Optimizing trajectories of social adaptive competencies after extreme prematurity during the first 1000 days.

Over 75% of surviving extremely preterm infants do not have major neurodevelopmental disabilities; however, more than half face difficulties with communication, coordination, attention, learning, social, and executive function abilities. These "minor" challenges can have a negative impact on educational and social outcomes, resulting in physical, behavioral, and social health problems in adulthood. We will review assessment tools for social-emotional and adaptive functional skills in early childhood as these determine family and early childhood supports. We highlight bronchopulmonary dysplasia as an example of the critical intersections of parental wellbeing, medical and developmental adaptive trajectories in infancy and early childhood, and partnerships between child neurologists and community medical and developmental professionals. We examine studies of engaging parents to promote developmental trajectories, with a focus on supporting parent-child interactions that underlie communication, social-adaptive behaviors, and learning in the first 1000 days of life. Recommendations for neurodevelopmental surveillance and screening of extremely preterm infants can also be applied to infants with other risk factors for altered neurodevelopment.

Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age.

OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.

OBJECTIVE: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. MATERIALS AND METHODS: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. RESULTS: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. CONCLUSION: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.

Assessment of 2-Year Neurodevelopmental Outcomes in Extremely Preterm Infants Receiving Opioids and Benzodiazepines.

Importance: Extremely preterm (EP) infants frequently receive opioids and/or benzodiazepines, but these drugs' association with neurodevelopmental outcomes is poorly understood. Objectives: To describe the use of opioids and benzodiazepines in EP infants during neonatal intensive care unit (NICU) hospitalization and to explore these drugs' association with neurodevelopmental outcomes at 2 years' corrected age. Design, Setting, and Participants: This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial, which was conducted among infants born between gestational ages of 24 weeks, 0 days, and 27 weeks, 6 days. Infants received care at 19 sites in the United States, and data were collected from December 2013 to September 2016. Data analysis for this study was conducted from March to December 2020. Exposures: Short (ie, ≤7 days) and prolonged (ie, >7 days) exposure to opioids and/or benzodiazepines during NICU stay. Main Outcomes and Measures: Cognitive, language, and motor development scores were assessed using the Bayley Scales of Infant Development-Third Edition (BSID-III). Results: There were 936 EP infants (448 [48%] female infants; 611 [65%] White infants; mean [SD] gestational age, 181 [8] days) included in the study, and 692 (74%) had neurodevelopmental outcome data available. Overall, 158 infants (17%) were not exposed to any drugs of interest, 297 (32%) received either opioids or benzodiazepines, and 481 (51%) received both. Infants exposed to both had adjusted odds ratios of 9.7 (95% CI, 2.9 to 32.2) for necrotizing enterocolitis and 1.7 (95% CI, 1.1 to 2.7) for severe bronchopulmonary dysplasia; they also had a longer estimated adjusted mean difference in length of stay of 34.2 (95% CI, 26.2 to 42.2) days compared with those who received neither drug. After adjusting for site and propensity scores derived for each exposure category, infants exposed to opioids and benzodiazepines had lower BSID-III cognitive, motor, and language scores compared with infants with no exposure (eg, estimated difference in mean scores on cognitive scale: -5.72; 95% CI, -8.88 to -2.57). Prolonged exposure to morphine, fentanyl, midazolam, or lorazepam was associated with lower BSID-III scores compared with infants without exposure (median [interquartile range] motor score, 85 [73-97] vs 97 [91-107]). In contrast, BSID-III scores for infants with short exposure to both opioids and benzodiazepines were not different than those of infants without exposure. Conclusions and Relevance: In this study, prolonged combined use of opioids and benzodiazepines was associated with a risk of poorer neurodevelopmental outcomes as measured by BSID-III at 2 years' corrected age.

Identification of variation in nutritional practice in neonatal units in England and association with clinical outcomes using agnostic machine learning.

We used agnostic, unsupervised machine learning to cluster a large clinical database of information on infants admitted to neonatal units in England. Our aim was to obtain insights into nutritional practice, an area of central importance in newborn care, utilising the UK National Neonatal Research Database (NNRD). We performed clustering on time-series data of daily nutritional intakes for very preterm infants born at a gestational age less than 32 weeks (n = 45,679) over a six-year period. This revealed 46 nutritional clusters heterogeneous in size, showing common interpretable clinical practices alongside rarer approaches. Nutritional clusters with similar admission profiles revealed associations between nutritional practice, geographical location and outcomes. We show how nutritional subgroups may be regarded as distinct interventions and tested for associations with measurable outcomes. We illustrate the potential for identifying relationships between nutritional practice and outcomes with two examples, discharge weight and bronchopulmonary dysplasia (BPD). We identify the well-known effect of formula milk on greater discharge weight as well as support for the plausible, but insufficiently evidenced view that human milk is protective against BPD. Our framework highlights the potential of agnostic machine learning approaches to deliver clinical practice insights and generate hypotheses using routine data.

The Prognosis of Preterm Infants Born at the Threshold of Viability: Fog Over the Gray Zone - Population-Based Studies of Extremely Preterm Infants.

The limit of viability for premature newborns has changed in recent decades, but whether to initiate or withhold active care for periviable infants remains a subject of debate because the chances of survival and the extent of severe neurological impairment can be unclear. In our review, we analyzed large population-based studies of periviable infants from the past 2 decades. We compared survival rates and the incidence of early complications among survivors, including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, and necrotizing enterocolitis. Moreover, we assessed the perinatal factors that may affect the survival of preterm infants. We analyzed 15 studies reporting data on preterm infants born between 22 and 28 gestational weeks. None of these studies reported survival of an infant born before 22 gestational weeks. Survival rates of infants born at 24 weeks' gestation were above 50% in most studies. The incidence of each complication was also higher among infants born at ≤24 weeks. Of the analyzed perinatal factors, antenatal corticosteroid therapy, birth weight, female sex, cesarean delivery, singleton pregnancy, and birth in a tertiary-level Neonatal Intensive Care Unit were found to be associated with improved survival in some studies. The different methodologies of the studies limited comparison of the results. Further investigations are needed to gain up-to-date information on the limit of viability, and standardized methods in future studies would enable more accurate comparisons of findings.

Does ADHD worsen inhibitory control in preschool children born very premature and/or with very low birth weight?

Abstract Introduction Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). Objective To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. Methods 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version (K-SADS-PL). IC was measured with Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. Conclusions ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children's EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

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.

Exacerbated mini-puberty of infancy in an ex-extreme preterm girl.

Vaginal bleeding can occur shortly after delivery in 3%-5% of newborns as a consequence of placental hormone withdrawal . Although usually benign, its differential diagnosis includes central precocious puberty, tumours and other pathological conditions. A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.

Postnatal dexamethasone exposure and lung function in adolescents born very prematurely.

We previously demonstrated corticosteroid administration on the neonatal intensive care unit was associated with reduced lung function at 11 to 14 years of age in children born very prematurely. The objective of this observational study was to assess if lung function remained impaired at 16 to 19 years of age in those who had received postnatal corticosteroids and whether the trajectory of lung function with increasing age differed between those who had and had not received corticosteroids. One hundred and fifty-nine children born prior to 29 weeks of gestational age had comprehensive lung function measurements; 49 had received postnatal dexamethasone. Lung function outcomes were compared between those who had and had not received postnatal dexamethasone after adjustment for neonatal factors. Forced expiratory flow at 75%, 50%, 25% and 25-75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes (total lung capacity and residual volume) were assessed. The majority of results were significantly lower in those who received dexamethasone (between 0.61 to 0.78 standard deviations). Lung function reduced as the number of courses of dexamethasone increased. Between 11 and 14 years and 16 to 19 years, lung function improved in the unexposed group, but forced expiratory flow at 75% of the expired vital capacity and forced expiratory volume in one second deteriorated in those who had received postnatal corticosteroids (p = 0.0006). These results suggest that prematurely born young people who received postnatal corticosteroids may be at risk of premature onset of chronic obstructive pulmonary disease.

Postnatal physiological changes in electrical activity of the diaphragm in extremely preterm infants.

OBJECTIVES: This study aimed to describe postnatal physiological changes in maximum values of peak electrical activity of the diaphragm (Edi) in extremely preterm infants during the preterm period. WORKING HYPOTHESIS: The amplitude and frequency of neural sigh are different at each postmenstrual age in extremely preterm infants. STUDY DESIGN: A retrospective, observational study. PATIENT-SUBJECT SELECTION: Edi values were evaluated in 14 extremely preterm infants with neurally-adjusted ventilatory assist. METHODOLOGY: Data of Edi peak and Edi minimum were collected from a ventilator. Edi-sigh was defined as the Edi peak value that was more than twice as large as the median Edi peak at each postmenstrual week in each patient. The frequency of Edi-sigh, and median values of Edi-sigh, Edi peak, and Edi minimum were evaluated at each postmenstrual week. The Jonckheere-Terpstra test was used to analyze the trend between postmenstrual weeks and Edi values. RESULTS: From 26 to 35 postmenstrual weeks, the number of Edi-sighs per hour significantly increased as postmenstrual weeks increased (P < .001). Furthermore, the median values of Edi-sigh significantly increased as postmenstrual weeks increased (16.9 µV at 26 weeks to 25.4 µV at 35 weeks, P < .001). There were no significant changes in the median values of Edi peak and Edi minimum at each week. CONCLUSIONS: The amplitude and frequency of neural sigh in extremely preterm infants increase with the number of postmenstrual weeks.

Cranial Ultrasound and Minor Motor Abnormalities at 2 Years in Extremely Low Gestational Age Infants.

OBJECTIVES: The objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities. METHODS: Infants born at <27 weeks in the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 2010, and December 31, 2014, who underwent neuroimaging with CUS at both <28 days and ≥28 days and were evaluated at 18 to 26 months' CA, were included. Follow-up included Bayley-3, neuromotor examination, Gross Motor Function Classification System (GMFCS) level, and parent questionnaires about special services and resource needs. Children were classified by the most severe motor abnormality at 18 to 26 months' CA as follows: none, minor, or major motor function abnormality. Minor motor abnormalities were defined as any of the following: (1) Bayley-3 motor composite, fine motor score, or gross motor score 1 to 2 SDs below the test normative means; (2) mild abnormalities of axial or extremity motor skills on standardized neuromotor examination; or (3) GMFCS level 1. RESULTS: A total of 809 (35%) of 2306 children had minor motor function abnormalities alone. This did not increase substantially with CUS findings (no intraventricular hemorrhage [IVH]: 37%, grade I IVH: 32%, grade II IVH: 38%, grade III/IV IVH: 30%, isolated ventriculomegaly: 33%, and cystic periventricular leukomalacia: 24%). The adjusted odds of minor axial and upper extremity function abnormalities and GMFCS level 1 were significantly higher in children with more severe CUS findings. Children with minor motor abnormalities had increased resource utilization and evidence of functional impairment compared with those without motor function abnormalities. CONCLUSION: Minor motor abnormalities at 2 years' CA are common and cannot be predicted by neonatal CUS abnormalities alone. Minor motor abnormalities are associated with higher resource utilization and evidence of functional impairment. These findings have important implications for early counseling and follow-up planning for extremely preterm infants.

Renal functional markers in extremely premature infants with and without twin-twin transfusion syndrome.

OBJECTIVE: Describe renal function of preterm infants <29 weeks of gestational age (GA) with twin-twin transfusion syndrome (TTTS) who received laser therapy. DESIGN: Retrospective analysis of premature TTTS compared with dichorionic-diamniotic (di-di) twins from 2006 to 2015. Primary outcome was biomarkers of renal injury. RESULTS: Thirty-three TTTS-laser and 101 di-di newborns with similar GA at birth (26.4 ± 1.4 vs 26.9 ± 1.6 weeks, p = 0.07) were included. Creatinine and urea levels were higher in TTTS-laser group at day of life (DOL) 2-7 (123.5 ± 12.4 vs 75.8 ± 2 µmol/L, p = 0.0001 and 11.9 ± 1.1 mmol/L vs 8.7 ± 0.3 mmol/L, p = 0.0001) and DOL 8-14, (98.1 ± 14.2 vs 64.8 ± 2.3 µmol/L, p = 0.0001 and 9.1 ± 1.2 vs 5.4 ± 0.3 mmol/L, p = 0.0001). There was a significant effect of TTTS status on creatinine level at DOL 8-14. CONCLUSION: In extremely preterm with TTTS treated by laser, biomarkers of renal function were higher compared with di-di twins in the first 2 weeks of life.

Sex differences in brain connectivity and male vulnerability in very preterm children.

Evidence indicates better cognitive and behavioral outcomes for females born very preterm (≤32 weeks gestation) compared to males, but the neurophysiology underlying this apparent resiliency of the female brain remains poorly understood. Here we test the hypothesis that very preterm males express more pronounced connectivity alterations as a reflection of higher male vulnerability. Resting state MEG recordings, neonatal and psychometric data were collected from 100 children at age 8 years: very preterm boys (n = 27), very preterm girls (n = 34), full-term boys (n = 15) and full-term girls (n = 24). Neuromagnetic source dynamics were reconstructed from 76 cortical brain regions. Functional connectivity was estimated using inter-regional phase-synchronization. We performed a series of multivariate analyses to test for differences across groups as well as to explore relationships between deviations in functional connectivity and psychometric scores and neonatal factors for very preterm children. Very preterm boys displayed significantly higher (p < .001) absolute deviation from average connectivity of same-sex full-term group, compared to very preterm girls versus full-term girls. In the connectivity comparison between very preterm and full-term groups separately for boys and girls, significant group differences (p < .05) were observed for boys, but not girls. Sex differences in connectivity (p < .01) were observed in very preterm children but not in full-term groups. Our findings indicate that very preterm boys have greater alterations in resting neurophysiological network communication than girls. Such uneven brain communication disruption in very preterm boys and girls suggests that stronger connectivity alterations might contribute to male vulnerability in long-term behavioral and cognitive outcome.

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.

Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis.

BACKGROUND: Reduced kidney volume (KV) following prematurity is a proxy for reduced nephron number and is associated with the development of hypertension and end-stage renal disease in adults. We investigated whether extreme prematurity affects KV, function, and blood pressure in school-aged children and if nephrocalcinosis (NC) developed during the neonatal period had additional effects. METHODS: We investigated 60 children at a mean age of 7.7 years: 20 born extremely preterm (EPT < 28 weeks gestational age with NC (NC+)), 20 born EPT without NC (NC-), and 19 born as full-term infants (control). We measured KV by ultrasound, collected blood and urine samples to evaluate renal function, and measured office and 24-h ambulatory blood pressure (ABPM). RESULTS: Children born EPT had significantly smaller kidneys (EPT (NC+ NC-) vs control (estimated difference, 11.8 (CI - 21.51 to - 2.09 ml), p = 0.018) and lower but normal cystatin C-based glomerular filtration rate compared with control (estimated difference, - 10.11 (CI - 0.69 to - 19.5), p = 0.035). KV and function were not different between NC+ and NC- groups. Change in KV in relation to BSA (KV/BSA) from the neonatal period to school age showed significantly more EPT children with neonatal NC having a negative evolution of KV (p = 0.01). Blood pressure was normal and not different between the 3 groups. Fifty percent of EPT had a less than 10% day-to-night decline in ABPM. CONCLUSIONS: Kidney growth and volume is affected by EPT birth with NC being a potential aggravating factor. Circadian blood pressure regulation seems abnormal in EPT-born children.

Intermittent hypoxemia and oxidative stress in preterm infants.

Intermittent hypoxemia events (IH) are common in extremely preterm infants and are associated with many poor outcomes including retinopathy or prematurity, wheezing, bronchopulmonary dysplasia, cognitive or language delays and motor impairment. More recent data in animal and rodent models have suggested that specific patterns of IH may increase the risk for morbidity. The pathway by which these high risk patterns of IH initiate a pathological cascade is unknown but animal models suggest that oxidative stress may play a role. This review describes early postnatal patterns of IH in preterm infants, their relationship with morbidity, oxidative stress biomarkers relevant to the newborn infant and the relationship between IH and reactive oxygen species.

Bronchopulmonary Dysplasia: When the Very Preterm Baby Comes Home.

Many infants with severe bronchopulmonary dysplasia (BPD) can be safely managed with oxygen at home. This review covers criteria for home oxygen therapy, monitoring, and weaning protocols for oxygen therapy in the outpatient setting. Although most infants with BPD are weaned from oxygen within a year, they continue to have pulmonary function abnormalities into adolescence. These infants also require evaluation for pulmonary hypertension, systemic hypertension, and a strong focus on adequate nutritional needs for growth.