Brain structure and function in the fourth decade of life after extremely low birth weight: An MRI and EEG study.

OBJECTIVE: To examine potential long-term effects of extremely low birth weight (ELBW; ≤ 1000 g) on adult brain structure, brain function, and cognitive-behavioral performance. METHODS: A subset of survivors from the prospectively-followed McMaster ELBW Cohort (n = 23, MBW = 816 g) and their peers born at normal birth weight (NBW; ≥ 2500 g; n = 14, MBW = 3361 g) provided T1-weighted magnetic resonance imaging (MRI) brain scans, resting electroencephalographic (EEG) recordings, and behavioral responses to a face-processing task in their early thirties. RESULTS: Visual discrimination accuracy for human faces, resting EEG alpha power, and long-distance alpha coherence were lower in ELBW survivors than NBW adults, and volumes of white matter hypointensities (WMH) were higher. Across groups, face-processing performance was correlated positively with posterior EEG spectral power and long-distance alpha and theta coherence, and negatively with WMH. The associations between face-processing scores and parietal alpha power and theta coherence were reduced after adjustment for WMH. CONCLUSIONS: Electrocortical activity, brain functional connectivity, and higher-order processing ability may be negatively affected by WMH burden, which is greater in adults born extremely preterm. SIGNIFICANCE: Decrements in electrocortical activity and behavioral performance in adult ELBW survivors may be partly explained by increased WMH volumes in this vulnerable population.

Long-term stability of frontal electroencephalogram alpha power and asymmetry at rest in adults born at extremely low or normal birth weight: A 10-year longitudinal study.

The idea that individual differences in resting frontal EEG alpha activity have "trait-like" features that are associated with stress vulnerabilities presumes that these physiological patterns should be stable across time. We know, however, relatively little regarding the very long-term (i.e., ≥10 years) stability of resting frontal EEG alpha power and asymmetry in typically or atypically developing populations. Here, we examined the long-term stability of regional electroencephalogram (EEG) alpha (8-13 Hz) power and asymmetry at rest across a decade in the oldest known prospectively followed cohort of extremely low birth weight (ELBW; <1000 g) adult survivors and normal birth weight (NBW; >2500 g) controls. Regional EEG was collected at rest from the left and right frontal (F3, F4) and parietal (P3, P4) scalp sites using a stretchable cap during baseline eyes-open and eyes-closed conditions in young adulthood (ages 21-25 years) and again in adulthood (ages 30-35 years). We found moderate stability in regional EEG absolute alpha spectral power measures across all scalp sites for each birth weight group between the young adulthood and adulthood assessments. As well, we found the frontal alpha asymmetry measure was stable, albeit weakly, between the two assessment periods only in the NBW group. However, parietal alpha asymmetry was weak-to-moderately stable for each birth weight group across the 10-year period. Findings are discussed in terms of their implications for understanding associations between individual differences in frontal and parietal brain activity at rest and long-term stress vulnerability in typical and atypical development.

DNA methylation profiles in adults born at extremely low birth weight.

Effects of stresses associated with extremely preterm birth may be biologically "recorded" in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions.

Brain, interrupted: alpha/delta EEG ratio in survivors of pre- and post-natal adversity.

RESULTS: Young adults born at extremely low birth weight (prenatal adversity; N = 64, Mage = 23.14 years, SDage = 1.26 years) had a lower alpha/delta ratio score compared to normal birth weight controls (N = 76, Mage = 23.60 years, SDage = 1.09 years), while youth exposed to child maltreatment (postnatal adversity; N = 39, Mage = 16.18 years, SDage = 1.15) had a higher alpha/delta ratio compared to controls (N = 23, Mage = 16.00 years, SDage = 1.50 years). CONCLUSIONS: Our results suggest that being exposed to pre- and post-natal adversity may have different long-term consequences on brain development. We speculate that these differences might be associated with some of the different functional outcomes known to characterize each type of adverse experience.

Cumulative risks predict epigenetic age in adult survivors of extremely low birth weight.

Long-term sequelae of extremely low birth weight (ELBW; ≤1000 g) may contribute to accelerated biological aging. This hypothesis was examined by analyzing a range of risk factors with a molecular age marker in adults born at ELBW or normal birth weight (NBW; ≥2500 g). DNAm age-the weighted average of DNA methylation at 353 cytosine-phosphate-guanine (CpG) sites from across the genome-was derived from a sample of 45 ELBW (Mage  = 32.35 years) and 47 NBW control (Mage  = 32.44 years) adults, using the Illumina 850k BeadChip Array. At two assessments undertaken 9 years apart (at 23 and 32 years), cumulative risks were summed from six domains with potential to affect physiological and psychological health: resting respiratory sinus arrhythmia, blood pressure, basal cortisol, grip strength, body mass index, and self-esteem. At age 32 years, cumulative risks were differentially associated with epigenetic age in ELBW survivors (interaction, p < 0.01). For each additional risk factor they possessed, ELBW survivors (B = 1.43) were biologically 2.16 years older than NBW adults (B = -0.73), by the fourth decade of life. Developmental change, epigenetic maintenance, and intervention targets are discussed.

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

BACKGROUND: Brush 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

Extremely low birth weight influences the relationship between stress and telomere length in adulthood.

This study examined the link between two biological markers of stress vulnerability at 22-26 years of age and telomere length at 30-35 among extremely low birth weight (ELBW; <1000 g) survivors and normal birth weight (NBW; >2500 g) control participants. Sixteen ELBW and 22 NBW participants provided baseline afternoon salivary cortisol samples and resting frontal electroencephalogram (EEG) alpha asymmetry data at 22-26 years. Buccal cells were assayed for telomere length at 30-35 years. Analyses controlled for sex, postnatal steroid exposure, childhood socioeconomic status, time of cortisol sample collection, and body mass index at 22-26 years. Salivary cortisol and frontal asymmetry at age 22-26 independently predicted telomere length at age 30-35, such that relatively higher cortisol and greater relative right frontal asymmetry at rest predicted telomere shortening among NBW controls, but not among ELBW survivors. However, similar associations were not noted in ELBW survivors, suggesting that ELBW survivors may have different mechanisms of stress coping as a result of their early-life exposures. These findings offer preliminary evidence in support of the role of stress in the genesis of cellular senescence at least among those born at NBW, but that these links may differ in those born preterm.

Crecimiento recuperador y factores asociados en niños de muy bajo peso al nacer / Catch-up growth and associated factors in very low birth weight infants

INTRODUCCIÓN: Las características del crecimiento recuperador en niños con muy bajo peso (MBP) al nacer no se han establecido con claridad. El objetivo del estudio fue analizar el crecimiento recuperador de talla y factores asociados en una cohorte de niños con MBP al nacer (< 1.500 g) desde el nacimiento hasta los 14 años de edad. MÉTODOS: Se recogieron datos retrospectivos de peso y talla a uno, 2, 3, 4, 6, 8, 10, 12 y 14 años de edad en una cohorte de 170 recién nacidos con MBP. Se compararon estos datos antropométricos con los registrados en un grupo de control. RESULTADOS: Treinta y siete niños (21,8%) nacieron con extremado bajo peso y 32 (18,8%) fueron pretérmino extremo. A los 10 años de edad, el 7% de los niños con MBP (1.000-1.500 g) y el 35% de los niños con extremado bajo peso (< 1.500 g) tenían talla baja (p = 0,001). Casi todos los niños con MBP que tenían una talla normal a los 2, 4 y 10 años de edad habían alcanzado un peso adecuado en evaluaciones previas. El extremado bajo peso al nacer y el nacimiento pretérmino extremo resultaron ser predictores independientes de un crecimiento recuperador de talla inadecuado. CONCLUSIÓN: El patrón de crecimiento de niños con MBP al nacer tiene unas características específicas. El crecimiento recuperador de peso parece ser un factor importante para el crecimiento recuperador de talla, por lo que se recomienda un seguimiento nutricional cuidadoso en estos niños

INTRODUCTION: The characteristics of catch-up growth in very low birth weight infants (VLBW) have not been clearly established. The aim of this study was to analyse the height catch-up and some associated factors in a cohort of VLBW (birth weight < 1,500 g) from birth to age 14 years. METHODS: We obtained retrospective data on weight and height at birth and ages one, 2, 3, 4, 6, 8, 10, 12 and 14 years in a cohort of 170 VLBW. We compared these anthropometric values with those documented in a control group. RESULTS: Thirty-seven children (21.8%) were born with an extremely low birth weight and 32 (18.8%) extremely preterm. At 10 years of age, 7% of VLBW (1,000-1,500 g) and 35% of extremely low birth weight (< 1,500 g) children had short stature (P = .001). Almost all VLBW children who had a normal height at ages 2, 4 and 10 years had exhibited adequate weight catch-up in previous evaluations. We found that extremely low birth weight and extremely preterm were independent predictors for inadequate height catch-up. CONCLUSION: The growth pattern of VLBW children has specific characteristics. The catch-up in weight seems to be an important factor for catch-up in height, and therefore a thorough nutritional follow-up is recommended in these children

Cardiovascular Health Profile at Age 25 Years in Adults Born Extremely Preterm or Extremely Low Birthweight.

Being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g birthweight) may predict increased cardiometabolic risk in adulthood, but other early life predictors are less well described. We aimed to (1) compare cardiovascular health profiles between 165 adults born EP/ELBW and 127 controls at age 25 years, drawn from a prospective longitudinal cohort study, recruited at birth in 1991 to 1992; and (2) in the EP/ELBW group, determine early life associations of cardiovascular health. Cardiovascular health profiles were calculated individually for measures of anthropometry, abdominal visceral fat, blood pressure, fasting plasma glucose, insulin, lipids, C-reactive protein, vascular indices, exercise tolerance and smoking status, and summed for an overall score. Cardiovascular health profiles were compared between groups; using logistic regression (individual scores) and the Mann-Whitney U test (cumulative score). Compared with controls, adults born EP/ELBW had less favorable cardiovascular health profiles; individually for abdominal visceral fat (odds ratio, 0.56 [95% CI, 0.33-0.96], P=0.03), blood pressure (odds ratio 0.38 [95% CI, 0.23-0.63], P<0.001), exercise capacity (odds ratio 0.37 [95% CI, 0.22-0.63], P<0.001), and fasting glucose (odds ratio 0.51 [95% CI, 0.31-0.84], P=0.01) and overall (median [interquartile range] 10 [7-11] versus 11 [9-12], P=0.007). Male sex predicted unfavorable abdominal visceral fat, blood pressure and fasting glucose, and favorable exercise capacity. Greater increases in weight Z scores between 2 and 8, and 8 and 18 years predicted less favorable profiles of exercise capacity and visceral fat. Longer-term follow-up is critical to determine the cardiovascular sequelae of adults born EP/ELBW.

Determinants of the Very Low-Birth-Weight Infant's Intestinal Microbiome: A Systematic Review.

The intestinal microbiome is the genetic material from microorganisms residing in the intestinal tract. Very low-birth-weight infants (VLBW; birth weight ≤1500 g) are a physiologically compromised population undergoing a unique period of initial intestinal microbiome establishment. Evidence supports a connection between the intestinal microbiome and gastrointestinal illness that disproportionately affects VLBW infants. Necrotizing enterocolitis, an inflammatory and often necrotic condition of the intestine, and late-onset sepsis, a bloodstream infection occurring after 3 days of life, are thought to be associated with delayed or abnormal intestinal microbiome development. Here, we review the determinants, or factors, that influence the VLBW infant's intestinal microbiome and discuss clinical implications. PubMed, Web of Science, EMBASE, and CINAHL were systematically searched for publications addressing factors with the potential to affect the intestinal microbiome of VLBW infants. Results indicate that infant's age and weight, mode of delivery, antibiotic exposure, medication use, feeding regime, environment, and perinatal-/infant-associated factors may be important determinants of the microbiome in this vulnerable population. Clinicians have opportunities to support positive development of the VLBW infant's intestinal microbiome through antibiotic stewardship, support of human milk feeding, and hygienic care practices.

Perinatal quality improvement bundle to decrease hypothermia in extremely low birthweight infants with birth weight less than 1000 g: single-center experience over 6 years.

Normothermia (36.5°C-37. 5°C) at the time of admission to the neonatal intensive care unit (NICU) in extremely low birthweight (ELBW) infants (birth weight <1000 g) is associated with decreased morbidity and mortality, decreased length of stay and hospital costs. We designed a thermoregulation bundle to decrease hypothermia (<36.5°C) in ELBW infants with a multidisciplinary perinatal quality improvement initiative that included the following key interventions: dedicated delivery room (DR)/operating room (OR) for all preterm deliveries of ≤32 weeks with DR/OR temperature set 24/7 at 74°F by the hospital engineering staff, use of exothermic mattress, preheated radiant warmer set at 100% for heat prior to delivery, servo-controlled mode after the neonate is placed on the warmer, and use of plastic wrap, head cap and warm towels. A total of 200 ELBW infants were admitted to our NICU between January 1, 2014 and December 31, 2019. Hypothermia (<36.5°C) occurred in 2.5% of infants, normothermia (36.5°C-37.5°C) in 91% of infants and transitional hyperthermia (>37.5°C) in 6.5% of ELBW infants. No case of moderate hypothermia (32°C-36°C) was seen in our infants. Our target rate of less than 10% hypothermia was reached in ELBW infants over the last 2 years with no cases of moderate hypothermia in 6 years. Eliminating hypothermia among ELBW remains a challenge and requires team effort and continuous quality improvement efforts.

Aerobic Capacity of Preterm Children with Very Low Birth Weight at School Age and its Associated Factors / Capacidad aeróbica de niños prematuros de muy bajo peso al nacer y edad escolar y sus factores asociados

INTRODUCTION: Respiratory morbidities of preterm infants can cause significant ventilatory impairment thus compromising the aerobic capacity in childhood and adolescence. Therefore, the present study was conducted to evaluate the aerobic capacity in school age preterm children with VLBW and its associated factors. METHODS: A cross-sectional study was conducted among preterm born with VLBW and term children, both aged 6-9 years. An individualized symptom-limited treadmill testing protocol performed aerobic capacity. Measured variables: oxygen pulse (PuO2), percentage of maximum heart rate for age (%HR max), tidal volume/inspiratory capacity ratio (TV/IC), oxygen consumption (VO2) peak, and the ratio of the anaerobic threshold of gas exchange to the predicted percentage of maximum VO2 (VO2@LA/%VO2 max.pred.) were compared between groups. Univariate and multiple linear regression analyses were used to determine the factors associated with aerobic capacity. RESULTS: Thirty-four preterm and 32 term children were included. Similar VO2 peak and the other variables were observed. The development of bronchopulmonary dysplasia (BPD) and being obese/overweight was positively associated with %HR max. The Z-score for height/age and birth weight < 1000 g was positively associated with PuO2 and peak VO2, and negatively associated with overweight/obesity and female sex. CONCLUSIONS: Aerobic capacity was similar in both groups. Sex, development of BPD, birth weight < 1000 g and factors related to body growth, such as Z-score for height/age and overweight/obesity, were associated with aerobic capacity in preterm children with VLBW

INTRODUCCIÓN: Las enfermedades respiratorias de los niños prematuros pueden causar importantes impedimentos ventilatorios que comprometen la capacidad aeróbica en la infancia y en la adolescencia. El presente estudio se llevó a cabo para evaluar la capacidad aeróbica de niños prematuros en edad escolar de muy bajo peso al nacer (BPN) y los factores asociados. MÉTODOS: Se llevó a cabo un estudio transversal con niños prematuros de muy BPN y con niños a término, ambos grupos con edades comprendidas entre los 6 y 9 años. Las siguientes variables se compararon entre los 2 grupos: el pulso de oxígeno (PuO2), el porcentaje de frecuencia cardíaca máxima (%FC máx.), la relación entre el volumen corriente y la capacidad inspiratoria (TV/IC), el consumo pico de oxígeno (VO2) y la relación entre el umbral anaeróbico de intercambio de gas y el porcentaje estimado de VO2 máximo (VO2@LA/%VO2 máx. pred.). Se llevaron a cabo análisis de regresión lineal univariante y multivariante para determinar los factores asociados con la capacidad aeróbica. RESULTADOS: Se incluyeron 34 niños prematuros y 32 niños a término. Se registraron valores similares de VO2 pico y de otras variables. El desarrollo de displasia broncopulmonar (BPD) y de obesidad/sobrepeso mostró una asociación positiva con el %FC máx. El Z-score para la altura/edad y el peso al nacer < 1.000 g se asoció positivamente con la SaO2 y el VO2 y negativamente con el sobrepeso/obesidad y el sexo femenino. CONCLUSIONES: La capacidad aeróbica fue similar entre los 2 grupos. El sexo, el desarrollo de BPD, peso al nacer < 1.000 g y factores relacionados con el crecimiento corporal, tales como el Z-score para la altura/edad y para el sobrepeso/obesidad se asociaron con la capacidad aeróbica en niños prematuros de muy BPN

Visual configural processing in adults born at extremely low birth weight.

Being born at extremely low birth weight (ELBW; ≤1,000 g) is associated with enduring visual impairments. We tested for long-term, higher order visual processing problems in the oldest known prospectively followed cohort of ELBW survivors. Configural processing (spacing among features of an object) was examined in 62 adults born at ELBW (Mage  = 31.9 years) and 82 adults born at normal birth weight (NBW; ≥2,500 g: Mage  = 32.5 years). Pairs of human faces, monkey faces, or houses were presented in a delayed match-to-sample task, where non-matching stimuli differed only in the spacing of their features. Discrimination accuracy for each stimulus type was compared between birth weight groups, adjusting for neurosensory impairment, visual acuity, binocular fusion ability, IQ, and sex. Both groups were better able to discriminate human faces than monkey faces (p < .001). However, the ELBW group discriminated between human faces (p < .001), between monkey faces (p < .001), and to some degree, between houses (p < .06), more poorly than NBW control participants, suggesting a general deficit in perceptual processing. Human face discrimination was related to performance IQ (PIQ) across groups, but especially among ELBW survivors. Coding (a PIQ subtest) also predicted human face discrimination in ELBW survivors, consistent with previously reported links between visuo-perceptive difficulties and regional slowing of cortical activity in individuals born preterm. Correlations with Coding suggested ELBW survivors may have used a feature-matching approach to processing human faces. Future studies could examine brain-based anatomical and functional evidence for altered face processing, as well as the social and memory consequences of face-processing deficits in ELBW survivors.

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children.

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

The children of preterm survivors: shyness, parenting, and parental stress.

Extremely low birth weight (ELBW) survivors have higher rates of shyness, a risk factor for poorer outcomes across the life span. Due to advances in fetal and neonatal medicine, the first generation of ELBW survivors have survived to adulthood and become parents. However, no studies have investigated the transmission of their stress vulnerability to their offspring. We explored this phenomenon using a population-based cohort of ELBW survivors and normal birth weight (NBW) controls. Using data from three generations, we examined whether the shyness and parenting stress of ELBW and NBW participants (Generation 2) mediated the relation between the parenting style of their parents (Generation 1) and shyness in their offspring (Generation 3), and the extent to which exposure to perinatal adversity (Generation 2) moderated this mediating effect. We found that among ELBW survivors, parenting stress (in Generation 2) mediated the relation between overprotective parenting style in Generation 1 (grandparents) and child shyness in Generation 3. These findings suggest that perinatal adversity and stress may be transmitted to the next generation in humans, as reflected in their perceptions of their children as shy and socially anxious, a personality phenotype that may subsequently place their children at risk of later mental and physical health problems.

High Blood Pressure in Young Adult Survivors Born Extremely Preterm or Extremely Low Birthweight in the Post Surfactant Era.

More infants born extremely preterm (<28 weeks' gestation) or extremely low birthweight (<1000 g) are surviving into adulthood in recent years. Preterm adolescents have higher blood pressure (BP) than normal birthweight controls, but how their BP changes with increasing age is not known. We compared BP at 25 years and trajectories of BP (change per year) from 18 to 25 years between survivors born <28 weeks/<1000 g and normal birthweight (>2499 g) controls born in the early 1990s, when survival rates began to rise. Participants were derived from 297 consecutive survivors born <28 weeks/<1000 g in 1991 to 1992 in Victoria, Australia, and 260 contemporaneous controls. At age 25 years, ambulatory BP was measured in 151 and 119 participants, respectively. Participants born <28 weeks/<1000 g had higher 24-hour systolic (mean difference 4.5 [95% CI, 1.2-7.7 mm Hg]), diastolic (3.4 [1.5-5.2 mm Hg]), and mean BPs (3.6 [1.4-5.8 mm Hg]) compared with the controls. Similar patterns were observed for both awake and asleep periods. Asleep ambulatory BP between 18 and 25 years increased more in participants born <28 weeks/<1000 g than in controls (systolic 0.56, diastolic 0.41, and mean 0.41 mm Hg increase per year; all P<0.05). Young adults born <28 weeks/<1000 g in the post surfactant era have higher BP and an increased trajectory of ambulatory BP compared with controls. With more survivors born <28 weeks/<1000 g now reaching adulthood, these findings are important for early detection and timely management of hypertension in this high-risk population.

Airway obstruction in young adults born extremely preterm or extremely low birth weight in the postsurfactant era.

BACKGROUND: It is unknown if adults born <28 weeks or <1000 g since surfactant has been available are reaching their full airway growth potential. OBJECTIVE: To compare expiratory airflow at 25 years and from 8 to 25 years of participants born <28 weeks or <1000 g with controls, and within the preterm group to compare those who had bronchopulmonary dysplasia with those who did not. METHODS: All survivors born <28 weeks or <1000 g in 1991-1992 in Victoria, Australia, were eligible. Controls were born contemporaneously, weighing >2499 g. At 8, 18 and 25 years, expiratory airflows were measured and the results converted to z-scores. Outcomes were compared between groups at age 25 years, and trajectories (change in z-scores per year) from childhood were contrasted between groups. RESULTS: Expiratory airflows were measured at 25 years on 164 of 297 (55%) preterm survivors and 130 of 260 (50%) controls. Preterm participants had substantially reduced airflow compared with controls at age 25 years (eg, zFEV1; mean difference -0.97, 95% CI -1.23 to -0.71; p<0.001). Preterm participants had lower airflow trajectories than controls between 8 and 18 years, but not between 18 and 25 years. Within the preterm group, those who had bronchopulmonary dysplasia had worse airflows and trajectories than those who did not. CONCLUSIONS: Young adults born <28 weeks or <1000 g in the surfactant era, particularly those who had bronchopulmonary dysplasia, have substantially reduced airway function compared with controls. Some are destined to develop COPD in later adult life.

Extremely Low Birth Weight Predisposes to Impaired Renal Health: A Pooled Analysis.

BACKGROUND: A number of studies examined the association between preterm delivery and kidney size and function later in life. However, the number of cases in published cohort studies is low. This study was aimed at performing a multicenter collaboration to pool data to obtain more accurate results to quantify the extent of renal impairment in former extremely low birth weight (ELBW; <1,000 g) children. METHODOLOGY: We performed a subject-level meta-analysis to pool data from Cracow (64 cases/34 controls) and Leuven (93 cases/87 controls). We assessed and analyzed cystatin C, estimated glomerular filtration rate (eGFR), ultrasound kidney length, and blood pressure (BP) in 11-year-old ELBW children compared with controls born at term. The prevalence of hypertension (HT) and prehypertension (preHT) in both groups was also analyzed. RESULTS: The study group comprised 157 former ELBW children (gestational age 23-33 weeks and birth weight 430-1,000 g) and 123 children born at term. Former ELBW children had lower mean eGFR (100.62 ± 16.53 vs. 111.89 ± 15.26 mL/min/1.73 m2; p < 0.001), smaller absolute kidney length (8.56 ± 0.78 vs. 9.008 ± 0.73 cm; <0.001), and higher systolic (111.8 ± 9.8 vs. 107.2 ± 9.07 mm Hg; p = 0.01) and diastolic (68.6 ± 6.8 vs. 66.3 ± 7.7 mm Hg; p = 0.03) BP. Smaller renal size in former ELBW children was positively associated with lower birth weight, shorter gestational age, and severity of perinatal complications (intraventricular hemorrhage, length of stay, mechanical ventilation, and oxygen therapy). CONCLUSION: ELBW is associated with lower eGFR and a high frequency of preHT and HT.

Resilience in Extremely Preterm/Extremely Low Birth Weight Kindergarten Children.

OBJECTIVES: Research on developmental outcomes of preterm birth has traditionally focused on adverse effects. This study investigated the prevalence and correlates of resilience in 146 extremely preterm/extremely low birth weight (EPT/ELBW) children (gestational age <28 weeks and/or birth weight <1000 g) attending kindergarten and 111 term-born normal birth weight (NBW) controls. METHODS: Adaptive competence (i.e., "resilience" in the EPT/ELBW group) was defined by scores within grade expectations on achievement tests and the absence of clinically elevated parent ratings of child behavior problems. The "adaptive" children who met these criteria were compared to the "maladaptive" children who did not on child and family characteristics. Additional analyses were conducted to assess the conjoint effects of group (ELBW vs. NBW) and family factors on adaptive competence. RESULTS: A substantial minority of the EPT/ELBW group (45%) were competent compared to a majority of NBW controls (73%), odds ratio (95% confidence interval)=0.26 (0.15, 0.45), p<.001. Adaptive competence was associated with higher cognitive skills, more favorable ratings of behavior and learning not used to define adaptive competence, and more advantaged family environments in both groups, as well as with a lower rate of earlier neurodevelopmental impairment in the EPT/ELBW group. Higher socioeconomic status and more favorable proximal home environments were associated with competence independent of group, and group differences in competence persisted across the next two school years. CONCLUSIONS: The findings document resilience in kindergarten children with extreme prematurity and highlight the role of environmental factors as potential influences on outcome. (JINS, 2019, 25, 362-374).

Statistical Modeling of Heart Rate Variability to Unravel the Factors Affecting Autonomic Regulation in Preterm Infants.

Analyzing heart rate variability (HRV) in preterm infants can help track maturational changes and subclinical signatures of disease. We conducted an observational study to characterize the effect of demographic and cardiorespiratory factors on three features of HRV using a linear mixed-effects model. HRV-features were tailored to capture the unique physiology of preterm infants, including the contribution of transient pathophysiological heart rate (HR) decelerations. Infants were analyzed during stable periods in the incubator and subsequent sessions of Kangaroo care (KC) - an intervention that increases comfort. In total, 957 periods in the incubator and during KC were analyzed from 66 preterm infants. Our primary finding was that gestational age (GA) and postmenstrual age (PMA) have the largest influence on HRV while the HR and breathing rate have a considerably smaller effect. Birth weight and gender do not affect HRV. We identified that with increasing GA and PMA, overall HRV decreased and increased respectively. Potentially these differences can be attributed to distinct trajectories of intra- and extrauterine development. With increasing GA, the propensity towards severe HR decelerations decreases, thereby reducing overall variability, while with increasing PMA, the ratio of decelerations and accelerations approaches unity, increasing overall HRV.