Postmenstrual Weeks Research Articles

Brain injury patterns in hypoxic ischemic encephalopathy of term neonates.

Topographic patterns of brain injury in neonates can help with differentiation and prognostic categorization of hypoxic ischemic encephalopathy (HIE). In this study, we quantitatively and objectively characterized the location of hypoxic ischemic lesions in term neonates with varying severity of HIE. We analyzed term neonates (born ≥37 postmenstrual gestational weeks) with MRI diffusion-weighted imaging (DWI) and diagnoses of HIE. Neonates' HIE was categorized into mild, moderate, and severe. The hypoxic ischemic lesions were segmented on DWI series with attention to T1- and T2-weighted images and then co-registered onto standard brain space to generate summation maps for each severity category. Applying voxel-wise general linear models, we also identified cerebral regions more likely to infarct with increasing severity of HIE, after correction for lesion volume and time-to-scan as covariates. We included 33 neonates: 20 with mild, eight with moderate, and five with severe HIE. Infarct volumes (p=.00052) and Appearance, Pulse, Grimace, Activity, and Respiration scores at 1minute (p=.032) differed between HIE severity categories. Hypoxic ischemic lesions in neonates with mild and moderate HIE were predominant in subcortical and deep white matter along the border zones of arterial supply territories, while severe HIE also involved basal ganglia, hippocampus, and thalamus. In voxel-wise analysis, higher severity of HIE was associated with the presence of lesions in hippocampus, thalamus, and lentiform nucleus. In term neonates, mild/moderate HIE is associated with infarctions of arterial territory watershed zones, whereas severe HIE distinctively involves basal ganglia, thalami, and hippocampi.

Mapping developmental regionalization and patterns of cortical surface area from 29 post-menstrual weeks to 2 years of age

Surface area of the human cerebral cortex expands extremely dynamically and regionally heterogeneously from the third trimester of pregnancy to 2 y of age, reflecting the spatial heterogeneity of the underlying microstructural and functional development of the cerebral cortex. However, little is known about the developmental patterns and regionalization of cortical surface area during this critical stage, due to the lack of high-quality imaging data and accurate computational tools for pediatric brain MRI data. To fill this critical knowledge gap, by leveraging 1,037 high-quality MRI scans with the age between 29 post-menstrual weeks and 24 mo from 735 pediatric subjects in two complementary datasets, i.e., the Baby Connectome Project (BCP) and the developing Human Connectome Project (dHCP), and state-of-the-art dedicated image-processing tools, we unprecedentedly parcellate the cerebral cortex into a set of distinct subdivisions purely according to the developmental patterns of the cortical surface. Our discovered developmentally distinct subdivisions correspond well to structurally and functionally meaningful regions and reveal spatially contiguous, hierarchical, and bilaterally symmetric patterns of early cortical surface expansion. We also show that high-order association subdivisions, where cortical folds emerge later during prenatal stages, undergo more dramatic cortical surface expansion during infancy, compared with the central regions, especially the sensorimotor and insula cortices, thus forming a distinct central-pole division in early cortical surface expansion. These results provide an important reference for exploring and understanding dynamic early brain development in health and disease.

Study Protocol: Gut microbiota profiles implicated in the onset of autism spectrum disorders in preterm infants: A two-year follow-up study

IntroductionPreterm infants are at high-risk of developing autism spectrum disorders (ASD). The underlying mechanisms that explain the link between prematurity and ASD are unclear. Perinatal environmental factors may disrupt the gut-brain communication, when the gut microbiome composition is established and brain programming occurs. Therefore, the disruption of the gut-brain axis communication in response to perinatal environmental events may shed light on the association between prematurity and ASD.ObjectivesTo describe a new research project protocol which aim is to develop a dynamic model of gut microbiota variation in response to environmental factors that modulate the ASD risk in preterm infants.MethodsA two-year prospective observational study will be carried out, in which preterm infants will be assessed at birth, 40th postmenstrual week, at 6, 12, and 24 months of corrected age. Two-hundred preterm infants will be recruited. A comprehensive assessment will be conducted by collecting data on sociodemographic characteristics, medical history, family functioning, neurodevelopment, ASD screening, and diagnosis. Microbiome composition and microbial activity will be determined from feces.ResultsThe expected results are: i) to characterize ASD since its early manifestations in an at-risk population, allowing an early diagnosis and intervention to improve clinical outcomes; ii) to identify early microbiota biomarkers in order to find potential pathophysiological pathways; iii) to understand the protective and risk factors associated to ASD since perinatal period.ConclusionsA two-year predictive model will be generated based on environmental and gut microbiota variables. This predictive model of ASD would allow prevention, early diagnosis, improvement of prognosis, and personalized treatments in preterm infants.DisclosureNo significant relationships.

Development of the human perihypoglossal nuclei from mid-gestation to the perinatal period: A morphological study

IntroductionMorphological data on the development of the human perihypoglossal nuclei (PHN) are scarce. This study describes the morphology of the human PHN from mid-gestation to the perinatal period. Materials and methodsTen brains were collected from infants aged 21–43 postmenstrual weeks (PW). Serial sections were cut and stained using the Klüver–Barrera method. Morphometric parameters [volume, neuronal numerical density (Nv) and total number (Nt), and neuronal profile area (PA)] were analyzed from microscopic observations. ResultsFour PHN [nucleus of Roller (RO), interfascicular nucleus (IF), intercalated nucleus (IC), and prepositus nucleus (PR)] were identified at 21 PW. Medium-sized to large, oval, or polygonal neurons were concentrated in the ventral nuclei (RO and IF) and localized regions near the IC–PR transition of the dorsal nuclei (IC and PR). Small to large neurons of various shapes were scattered across the dorsal nuclei. The PR showed rostrocaudal differences in the neuronal cytoarchitecture. The volume of each nucleus increased between 21 and 43 PW, with a typical exponential increase for the dorsal nuclei. The Nv in each nucleus exponentially decreased, whereas the Nt was almost stable. The median PA linearly increased for every nucleus, and the increasing rates were greater for the ventral nuclei than those for the dorsal nuclei. ConclusionsThe dorsal and ventral PHN are identifiable at mid-gestation. The topographic relationships of the four nuclei are conserved until the perinatal period. The characteristic neuronal cytoarchitecture of each group is rapidly formed by 28–30 PW.

Aberrant newborn T cell and microbiota developmental trajectories predict respiratory compromise during infancy

SummaryNeonatal immune-microbiota co-development is poorly understood, yet age-appropriate recognition of – and response to – pathogens and commensal microbiota is critical to health. In this longitudinal study of 148 preterm and 119 full-term infants from birth through one year of age, we found that postmenstrual age or weeks from conception is a central factor influencing T cell and mucosal microbiota development. Numerous features of the T cell and microbiota functional development remain unexplained; however, by either age metric and are instead shaped by discrete perinatal and postnatal events. Most strikingly, we establish that prenatal antibiotics or infection disrupt the normal T cell population developmental trajectory, influencing subsequent respiratory microbial colonization and predicting respiratory morbidity. In this way, early exposures predict the postnatal immune-microbiota axis trajectory, placing infants at later risk for respiratory morbidity in early childhood.

Fatty acid composition of milk from mothers giving birth at extremely low gestation in Sweden

Abstract Preterm infants show postnatal deficits of long-chain polyunsaturated fatty acids (LCPUFAs) which are essential for adequate growth and neurodevelopment. Human milk is a primary source of fatty acids (FAs) for the preterm infant, and therefore, knowledge about milk FA levels is required to design appropriate supplementation strategies. Here, we expanded on our previous study (Nilsson et al., 2018, Acta Paediatrica, 107, 1020–1027) determining FA composition in milk obtained from mothers of extremely low gestational age (<28 weeks) infants on three occasions during lactation. There was a clear difference in FA composition in milk collected at Day 7 and milk collected at postmenstrual weeks (PMW) 32 or PMW 40. Notably, the proportion of LCPUFAs was low and declined significantly during milk maturation. These results strengthen previous data that the content of FAs required by the preterm infant is not supplied in sufficient amounts when the mother’s own milk is the sole source of these essential nutrients.

The clinical use of ultra – Wide field imaging and intravenous fluorescein angiography in infants with retinopathy of prematurity

PurposeTo investigate the potential benefits and practicality of ultra – wide field (UWF) imaging and intravenous UWF fluorescein angiography (IV UWF – FA) in infants with retinopathy of prematurity (ROP) using an Optos® California device. MethodsThis retrospective study involved 46 infants with a history of ROP who underwent UWF imaging with or without IV UWF – FA. ROP characteristics were identified using UWF color imaging. Retinal vascular findings following treatment were also assessed at IV UWF – FA analysis. All imaging sessions were performed under topical anesthesia without sedation. Main outcomes were the appearance of ROP at UWF color imaging and IV UWF–FA analysis, including status of ROP, neovascularizations, presence of plus disease, retinal vascular details, and resolution after treatment. ResultsSeven (three girls) of the 46 infants (22 girls) underwent IV UWF–FA. Twelve IV UWF–FA sessions were performed in total. The oldest infant during IV UWF–FA analysis was at 55 postmenstrual weeks. Clinical characteristics of disease were easily identified at UWF color imaging. IV UWF–FA images also clearly revealed non-perfused retinal areas, fluorescein leakage, macular edema, retinal vascular abnormalities, and the status of the peripheral vascular termini. Complications of IV UWF–FA occurred in one infant in the form of patchy yellow skin discoloration around the injection site which completely disappeared on the first day following the procedure. ConclusionsProviding a high resolution panoramic view of the retina in a single image capture with no need for contact with the cornea appear to represent potential advantages of UWF imaging in infants with ROP. IV UWF–FA also seems to be a safe procedure which can be performed under topical anesthesia and that shows detailed retinal vascular alterations in patients with ROP.

Stillbirth or neonatal death before 45 post‐menstrual weeks in relation to gestational duration in pregnancies at 39 weeks of gestation or beyond: the impact of parity and body mass index. A national cohort study

To investigate the risk of stillbirth or neonatal death before 45 post-menstrual weeks in relation to gestational duration, stratified by body mass index (BMI) and parity. Retrospective study. Data from the Swedish Medical Birth Register. Singleton, cephalic births at between 39+0 and 42+2 weeks of gestation, 2005-2016 (n = 892 339). Relative risk ratios for mortality in relation to gestational duration were stratified by parity and BMI, and were adjusted for maternal age, smoking, country of birth and educational level. Primary outcome: stillbirth or neonatal death before 45 post-menstrual weeks. stillbirth. Among children of primiparous women, children born at 41+3 weeks of gestation, or later, were at increased risk of stillbirth or neonatal death before 45 post-menstrual weeks compared with children born between 39+0 and 40+2 weeks of gestation (aRR 1.29, 95% CI 1.10-1.52). For primiparous women with BMIs of <25, 25-29.9 and 30 kg/m2 , the corresponding aRRs were: 1.04 (95% CI 0.81-1.34), 1.25 (95% CI 0.94-1.66) and 1.52 (95% CI 1.10-2.10), respectively. No significant increase in risk with gestational age was detected for multiparous women, regardless of BMI class. Among primipara, the risk of stillbirth increased with gestational duration in all BMI classes, with the highest risk increase for BMI ≥ 30 kg/m2 , from 0.8/1000 at 40+3 -40+6 weeks of gestation to 4.0/1000 at 42+0 -42+2 weeks of gestation. At 41+3 -42+2 weeks of gestation, pregnancy duration was associated with an increased risk for stillbirth or neonatal death before 45 post-menstrual weeks among primiparous women, especially among women who were obese. For multiparous women, no significant association between gestational duration and mortality was found. In term pregnancies the risk for stillbirth and neonatal death is affected by gestational age, parity and BMI.

Development of the human hypoglossal nucleus from mid-gestation to the perinatal period: A morphological study

IntroductionThe human hypoglossal nucleus (nXII) was morphologically examined from mid-gestation to the perinatal period. Materials/methodsSerial brain sections from 6 preterm and 4 perinatal infants aged 21–43 postmenstrual weeks (PW) were stained with the Klüver–Barrera method. Following microscopic observation, morphometric parameters (volume, neuronal number, and neuronal profile area [PA]) were analysed. ResultsTwo types of neurons, motor and non-motor neurons, were observed at 21 PW. The motor neurons were distributed into clusters, which were not completely separated. The non-motor neurons were dispersed among the motor neurons. Myelination of the hypoglossal nerve roots was noted at 21 PW, when degenerated neurons were sporadically encountered. To a lesser extent, they were seen until 35 PW. The nXII volume increased exponentially with age. Conversely, the neuronal numerical density decreased exponentially, while the total number remained relatively stable. The neuronal PA increased gradually, with a greater rate of increase measured in the caudal part. ConclusionsIn the human nXII, motor and non-motor neurons are distinguishable from mid-gestation. Then, while the nXII expands exponentially in volume, the two types of neurons change in number and PA almost in parallel during the second half of gestation. Natural neuronal death may also occur.

Trajectory of the incidence of brushes on preterm electroencephalogram and its association with neurodevelopment in extremely low birth weight infants

BackgroundBrush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. MethodsWe analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. ResultsThe median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. ConclusionThe incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

Is fetal magnetic resonance imaging volumetry of eventrated organs in gastroschisis predictive for surgical treatment?

BackgroundFetal MRI is increasingly used in congenital abdominal wall defects. In gastroschisis, the role of fetal MRI in surgical therapy is poorly understood. Currently, the type of repair is determined primarily by clinical presentation and institutional preference.ObjectiveTo evaluate the feasibility of fetal MRI volumetry in gastroschisis treatment.Materials and methodsWe included 22 cases of gastroschisis in this retrospective single-center study. Routine fetal MRI scans were acquired between Jan. 1, 2006, and July 1, 2018, at gestational ages of 19–34 postmenstrual weeks. Fetal-MRI-based manual segmentation and volumetry were performed utilizing steady-state free precision and T2-weighted sequences. Acquired parameters included intraabdominal volume, eventrated organ volume and total fetal body volume, and we calculated a volume ratio between eventrated organ volume and intraabdominal volume (E/I ratio).ResultsPrimary closure was conducted in 13 cases and silo bag treatment with delayed closure in 9 cases. Prenatal MRI volumetry showed a significantly higher E/I ratio in patients with silo bag treatment with delayed closure (mean [M]=0.34; 95% confidence interval [CI] 0.30, 0.40) than in primary closure (M=0.23, 95% CI 0.19, 0.27; P=0.004). We propose a volume ratio cutoff value of 0.27 for predicting silo bag treatment.ConclusionFetal MRI predicted silo bag treatment in patients with gastroschisis in 90% of the cases in our cohort and might facilitate prenatal counseling and treatment planning.

Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial.

Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (<1500 g), while the effect on extremely low birth weight infants (ELBW, <1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6′-sialyllactose in mother’s milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.

Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity

BackgroundExtremely preterm infants are at risk of developing retinopathy of prematurity (ROP) that can cause impaired vision or blindness. Changes in blood lipids have been associated with ROP. This study aimed to monitor longitudinal changes in the serum sphingolipidome of extremely preterm infants and investigate the relationship to development of severe ROP. MethodsThis is a prospective study that included 47 infants born <28 gestational weeks. Serum samples were collected from cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks (PMW) 32, 36, and 40. Serum sphingolipids and phosphatidylcholines were extracted and analyzed by LC-MS/MS. Associations between sphingolipid species and ROP were assessed using mixed models for repeated measures. ResultsThe serum concentration of all investigated lipid classes, including ceramide, mono- di- and trihexosylceramide, sphingomyelin, and phosphatidylcholine displayed distinct temporal patterns between birth and PMW40. There were also substantial changes in the lipid species composition within each class. Among the analyzed sphingolipid species, sphingosine-1-phosphate showed the strongest association with severe ROP, and this association was independent of gestational age at birth and weight standard deviation score change. ConclusionsThe serum phospho- and sphingolipidome undergoes significant remodeling during the first weeks of the preterm infant's life. Low postnatal levels of the signaling lipid sphingosine-1-phosphate are associated with the development of severe ROP.

Effects of Lactobacillus reuteri supplementation on the gut microbiota in extremely preterm infants in a randomized placebo-controlled trial

SummaryExtremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of Lactobacillus reuteri supplementation, from birth to post-menstrual week (PMW)36, on infant gut microbiota. We performed 16S amplicon sequencing in 558 stool samples from 132 ELBW preterm infants at 1 week, 2 weeks, 3 weeks, 4 weeks, PMW36, and 2 years. Probiotic supplementation results in increased bacterial diversity and increased L. reuteri abundance during the 1st month. At 1 week, probiotic supplementation also results in a lower abundance of Enterobacteriaceae and Staphylococcaceae. No effects were found at 2 years. In conclusion, probiotics may exert benefits by modulating the gut microbiota composition during the 1st month in ELBW infants.

Progressive retinal vessel malformation in a premature infant with Sturge-Weber syndrome: a case report and a literature review of ocular manifestations in Sturge-Weber syndrome

BackgroundSturge-Weber syndrome is a disorder marked by a distinctive facial capillary malformation, neurological abnormalities, and ocular abnormalities such as glaucoma and choroidal hemangioma.Case presentationWe report a case of progressively formed retinal vessel malformation in a premature male infant with Sturge-Weber syndrome and retinopathy of prematurity, after treatment with intravitreal anti-vascular endothelial growth factor (VEGF). The baby was born at 30 weeks gestation with a nevus flammeus involving his left eyelids and maxillary area. On postmenstrual age week 39, he received intravitreal anti-VEGF. Diffuse choroidal hemangioma became evident at 40 weeks, with the classic “tomato catsup fundus” appearance. These clinical findings characterized Sturge-weber syndrome. He presented with posterior retinal vessel tortuosity and vein-to-vein anastomoses at 44 weeks.ConclusionThis is a rare case of documented progression of retinal vessel malformations in a patient with Sturge-Weber syndrome and retinopathy of prematurity.

Extreme prematurity and sepsis strongly influence frequencies and functional characteristics of circulating γδ T and natural killer cells.

ObjectivesExtremely low gestational age neonates with extremely low birthweight (ELGAN/ELBW) are highly susceptible to infection. This is linked to their relatively immature immune system which is not yet fully compatible with an extra‐uterine environment. Here, we performed a longitudinal characterisation of unconventional T and natural killer (NK) cells in ELGAN/ELBW during their first months of life.MethodsPeripheral blood mononuclear cells were collected from 97 ELGAN/ELBW at 14 and 28 days of life and at a time point corresponding to postmenstrual week 36 + 0. γδ T‐cell, NKT‐cell, mucosa‐associated invariant T‐cell and NK cell frequencies and characteristics were analysed by flow cytometry. As control, cells from 14‐day‐old full‐term (FT) infants were included.ResultsExtreme prematurity had significant bearing on γδ T‐cell and NK cell frequencies and characteristics. ELGAN/ELBW had significantly higher proportions of γδ T cells that were skewed towards effector and effector memory phenotypes, characteristics that were maintained throughout the study period. Expression of the gut homing receptor CCR9 was also more common in γδ T cells from ELGAN/ELBW. Conversely, NK cell frequencies were markedly lower and skewed towards a cytotoxic phenotype in the ELGAN/ELBW group at 14 days of age. Culture‐proven sepsis with an onset during the first 14 days after birth further manifested these differences in the γδ T‐ and NK cell populations at 14 days of age.ConclusionPrematurity strongly influences the levels of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life.

Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity.

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis.

A Universal Pharmacokinetic Model for Dexmedetomidine in Children and Adults.

A universal pharmacokinetic model was developed from pooled paediatric and adult data (40.6 postmenstrual weeks, 70.8 years, 3.1–152 kg). A three-compartment pharmacokinetic model with first-order elimination was superior to a two-compartment model to describe these pooled dexmedetomidine data. Population parameter estimates (population parameter variability%) were clearance (CL) 0.9 L/min/70 kg (36); intercompartmental clearances (Q2) 1.68 L/min/70 kg (63); Q3 0.62 L/min/70 kg (90); volume of distribution in the central compartment (V1) 25.2 L/70 kg (103.9); rapidly equilibrating peripheral compartment (V2) 34.4 L/70 kg (41.8); slow equilibrating peripheral compartment (V3) 65.4 L/70 kg (62). Obesity was best described by fat-free mass for clearances and normal fat mass for volumes with a factor for fat mass (FfatV) of 0.293. Models describing dexmedetomidine pharmacokinetics in adults can be applied to children by accounting for size (allometry) and age (maturation). This universal dexmedetomidine model is applicable to a broad range of ages and weights: neonates through to obese adults. Lean body weight is a better size descriptor for dexmedetomidine clearance than total body weight. This parameter set could be programmed into target-controlled infusion pumps for use in a broad population.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity

BackgroundContinuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited.MethodsThis is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50–80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels.ResultsNeonates were categorized by postmenstrual age: < 33 (n = 155), 33–36 (n = 192) and > 36 (n = 1031) weeks.From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24–28) n = 2603; 34 (33–35) n = 2501; and 38 (37–39) n = 21,058. The chance of normoxemia (65, 95%-CI 64–67%) was similar across the SpO2 range of 88–95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21–29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18–33%), for infants 33–36 weeks at 97% SpO2 (24, 95%-CI 14–25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17–22%).ConclusionsThe risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

Phase-amplitude coupling of delta brush unveiling neuronal modulation development in the neonatal brain

IntroductionDelta brushes are an indicator of brain maturity on a neonatal EEG. We investigated phase-amplitude coupling (PAC) between slow delta waves and superimposed alpha–beta activity in delta brushes to elucidate the spatiotemporal developments of the delta brush with post-menstrual weeks (PMW). MethodsThe subjects were 18 neurologically intact patients (seven girls). We analyzed EEG within 42 PMW. Patients were divided into four age groups as follows: PMW ≤30w; 31–34 w; 35–38 w; and 39–42 w. We selected up to three epochs of 2-minute EEG segments including delta brushes. We calculated the modulation index (MI), direct mean vector length (dMVL), and mean of phase angle of coupling by PAC between slow waves (0.5–1.5 Hz) and fast activities (8–25 Hz) in four regions (F: Fp1 and Fp2, C: C3 and C4, T: T3 and T4, O: O1 and O2). ResultsWe collected data from 18 patients and 31 epochs between 29 and 42 PMW, which comprised one, four, five, and eight patients, and two, seven, eight, and 14 epochs in the ≤30w, 31–34 w, 35–38 w, and 39–42 w groups, respectively. There were significant differences in the dMVL between the four regions in age groups ≤30w (P = 0.033) and 31–34w (0.017). Both MI and dMVL showed that delta brushes became higher in the occipital region from 32 to 36 PMW. The mean phase angle of coupling concentrated around either 0° or 180° for all age groups. ConclusionsPAC analysis revealed the spatiotemporal relations of alpha–beta activities that are modulated by slow delta waves in neonatal delta brushes. The delta brushes appeared to be at a maximum around 32–36 PMW with the predominant occipital distribution. The PAC of the delta brush might represent the cortical neuronal fast activity that is modulated by slow delta waves of subcortical regions during a particular neonatal period.