The Alberta Neonatal Abstinence Syndrome Mother-Baby Care ImprovEmeNT (NASCENT) program: protocol for a stepped wedge cluster randomized trial of a hospital-level Neonatal Abstinence Syndrome rooming-in intervention.

BACKGROUND: Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model's key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation's impact/outcomes. METHODS: A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation. DISCUSSION: The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.

Unintentional Tobacco Smoke Exposure in Children.

Secondhand smoke (SHS) exposure increases the prevalence and severity of sinopulmonary diseases in children. The primary source of SHS exposure in children is through adults who live in the same house; however, the level of exposure may vary based on the adult smoking habits at home. This prospective cross-sectional study in Alberta, Canada, investigated the relationship between self-reported caregiver smoking, location, outdoor temperature and children's' urine cotinine: creatinine ratio (CCR), a marker of nicotine metabolism. Participants aged 0−9 were recruited from the Child Health Clinics at the Misericordia Community Hospital in Edmonton, Alberta, from 8 January to 24 February 2016 and 30 June to 18 August 2016. Participant CCR levels were compared to caregiver-reported smoking location and environmental factors such as temperature and season. Of the 233 participants who reported smoking status, 21% reported smoking, in keeping with local smoking rates. More participants smoked indoors during the winter than the summer; however, some families limited indoor smoking to a garage. Of the 133 parent−child dyads who provided smoking information and a child urine sample, 18 had an elevated cotinine:creatinine ratio, suggestive of significant tobacco smoke exposure, 15 of whom were from homes that reported smoking. Age < 1 year and number of cigarettes smoked in the home weekly were risks for significant exposure while season, outdoor temperature and smoking location in the home did not reach significance. Smokers should be counseled to protect children, particularly infants, from exposure by limiting the number of cigarettes smoked and isolating smoking to outside the home. Segregated areas such as a garage may provide a useful harm mitigation strategy for indoor smokers, provided the garage does not share ventilation or is not in close proximity to high-traffic areas of the home.

Multimodal Assessment of Systemic Blood Flow in Infants.

The assessment of systemic blood flow is a complex and comprehensive process with clinical, laboratory, and technological components. Despite recent advancements in technology, there is no perfect bedside tool to quantify systemic blood flow in infants that can be used for clinical decision making. Each option has its own merits and limitations, and evidence on the reliability of these physiology-based assessment processes is evolving. This article provides an extensive review of the interpretation and limitations of methods to assess systemic blood flow in infants, highlighting the importance of a comprehensive and multimodal approach in this population.

The impact of identifying laryngeal obstruction syndromes on reducing treatment of pediatric asthma: A systematic review.

Inducible laryngeal obstruction (ILO) in children is underrecognized. This systematic review characterizes the scientific evidence on the impact of pediatric ILO diagnosis and treatment on asthma medication use. This review, registered with PROSPERO (CRD42020209168), utilized database searches in MEDLINE, EMBASE, CINAHL, and Web of Science from inception to October 2020. Both experimental and observational studies on ILO and asthma outcomes in patients ≤18 years were included. Population characteristics (sample size, sex, age, and comorbidities) and study outcomes (medication usage and respiratory symptoms) were extracted. The risk of bias was assessed with the National Toxicology Program's Office of Health Assessment and Risk of Bias Rating Tool. Data are presented narratively due to study heterogeneity. Of 1091 studies, 1076 titles and abstracts were screened after duplicate removal. Screening 31 full texts yielded eight pre-post studies. Patients were an average of 14.1 years old, 15% male, and >90% used asthma medication; 40% reported allergies, 30% gastroesophageal reflux, and 20% anxiety or depression. Most patients received at least one intervention, with 75% showing symptomatic improvement and >75% decreasing or stopping asthma medications. Studies were small with a high risk of selection, confounding, and detection bias. Asthma management was not a primary outcome in any of the studies. Overall, ILO patients were often diagnosed with or treated for asthma before ILO diagnosis. Evidence from individual studies suggests that comorbidities including ILO, gastroesophageal reflux, allergies, and anxiety should be considered in pediatric patients with asthma not responsive to medical therapy. Further research is required to determine the proportion of impacted asthma patients.

Hospital-related, maternal, and fetal risk factors for neonatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy: a retrospective cohort study.

AIM: A previous large US study had documented an increased risk of asphyxia in small volume and rural hospitals. Our objective was to evaluate this in all hospitals in Alberta, a Canadian province. METHODS: Retrospective cohort study of all singleton births ≥ 35-week gestation, in Alberta, from 2002-16 recorded in a perinatal database. Asphyxia was defined as intrapartum stillbirth or neonatal death from asphyxia or Neonatal Intensive Care Unit admission and at least two of the following: a. Apgar score of ≤ 5 at 10 minutes; b. mechanical ventilation or chest compressions for resuscitation within 10 minutes; c. cord pH < 7.00 (venous or arterial), or arterial base excess ≥ 12 at birth. Urban hospitals were defined as those serving a population of ≥ 50 000. Hospital volume was categorized by the following: urban: < 1200, 1200-2399, 2400-3600, > 3600 annual births and Rural: < 50, 50-599, 600-1699 annual births. Data on moderate-severe neonatal hypoxic-ischemic encephalopathy was also obtained from two provincial asphyxia databases for 2010-2016. RESULTS: The overall rate of neonatal asphyxia was 2.28 per 1000 births for the study period and was 2.5/1000 in the urban hospitals and 1.35/1000 in the rural hospitals, OR: 1.86 95% CI (1.58, 2.19). The rate of moderate or severe neonatal hypoxic-ischemic encephalopathy was 0.9/1000 and was not associated with urban hospital birth; OR: 1.12 95%CI (0.82, 1.53) hospital volume was also not associated with asphyxia or moderate or severe neonatal hypoxic-ischemic encephalopathy. CONCLUSIONS: This study observed similar rates of asphyxia and moderate or severe neonatal hypoxic-ischemic encephalopathy for rural and urban hospitals in Alberta and no association with hospital volume.

Early Risk Factors for Retinopathy of Prematurity in Very and Extremely Preterm Chinese Neonates.

Objective: To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in very and extremely preterm (28+0- <32+0, and <28+0 weeks gestation, respectively) neonates, and the predictive factors for ROP in the early hours after birth and during hospitalization. Methods: Using a prospective database supplemented with a retrospective chart review, we identified preterm neonates born at gestation <32 weeks at the University of Hong Kong-Shenzhen Hospital between January 2015 and August 2018. Demographic and clinical variables were studied including indicators of disease acuity in the first 24 h after birth. We also compared the difference in risk factors between survivors with ROP and survivors without ROP. Results: During the study period, there were 529 preterm neonates admitted to our neonatal intensive care unit with 120 (23%) born at <32 weeks' gestation. Thirteen (11%) neonates died. Among the 107 survivors, 23 (21%) had ROP, of whom five (22%) received laser and/or medical therapy for severe ROP. Compared with survivors without ROP, infants with ROP had lower mean blood pressure in the first 12 and 24 h after birth, respectively. Using multivariate regression, gestation age, mean blood pressure in the first 12 h after birth, hospital length of stay, and total days of blood gases pH <7.2 were independent risk factors for ROP. Conclusions: In this small cohort of Chinese neonates born <32+0 weeks' gestation, survivors with ROP had a lower blood pressure in the early hours after birth, younger gestation, longer hospital stay, and duration of acidosis when compared to those without ROP.

Gly184 of the Escherichia coli cAMP receptor protein provides optimal context for both DNA binding and RNA polymerase interaction.

The Escherichia coli cAMP receptor protein (CRP) utilizes the helix-turn-helix motif for DNA binding. The CRP's recognition helix, termed F-helix, includes a stretch of six amino acids (Arg180, Glu181, Thr182, Val183, Gly184, and Arg185) for direct DNA contacts. Arg180, Glu181 and Arg185 are known as important residues for DNA binding and specificity, but little has been studied for the other residues. Here we show that Gly184 is another F-helix residue critical for the transcriptional activation function of CRP. First, glycine was repeatedly selected at CRP position 184 for its unique ability to provide wild type-level transcriptional activation activity. To dissect the glycine requirement, wild type CRP and mutants G184A, G184F, G184S, and G184Y were purified and their in vitro DNA-binding activity was measured. G184A and G184F displayed reduced DNA binding, which may explain their low transcriptional activation activity. However, G184S and G184Y displayed apparently normal DNA affinity. Therefore, an additional factor is needed to account for the diminished transcriptional activation function in G184S and G184Y, and the best explanation is perturbations in their interaction with RNA polymerase. The fact that glycine is the smallest amino acid could not fully warrant its suitability, as shown in this study. We hypothesize that Gly184 fulfills the dual functions of DNA binding and RNA polymerase interaction by conferring conformational flexibility to the F-helix.

Early childhood language outcomes after arterial switch operation: a prospective cohort study.

BACKGROUND: Developmental and language outcomes at 2 years of age of children who had arterial switch operation (ASO) for transposition of the great arteries 2004-2010 are described. METHODS: In this prospective cohort study, 91/98 (93 %) children who underwent ASO were assessed at 2 years of age with the Bayley Scales of Infant & Toddler Development-3rd Edition. Outcomes were compared by patient and perioperative variables using bivariate and multivariate regression analyses to identify predictors of language delay. RESULTS: Infants without ventricular septal defect (VSD) (n = 60) were more likely to be outborn (73 vs 58 %, p = 0.038), require septostomy (80 vs 58 %, p = 0.026), have a shorter cross clamp time (min) (62.7 vs 73.0, p = 0.019), and a lower day 1 post-operative plasma lactate (mmol/L) (3.9 vs 4.8, p = 0.010). There were no differences in cognitive, motor and language outcomes based on presence of a VSD. Language delay (<85) of 29 % was 1.8 times higher than the normative sample; risk factors for this in multivariate analyses included <12 years of maternal education (AOR 19.3, 95 % CI 2.5-148.0) and cross-clamp time ≥70 min (AOR 14.5, 95 % CI 3.1-68.5). Maternal education <12 years was associated with lower Language Composite Scores (-20.2, 95 % CI -32.3 to -9.1). CONCLUSIONS: Outcomes at 2 years of age in children who undergo ASO are comparable to the normative sample with the exception of language. There is a risk of language delay for which maternal education and cross-clamp duration are predictors. These findings suggest that focused post-operative early language interventions could be considered.

Directed evolution of the Escherichia coli cAMP receptor protein at the cAMP pocket.

The Escherichia coli cAMP receptor protein (CRP) requires cAMP binding to undergo a conformational change for DNA binding and transcriptional regulation. Two CRP residues, Thr(127) and Ser(128), are known to play important roles in cAMP binding through hydrogen bonding and in the cAMP-induced conformational change, but the connection between the two is not completely clear. Here, we simultaneously randomized the codons for these two residues and selected CRP mutants displaying high CRP activity in a cAMP-producing E. coli. Many different CRP mutants satisfied the screening condition for high CRP activity, including those that cannot form any hydrogen bonds with the incoming cAMP at the two positions. In vitro DNA-binding analysis confirmed that these selected CRP mutants indeed display high CRP activity in response to cAMP. These results indicate that the hydrogen bonding ability of the Thr(127) and Ser(128) residues is not critical for the cAMP-induced CRP activation. However, the hydrogen bonding ability of Thr(127) and Ser(128) was found to be important in attaining high cAMP affinity. Computational analysis revealed that most natural cAMP-sensing CRP homologs have Thr/Ser, Thr/Thr, or Thr/Asn at positions 127 and 128. All of these pairs are excellent hydrogen bonding partners and they do not elevate CRP activity in the absence of cAMP. Taken together, our analyses suggest that CRP evolved to have hydrogen bonding residues at the cAMP pocket residues 127 and 128 for performing dual functions: preserving high cAMP affinity and keeping CRP inactive in the absence of cAMP.

Secured web-based video repository for multicenter studies.

BACKGROUND: We developed a novel secured web-based dystonia video repository for the Dystonia Coalition, part of the Rare Disease Clinical Research network funded by the Office of Rare Diseases Research and the National Institute of Neurological Disorders and Stroke. A critical component of phenotypic data collection for all projects of the Dystonia Coalition includes a standardized video of each participant. We now describe our method for collecting, serving and securing these videos that is widely applicable to other studies. METHODS: Each recruiting site uploads standardized videos to a centralized secured server for processing to permit website posting. The streaming technology used to view the videos from the website does not allow downloading of video files. With appropriate institutional review board approval and agreement with the hosting institution, users can search and view selected videos on the website using customizable, permissions-based access that maintains security yet facilitates research and quality control. RESULTS: This approach provides a convenient platform for researchers across institutions to evaluate and analyze shared video data. We have applied this methodology for quality control, confirmation of diagnoses, validation of rating scales, and implementation of new research projects. CONCLUSIONS: We believe our system can be a model for similar projects that require access to common video resources.

Child guardianship in a Canadian home visitation program for women who use substances in the perinatal period.

BACKGROUND: Retaining guardianship of one's infant is often a priority for pregnant women who use substances, and may be beneficial to infants when they are safe in their mothers' care. Previous studies from the United States have identified several maternal psychosocial characteristics associated with the ability to keep an infant free from abuse or neglect; however, little is known about the impact of multiple risk factors on guardianship, particularly in Canadian intervention programs. OBJECTIVE: To describe maternal characteristics associated with child guardianship among pregnant women at risk of an alcohol and/or substance exposed pregnancy who attended a Canadian home visitation program. METHODS: Guardianship status at 6 months post-enrolment was extracted from a provincial program's records for all women enrolled between November 1999 and May 2005 (n=64). Bivariate analyses were performed to determine client characteristics most likely to have retained guardianship. RESULTS: At follow-up, 70% of participants were guardians of the index infant. Higher income, more prenatal care, no history of sexual abuse, better alcohol and psychiatric scores, and fewer risk factors on a cumulative risk index were significantly associated with retaining guardianship at 6 month follow-up (p<0.05). CONCLUSIONS: Retaining child guardianship may be the greatest challenge and opportunity for women experiencing problems in multiple domains of their lives, including those associated with substance dependence. Programs targeted at women who use substances while pregnant may best assist mothers to retain guardianship of their infants by supporting clients to address the complex social and health problems often found in conjunction with addictions.

Rural-urban differences in provider practice related to preconception counselling and fetal alcohol spectrum disorders.

OBJECTIVE: Fetal alcohol spectrum disorders (FASDs) are the most common form of nongenetic birth defect in North America with devastating, long-term consequences. Physicians are the primary providers of medical care for pregnant women and they play an important role in the prevention and diagnosis of FASD. We sought to determine whether differences exist between rural and urban health care providers in knowledge of, attitudes about and awareness of FASD and preconception counselling. METHODS: Surveys were mailed to a national, random sample of Canadian health care providers (n = 5361) between October 2001 and May 2002. Bivariate data analysis was completed using SPSS 14.0. RESULTS: Compared with their urban counterparts, rural providers were more likely to report being prepared to access resources related to alcohol use and dependency, yet they were less likely to agree that it was the physician's role to manage these issues (78.4% v. 82.8%, p < 0.05). Rural providers were more likely than urban providers to use a standardized tool to screen patients for alcohol use, to ask all pregnant women if they were drinking, to have cared for a patient with an FASD (56.7% v. 48.8%), to agree that providers do not make a diagnosis because of lack of time and training, and to recognize legal issues and inappropriate behaviour as secondary outcomes of FASD. Rural and urban providers were similar in their diagnostic knowledge of FASD. CONCLUSION: Few differences between rural and urban providers exist with regard to knowledge and diagnosis of FASD; however, rural providers are more prepared to access resources for women with addiction issues and are more likely to care for patients with an FASD.

Triplet infants with birthweight < or = 1250 grams: how well do they compare with twin and singleton infants at 36 to 48 months of age?

The purpose of this study was to determine if triplet infants with birthweight < or = 1250 g were at increased risk of long-term disability compared with similar birthweight and gestational age singletons and twins. This was a retrospective cohort study of < or = 1250-g infants admitted to a regional neonatal intensive care unit from 1986 to 2001 with follow-up to 36 to 48 months corrected gestational age. Outcomes studied were cognitive ability, cerebral palsy, and neurosensory impairment at 36 to 48 months. Enrollment was 1717 infants: 59 triplets, 402 twins, and 1256 singletons. Triplet infants differed from twin or singleton infants because they were more likely to have older, married mothers (relative risk [RR] 3.62, 95% CI 1.31, 5.94), be products of assisted reproductive technology pregnancies (RR 29.59, 95% CI 13.97, 62.68), be exposed to antenatal steroids (RR 1.55, 95% CI 1.38, 1.75), and were all delivered by cesarean section. Triplet infants had lower risk of having intraventricular hemorrhage (RR 0.19, 95% CI 0.05, 0.75). The risk of cerebral palsy, cognitive delay, total major disability, or chronic lung disease was similar in triplet and twin infants compared with singleton infants. The lower risk of having intraventricular hemorrhage in triplet infants may have been due to the use of antenatal corticosteroids and cesarean section delivery.

Pre-conception practices among family physicians and obstetrician-gynaecologists: results from a national survey.

OBJECTIVE: To determine the pre-conception practices among obstetrician-gynaecologists and family physicians in Canada. METHODS: Between October 2001 and May 2002, a survey was mailed to a national random sample of obstetricians and gynaecologists (n = 539) and family physicians (n = 2378) who were current members of the College of Family Physicians of Canada or the Society of Obstetricians and Gynaecologists of Canada. RESULTS: Response rates were 41.7% among obstetrician-gynaecologists and 31.1% among family physicians. More than 85% of physicians frequently discussed birth control and Pap testing with women of childbearing age, but fewer than 60% frequently obtained a detailed history of alcohol use. Fewer than 50% of physicians frequently discussed the following with women of childbearing age: weight management, workplace stress, mental health, addiction history, or the risks of substance use during pregnancy. Fewer than 15% enquired about a history of sexual or emotional abuse. Family physicians were significantly more likely than obstetrician-gynaecologists to discuss mental health (41.1% vs. 28.1%), depression (44.5% vs. 29.0%), and history of alcohol use (59.8% vs. 47.9%) with women of childbearing age (all P < 0.05). Obstetrician-gynaecologists were significantly more likely than family physicians to discuss folic acid (57.8% vs. 47.2%), sexual abuse (18.2% vs. 10.8%), smoking (56.0% vs. 46.1%), and drug use (45.8% vs. 35.9%) (all P < 0.05) with women of childbearing age who were not pregnant. CONCLUSION: There are missed opportunities in pre-conception screening to identify women with suboptimal reproductive health status who are at risk for adverse conception, pregnancy, and birth outcomes. Physician training in identification of women at risk would allow for increased primary and secondary prevention efforts through referral to appropriate treatment and resources.

Variation in health care provider definitions of moderate consumption of alcohol as related to recommendations regarding alcohol consumption during pregnancy: results from a Canadian survey.

Women rely on health care providers for general health care and preconception counseling, including advice on alcohol consumption. Definitions of moderate consumption may differ by individual provider, resulting in inconsistency in advice and lack of clarity for patients both before and during pregnancy. The objective of this study was to determine if health care providers' definition of moderate alcohol consumption was associated with advice to pregnant women regarding alcohol use during pregnancy and to describe health care providers' communication regarding alcohol consumption. Between October 2001 and October 2002, a survey was mailed to a national random sample of 3114 Canadian obstetricians and gynecologists, midwives, and family physicians. The main outcome measure was questionnaire responses regarding knowledge and prevention issues related to alcohol and pregnancy as well as provider characteristics. Response rates ranged from 31.1% among family physicians to 63.5% among midwives. Moderate alcohol consumption among nonpregnant women was defined as 1 to 2 drinks per occasion by about 89% of providers and did not relate to recommendations during pregnancy. Those who recommended abstinence during pregnancy were more likely to define moderation as 4 or more occasions per week as compared with those who did not recommend abstinence (P=0.022). Fewer than 50% of providers frequently defined "moderation" for their patients. More family physicians (90.0%) than obstetricians (83.9%) or midwives (81.1%) recommended alcohol abstinence during pregnancy (overall 87.8%, P=0.005). Thus, there is opportunity for providers to appropriately counsel their patients by advising alcohol abstinence during pregnancy and more frequently defining "moderation" for all clients.

Clinical practice characteristics and preconception counseling strategies of health care providers who recommend alcohol abstinence during pregnancy.

OBJECTIVE: National initiatives on fetal alcohol syndrome in Canada and the United States aimed at prevention, identification, and treatment of individuals who are affected by alcohol exposure in utero recommend that women abstain from consuming alcohol during pregnancy. Health care providers are key educators regarding appropriate alcohol use. The objective of this study was to describe characteristics of physicians who recommend alcohol abstinence during pregnancy with regard to knowledge of fetal alcohol syndrome and preconception counseling strategies. METHODS: A survey was mailed to Canadian physicians and midwives between 2001 and 2002. Participants consisted of a national random sample of 1090 Canadian obstetricians and gynecologists, midwives, and family physicians who were current members of provincial and national professional organizations. The main outcome measure was questionnaire responses to knowledge, prevention, and diagnosis of issues related to alcohol use during pregnancy. RESULTS: Response rates ranged from 31.1% among family physicians to 63.5% among midwives. Overall, 91.2% of providers recommended abstinence from alcohol during pregnancy. These providers were significantly more likely to believe that there is sufficient information about alcohol use and that clients were interested in discussing alcohol (p < 0.05). They were also significantly more likely to discuss depression, personal alcohol use, partner's use of alcohol, and family history of alcohol misuse with women of childbearing age (p < 0.05). Once a patient became pregnant, fewer practice differences were noted, although those who recommended alcohol abstinence were significantly more likely to take clinical action when pregnant patients were consuming moderate amounts of alcohol (p < 0.05). CONCLUSIONS: It is encouraging that almost 90% of Canadian health care providers recommend abstinence from alcohol during pregnancy. However, differences in clinical practice exist between providers who recommend alcohol abstinence during pregnancy as compared with those who recommend a "glass in moderation."