Medial anterior prefrontal cortex stimulation downregulates implicit reactions to threats and prevents the return of fear.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.

Follow-up of a randomized trial optimizing neonatal nutrition in preterm very low birthweight infants: growth, serum adipokines, renal function and blood pressure.

OBJECTIVE: The primary objectives were to compare body mass index (BMI) Z-score (Z), systolic blood pressure (SBP), serum leptin:adiponectin (L:A) ratio and estimated glomerular filtration rate (eGFR) at ~3 years adjusted age between two arms of a randomized controlled trial (RCT) comparing two modes of human milk fortification for very low-birthweight infants in the neonatal intensive care unit. STUDY DESIGN: Follow-up of RCT at 33-48 months. RESULTS: Follow-up data are available in 82/120 infants. Infants in the experimental arm have anthropometric data consistent with central obesity and higher serum L:A ratio (sensitivity analysis adjusting for sex and using all available data), but have similar eGFR and SBP at follow-up compared with controls. Serum L:A ratio is strongly correlated with anthropometric measurements suggesting central obesity. CONCLUSIONS: Infants in the experimental arm have central obesity and higher serum L:A ratio compared with controls. Notably, serum L:A ratio is strongly correlated with weight gain. TRIAL REGISTRATION: This randomized controlled trial was registered at ClinicalTrials.gov NCT02372136.

Relationship between Ventricular Size on Latest Ultrasonogram and the Bayley Scores ≥ 18 Months in Extremely Low Gestational Age Neonates: A Retrospective Cohort Study.

OBJECTIVE: A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age. STUDY DESIGN: The present study is a single-center retrospective cohort study. RESULTS: The study included 270 preterm infants born at 230/7 to 286/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive (p = 0.002), language (p = 0.004), and motor (p < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage. CONCLUSION: In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores. KEY POINTS: · Mean values of VBI are stable with postmenstrual age.. · Values at the foramen of Monro are reliable and reproducible.. · VBI is negatively associated with Bayley scores.. · The association is observed even before term age..

Double-blinded randomized controlled trial of optimizing nutrition in preterm very low birth weight infants: Bayley scores at 18-38 months of age.

BACKGROUND: Human milk supplementation for preterm infants in the neonatal intensive care unit (NICU) can be based on optimized nutrition (feeding adjustments based on growth and measurements of serum nutrients) or individualized nutrition (measurements of macronutrients in mother's own milk). OBJECTIVE: To compare Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18-38mo adjusted age in infants who had been randomly allocated to individualized+optimized nutrition (experimental group) vs optimized nutrition alone (control) in the NICU. METHODS: Double-blinded randomized controlled trial in neonates <29wks gestational age (GA) and those <34wks GA and small for GA. RESULTS: Bayley scores were assessed in 91/114 (80%) infants. The two study groups had similar frequencies of low cognitive, motor and language Bayley scores and similar age-adjusted Bayley scores in bivariate and multivariate analyses. CONCLUSIONS: The type of human milk supplementation provided had no significant effect on Bayley scores assessed at 18-38mo. TRIAL REGISTRATION: This randomized controlled trial was registered at ClinicalTrials.gov NCT02372136.

Quality improvement project designed to reduce disproportionate growth in extremely low gestational age neonates: cognitive neurodevelopmental outcome at 18-41 months.

OBJECTIVE: To assess if the adjusted odds of low composite cognitive Bayley-III scores changed after implementing a single-institution quality improvement (QI) project designed to decrease discharge Z-scores for weight, body mass index (BMI), and weight-for-length, but not length or fronto-occipital circumference (FOC) in infants 23-28 weeks gestational age (GA). METHODS: Compare Bayley-III outcomes at ≥18 months corrected age (postnatal age adjusted for prematurity) in infants tested before (Epoch-1) and after (Epoch-2) QI implementation. RESULTS: Bayley testing was available in 134/156 infants (86%) in Epoch-1 and 139/175 (79%) in Epoch-2. There was no change in frequency of low (<85) cognitive score (p = 0.5) or in median cognitive scores (80 in Epoch-1 vs. 85 Epoch-2, p = 0.35). The adjusted odds of low cognitive scores was not different between Epochs. CONCLUSION: No change in cognitive outcome at ≥18 months corrected age was observed after implementing a QI project designed to reduce discharge weight-for-length disproportion in very preterm infants.

Zinc deficiency limiting head growth to discharge in extremely low gestational age infants with insufficient linear growth: a cohort study.

OBJECTIVE: To assess the relationship of size for age with zinc deficiency in extremely low gestational age (GA) infants (23-28 weeks, ELGANs) who had insufficient linear growth despite optimizing other nutrients and to analyze changes in fronto-occipital circumference (FOC), weight and length with zinc supplementation. STUDY DESIGN: Retrospective cohort study. RESULTS: Among 302 ELGANs, a serum zinc concentration was obtained in 52 with insufficient linear growth (17%). Zinc deficiency (serum concentration <0.74 mcg/ml) was diagnosed in 8 of 24 (33%) small for GA (SGA) compared to 35 of 278 (13%) non-SGA infants (P = 0.01). Zinc supplementation for >2 weeks improved FOC growth to discharge or 50 weeks postmenstrual age in infants with Zn deficiency. However, neither linear growth nor weight gain improved with Zn supplementation. CONCLUSION: Zinc deficiency was diagnosed in 14% ELGANs in this cohort. Zinc supplementation for >2 weeks improved FOC growth but not linear growth or weight gain.

Association of age of initiation and type of complementary foods with body mass index and weight-for-length at 12 months of age in preterm infants.

OBJECTIVE: To assess whether in very preterm infants (1) body mass index (BMI) Z-score and weight-for-length (WtFL) Z-score at 1 year of age and (2) head growth from discharge to 1 year are associated with breastfeeding at discharge and the age of onset and type of complementary foods. STUDY DESIGN: Observational cohort study. RESULTS: Infants started on only ready-made complementary (RMC) feedings at ≤26 weeks adjusted age had the highest adjusted BMI Z-score and WtFL Z-score at 1 year of age. Adjusted change in fronto-occipital circumference was highest in infants either discharged on breastmilk or receiving home-made complementary food with/without RMC (HMM) at ≤26 weeks adjusted age. CONCLUSIONS: Infants started on RMC ≤26 weeks adjusted age had the highest BMI Z-score and WtFL Z-score at 1 year. Head growth from discharge to 1 year was highest in infants either discharged on breastmilk or receiving HMM at ≤26 weeks adjusted age.

Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial.

OBJECTIVE: In preterm neonates fed human milk, fortification may be adjusted by (1) optimization, based on growth rate and serum nutrient analyses, or (2) individualization, based on serial milk nutrient analyses. The primary aim was to determine whether individualized plus optimized nutrition (experimental) improves velocity of weight gain and linear growth from birth to endpoint (36 weeks postmenstrual age or discharge) when compared with optimized nutrition alone (controls). STUDY DESIGN: Double-blinded parallel group randomized trial in 120 neonates <29 weeks gestational age (GA) or <35 weeks and small for GA (birth weight < 10th centile). RESULT: Weight-gain velocity (13.1 ± 2.1, n = 57 controls, vs. 13.0 ± 2.6 g kg-1 day-1, n = 59 experimental, P = 0.87), linear growth (0.9 ± 0.2, n = 55, vs. 0.9 ± 0.2 cm week-1, n = 52, P = 0.90) and frequency of weight/length disproportion (2% vs. 2%, P = 0.98) were similar in both groups. CONCLUSIONS: Individualized plus optimized nutrition does not improve weight gain, linear growth, or weight/length disproportion at endpoint versus optimized nutrition alone.

Correction to: Adjustable feedings plus accurate serial length measurements decrease discharge weight-length disproportion in very preterm infants: quality improvement project.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Adjustable feedings plus accurate serial length measurements decrease discharge weight-length disproportion in very preterm infants: quality improvement project.

BACKGROUND: Preterm very-low-birth-weight (≤1500 g) infants exhibit disproportionate weight-for-length growth in the Neonatal Intensive Care Unit. LOCAL PROBLEM: High frequency of body mass index (BMI) > 90th centile at discharge and 1-year postnatal age associated with elevated blood pressure and serum leptin in infancy and adolescence. METHODS: Single-institution quality improvement project in appropriately grown infants born at 230/7-286/7 weeks gestational age and discharged home. INTERVENTION: Adjustable feeding protocol based on valid serial length measurements (board or caliper). RESULTS: The average monthly percentage of weight-for-length disproportion at discharge decreased from 13% in Epoch 1 to 0% in Epoch 2 (P < 0.05). Although the average Z-score for BMI at discharge was lower in Epoch 2 versus Epoch 1 (P < 0.01), this was absent by 1 year follow-up (P = 0.91). CONCLUSIONS: Adjustable feedings plus use of accurate serial length measurements decreases weight-for-length disproportion at hospital discharge but not at 1 year.