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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.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.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.• 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. more...

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla... more...

ObjectivesHealth 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.MethodsInfants 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.ResultsOf 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.ConclusionMost 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. more...

ObjectiveInformed 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.DesignSubgroup analysis of infants enrolled in a randomised controlled trial conducted from 2004 to 2010.SettingA multicentre trial with 38 participating centres.ParticipantsInfants 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 measureThe difference in mortality between consent groups.ResultsNo 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%, pConclusions and relevanceResearch 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. more...

To determine postdischarge iron status and associated factors in very preterm infants.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 ferritin20 g/L at 4 months or12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency.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 age27 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).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. more...

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. more...

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. more...

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.Retrospective study of infants born29 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) score85, cerebral palsy ≥ grade one, and visual or hearing impairment. Significant NDI (sNDI) was defined as any Bayley Scales of Infant Development (BSID-III) score70, cerebral palsy ≥ grade three, or severe vision or hearing impairment.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)].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. 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. more...

To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses.We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates.We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada.NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates. more...

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. more...

BACKGROUND: Umbilical cord milking at birth has been reported to have short-term benefits to preterm infants. Long-term neurodevelopmental outcomes need more exploration. OBJECTIVES: To compare the effects of cord milking (CM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months corrected age. DESIGN/METHODS: Preterm infants more...

To examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN).This was a population-based cohort study of infants born at33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding.Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12).Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge. more...

Background One of the controversies in the management of twin gestations relates to mode of delivery, especially when the second twin is in a nonvertex presentation (Vertex/nonVertex pairs) and birth is imminent at extremely low gestation. Objective We hypothesized that, for Vertex/nonVertex twins born before 28 weeks’ gestation, cesarean delivery would be associated with a lower risk of adverse neonatal outcomes than trial of vaginal delivery. Our aim was to test this hypothesis by comparing the neonatal outcomes of Vertex/nonVertex twins born before 28 weeks’ gestation by mode of delivery using a large national cohort. Study Design This work is a retrospective cohort study of all twin infants born at 240/7 to 276/7 weeks’ gestation and admitted to level III neonatal intensive care units participating in the Canadian Neonatal Network (2010–2017). Exposure is defined a trial of vaginal delivery for Vertex/nonVertex twins. Nonexposed (control) groups are defined as cases where both twins were delivered by cesarean delivery, either in vertex or nonvertex presentation (control group 1) or owing to the nonvertex presentation of the first twin (control group 2). Outcome measures are defined as a composite of neonatal death, severe neurologic injury, or birth trauma. Results A total of 1082 twin infants (541 twin pairs) met the inclusion criteria: 220 Vertex/nonVertex pairs, of which 112 had a trial of vaginal delivery (study group) and 108 had cesarean delivery for both twins (control group 1); 170 pairs with the first twin in nonvertex presentation, all of which were born by cesarean delivery (control group 2); and 151 pairs with both twins in vertex presentation (vertex or nonvertex). In the study group, the rate of urgent cesarean delivery for the second twin was 30%. The rate of the primary outcome in the study group was 42%, which was not significantly different compared with control group 1 (37%; adjusted relative risk, 0.93; 95% confidence interval, 0.71–1.22) or control group 2 (34%; adjusted relative risk, 1.20; 95% confidence interval, 0.92–1.58). The findings remained similar when outcomes were analyzed separately for the first and second twins. Conclusion For preterm Vertex/nonVertex twins born at more...

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. more...

Background: Iron is an essential micronutrient, especially in infants and young children and is required for erythropoiesis and development of the central nervous system. However, iron deficiency (ID) is the most common micronutrient deficiency worldwide. ID and iron deficiency anemia (IDA) have been associated with poor neurodevelopmental and behavioural outcomes later in life. Preterm infants are particularly at risk of developing ID in early life due to lower iron stores at birth, accelerated growth in the first weeks of life and multiple phlebotomies while in hospital. Therefore, international recommendations suggest prophylactic iron therapy of 2-4 mg/kg/day starting at 2-6 weeks of age until at least 6-12 months in preterm and low birth weight infants. This prophylactic iron supplementation has been shown to be effective at reducing the incidence of ID and IDA. However, the published work mainly involves moderate to late preterm infants and the research is lacking on iron status after discharge in very preterm infants (VPI, Objective: To investigate the risk factors associated with development of ID Methods: A retrospective cohort study was conducted at the IWK Health Centre using a population based provincial Perinatal Follow-Up Program database. All live-born VPIs born in Nova Scotia between 2005-2018 were included. Patients with congenital malformations, chromosomal anomalies, or who died prior to outcome assessment were excluded. As a standard of care, all these infants were started on prophylactic iron supplements (2-3 mg/kg/day) at 2-4 weeks of chronological age. Iron dosage was regularly adjusted during the hospital stay as guided by serum ferritin levels. At discharge, it was recommended to continue iron prophylaxis until 9-12 months corrected age. All these infants underwent a blood test during their first neonatal follow-up visit at 4-6 months corrected age to check for hemoglobin, reticulocyte count and serum ferritin. ID was defined as serum ferritin Results: Of 411 infants included in the study, 32.1% (n=132) had ID. The prevalence of ID decreased over time (37.6% in 2005-2011 vs 25.8% in 2012-2018 cohort). Table 1 compares the antenatal and neonatal characteristics of the ID and non-ID groups. Table 2 compares sociodemographic variables and clinical variables at the time of follow up of the two groups. Independent risk factors for ID were: gestational age (27 weeks) (OR:1.7 (1.0-2.9), p=0.04) and gestational hypertension (OR: 2.1(1.2-3.7), p=0.009). Independent factors protective for ID were: mixed feeding (breast milk and formula compared to formula alone) (OR: 0.5 (0.2-0.9), p=0.021) and iron supplementation at follow-up (OR:0.5 (0.3-0.9), p=0.02). Conclusion(s): Despite prophylactic iron supplementation, one-third of VPIs had ID at 4-6 months corrected age. Gestational hypertension in mother and gestational age < 27 weeks were independent risk factors for ID. In addition, despite adjusting for iron supplementation at follow-up, the formula feeding group was more likely to have ID compared to the mixed feeding group. This may be because of the sub-therapeutic iron intake in the formula fed infants. It is often thought that formula milk may have sufficient iron to meet the demands of growing infants and thus, they are less likely to receive higher doses of supplemental iron beyond what is contained in the formula. However, this may not be true since the iron present in formula may not have the same bioavailability as breast milk. Future prospective studies are required to further validate these observations. Nonetheless, the study identified important areas to mitigate ID in VPIs. Disclosures No relevant conflicts of interest to declare. more...

To compare mortality and neurodevelopmental outcomes of extremely low gestational age neonates who received delivery room extensive cardiopulmonary resuscitation (DR-CPR) to those who did not require DR-CPR.Preterm neonates born at29 weeks' gestational age between January 2010 and September 2011 and assessed at Canadian Neonatal Follow-Up Network centers were studied. Neonates who received DR-CPR were compared to those who did not require DR-CPR using univariate and multivariable analyses. The primary outcome was a composite of mortality or any neurodevelopmental impairment at 18 to 24 months corrected age defined as the presence of any one or more of the following: cerebral palsy; Bayley-III cognitive, language, or motor composite scores85 on any one of the components; sensorineural/mixed hearing loss or unilateral or bilateral visual impairment. Secondary outcomes were the individual components of the composite outcomes.Of the 2760 neonates born, 173 were excluded and remaining 2587 eligible neonates were included in our study. Of these 2068 had outcome data (80%) of whom 190 (9.2%) received DR-CPR. DR-CPR was independently associated with mortality or neurodevelopmental impairment (adjusted odds ratio [aOR] 1.76; 95% CI 1.21-2.55) and mortality alone (aOR1.94; 95% CI 1.33-2.83). DR-CPR was also associated with increased odds of motor impairment (aOR 2.03; 95% CI 1.28-3.23).In extremely low gestational age neonates, DR-CPR was associated with higher odds of the composite outcome of mortality or neurodevelopmental impairment, mortality alone, and lower motor scores at 18 to 24 months' corrected age. more...

BACKGROUND Normal saline bolus is commonly used in clinical practice for treating hypotension in very preterm infants during resuscitation at an early age despite the paucity of high quality evidence supporting this practice. OBJECTIVES To determine the effects of early ( more...

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. All live-born VPIs between 22 and more...

BACKGROUND: Systemic hypertension (SH) has been reported in 0.2–3% of Neonatal Intensive Care Unit (NICU) patients. The epidemiology of the disease in preterm infants needs further exploration. OBJECTIVES: To assess the incidence, temporal trend, risk factors, clinical characteristics, management and associated outcomes of preterm infants with SH. DESIGN/METHODS: A retrospective population-based study including all infants born between January 2002 and December 2016 at < 31 weeks gestation in Nova Scotia. Patients diagnosed with SH (systolic blood pressure > 100mmHg requiring treatment, before discharge from NICU, or on 3 consecutive occasions during outpatient follow-up), were identified from the Provincial Perinatal Follow-up Database and patients’ charts. All SH patients were compared with matched controls (for gestational age, sex and birth weight). Perinatal data, details of SH and neonatal course were reviewed. Infants who died < 7 days of age were excluded. RESULTS: Out of 935 infants who met inclusion criteria, 109 (13.1%) had SH. Mean gestational age was 27.2 weeks (±1.9) and mean birth weight was 1039.3 g (±281.9) Table 1. Median post-menstrual age at diagnosis was 40 weeks Table 2. There was no significant difference in the temporal trend between the three study epochs (Figure 1). On logistic regression analysis, presence of major congenital anomaly was the only risk factor for SH (aOR 14.7, 95% CI:1.54, 141.2). Antenatal magnesium sulfate was protective (aOR 0.39, 95% CI: 0.20,0.75). 64 SH infants (59%) had nephrocalcinosis at time of diagnosis and the majority (79, 72.5%) were treated with ACE inhibitors. There was no significant difference in mortality (p=1.0) but the median length of stay was higher in the SH patients (p more...

To develop a prediction model for neonatal mortality using information readily available in the antenatal period.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.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.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. more...

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. more...

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. more...

The birth prevalence of cerebral palsy varies over time among very preterm infants, and the reasons are poorly understood.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.A population-based cohort of very preterm infants was evaluated over a 20-year period (1988 to 2007) divided into four equal epochs.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.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.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.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.Les chercheurs ont évalué une cohorte de nourrissons très prématurés sur 20 ans (1988 à 2007), divisée en quatre périodes d’égale longueur.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.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. more...

BACKGROUND: Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) are associated with multiple risk factors, but the etiologies and pathophysiology of these conditions are not completely understood. Recent evidence suggests that poor postnatal weight gain may contribute to the development of both ROP and BPD. OBJECTIVES: This study aimed to investigate if in preterm infants, poor growth velocity, defined as weight gain velocity (WGV) more...

Objectives Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with neonatal mortality, acute neurological injury and long-term neurodevelopmental disabilities; the role of intrapartum factors remains unclear. Methods This population-based cohort study employed linked obstetrical and newborn data derived from the Nova Scotia Atlee Perinatal Database (NSAPD, 1988-2015) and the Perinatal Follow-Up Program Database (2006-2015) for all pregnancies with live, non-anomalous newborns ?35 weeks, born without pre-labour caesarean section. HIE was defined using standard definitions. Temporal trends in HIE incidence are described; Fisher's exact test and logistic regression were used to test the associations of intrapartum factors with HIE. Results The NSAPD identified 227 HIE cases out of a population of 226,711 pregnancies from 1988 to 2015, with a decrease in incidence from 0.14% to 0.1% through those years (P=0.01). Women with clinical chorioamnionitis in labour (OR 8.0, 95% CI 4.7-17), emergency operative delivery (OR 9.9, 95% CI 7.3-13), shoulder dystocia (OR 3.4, 95% CI 2.1-5.4), placental abruption (OR 19, 95% CI 12-29), and cord prolapse (OR 32, 95% CI 17-61) were more likely to have newborns with HIE. Two-thirds of newborns with HIE had an abnormal intrapartum FHR tracing. There was an infant mortality rate of 28% by age 3; neurodevelopmental outcomes in the surviving infants with HIE were normal in 33% and showed severe developmental delay in 37%. Conclusions Overall, the rate of HIE was low in late-preterm and term infants. The identification of associated intrapartum factors should promote increased surveillance and careful management to optimize newborn outcomes. more...

Developmental delay, as measured by the Bayley Scales of Infant Development III (BSITD-III), refers to a limitation in gross motor, fine motor, cognitive, language or personal-social skills in comparison with norm-referenced performance (1). Early detection of delay can result in earlier intervention to improve outcomes (2). Conditions that are known to increase risk of developmental delay include prematurity, low birth weight and neurological injury at birth (3). Family physicians, paediatricians and/or neonatologists typically have contact with high-risk infants for medical follow-up, and are often the health care providers involved with the identification of developmental delay. The BSITD-III is a well-documented assessment tool to detect developmental delay but is costly and lengthy to administer, and not the choice for surveillance or screening. The Rourke Baby Record (Rourke) is a relatively recent, comprehensive, evidence-based, integrated primary care practice tool, which includes a section designed to support developmental surveillance (4). As a surveillance tool, its ability to identify developmental delay is dependent on assessment over time. This differs from a screening tool, which provides a brief, one-time assessment to assist in the identification of delay (5). The Rourke is used by many physicians and is endorsed by both the College of Family Physicians of Canada and the Canadian Paediatric Society. However, the capability of the Rourke to identify developmental concern is largely undetermined. The Nipissing District Developmental Screen (NDDS) is similar to the Rourke in that it is widely used but has minimal literature to support its ability to detect delayed development (6). An ideal tool needs to be not only time efficient for a medical practice but also sensitive enough to detect deficits in development. The objective of the present pilot study was to test participant recruitment procedures and methodology to determine the feasibility of completion of a full-scale, adequately powered observational study to determine the test characteristics of the Rourke and NDDS. As well, the present project aimed to provide preliminary findings of the test characteristics of the Rourke and the NDDS compared with the BSITD-III in the detection of delay in high-risk children. more...

Objective A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. Methods Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale Women were also asked to evaluate their study participation Results Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. Conclusion In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again. more...

Objectives To determine if dexamethasone given to premature infants with bronchopulmonary dysplasia would result in cardiac diastolic dysfunction in early childhood, a topic unstudied in humans. Study design We compared seven children ages 3 to 8 years born at 26 weeks’ gestation and given dexamethasone for bronchopulmonary dysplasia with eight gestation-matched and age-matched control children using echocardiography to assess measures of systolic and diastolic function. All dexamethasone patients had resolved hypertrophic cardiomyopathy. Results Dexamethasone patients had the same normal τ and isovolumic relaxation time (24.9 ± 2.8 and 54.6 ± 6.3 ms) as control patients (22.1 ± 3.0 and 48.8 ± 6.7 ms). Peak A velocities were the same in dexamethasone patients as in control patients (59.5 ± 15 versus 49.4 ± 5.8 cm/s, P = .10), resulting in unchanged E:A ratios (1.89 ± 0.57 versus 2.15 ± 0.43, P = .22). Peak E velocity and E-wave deceleration times were not different. We found no significant differences in measures of systolic function (heart rate–corrected velocity of circumferential fiber shortening, wall stress, and ejection fraction). Left ventricular mass was the same between the groups confirming resolution of hypertrophic cardiomyopathy. Conclusions These data are consistent with normal myocardial relaxation, suggesting that long-term diastolic function is reassuringly normal in children who received dexamethasone as premature infants with resolution of hypertrophic cardiomyopathy. more...

Objective To assess the impact of variations in the definition of severe neurodevelopmental impairment (NDI) on the incidence of severe NDI and the association with risk factors using the Canadian Neonatal Follow-Up Network cohort. Study design Literature review of severe NDI definitions and application of these definitions were performed in this database cohort study. Infants born at 23-28 completed weeks of gestation between 2009 and 2011 (n = 2187) admitted to a Canadian Neonatal Network neonatal intensive care unit and assessed at 21 months' corrected age were included. The incidence of severe NDI, aORs, and 95% CIs were calculated to express the relationship between risk factors and severe NDI using the definitions with the highest and the lowest incidence rates of severe NDI. Results The incidence of severe NDI ranged from 3.5% to 14.9% (highest vs lowest rate ratio 4.29; 95% CI 3.37-5.47). The associations between risk factors and severe NDI varied depending on the definition used. Maternal ethnicity, employment status, antenatal corticosteroid treatment, and gestational age were not associated consistently with severe NDI. Although maternal substance use, sex, score of neonatal acute physiology >20, late-onset sepsis, bronchopulmonary dysplasia, and brain injury were consistently associated with severe NDI irrespective of definition, the strength of the associations varied. Conclusions The definition of severe NDI significantly influences the incidence and the associations between risk factors and severe NDI. A standardized definition would facilitate site comparisons and scientific communication. more...

To compare mortality and neurodevelopmental outcomes of outborn and inborn preterm infants born at29 weeks of gestation admitted to Canadian neonatal intensive care units (NICUs).Data were obtained from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases for infants born at29 weeks of gestation admitted to NICUs from April 2009 to September 2011. Rates of death, severe neurodevelopmental impairment (NDI), and overall NDI were compared between outborn and inborn infants at 18-21 months of age, corrected for prematurity.Of 2951 eligible infants, 473 (16%) were outborn. Mean birth weight (940 ± 278 g vs 897 + 237 g), rates of treatment with antenatal steroids (53.9% vs 92.9%), birth weight small for gestational age (5.3% vs 9.4%), and maternal college education (43.7% vs 53.9%) differed between outborn and inborn infants, respectively (all P values.01). The median Score for Neonatal Acute Physiology-II (P = .01) and Apgar score at 5 minutes (P .01) were higher in inborn infants. Severe brain injury was more common among outborn infants (25.3% vs 14.7%, P .01). Outborn infants had higher odds of death or severe NDI (aOR 1.7, 95% CI 1.3-2.2), death or overall NDI (aOR 1.6, 95% CI 1.2-2.2), death (aOR 2.1, 95% CI 1.5-3.0), and cerebral palsy (aOR 1.9, 95% CI 1.1-3.3).The composite outcomes of death or neurodevelopmental impairment were significantly higher in outborn compared with inborn infants admitted to Canadian NICUs. Adverse outcomes were mainly attributed to increased mortality and cerebral palsy in outborn neonates. more...

To determine whether mutations in the FZD4 gene are a risk factor for developing severe ROP.Three Canadian tertiary care centers recruited premature infants prospectively and retrospectively, and assigned affectation status based on the maximum degree of severity of ROP recorded in both eyes. Mutation screening of the FZD4 gene was performed using direct sequencing. All sequence changes were evaluated for functional significance.Two novel FZD4 mutations (Ala370Gly or Lys203Asn) were identified in two infants from the severe ROP group (n=71). No mutation was detected in the mild to no ROP group (n=33), and the two novel mutations were absent in 173 random Caucasian samples. Mutation Ala370Gly was also found in one sibling and one parent of the affected infant, but no signs of familial exudative vitreoretinopathy (FEVR), a condition with phenotypic overlap with ROP known to be caused by FZD4 mutations, were present in either family member.Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe ROP and accounts for approximately 3% of severe ROP in Caucasian premature infants. more...

OBJECTIVES. It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age.METHODS. A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993–1997 and 1998–2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates.RESULTS. A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate.CONCLUSION. Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality. more...

Objective: To examine the causes and consequences of the recent increase in preterm birth among twins. Methods: We studied all twin births among residents of the province of Nova Scotia, Canada, between 1988 and 1997. Rates of preterm birth, preterm labor induction, preterm cesarean, small-for-gestational age (SGA), respiratory distress syndrome (RDS), stillbirth, perinatal mortality, and infant mortality were compared between past and more recent years. Changes in perinatal mortality were examined using logistic regression to adjust for the effects of other determinants. Results: The study included 2516 twin births (73 stillbirths and 2443 live births). The rate of preterm birth increased from 42.3% in 1988–1992 to 48.2% of twin live births in 1993–1997 (14% increase, P = .04). Twin live births born after preterm labor induction increased from 3.5% in 1988–1989 to 8.6% in 1996–1997 ( P for trend = .007). Of live births between 34 and 36 weeks’ gestation, the proportion born SGA decreased from 17.5% in 1988–1992 to 9.2% in 1993–1997 ( P = .005). Over the same period, rates of prophylactic maternal steroid therapy increased substantially and rates of RDS declined. Perinatal mortality rates among pregnancies reaching 34 weeks decreased from 12.9 per 1000 total births in 1988–1992 to 4.2 per 1000 total births in 1993–1997 ( P = .05). Conclusion: Increases in preterm labor induction appear to be responsible for the recent increase in preterm birth among twins. These changes have been accompanied by decreases in perinatal morbidity and mortality among twin pregnancies that reach 34 weeks’ gestation. more...

The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known.Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy.Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin.In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage. more...

This statement is intended for health care professionals caring for neonates (preterm to 1 month of age). The objectives of this statement are to: 1. Increase awareness that neonates experience pain;2. Provide a physiological basis for neonatal pain and stress assessment and management by health care professionals;3. Make recommendations for reduced exposure of the neonate to noxious stimuli and to minimize associated adverse outcomes; and4. Recommend effective and safe interventions that relieve pain and stress. more...

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. 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. 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. ClinicalTrials.gov Identifier: NCT01561547 . more...

Introduction Immediate postnatal hypothermia is an independent risk factor for death in premature newborns. Three randomized controlled trials (RCTs) and five historical controlled trials show statistically significant differences in admission temperature between infants wrapped in occlusive skin wrap and unwrapped infants. This paper presents a study protocol for The Vermont Oxford Network (VON) Heat Loss Prevention (HeLP) Trial, a multicentre RCT of two interventions (standard of care vs. occlusive wrap) that investigates the effect of polyethylene occlusive wrap applied immediately after birth on mortality in infants born 24 + 0/7 to 27 + 6/7 week gestation. Methods Inclusion criteria include: infants 24 + 0/7 to 27 + 6/7 weeks gestational age and a firm decision prior to birth to provide full resuscitative measures. Exclusion criteria comprise infants born with blistering skin conditions or congenital anomalies that are not covered by skin. The primary outcome measure is all-cause mortality until discharge from the hospital or at six months corrected gestational age. The secondary outcome measures include baseline and post-stabilization axillary temperatures, acidosis, hypotension, hypoglycaemia, seizures in the first 12 h, patent ductus arteriosus, and respiratory distress syndrome. Long-term follow-up at 18 to 24 months corrected age will be assessed with the combined risk of death and major neurosensory disability as the primary outcome. Discussion Key covariates and protocol deviations are addressed and steps to monitor these are described. Wrapping may prove an inexpensive and easy method to benefit premature newborns in level I and II nurseries, in both developed and developing countries, as well as large tertiary care centres. REB approval Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada—355-2003 University of Alberta, Edmonton, Alberta, Canada—Pro00003810 Vermont Oxford Network, Burlington, Vermont, USA—CHRMS: M04-295 more...

Identify determinants of neurodevelopmental outcome in preterm children.Prospective national cohort study of children born between 2009 and 2011 at29 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 score85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III70, severe CP, blind or hearing aided and sNDI or death.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 of70 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.Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes. more...

This study determined outcomes at 12-months adjusted age of 957 infants weighing more than 1250 gm at birth who were subjects in a randomized, double-blind, controlled trial of synthetic surfactant or air placebo administered in a rescue trial at 23 hospitals in the United States and 13 hospitals in Canada. Follow-up results were available for 475 of 563 surviving infants who received air placebo (84%) and 482 of 571 infants who received synthetic surfactant (84%). Developmental outcome was equivalent in the two groups. Morbidity was less in the synthetic surfactant group as assessed by the need for medication for chronic lung disease (52 of 475 [11%] for the air placebo group vs 32 of 482 [7%] for the synthetic surfactant group) or respiratory support (10 of 475 [2%] for the air placebo group vs 1 of 482 [ EDIATR 1995;126:S75-80) more...

Double-blind neurodevelopmental and physical evaluations were conducted at 1-year adjusted age in 89 infants with birth weights of 500 to 749 gm who had respiratory distress syndrome in the neonatal period and were randomized to receive two rescue doses of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) or air placebo. The trial used a common protocol and was conducted at 13 hospitals; patients were entered in the trial between February 1988 and September 1990. Ninety-five percent of surviving infants were assessed. Growth and development in the two groups were equivalent. Mean Bayley Scales of Infant Development scores were comparable (mental development index, 79 ± 22 vs 87 ± 20; psychomotor development index, 73 ± 18 vs 81 ± 19 for air placebo and synthetic surfactant, respectively). The incidence of severe retinopathy of prematurity was significantly decreased in the surfactant group compared with the air placebo group (15% vs 34%; relative risk 0.428; 95% confidence interval 0.2 to 0.9). Overall, administration of surfactant appeared to increase the probability of a favorable outcome. Confirmation of the trends observed in this study would provide a strong rationale for the rescue use of synthetic surfactant in extremely low birth weight infants with respiratory distress syndrome even if overall mortality is not reduced. (J P EDIATR 1995;126:S53-60) more...

Objective To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy (HIE). Data Sources Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews. Study Selection Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE. Intervention Therapeutic hypothermia. Main Outcome Measures Death or major neurodevelopmental disability at 18 months. Results Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability (RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93, respectively). Conclusion Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE. Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns. more...

Objective To estimate the influence of changing practice patterns of post-term induction of labour on severe neonatal morbidity. Methods This population-based cohort study used data from the Nova Scotia Atlee Perinatal Database to evaluate the effect of post-term induction of labour on stillbirth and neonatal mortality and severe neonatal morbidity in low-risk pregnancies. The study population included all pregnant women ≥ 40 weeks' gestation delivering in Nova Scotia from 1988 to 2008 who underwent induction of labour with a single fetus in cephalic presentation. Major congenital anomalies and pre-existing or severe gestational hypertension and diabetes were excluded. Women delivering post-term from 1994 to 2008 (after the Post-term Pregnancy Trial) were compared with women delivering from 1988 to 1992 to evaluate outcomes with changing maternal characteristics and obstetric practice patterns. Results Evaluation and comparison of time epochs (1988 to 1992, 1994 to 1998, 1999 to 2003, and 2004 to 2008) demonstrated an increased risk for perinatal mortality or severe neonatal morbidity, especially low five-minute Apgar score, among both nulliparous and multiparous women. There were no significant differences in the risks for stillbirth or perinatal mortality over time. Comparable relationships were demonstrated in a subgroup of lower risk women. Conclusion The increase in post-term induction of labour with time is associated with a significant increase in severe neonatal morbidity, especially among infants born to multiparous women. Evaluation of the antepartum and intrapartum management of these low-risk pregnancies may provide additional information to reduce morbidity. more...

We report on a third case of hypomandibular faciocranial dysostosis and review the literature. Manifestations include craniosynostosis, prominent eyes, deficient midface and zygomatic arches, short nose with anteverted nares, protruding lower face, minute oral aperture, persistent buccopharyngeal membrane, and severe mandibular hypoplasia. In contrast to coronal synostosis found in the 2 earlier cases, our patient had multiple sutural synostosis. The 2 affected sibs reported earlier suggest the possibility of autosomal recessive inheritance. However, gonadal mosaicism for a dominant mutation or an undetected microdeletion must also be considered at this early stage in the delineation of this disorder. © 1993 Wiley-Liss, Inc. more...

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.A double-blind, randomized placebo controlled trial.Level-III neonatal intensive care unit.Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected. more...

Hyperbilirubinemia is a common problem in the clinical course of the very low birth weight infant, and although readily treated with phototherapy, controversy remains as to the most effective way of using phototherapy in these infants (1). Elevated serum bilirubin levels in neonates can be damaging to the developing neural system if not adequately monitored and treated, resulting in abnormal neurological signs known as bilirubin encephalopathy or kernicterus (2,3). Safe bilirubin levels in very low birth weight infants have not been delineated (4–7). Very low birth weight infants have not completed brain growth and development, which places them at greater risk than their term counterparts for neurological sequelae at similar or even lower serum bilirubin levels (8). They are relatively deficient in albumin, which limits the amount of bound bilirubin that can be safely carried in the bloodstream. Because of these factors, it has been suggested that phototherapy be used in a prophylactic manner in infants weighing less than 1500 g at birth (9). In a cohort study, Oh et al (7) noted a direct correlation of peak serum bilirubin level and death, neurodevelopmental impairment and hearing impairment in extremely low birth weight infants, and suggested that a randomized, controlled trial of aggressive versus conservative phototherapy was needed. There are adverse effects of phototherapy which may be significant for extremely low birth weight infants including dehydration, temperature instability, electrolyte imbalance, and more limited access to the infant by both caregivers and parents (10–12). In a randomized, controlled study (13) comparing routine prophylactic phototherapy with the institution of phototherapy when the unconjugated serum bilirubin level exceeded 5 mg/dL (85 μmol/L), no difference was found in mean peak bilirubin levels but a decrease of 28% in hours of phototherapy was noted. The present randomized, controlled trial was conducted to determine whether the initiation of conservative phototherapy when serum bilirubin levels exceeded 150 μmol/L compared with aggressive phototherapy initiated within 12 h of birth in very low birth weight infants would provide an equal reduction in peak bilirubin levels, while decreasing the total number of hours of phototherapy. A secondary objective was to examine the 18-month neurodevelopmental outcome. more...