Effect of exogenous and endogenous ketones on respiratory exchange ratio and glucose metabolism in healthy subjects.

This study examined the effect of exogenous ketone bodies (KB) on oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and glucose metabolism. The data were compared with the effects of endogenous ketonemia during both, a ketogenic diet or fasting. Eight healthy individuals [24.1 ± 2.5 yr, body mass index (BMI) 24.3 ± 3.1 kg/m2] participated in a crossover intervention study and were studied in a whole-room indirect calorimeter (WRIC) to assess macronutrient oxidation following four 24-h interventions: isocaloric controlled mixed diet (ISO), ISO supplemented with ketone salts (38.7 g of ß-hydroxybutyrate/day, EXO), isocaloric ketogenic diet (KETO), and total fasting (FAST). A physical activity level of 1.65 was obtained. In addition to plasma KB, 24-h C-peptide and KB excretion rates in the urine and postprandial glucose and insulin levels were measured. Although 24-h KB excretion increased in response to KETO and FAST, there was a modest increase in response to EXO only (P < 0.05). When compared with ISO, V̇o2 significantly increased in KETO (P < 0.01) and EXO (P < 0.001), whereas there was no difference in FAST. V̇co2 increased in EXO but decreased in KETO (both P < 0.01) and FAST (P < 0.001), resulting in 24-h respiratory exchange ratios (RER) of 0.828 ± 0.024 (ISO) and 0.811 ± 0.024 (EXO) (P < 0.05). In response to EXO there were no differences in basal and postprandial glucose and insulin levels, as well as in insulin sensitivity. When compared with ISO, EXO, and KETO, FAST increased homeostatic model assessment ß-cell function (HOMA-B) (all P < 0.05). In conclusion, at energy balance exogenous ketone salts decreased respiratory exchange ratio without affecting glucose tolerance.NEW & NOTEWORTHY Our findings revealed that during isocaloric nutrition, additional exogenous ketone salts increased V̇o2 and V̇co2 while lowering the respiratory exchange ratio (RER). Ketone salts had no effect on postprandial glucose metabolism.

Application of desirability of outcome ranking to the milking in non-vigorous infants trial.

OBJECTIVES: Neonatal trials have traditionally used binary composite short-term (such as death or bronchopulmonary dysplasia) or longer-term (such as death or severe neurodevelopmental impairment) outcomes. We applied the Desirability Of Outcome Ranking (DOOR) method to rank the overall patient outcome by best (no morbidities) to worst (death). STUDY DESIGN: Using a completed large multicenter trial (Milking In Non-Vigorous Infants [MINVI]) of umbilical cord milking (UCM) vs. early cord clamping (ECC), we applied the DOOR methodology to neonatal outcomes. Six outcomes were chosen and ranked: no interventions or NICU admission (most desirable); received initial cardiorespiratory support at birth; neonatal intensive care unit (NICU) admission for predefined criteria; mild hypoxic-ischemic encephalopathy (HIE); moderate to severe HIE; and death (least desirable). RESULTS: 1524 non-vigorous newborns born between 35 and 42 weeks' gestation had data for analysis. The DOOR distribution was different between the UCM and ECC arms, with a significantly greater probability (55.8 % [95 % CI 53.1-58.5 %; p < 0.0001]) of a randomly selected neonate having a more desirable outcome if they were in the UCM arm. DOOR probabilities of averting individual adverse outcomes such as NICU admission for predefined criteria (52.8 %; 95%CI 50.5-55.1 %) and cardiorespiratory support (54.0 %; 95%CI 51.6-56.4 %) were significantly higher among those in the UCM group. CONCLUSION: DOOR provides an overall assessment of the benefits and harms with greater insight than typical binary composite measures to clinicians and parents when evaluating an intervention. Future neonatal trials should consider the a priori use of the DOOR methodology to evaluate trial outcomes.

Parental perspectives on a trial using waived informed consent at birth.

OBJECTIVES: To determine parental perspectives in a trial with waived consent. STUDY DESIGN: Anonymous survey of birth parents with term infants who were randomized using a waiver of consent, administered after infant discharge. RESULTS: 121 (11%) survey responses were collected. Of the 121 responding parents 111 (92%) reported that this form of consent was acceptable and 116 (96%) reported feeling comfortable having another child participate in a similar study. 110 (91%) respondents reported that they both understood the information provided in the consent process and had enough time to consider participation. Four percent had a negative opinion on the study's effect on their child's health. CONCLUSIONS: Most responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Parental Perspectives on a Trial Using Waived Informed Consent at Birth.

Objectives: To determine parental perspectives in a trial with waived consent. Study Design: Biological parents of non-vigorous term infants randomized using a waiver of consent for a delivery room intervention completed an anonymous survey after discharge. Results: 121 survey responses were collected. Most responding parents reported that this form of consent was acceptable (92%) and that they would feel comfortable having another child participate in a similar study (96%). The majority (> 90%) also reported that the information provided after randomization was clear to understand future data collection procedures. Four percent had a negative opinion on the study's effect on their child's health. Conclusions: The majority of responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Life on the Frontlines: Caregiver Experience of Pediatric Cerebrospinal Shunt Malfunction.

BACKGROUND: We aimed to characterize the caregiver experience in the detection and evaluation of pediatric cerebrospinal shunt malfunction. METHODS: In this descriptive qualitative study, we recruited English-speaking caregivers of children aged five years or less in collaboration with a stakeholder organization. Semistructured interviews were completed; content targeted the caregiver experience of shunt malfunction. Interviews were audio-recorded, transcribed, and deidentified. Qualitative data were analyzed using a conventional content analysis approach. RESULTS: We enrolled 20 caregivers (n = 20 mothers). The median child age at the time of the interview was 2.8 years; about half (n = 11) were born prematurely and the majority (n = 15) had shunts placed at age less than six months. Caregiver experiences of shunt malfunction were grouped into three major themes: (1) my error could be life or death: the high stakes of shunt malfunction and the ambiguity of malfunction symptoms exacerbated baseline caregiver vigilance; (2) finding and engaging people who can help: hurdles during malfunction evaluation included locating trusted clinicians and advocating for parental intuition; and (3) how the shunt defines our family: caregivers described evolving expertise and modifications made to everyday life due to the threat of malfunction. CONCLUSIONS: In this study, caregivers highlighted the challenges associated with recognizing shunt malfunction, accessing necessary treatment, and the impact of their child's shunt on family life. Future work should leverage these findings to inform counseling about shunt malfunction, develop interventions to better support families in shunt malfunction identification, and educate medical providers.

Optimizing transition: Providing oxygen during intact cord resuscitation.

Delayed clamping and cutting of the umbilical cord at birth is standard practice for management for all newborns. Preterm infants may additionally benefit from a combination of ventilation and oxygen provision during intact cord resuscitation. This review highlights both the potential benefits of such a combined approach and the need for further rigorous studies, including randomized controlled trials, of delivery room management in this population.

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants.

BACKGROUND & AIMS: Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as ß-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception. METHODS: Eight healthy young adults (4 women, 4 men, age 24 ± 3 years, BMI 24.3 ± 3.1 kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7 g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured. RESULTS: Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p > 0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110 ± 54 kcal/d vs. ISO, p < 0.05) and SEE (+201 ± 90 kcal/d vs. ISO, p < 0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48 ± 27 g/d, p < 0.05) resulting in a positive CHO balance (p < 0.05). No differences between the interventions were found for subjective appetite ratings (all p > 0.05). CONCLUSION: A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance. CLINICAL TRIAL REGISTRATION: NCT04490226 https://clinicaltrials.gov/.

Validity and reproducibility of a whole-room indirect calorimeter for the estimation of VO2 , VCO2 , and resting metabolic rate.

Whole-room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests (n = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run-in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO2 ; 2.67% for VCO2 ; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO2 (94%), VCO2 (96%) and RMR (95%). Excluding participants that deviated from the run-in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.

Symptoms of Cerebrospinal Shunt Malfunction in Young Children: A National Caregiver Survey.

Objective: This study aimed to describe shunt malfunction symptoms in children ≤5 years old. Results: In a national survey of 228 caregivers, vomiting (23.1%), irritability (20.8%), and sleepiness (17.2%) were the most frequent symptoms of malfunction. These symptoms also occurred in over 1/3 of "false alarms" experienced by 75% of respondents. Compared with malfunctions, irritability (OR = 1.39, 95% CI [1.05, 1.85], p = 0.022) and fever (OR = 2.22, 95% CI [1.44, 3.44], p < 0.001) were more likely false alarms. Caregivers counseled about "most" symptoms were more confident detecting malfunctions than those informed of "some" (p = 0.036). The majority of caregivers (85%) first contacted a neurosurgeon with concerns about malfunction, followed by neurologists (22%) and family/friends (19%). Most (85%) struggled to differentiate malfunction from regular development. Conclusions: Vomiting, irritability, and sleepiness were the most common symptoms of shunt malfunction and false alarms for children ≤5 years. Most caregivers reported challenges differentiating malfunctions from their child's development.

[Intersectoral management of patients with abnormal liver enzymes and non-alcoholic fatty liver disease (NAFLD)]. / Intersektorales Management von Patienten mit unklarer Leberwerterhöhung und nichtalkoholischer Fettlebererkrankung (NAFLD).

The prevalence of fatty liver disease has increased significantly in Germany in recent years. With an estimated 18 million German citizens being affected, it is now among the most prevalent diseases. Furthermore, it is also considered a relevant and independent risk factor for other common cardiovascular diseases such as heart attack or stroke. Finally, diabetes mellitus promotes the development of and an unfavorable course of fatty liver disease. Given the high prevalence and complications, the German healthcare system is reaching its limits.Therefore, close coordination of all healthcare providers and specialists involved in the treatment of these patients is essential. In an expert consensus involving private practice and hospital doctors from the fields of gastroenterology, endocrinology, cardiology, general practitioners and laboratory physicians, as well as in close coordination with patient representatives, we have designed a concept for the care of these patients in the German healthcare system. Necessary developments are also addressed. In addition to being useful as a practical guideline, this should also support health policy work, especially in the development of practical care solutions at the medical level.

Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn.

BACKGROUND: Management strategies for preterm neonates with respiratory distress syndrome include early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen and may include the use of less invasive surfactant administration (LISA) to avoid the need for endotracheal intubation. This randomized trial investigated whether early administration of caffeine and LISA would decrease the need for endotracheal intubation in the first 72 hours of life (HoL) compared with caffeine and CPAP alone. METHODS: Eligible neonates born at 24 weeks 0 days to 29 weeks 6 days of gestational age were randomly assigned to receive intravenous caffeine in the first 2 HoL followed by surfactant administration via the LISA method (intervention) or caffeine followed by CPAP (control). The primary outcome was the frequency of neonates requiring endotracheal intubation or meeting respiratory failure criteria between groups (caffeine and LISA vs. caffeine and CPAP) within the first 72 HoL. Multivariable logistic regression modeling was used to adjust for gestational age strata in normally distributed primary and secondary outcomes. RESULTS: Enrollment occurred between January 2020 and December 2022. Endotracheal intubation or meeting respiratory failure criteria within the first 72 HoL occurred in 21 (23%) of 92 neonates randomly assigned to receive caffeine and LISA compared with 47 (53%) of 88 neonates in the caffeine and CPAP group (odds ratio, 0.258; 95% confidence interval, 0.136 to 0.490; P<0.001), which remained significant after adjusting for gestational age strata (odds ratio, 0.227; 95% confidence interval, 0.112 to 0.460; P<0.001). Adverse events were similar between groups, except bronchopulmonary dysplasia, which occurred in 26% of the LISA group and 39% of the control group (P=0.049). CONCLUSIONS: In preterm neonates supported with CPAP, early caffeine and LISA resulted in a lower frequency of endotracheal intubation within the first 72 HoL. (Funded by Chiesi USA; ClinicalTrials.gov number, NCT04209946.)

A randomized, controlled trial of an innovative, multimedia instructional program for acquiring auditory skill in identifying pediatric heart murmurs.

Objective: To create a brief, acceptable, innovative method for self-paced learning to enhance recognition of pediatric heart murmurs by medical students, and to demonstrate this method's effectiveness in a randomized, controlled trial. Materials and methods: A curriculum of six 10-min online learning modules was designed to enable deliberate practice of pediatric cardiac auscultation, using recordings of patients' heart murmurs. Principles of andragogy and multimedia learning were applied to optimize acquisition of this skill. A pretest and posttest, given 4 weeks apart, were created using additional recordings and administered to 87 3rd-year medical students during their pediatric clerkship. They were randomized to have access to the modules after the pretest or after the posttest, and asked to use at least the first 2 of the modules. Results: 47 subjects comprised the Intervention group, and 40 subjects the Control group. On our primary outcome, distinguishing innocent from pathological with at least moderate confidence, the posttest scores were significantly higher for the Intervention group (60.5%) than for the Control group (20.0%). For our secondary outcomes, the 2 groups also differed significantly in the ability to distinguish innocent from pathological murmurs, and in identifying the actual diagnosis. On all 3 outcomes, those Intervention group subjects who accessed 4-6 modules scored higher than those who accessed 0-3 modules, who in turn scored higher than the Control group. Summary: Applying current principles of adult learning, we have created a teaching program for medical students to learn to recognize common pediatric murmurs. Its effectiveness was demonstrated in a randomized, controlled trial. The program results in a meaningful gain in this skill from 1 h of self-paced training with high acceptance to learners.

Validation of energy expenditure and macronutrient oxidation measured by two new whole-room indirect calorimeters.

OBJECTIVE: The aim of this study was to validate two new whole-room indirfect calorimeters according to Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0). METHODS: For technical validation, 16 propane combustion tests were performed to determine accuracy and precision of energy expenditure (EE) and ventilation rates of oxygen (VO2 ), carbon dioxide (VCO2 ), and respiratory exchange ratio (VCO2 /VO2 ). For biological validation, eight participants (mean [SD], age 24.1 [2.5] years; BMI 24.3 [3.1] kg/m2 ) underwent four 24-hour protocols under highly standardized conditions: (1) isocaloric sedentary, (2) fasting sedentary, (3) isocaloric active, and (4) fasting active. Reliability (coefficients of variation [CV]) and minimal detectable changes (MDC) were calculated for 24-hour EE, sleeping metabolic rate (SMR), physical activity energy expenditure (PAEE), thermic effect of food (TEF), and macronutrient oxidation rates. RESULTS: Technical validation showed high reliability and recovery rates for VO2 (0.75% and 100.8%, respectively), VCO2 (0.49% and 100.6%), and EE (0.54% and 98.2%). Biological validation revealed CV and MDC for active conditions of 1.4% and 4.3% for 24-hour EE, 1.7% and 5.9% for SMR, and 30.2% and 38.4% for TEF, as well as 5.8% and 10.5% for PAEE, respectively. Mean CV and MDC for macronutrient oxidation rates were 9.9% and 22.9%, respectively. CONCLUSIONS: The precision of 24-hour EE and SMR was high, whereas it was lower for PAEE and poor for TEF.

Isolated and On Guard: Preparing Neonatal Intensive Care Unit Families for Life with Hydrocephalus.

OBJECTIVE: This study was aimed to characterize the parent experience of caring for a child with posthemorrhagic hydrocephalus and to describe parent preferences for counseling in the neonatal period and beyond. STUDY DESIGN: This was a qualitative interview study. Parents of infants born preterm with posthemorrhagic hydrocephalus completed semistructured interviews. Data were analyzed using a content analysis approach. RESULTS: Thematic saturation was reached on parent communication preferences after 10 interviews. Parent experiences of infant hydrocephalus broadly fell into two time periods, the neonatal intensive care unit (NICU) and after NICU discharge. The themes of uncertainty, isolation, hypervigilance, and the need for advocacy were common to each phase. CONCLUSION: Parents expressed interest in the development of tiered NICU counseling tools that would provide evidence-based and family-centric information to (1) initiate connections with community and peer resources and (2) combat the isolation and hypervigilance that characterized their family experience of living with hydrocephalus. KEY POINTS: · Infants with posthemorrhagic hydrocephalus are at risk for adverse neurodevelopmental outcomes.. · The parent experience of caring for a child with posthemorrhagic hydrocephalus is not well-described. In this interview study, parents described uncertainty, isolation, and hypervigilance.. · These findings call for structured NICU counseling and longitudinal family supports after discharge..

Non-alcoholic fatty liver disease: A patient guideline.

This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.

Understanding the photophysics of stercobilin-Zn(II) and urobilin-Zn(II) complexes towards faecal pigment analysis.

A detailed photophysical study of two faecal pigments (FPs), Urobilin (UB) and Stercobilin (SB), and their zinc complexes [FP-Zn(II)] was carried out. The enhancement of UB and SB fluorescence resulting from the formation of their Zn(II) complexes was attributed to the complexation-induced rigidity of the chromophoric units, and the corresponding decrease of nonradiative decay rate constants of the excited singlet states (knr). The effect of various physicochemical environments was also studied in detail in order to understand the fluorescence behaviour of the Zn(II) complexes. FP-Zn(II) complexes have a lower solubility in water that results in the formation of molecular aggregates. The aggregation-induced loss of fluorescence of FP-Zn(II) complexes could be overcome by using the appropriate mixture of ethanol and water (70:30). Molecular orbital calculations on the FP-Zn(II) complexes provided a good idea of the geometry of the complexes and helped rationalise the enhancement of fluorescence after complexation. This study could pave the way towards developing a convenient non-extraction aqueous phase analytical procedure for detection of FPs using Zn(II) complexation method.

Parent preferences for neurodevelopmental screening in the neonatal intensive care unit.

AIM: To determine whether, and how, neonatal intensive care unit (NICU) parents want to receive early neurodevelopmental screening information about their child's future risk of cerebral palsy and other disabilities. METHOD: This was a qualitative interview study. Parents of hospitalized infants born preterm completed semi-structured interviews. Data were analysed using a directed content analysis approach. RESULTS: Thematic saturation was achieved after 19 interviews. Four themes characterized parent perceptions of early neurodevelopmental screening: (1) acceptability: most parents were in favour of neurodevelopmental screening if parents could refuse; (2) disclosure of results: parents want emotional preparation for results, especially false positives; (3) emotional burden of uncertainty: parents of children in the NICU balance taking their infant's illness 'day by day' and preparing for an uncertain future. Parents expressed distress with screening that increased uncertainty about the future; and (4) disability: prior experience with disability informs parent concerns. INTERPRETATION: Parents interpret the risks and benefits of NICU developmental screening through the lens of prior experiences with disability. Most expressed interest in screening and emphasized a desire for autonomy, pretest counselling, and emotional preparation. WHAT THIS PAPER ADDS: Most parents with infants in the neonatal intensive care unit expressed interest in early screening for developmental disability. Prior experience with disability informed concerns about specific deficits. Parents emphasized a desire for autonomy, pretest counselling, and emotional preparation.

Self-testing for liver disease - response to an online liver test questionnaire.

Background: Elevated liver enzymes and chronic liver disease are associated with increased morbidity and mortality. Broad availability of internet questionnaires obtains representative insights into awareness of (chronic) liver disease in the general population. Also, these tools may be used to identify persons and populations at risk to prevent advanced liver disease.Methods: An online questionnaire regarding awareness of liver disease, risk behavior and awareness of own liver tests was implemented online. During 43 months study period, 210,230 participants accessed the online questionnaire. Of these, 117,446 individuals completed the survey. All database access and input were registered and collected in a SQL based database for further evaluation.Results: Awareness of own liver status was lower than expected. About 50.7% of all participants were uncertain about their liver enzyme status. In turn, risk behavior continues to be considerably high as 38.8% of participants stated high-risk behavior for alcohol consumption and 2.2% high-risk substance abuse such as cocaine or heroin. Our questionnaire was predominantly answered by participants under 65 years of age. Participants with high BMI may have been underrepresented.Conclusion: Our study demonstrated the urgent need for improved liver screening, health education regarding risk behavior and improved awareness campaigns on liver disease. Interest of the general population may be presumed as more than 200,000 people accessed our test of their own accord.

Early neurodevelopmental outcome in preterm posthemorrhagic ventricular dilatation and hydrocephalus: Neonatal ICU Network Neurobehavioral Scale and imaging predict 3-6-month motor quotients and Capute Scales.

OBJECTIVE: Brain injury remains a serious complication of prematurity. Almost half of infants with severe intraventricular hemorrhage (IVH) develop posthemorrhagic ventricular dilatation (PHVD) and 20% need surgery for posthemorrhagic hydrocephalus (PHH). This population is associated with an increased risk of later neurodevelopmental disability, but there is uncertainty about which radiological and examination features predict later disability. In this study the authors sought to devise and describe a novel combination of neurobehavioral examination and imaging for prediction of neurodevelopmental disability among preterm infants with PHVD and PHH. METHODS: The study patients were preterm infants (< 36 weeks gestation) with IVH and PHVD, with or without PHH. Ventricular index (VI), anterior horn width (AHW), thalamooccipital distance (TOD), ventricle/brain (V/B) ratio, and resistive indices (RIs) were recorded on the head ultrasound (HUS) just prior to surgery, or the HUS capturing the worst PHVD when surgery was not indicated. The posterior fossa was assessed with MRI. Neonatal ICU Network Neurobehavioral Scale (NNNS) examinations were performed at term age equivalent for each infant. A neurodevelopmental assessment using the Capute Scales (Capute Cognitive Adaptive Test [CAT] scores and Capute Clinical Linguistic Auditory Milestone Scale [CLAMS] scores) and a motor quotient (MQ) assessment were performed between 3 and 6 months of age corrected for degree of prematurity (corrected age). MQs < 50 reflect moderate to severe delays in early motor milestone attainment, CAT scores < 85 reflect delays in early visual and problem-solving abilities, and CLAMS scores < 85 reflect delays in early language. RESULTS: Twenty-one infants underwent assessments that included imaging and NNNS examinations, Capute Scales assessments, and MQs. NNNS nonoptimal reflexes (NOR) and hypertonicity subscores and AHW were associated with MQs < 50: NOR subscore OR 2.46 (95% CI 1.15-37.6, p = 0.034), hypertonicity subscore OR 1.68 (95% CI 1.04-3.78, p = 0.037), and AHW OR 1.13 (95% CI 1.01-1.39, p = 0.041). PVHI, cystic changes, and neurosurgical intervention were associated with CAT scores < 85: PVHI OR 9.2 (95% CI 1.2-73.2, p = 0.037); cystic changes OR 12.0 (95% CI 1.0-141.3, p = 0.048), and neurosurgical intervention OR 11.2 (95% CI 1.0-120.4, p = 0.046). Every 1-SD increase in the NOR subscore was associated with an increase in odds of a CAT score < 85, OR 4.0 (95% CI 1.0-15.0, p = 0.044). Worse NNNS NOR subscores were associated with early language delay: for a 1-SD increase in NOR subscore, there was an increase in the odds of a CLAMS score < 85, OR 19.5 (95% CI 1.3-303, p = 0.034). CONCLUSIONS: In former preterm children with severe IVH and PHVD, neonatal neurological examination findings and imaging features are associated with delays at 3-6 months in motor milestones, visual and problem-solving abilities, and language.

The Relationship Between Clinical Imaging and Neurobehavioral Assessment in Posthemorrhagic Ventricular Dilation of Prematurity.

Introduction: Neonatal intraventricular hemorrhage (IVH) and subsequent posthemorrhagic ventricular dilation and hydrocephalus of prematurity are associated with brain injury and neurodevelopmental impairment in the preterm population. Neuroimaging assesses cerebral injury and guides neurosurgical intervention; however, the relationship of head ultrasound (HUS) and magnetic resonance imaging (MRI) parameters to neonatal exams in this group has not been well described. The NICU Network Neurobehavioral Scale (NNNS) is a reproducible, highly reliable battery with motor and cognitive domain scores. Objective: To evaluate the relationship between neonatal neurobehavioral findings on the NNNS and measures of ventricular dilation and associated brain injury on HUS and MRI. Materials and Methods: Neonates with IVH and ventricular dilatation with and without posthemorrhagic hydrocephalus were enrolled. NNNS exams were performed at approximately term age equivalent. HUS indices were measured on the last HUS before initial neurosurgical procedure or that with worst ventriculomegaly if no intervention. The posterior fossa was assessed with MRI at term. Descriptive statistics including medians, interquartile ranges, means, and percentages were performed. Correlations were estimated using Pearson's method. Results: 28 patients had NNNS and HUS, and 18 patients also had an MRI. Ventricle size measures for the cohort were significantly above normal. Motor and cognitive subscores on the NNNS exam varied from established baseline scores for postmenstrual age. Children who required neurosurgical intervention had higher ventricle/brain ratios and worse NNNS habituation scores. Ventricle sizes were modestly correlated with motor abnormalities (0.24-0.59); larger anterior horn width correlated with nonoptimal reflexes, hypertonicity and hypotonicity. Ventricle sizes were modestly correlated with cognitive scores (-0.44 to 0.27); larger ventricular index correlated with worse attention. Periventricular hemorrhagic infarction correlated with worse habituation. Conclusion: For this cohort of preterm infants with IVH, surgical intervention for posthemorrhagic hydrocephalus correlated with both larger degrees of ventriculomegaly and worse NNNS exams. Findings on both HUS and MRI correlated with motor and cognitive abnormalities on neonatal neurobehavioral exam, suggesting that larger neonatal ventricle sizes and white matter injury have detectable correlates on exam. The NNNS exam provides important additional information when assessing posthemorrhagic ventricular dilation and hydrocephalus of prematurity.