Teachers reported that children with special health care needs displayed more attention problems.

AIM: Children with special health care needs (SHCN) perform more poorly at school compared to their classmates. Specific causal pathways have not yet been extensively studied. Therefore, we investigated teacher-rated global attention, an important prerequisite for educational attainment, in children with SHCN. METHODS: Data of a population-based prospective cohort study, which recruited preschool children from the Mainz-Bingen area, Germany, were analysed. Children with SHCN were identified by the Children with Special Health Care Needs screening tool. In 2016, global attention was reported by teachers at the end of first grade (mean age: 7.3 years) on a 5-point rating scale ranging from -2 through +2. Associations between SHCN consequences and teacher-rated attention were estimated by linear mixed models, adjusted for confounding variables. RESULTS: We included 1921 children (51% males); of these, 14% had SHCN. Compared to their classmates, children with SHCN had poorer teacher-rated attention scores (adjusted mean difference: -0.35, 95% CI: -0.52 to -0.17). The effect was strongest among children with treatment or counselling for mental health problems or functional limitations. The effect remained after excluding children with attention deficit hyperactivity disorder from the analysis. CONCLUSION: Children with SHCN showed more teacher-rated attention problems, which could explain their lower educational attainment.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences.

ImportanceProphylactic cyclo-oxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks' gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Our objective was to develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants. The Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including 5 experienced neonatal care providers, 2 methods experts, 1 pharmacist, 2 parents of former extremely preterm infants and 2 adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants (conditional recommendation, moderate certainty in estimate of effects). Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group (conditional recommendation, low certainty in the estimate of effects). The panel strongly recommended against use of prophylactic acetaminophen (strong recommendation, very low certainty in estimate of effects) until further research evidence is available.

Building a better model: abandon kitchen sink regression.

This paper critically examines 'kitchen sink regression', a practice characterised by the manual or automated selection of variables for a multivariable regression model based on p values or model-based information criteria. We highlight the pitfalls of this method, using examples from perinatal/neonatal medicine, and propose more robust alternatives. The concept of directed acyclic graphs (DAGs) is introduced as a tool for describing and analysing causal relationships. We highlight five key issues with 'kitchen sink regression': (1) the disregard for the directionality of variable relationships, (2) the lack of a meaningful causal interpretation of effect estimates from these models, (3) the inflated alpha error rate due to multiple testing, (4) the risk of overfitting and model instability and (5) the disregard for content expertise in model building. We advocate for the use of DAGs to guide variable selection for models that aim to examine associations between a putative risk factor and an outcome and emphasise the need for a more thoughtful and informed use of regression models in medical research.

School absenteeism in children with special health care needs. Results from the prospective cohort study ikidS.

OBJECTIVE: Children with special health care needs (SHCN) due to a chronic health condition perform more poorly at school compared to their classmates. There is still little knowledge on the causal pathways and which factors could be targeted by interventions. We, therefore, investigated school absenteeism in children with SHCN compared to their peers. METHODS: This study was based on data from the German population-based prospective cohort study ikidS (German for: I will start school). Children with SHCN were identified by the Children with Special Health Care Needs screener that captures five consequences of physical or mental chronic health conditions: (1) use or need of prescription medication, (2) above average use or need of medical, mental health, or educational services, (3) functional limitations compared with others of the same age, (4) use or need of specialized therapies, and (5) treatment or counseling for emotional, behavioral, or developmental problems. School absenteeism was defined as days absent from school due to illness during first grade and was reported by classroom teachers. Associations between SHCN consequences and school absenteeism were investigated by negative binomial regression models. Effect estimates were adjusted for confounding variables identified by a causal framework and directed acyclic graphs. RESULTS: 1,921 children (mean age at follow-up 7.3 years, standard deviation 0.3; 49% females) were included; of these, 14% had SHCN. Compared to their classmates, children with SHCN had more days absent (adjusted rate ratio: 1.37; 95% confidence interval 1.16, 1.62). The effect was strongest among children with i) functional limitations, ii) treatment or counseling for emotional, behavioral, or developmental problems, and iii) those who experienced two or more SHCN consequences. CONCLUSIONS: Children with SHCN have higher school absenteeism, which could-at least partly-explain their poorer school performance and lower educational attainment. SHCN-specific targeted interventions may reduce the adverse effects of SHCN on educational outcomes in children.

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.

Risk factors for mechanical complications of peripherally inserted central catheters in children.

OBJECTIVE: To determine risk factors for mechanical (noninfectious) complications in peripherally inserted central catheters (PICCs) in children. DESIGN: Retrospective cohort study. SETTING: Pediatric tertiary-care center in Nova Scotia, Canada. PATIENTS: Pediatric patients with a first PICC insertion. METHODS: All PICCs inserted between January 2001 until 2016 were included. Age-stratified (neonates vs non-neonates) Fine-Grey competing risk proportional hazard models were used to model the association between each putative risk factor and the time to mechanical complication or removal of the PICC for reasons not related to a mechanical complication. Models were adjusted for confounding variables identified through directed acyclic graphs. RESULTS: Of 3,205 patients with PICCs, 706 had mechanical complications (22% or 14 events/1000 device days). For both neonates and older children, disease group, lumen count, and prior leak were all associated with mechanical complications in the adjusted proportional hazards model. Access vein and prior infection were also associated with mechanical complications for neonates, and age group was associated with mechanical complications among non-neonates. CONCLUSIONS: We have identified several risk factors for mechanical complications in patients with PICCs that will help improve best practices for PICC insertion and care.

Health Care Utilization in the First 7 Years in Children with Fetal Growth Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: To investigate the relationship between birth weight for gestational age and health care utilization of term offspring from birth to 7 years. STUDY DESIGN: We used a population-based retrospective cohort study of infants (≥37 weeks' gestational age) born between 2003 and 2007 in the Canadian province of Nova Scotia (n = 42 050). Perinatal records were linked to provincial administrative health data from birth to age 7 years. The primary outcome was health care utilization (physician visits and hospital admissions) and costs. Birth weight was categorized as small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA), or large for gestational age (LGA, >90th percentile). Regression models adjusted for potential confounders were used to investigate the associations. RESULTS: Children born SGA had a higher number of specialist visits and hospital admissions, a longer length of stay for the birth admission, and, as a result, higher physician and hospital costs amounting to a cost differential of Can $1222 during the first 7 years of life compared with children born AGA. By contrast, health care use and costs did not differ between children born LGA and AGA. CONCLUSION: Former SGA term infants have a moderate increase in health care use and costs in early childhood compared with former AGA infants, and LGA birth at term is not associated with higher health care utilization.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis.

BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX-I) may prevent PDA-related complications. Controversy exists on which COX-I drug is the most effective and has the best safety profile in preterm infants. OBJECTIVES: To compare the effectiveness and safety of prophylactic COX-I drugs and 'no COXI prophylaxis' in preterm infants using a Bayesian network meta-analysis (NMA). SEARCH METHODS: Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP). MAIN RESULTS: We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random-effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1-3; high-certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1-3; moderate-certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1-3; low-certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1-4; low-certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1-3; high-certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1-3; very low-certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1-4; very low-certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1-4; very low-certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1-3; very low-certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically-significant differences were observed between the COX-I drugs for any of the relevant outcomes. AUTHORS' CONCLUSIONS: Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate-certainty), may result in a small increase in CLD (low-certainty) and results in trivial differences in NEC (high-certainty), gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction in mortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically-relevant outcomes.

Maternal cannabis use during pregnancy and maternal and neonatal outcomes: A retrospective cohort study.

OBJECTIVE: To examine the relationship between reported prenatal cannabis use and neonatal and maternal outcomes and whether the legalisation of cannabis in Canada affected the rates of reported use or the association with maternal and neonatal outcomes. DESIGN: Population-based retrospective cohort study. SETTING: Routinely collected data in a real-world setting. POPULATION: All women in the Canadian province of Nova Scotia with singleton births between 1 January 2004 and 30 June 2021. METHODS: The association between cannabis use and maternal and neonatal outcomes was examined using generalised linear models with inverse probability weighting. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes in the peripartum and postpartum period. RESULTS: Rates of reported cannabis use in pregnancy increased from 1.3% to 7.5% over the study period with no appreciable change in slope after legalisation in 2018. Infants of mothers reporting cannabis use in pregnancy were more likely to have major anomalies and a 5-minute Apgar score ≤7, require neonatal intensive care unit admission, and had lower birthweight, head circumference and birth length than infants of mothers not reporting cannabis use. These associations did not differ before and after legalisation. CONCLUSIONS: Reported cannabis use during pregnancy is associated with early postnatal complications and reduced fetal growth, even after taking into account a range of confounding factors. Rates of reported cannabis use during pregnancy increased over the past 5 years in Nova Scotia with no apparent additional effect of legalisation.

Canadians Reporting Sport-Related Concussions: Increasing and Now Stabilizing.

BACKGROUND: Canada is currently engaged in a national harmonization of strategies to prevent and manage sport-related concussions. OBJECTIVE: To examine the annual incidence rates of reported sport-related concussions or other brain injuries by participants in the Canadian Community Health Survey, a national public health survey which provides nearly 2 decades of serial data using consistent methodology. DESIGN: Serial cross-sectional survey. SETTING: Population-based Canadian survey from 2000 to 2018 that collects data on "concussions or other brain injuries." PARTICIPANTS: Respondents 12 years and older. INDEPENDENT VARIABLES: Sex and age categorized 12 to 14 years, 15 to 19 years, 20 to 29 years, and 30+ years. OUTCOME MEASURES: National incidence rates of participants reporting concussions or other brain injuries occurring within the previous year while engaged in "organized sports/leisure sports or physical exercise." RESULTS: Data were available for 2000/01, 2003, 2005/6, 2009/10, 2013/4, and 2017/8 (N = 757 383). A previously stable annual incidence of reported sport-related concussions or other brain injuries increased nearly 2 and a half-fold from 2005/06 through 2013/14 (P < 0.0001) but seems to have stabilized recently (2013/14 vs 2017/8, P = 0.35). This trend is similar for both men and women but is manifest primarily within youth (12-19 years) as opposed to adults (>19 years). Approximately 1 in 450 Canadians 12 years and older report sport-related concussions or other brain injuries as their most significant injury associated with disability in the previous year (2017-2018: 221 per 100 000 population, 95% confidence interval: 179-264). CONCLUSIONS: In Canada, the annual incidence rates of reported sport-related concussions or other brain injuries is changing and may reflect improved reporting and recognition.

Urinary phthalates and body mass index in preschool children: The MIREC Child Development Plus study.

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass index (BMI) and skinfolds among children between the ages of two and five years. We collected anthropometric measures and biomonitoring data on approximately 200 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study. We measured 22 phthalate metabolites in children's urine and used the 19 metabolites detected in at least 40% of samples. Our primary outcome was BMI z-scores calculated using the World Health Organization growth standards. Skinfold z-scores were secondary outcomes. We used multivariable linear regression to evaluate the association between tertiles of phthalate concentrations and each anthropometric measure. We also used weighted quantile sum regression to identify priority exposures of concern. Our analytic sample included 189 singleton-born children with complete anthropometric data. Children with concentrations of the parent compound di-n-butyl phthalate (∑DnBP) in the third tertile had 0.475 (95% CI: 0.068, 0.883) higher BMI z-scores than those in the lower tertile. ∑DnBP was identified as a priority exposure in the weighted quantile sum regression BMI model. In this population of Canadian preschool aged children, we identified DnBP as a potential chemical of concern in regard to childhood obesity. Future research with serial phthalate measurements and anthropometric measurements in young children will help confirm these findings.

School quality of life: Cross-national comparison of students' perspectives.

BACKGROUND: Cross-national comparisons of students' school quality of life (QoL) can support our understanding of factors that may affect students' health and well-being at school. OBJECTIVE: To compare Canadian and Israeli students' perception of their school QoL. METHODS: The Quality of Life at School Questionnaire (QoLS) was administered to 1231 students in 4th to 6th grades from Canada (n = 629) and Israel (n = 602), measuring: Physical Environment, Positive Attitudes, Student-Teacher Relationship, and Psychosocial. RESULTS: The Canadian students scored significantly higher than the Israeli students on all domains. The two-way ANOVA did not show a statistically significant interaction between country and gender nor age. However, within each country, girls and 4th grade students reported higher overall QoLS. CONCLUSIONS: This study lends support for the universal aspects of perceived QoL at school. This information may serve clinicians and educators in setting goals and developing programs to enhance students' school QOL.

The Association Between Caesarean Section and Inflammatory Bowel Disease in Childhood and Young Adulthood: Findings From 2 Retrospective Cohort Studies.

OBJECTIVE: The aim of the study was to examine the association of Caesarean section (CS) with inflammatory bowel disease (IBD) in Nova Scotian children. METHODS: The study consisted of 2 retrospective cohorts in the Canadian province of Nova Scotia: all births between 1988 and 2014 (n = 262,729) linked with a clinical registry of all children diagnosed with IBD at the IWK Health Centre, Halifax (Clinical Cohort) and all births from 1989 to 1993 (n = 42,999) linked with provincial administrative health data (Administrative Cohort). The primary outcome was a diagnosis of IBD; the outcome in the Administrative Cohort was ascertained using a previously validated algorithm. Information on the exposures and confounding variables was obtained from the Nova Scotia Atlee Perinatal Database. The association between CS and time to diagnosis of IBD was examined using survival analysis. RESULTS: The population incidence of IBD in the Clinical and Administrative Cohort were 13.0 and 20.6, respectively, per 100,000 person-years; 23% and 19% of children were born by CS in the 2 cohorts. There was no association of CS with IBD in the 2 cohorts. CONCLUSIONS: Findings from 2 population-based cohorts in Atlantic Canada did not provide any evidence for an association between CS and IBD in childhood and young adulthood.

Birth by Caesarean section and otitis media in childhood: a retrospective cohort study.

The objective of the present study was to examine the association between birth by Caesarean section (CS) and otitis media (OM) in childhood. We assembled a retrospective cohort of children born between 2003 and 2007 in Nova Scotia and followed them through to 2014. The cohort was derived through a linkage of the Nova Scotia Atlee Perinatal Database with provincial administrative health data. Cox proportional hazards, negative binomial regression and logistic regression were used to examine the association between CS and OM. Among the 36,318 children, 27% were born by CS, and 78% had at least one OM episode (median 2 episodes). Children born by CS were at a slightly higher risk of OM (hazard ratio 1.06, 95% confidence interval (CI) 1.03, 1.09), had more OM episodes in the first 7 years of life (incidence rate ratio 1.04, 95% CI 1.01, 1.07), and were more likely to be above the 95th percentile for OM episodes than children born vaginally (odds ratio 1.10, 95% CI 0.99, 1.23). Our study shows that birth by CS is weakly associated with OM in childhood, but the clinical and public health impact of these findings is small.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

BACKGROUND: The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. OBJECTIVES: This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. POPULATION: The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. DESIGN: Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. METHODS: The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. PRELIMINARY RESULTS: As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. CONCLUSIONS: The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Anti-inflammatory medications for obstructive sleep apnoea in children.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA, with adenotonsillar hypertrophy being the most common underlying risk factor. Surgical removal of enlarged adenoids or tonsils is the currently recommended first-line treatment for OSA due to adenotonsillar hypertrophy. Given the perioperative risk and an estimated recurrence rate of up to 20% following surgery, there has recently been an increased interest in less invasive alternatives to adenotonsillectomy. As the enlarged adenoids and tonsils consist of hypertrophied lymphoid tissue, anti-inflammatory drugs have been proposed as a potential non-surgical treatment option in children with OSA. OBJECTIVES: To assess the efficacy and safety of anti-inflammatory drugs for the treatment of OSA in children. SEARCH METHODS: We identified trials from searches of the Cochrane Airways Group Specialised Register, CENTRAL and MEDLINE (1950 to 2019). For identification of ongoing clinical trials, we searched ClinicalTrials.gov and the World Health Organization (WHO) trials portal. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing anti-inflammatory drugs against placebo in children between one and 16 years with objectively diagnosed OSA (apnoea/hypopnoea index (AHI) ≥ 1 per hour). DATA COLLECTION AND ANALYSIS: Two authors independently performed screening, data extraction, and quality assessment. We separately pooled results for the comparisons 'intranasal steroids' and 'montelukast' against placebo using random-effects models. The primary outcomes for this review were AHI and serious adverse events. Secondary outcomes included the respiratory disturbance index, desaturation index, respiratory arousal index, nadir arterial oxygen saturation, mean arterial oxygen saturation, avoidance of surgical treatment for OSA, clinical symptom score, tonsillar size, and adverse events. MAIN RESULTS: We included five trials with a total of 240 children aged one to 18 years with mild to moderate OSA (AHI 1 to 30 per hour). All trials were performed in specialised sleep medicine clinics at tertiary care centres. Follow-up time ranged from six weeks to four months. Three RCTs (n = 137) compared intranasal steroids against placebo; two RCTs compared oral montelukast against placebo (n = 103). We excluded one trial from the meta-analysis since the patients were not analysed as randomised. We also had concerns about selective reporting in another trial. We are uncertain about the difference in AHI (MD -3.18, 95% CI -8.70 to 2.35) between children receiving intranasal corticosteroids compared to placebo (2 studies, 75 participants; low-certainty evidence). In contrast, children receiving oral montelukast had a lower AHI (MD -3.41, 95% CI -5.36 to -1.45) compared to those in the placebo group (2 studies, 103 participants; moderate-certainty evidence). We are uncertain whether the secondary outcomes are different between children receiving intranasal corticosteroids compared to placebo: desaturation index (MD -2.12, 95% CI -4.27 to 0.04; 2 studies, 75 participants; moderate-certainty evidence), respiratory arousal index (MD -0.71, 95% CI -6.25 to 4.83; 2 studies, 75 participants; low-certainty evidence), and nadir oxygen saturation (MD 0.59%, 95% CI -1.09 to 2.27; 2 studies, 75 participants; moderate-certainty evidence). Children receiving oral montelukast had a lower respiratory arousal index (MD -2.89, 95% CI -4.68 to -1.10; 2 studies, 103 participants; moderate-certainty evidence) and nadir of oxygen saturation (MD 4.07, 95% CI 2.27 to 5.88; 2 studies, 103 participants; high-certainty evidence) compared to those in the placebo group. We are uncertain, however, about the difference in desaturation index (MD -2.50, 95% CI -5.53 to 0.54; 2 studies, 103 participants; low-certainty evidence) between the montelukast and placebo group. Adverse events were assessed and reported in all trials and were rare, of minor nature (e.g. nasal bleeding), and evenly distributed between study groups. No study examined the avoidance of surgical treatment for OSA as an outcome. AUTHORS' CONCLUSIONS: There is insufficient evidence for the efficacy of intranasal corticosteroids for the treatment of OSA in children; they may have short-term beneficial effects on the desaturation index and oxygen saturation in children with mild to moderate OSA but the certainty of the benefit on the primary outcome AHI, as well as the respiratory arousal index, was low due to imprecision of the estimates and heterogeneity between studies. Montelukast has short-term beneficial treatment effects for OSA in otherwise healthy, non-obese, surgically untreated children (moderate certainty for primary outcome and moderate and high certainty, respectively, for two secondary outcomes) by significantly reducing the number of apnoeas, hypopnoeas, and respiratory arousals during sleep. In addition, montelukast was well tolerated in the children studied. The clinical relevance of the observed treatment effects remains unclear, however, because minimal clinically important differences are not yet established for polysomnography-based outcomes in children. Long-term efficacy and safety data on the use of anti-inflammatory medications for the treatment of OSA in childhood are still not available. In addition, patient-centred outcomes like concentration ability, vigilance, or school performance have not been investigated yet. There are currently no RCTs on the use of other kinds of anti-inflammatory medications for the treatment of OSA in children. Future RCTs should investigate sustainability of treatment effects, avoidance of surgical treatment for OSA, and long-term safety of anti-inflammatory medications for the treatment of OSA in children and include patient-centred outcomes.

An examination of sex differences in associations between cord blood adipokines and childhood adiposity.

BACKGROUND: Though the physiological roles of adipokines in metabolism, insulin resistance and satiety are clear, literature regarding associations between cord blood adipokine levels and childhood adiposity is equivocal. OBJECTIVES: To determine whether cord blood levels of leptin and adiponectin are associated with adiposity in children 2 to 5 years of age, and whether such associations are modified by sex. METHODS: Leptin and adiponectin levels were measured in cord blood and anthropometric measures were completed on 550 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study (MIREC-CD Plus). We used multivariable linear and Poisson regression models to determine associations between cord blood adipokine levels and child body mass index (BMI), triceps and subscapular skinfold thickness and risk of overweight/obesity and to assess effect modification by child sex. RESULTS: Cord blood adiponectin was significantly associated with modest increases in BMI and the sum of triceps and subscapular skinfold z-scores in boys but not girls. A doubling of adiponectin levels was associated with a 30% increased risk of overweight/obesity in boys (RR = 1.30; 95% CI: 1.02, 1.64). Leptin was not associated with anthropometric measures in either sex. CONCLUSIONS: The observed associations between adiponectin and adiposity in boys were statistically significant, of moderate magnitude, and underscore the value of considering sex-specific patterns.

Blood metal levels and early childhood anthropometric measures in a cohort of Canadian children.

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 µg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

Cesarean Delivery and Healthcare Utilization and Costs in the Offspring: A Retrospective Cohort Study.

OBJECTIVE: To examine the association between cesarean delivery and healthcare utilization and costs in offspring from birth until age 7 years. STUDY DESIGN: A retrospective cohort study of singleton term births in the Canadian province of Nova Scotia between 2003 and 2007 followed until age 7 years was conducted using data from the Nova Scotia Atlee Perinatal Database and administrative health data. The main exposure was mode of delivery (cesarean delivery vs vaginal birth); the outcome was healthcare utilization and costs during the first 7 years of life. Associations were modeled using multiple regression adjusting for maternal prepregnancy weight and sociodemographic factors. RESULTS: In total, 32 464 births were included in the analysis. Compared with children born by vaginal birth, children born by cesarean delivery had more physician visits (incidence rate ratio 1.06, 95% CI 1.05-1.08) and longer hospital stays (incidence rate ratio 1.12, 95% CI 1.03-1.21) and were more likely to be high utilizers of physician visits (OR 1.23, 95% CI 1.10-1.37). Physician and hospital costs were $775 higher for children born by cesarean delivery compared with vaginal birth. CONCLUSIONS: Cesarean delivery compared with vaginal birth is associated with small but statistically significant increases in healthcare utilization and costs during the first 7 years of life.