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Introduction: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. Methods: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. Results: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. Conclusion: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.

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

To assess the association between time of birth and mortality among preterm infants. Population-based study of infants born 22–36 weeks gestation (GA) in Canada from 2010 to 2015 (n = 173 789). Multivariable logistic regression models assessed associations between timing of birth and mortality. Among infants 22–27 weeks GA, evening birth was associated with higher mortality than daytime birth (adjusted odds ratio [AOR] 1.14, 95% CI 1.01–1.29). Among infants 28–32 weeks GA and 33–36 weeks GA, night birth was associated with lower mortality than daytime birth (AOR 0.75, 95% CI 0.59–0.95; AOR 0.78, 95% CI 0.62–0.99, respectively). Sensitivity analysis excluding infants with major congenital anomaly revealed that associations between hour of birth and mortality among infants born 28–32 and 33–36 weeks GA decreased or were not statistically significant. Higher mortality among extremely preterm infants during off-peak hours may suggest variations in available resources based on time of day.

IMPORTANCE: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts. OBJECTIVES: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population. DESIGN, SETTING, AND PARTICIPANTS: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2–affected pregnancies in Canada. This analysis presents exploratory, population-level data from 6 Canadian provinces for the period of March 1, 2020, to October 31, 2021. A total of 6012 pregnant persons with a positive SARS-CoV-2 polymerase chain reaction test result at any time in pregnancy (primarily due to symptomatic presentation) were included and compared with 2 contemporaneous groups including age-matched female individuals with SARS-CoV-2 and unaffected pregnant persons from the pandemic time period. EXPOSURE: SARS-CoV-2 infection during pregnancy. Incident infections in pregnancy were reported to CANCOVID-Preg by participating provinces/territories. MAIN OUTCOMES AND MEASURES: Maternal and perinatal outcomes associated with SARS-CoV-2 infection as well as risk factors for severe disease (ie, disease requiring hospitalization, admission to an intensive care unit/critical care unit, and/or oxygen therapy). RESULTS: Among 6012 pregnant individuals with SARS-CoV-2 in Canada (median age, 31 [IQR, 28-35] years), the greatest proportion of cases were diagnosed at 28 to 37 weeks’ gestation (35.7%). Non-White individuals were disproportionately represented. Being pregnant was associated with a significantly increased risk of SARS-CoV-2–related hospitalization compared with SARS-CoV-2 cases among all women aged 20 to 49 years in the general population of Canada (7.75% vs 2.93%; relative risk, 2.65 [95% CI, 2.41-2.88]) as well as an increased risk of intensive care unit/critical care unit admission (2.01% vs 0.37%; relative risk, 5.46 [95% CI, 4.50-6.53]). Increasing age, preexisting hypertension, and greater gestational age at diagnosis were significantly associated with worse maternal outcomes. The risk of preterm birth was significantly elevated among SARS-CoV-2–affected pregnancies (11.05% vs 6.76%; relative risk, 1.63 [95% CI, 1.52-1.76]), even in cases of milder disease not requiring hospitalization, compared with unaffected pregnancies during the same time period. CONCLUSIONS AND RELEVANCE: In this exploratory surveillance study conducted in Canada from March 2020 to October 2021, SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm birth.

Background and ObjectivesNo evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression.MethodsEnglish-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression.ResultsFive studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4–6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36–3.37; I2= 0). We did not observe any significant difference between NEDA-4 and NEDA-3 in the comparative analyses.DiscussionIn patients with RRMS, NEDA-4 at 1–2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3.

Background and ObjectivesWe conducted a systematic review and meta-analysis to evaluate the relationship between no evidence of disease activity (NEDA) and no long-term disability progression on low- and high-efficacy therapy in relapsing-remitting multiple sclerosis (RRMS).MethodsMEDLINE, Embase, and the Cochrane Database were searched from January 1, 2006, to January 26, 2021. We selected studies that evaluated NEDA-3 (no relapse, new MRI lesion, or confirmed disability progression) at 1 or 2 years and had a minimum of 4 years of follow-up for determination of disability progression. Data were extracted by 2 independent reviewers and were meta-analyzed with a random-effects model. Primary outcome of no disability progression was defined as no confirmed progression on the Expanded Disability Status Scale during follow-up. We assessed the odds ratio (OR) for no disability progression with NEDA vs evidence of disease activity (EDA). Positive predictive value (PPV) of NEDA for no disability progression was summarized for studies with prevalence of no progression >80% vs ≤80% separately.ResultsWe included 29 studies in our qualitative synthesis, of which 27 (16 low efficacy, 11 high efficacy) were included in the meta-analysis (N = 10,935 participants). Median follow-up was 5.6 years (interquartile range 4.3–8.0 years). The pooled ORs for no progression with NEDA-3 vs EDA were 2.32 (95% CI 1.58–3.42; I2 = 73%) for low-efficacy therapy and 3.19 (95% CI 1.86–5.47; I2 = 86%) for high-efficacy therapy. Among studies with prevalence of no progression at follow-up >80%, the pooled PPV for low efficacy therapy was 91% (95% CI 89%–93%) and for high-efficacy therapy was 92% (95% CI 88%–94%). Among studies with prevalence of no progression ≤80%, the pooled PPV for low-efficacy therapy was 81% (95% CI 75%–86%) and for high-efficacy therapy was 86% (95% CI 80%–90%).DiscussionNEDA-3 is associated with no long-term disability progression in RRMS on both low- and high-efficacy therapies. Further studies of early composite outcome measures incorporating easily measurable biomarkers and longer follow-up may help to improve the prognostic value of NEDA-3 in RRMS.Trial Registration InformationInternational Prospective Register of Systematic Reviews Identifier: CRD42020189316.

To examine rates and determinants of home nasogastric (NG)-tube feeding at hospital discharge in a cohort of very preterm infants within the Canadian Neonatal Network (CNN).This was a population-based cohort study of infants born33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2010, and December 31, 2018. We excluded infants who had major congenital anomalies, required gastrostomy-tube, or were discharged to non-CNN facilities. Multivariable logistic regression analysis was used to identify independent determinants of home NG-tube feeding at hospital discharge.Among the 13 232 infants born very preterm during the study period, 333 (2.5%) were discharged home to receive NG-tube feeding. Rates of home NG-tube feeding varied across Canadian NICUs, from 0% to 12%. Determinants of home NG-tube feeding were gestational age (aOR 0.94 per each gestational week increase, 95% CI 0.88-0.99); duration of mechanical ventilation (aOR 1.02 per each day increase, 95% CI 1.01-1.02); high illness severity at birth (aOR 1.32, 95% CI 1.01-1.74); small for gestational age (aOR 2.06, 95% CI 1.52-2.78); male sex (aOR 0.61, 95% CI 0.49-0.77); severe brain injury (aOR 1.60, 95% CI 1.10-2.32); and bronchopulmonary dysplasia (aOR 2.22, 95% CI 1.67-2.94).Rates of home NG-tube feeding varied widely between Canadian NICUs. Higher gestational age and male sex reduced the odds of discharge home to receive NG-tube feeding; and in contrast small for gestational age, severe brain injury, prolonged duration on mechanical ventilation and bronchopulmonary dysplasia increased the odds.

Objective Survivors of extremely preterm birth are at risk of re-hospitalization but risk factors in the Canadian population are unknown. Our objective is to identify neonatal, sociodemographic, and geographic characteristics that predict re-hospitalization in Canadian extremely preterm neonates. Methods This is a retrospective analysis of a prospective observational cohort study that included preterm infants born 22 to 28 weeks’ gestational age from April 1, 2009 to September 30, 2011 and seen at 18 to 24 months corrected gestational age in a Canadian Neonatal Follow-Up Network clinic. Characteristics of infants re-hospitalized versus not re-hospitalized are compared. The potential neonatal, sociodemographic, and geographic factors with significant association in the univariate analysis are included in a multivariate model. Results From a total of 2,275 preterm infants born at 22 to 28 weeks gestation included, 838 (36.8%) were re-hospitalized at least once. There were significant disparities between Canadian provincial regions, ranging from 25.9% to 49.4%. In the multivariate logistic regression analysis, factors associated with an increased risk for re-hospitalization were region of residence, male sex, bronchopulmonary dysplasia, necrotizing enterocolitis, prolonged neonatal intensive care unit (NICU) stay, ethnicity, Indigenous ethnicity, and sibling(s) in the home. Conclusion Various neonatal, sociodemographic, and geographic factors predict re-hospitalization of extremely preterm infants born in Canada. The risk factors of re-hospitalization provide insights to help health care leaders explore potential preventative approaches to improve child health and reduce health care system costs.

OBJECTIVES: To determine the impact of neighbourhood income and maternal residence population density on mortality and various morbidities at discharge or transfer from the NICU among extremely preterm neonates (

Many women have high gestational weight gain (GWG), but potential neonatal consequences are not yet well quantified. We sought to determine the relationship between high GWG and preterm birth (PTB) and low birth weight (LBW) in singleton births.We searched Medline and Embase and reference lists.Two assessors independently performed all steps. We selected studies assessing high total or weekly GWG on PTB (37 weeks) and LBW (2500 grams).Thirty-eight studies, 24 cohort and 14 case-control, were included involving 2 124 907 women. Most contained unadjusted data. Women with high total GWG had a decreased risk overall of PTB37 weeks (relative risk [RR] 0.75; 95% CI 0.60 to 0.96), PTB 32 to 36 weeks (RR 0.70; 95% CI 0.70 to 0.71), and32 weeks (RR 0.87; 95% CI 0.85 to 0.90). High GWG was associated with lower risk of LBW (RR 0.64; 95% CI 0.53 to 0.78). Women with the highest GWG had lower risks of LBW (RR 0.55; 95% CI 0.32 to 0.94) than women with moderately high GWG (RR 0.73; 95% CI 0.60 to 0.89). Women with the highest weekly GWG had greater risks of PTB (RR 1.51; 95% CI 1.47 to 1.55) than women with moderately high weekly GWG (RR 1.09; 95% CI 1.05 to 1.13). Women with high weekly GWG were at increased risk of PTB 32 to 36 weeks (RR 1.14; 95% CI 1.10 to 1.17 and32 weeks (RR 1.81; 95% CI 1.73 to 1.90).Although women with high total GWG have lower unadjusted risks of PTB and LBW, high weekly GWG is associated with increased PTB, and more adjusted studies are needed, as are more studies in obese women. Potential benefits of high GWG for the infant must be balanced against maternal risks and other known infant risks such as high birth weight.

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

The PRISMA-P checklist has been utilized and uploaded as required by the Systematic Reviews author guidelines. (DOC 80Â kb)

STROBE Statement—checklist of items that should be included in reports of observational studies. (DOC 84 kb)

To study the efficacy of early meconium evacuation using per rectal laxatives on the level of serum bilirubin and the need for phototherapy in healthy term infants.Systematic review of randomized controlled trials comparing per rectal laxatives versus no intervention was conducted using English language articles identified from the Cochrane Central Register of Controlled Trials, Medline, Ovid, and CINAHL databases and bibliographies of selected articles. Eligible studies were assessed for the risk of bias in conduct and reporting.A total of three trials (n = 469) mostly with "unclear risk" were eligible for inclusion. Two trials used glycerin suppository whereas one used glycerin enema for meconium evacuation. Meta-analysis was not possible due to clinical heterogeneity in the choice of laxatives and frequency of intervention. In all the three studies, serum bilirubin levels at 48 h and the need for phototherapy was not significantly different between the two groups. Passage of first meconium and the transitional stools occurred significantly early in the intervention group compared to controls.Early evacuation of meconium using per rectal laxatives does not offer any significant clinical advantage for neonatal jaundice.

Identify determinants of neurodevelopmental outcome in preterm children.Prospective national cohort study of children born between 2009 and 2011 at29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III70, severe CP, blind or hearing aided and sNDI or death.Of the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%-51%) had a NDI, 17% (11%-23%) had a sNDI, 6.4% (3.1%-8.6%) had CP, 2.6% (2.5%-13.3%) had hearing aids or cochlear implants and 1.6% (0%-3.1%) had a bilateral visual impairment. Bayley-III composite scores of70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3-4.3, 0.04-3.5 and 0.12-1.96, respectively.Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

The aims of this study were to review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support or ex utero intrapartum treatment and to discuss implications for future management of these complex and rare cases.We have presented a retrospective case series of 12 neonates requiring airway management on placental support at a single tertiary care, academic center.One mother experienced significant blood loss. Operative recovery times were unremarkable. Eight neonates required airway management due to mass obstruction, two for removal of an endotracheal balloon for fetoscopic treatment of congenital diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia. One of our series is an unusual case of management on placental support after vaginal delivery. Another child would have ideally been managed on placental support, but an extremely short umbilical cord prevented this. Even though the airway was secured in all 12 cases, five neonates died in the perinatal period.These procedures have a risk for substantial maternal blood loss. Despite excellent rates of success securing the neonatal airway, children who require management on placental support still have high mortality. A formalized multidisciplinary approach at our institution has enhanced preparedness for these cases.

Objectives To examine variations in the registration of extremely low birthweight and early gestation births and to assess their effect on perinatal and infant mortality rankings of industrialised countries. Design Retrospective population based study. Setting Australia, Canada, European countries, and the United States for 2004; Australia, Canada, and New Zealand for 2007. Population National data on live births and on fetal, neonatal, and infant deaths. Main outcome measures Reported proportions of live births with birth weight/gestational age of less than 500 g, less than 1000 g, less than 24 weeks, and less than 28 weeks; crude rates of fetal, neonatal, and infant mortality; mortality rates calculated after exclusion of births under 500 g, under 1000 g, less than 24 weeks, and less than 28 weeks. Results The proportion of live births under 500 g varied widely from less than 1 per 10 000 live births in Belgium and Ireland to 10.8 per 10 000 live births in Canada and 16.9 in the United States. Neonatal deaths under 500 g, as a proportion of all neonatal deaths, also ranged from less than 1% in countries such as Luxembourg and Malta to 29.6% in Canada and 31.1% in the United States. Rankings of countries based on crude fetal, neonatal, and infant mortality rates differed substantially from rankings based on rates calculated after exclusion of births with a birth weight of less than 1000 g or a gestational age of less than 28 weeks. Conclusions International differences in reported rates of extremely low birthweight and very early gestation births probably reflect variations in registration of births and compromise the validity of international rankings of perinatal and infant mortality.

LUNG LESIONS WITH A SYSTEMIC ARTERIAL SUPPLY GREG RYAN, DICK OEPKES, JACK LANGER, FAWAZ ALKAZALEH, MURRAY ASCH, FRANS KLUMPER, GARETH SEAWARD, RORY WINDRIM, PRAKESH SHAH, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada Leiden University Medical Center, Leiden, The Netherlands Hospital for Sick Children, University of Toronto, Toronto, Ontario OBJECTIVE: To report innovative minimally invasive fetal therapy for massive lung lesions associated with hydrops. STUDY DESIGN: 2 cases, followed prospectively. RESULTS: 2 hydropic fetuses, at 19 and 23 wks, respectively, had massive bronchopulmonary sequestrations occupyingmost of the chest and everting the diaphragm well into the abdomen. A large aortic feeding vessel was identified in each case. Using IV sedation and continuous ultrasound guidance, an 18g needle was placed intra-amniotically, through which a longer 22g needle was advanced into the fetal IHV to sample, paralyze, and anesthetize the fetus. This was then redirected into one of the larger cysts, and microbubble contrast agent (Levovist) was injected to document cyst communication. A 600-micron ND: YAG laser fiber was passed through the 18g needle, and the tip was placed adjacent to the feeding vessel, which was successfully ablated in each case. In the first case at 19 wks, finally a fetal Rocket pleuroamniotic shunt was placed, traversing several cysts. The left-sided mass resolved dramatically in size over the next 3 wks, and hydrops resolved completely. A healthy 3.7-kgmale, requiring no assisted ventilation, was born at 39 wks. The involved lobe was resected the next day; pediatric follow-up is entirely normal. At 23 wks, GA was used for the 2nd right-sided mass and no shunt was placed: 2 wks later, there has been some mass shrinkage; so far, hydrops persists. The pregnancy is ongoing. CONCLUSION: The prognosis for large fetal cystic chest masses associated with hydrops is dismal—all die. This has prompted attempts at treatment by open fetal surgery, with mixed results and a high risk of premature labor. We have demonstrated an excellent outcome by US-guided laser ablation of the systemic arterial supply. This is a preferable, much less invasive approach to such lesions—with far less risk of premature labor. A fetal pleuroamniotic shunt may have a beneficial adjunctive effect.

Consensus definitions of important variables. Definitions of neonatal outcomes with consensus definitions agreed upon by the CNN, ANZNN and SNQ. Table S2: Stratified outcomes between networks. (a): Unadjusted perinatal risks, mortality and major neonatal morbidities among SNQ, ANZNN and CNN infants during 2008–2011 by gestational age groups. (b): Unadjusted perinatal risks, mortality and major neonatal morbidities among SNQ, ANZNN and CNN infants during 2008–2011 by birth weight groups. Table S3: Cross comparison of predictive power of very low birth weight (VLBW) and very low gestational age (VLGA) based models. Table S4: Comparisons of infant and perinatal characteristics and neonatal outcomes among networks (ANZNN, CNN, SNQ) for the 2 extreme components of the very low gestational age cohort and very low birth weight cohort 2008–2011 admissions [25–27, 57–59]. (DOC 174 kb)

Consensus definitions of important variables. Definitions of neonatal outcomes with consensus definitions agreed upon by the CNN, ANZNN and SNQ. Table S2: Stratified outcomes between networks. (a): Unadjusted perinatal risks, mortality and major neonatal morbidities among SNQ, ANZNN and CNN infants during 2008–2011 by gestational age groups. (b): Unadjusted perinatal risks, mortality and major neonatal morbidities among SNQ, ANZNN and CNN infants during 2008–2011 by birth weight groups. Table S3: Cross comparison of predictive power of very low birth weight (VLBW) and very low gestational age (VLGA) based models. Table S4: Comparisons of infant and perinatal characteristics and neonatal outcomes among networks (ANZNN, CNN, SNQ) for the 2 extreme components of the very low gestational age cohort and very low birth weight cohort 2008–2011 admissions [25–27, 57–59]. (DOC 174 kb)