scholarly journals Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

2021 ◽  
Author(s):  
Ralica Dimitrova ◽  
Maximilian Pietsch ◽  
Judit Ciarrusta ◽  
Sean P Fitzgibbon ◽  
Logan ZJ Williams ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Cortical Thickness ◽  
Tissue Water ◽  
Normative Development ◽  
Equivalent Age ◽  
Neurite Density ◽  
Postmenstrual Age ◽  
Cortical Maturation ◽  
Age At Birth

Introduction: The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. Methods: We sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. Results: In the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. Conclusion: We showed that preterm birth alters cortical micro and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

scholarly journals Phenotyping the Preterm Brain: Characterizing Individual Deviations From Normative Volumetric Development in Two Large Infant Cohorts

2021 ◽  
Author(s):  
Ralica Dimitrova ◽  
Sophie Arulkumaran ◽  
Olivia Carney ◽  
Andrew Chew ◽  
Shona Falconer ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Gaussian Process Regression ◽  
Large Degree ◽  
Brain Maturation ◽  
Independent Dataset ◽  
Normative Development ◽  
Equivalent Age ◽  
The Individual

Abstract The diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterizing brain volumetric development in 274 term-born infants, modeling for age at scan and sex. We then compared 89 preterm infants scanned at term-equivalent age with these normative charts, relating individual deviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalizability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, nonuniform brain growth during the neonatal period. In both preterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguises a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterization of the cerebral consequences of preterm birth by profiling the individual neonatal brain.

Infection and premature rupture of the membranes

1990 ◽  
Vol 2 (1) ◽  
pp. 1-19
Author(s):  
Kyung Seo ◽  
James A McGregor ◽  
Janice I French
Keyword(s):  
Health Care ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Important Determinant ◽  
Premature Rupture ◽  
Neonatal Deaths ◽  
Financial Costs ◽  
The Usa ◽  
Gestational Age At Birth ◽  
Age At Birth

Premature rupture of the membranes (PROM) and preterm birthPreterm birth remains a paramount problem in health care worldwide. In the USA, approximately 6–10% of births occur preterm.1–3Gestational age at birth is the most important determinant of an infant's morbidity and mortality. Preterm infants account for approximately 75% of neonatal deaths,3–5as well as incalculable direct and indirect financial costs and morbidity.6–9

scholarly journals Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

2018 ◽  
Author(s):  
Todd M. Everson ◽  
Carmen J. Marsit ◽  
T. Michael O’Shea ◽  
Amber Burt ◽  
Karen Hermetz ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Developmental Trajectories ◽  
P Value ◽  
Buccal Cells ◽  
Neurobehavioral Performance ◽  
Very Preterm Infants ◽  
Equivalent Age ◽  
Epigenetic Age ◽  
Postmenstrual Age ◽  
Near Term

AbstractBackground & ObjectivesNeonatal neurobehavioral performance measures, such as the NICU Network Neurobehavioral Scale (NNNS), have been developed to assess the neurobehavioral characteristics of infants and provide insights into future developmental trajectories. The identification of molecular biomarkers of very early life neurobehavioral experiences could lead to better predictions of the long-term developmental outcomes of high-risk infants including preterm infants. To this end, we aimed to examine whether variability in DNA methylation (DNAm) or epigenetic age from surrogate tissues are associated with NNNS profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA).MethodsThis study was performed within the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study and included those infants with complete NNNS assessment data and DNAm measured from buccal cells, collected at near term-equivalent age using the Illumina EPIC array (N=536). We tested whether epigenetic age and age acceleration differed between infants based on their NNNS profile classifications. Then we performed an epigenome-wide association study, to test whether DNAm at individual epigenetic loci varied between these NNNS profile groupings. Models were adjusted for recruitment site, infant sex, postmenstrual age, and estimated tissue heterogeneity.ResultsWe found that infants with an optimal NNNS profile had slightly older epigenetic age than other NOVI infants (β1 = 0.201, p-value = 0.026), and that infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). The genes annotated to these differentially methylated CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders.ConclusionsGreater epigenetic age is associated with optimal NNNS responses while altered DNAm of multiple genes are associated with an atypical neurobehavioral profile at near-term equivalent age. These findings build upon the existing evidence that epigenetic variations in buccal cells may serve as markers of neonatal neurobehavior and might facilitate early identification of children at risk for abnormal developmental outcome.

scholarly journals Retinal vascular development in an immature retina at 33–34 weeks postmenstrual age predicts retinopathy of prematurity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ji Hye Jang ◽  
Yu Cheol Kim
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Gestational Age ◽  
Retinopathy Of Prematurity ◽  
Retinal Images ◽  
Wide Field ◽  
Proliferative Phase ◽  
Postmenstrual Age ◽  
Zone Ii ◽  
Retinal Vascularization

Abstract In preterm birth, the immature retina can develop a potentially blinding disorder of the eye known as retinopathy of prematurity (ROP). The vaso-proliferative phase of ROP begins at an approximate postmenstrual age (PMA) of 32 weeks. There is little or no evidence of an association between ROP development and retinal status in the early vaso-proliferative phase. We aimed to evaluate the retinal vascular findings of infants at 33–34 weeks PMA to determine their risk of ROP. We reviewed 130 serial wide-field retinal images from 65 preterm infants born before the gestational age of 31 weeks. ROP occurred more frequently in infants having a leading vascular edge within posterior Zone II. This was in contrast to normal infants, who are characterized by complete retinal vascularization up to Zone II at 34 weeks PMA. The probability of ROP development in preterm infants with retinal edge hemorrhage was 24.58 times higher than in preterm infants without retinal edge hemorrhage. Eyes with ROP that required treatment showed significantly delayed retinal vascularization accompanied by pre-plus disease. In conclusion, retinal status in the early vaso-proliferation phase might determine the risk of ROP.

scholarly journals Preterm Birth Affects Early Motor Development in Pigs

2021 ◽  
Vol 9 ◽  
Author(s):  
Charlotte Vanden Hole ◽  
Miriam Ayuso ◽  
Peter Aerts ◽  
Steven Van Cruchten ◽  
Thomas Thymann ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Motor Skills ◽  
Gestational Age ◽  
Gait Pattern ◽  
Gestation Length ◽  
Gestation Time ◽  
Gestational Age At Birth ◽  
Normal Gestation ◽  
Age At Birth

Background: Preterm infants frequently show neuromotor dysfunctions, but it is not clear how reduced gestational age at birth may induce developmental coordination disorders. Advancing postnatal age, not only post-conceptional age, may determine neuromuscular development, and early interventions in preterm newborns may improve their later motor skills. An animal model of preterm birth that allows early postnatal detection of movement patterns may help to investigate this hypothesis.Methods: Using pigs as a model for moderately preterm infants, preterm (106-day gestation, equivalent to 90% of normal gestation time; n = 38) and term (115-day gestation, equivalent to 99% of normal gestation time; n = 20) individuals were delivered by cesarean section and artificially reared until postnatal day 19 (preweaning period). The neuromotor skills of piglets were documented using spatiotemporal gait analyses on video recordings of locomotion at self-selected speed at postnatal age 3, 4, 5, 8, and 18 days. Results were controlled for effects of body weight and sex.Results: Both preterm and term piglets reached mature neuromotor skills and performance between postnatal days 3–5. However, preterm pigs took shorter steps at a higher frequency, than term piglets, irrespective of their body size. Within preterm pigs, males and low birth weight individuals took the shortest steps, and with the highest frequency.Conclusion: Postnatal development of motor skills and gait characteristics in pigs delivered in late gestation may show similarity to the compromised development of gait pattern in preterm infants. Relative to term pigs, the postnatal delay in gait development in preterm pigs was only few days, that is, much shorter than the 10-day reduction in gestation length. This indicates rapid postnatal adaptation of gait pattern after reduced gestational age at birth. Early-life physical training and medical interventions may support both short- and long-term gait development after preterm birth in both pigs and infants.

scholarly journals Individualized characterization of volumetric development in the preterm brain

2020 ◽  
Author(s):  
Ralica Dimitrova ◽  
Sophie Arulkumaran ◽  
Olivia Carney ◽  
Andrew Chew ◽  
Shona Falconer ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Gestational Age ◽  
Significant Risk ◽  
Gaussian Process Regression ◽  
Large Degree ◽  
Magnetic Resonance Images ◽  
Single Individual ◽  
Equivalent Age

AbstractObjectivePreterm birth carries a significant risk for atypical development. While studies comparing group means have identified a number of early brain correlates of prematurity, they may ‘average out’ effects significant in a single individual. To understand better the cerebral consequences of prematurity, we created normative ‘growth curves’ characterizing neonatal brain development and explored the effect of preterm birth and related clinical risks in individual infants.MethodsWe used Gaussian process regression to map typical volumetric development in 275 healthy term-born infants, modelling for age at scan and sex. We compared magnetic resonance images of 89 preterm infants (born 28.7–34 weeks gestational age) scanned at term-equivalent age to these normative charts and related deviations from typical volumetric development to both perinatal clinical variables and neurocognitive scores at 18 months. We then tested if this approach can be generalized to an independent dataset of 253 preterm infants (born 28–31.6 weeks gestational age) also scanned at term-equivalent age but using different acquisition parameters and scanner, who were followed-up at 20 months.ResultsIn both preterm cohorts, cerebral atypicalities were widespread and often multiple, but varied highly between individual infants. Deviations from normative brain volumetric development were associated with perinatal factors including respiratory support, nutrition and postnatal growth, as well as with later neurocognitive outcome.ConclusionGroup-level understanding of the preterm brain might disguise a large degree of individual differences. We provide a method and a normative dataset for clinicians and researchers to profile the individual brain. This will allow a more precise characterization of the cerebral consequences of prematurity and improve the predictive power of neuroimaging.

scholarly journals Population Pharmacokinetics of Metronidazole Evaluated Using Scavenged Samples from Preterm Infants

2012 ◽  
Vol 56 (4) ◽  
pp. 1828-1837 ◽  
Author(s):  
Michael Cohen-Wolkowiez ◽  
Daniele Ouellet ◽  
P. Brian Smith ◽  
Laura P. James ◽  
Ashley Ross ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Gestational Age ◽  
Minimal Risk ◽  
Dosing Regimen ◽  
Data Set ◽  
Relative Standard ◽  
Population Pk ◽  
Postmenstrual Age ◽  
Gestational Age At Birth ◽  
Age At Birth

ABSTRACTPharmacokinetic (PK) studies in preterm infants are rarely conducted due to the research challenges posed by this population. To overcome these challenges, minimal-risk methods such as scavenged sampling can be used to evaluate the PK of commonly used drugs in this population. We evaluated the population PK of metronidazole using targeted sparse sampling and scavenged samples from infants that were ≤32 weeks of gestational age at birth and <120 postnatal days. A 5-center study was performed. A population PK model using nonlinear mixed-effect modeling (NONMEM) was developed. Covariate effects were evaluated based on estimated precision and clinical significance. Using the individual Bayesian PK estimates from the final population PK model and the dosing regimen used for each subject, the proportion of subjects achieving the therapeutic target of trough concentrations >8 mg/liter was calculated. Monte Carlo simulations were performed to evaluate the adequacy of different dosing recommendations per gestational age group. Thirty-two preterm infants were enrolled: the median (range) gestational age at birth was 27 (22 to 32) weeks, postnatal age was 41 (0 to 97) days, postmenstrual age (PMA) was 32 (24 to 43) weeks, and weight was 1,495 (678 to 3,850) g. The final PK data set contained 116 samples; 104/116 (90%) were scavenged from discarded clinical specimens. Metronidazole population PK was best described by a 1-compartment model. The population mean clearance (CL; liter/h) was determined as 0.0397 × (weight/1.5) × (PMA/32)2.49using a volume of distribution (V) (liter) of 1.07 × (weight/1.5). The relative standard errors around parameter estimates ranged between 11% and 30%. On average, metronidazole concentrations in scavenged samples were 30% lower than those measured in scheduled blood draws. The majority of infants (>70%) met predefined pharmacodynamic efficacy targets. A new, simplified, postmenstrual-age-based dosing regimen is recommended for this population. Minimal-risk methods such as scavenged PK sampling provided meaningful information related to development of metronidazole PK models and dosing recommendations.

Timing of Discharge From the NICU Among Preterm Infants Is Related to Motor Outcome

2021 ◽  
Vol 75 (Supplement_2) ◽  
pp. 7512510281p1-7512510281p1
Author(s):  
Polly Kellner ◽  
Jenny Kwon ◽  
Roberta Pineda
Keyword(s):  
Early Childhood ◽  
High Risk ◽  
Preterm Infants ◽  
Language Delay ◽  
Due Date ◽  
Motor Outcome ◽  
Postmenstrual Age ◽  
Gestational Age At Birth ◽  
Age At Birth ◽  
Primary Author

Abstract Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. The incidence of motor, cognitive, and language delay among children who were born preterm (&lt; 32 weeks gestation) is high. Estimated gestational age at birth appears to influence the timing of discharge, with infants born earlier being discharged later after accounting for the degree of prematurity. Postmenstrual age at discharge appears to be related to motor outcome in early childhood, shedding light on the high-risk nature of this population of infants still hospitalized after their due date. Primary Author and Speaker: Polly Kellner Additional Authors and Speakers: Jenny Kwon Contributing Authors: Roberta Pineda

scholarly journals A birth population-based survey of preterm morbidity and mortality by gestational age

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaojing Guo ◽  
Xiaoqiong Li ◽  
Tingting Qi ◽  
Zhaojun Pan ◽  
Xiaoqin Zhu ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Birth Defects ◽  
Gestational Age ◽  
Death Rate ◽  
Preterm Births ◽  
Mortality Rates ◽  
Morbidity And Mortality ◽  
Hospital Death

Abstract Background Despite 15–17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai’an in 2015, an emerging prefectural region of China. Methods Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai’an Women and Children’s Hospital (HWCH) and non-HWCH hospitals in 2018–2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression. Results The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks. Conclusions The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.

Sign in / Sign up

Export Citation Format

Share Document