•Few data on neurologic outcomes after in utero exposure to general anesthesia (GA).•Secondary analysis of randomized trial of maternal magnesium and cerebral palsy.•Exposure to GA was not associated ...with impaired neurodevelopment overall.•Only severe motor delay was significantly more common among infants exposed to GA.•Findings are reassuring regarding a single, short in utero exposure to GA.
In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment.
A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders.
Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010).
General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.
This study assessed the efficacy of
FaceSay
, a computer-based social skills training program for children with Autism Spectrum Disorders (ASD). This randomized controlled study (
N
= 49) indicates ...that providing children with low-functioning autism (LFA) and high functioning autism (HFA) opportunities to practice attending to eye gaze, discriminating facial expressions and recognizing faces and emotions in FaceSay’s structured environment with interactive, realistic avatar assistants improved their social skills abilities. The children with LFA demonstrated improvements in two areas of the intervention: emotion recognition and social interactions. The children with HFA demonstrated improvements in all three areas: facial recognition, emotion recognition, and social interactions. These findings, particularly the measured improvements to social interactions in a natural environment, are encouraging.
ObjectiveThe Bayley Scales of Infant Development (BSID) is the most used diagnostic tool to identify neurodevelopmental disorders in children under age 3 but is challenging to use in low-resource ...countries. The Ages and Stages Questionnaire (ASQ) is an easy-to-use, low-cost clinical tool completed by parents/caregivers that screens children for developmental delay. The objective was to determine the performance of ASQ as a screening tool for neurodevelopmental impairment when compared with BSID second edition (BSID-II) for the diagnosis of moderate-to-severe neurodevelopmental impairment among infants at 12 and 18 months of age in low-resource countries.MethodsStudy participants were recruited as part of the First Bites Complementary Feeding trial from the Democratic Republic of Congo, Zambia, Guatemala and Pakistan between October 2008 and January 2011. Study participants underwent neurodevelopmental assessment by trained personnel using the ASQ and BSID-II at 12 and 18 months of age.ResultsData on both ASQ and BSID-II assessments of 1034 infants were analysed. Four of five ASQ domains had specificities greater than 90% for severe neurodevelopmental delay at 18 months of age. Sensitivities ranged from 23% to 62%. The correlations between ASQ communications subscale and BSID-II Mental Development Index (MDI) (r=0.38) and between ASQ gross motor subscale and BSID-II Psychomotor Development Index (PDI) (r=0.33) were the strongest correlations found.ConclusionAt 18 months, ASQ had high specificity but moderate-to-low sensitivity for BSID-II MDI and/or PDI <70. ASQ, when administered by trained healthcare workers, may be a useful screening tool to detect severe disability in infants from rural low-income to middle-income settings.Trial registration numberNCT01084109.
Prion propagation involves a templating reaction in which the infectious form of the prion protein (PrPSc) binds to the cellular form (PrPC), generating additional molecules of PrPSc. While several ...regions of the PrPC molecule have been suggested to play a role in PrPSc formation based on in vitro studies, the contribution of these regions in vivo is unclear. Here, we report that mice expressing PrP deleted for a short, polybasic region at the N terminus (residues 23-31) display a dramatically reduced susceptibility to prion infection and accumulate greatly reduced levels of PrPSc. These results, in combination with biochemical data, demonstrate that residues 23-31 represent a critical site on PrPC that binds to PrPSc and is essential for efficient prion propagation. It may be possible to specifically target this region for treatment of prion diseases as well as other neurodegenerative disorders due to beta -sheet-rich oligomers that bind to PrPC.
Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient ...supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m
: adjusted mean difference (aMD) -0.1195% CI -0.47, 0.25,
= 0.54; 3 trials,
= 333). Supplementation increased length (cm: aMD 0.370.01, 0.72,
= 0.04; 18 trials,
= 2008) and bone mineral content (g: aMD 10.220.52, 19.92,
= 0.04; 6 trials,
= 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.200.02, 0.37,
= 0.03; 10 trials,
= 595) but not in females, and no significant sex interaction was observed (
= 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.
Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements ...on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials,
= 1410; adjusted relative risk (aRR) 0.88 95% CI 0.68, 1.13;
= 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials,
= 438; aRR 0.94 0.76, 1.17;
= 0.59). However, supplementation reduced motor impairment in toddlers (13 trials,
= 1406; aRR 0.76 0.60, 0.97;
= 0.03), and improved motor scores overall (13 trials,
= 1406; adjusted mean difference 1.57 0.14, 2.99;
= 0.03) and in girls not boys (
= 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.
Blue wine, recently appeared on the French market, is part of the effort made by winemakers in creating new and attractive wine, while maintaining traditional manufacturing processes. According to ...the labels on the bottles, the blue wine prides itself on being a natural wine, whose blue color is also obtained in a natural way by means of a very particular wine-making process. This study reports first analyses carried out on two blue wines to determine the origin of the blue color. The results show that a well-known coloring food additive was used in the wine and identified as Brilliant Blue FCF by UV–Vis spectroscopy and high-resolution mass spectrometry. The amounts of Brilliant Blue FCF were assessed in the two wines by high-performance liquid chromatography coupled to UV–Vis spectroscopy and found to be 8.62 ± 0.04 mg L
−1
and 5.46 ± 0.01 mg L
−1
in Vindigo and Imajyne wines, respectively. Such addition was, however, not specified by the winemakers.
IMPORTANCE: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants ...receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. OBJECTIVE: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months’ corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days’ gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. INTERVENTION: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. MAIN OUTCOMES AND MEASURES: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months’ corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months’ corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. RESULTS: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent’s race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months’ corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, −0.77 95% CI, −3.93 to 2.39, which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, −1% 95% CI, −4% to 2%). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, −5% 95% CI, −9% to −2%). Weight gain was slower in the donor milk group (22.3 g/kg/d 95% CI, 21.3 to 23.3 g/kg/d) compared with the preterm formula group (24.6 g/kg/d 95% CI, 23.6 to 25.6 g/kg/d). CONCLUSIONS AND RELEVANCE: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months’ corrected age did not differ between infants fed donor milk or preterm formula. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01534481
To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death.
This is a secondary analysis of data from a multicenter ...placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (
= 11) and demographic and clinical factors (
= 10) evident by the time of discharge among surviving infants (
= 1889) and the primary outcome of death or moderate/severe CP at age 2 (
= 73) was estimated, and a prediction model was created.
Gestational age in weeks at delivery (odds ratio OR: 0.74, 95% confidence interval CI: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants.
IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae.
· Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge..
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