School functioning in 8- to 18-year-old children born after in vitro fertilization

The aim of this study was to examine the school functioning of 8- to 18-year-old children born after in vitro fertilization (IVF). We compared 233 children born after IVF to 233 matched control children born spontaneously from parents with fertility problems on measures of education level, general cognitive ability, school performance (need for extra help, repeating a grade, special education), and rates of learning and developmental disorders. No differences were found between IVF and control children on these measures of school functioning. More than 60% of adolescents at secondary school attended high academic levels (with access to high school or university). We conclude that children and adolescents born after IVF show good academic achievement and general cognitive ability. They do not experience any more educational limitations than the naturally conceived children and adolescents of the control group. The tendency of reassuring school functioning already found in younger IVF children has been shown to continue at secondary school age

Evidence for genetic factors explaining the association between birth weight and low-density lipoprotein cholesterol and possible intrauterine factors influencing the association between birth weight and high-density lipoprotein cholesterol: Analysis in twins

Recent studies have demonstrated an association between low weight at birth and an atherogenic lipid profile in later life. To examine the influences of intrauterine and genetic factors, we investigated 53 dizygotic and 61 monozygotic adolescent twin pairs. Regression analysis demonstrated that low birth weight was associated with high levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (-0.17 mmol/liter per kg, P = 0.07; -0.18 mmol/liter per kg, P = 0.04; and -0.07 g/liter per kg, P = 0.02, respectively) and with low levels of high-density lipoprotein (HDL) cholesterol (+0.04 mmol/liter per kg, P = 0.1), after adjustment for age, sex, and body mass index. Intrapair differences in birth weight were significantly associated with differences in total cholesterol, LDL cholesterol, and apolipoprotein B in dizygotic twins after adjustment for differences in current body mass index (-0.49 mmol/liter per kg, P = 0.02; -0.51 mmol/liter per kg, P = 0.01; and -0.10 g/liter per kg, P = 0.04, respectively), demonstrating that the larger the difference in birth weight, the higher these risk factors in the twin with the lower birth weight, compared with the cotwin with the higher birth weight. In monozygotic twins, however, the associations between intrapair differences in birth weight and differences in total cholesterol, LDL cholesterol, and apolipoprotein B were in the opposite direction (+0.32 mmol/liter per kg, P = 0.03; +0.23 mmol/liter per kg, P = 0.08; and +0.06 g/liter per kg, P = 0.04, respectively). The association between intrapair differences in birth weight and differences in HDL cholesterol was not significant in dizygotic twins (+0.04 mmol/liter per kg, P = 0.6) and of borderline significance in monozygotic twins (+0.11 mmol/liter per kg, P = 0.05). These data suggest that genetic factors account for the association of low birth weight with high levels of total cholesterol, LDL cholesterol, and apolipoprotein B, whereas intrauterine factors possibly play a role in the association between birth weight and HDL cholesterol

Propofol in neonates causes a dose-dependent profound and protracted decrease in blood pressure

Aim: To analyse the effects of different propofol starting doses as premedication for endotracheal intubation on blood pressure in neonates. Methods: Neonates who received propofol starting doses of 1.0 mg/kg (n = 30), 1.5 mg/kg (n = 23) or 2.0 mg/kg (n = 26) as part of a previously published dose-finding study were included in this analysis. Blood pressure in the 3 dosing groups was analysed in the first 60 minutes after start of propofol. Results: Blood pressure declined after the start of propofol in all 3 dosing groups and was not restored 60 minutes after the start of propofol. The decline in b

Impact of a Multi-Strain Probiotic on Healthcare-Associated Bloodstream Infection Incidence and Severity in Preterm Neonates

Aim:Hospital acquired bloodstream infection (HA-BSI) is a major contributor to morbidity and mortality in preterm, very low birthweight infants, especially in low-to-middle- income countries.Materials and Methods:We conducted a double-blind, placebo-controlled, randomized clinical trial to investigate the effect of a multi-strain probiotic formulation (LabinicTM) on the incidence and severity of HA-BSI in preterm neonates.Results:Two hundred neonates (100 per arm) were included in this trial. Fifteen neonates developed HA-BSI events (2 in the probiotic arm and 13 in the placebo arm). The median day of life at HA-BSI onset for the probiotic group was 10.5±3.5, and for the placebo group, it was 11.2±6.4. The incidence of HA-BSI in neonates receiving the probiotic was significantly lower compared to those receiving the placebo [0.93 versus 5.99 HA-BSI events/1,000 neonate-days; incidence rate ratio (IRR) of 0.156 [95% confidence interval (CI): 0.017 to 0.691], p=0.0046]. Calculating the incidence rate of the combined outcome (sepsis/death) was also lower in the probiotic group versus the placebo group [2.34 versus 6.45 events/1,000 neonate days; IRR 0.33 (95% CI: 0.11 to 0.97), p=0.043].Conclusion:The use of a multi-strain probiotic significantly reduced HA-BSI incidence in this cohort of preterm neonates

Propofol for endotracheal intubation in neonates: A dose-finding trial

Objective: To find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA). Design and setting: Prospective multicentere dose-finding study in 3 neonatal intensive care units. Patients: Neonates with a PNA <28 days requiring non-emergency endotracheal intubation. Interventions: Neonates were stratified into 8 groups based on GA and PNA. The first 5 neonates in every group received a dose of 1.0 mg/kg propofol. Based on sedative effect and side effects, the dose was increased or decreased in the next 5 patients until the optimal dose was found. Main outcome measures: The primary outcome was the optimal single propofol starting dose that provides effective sedation without side effects in each age group. Results: After inclusion of 91 patients, the study was prematurely terminated because the primary outcome was only reached in 13% of patients. Dose-finding was completed in 2 groups, but no optimal propofol dose was found. Effective sedation without side effects was achieved more often after a starting dose of 2.0 mg/kg (28%) than after 1.0 mg/kg (3%) and 1.5 mg/kg (9%). Propofol-induced hypotens

Low birth weight is associated with increased sympathetic activity

Background - Low birth weight may be associated with high blood pressure in later life through genetic factors, an association that may be explained by alterations in sympathetic and parasympathetic activity. We examined the association of birth weight with cardiac pre-ejection period and respiratory sinus arrhythmia (indicators of cardiac sympathetic and parasympathetic activity, respectively) and with blood pressure in 53 dizygotic and 61 monozygotic adolescent twin pairs. Methods and Results - Birth weight of the twins was obtained from the mothers. Pre-ejection period and respiratory sinus arrhythmia were measured with electrocardiography and impedance cardiography at rest, during a reaction time task, and during a mental arithmetic task. In the overall sample, lower birth weight was significantly associated with shorter pre-ejection period at rest, during the reaction time task, and during the mental arithmetic task (P=0.0001, P<0.0001, and P=0.0001, respectively) and with larger pre-ejection period reactivity to the stress tasks (P=0.02 and P=0.06, respectively). In within-pair analyses, differences in birth weight were associated with differences in pre-ejection period at rest and during both stress tasks in dizygotic twin pairs (P=0.01, P=0.06, and P=0.2, respectively) but not in monozygotic twin pairs (P=0.9, P=1.0, and P=0.5, respectively). Shorter pre-ejection period explained approximately 63% to 84% of the birth weight and blood pressure relation. Conclusions - Low birth weight is associated with increased sympathetic activity, and this explains a large part of the association between birth weight and blood pressure. In addition, our findings suggest that the association between birth weight and sympathetic activity depends on genetic factors

Protocol of a randomised controlled trial of real-time continuous glucose monitoring in neonatal intensive care 'REACT'.

INTRODUCTION: Hyperglycaemia is common in the very preterm infant and has been associated with adverse outcomes. Preventing hyperglycaemia without increasing the risk of hypoglycaemia has proved challenging. The development of real-time continuous glucose monitors (CGM) to inform treatment decisions provides an opportunity to reduce this risk. This study aims to assess the feasibility of CGM combined with a specifically designed paper guideline to target glucose control in the preterm infant. METHODS AND ANALYSES: The Real Time Continuous Glucose Monitoring in Neonatal Intensive Care (REACT) trial is an international multicentre randomised controlled trial. 200 preterm infants ≤1200 g and ≤24 hours of age will be randomly allocated to either real-time CGM or standard care (with blinded CGM data collection). The primary outcome is time in target 2.6-10 mmol/L during the study intervention assessed using CGM. Secondary outcomes include efficacy relating to glucose control, utility including staff acceptability, safety outcomes relating to incidence and prevalence of hypoglycaemia and health economic analyses. ETHICS AND DISSEMINATION: The REACT trial has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge Central); Medical Ethics Review Committee, VU University Medical Centre, Amsterdam, The Netherlands and the Research Ethics Committee, Sant Joan de Déu Research Foundation, Barcelona, Spain. Recruitment began in July 2016 and will continue until mid-2018. The trial has been adopted by the National Institute of Health Research Clinical Research Network portfolio (ID: 18826) and is registered with anInternational Standard Randomised Control Number (ISRCTN registry ID: 12793535). Dissemination plans include presentations at scientific conferences, scientific publications and efforts at stakeholder engagement. TRIAL REGISTRATION NUMBER: ISRCTN12793535; Pre-results

Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.

UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.This work was supported by a European Commission FP7 project 305485 PREVENT-ROP grant to all of the authors.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1111/apa.1335

Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial.

BACKGROUND: Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care. METHODS: This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6-10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535. FINDINGS: Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95% CI 5-21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection. INTERPRETATION: Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes. FUNDING: National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.NIHR EM