Reginald S. Sauve

Impact of intrauterine growth restriction on neurodevelopmental and growth outcomes in very low birthweight infants

The impact of intrauterine growth restriction (IUGR) in very low birthweight preterm infants weighing ≤ 1250g was determined by comparing longitudinal growth and neurodevelopmental outcome to an adjusted age of 36 months in 52 intrauterine growth restricted children, with 55 birthweight‐matched and 56 gestational age‐matched children. None of these children had chromosomal anomalies, congenital infections, or major congenital malformations. Gestational ages of intrauterine growth restricted, birthweight‐ and gestational age‐matched infants were 30 (± 3), 26 (± 2), 29 (± 2) weeks; birthweights were 842 (± 232), 872 (± 201) and 1094 (± 142) g, respectively. Intrauterine growth restricted children had fewer complications during initial hospitalization (p < 0.05), and had lower weights and head circumferences at follow‐up (p> 0.05). No significant differences were present in major neurodevelopmental disabilities between the intrauterine growth restricted and two comparison groups. Persistence of microcephaly was associated with adverse neurodevelopmental outcome.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants

OBJECTIVE To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight ≤1250 g?

Aim:  To compare the long‐term growth and neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birthweight (BW) ≤ 1250 g) with necrotising enterocolitis (NEC) with BW‐matched controls.

The Incidence of Positional Plagiocephaly: A Cohort Study

OBJECTIVE: The objective of this study was to estimate the incidence of positional plagiocephaly in infants 7 to 12 weeks of age who attend the 2-month well-child clinic in Calgary, Alberta, Canada. METHODS: A prospective cohort design was used to recruit 440 healthy full-term infants (born at ≥37 weeks of gestation) who presented at 2-month well-child clinics for public health nursing services (eg, immunization) in the city of Calgary, Alberta. The study was completed in 4 community health centers (CHCs) from July to September 2010. The CHCs were selected based on their location, each CHC representing 1 quadrant of the city. Argentas (2004) plagiocephaly assessment tool was used to identify the presence or absence of plagiocephaly. RESULTS: Of the 440 infants assessed, 205 were observed to have some form of plagiocephaly. The incidence of plagiocephaly in infants at 7 to 12 weeks of age was estimated to be 46.6%. Of all infants with plagiocephaly, 63.2% were affected on the right side and 78.3% had a mild form. CONCLUSIONS: To our knowledge, this is the first population-based study to investigate the incidence of positional plagiocephaly using 4 community-based data collection sites. Future studies are required to corroborate the findings of our study. Research is required to assess the incidence of plagiocephaly using Argentas plagiocephaly assessment tool across more CHCs and to assess prevalence at different infant age groups. The utility of using Argentas plagiocephaly assessment tool by public health nurses and/or family physicians needs to be established.

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.

Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials☆☆☆★

Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.

Histological chorioamnionitis and bronchopulmonary dysplasia: a retrospective cohort study

Objective:To examine the association between histological chorioamnionitis (HC) with or without fetal inflammatory response (FIR) and bronchopulmonary dysplasia (BPD) in preterm infants.Study Design:We conducted a retrospective cohort study of infants born at <29 weeks gestation admitted to the neonatal intensive care unit from 2000 to 2006, who had placental histology. We compared the incidence of BPD among three groups: No HC group, HC without FIR group and HC with FIR group. The multivariable model based on generalized estimating equation was fitted to estimate the adjusted risk ratios (aRR) and 95% confidence intervals (CIs) for BPD and combined outcome of BPD or death.Result:Of 529 infants, 84 (16%) had HC without FIR, 186 (35%) had HC with FIR and 259 (49%) had no HC. Compared with the no HC group, HC with and without FIR group infants were of lower gestational age and singleton births. Multivariable modeling based on generalized estimating equation revealed that HC with FIR is associated with decreased risk of both BPD (aRR 0.88, 95% CI 0.81 to 0.95) and the combined outcome of BPD or death (aRR 0.91, 95% CI 0.86 to 0.97). HC without FIR showed a trend toward reduction in BPD (aRR 0.93, 95% CI 0.86 to 1.00).Conclusions:HC with FIR is associated with decreased risk of both BPD and the combined outcome of BPD or death in preterm infants.

Bisphenol A exposure and children’s behavior: A systematic review

Bisphenol A (BPA) is an endocrine disrupting chemical used to synthesize polycarbonate plastics and epoxy resins. Previous research suggests that exposure to it can alter children’s behavior. The objective of this study is to conduct a systematic review of the existing literature, examining associations between prenatal and childhood BPA exposure and behavior in children up to 12 years of age. We searched electronic bibliographic databases (MEDLINE, PubMed, EMBASE, PsycINFO, CINAHL, and ERIC), reference lists of included articles, and conference abstracts (American Psychiatric Association, American Academy of Neurology, Pediatric Academic Societies, and International Society of Environmental Epidemiology). We included original studies reporting on the association between prenatal and childhood BPA exposure that measured BPA metabolites in urine and children’s behavioral outcomes. From 2811 citations, 11 articles met our inclusion criteria. Descriptive analyses indicated that prenatal exposure to maternal BPA concentrations were related to higher levels of anxiety, depression, aggression, and hyperactivity in children. BPA exposure in childhood was associated with higher levels of anxiety, depression, hyperactivity, inattention, and conduct problems. Limited observational evidence suggests an association between both prenatal and childhood exposure to BPA and adverse behavioral outcomes in children. Prospective cohort studies are needed to clarify these associations.

Hormonal Contraceptives and Cerebral Venous Thrombosis Risk: A Systematic Review and Meta-Analysis

Objectives: Use of oral contraceptive pills (OCP) increases the risk of cerebral venous sinus thrombosis (CVST). Whether this risk varies by type, duration, and other forms of hormonal contraceptives is largely unknown. This systematic review and meta-analysis update the current state of knowledge. Methods: We performed a search to identify all published studies on the association between hormonal contraceptive use and risk of CVST in women aged 15–50 years. Results: Of 861 studies reviewed, 11 were included. The pooled odds of developing CVST in women aged 15–50 years taking OCPs was 7.59 times higher compared to women not taking OCPs (OR = 7.59, 95% CI 3.82–15.09). Data are insufficient to make conclusions about duration of use and other forms of hormonal contraceptives. Conclusion: Oral contraceptive pills use increases the risk of developing CVST in women of reproductive age. Future studies are required to determine if duration and type of hormonal contraceptives modify this risk.

Outcome at 1-year adjusted age of 957 infants weighing more than 1250 grams with respiratory distress syndrome randomized to receive synthetic surfactant or air placebo

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 (< 1%) for the synthetic surfactant group) at 1-year adjusted age. Bayley Scales of Infant Development (mental development Index: 102 for both the air placebo and synthetic surfactant groups; psychomotor development index: 95 for the air placebo group vs 94 for the synthetic surfactant group) and impairment rates (94 of 475 (20%) for the air placebo group vs 86 of 482 (18%) for the synthetic surfactant group) were similar in the two groups. Infants weighing more than 1250 gm who have respiratory distress syndrome have previously been shown to have improved survival rates and lower neonatal morbidity after treatment with synthetic surfactant. These follow-up data confirm that developmental outcome as determined at 12-months adjusted age is at least as good in those receiving synthetic surfactant.