Grading of Intraventricular Hemorrhage and Neurodevelopment in Preterm <29 Weeks' GA in Canada

Objective: The aim of this study was to evaluate the neurodevelopmental outcome at 18−24 months in surviving preterm infants with grades I−IV intraventricular hemorrhages (IVHs) compared to those with no IVH. Study Design: We included preterm survivors <29 weeks' GA admitted to the Canadian Neonatal Network's NICUs from April 2009 to September 2011 with follow-up data at 18−24 months in a retrospective cohort study. The neonates were grouped based on the severity of the IVH detected on a cranial ultrasound scan and recorded in the database: no IVH; subependymal hemorrhage or IVH without ventricular dilation (grades I−II); IVH with ventricular dilation (grade III); and persistent parenchymal echogenicity/lucency (grade IV). The primary outcomes of neurodevelopmental impairment (NDI), significant neurodevelopmental impairment (sNDI), and the effect modification by other short-term neonatal morbidities were assessed. Using multivariable regression analysis, the adjusted ORs (AOR) and 95% of the CIs were calculated. Results: 2327 infants were included. The odds of NDI were higher in infants with grades III and IV IVHs (AOR 2.58, 95% CI 1.56, 4.28 and AOR 2.61, 95% CI 1.80, 3.80, respectively) compared to those without IVH. Infants with an IVH grade ≤II had similar outcomes for NDI (AOR 1.08, 95% CI 0.86, 1.35) compared to those without an IVH, but the odds of sNDI were higher (AOR 1.58, 95% CI 1.16, 2.17). Conclusions: There were increased odds of sNDI in infants with grades I−II IVHs, and an increased risk of adverse NDI in infants with grades ≥III IVHs is corroborated with the current literature.

Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants < 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. CONCLUSION: Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes. WHAT IS NEW: • Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth.

OBJECTIVE: To determine postdischarge iron status and associated factors in very preterm infants. STUDY DESIGN: A retrospective cohort study was conducted through a provincial database on all very preterm infants born in Nova Scotia between 2005 and 2018. As a standard of care, all infants received prophylactic iron supplements starting at 2-4 weeks of chronological age and were tested for iron deficiency at 4 or 6 months corrected age. Iron deficiency was defined as serum ferritin <20 g/L at 4 months or <12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency. RESULTS: Among 411 infants, 132 (32.1%) had iron deficiency and 11 (2.7%) had iron deficiency anemia. The prevalence of iron deficiency decreased over time, from 37.6% in 2005-2011 to 25.8% in 2012-2018. Gestational hypertension in the mother (P = .01) and gestational age <27 weeks (P = .02) were independent risk factors for iron deficiency. In addition, the odds of iron deficiency were lower in the mixed-fed group (ie, with breast milk and formula combined) compared with the exclusive formula-fed group (P = .01). CONCLUSIONS: Iron deficiency was prevalent in 32% of the very preterm infants despite early iron prophylaxis. These results demonstrate the importance of monitoring iron stores during preterm follow-up. Information about risk factors is important to mitigate iron deficiency in very preterm infants.

Parent-reported health status of preterm survivors in a Canadian cohort.

OBJECTIVES: Health status (HS)/ health-related quality of life measures, completed by self or proxy, are important outcome indicators. Most HS literature on children born preterm includes adolescents and adults with limited data at preschool age. This study aimed to describe parent-reported HS in a large national cohort of extreme preterm children at preschool age and to identify clinical and sociodemographic variables associated with HS. METHODS: Infants born before 29 weeks' gestation between 2009 and 2011 were enrolled in a prospective longitudinal national cohort study through the Canadian Neonatal Network (CNN) and the Canadian Neonatal Follow-Up Network (CNFUN). HS, at 36 months' corrected age (CA), was measured with the Health Status Classification System for Pre-School Children tool completed by parents. Information about HS predictors was extracted from the CNN and CNFUN databases. RESULTS: Of 811 children included, there were 79, 309 and 423 participants in 23-24, 25-26 and 27-28 weeks' gestational age groups, respectively. At 36 months' CA, 78% had a parent-reported health concern, mild in >50% and severe in 7%. Most affected HS attributes were speech (52.1%) and self-care (41.4%). Independent predictors of HS included substance use during pregnancy, infant male sex, Score for Neonatal Acute Physiology-II, bronchopulmonary dysplasia, severe retinopathy of prematurity, caregiver employment and single caregiver. CONCLUSION: Most parents expressed no or mild health concerns for their children at 36 months' CA. Factors associated with health concerns included initial severity of illness, complications of prematurity and social factors.

Differences in demographics and outcomes based on method of consent for a randomised controlled trial on heat loss prevention in the delivery room.

OBJECTIVE: Informed consent is standard in research. International guidelines allow for research without prior consent in emergent situations, such as neonatal resuscitation. Research without prior consent was incorporated in the Vermont Oxford Network Heat Loss Prevention Trial. We evaluated whether significant differences in outcomes exist based on the consent method. DESIGN: Subgroup analysis of infants enrolled in a randomised controlled trial conducted from 2004 to 2010. SETTING: A multicentre trial with 38 participating centres. PARTICIPANTS: Infants born 24-27 weeks of gestation. 3048 infants assessed, 2231 excluded due to fetal congenital anomalies, failure to obtain consent or gestation less than 24 weeks. 817 randomised, 4 withdrew consent, total of 813 analysed. MAIN OUTCOME MEASURE: The difference in mortality between consent groups. RESULTS: No significant differences were found in mortality at 36 weeks (80.2%, 77.4%, p=0.492) or 6 months corrected gestational age (80.7%, 79.7%, p=0.765). Infants enrolled after informed consent were more likely to have mothers who had received antenatal steroids (95.2%, 84.0%, p<0.0001). They also had significantly higher Apgar scores at 1 (5.0, 4.4, p=0.019), 5 (7.3, 6.7, p=0.025) and 10 min (7.5, 6.3, p=0.0003). CONCLUSIONS AND RELEVANCE: Research without prior consent resulted in the inclusion of infants with different baseline characteristics than those enrolled after informed consent. There were no significant differences in mortality. Significantly higher Apgar scores in the informed consent group suggest that some of the sicker infants would have been excluded from enrolment under informed consent. Research without prior consent should be considered in neonatal resuscitation research.

Incidence, Intrapartum Risk Factors, and Prognosis of Neonatal Hypoxic-Ischemic Encephalopathy Among Infants Born at 35 Weeks Gestation or More.

INTRODUCTION: Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with neonatal mortality, acute neurological injury, and long-term neurodevelopmental disabilities; however, the association between intrapartum factors and HIE remains unclear. METHODS: This population-based cohort study used linked obstetrical and newborn data derived from the Nova Scotia Atlee Perinatal Database (NSAPD, 1988-2015) and the AC Allen Perinatal Follow-Up Program Database (2006-2015) for all pregnancies with live, non-anomalous newborns ≥35 weeks gestation, not delivered by pre-labour cesarean section. Temporal trends in HIE incidence were described, and logistic regression estimated odds ratios (OR) with 95% confidence intervals (CI) for the association of intrapartum factors with HIE. RESULTS: The NSAPD identified 227 HIE cases in the population of 226 711 deliveries from 1988 to 2015. Women with clinical chorioamnionitis in labour (OR 8.0; 95% CI 3.9-16), emergency cesarean delivery (OR 10; 95% CI 7.6-14), shoulder dystocia (OR 3.5; 95% CI 2.1-5.7), placental abruption (OR 18; 95% CI 11-29), and cord prolapse (OR 30; 95% CI 15-61) were more likely to have newborns with HIE. Two-thirds of newborns with HIE had an abnormal intrapartum fetal heart rate tracing. The mortality rate among infants with HIE was 27% by 3 years of age. Neurodevelopmental outcomes in the surviving infants were normal in 43% and showed severe developmental delay in 40%. CONCLUSION: Overall, the rate of HIE was low in infants born at ≥35 weeks gestation. The identification of associated intrapartum factors should promote increased surveillance in these clinical situations and emphasize the importance of careful management to optimize newborn outcomes.

Epidemiology of neonatal stroke: A population-based study.

OBJECTIVE: The goal of this study was to obtain population-based data on the incidence, clinical presentation, management, imaging features, and long-term outcomes of patients with all types of neonatal stroke (NS). METHODS: Full-term neonates with NS born between January 2007 and December 2013 were identified through the Nova Scotia Provincial Perinatal Follow-up Program Database. Perinatal data and neonatal course were reviewed. Neurodevelopmental outcomes were assessed at 18 and 36 months of age using standardized testing. RESULTS: Twenty-nine neonates with NS were identified during the study period, giving an incidence of 47 per 100,000 live births in Nova Scotia. Arterial ischemic stroke was the most common stroke type (76%), followed by neonatal hemorrhagic stroke (17%), then cerebral sinovenous thrombosis (7%). The majority of neonates presented with seizures (86%) on the first day of life (76%). At 36 months of age, 23 (79%) of the children had a normal outcome, while 3 (10%) were diagnosed with cerebral palsy (2 with neonatal arterial stroke and one with neonatal hemorrhagic stroke) and 3 (10%) had recurrent seizures (1 patient from each stroke subtype group). CONCLUSION: The incidence of NS in Nova Scotia is higher than what has been reported internationally in the literature. However, the neurodevelopmental outcomes at 3 years of age are better. Further studies are required to better understand the reasons for these findings.

Sustained efficacy of kangaroo care for repeated painful procedures over neonatal intensive care unit hospitalization: a single-blind randomized controlled trial.

Preterm neonates hospitalized in the neonatal intensive care unit undergo frequent painful procedures daily, often without pain treatment, with associated long-term adverse effects. Maternal-infant skin-to-skin contact, or kangaroo care (KC), and sweet-tasting solutions such as sucrose are effective strategies to reduce pain during a single procedure; however, evidence of sustained efficacy over repeated procedures is limited. We aimed to determine the relative sustained efficacy of maternal KC, administered alone or in combination with 24% sucrose, to reduce behavioral pain intensity associated with routine neonatal procedures, compared with 24% sucrose alone. Stable preterm infants (n = 242) were randomized to receive KC and water, KC and 24% sucrose, or 24% sucrose before all routine painful procedures throughout their neonatal intensive care unit stay. Pain intensity, determined using the Premature Infant Pain Profile, was measured during 3 medically indicated heel lances distributed across hospitalization. Maternal and neonatal baseline characteristics, Premature Infant Pain Profile scores at 30, 60, or 90 seconds after heel lance, the distribution of infants with pain scores suggesting mild, moderate, or severe pain, Neurobehavioral Assessment of the Preterm Infant scores, and incidence of adverse outcomes were not statistically significantly different between groups. Maternal KC, as a pain-relieving intervention, remained efficacious over time and repeated painful procedures without evidence of any harm or neurological impact. It seemed to be equally effective as 24% oral sucrose, and the combination of maternal KC and sucrose did not seem to provide additional benefit, challenging the existing recommendation of using sucrose as the primary standard of care.

Parallel Exploratory RCT of Polyethylene Wrap for Heat Loss Prevention in Infants Born at Less than 24 Weeks' Gestation.

BACKGROUND: The treatment effect of occlusive wrap applied immediately after delivery in infants born 24-28 weeks' gestation has been studied, but the effect is not known in infants born at less than 240/7 weeks' gestation. OBJECTIVES: To determine if the use of occlusive wrap applied immediately after birth in infants born at less than 240/7 weeks' gestation results in any differences in outcomes when compared to non-wrapped infants. METHODS: Parallel exploratory randomized controlled trial with a convenience sample of 28 inborn infants born at less than 240/7 weeks' gestation enrolled during the duration of the HeLP trial. Infants were randomized to either the wrap or standard of care (no wrap) group. RESULTS: Twenty-eight infants (wrap n = 14; no wrap n = 14) were randomized and data on all infants was available for intention-to-treat analysis. There were no differences in baseline population characteristics. There was no statistically significant difference in mortality (n = 8/14 wrap, 8/14 no wrap). There was no statistically significant difference in baseline temperature (35.9°C, SD = 1.12, wrap vs. 35.1°C, SD = 1.16, no wrap, p = 0.16) or post-stabilization temperature (36.4°C, SD = 0.84, wrap vs. 36.1°C, SD = 1.2, no wrap, p = 0.56). There was a trend towards increased baseline temperature in the wrap group. CONCLUSION: Application of occlusive wrap to infants born at less than 240/7 weeks' gestation immediately after birth did not reduce mortality or effect baseline or post-stabilization temperature in this small exploratory study. This small sample provides the first estimate of treatment effect for this high-risk population.

A population-based study of cystic white matter injury on ultrasound in very preterm infants born over two decades in Nova Scotia, Canada.

OBJECTIVE: To identify the temporal trends, risk factors and outcomes of cystic white matter injury (WMI) detected by ultrasound in a population-based cohort of very preterm infants (VPI) with a minimal risk of selection bias. STUDY DESIGN: All live-born VPIs between 22 and < 31 weeks gestational age born in Nova Scotia, Canada from 1993 to 2013. RESULTS: Cystic WMI was identified in 87 (7%) out of 1184 eligible infants. The gestational age and mortality adjusted prevalence of cystic WMI decreased over time (p = 0.04). In multivariable analysis, chorioamnionitis, antenatal steroids, admission hypothermia, ventilator support, inotropes, and non-Coagulase-negative Staphylococcal and fungal infections were independently associated with cystic WMI. Cerebral palsy was the most common disability in the survivors, however, half of the survivors had none or mild disability. CONCLUSIONS: This cohort study demonstrated a decreasing trend in the incidence of cystic WMI and reported population-based neurological outcomes with cystic WMI, which is important for health-care planning and parental counseling.

Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study.

BACKGROUND: Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. METHODS: Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 µg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. RESULTS: The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO2 at a dose of 800 µg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. CONCLUSIONS: Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 µg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. TRIAL REGISTRATION: This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .

Inhaled and systemic steroid exposure and neurodevelopmental outcome of preterm neonates.

OBJECTIVES: To compare death and/or neurodevelopmental outcomes of preterm infants exposed to inhaled and/or systemic steroids with those without exposure, and examine the impact of timing of exposure. METHODS: Retrospective study of infants born <29 weeks gestation and assessed at 18-21 months corrected age (CA). Neurodevelopmental impairment (NDI) was defined as any Bayley Scales of Infant and Toddler Development-III (BSID-III) score <85, cerebral palsy ≥ grade one, and visual or hearing impairment. Significant NDI (sNDI) was defined as any Bayley Scales of Infant Development (BSID-III) score <70, cerebral palsy ≥ grade three, or severe vision or hearing impairment. RESULTS: Of 2570 neonates, 1811 had no exposure, 125 were exposed to inhaled steroids, 522 to systemic steroids and 112 to both. Infants exposed to inhaled steroids had lower odds of bronchopulmonary dysplasia [adjusted odds ratio (AOR) 0.51, (0.33, 0.79)], and displayed no difference in death/NDI or death/significant neurodevelopmental impairment (sNDI), regardless of timing of exposure. Infants only exposed to systemic steroids before 4 weeks of age were at increased odds of death/NDI [AOR 1.83 (1.43, 2.34)] and death/sNDI [AOR 2.28 (1.76, 2.96)]. CONCLUSIONS: Exposure to inhaled steroids was not associated with increased odds of death/NDI or death/sNDI. Systemic steroids use before 4 weeks of age was associated with significantly worse outcomes.

Determinants of developmental outcomes in a very preterm Canadian cohort.

OBJECTIVES: Identify determinants of neurodevelopmental outcome in preterm children. METHODS: Prospective national cohort study of children born between 2009 and 2011 at <29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score < 85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III < 70, severe CP, blind or hearing aided and sNDI or death. RESULTS: Of the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%-51%) had a NDI, 17% (11%-23%) had a sNDI, 6.4% (3.1%-8.6%) had CP, 2.6% (2.5%-13.3%) had hearing aids or cochlear implants and 1.6% (0%-3.1%) had a bilateral visual impairment. Bayley-III composite scores of <70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3-4.3, 0.04-3.5 and 0.12-1.96, respectively. CONCLUSION: Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

Type of Labour in the First Pregnancy and Cumulative Perinatal Morbidity.

OBJECTIVE: To estimate cumulative perinatal morbidity among infants delivered at term, according to the type of labour in the first pregnancy, when the first pregnancy was low risk. METHODS: In a 26-year population-based cohort study (1988-2013) using the Nova Scotia Atlee Perinatal Database, we identified the type of labour in successive pregnancies in low-risk, nulliparous women at term in their first pregnancy (who had at least one subsequent pregnancy), and also identified perinatal outcomes in subsequent deliveries according to the type of labour in the first pregnancy. RESULTS: A total of 37 756 pregnancies satisfied inclusion and exclusion criteria; of these, 1382 (3.7%) had a Caesarean section without labour in the first pregnancy. Rates of most adverse perinatal outcomes were low (≤ 1%). The risks for stillbirth were low in subsequent deliveries, including those that followed CS without labour in the first pregnancy, and the risks for the overall severe perinatal morbidity outcome were less than 10% for all subsequent deliveries. CONCLUSION: The absolute risks for severe perinatal morbidity outcomes in a population of low-risk women (with up to four additional pregnancies) were small, regardless of type of labour in the first pregnancy. This finding provides important information on perinatal outcomes in subsequent pregnancies when considering type of labour in the first pregnancy.

An Algorithm for Predicting Neonatal Mortality in Threatened Very Preterm Birth.

OBJECTIVE: To develop a prediction model for neonatal mortality using information readily available in the antenatal period. METHODS: A multiple logistic regression model of a complete population-based geographically defined cohort of very preterm infants of 23+0 to 30+6 weeks' gestation was used to identify antenatal factors which were predictive of mortality in this population. Infants lt; 23 weeks and those with major anomalies were excluded. RESULTS: Between 1996 and 2012, 1240 live born infants lt; 31 weeks' gestation were born to women residing in Nova Scotia. Decreasing gestational age strongly predicted an increased mortality rate. Other factors significantly contributing to increased mortality included classification as small for gestational age, oligohydramnios, maternal psychiatric disorders, antenatal antibiotic therapy, and monochorionic twins. Reduced neonatal mortality was associated with antenatal use of antihypertensive agents and use of corticosteroids of any duration of therapy given at least 24 hours before delivery. An algorithm was developed to estimate the risk of mortality without the need for a calculator. CONCLUSION: Prediction of the probability of neonatal mortality is influenced by maternal and fetal factors. An algorithm to estimate the risk of mortality facilitates counselling and informs shared decision making regarding obstetric management.

Objectif : Élaborer un modèle prédictif en ce qui concerne la mortalité néonatale au moyen de renseignements faciles à obtenir au cours de la période prénatale. Méthodes : Nous avons eu recours au modèle de régression logistique multiple d'une cohorte exhaustive, populationnelle et définie géographiquement de nouveau-nés très prématurés (âge gestationnel : de 23+0 à 30+6 semaines) pour identifier les facteurs prénataux permettant de prédire la mortalité au sein de cette population. Les nouveau-nés dont l'âge gestationnel était inférieur à 23 semaines et ceux qui présentaient des anomalies majeures ont été exclus. Résultats : Entre 1996 et 2012, 1 240 enfants nés vivants à moins de 31 semaines de gestation ont été issus de femmes résidant en Nouvelle-Écosse. La baisse de l'âge gestationnel constituait un facteur solide permettant de prédire une hausse du taux de mortalité. Parmi les autres facteurs contribuant de façon significative à la hausse du taux de mortalité, on trouvait l'hypotrophie fœtale, l'oligohydramnios, les troubles psychiatriques maternels, l'antibiothérapie prénatale et les jumeaux monozygotes. La baisse du taux de mortalité néonatale était associée à l'utilisation prénatale d'antihypertenseurs et à l'utilisation de corticostéroïdes (peu importe la durée du traitement) administrés au moins 24 heures avant l'accouchement. Nous avons élaboré un algorithme pour estimer le risque de mortalité sans avoir recours à une calculatrice. Conclusion : La prévision de la probabilité de la mortalité néonatale est influencée par des facteurs maternels et fœtaux. Le fait de disposer d'un algorithme pour estimer le risque de mortalité facilite le counseling et éclaire le processus décisionnel partagé en ce qui concerne la prise en charge obstétricale.

Temporal trends of intraventricular hemorrhage of prematurity in Nova Scotia from 1993 to 2012.

OBJECT Intraventicular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PHH) are common in premature newborns. The epidemiology of these conditions has been described, but selection bias remains a significant concern in many studies. The goal of this study was to review temporal trends in the incidence of IVH, PHH, and shunt surgery in a population-based cohort of very preterm infants with no selection bias. METHODS All very preterm infants (gestational age ≥ 20 and ≤ 30 weeks) born from 1993 onward to residents of Nova Scotia were evaluated by the IWK Health Centre's Perinatal Follow-Up Program, and were entered in a database. Infants born to residents of Nova Scotia from January 1, 1993, to December 31, 2012, were included in this study. The incidences of IVH, PHH, and shunt surgery were calculated, basic demographic information was described, and chi-square test for trends over time was determined. RESULTS Of 1334 successfully resuscitated very preterm infants who survived to their initial screening ultrasound, 407 (31%) had an IVH, and 149 (11%) had an IVH Grade 3 or 4. No patients with IVH Grade 1 or 2 developed PHH. The percentage of very preterm infants with IVH Grade 3 or 4 has significantly increased over time (p = 0.013), as have the incidence of PHH and shunt surgery (p = 0.001 and p = 0.011, respectively) in infants with Grade 3 or 4 IVH. The proportion of patients with PHH receiving a shunt has not changed over time (p = 0.813). CONCLUSIONS The increasing incidence of high-grade IVH-and PHH and shunt surgery in infants with high-grade IVH-over time is worrisome. This study identifies a number of associated factors, but further research to identify preventable and treatable causal factors is warranted.

Outcomes of intraventricular hemorrhage and posthemorrhagic hydrocephalus in a population-based cohort of very preterm infants born to residents of Nova Scotia from 1993 to 2010.

OBJECT Intraventicular hemorrhage (IVH) is a common complication of preterm birth, and the prognosis of IVH is incompletely characterized. The objective of this study was to describe the outcomes of IVH in a population-based cohort with minimal selection bias. METHODS All very preterm (≥ 30 completed weeks) patients born in the province of Nova Scotia were included in a comprehensive database. This database was screened for infants born to residents of Nova Scotia from January 1, 1993, to December 31, 2010. Among very preterm infants successfully resuscitated at birth, the numbers of infants who died, were disabled, developed cerebral palsy, developed hydrocephalus, were blind, were deaf, or had cognitive/language scores assessed were analyzed by IVH grade. The relative risk of each outcome was calculated (relative to the risk for infants without IVH). RESULTS Grades 2, 3, and 4 IVH were significantly associated with an increased overall mortality, primarily in the neonatal period, and the risk increased with increasing grade of IVH. Grade 4 IVH was significantly associated with an increased risk of disability (RR 2.00, p < 0.001), and the disability appeared to be primarily due to cerebral palsy (RR 6.07, p < 0.001) and cognitive impairment (difference in mean MDI scores between Grade 4 IVH and no IVH: -19.7, p < 0.001). No infants with Grade 1 or 2 IVH developed hydrocephalus, and hydrocephalus and CSF shunting were not associated with poorer outcomes when controlling for IVH grade. CONCLUSIONS Grades 1 and 2 IVH have much better outcomes than Grades 3 or 4, including a 0% risk of hydrocephalus in the Grade 1 and 2 IVH cohort. Given the low risk of selection bias, the results of this study may be helpful in discussing prognosis with families of very preterm infants diagnosed with IVH.

Randomized trial of occlusive wrap for heat loss prevention in preterm infants.

OBJECTIVE: To determine whether the application of occlusive wrap applied immediately after birth will reduce mortality in very preterm infants. STUDY DESIGN: This was a prospective randomized controlled trial of infants born 24 0/7 to 27 6/7 weeks' gestation who were assigned randomly to occlusive wrap or no wrap. The primary outcome was all cause mortality at discharge or 6 months' corrected age. Secondary outcomes included temperature, Apgar scores, pH, base deficit, blood pressure and glucose, respiratory distress syndrome, bronchopulmonary dysplasia, seizures, patent ductus arteriosus, necrotizing enterocolitis, gastrointestinal perforation, intraventricular hemorrhage, cystic periventricular leukomalacia, pulmonary hemorrhage, retinopathy of prematurity, sepsis, hearing screen, and pneumothorax. RESULTS: Eight hundred one infants were enrolled. There was no difference in baseline population characteristics. There were no significant differences in mortality (OR 1.0, 95% CI 0.7-1.5). Wrap infants had statistically significant greater baseline temperatures (36.3°C wrap vs 35.7°C no wrap, P < .0001) and poststabilization temperatures (36.6°C vs 36.2°C, P < .001) than nonwrap infants. For the secondary outcomes, there was a significant decrease in pulmonary hemorrhage (OR 0.6, 95% CI 0.3-0.9) in the wrap group and a significant lower mean one minute Apgar score (P = .007) in the wrap group. The study was stopped early because continued enrollment would not result in the attainment of a significant difference in the primary outcome. CONCLUSION: Application of occlusive wrap to very preterm infants immediately after birth results in greater mean body temperature but does not reduce mortality.

Trends in the prevalence of cerebral palsy among very preterm infants (<31 weeks' gestational age).

BACKGROUND: The birth prevalence of cerebral palsy varies over time among very preterm infants, and the reasons are poorly understood. OBJECTIVE: To describe the variation in the prevalence of cerebral palsy among very preterm infants over time, and to relate these differences to other maternal or neonatal factors. METHODS: A population-based cohort of very preterm infants was evaluated over a 20-year period (1988 to 2007) divided into four equal epochs. RESULTS: The prevalence of cerebral palsy peaked in the third epoch (1998 to 2002) while mortality rate peaked in the second epoch (1993 to 1997). Maternal anemia, tocolytic use and neonatal need for home oxygen were highest in the third epoch. CONCLUSIONS: Lower mortality rates did not correlate well with the prevalence of cerebral palsy. Maternal risk factors, anemia and tocolytic use, and the newborn need for home oxygen were highest during the same epoch as the peak prevalence of cerebral palsy.

HISTORIQUE: La prévalence de paralysie cérébrale à la naissance varie au fil du temps chez les nourrissons très prématurés, et on en comprend mal les raisons. OBJECTIF: Décrire la variation de la prévalence de paralysie cérébrale chez les nourrissons très prématurés au fil du temps et les relier à d'autres facteurs relatifs à la mère ou à la période néonatale. MÉTHODOLOGIE: Les chercheurs ont évalué une cohorte de nourrissons très prématurés sur 20 ans (1988 à 2007), divisée en quatre périodes d'égale longueur. RÉSULTATS: La prévalence de paralysie cérébrale a atteint un pic pendant la troisième période (1998 à 2002), tandis que le pic du taux de mortalité est survenu pendant la deuxième période (1993 à 1997). L'anémie et l'utilisation de tocolytiques chez la mère, ainsi que l'assistance ventilatoire néonatale à domicile, étaient plus élevées pendant la troisième période. CONCLUSIONS: Les taux de mortalité plus faibles n'étaient pas bien corrélés avec la prévalence de paralysie cérébrale. Les facteurs de risque de la mère, c'est-à-dire l'anémie et l' utilisation de tocolytiques, de même que l'assistance ventilatoire du nouveau-né à domicile, étaient tous plus élevés pendant la période qui s'associait à la plus forte prévalence de paralysie cérébrale.

Trial of repeated analgesia with Kangaroo Mother Care (TRAKC Trial).

BACKGROUND: Skin-to-skin contact (SSC) between mother and infant, commonly referred to as Kangaroo Mother Care (KMC), is recommended as an intervention for procedural pain. Evidence demonstrates its consistent efficacy in reducing pain for a single painful procedure. The purpose of this study is to examine the sustained efficacy of KMC, provided during all routine painful procedures for the duration of Neonatal Intensive Care Unit (NICU) hospitalization, in diminishing behavioral pain response in preterm neonates. The efficacy of KMC alone will be compared to standard care of 24% oral sucrose, as well as the combination of KMC and 24% oral sucrose. METHODS/DESIGN: Infants admitted to the NICU who are less than 36 6/7 weeks gestational age (according to early ultrasound), that are stable enough to be held in KMC, will be considered eligible (N = 258). Using a single-blinded randomized parallel group design, participants will be assigned to one of three possible interventions: 1) KMC, 2) combined KMC and sucrose, and 3) sucrose alone, when they undergo any routine painful procedure (heel lance, venipuncture, intravenous, oro/nasogastric insertion). The primary outcome is infant's pain intensity, which will be assessed using the Premature Infant Pain Profile (PIPP). The secondary outcome will be maturity of neurobehavioral functioning, as measured by the Neurobehavioral Assessment of the Preterm Infant (NAPI). Gestational age, cumulative exposure to KMC provided during non-pain contexts, and maternal cortisol levels will be considered in the analysis. Clinical feasibility will be accounted for from nurse and maternal questionnaires. DISCUSSION: This will be the first study to examine the repeated use of KMC for managing procedural pain in preterm neonates. It is also the first to compare KMC to sucrose, or the interventions in combination, across time. Based on the theoretical framework of the brain opioid theory of attachment, it is expected that KMC will be a preferred standard of care. However, current pain management guidelines are based on minimal data on repeated use of either intervention. Therefore, regardless of the outcomes of this study, results will have important implications for guidelines and practices related to management of procedural pain in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01561547.