intervention. For infants born after 32 gestational weeks, the exclusive breastfeeding rate was positively associated with a strong vacuum. [ABSTRACT FROM AUTHOR]

Aim: Although exclusive breastfeeding is recommended for all newborn in the first 6 months of life, only 13% of Danish premature infants complies with this. This trial aimed to examine whether oral stimulation prolonged exclusive breastfeeding in premature infants. Method: A randomised controlled trial was conducted at the Neonatal Intensive Care Unit, Hvidovre Hospital, Denmark between 2016 and 2018. Systematic oral stimulation was performed by the parents after training by occupational therapists. Primary outcome was exclusive breastfeeding duration with 6 months' follow‐up, analysed by intention‐to‐treat. Results: Included were 211 infants (53% boys) with a mean gestational age of 231 days, allocated in ratio 1:1 to oral stimulation or standard care. There was no difference in exclusive breastfeeding duration between infants orally stimulated and control infants. Thus, for orally stimulated infants, median duration was 122 days (interquartile range 40‐183) in contrast to 154 days (interquartile range 61‐183) for the controls, P value.16. At 6 months of age, 27% of orally stimulated infants were exclusively breastfed compared with 25% of controls. Conclusion: In healthy premature infants, oral stimulation performed by parents has no long‐lasting effect on breastfeeding duration. Attention should be directed to parental education and involvement. [ABSTRACT FROM AUTHOR]

Introduction: In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB. Material and methods: Mother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013. Results: We included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery. Conclusion: Offspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth. [ABSTRACT FROM AUTHOR]

The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) may have beneficial non-specific effects (NSEs) beyond the protection against TB. This may be related to modifications of the innate immune system. We investigated the effect of BCG at birth on differential white blood cell (WBC) count in healthy, Danish infants. The Danish Calmette Study randomised newborns to BCG at birth (Danish strain 1331, Statens Serum Institut) or no intervention. A sub-group of infants had blood samples collected 4 days after randomisation (n = 161), and at age 3 months (n = 152) and 13 months (n = 300). We evaluated the effect of BCG on WBC differential count (total leucocytes, lymphocytes, monocytes, eosinophil, neutrophil and basophil granulocytes (109 cells/L)) measured in peripheral blood. Overall, we found no effect of BCG on differential WBC counts at any time point. BCG at birth did not affect WBC count in our cohort of healthy, Danish infants. [ABSTRACT FROM AUTHOR]

Background The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non–tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. Methods A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. Results In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85–1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86–1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45–0.94); the HR for children who had a non–BCG-vaccinated mother was 1.10 (95% CI, 0.93–1.29) (P =.01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54–0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92–1.30] in other children; P =.02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95–3.43), whereas the HR was 0.94 (95% CI, 0.82–1.08) for children born at term (P =.05). Conclusion BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration. [ABSTRACT FROM AUTHOR]

Background: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size.Methods: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence or absence of a BCG scar and the size the scar was measured at 13 months of age.Results: Of 492 infants included, 87% had a wheal after vaccination, 11% had a bulge, and 2% had no reaction. The mean wheal size was 3.8 mm (95% confidence interval 3.7-3.9). Overall, 95% (442/466, 26 lost to follow-up) of BCG-vaccinated infants had a scar at 13 months of age. In infants with a wheal, the probability of developing a scar was 96%, declining to 87% in the case of a bulge, and to 56% in the case of no reaction (p for same probability = 0.03). Wheal size was positively correlated with the probability of getting a scar and scar size.Conclusion: Scarring after BCG vaccination has been associated with lower infant mortality. In a high-income setting, we found that correct injection technique is highly important for the development of a BCG scar and that registration of the category of BCG skin reaction (as wheal, bulge, or no reaction) may be used to identify infants at risk of scar failure. Finally, the wheal size was positively associated with both the probability of getting a scar and scar size.Trial Registration: The study was registered at www.ClinicalTrials.gov with trial registration number NCT01694108 . [ABSTRACT FROM AUTHOR]

Introduction BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. Methods Within 7 days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12 months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 ( Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4 weeks after the third vaccine dose. Results Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by ‘age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. Conclusions and relevance Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed. [ABSTRACT FROM AUTHOR]

Background: Bacillus Calmette-Guérin vaccine (BCG) induces a complex, pro-inflammatory immune response. Obesity is associated with low-grade inflammation.Aims: The purpose of the study was to test whether BCG at birth has effects on infant growth and body composition.Study Design, Subjects, and Outcome Measures: The Danish Calmette Study is a randomized, clinical trial. The study was conducted at three university hospitals and randomized 4262 children of gestational age ≥32weeks to receive BCG within seven days of birth or to a no-intervention control group. Follow-up consisted of clinical examinations. Outcome measures were weight and length at 3months, and weight, length, mid upper-arm circumference, and triceps and subscapular skinfold at 13months. Data collectors were blinded to allocation. Anthropometric measurements were converted to z-scores using WHO reference population.Results: Follow-up was 94% complete at 3 and 13months after birth. The children were bigger than the WHO reference population. There was no effect of BCG on weight z-score at 13months (-0.028 [95% confidence interval: -0.085 to 0.029], p=0.34). There was no effect on weight and length at 3months, or length, mid-upper-arm circumference, or triceps and subscapular skinfold at 13months.Conclusion: In this study, vaccination with BCG at birth did not have effects on child growth or body composition at 13months.Trial Registration: www.clinicaltrials.gov, registration number NCT01694108. [ABSTRACT FROM AUTHOR]

Objective To evaluate adverse reactions of the Bacillus Calmette–Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. Design A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age. Setting Pediatric and maternity wards at three Danish university hospitals. Participants All women planning to give birth at the three study sites ( n = 16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. Main outcome and measure Trial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. Results Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected ( p -value <0.001). Conclusions and relevance BCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications. Trial registration Trial registration number NCT01694108 at www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Objectives: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. Design: This is a pre-specified secondary outcome from a randomised, clinical trial. Setting: Maternity units and paediatric wards at three university hospitals in Denmark. Participants: Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA < 37 weeks). There were 2129 children (71 premature) randomised to BCG and 2133 randomised (73 premature) to the control group. Interventions: BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation. Main outcome measures: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age < 37 weeks) completed an ASQ at 6 and 22 months. Developmental assessment was available for 3453/4262 (81%). Results: The mean difference in ASQ score at 12 months adjusted for age and prematurity was -0.7 points (BCG vs. control, 95% confidence interval; -3.7 to 2.4), p = 0.67, corresponding to an effect size of Cohen’s d = -0.015 (-0.082 to 0.052). The mean difference in ASQ score for premature children at 22 months was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). Conclusions: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Introduction: Offspring of obese women have both short-term and long-term increased morbidities. We investigated the relationship between maternal 2-h plasma glucose level determined by an oral glucose tolerance test, degree of obesity, gestational weight gain and total fat, abdominal fat, and fat-free masses in the offspring of obese mothers.Material and Methods: Obese mother-newborn dyads were recruited and 2-h plasma glucose levels were assessed during gestational weeks 27-30; neonatal body composition was measured by dual-energy X-ray absorptiometry scanning (DXA) within 48 h of birth.Results: Among 264 term, healthy, and singleton infants eligible for inclusion, 248 were included. Of these, 205 (83%) obese mother-newborn dyads had a DXA scan and 2-h plasma glucose measurements. Linear regression analysis showed that birthweight z-scores correlated with 2-h plasma glucose levels (p = 0.002) after adjusting for gestational weight gain, maternal age, education, smoking, prepregnancy degree of obesity, parity, and birth length. Total (p = 0.012) and abdominal (p = 0.039) fat masses correlated with 2-h plasma glucose levels after adjusting for gestational weight gain, maternal age, education, smoking, prepregnancy degree of obesity, parity, gestational age, and newborn sex. There was no association between total (p = 0.88) and abdominal (p = 0.61) fat-free masses and 2-h plasma glucose.Conclusion: At 27-30 weeks of gestation, 2-h plasma glucose levels are related to total and abdominal newborn fat masses, but not to fat-free mass. Interventions targeting maternal postprandial glucose levels may induce more appropriate birthweight, thereby reducing the risk of subsequent morbidity. [ABSTRACT FROM AUTHOR]

Background: Lifestyle interventions targeting obese pregnant women often result in modest reduction in gestational weight gain, pregnancy complications and related risk factors. Examining adherence to the intervention can, however, provide valuable information on the importance of the different factors targeted. Objective: To evaluate improvements and relevance of different dietary factors targeted with respect to gestational weight gain in a 3-arm Randomised Controlled Trial (n=342) among obese pregnant women with BMI≥30 kg/m2. Methods: Randomisation 1:1:1 to either hypocaloric Mediterranean type of diet and physical activity intervention (D+PA); physical activity intervention alone (PA); or control (C). Diet was assessed at baseline (weeks 11–14) and endpoint (weeks 36–37) using a validated food frequency questionnaire. Results: During the intervention women in the D+PA group significantly lowered their intakes of added sugars and saturated fat and increased their protein intake by ~1% of total energy compared to controls. Of these dietary variables only intakes of added sugar appeared to be related to GWG, while no association was observed for saturated fat or protein. Further analyses revealed that foods that contributed to intake of added sugars, including sweets, snacks, cakes, and soft drinks were strongly associated with weight gain, with women consuming sweets ≥2/day having 5.4 kg (95% CI 2.1-8.7) greater weight gain than those with a low (<1wk) intake. The results for soft drinks were more conflicting, as women with high weight gain tended to favour artificially sweetened soft drinks. Conclusion: In our sample of obese pregnant women, craving for sweets, snacks, and soft drinks strongly predicts GWG. Emphasis on reducing intakes of these foods may be more relevant for limiting gestational weight gain than encouraging strict compliance to more specific diets. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I). Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I. Methods: We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA) within 48 hours of birth. Results: Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52%) infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001). Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001) and IGF-I (p = 0.004). Conclusion: Peripheral fat tissue accumulation was associated with cord blood C-peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I. [ABSTRACT FROM AUTHOR]

Background Studies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly allergic diseases. The potential clinical value of these non-specific effects has not yet been examined in a large randomised trial in high-income countries. Methods The Danish Calmette Study is a multicentre randomised clinical trial conducted between October 2012 and November 2015. Within the first 7 days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age 4 days, 3 and 13 months. Thymus index was assessed by ultrasound in a subgroup at randomisation and at 3 months. The primary study outcome is hospitalisation within the first 15 months of life as assessed in Danish health registers. Secondary outcomes include infectious disease hospitalisations, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered. Discussion With participation of 4184 families and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting. [ABSTRACT FROM AUTHOR]

Aim: There is a lack of evidence on the best treatment option for umbilical granuloma. The primary aim of this study was to compare three treatments for umbilical granuloma: standard treatment with topical silver nitrate, clobetasol propionate cream (0.05%) and ethanol wipes. The secondary aim was to evaluate whether the treatment could be successfully administered by a parent at home, rather than in the outpatient clinic. Methods: A total of 109 infants were randomised to one of three groups and 94 infants completed the assigned treatment: 30 infants received standard treatment with silver nitrate (99%) in the outpatient clinic, 30 infants had topical clobetasol propionate cream (0.05%) applied at home, and 34 infants received cleansing with ethanol wipes (82%) at home. Results: Silver nitrate and clobetasol propionate cream (0.05%) were significantly superior to ethanol wipes, with shorter healing times and higher resolution rates (p = 0.0001). Healing time and resolution rates were identical for silver nitrate and clobetasol propionate cream (0.05%). Mild side effects were occasionally reported, all of which were self-limiting. Conclusion: Treating umbilical granuloma with topical clobetasol propionate cream (0.05%) at home is as effective as treating it with topical silver nitrate (99%) in the clinic. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. Methods: Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy). Results: Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05). Conclusion: We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Abstract: Abnormal central dopamine (DA) neurotransmission has been implicated in the impulsivity, inattention, and hyperactivity of attention deficit hyperactivity disorder (ADHD). We hypothesized that a pharmacological challenge with methylphenidate (MP) at a therapeutic dose increases extracellular DA concentrations in proportion to the severity of these specific ADHD symptoms. To test this hypothesis, we measured by PET the effect of acute challenge with MP on the availability of striatal binding sites for [11C]raclopride (pB), an index of altered interstitial DA concentration, in nine unmedicated adolescents (1 female, 8 males; age 13.7 ± 1.8 years) with a current diagnosis of ADHD. We estimated the pB of [11C]raclopride for brain dopamine D2/3 receptors first in a baseline resting condition, and again after an acute challenge with MP (0.3 mg/kg, p.o.), and calculated the percentage change in (%ΔpB) in left and right striatum. On another day, measurements of impulsivity and inattention were performed using a computerized continuous performance test. There was a significant correlation between the magnitude of %ΔpB in the right striatum and the severity of inattention and impulsivity. MP-evoked %ΔpB correlated with standard scores for impulse control (r = 0.68; P = 0.02), attention (r = 0.81; P = 0.005), information processing (r = 0.66; P = 0.02), and consistency of attention, or variability (r = 0.60; P = 0.04). In conclusion, the results link inattention and impulsivity with sensitivity of brain DA receptor availability to an MP challenge, corroborating the hypothesis that MP serves to potentiate decreased DA neurotransmission in ADHD. [Copyright &y& Elsevier]

Objective: To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis.Design: Double-blind, randomised, placebo-controlled, multi-centre trial.Setting: Fourteen Danish obstetric departments.Population: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children.Methods: Women were randomised to receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire.Main Outcome Measure: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP.Results: The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65).Conclusions: Antenatal MgSO4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis.Tweetable Abstract: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Treating umbilical granuloma with topical clobetasol propionate cream at home is as effective as treating it with topical silver nitrate in the clinic" in the previous issue of the journal is presented.

The article discusses a study based on randomized clinical trial (RCT) for assessing whether magnesium sulphate given to women prior to preterm birth can protect their children against cerebral palsy. It informs that 1240 women from Denmark, Sweden, and Iceland, who are at risk of preterm birth at 24-32 weeks of gestation, will receive intravenous magnesium sulfate randomly. It mentions that children will be followed up after 18 months of age by forwarding a questionnaire to the parents.