ELGA Infants Research Articles

Incidence and risk factors for retinopathy of prematurity in premature, extremely low birth weight and extremely low gestational age infants

BackgroundThe aim of the study was to determine the incidence and risk factors of retinopathy of prematurity (ROP) in premature, extremely low birth weight (BW, ELBW) and extremely low gestational age (GA, ELGA) infants.MethodsThe medical records of preterm infants who were screened for ROP between January 2012 and December 2020 were retrospectively reviewed. Only one eye of each infant with higher grade ROP was included in the study. BW; GA; medical characteristics; the presence, severity, and need for treatment of ROP were recorded. Infants were divided into groups according to BW (≤1000 g, 1001-1750 g, > 1750 g) and GA (≤25w, 26-28w, 29-31w, 32-34w, ≥35w) and data were analyzed.ResultsData of 2186 infants were evaluated. The overall incidences of any stage ROP and ROP requiring treatment were 43.5 and 8.0%, respectively. These rates were 81.1 and 23.9% in ELBW (≤1000 g) infants and were 92.9 and 64.3% in ELGA (≤25w) infants, respectively. The rates of ROP, the median duration of oxygen therapy and systemic diseases increased significantly as BW and GA decreased. The median duration of oxygen therapy and the rates of sepsis, pulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH) were statistically higher in infants with ROP compared to those without ROP (p < 0.001). Multivariate regression analysis demonstrated that low BW and GA; prolonged duration of oxygen therapy; presence of PDA and necrotizing enterocolitis (NEC) were important risk factors for ROP.ConclusionsELBW and ELGA infants develop higher rates of ROP and severe ROP. Prolonged duration of oxygen therapy, the presence of concomitant neonatal sepsis, BPD, IVH, PDA, and NEC further increases the risk of ROP.

Diffuse correlation spectroscopy blood flow monitoring for intraventricular hemorrhage vulnerability in extremely low gestational age newborns

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6–24 h between days 2–5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

277-OR: Use of Noncarbohydrate Fuels Is Associated with Materno-Fetal Complications in Type 1 Diabetes Pregnancy: Metabolomics Analysis of the CONCEPTT Trial

Aims: We assessed metabolomic signatures in maternal and cord blood associated with suboptimal outcomes in the continuous glucose monitoring in women with type 1 diabetes in pregnancy trial (CONCEPTT). Methods: Serum samples from 162 mothers (12, 24 and 34 weeks’ gestation) and 93 cord blood samples were analysed for 1049 metabolites and 1041 lipids using ultra-performance liquid chromatography-tandem mass spectroscopy. We used adjusted and unadjusted logistic regression of metabolomic variables using adjudicated outcomes: extremely-large-for-gestational-age (ELGA; &amp;gt;97.5th centile), pre-eclampsia and neonatal hypoglycaemia with modified Bonferroni false discovery rate p≤0.001. Results: All materno-fetal complications studied were associated with reliance on non-carbohydrate sources of fuel. Lipids through beta oxidation were the main fuel source in ELGA (24 and 34 weeks), neonatal hypoglycaemia (12 weeks only) and pre-eclampsia (12 and 24 weeks). Marked protein catabolism was evident in neonatal hypoglycaemia (34 weeks) and pre-eclampsia (24 and 34 weeks). Cord blood in ELGA infants showed evidence of simultaneous beta oxidation and de novo lipogenesis, a biologically futile cycle of creating and destroying lipids, which consumes excess energy and substrate. Cord blood from infants with neonatal hypoglycaemia showed evidence of pronounced protein catabolism providing glucogenic amino acids for gluconeogenesis. Conclusions: Reliance on lipid or protein sources for fuel was associated with ELGA, neonatal hypoglycaemia and pre-eclampsia. Carbohydrate metabolism was insufficient to meet cellular energy demands, possibly due to insufficient insulin, insufficient dietary carbohydrate or both. Improving outcomes in type 1 diabetes pregnancy may require greater focus on normalising carbohydrate metabolism through optimal carbohydrate intake and matched insulin dosing. Disclosure C. L. Meek: None. Z. Stewart: None. S. Furse: None. J. M. Yamamoto: None. D. Feig: Advisory Panel; Self; Novo Nordisk. A. Koulman: None. H. R. Murphy: None. Funding JDRF (17/2011/533, 80/2010/585); Diabetes UK (DUK-HKF 17/0005712, DUK-PG 17/0005633.BBSRC BB/M027252/1)

Do 6-Month Motor Skills Have Cascading Effects on 12-Month Motor and Cognitive Development in Extremely Preterm and Full-Term Infants?

In this study, we analyzed whether 6-month gross and fine motor skills were related to 12-month gross and fine motor skills and cognitive development, controlling for 6-month cognitive skills, and neonatal status (extremely low gestational age ELGA ≤ 28 weeks vs. full-term FT ≥ 37 weeks). We also investigated, at 6 months, predictive indexes for motor and cognitive delay at 12-months. We assessed 40 infants (20 ELGA and 20 FT) at 6 and 12 months (corrected age for the ELGA infants). Six-month gross motor skills were related to 12-month gross motor, fine motor, and cognitive skills and predicted 12-month gross motor delay. Six-month cognitive skills explained an additional amount of variance of 12-month gross motor skills, whereas neonatal status explained an additional amount of variance of 12-month cognitive skills. Considering the intradomain and cross-domain cascading effects of early gross motor skills on later motor and cognitive development, these skills should be repeatedly assessed in ELGA infants in the first year of life for early identification of infants with delayed gross motor skills and implementation of customized interventions.

Low Rates of Pointing in 18-Month-Olds at Risk for Autism Spectrum Disorder and Extremely Preterm Infants: A Common Index of Language Delay?

Infants with an older sibling with an Autism Spectrum Disorder diagnosis (Sibs ASD) are at high risk for language delay (LD) as well as infants born preterm, especially those with an extremely low gestational age (ELGA, GA ≤ 28 weeks). Gestures play a crucial role in language development and delays in gesture production may have negative cascading effects on it. The present exploratory study examined gesture production in 18-month-old infants with different underlying risks for LD. Seventy monolingual United States infants (41 Sibs ASD with no eventual ASD diagnosis and 29 infants with a typically developing older sibling -Sibs TD) and 40 monolingual Italian infants (20 ELGA without major cerebral damages, congenital malformations or sensory impairments and 20 full-term - FT infants, GA ≥ 37 weeks) were included. Both groups were followed longitudinally from 18 to 24, 30, and 36 months (corrected for ELGA infants). A 30-minute mother-infant play session with age-appropriate toys was video recorded at 18 months of age. Deictic (requesting, pointing, showing and giving), conventional, and representational gestures spontaneously produced by infants were coded; rate per 10 min was calculated. LD was defined as a score ≤10th percentile on the American English or Italian version of the MacArthur-Bates CDI on at least two time points between 18 and 36 months. Fifteen Sibs ASD and 9 ELGA infants were identified as infants with LD. Sibs ASD-LD and Sibs ASD-no LD produced fewer pointing gestures compared to Sibs TD (p = 0.038; p = 0.004); ELGA-LD infants produced significantly fewer pointing gestures than ELGA-no LD (p = 0.024) and FT (p = 0.006) infants. Low rates of pointing at 18 months are a marker of LD in Sibs ASD and ELGA infants. The potential implications of reduced pointing production and characteristics of different populations at risk for LD should be considered for understanding the emergence of LD.

Survival analysis of a cohort of extremely preterm infants born in Finland during 2005–2013

Objective This study aimed to analyze the mortality of extremely preterm infants (ELGA born alive before 28 weeks) until the postconceptional age of 42 weeks, death, or home discharge, whichever came first. It was focused especially on studying the relationship between antenatal risk factors, the time of death, and the postnatal morbidities associated with mortality. Study design The original data obtained from the nationwide Finnish medical birth register of extremely preterm and low birthweight infants born during 2005–2013 were analyzed. The total population consisted of 1353 ELGA infants after the exclusion of 18 infants born with lethal congenital anomalies or genetic defects. Mortality risks were adjusted according to the length of gestation, the administration of antenatal steroids, and the delivery hospital. Results During the first 48 hours, extreme immaturity was seen to be the prominent cause of death, and intrauterine growth did not influence mortality. The ELGA population surviving for at least 48 hours (N = 1135) was submitted for mortality risk analysis. After the adjustments, small-for-gestational-age (SGA) (birth weight below −2 SD) was found to be the factor with the highest risk for demise [OR 6.2; 95% CI (3.9–10.0) p < .001]. Multiple deliveries were associated with increased risk for death [OR 1.5; 95% CI (1.0–2.1), p = .048] to a lesser extent. The main neonatal morbidities associated with the risk of mortality after 48 postnatal hours of life were severe intraventricular hemorrhage (IVH) [OR 4.4; 95% CI (3.0–6.7), p < .001], respiratory distress syndrome (RDS) [OR 2.6; 95% CI (1.3–5.0), p = .006], and necrotizing enterocolitis (NEC) [OR 2.3; 95% CI (1.5–3.4), p < .001]. The major morbidities associated with deaths among non-SGA infants were severe IVH (32.1% of all deaths), NEC (19.1%), and sepsis (8.4%). In SGA infants, severe respiratory disease (RDS, severe bronchopulmonary dysplasia, pulmonary hemorrhage, or pulmonary hypertension) was the main cause of death (60.9% of all deaths). Medical or surgical PDA treatment was not found to be associated with increased risk of death [OR 0.4; 95% CI (0.2–0.5), p < .001] compared to infants who had survived for more than 2 days. Severe preeclampsia was found to be associated with 42% of all ELGA-SGA births. After the adjustments, ELGA infants from pregnancies complicated by preeclampsia of the mother exhibited a significantly lower risk of severe IVH [OR 0.3; 95% CI (0.2–0.5), p < .001] compared to the non-preeclamptic mothers’ infants. The low incidence of severe IVH was evident regardless of fetal growth in this patient group. Conclusions SGA infants with less than 28 gestational weeks, who had survived for at least 2 days, had excessively high mortality due to severe pulmonary disease. Intrauterine growth had no influence on the risk of death, other than pulmonary causes. The infants of preeclamptic mothers exhibited an increased risk of intrauterine growth retardation; however, despite this serious complication, these infants exhibited a significant decrease in the risk for severe IVH.

Impact of feeding difficulties in the NICU on neurodevelopmental outcomes at 8 and 20 months corrected age in extremely low gestational age infants.

The objective of this study is to examine the relationship between neonatal risk factors and feeding difficulties (FDs) in the NICU and the impact of FD on neurodevelopmental (ND) outcome in ELGA infants. Two hundred and eighteen ELGA infants (59 FDs and 159 no-FDs) were compared for neonatal morbidities, feeding milestones, and Bayley-III scores at 8 and 20 mo CA. Multiple regression analyses adjusted for the effect of risk factors on FD and ND outcome. Twenty-seven percent of infants had FD. Postmenstrual age (PMA) at start of oral feeds was the only predictor of FD. At 8 mo CA, FD was the strongest predictor of cognitive <85 (p = 0.018) and motor index <70 (p = 0.019). In linear regression, PMA at start of oral feeds was the only predictor of 8 mo cognitive and motor index (p = 0.006). FD did not predict ND outcome at 20 months CA. FDs are common in ELGA infants and are associated with worse cognitive and motor outcomes in the first year of life.

Object exploration in extremely preterm infants between 6 and 9 months and relation to cognitive and language development at 24 months

Although early object exploration is considered a key ability for subsequent achievements, very few studies have analyzed its development in extremely low gestational age infants (ELGA- GA <28 weeks), whose early motor skills are delayed. Moreover, no studies have examined its developmental relationship with cognitive and language skills. The present study examined developmental change in Motor Object Exploration (MOE) and different types of MOE (Holding, Oral, Manual and Manual Rhythmic Exploration) in 20 ELGA and 20 full term (FT) infants observed during mother-infant play interaction at 6 and 9 months. It also explored whether specific types of MOE were longitudinally related to 24-month language and cognitive abilities (GMDS-R scores). ELGA infants increased MOE duration from 6 to 9 months, eliminating the initial difference with FT infants. In addition, ELGA infants showed a different pattern of Oral Exploration, that did not increase at 6 months and decrease at 9 months. Oral and Manual Exploration durations at 6 months were longitudinally related to 24-month GMDS-R language and cognitive performance scores respectively. We discuss the relevance of assessing early exploratory abilities in ELGA infants in order to implement customized intervention programs for supporting the development of these skills.

Object engagement and manipulation in extremely preterm and full term infants at 6 months of age

Delays in the motor domain have been frequently observed in preterm children, especially those born at an extremely low gestational age (ELGA;<28 weeks GA). However, early motor exploration has received relatively little attention despite its relevance for object knowledge and its impact on cognitive and language development. The present study aimed at comparing early object exploration in 20 ELGA and 20 full-term (FT) infants at 6 months of age during a 5-minute mother-infant play interaction. Object engagement (visual vs manual), visual object engagement (no act vs reach), manual object engagement (passive vs active), and active object manipulation (mouthing, transferring, banging, turn/rotating, shaking, fingering) were analyzed. Moreover, the Griffiths Mental Development Scales 0-2 years (1996) were administered to the infants. Relative to FT peers, ELGA infants spent more time in visual engagement, and less time in manual engagement, active manipulation, mouthing, and turning/rotating. Moreover, they had lower scores on general psychomotor development, eye & hand coordination, and performance abilities. Close relationships emerged between manual object engagement and psychomotor development. Clinical implications of these results in terms of early evaluation of action schemes in ELGA infants and the provision of intervention programs for supporting these abilities are discussed.

Early communicative behaviors and their relationship to motor skills in extremely preterm infants

Despite the predictive value of early spontaneous communication for identifying risk for later language concerns, very little research has focused on these behaviors in extremely low-gestational-age infants (ELGA<28 weeks) or on their relationship with motor development. In this study, communicative behaviors (gestures, vocal utterances and their coordination) were evaluated during mother–infant play interactions in 20 ELGA infants and 20 full-term infants (FT) at 12 months (corrected age for ELGA infants). Relationships between gestures and motor skills, evaluated using the Bayley-III Scales were also examined. ELGA infants, compared with FT infants, showed less advanced communicative, motor, and cognitive skills. Giving and representational gestures were produced at a lower rate by ELGA infants. In addition, pointing gestures and words were produced by a lower percentage of ELGA infants. Significant positive correlations between gestures (pointing and representational gestures) and fine motor skills were found in the ELGA group. We discuss the relevance of examining spontaneous communicative behaviors and motor skills as potential indices of early development that may be useful for clinical assessment and intervention with ELGA infants.

Optimal ventilation strategy

Premature delivery, is always associated to the failure of respiratory transition and a delayed achievement of an adequate functional residual capacity. For this reason preterm babies (expecially the Extremely Low for Gestational Age -ELGA- infants) frequently need a respiratory support. Non-invasive ventilation (NIV) is widespread used in the management of respiratory distress even in ELGA infants without increasing of neonatal mortality or neurological impairment. The most recent meta-analysis and reviews on NIV approach demonstrated that NIV is a valid alternative to mechanical ventilation (MV) in the management of respiratory failure and resulted in significant reductions in the incidence of Bronchopulmonary dysplasia (BPD) amongst surviving infants [1,2]. Nevertheless, even if non-invasive respiratory support seems to be very efficacious in preterm babies, sometimes ELGA infants require MV. Pressure-limited ventilation is yet the standard mode in neonatal intensive care unit, because the attempts to use traditional volume-controlled ventilation it has been often impractical in very small preterm infants. Moreover pressure-limited ventilation continues to be the primary mode of ventilation in neonates because of its relative simplicity and ability to ventilate effectively despite large ETT leak. The major disadvantage of pressure-limited ventilation is that the tidal volume (VT) varies with changes in lung compliance (e.g after surfactant therapy). The consequences of such rapid improvements in compliance are inadvertent hyperventilation and lung injury from excessively large VT (volutrauma); inadvertent hyperventilation may induce hypocapnia, with high risk of cerebral damage. In literature there are extensive evidence that excessive volume, rather than pressure, is the key determinant of ventilator-induced lung injury (VILI). Inadequate (too small) VT also causes significant problems (atelectrauma): in particular inefficient gas exchange due to increased dead-space to VT ratio. Therefore in the last years volume-targeted ventilation has become an important standard of care in neonatal and pediatric respiratory support too. There are many volume-targeted ventilation modes to be used in neonatal period, but Volume Guarantee (VG) ventilation, it is the most extensively studied volume-targeted ventilation mode in the neonate with respiratory distress. The Cochrane review on volume-targeted ventilation resulted in significant reductions in duration of ventilation, rates of pneumothorax, significant reduction in intraventricular haemorrhage (IVH) and a reduction in the incidence of BPD amongst surviving infants, of borderline statistical significance [3]. The VG ventilation plus adequate PEEP and an open lung strategy [4], seems to be an adequate alternative to High frequency Oscillatory Ventilation (HFOV) in mechanically ventilated infants for RDS.

Dyadic co-regulation, affective intensity and infant's development at 12 months: A comparison among extremely preterm and full-term dyads

Extremely low gestational age children (ELGA, born below 28 weeks of GA) represent the most at-risk preterm group in terms of survival, developmental sequelae and rates of impairment and cognitive delays. However, the impact of an extremely preterm birth on mother–infant co-regulation and affective intensity which may affect early infant's development has not been investigated. Based on a relational dynamic system approach, our study aimed to investigate the quality of co-regulation and affective intensity during spontaneous play interaction in 20 mother–infant ELGA dyads compared to 20 full-term (FT) dyads at 12 months (corrected age for ELGA infants). Relationships between the quality of dyadic co-regulation and the infant's level of cognitive, motor and language development were also investigated. The quality of dyadic co-regulation was assessed using the Revised Relational Coding System (R-RCS) by Fogel et al. (2003), the mothers’ and infants’ affective intensity was coded using a coding system by Lunkenheimer, Olson, Hollenstein, Sameroff, and Winter (2011). Infants’ development was assessed using the Bayley Scales (BSID-III, 2006). With respect to FT dyads, ELGA dyads were characterised by less frequent symmetric and more frequent unilateral co-regulation patterns and by less positive and more neutral affective intensity of both infants and mothers. Cognitive, motor and language scores were lower in ELGA infants than in FT infants. Symmetrical co-regulation was related to motor scores in ELGA infants, and to cognitive scores in FT infants. Our findings contribute to the literature by demonstrating the difficulties of ELGA mother–infant dyads at 12 months in sharing the symmetric co-regulation and positive affective intensity and how symmetric co-regulation is strictly related to motor development in ELGA infants. Based on these findings, intervention programmes to foster joint attention, active involvement and positive affective intensity in ELGA dyads and infants’ development in the first year of life should be designed.

Pain behaviours in Extremely Low Gestational Age infants

Background To date, there are over 40 infant pain measures. Despite this plethora of measures, only 8 have included preterm infants and only 2 have included Extremely Low Gestational Age (ELGA; infants < 28 weeks GA) in their development. Without reliable, valid and clinically useful indicators for procedural pain in ELGA infants, clinicians have no means to interpret the responses from an immature infant who may respond differently from infants of older GA. Objective To examine the physiological, behavioural and biochemical responses to painful and non-painful procedures in ELGA infants and the influence of GA and sex. Design/methods A prospective crossover design with 50 ELGA infants from one Canadian tertiary level NICU was conducted. Infants were assessed in random order during standardized painful (heel lance) and non-painful (diaper change) procedures. Physiological (heart rate, oxygen saturation) and behavioural (facial and body movement) indicators were continuously collected during 4 phases of the procedures. Biochemical (salivary cortisol) indicators were collected immediately before and 20 min following the procedures. Results Four facial actions (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch) increased immediately following the heel lance. There were no specific changes in physiological, body movement or cortisol indicators following the heel lance. ELGA infants demonstrated greater body movements during the diaper change, which may reflect immature motor coordination. No differences in pain responses were found for infants born between 23-25 6/7 weeks GA and those between 26-28 weeks GA. Similarly, no gender differences were found. Conclusions Changes in 4 facial actions were the most sensitive indicators of pain in ELGA infants. This finding is consistent with existing measures where facial actions are the most prominent pain indicators. Specific body movements such as those included in NIDCAP, may provide more information about pain in ELGA infants. Movements such as hand-on-face, finger splaying, fisting, arching or yawning need to be examined in future research.

Altered Basal Cortisol Levels at 3, 6, 8 and 18 Months in Infants Born at Extremely Low Gestational Age

Little is known about the developmental trajectory of cortisol levels in preterm infants after hospital discharge. In a cohort of 225 infants (gestational age at birth <33 weeks) basal salivary cortisol levels were compared in infants born at extremely low gestational age (ELGA, 23-28 weeks), very low gestational age (29-32 weeks), and term (37-42 weeks) at 3, 6, 8, and 18 months corrected age (CA). Infants with major neurosensory or motor impairment were excluded. At 3 months CA, salivary cortisol levels were lower in both preterm groups compared with the term infants (P = .003). Conversely, at 8 and 18 months CA, the ELGA infants had significantly higher basal cortisol levels than the very low gestational age and term infants (P = .016 and P = .006, respectively). In ELGA infants, the shift from low basal cortisol levels at 3 months to significantly high levels at 8 and 18 months CA suggests long-term "resetting" of endocrine stress systems. Multiple factors may contribute to these higher cortisol levels in the ELGA infants, including physiological immaturity at birth, cumulative stress related to multiple procedures, and mechanical ventilation during lengthy hospitalization. Prolonged elevation of the cortisol "set-point" may have negative implications for neurodevelopment and later health.

Relationships between adrenocorticotropic hormone and cortisol are altered during clustered nursing care in preterm infants born at extremely low gestational age

Background Little is known about the effects of clustered nursing care on hypothalamic pituitary axis (HPA) responses in preterm infants in the neonatal intensive care unit. Aims To examine facial responses, adrenocorticotropic hormone (ACTH) and cortisol levels, and the relationship between ACTH and cortisol in preterm infants in two gestational age groups (extremely low gestational age [ELGA: ≤ 28 weeks]; very low gestational age [VLGA: 29–31 weeks]) under basal conditions and in response to routine nursing procedures. Study design Within subjects' cross-over design in random order. Subjects Ninety preterm infants with no postnatal steroid exposure were studied at 32 ± 1 weeks postconceptional age. Outcome measures Facial actions, ACTH and cortisol levels were measured after a 30 minute rest period and in response to routine clustered nursing care (CC). Changes in facial actions were analyzed using repeated measures ANOVA. MANOVA or Mann–Whitney U tests were used to determine differences in ACTH and cortisol between gestational age groups. Spearman rank correlations were used to examine relationships between perinatal variables and facial, ACTH and cortisol levels. Results All infants had significantly increased facial responses to CC ( p = 0.001). Infants having experienced higher numbers of skin breaking procedures 24 h before basal assessment had higher basal cortisol levels ( r = 0.30, p = 0.01). In response to CC, ELGA infants showed no correlation between ACTH and cortisol levels; VLGA infants showed a strong, positive correlation ( r = 0.62, p = 0.02). Conclusion The pattern of relationship between ACTH and cortisol differs depending on gestational age at birth in response to clustered nursing care. Prior pain alters responsiveness and HPA dysregulation is apparent in ELGA infants.

176 Non-Cystic White Matter Damage in ELGA Infants – A Swedish Population Based Study

Top of pageAbstract Aim/ subject: Magnetic resonance imaging (MRI) has contributed to the understanding of brain damage in infants with extremely low gestational age (ELGA, <27w). Data from Scandinavia, which has a long tradition of minimal intervention in the treatment of preterm infants, have not been reported yet. In this abstract we present the first results of an ongoing population based MRI study performed in the Stockholm area of Sweden. Methods: All ELGA infants born in the Stockholm area in 2004 (n=51; birth weight: mean 770g, range 465 - 1114g; gestational age: mean 25+2w, range 23+2 - 26+6w) were included. Perinatal data and clinical courses were prospectively collected. At term equivalent age infants were scanned with conventional MRI using a 1.5 Tesla magnetic resonance system (Philips Intera). Images were reviewed by 3 independent observers using a scoring system for grey and white matter abnormalities (Inder et al 2003). Results: 33 infants (birth weight: mean 805g (range 554 - 1114g); mean GA 25+4w (range 23+5 - 26+6w) were included in the analysis. Out of 51, 10 had died before term age, in 2 no parental consent was obtained, one was excluded because of chromosomal disorder, 2 because of connatal CMV infection, 1 moved outside Sweden, 2 have not reached term age yet. Normal white matter (WM) was found in 21%, mild WM abnormalities in 58%, moderate to severe non-cystic WM abnormalities in 21%, cystic WM abnormalities in none. GM scores were normal in 90% and abnormal in 10%. Conclusion: Cystic WM damage was not seen in any infant. Non-cystic white matter abnormalities were found in 79% and abnormal grey matter in 10% of our ELGA infant population. To evaluate the clinical relevance of these findings neurological follow-up of these children is ongoing.

Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months.

Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; < or =28 weeks), very low gestational age (VLGA; 29-32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit. Seventy-six infants, 54 preterm (< or =32 weeks' GA at birth) and 22 term-born infants who were seen at 8 months CCA composed the study sample, after excluding those with major sensory, motor, or cognitive impairment. Salivary cortisol was measured before (basal) and 20 minutes after introduction of novel toys (post 1) and after developmental assessment (post 2). Salivary cortisol was significantly higher in ELGA infants at 8 months, compared with the VLGA and term groups before and after introduction of visual novelty. Term-born and VLGA infants showed a slight decrease in cortisol when playing with novel toys, whereas the ELGA group showed higher basal and sustained levels of cortisol. After controlling for early illness severity and duration of supplemental oxygen, higher basal cortisol levels in preterm infants at 8 months' CCA were associated with higher number of neonatal skin-breaking procedures. In contrast, cortisol responses to novelty were predicted equally well by neonatal pain or GA at birth. No relationship between morphine dosing and cortisol response was demonstrated in these infants. ELGA preterm infants show a different pattern of cortisol levels before and after positive stimulation of visual novelty than more maturely born, VLGA preterm and term-born infants. Exposure to high numbers of skin-breaking procedures may contribute to "resetting" basal arousal systems in preterm infants.

HAS THE 18-MONTH OUTCOME FOR EXTREMELY LOW GESTATIONAL AGE (ELGA) INFANTS OF 23-25 WEEKS GESTATION IMPROVED? † 1614

Our purpose was to examine the neurodevelopmental outcome at 18 months corrected age of surviving ELGA infants of 23-25 weeks gestation born in 1991-3, and to compare the results with those from an earlier cohort born in 1983-9 (Synnes A et al J Pediatr 1994:125:952-60). ELGA infants delivered in British Columbia's tertiary perinatal center had their gestational age (GA) ascertained as accurately as possible by early ultrasound and dates using predetermined criteria. There were no survivors at <23 weeks in the two time periods. The results of multidisciplinary assessments performed at a corrected age of 18 months were reviewed for survivors of 23-25 weeks GA. Major impairment was defined as a Bayley MDI below -2 s.d., definite signs of cerebral palsy (CP), visual acuity in the better eye with optimal refractive correction worse than 20/200, or sensorineural hearing loss requiring amplification. Of 111 live births, 48 survived to 18 months corrected age and follow-up data was available in 35 (73%). 4 of 12 infants with major impairment, had multiple impairments. The recent cohort was smaller in size(3-year vs 7-year period) and the follow-up rate was lower (73% vs 93%), with a sampling bias toward the lower birthweight infants. Survival rate (to discharge) for 23-25 weeks GA has not improved (44% vs 44%) and the survivors had comparable incidence of major impairment at 18 months (34%; vs 36% resp.). Of children with impairments, multiple impairments were present in 33% (vs 38% in earlier cohort). As there were so few 23 week babies, the results were re-analyzed for infants 24-25 weeks GA. Survival (53% vs 50%) and impairment rate (32% vs 34%) remained not statistically different. There is no evidence in this survey that the introduction of recent innovations such as surfactant therapy has produced any improvement in outcomes for the smallest babies.Table