Neurocognitive outcomes in moderately preterm born adolescents.

BACKGROUND: Early preterm (EP) born children are at risk of neurocognitive impairments persisting into adulthood. Less is known about moderately to late (MLP) preterm born children, especially after early childhood. The aim of this study was to assess neurocognitive functioning of MLP adolescents regarding intelligence, executive and attentional functioning, compared with EP and full-term (FT) adolescents. METHODS: This study was part of the Longitudinal Preterm Outcome Project (LOLLIPOP), a large community-based observational cohort study. In total 294 children (81 EP, 130 MLP, and 83 FT) were tested at age 14 to 16 years, regarding intelligence, speed of processing, attention, and executive functions. We used the Dutch version of the Wechsler Intelligence Scale for Children-Third Edition-Dutch Version (WISC-III-NL), the Test of Everyday Attention for Children, and the Behavioural Assessment of the Dysexecutive Syndrome for Children. We assessed differences between preterm-born groups with the FT group as a reference. RESULTS: Compared to the FT group, MLP adolescents scored significantly lower on two subtasks of the WISC-III-NL, i.e. Similarities and Symbol Search. EP adolescents performed significantly lower on all neuropsychological tests than their FT peers, except for the subtask Vocabulary. The MLP adolescents scored in between FT and EP adolescents on all tasks, except for three WISC-III-NL subtasks. CONCLUSIONS: Neurocognitive outcomes of MLP adolescents fell mostly in between outcomes of their EP and FT peers. MLPs generally performed on a low-average to average level, and appeared susceptible to a variety of moderate neurodevelopmental problems at adolescent age, which deserves attention in clinical practice.

Effects of olfactory and/or gustatory stimuli on feeding of preterm infants: A systematic review and meta-analysis.

AIM: To evaluate the effect of olfactory and/or gustatory stimulation interventions on feeding outcomes in preterm infants. METHODS: We conducted systematic searches across various academic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, the Wanfang Database, and the Wipu Database. These searches aimed to identify randomized controlled trials investigating the impact of olfactory and/or gustatory stimulation on preterm infants. The search period spanned from the inception of the databases until December 2022. Two independent evaluators autonomously reviewed the literature, extracted pertinent data, assessed the quality of the included studies, and conducted a meta-analysis using RevMan 5.3 software. RESULTS: A total of 7 randomized controlled trials or quasi-experimental studies were included, with a total of 871 participants. Olfactory and gustatory stimulation demonstrated a reduction in the time to full enteral feeds in preterm infants when compared to usual care (MD = -1.60 days; 95% CI = -2.31, -0.89; p<0.0001). No substantial evidence was identified regarding the influence of olfactory and gustatory stimulation on the duration of gastric tube placement, length of hospitalization, incidence of necrotizing enterocolitis, or occurrence of spontaneous bowel perforation in preterm infants. CONCLUSIONS: Olfactory and gustatory stimulation show potential benefits for preterm infants. However, due to the low to very low level of certainty associated with the available data, our ability to assess the effects is limited. Further trials and studies are essential to enhance our understanding of the mechanisms and effectiveness of olfactory and gustatory stimulation therapies.

Randomized Controlled Trial Protocol on the Effects of a Sensory Motor Intervention Associated with Kangaroo Skin-to-Skin Contact in Preterm Newborns.

There is still very limited evidence on the effects of neonatal interventions on infant neurodevelopmental outcomes, including general movements (GMs). This research will primarily assess the effects of a sensory motor physical therapy intervention combined with kangaroo skin-to-skin contact on the GMs of hospitalized preterm newborns. Secondary outcomes include body weight, posture and muscle tone, behavioral state, length of hospital stay, and breastfeeding. This study protocol details a two-arm parallel clinical trial methodology, involving participants with a postmenstrual age of 34-35 weeks admitted to a Neonatal Intermediate Care Unit (NInCU) with poor repertoire GMs. Thirty-four participants will be randomly assigned to either the experimental group, receiving a 10-day sensory motor physical therapy associated with kangaroo skin-to-skin contact, or the control group, which will only receive kangaroo skin-to-skin contact. The study will measure GMs (primary outcome), and body weight, posture and muscle tone, behavioral state, length of hospital stay, and breastfeeding (secondary outcomes). Data collection occurs in the NInCU before and after the intervention, with follow-up measurements post discharge at 2-4 weeks and 12-15 weeks post-term. SPSS will be used for data analyses. The results will provide novel information on how sensory motor experiences may affect early neurodevelopment and clinical variables in preterm newborns.

Executive function and preterm birth: A longitudinal study.

Infants born low birth weight (LBW) and preterm are at risk for developmental delay and cognitive deficits. These deficits can lead to lifelong learning difficulties and high-risk behaviors. Preterm (PT) and full-term (FT) groups were compared across infant and toddler measures of behavior and development to extract early indicators of executive function (EF). The goal was to extract indicators of EF from standardized infant assessments. PT (<2500 grams and <37 weeks) and FT (> 2500 grams and >37 weeks) were compared across assessment and EF components were identified from the BSID-III. A multivariate linear model was used to examine group differences. All children (99 PT and 46 FT) were administered the Bayley III and the DMQ assessments for session 1 (6-8 months). During session 2, N=78 PT and 37 FT (18-20 months), the CBCL was added to previous assessments, and the BRIEF-P was added to previous assessments in session 3, N= 52 PT and 36 FT for session 3 (See Table 1). Significant change scores were found on BSID-III subtests and EF components across all 3 sessions. The PT group also showed significantly more behavioral concerns on the CBCL at 18 months and 36 months and had lower scores on the BRIEF-P than their FT peers. The number of children born PT (N = 27, 52%) who were in Early Intervention (EI) increased across the 3 sessions. Examining early indicators of EFs supported the development of early identification that could lead to decrease adverse outcomes often associated with preterm birth.

Effects of human milk odor stimulation on feeding in premature infants: a systematic review and meta-analysis.

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants.

Effects of implementing non-nutritive sucking on oral feeding progression and outcomes in preterm infants: A systematic review and meta-analysis.

BACKGROUND: Preterm infants have imperfect neurological development, uncoordinated sucking-swallowing-breathing, which makes it difficult to realize effective oral feeding after birth. How to help preterm infants achieve complete oral feeding as soon as possible has become an important issue in the management of preterm infants. Non-nutritive sucking (NNS), as a useful oral stimulation, can improve the effect of oral feeding in preterm infants. This review aimed to explore the effect of NNS on oral feeding progression through a meta-analysis. METHODS: We systematically searched PubMed, CINHAL, Web of Science, Embase, Cochrane databases, China's National Knowledge Infrastructure (CNKI), Wanfang and VIP database from inception to January 20, 2024. Search terms included 'non-nutritive sucking' 'oral feeding' and 'premature.' Eligibility criteria involved randomized controlled studies in English or Chinese. Studies were excluded if they were reviews, case reports, or observational studies from which valid data could not be extracted or outcome indicators were poorly defined. The meta-analysis will utilize Review Manager 5.3 software, employing either random-effects or fixed-effects models based on observed heterogeneity. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous data, and estimated pooled odds ratios (ORs) for dichotomous data. Sensitivity and publication bias analyses were conducted to ensure robust and reliable findings. We evaluated the methodological quality of randomized controlled trials (RCTs) utilizing the assessment tool provided by the Cochrane Collaboration. RESULTS: A total of 23 randomized controlled trials with 1461 preterm infants were included. The results of the meta-analysis showed that NNS significantly shortened time taken to achieve exclusive oral feeding (MD = -5.37,95%CI = -7.48 to-3.26, p<0.001), length of hospital stay(MD = -4.92, 95% CI = -6.76 to -3.09, p<0.001), time to start oral feeding(MD = -1.41, 95% CI = -2.36 to -0.45, p = 0.004), time to return to birth weight(MD = -1.72, 95% CI = -2.54 to -0.91, p<0.001). Compared to the NNS group, the control group had significant weight gain in preterm infants, including weight of discharge (MD = -61.10, 95% CI = -94.97 to -27.23, p = 0.0004), weight at full oral feeding (MD = -86.21, 95% CI = -134.37 to -38.05, p = 0.0005). In addition, NNS reduced the incidence of feeding intolerance (OR = 0.22, 95% CI = 0.14 to 0.35, p<0.001) in preterm infants. CONCLUSION: NNS improves oral feeding outcomes in preterm infants and reduces the time to reach full oral feeding and hospitalization length. However, this study was limited by the relatively small sample size of included studies and did not account for potential confounding factors. There was some heterogeneity and bias between studies. More studies are needed in the future to validate the effects on weight gain and growth in preterm infants. Nevertheless, our meta-analysis provides valuable insights, updating existing evidence on NNS for improving oral feeding in preterm infants and promoting evidence-based feeding practices in this population.

Prechtl's method to assess general movements: Inter-rater reliability during the preterm period.

INTRODUCTION: Prechtl's method (GMA) is a test for the functional assessment of the young nervous system. It involves a global and a detailed assessment of the general movements (GMs) and has demonstrated validity. Data on the reliability of both assessments in the preterm period are scarce. This study aimed to evaluate the inter-rater reliability for the global and detailed assessments of the preterm writhing GMA. MATERIALS AND METHODS: The study participants were 69 infants born at <37 gestational weeks and admitted to the neonatal intensive care unit. They were randomly assigned to five pairs of raters. Raters assessed infants' GMs using preterm videos. Outcome variables were (a) the GMs classification (normal versus abnormal; normal versus abnormal subcategories) and (b) the general movements optimality score (GMOS), obtained through the global and detailed assessments. The Gwet's AC1 and the intraclass correlation coefficient (ICC) were calculated for the GMs classification and the GMOS, respectively. RESULTS: The global assessment presented an AC1 = 0.84 [95% CI = 0.54,1] for the GMs binary classification and an AC1 = 0.67 [95% CI = 0.38,0.89] for the GMs classification with abnormal subcategories. The detailed assessment presented an ICC = 0.72 [95% CI = 0.39,0.90] for the GMOS. CONCLUSIONS: Inter-rater reliability was high and substantial for the global assessment and good for the detailed assessment. However, the small sample size limited the precision of these estimates. Future research should involve larger samples of preterm infants to improve estimate precision. Challenging items such as assessing the neck and trunk, poor repertoire GMs, and tremulous movements may impact the preterm writhing GMA's inter-rater reliability. Therefore, ongoing training and calibration among raters is necessary. Further investigation in clinical settings can enhance our understanding of the preterm writhing GMA's reliability.

Parametric analysis of an integrated cardio-respiratory model in preterm newborns during apnea.

The analysis of the complex interactions involved in the acute physiological response to apnea-bradycardia events in preterm newborns remains a challenging task. This paper presents a novel integrated model of cardio-respiratory interactions, adapted to preterm newborns. A sensitivity analysis, based Morris' screening method, was applied to study the effects of physiological parameters on heart rate and desaturation, during the simulation of a 15-seconds apnea-bradycardia episode. The most sensitive parameters are associated with fundamental, integrative physiological mechanisms involving: (i) respiratory mechanics (intermediate airways and lung compliance), (ii) fraction of inspired oxygen, (iii) metabolic rates (oxygen consumption rate), (iv) heart rate regulation and (v) chemoreflex (gain). Results highlight the relevant influence of physiological variables, involved in preterm apnea-bradycardia events.

Effects of the use of a cocoon on the autonomic, motor, and regulatory systems in preterm newborns: Randomized clinical trial.

INTRODUCTION: The wrapping of the newborn in an orthopedic tubular mesh, simulating a cocoon, can allow the infant to regain the feeling of security and stability experienced in the uterus given that the movement of one of the parts of the body exerts tactile and pressure variation in others. OBJECTIVE: We aimed to evaluate the influence of an orthopedic tubular mesh, simulating a cocoon, in therapeutic positioning, on the variables of the autonomous, motor, and regulatory systems of preterm newborns. METHODS: A controlled and randomized clinical trial was conducted with preterm newborns positioned in dorsal decubitus and divided into two groups: (a) cocoon - newborns covered with an orthopedic tubular mesh, and (b) control - newborns positioned according to the sector's routine and without the use of an orthopedic mesh. During the follow-up, each newborn was placed in the position for 30 min and was recorded for a total of 2 min, once at the beginning and again at the end of the observation period. Variables related to the autonomous system (heart rate, respiratory rate, and peripheral oxygen saturation), motor system (general movements), and regulatory system (Neonatal Infant Pain Scale) were evaluated before and after the intervention. The videos were evaluated by a researcher blind to the purpose of the study, and the resulting data were analyzed using SPSS. RESULTS: Of the 40 preterm newborns evaluated (32.5 ± 1.83 weeks), 21 were female, and 20 were allocated to the cocoon group. The variables related to the autonomous, motor, and regulatory systems remained unchanged following the positioning in the cocoon, as compared to the typical positioning employed in the neonatal unit. CONCLUSION: The simulation of a cocoon, utilizing an orthopedic tubular mesh, when applied to preterm newborns admitted to a neonatal intensive care unit can contribute to maintaining low levels of stress, without altering variables of the autonomous, motor, and regulatory systems.

Effects of increased physical therapy staffing in the neonatal intensive care unit on oral feeding maturation and neurodevelopment of extremely low birth weight infants.

BACKGROUND: It remains a matter of debate as to what extent early intervention may facilitate long-term functional outcomes of preterm infants in the neonatal intensive care unit (NICU). We aimed to examine the effect of increasing physical therapy (PT) staff dedicated to the NICU on temporal changes (initiation, duration) of PT interventions and functional outcomes (acquisition of full oral feeding and Hammersmith Neonatal Neurological Examination). METHODS: Extremely low birth weight infants, retrospectively collected from an academic medical center, were allocated to two subgroups, either a baseline period (N = 48) without NICU-dedicated PT staff (non-dedicated group) or a quality improvement period (N = 42) with additional dedicated staff (dedicated group). RESULTS: Compared to those in the non-dedicated group, NICU infants in the dedicated group started PT earlier and had increased PT treatment for additional 14 min per day when achieving full oral feeding. The infants in the dedicated group significantly achieved full oral feeding earlier than the non-dedicated group. As for Hammersmith Neonatal Neurological Examination, there were significant differences in two items (total and tone) between the groups. CONCLUSIONS: Additional NICU-dedicated PT staff facilitated earlier intervention and increased PT treatment in terms of daily duration. Moreover, the dedication shortened the completion of full oral feeding and improved neurological development, presumably resulting in better developmental outcome.

Generalized Camera-Based Infant Sleep-Wake Monitoring in NICUs: A Multi-Center Clinical Trial.

The infant sleep-wake behavior is an essential indicator of physiological and neurological system maturity, the circadian transition of which is important for evaluating the recovery of preterm infants from inadequate physiological function and cognitive disorders. Recently, camera-based infant sleep-wake monitoring has been investigated, but the challenges of generalization caused by variance in infants and clinical environments are not addressed for this application. In this paper, we conducted a multi-center clinical trial at four hospitals to improve the generalization of camera-based infant sleep-wake monitoring. Using the face videos of 64 term and 39 preterm infants recorded in NICUs, we proposed a novel sleep-wake classification strategy, called consistent deep representation constraint (CDRC), that forces the convolutional neural network (CNN) to make consistent predictions for the samples from different conditions but with the same label, to address the variances caused by infants and environments. The clinical validation shows that by using CDRC, all CNN backbones obtain over 85% accuracy, sensitivity, and specificity in both the cross-age and cross-environment experiments, improving the ones without CDRC by almost 15% in all metrics. This demonstrates that by improving the consistency of the deep representation of samples with the same state, we can significantly improve the generalization of infant sleep-wake classification.

Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Computational methodology to support functional vision assessment in premature infants: A viability study.

BACKGROUND: Premature newborns have a higher risk of abnormal visual development and visual impairment. OBJECTIVE: To develop a computational methodology to help assess functional vision in premature infants by tracking iris distances. METHODS: This experimental study was carried out with children up to two years old. A pattern of image capture with the visual stimulus was proposed to evaluate visual functions of vertical and horizontal visual tracking, visual field, vestibulo-ocular reflex, and fixation. The participants' visual responses were filmed to compose a dataset and develop a detection algorithm using the OpenCV library allied with FaceMesh for the detection and selection of the face, detection of specific facial points and tracking of the iris positions is done. A feasibility study was also conducted from the videos processed by the software. RESULTS: Forty-one children of different ages and diagnoses participated in the experimental study, forming a robust dataset. The software resulted in the tracking of iris positions during visual function evaluation stimuli. Furthermore, in the feasibility study, 8 children participated, divided into Pre-term and Term groups. There was no statistical difference in any visual variable analyzed in the comparison between groups. CONCLUSION: The computational methodology developed was able to track the distances traveled by the iris, and thus can be used to help assess visual function in children.

The Effect of Oral Motor Stimulation on the Transition to Full Oral Feeding, Breastfeeding, and Length of Hospital Stay in Preterm Infants.

Objective: To determine the effect of oral motor stimulation (OMS) applied to preterm infants on their sucking and swallowing abilities to establish a successful and safe oral feeding experience. Methods: A pre-post intervention study was conducted between December 2019 and December 2020, which included preterm infants born at <35 weeks of gestational age and admitted to the neonatal intensive care unit. Patients with major congenital abnormalities (including cardiac, facial, and jaw deformities), severe NEC, stage 3-4 IVH were excluded from the study. Patients who received OMS by a speech and language therapist between June 2020 and December 2020 were assigned to Group 1, while patients who received no intervention between December 2019 and May 2020 were assigned to Group 2. The time to achieve full oral feeding (FOF), acquisition of breastfeeding rates at discharge, and the length of hospital stay (LOS) were compared between the groups. Results: A total of 62 patients were included in the study (31 in Group 1 and 31 in Group 2). There were no significant differences in birth weight and demographic data between the groups. The mean time to achieve FOF was found to be significantly shorter in Group 1 (31 ± 23.6 and 46.7 ± 22.3 days, respectively, p = 0.013). The mean LOS was also found to be shortened with a mean duration of 10 days in Group 1, without statistical significance (56.4 ± 35.3 days versus 66.0 ± 42.9 days, respectively, p = 0.34). Acquisition of breastfeeding rates was significantly higher in the intervention group (p < 0.05) Conclusions: OMS accelerates the transition to FOF in preterm infants and increases the rates of acquiring breastfeeding skills at discharge.

Infant periodic breathing and apneic threshold.

A mathematical model was proposed to predict the role played by apneic threshold in periodic breathing in preterm infants. Prior models have mainly applied linear control theory which predicted instability but could not explain sustained periodic breathing. Apneic threshold to CO2 which has been postulated to play a major role in infant periodic breathing is a nonlinear effect and cannot be described by linear theory. Another previously unexplored nonlinear factor affecting instability is brain vascular volume change with CO2 which affects time delay to chemoreceptors. The current model explored the influences of apneic threshold, central and peripheral chemoreceptor gains, cardiac output, lung volume, and circulatory time delay on periodic breathing. Apneic threshold was found to play a major role in ventilatory responses to spontaneous sighs. Sighs led to apneic pauses followed by periods of periodic breathing with peripheral chemoreceptor CO2 gain, cardiac output, and lung volume were at reported normal levels. Apneic threshold when exceeded was observed to cause an asymmetry in the periodic breathing cycling and an increased periodic breathing frequency. Sighs in infants occur frequently enough to lead to repeated stimulation within the epoch duration of periodic breathing for a single sigh. Multiple sighs may then play a major role in promoting continuous periodic breathing in infants. Peripheral chemoreceptor gain estimated using endogenous CO2 led to validated predicted periodic breathing cycle duration as a function of age. Brain vascular volume increase with CO2 contributes to periodic breathing in very young (1-2 day old) preterm infants.

Sleep characteristics, early spontaneous movements, and developmental functioning in preterm infants in the early postnatal period.

OBJECTIVE: This study aimed to investigate the following: (i) sleep characteristics in preterm infants at 9-20 weeks of corrected age, and (ii) differences in early spontaneous movements and developmental functioning results between the groups based on some sleep characteristics. METHODS: Seventy-four preterm infants (36 female) were included. Sleep characteristics were assessed according to the Brief Infant Sleep Questionnaire (BISQ). The infants were divided into two groups based on total sleep duration: less than 12 h (38 infants), and 12 h and more (36 infants). Video recordings were made for the General Movements Assessment (GMA) and evaluated using the Motor Optimality Score for 3- to 5-Month-Old-Infants-Revised (MOS). Cognitive, language, and motor development were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). RESULTS: The total sleep duration of all preterm infants (mean ± SD) was 11.8 ± 3.3 h. Infants who had absent fidgety movements slept less than 12 h, and fidgety movements differed between the groups (p = 0.012). Infants who slept 12 h or more had significantly higher MOS (p = 0.041), cognitive (p = 0.002), language (p < 0.001), and motor (p = 0.002) development results. Infants who snored had lower MOS (p = 0.001), cognitive (p = 0.004), language (p = 0.002), and motor (p = 0.001) development results. Infants with fewer than three nocturnal awakenings had significantly higher Bayley-III cognitive (p = 0.007), language (p = 0.032), and motor (p = 0.005) domain results. Prone and supine sleeping positions showed higher motor domain results than lateral positions (p = 0.001). CONCLUSIONS: Sleep in preterm infants might be a key factor in early developmental functioning processes and nervous system integrity. Even in the first months of life, there are substantial differences in cognitive, language, and motor development in association with sleep characteristics.

Heart rate variability in school-age children born moderate-to-late preterm.

BACKGROUND: Prematurity is associated with reduced cardiac autonomic function. This study aimed to investigate the heart rate variability (HRV) in school-age children born moderately to late preterm (MLPT). METHODS: This cross-sectional study investigated school-age children, aged 5 to 10 years, born moderate-to-late preterm. Electrocardiograms recordings were performed during fifteen-minutes. Time and frequency domain parameters were calculated, corrected for heart rate and compared between the groups. RESULTS: A total of 123 children were evaluated and 119 were included in this study. HRV measures, studied in the time and frequency domains, were similar in both groups. Corrected values of root mean square of successive differences between normal cycles (RMSSD), percentage of successive cycles with a duration difference >50 ms (pNN50%), and high frequency (HF), indices that predominantly represent the parasympathetic activity of the autonomic nervous system, were 1.6E-7 and 1.8E-7 (p=0.226); 1.6E-13 and 1.6E-13 (p=0.506); 6.9E-12 and 7.4E-12 (p=0.968) in the preterm and control groups, respectively. CONCLUSION: This study did not find differences in heart rate variability between school-age children born MLPT and those born at term, suggesting that plasticity of cardiac autonomic modulation continues to occur in children up to school age or there is less impairment of the autonomic system in MLPT.

Sensory event-related potential morphology predicts age in premature infants.

OBJECTIVE: We investigated whether sensory-evoked cortical potentials could be used to estimate the age of an infant. Such a model could be used to identify infants who deviate from normal neurodevelopment. METHODS: Infants aged between 28- and 40-weeks post-menstrual age (PMA) (166 recording sessions in 96 infants) received trains of visual and tactile stimuli. Neurodynamic response functions for each stimulus were derived using principal component analysis and a machine learning model trained and validated to predict infant age. RESULTS: PMA could be predicted accurately from the magnitude of the evoked responses (training set mean absolute error and 95% confidence intervals: 1.41 [1.14; 1.74] weeks,p = 0.0001; test set mean absolute error: 1.55 [1.21; 1.95] weeks,p = 0.0002). Moreover, we show that their predicted age (their brain age) is correlated with a measure known to relate to maturity of the nervous system and is linked to long-term neurodevelopment. CONCLUSIONS: Sensory-evoked potentials are predictive of age in premature infants and brain age deviations are related to biologically and clinically meaningful individual differences in nervous system maturation. SIGNIFICANCE: This model could be used to detect abnormal development of infants' response to sensory stimuli in their environment and may be predictive of neurodevelopmental outcome.

Predicting the effectiveness of drugs used for treating cardiovascular conditions in newborn infants.

BACKGROUND: Cardiovascular support (CVS) treatment failure (TF) is associated with a poor prognosis in preterm infants. METHODS: Medical charts of infants with a birth weight <1500 g who received either dopamine (Dp) or dobutamine (Db), were reviewed. Treatment response (TR) occurred if blood pressure increased >3rd centile for gestational age or superior vena cava flow was maintained >55 ml/kg/min, with decreased lactate or less negative base excess, without additional CVS. A predictive model of Dp and Db on TR was designed and the impact of TR on survival was analyzed. RESULTS: Sixty-six infants (median gestational age 27.3 weeks, median birth weight 864 g) received Dp (n = 44) or Db (n = 22). TR occurred in 59% of the cases treated with Dp and 31% with Db, p = 0.04. Machine learning identified a model that correctly labeled Db response in 90% of the cases and Dp response in 61.4%. Sixteen infants died (9% of the TR group, 39% of the TF group; p = 0.004). Brain or gut morbidity-free survival was observed in 52% vs 30% in the TR and TF groups, respectively (p = 0.08). CONCLUSIONS: New predictive models can anticipate Db but not Dp effectiveness in preterm infants. These algorithms may help the clinicians in the decision-making process. IMPACT: Failure of cardiovascular support treatment increases the risk of mortality in very low birth weight infants. A predictive model built with machine learning techniques can help anticipate treatment response to dobutamine with high accuracy. Predictive models based on artificial intelligence may guide the clinicians in the decision-making process.

Maternal singing sustains preterm hospitalized newborns' autonomic nervous system maturation: an RCT.

BACKGROUND: Premature birth is known to affect the newborn's autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants' autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters. METHODS: In this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking. RESULTS: The intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037). CONCLUSIONS: The preterm infant's vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition. IMPACT: Maternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU. No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation. Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant's development and it can be easily implemented in the care of preterm infants. TRIAL REGISTRATION: NCT04759573, retrospectively registered, 17 February 2021.