Objective The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy‐related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally. Design Landscape analysis. Setting Global (focus on low‐ and middle‐income countries, LMICs). Sample Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction. Methods A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive. Main Outcomes Measures Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility. Results Of the 444 unique candidates in the database across all five pregnancy‐related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l‐arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high‐potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega‐3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP). Conclusions l‐Arginine, aspirin and vitamin D are promising, high‐potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future.
Background Breastfeeding has many health, economic and environmental benefits for both the infant and pregnant individual. Due to these benefits, the World Health Organization and Health Canada recommend exclusive breastfeeding for the first six months of life. The purpose of this study is to examine the prevalence of exclusive and any breastfeeding in Canada for at least six months, and factors associated with breastfeeding cessation prior to six months. Methods We performed a secondary analysis of breastfeeding-related questions asked on the cross-sectional 2017–2018 Canadian Community Health Survey. Our sample comprised 5,392 females aged 15–55 who had given birth in the five years preceding the survey. Descriptive statistics were carried out to assess the proportion of females exclusively breastfeeding and doing any breastfeeding for at least six months by demographic and behavioural factors. We also assessed, by baby’s age, trends in the introduction of solids and liquids, breastfeeding cessation and the reasons females stopped breastfeeding. Multivariate log binominal regression was used to examine the association between breastfeeding at six months and selected maternal characteristics hypothesized a priori to be associated with breastfeeding behaviour. Results Overall, for at least six months, 35.6% (95% confidence interval (CI): 33.3%-37.8%) of females breastfed exclusively and 62.2% (95% CI: 60.0%-64.4%) did any breastfeeding. The largest decline in exclusive breastfeeding occurred in the first month. Factors most strongly associated with breastfeeding for at least six months were having a bachelor’s or higher degree, having a normal body mass index, being married and daily co-sleeping. Insufficient milk supply was given as the most common reason for breastfeeding cessation irrespective of when females stopped breastfeeding. Conclusion Six-month exclusive breastfeeding rates in Canada remain below targets set by the World Health Assembly. Continued efforts, including investment in monitoring of breastfeeding rates, are needed to promote and support exclusive breastfeeding, especially among females vulnerable to early cessation.
Background Breastfeeding has many health, economic and environmental benefits for both the infant and pregnant individual. Due to these benefits, the World Health Organization and Health Canada recommend exclusive breastfeeding for the first six months of life. The purpose of this study is to examine the prevalence of exclusive and any breastfeeding in Canada for at least six months, and factors associated with breastfeeding cessation prior to six months. Methods We performed a secondary analysis of breastfeeding-related questions asked on the cross-sectional 2017–2018 Canadian Community Health Survey. Our sample comprised 4,845 females aged 15–55 who had given birth in the five years preceding the survey. Descriptive statistics were carried out to assess the proportion of females exclusively breastfeeding and doing any breastfeeding for at least six months by demographic and behavioural factors. We also assessed, by baby’s age, trends in the introduction of solids and liquids, breastfeeding cessation and the reasons females stopped breastfeeding. Multivariate log binominal regression was used to examine the association between breastfeeding at six months and selected maternal characteristics hypothesized a priori to be associated with breastfeeding behaviour. Results Overall, for at least six months, 35.6% (95% confidence interval (CI): 33.3%-37.8%) of females breastfed exclusively and 62.2% (95% CI: 60.0%-64.4%) did any breastfeeding. The largest decline in exclusive breastfeeding occurred in the first month. Factors most strongly associated with breastfeeding for at least six months were having a bachelor’s or higher degree, having a normal body mass index, being married and daily co-sleeping. Insufficient milk supply was given as the most common reason for breastfeeding cessation irrespective of when females stopped breastfeeding. Conclusion Six-month exclusive breastfeeding rates in Canada remain below targets set by the World Health Assembly. Continued efforts, including investment in monitoring of breastfeeding rates, are needed to promote and support exclusive breastfeeding, especially among females vulnerable to early cessation.
Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from April 2020—May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1—13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included technology dependence (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.
Background Acetaminophen is a frequently used analgesic for pain and fever. There have been reports of adverse neurodevelopmental outcomes associated with in utero acetaminophen exposure. However, it is unclear whether this association is related directly to acetaminophen use, or the reasons for use. Objectives To summarise the literature on the association between in utero acetaminophen exposure and child neurodevelopmental outcomes, and assess the extent to which the association is due to confounding by indication. Data Sources OVID for Medline, Embase, and PsycINFO, and EBSCO for CINAHL, from inception to August 18, 2022. Study Selection and Data Extraction We searched for peer‐reviewed, English‐language studies on in utero acetaminophen exposure and child neurodevelopmental outcomes. Data were extracted using a standardised form created a priori, and quality was assessed using the Systematic Assessment of Quality in Observational Research. Synthesis We generated pooled risk ratios (RR) for outcomes examined by ≥3 studies using random‐effects models; outcomes that could not be meta‐analysed were narratively summarised following Synthesis Without Meta‐Analysis guidelines. Results Twenty‐two studies including 23 cohorts were eligible (n = 367,775 total participants; median: 51.7% with acetaminophen exposure). Studies were primarily prospective cohort studies from Europe and the US, with attention deficit/hyperactivity disorder (ADHD) being the most common outcome. Quality assessments resulted in 13.6% of studies being classified as high, 59.1% as medium, 22.7% as low, and 4.5% as very low quality. In utero acetaminophen exposure was associated with an elevated risk of ADHD (unadjusted pooled RR 1.32, 95% confidence interval [CI] 1.20, 1.44; I2 = 47%, n = 7 studies), with little difference after adjusting for confounders, including indications for acetaminophen use (adjusted pooled RR 1.34, 95% CI 1.15, 1.55; I2 = 50%, n = 4 studies). Conclusions Confounding by indication did not explain the association between in utero acetaminophen exposure and child ADHD. Further, high‐quality research is needed on this and other neurodevelopmental outcomes.
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