Diabetes mellitus in pregnancy across Canada.

BACKGROUND: Contemporary estimates of diabetes mellitus (DM) rates in pregnancy are lacking in Canada. Accordingly, this study examined trends in the rates of type 1 (T1DM), type 2 (T2DM) and gestational (GDM) DM in Canada over a 15-year period, and selected adverse pregnancy outcomes. METHODS: This study used repeated cross-sectional data from the Canadian Institute of Health Information (CIHI) hospitalization discharge abstract database (DAD). Maternal delivery records were linked to their respective birth records from 2006 to 2019. The prevalence of T1DM, T2DM and GDM were calculated, including relative changes over time, assessed by a Cochrane-Armitage test. Also assessed were differences between provinces and territories in the prevalence of DM. RESULTS: Over the 15-year study period, comprising 4,320,778 hospital deliveries in Canada, there was a statistically significant increase in the prevalence of GDM and T1DM and T2DM. Compared to pregnancies without DM, all pregnancies with any form of DM had higher rates of hypertension and Caesarian delivery, and also adverse infant outcomes, including major congenital anomalies, preterm birth and large-for-gestational age birthweight. CONCLUSION: Among 4.3 million pregnancies in Canada, there has been a rise in the prevalence of DM. T2DM and GDM are expected to increase further as more overweight women conceive in Canada.

Maternal deaths by suicide and drug overdose in two Canadian provinces; retrospective review.

OBJECTIVE: To identify and review factors associated with maternal deaths by suicide and drug overdose in the Canadian Coroner and Medical Examiners Database (CCMED), from 2017-2019. METHODS: We identified potential maternal deaths in Ontario and British Columbia by searching the CCMED narratives of deaths to females 10 to 60 years old for pregnancy-related terms. Identified narratives were then qualitatively reviewed in quadruplicate to determine if they were maternal deaths by suicide or drug overdose, and to extract information on maternal characteristics, the manner of death, and factors associated with each death. RESULTS: Of the 90 deaths identified in this study, 15 (16.7%) were due to suicide and 20 (22.2%) were due to a drug overdose. These deaths occurred to women of varying ages and across the pregnancy-postpartum period. Among the suicides, 10 were by hanging, and among the overdose-related deaths, 15 had fentanyl detected. Notably, 13 (37.1%) of the 35 deaths to suicide or drug overdose occurred beyond 42 days after pregnancy, 19 (54.3%) followed a miscarriage or induced abortion, and in 23 (65.7%) there was an established history of mental health illness. Substance use disorders were documented in 4 of the 15 suicides (26.7%), and 18 of the 20 overdose-related deaths (90.0%). CONCLUSION: Suicide and drug overdose may contribute more to maternal deaths in Canada than previously realized. Programs are needed to identify women at risk of these outcomes, and to intervene during pregnancy and beyond the conventional postpartum period.

Early neonatal heart rate variability patterns in different subtypes of perinatal hypoxic-ischemic brain injury.

BACKGROUND: This study aims to compare the longitudinal changes in heart rate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury. METHODS: HRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3-5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age. RESULTS: Among 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression (HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p < 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24-30 h in all brain injury subtypes. CONCLUSION: Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy. IMPACT: Our study suggests that suppression of heart rate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury. Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heart rate variability measures. Heart rate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI.

Les tests et le dépistage génétiques chez les enfants.

Les tests génétiques, qui ont évolué rapidement depuis vingt ans, deviennent monnaie courante en pédiatrie. Le présent document de principes procure un aperçu des récents développements qui peuvent avoir des répercussions sur les tests génétiques chez les enfants. La génétique est un domaine en constante évolution, et le présent document de principes s'attarde tout particulièrement au dépistage néonatal élargi, au séquençage de nouvelle génération, aux découvertes fortuites, aux tests commercialisés directement auprès des consommateurs, aux tests d'histocompatibilité et aux tests génétiques dans le contexte de la recherche.

Genetic testing and screening in children.

Genetic testing has progressed rapidly over the past two decades and is becoming common in paediatrics. This statement provides an overview of recent developments that may impact genetic testing in children. Genetics is a rapidly evolving field, and this statement focuses specifically on expanded newborn screening, next generation sequencing (NGS), incidental findings, direct-to-consumer testing, histocompatibility testing, and genetic testing in a research context.

Time trends, geographic variation and risk factors for gastroschisis in Canada: A population-based cohort study 2006-2017.

BACKGROUND: Previous studies showed increases in rates of gastroschisis in Canada in the first decade of the 21st century. OBJECTIVE: We sought to examine the epidemiologic characteristics of gastroschisis in Canada in recent years. METHODS: We conducted a retrospective population-based cohort study of all livebirths and stillbirths delivered in Canada (excluding Quebec) from 2006 to 2017, with information obtained from the Canadian Institute for Health Information. Gastroschisis rates by maternal age, region of residence, and maternal and infant characteristics were quantified using prevalence rate ratios (RR) and 95% confidence intervals (CI). Log-binomial regression was used to quantify the associations between risk factors and gastroschisis. RESULTS: There were 1314 gastroschisis cases among 3 364 116 births. The prevalence rate was 3.7 per 10 000 total births in 2006 and 3.4 per 10 000 total births in 2017, with substantial annual variation in rates. The proportion of mothers aged 20-24 years decreased from 16.5% in 2006 to 11.3% in 2017, while the proportion of mothers aged <20 years halved from 4.8% to 2.3%. The prevalence of gastroschisis at birth remained unchanged among mothers aged <20, 20-24 and 30-49 years but increased among mothers aged 25-29 years. The age-adjusted prevalence rate of gastroschisis increased across the period (for 2016-2017 versus 2006-2007 rate ratio [RR] 1.28, 95% CI 1.05, 1.56), and there was substantial regional variation. Risk factors included problematic use of substances (RR 2.61, 95% CI 2.01, 3.39) and hypothyroidism (RR 2.76, 95% CI 1.56, 4.88). There was a North-to-South difference in gastroschisis prevalence (adjusted RR Far North compared with South 1.54, 95% CI 1.11, 2.15). CONCLUSION: Gastroschisis birth prevalence rates in Canada have stabilised in recent years compared with the increase documented previously. The substantial geographic variation and North-to-South difference in gastroschisis prevalence may indicate variation in socio-economic status, lifestyle and nutritional patterns.

Prenatally diagnosed omphaloceles: Report of 92 cases and association with Beckwith-Wiedemann syndrome.

OBJECTIVE: Describe the prevalence, perinatal and long-term outcomes of Beckwith-Wiedemann syndrome (BWS) among prenatally detected omphaloceles. METHODS: All prenatally diagnosed omphaloceles from 2010 to 2015 within a single tertiary care centre were identified. An echocardiogram and detailed fetal ultrasound were performed, and amniocentesis was offered with karyotype/microarray analysis and BWS molecular testing. Perinatal, neonatal, and long-term outcomes were retrieved for BWS cases. RESULTS: Among 92 omphaloceles, 62 had additional anomalies. Abnormal karyotypes were identified in 23/62 (37%) non-isolated and 2/30 (7%) isolated cases. One BWS case (5%) was identified among non-isolated omphaloceles and six BWS cases (37.5%) were identified among isolated omphaloceles after exclusion of aneuploidy. Among 19 BWS cases, 21% were conceived by ART. All omphaloceles underwent primary closure. Prenatally, macrosomia and polyhydramnios were seen in 42%. Macroglossia and nephromegaly were more commonly detected postnatally. Preterm birth occurred in 10/19 (53%) cases and cesarean deliveries were performed in 7/19 (40%) cases. Overall mortality was 20% (4/19). Embryonal tumors were diagnosed in 2/16 (12.5%) children, and neurodevelopmental outcomes were normal in 9/12 (75%) survivors. CONCLUSIONS: After excluding aneuploidy, BWS was identified in 37.5% and 5% of isolated and non-isolated omphaloceles, respectively. Omphaloceles were small-moderate size with good long-term surgical and neurodevelopmental outcomes when isolated.

Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study.

OBJECTIVES: To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. STUDY DESIGN: Neonates born at full term with encephalopathy were enrolled within 6 hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3 days. Episodes of hypoglycemia (≤50 mg/dL; ≤2.8 mmol/L) and hyperglycemia (>144 mg/dL; >8.0 mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). RESULTS: Forty-five infants (gestational age 39.5 ± 1.4 weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220 minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125 minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P < .001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P < .001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P = .001), after adjusting for hypoxia-ischemia severity. CONCLUSIONS: In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.

Adverse childhood experiences: Basics for the paediatrician.

In 1998, the Centers for Disease Control and Prevention Adverse Childhood Experiences study established the profound effects of early childhood adversity on life course health. The burden of cumulative adversities can affect gene expression, immune system development and condition stress response. A scientific framework provides explanation for numerous childhood and adult health problems and high-risk behaviours that originate in early life. In our review, we discuss adverse childhood experiences, toxic stress, the neurobiological basis and multigenerational and epigenetic transmission of trauma and recognized health implications. Further, we outline building resilience, screening in the clinical setting, primary care interventions, applying trauma-informed care and future directions. We foresee that enhancing knowledge of the far-reaching effects of adverse childhood events will facilitate mitigation of toxic stress, promote child and family resilience and optimize life course health trajectories.

Neonatal oesophageal perforation: The role for non-operative management.

AIM: Isolated oesophageal perforation in neonates is a rare but potentially life-threatening condition. Although management has historically been operative, conservative management (antibiotics, bowel rest, parenteral nutrition) is now more routinely used. The aim of this study was to evaluate the management of this condition in two large neonatal surgical centres. METHODS: A retrospective cohort study was conducted for neonates admitted to The Hospital for Sick Children (Toronto, Canada) or The Royal Children's Hospital (Melbourne, Australia) with a diagnosis of oesophageal perforation, from 2006 to 2016. Patients with oesophageal atresia or tracheo-oesophageal fistula were excluded. Data were collected from chart review regarding demographics, clinical course, management and outcomes. RESULTS: Eleven neonates with oesophageal perforation were identified over a 10-year period at the two centres. Median gestational age at birth was 25.3 weeks (interquartile range 24.2-28.8) and the majority (7/11, 64%) of neonates were extremely low birthweight. Diagnosis was made on day 1 of life for 9 of 11 (81%) neonates and was secondary to nasogastric tube insertion in 10 of 11 (91%) neonates. Only four (36%) neonates had symptomatic complications. All neonates were managed with bowel rest and intravenous antibiotics for a median of 7 days (interquartile range 7-10); two patients required operative intervention. Three neonates (27%) developed chronic lung disease and two (19%) died prior to discharge. CONCLUSIONS: Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming.

OBJECTIVE: This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS: Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. RESULTS: Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. CONCLUSION: Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Early life environment and social determinants of cardiac health in children with congenital heart disease.

Congenital heart disease is a significant cause of infant mortality. Epidemiology and social context play a crucial role in conditioning disease burden and modulating outcomes, while diagnosis and treatment remain resource intensive. This review will address the role of social demographics, environmental exposure, epigenetics and nutrition in the aetiology of congenital heart disease. We then discuss the determinant effect of social factors on the provision and outcomes of care for congenital heart disease and implications for practice. It is our hope that enhanced knowledge of the intersection of social determinants of health and congenital heart disease will facilitate effective preventative strategies at the individual and population levels to optimize heart health outcomes across the life course.

Human exposure to environmental contaminants and congenital anomalies: a critical review.

Congenital anomalies are an important cause of infant mortality and disability. Developmental exposure to environmental contaminants is thought to increase the risk for congenital anomalies. Herein, we describe a critical review of the literature conducted between February and March 2014 yielding 3057 references from which 97 unique relevant articles published from 2003 through 2014 were evaluated. Common congenital anomalies including hypospadias, cryptorchidism, anogenital distance (AGD), congenital heart defects and oral clefts were well represented in the literature whereas other outcomes such as neural tube defects, limb deficiency defects and gastroschisis were rarely described. While definitions used for congenital anomalies and methods of ascertainment were usually consistent across studies, inconsistencies were frequently found in grouping of different congenital heart defects. Despite strong links between some congenital anomalies and parental occupation, these studies are unable to provide clear insight into the specific chemicals responsible owing to lack of direct measures of exposure. In comparison, data are mixed for contaminant exposures at concentrations representative of results from contemporary biomonitoring studies. Of the environmental contaminants studied, the association between phthalate exposures and developmental abnormalities of the male reproductive tract received the greatest attention. Important limitations of the literature studied relate to adequacy of sample size, absence of or weaknesses in exposure assessment methodologies, failure to account for biological plausibility and grouping of congenital anomalies with divergent mechanisms. We conclude that the literature is inadequate at this time to support a conclusion that exposure to environmental contaminants are or are not associated with increased risks for congenital anomalies in the general population.

Changes in the incidence and surgical treatment of ankyloglossia in Canada.

BACKGROUND: Recent reports show increases in rates of ankyloglossia and frenotomy in British Columbia. We carried out a study to determine temporal trends and regional variations in ankyloglossia and frenotomy in Canada. METHODS: The study included all hospital-based live births in Canada (excluding Quebec) between April 2002 and March 2015, with information obtained from the Canadian Institute for Health Information. Information on ankyloglossia and frenotomy was obtained from records of hospital admission for childbirth. Temporal trends and provincial/territorial variations were quantified using rate ratios (RR) and 95% confidence intervals (CI). RESULTS: Ankyloglossia rates increased from 6.86 in 2002 to 22.6 per 1000 live births in 2014 (P for trend < 0.001), while frenotomy rates increased from 3.76 in 2002 to 14.7 per 1000 live births in 2014 (P for trend < 0.001). Frenotomy rates among infants with ankyloglossia increased from 54.7% in 2002 to 63.9% in 2014 (RR: 1.18, 95% CI: 1.13-1.24). Compared with British Columbia, rates of ankyloglossia were over three-fold higher in Saskatchewan (RR: 3.40, 95% CI: 3.16-3.67), Alberta (RR: 3.50, 95% CI: 3.29-3.72) and the Yukon (RR: 3.62, 95% CI: 2.67-4.92), while rates of frenotomy were three- to four-fold higher in the Yukon (RR: 3.41, 95% CI: 2.28-5.10), Alberta (RR: 4.01, 95% CI: 3.71-4.33) and Saskatchewan (RR: 4.12, 95% CI: 3.76-4.52). CONCLUSION: A desire to increase rates of breast feeding initiation and absence of standardized criteria for the diagnosis of ankyloglossia have resulted in runaway rates of frenotomy for newborn infants in some parts of Canada.

Three hundred babies born to underhoused mothers in Toronto-understanding the problem and how we can help.

Little is known about pregnancy in underhoused women, possibly because the number of underhoused mothers with babies in Toronto has been significantly underestimated. Using a novel data collection method, it has been found that there are approximately 300 babies being born each year to underhoused women in Toronto. This finding has significant public health implications, as these women are at increased risk of multiple issues related to physical health, mental health, child protection, poverty and safety. This commentary presents a new data collection strategy, highlights the importance of accurate data collection and offers suggestions for supports for this over-looked population.

Associations of Perinatal Clinical and Magnetic Resonance Imaging Measures with Developmental Outcomes in Children Born Very Preterm.

OBJECTIVE: To identify perinatal risk factors associated with long-term neurocognitive and behavioral impairments in children born very preterm using a multivariate, partial least squares approach. STUDY DESIGN: Twenty-seven perinatal clinical and magnetic resonance imaging measures were collected at birth and during the neonatal intensive care stay for 105 neonates born very preterm (≤ 32 weeks gestational age). One-half of the children returned for neuropsychological assessments at 2 and 4 years of age. Parent-reported behavioral measures were also obtained at 4 years of age. Three partial least squares analyses were performed to determine associations between clinical and radiologic measures with cognitive outcomes at 2 and 4 years of age, as well as with behavioral measures at 4 years of age. RESULTS: Within the first components of each analysis, only intrauterine growth restriction, male sex, and absence of antenatal corticosteroid use were associated with poorer cognitive and language ability at 2 and 4 years of age, accounting for 79.6% and 71.4% of the total variance, respectively. In addition, white matter injury at term-equivalent age contributed to more problematic internalizing behaviors, behavioral symptoms, and impaired executive function at 4 years of age, accounting for 67.9% of the total variance. CONCLUSIONS: Using this data-driven multivariate approach, specific measures in prenatal and early postnatal life are shown to be selectively and significantly associated with cognitive and behavioral outcomes in children born very preterm. Early detection of risk factors can help inform prognoses of children at greatest risk of long-term impairments.

Low birthweight, gestational age, need for surgical intervention and gram-negative bacteraemia predict intestinal failure following necrotising enterocolitis.

AIM: Necrotising enterocolitis (NEC) is associated with high morbidity and mortality. The aim of this study was to identify predictors of intestinal failure (IF), morbidity and mortality following NEC. METHODS: We performed a retrospective study of all neonates treated for NEC stage II or greater at a tertiary referral NICU between 2000 and 2009. Demographic data, need for surgery, residual bowel length and rates of bacteraemia, cholestasis, IF and mortality were analysed. RESULTS: During the 10-year period, 301 patients were referred with NEC and 152 had surgical intervention. Overall mortality was 32%. Of the 230 infants who survived >42 days, 97 (42%) had IF at 42 days, decreasing to 15% at >90 days. The rate of IF was significantly higher in the surgical group than the medical group (OR 2.04, 95% CI, 1.25-3.35, p < 0.004), but 23% of the medically treated infants with NEC also developed IF. There was a significant relationship between IF and gram-negative bacteraemia, the need for surgery, cholestasis, liver failure and mortality. CONCLUSION: Intestinal failure occurred in a significant proportion of infants with NEC. Predictors for IF among infants with NEC were low birthweight, low gestational age, need for surgical intervention and gram-negative bacteraemia.

Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.

OBJECTIVE: To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the proper use and dosage of folic acid/multivitamin supplementation before and during pregnancy. EVIDENCE: Published literature was retrieved through searches of PubMed, Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary and key words (e.g., folic acid, prenatal multivitamins, folate sensitive birth defects, congenital anomaly risk reduction, pre-conception counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1985 and June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Costs, risks, and benefits: The financial costs are those of daily vitamin supplementation and eating a healthy folate-enriched diet. The risks are of a reported association of dietary folic acid supplementation with fetal epigenetic modifications and with an increased likelihood of a twin pregnancy. These associations may require consideration before initiating folic acid supplementation. The benefit of folic acid oral supplementation or dietary folate intake combined with a multivitamin/micronutrient supplement is an associated decrease in neural tube defects and perhaps in other specific birth defects and obstetrical complications. VALUES: The quality of evidence in the document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Summary Statement In Canada multivitamin tablets with folic acid are usually available in 3 formats: regular over-the-counter multivitamins with 0.4 to 0.6 mg folic acid, prenatal over-the-counter multivitamins with 1.0 mg folic acid, and prescription multivitamins with 5.0 mg folic acid. (III) Recommendations 1. Women should be advised to maintain a healthy folate-rich diet; however, folic acid/multivitamin supplementation is needed to achieve the red blood cell folate levels associated with maximal protection against neural tube defect. (III-A) 2. All women in the reproductive age group (12-45 years of age) who have preserved fertility (a pregnancy is possible) should be advised about the benefits of folic acid in a multivitamin supplementation during medical wellness visits (birth control renewal, Pap testing, yearly gynaecological examination) whether or not a pregnancy is contemplated. Because so many pregnancies are unplanned, this applies to all women who may become pregnant. (III-A) 3. Folic acid supplementation is unlikely to mask vitamin B12 deficiency (pernicious anemia). Investigations (examination or laboratory) are not required prior to initiating folic acid supplementation for women with a risk for primary or recurrent neural tube or other folic acid-sensitive congenital anomalies who are considering a pregnancy. It is recommended that folic acid be taken in a multivitamin including 2.6 ug/day of vitamin B12 to mitigate even theoretical concerns. (II-2A) 4. Women at HIGH RISK, for whom a folic acid dose greater than 1 mg is indicated, taking a multivitamin tablet containing folic acid, should be advised to follow the product label and not to take more than 1 daily dose of the multivitamin supplement. Additional tablets containing only folic acid should be taken to achieve the desired dose. (II-2A) 5. Women with a LOW RISK for a neural tube defect or other folic acid-sensitive congenital anomaly and a male partner with low risk require a diet of folate-rich foods and a daily oral multivitamin supplement containing 0.4 mg folic acid for at least 2 to 3 months before conception, throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues. (II-2A) 6. Women with a MODERATE RISK for a neural tube defect or other folic acid-sensitive congenital anomaly or a male partner with moderate risk require a diet of folate-rich foods and daily oral supplementation with a multivitamin containing 1.0 mg folic acid, beginning at least 3 months before conception. Women should continue this regime until 12 weeks' gestational age. (1-A) From 12 weeks' gestational age, continuing through the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (II-2A) 7. Women with an increased or HIGH RISK for a neural tube defect, a male partner with a personal history of neural tube defect, or history of a previous neural tube defect pregnancy in either partner require a diet of folate-rich foods and a daily oral supplement with 4.0 mg folic acid for at least 3 months before conception and until 12 weeks' gestational age. From 12 weeks' gestational age, continuing throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (I-A). The same dietary and supplementation regime should be followed if either partner has had a previous pregnancy with a neural tube defect. (II-2A).

Objectif : Offrir des renseignements à jour sur l'utilisation pré et postconceptionnelle d'acide folique par voie orale, avec ou sans supplément de multivitamines / micronutriments, aux fins de la prévention des anomalies du tube neural et d'autres anomalies congénitales. Ces renseignements aideront les médecins, les sages-femmes, les infirmières et les autres professionnels de la santé à contribuer aux efforts de sensibilisation des femmes quant à l'utilisation et aux posologies adéquates de la supplémentation en acide folique / multivitamines, avant et pendant la grossesse. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed, Medline, CINAHL et la Cochrane Library en janvier 2011 au moyen d'un vocabulaire contrôlé et de mots clés appropriés (p. ex. « folic acid ¼, « prenatal multivitamins ¼, « folate sensitive birth defects ¼, « congenital anomaly risk reduction ¼, « pre-conception counselling ¼). Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre 1985 et juin 2014. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2014. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques, et auprès de sociétés de spécialité médicale nationales et internationales. Coûts, risques et avantages : Les coûts financiers sont ceux de la supplémentation quotidienne en vitamines et de la consommation d'un régime alimentaire santé enrichi en folate. Les risques sont ceux qui sont liés à une association signalée entre la supplémentation alimentaire en acide folique et des modifications épigénétiques fœtales / la probabilité accrue d'obtenir une grossesse gémellaire. Ces associations pourraient devoir être prises en considération avant la mise en œuvre d'une supplémentation en acide folique. La supplémentation en acide folique par voie orale (ou l'apport alimentaire en folate combiné à un supplément de multivitamines / micronutriments) a pour avantage de mener à une baisse connexe du taux d'anomalies du tube neural et peut-être même des taux d'autres complications obstétricales et anomalies congénitales particulières. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Déclaration sommaire 1. Au Canada, les comprimés de multivitamines comptant de l'acide folique sont habituellement offerts en 3 formats : multivitamines régulières en vente libre comptant de 0,4 à 0,6 mg d'acide folique, multivitamines prénatales en vente libre comptant 1,0 mg d'acide folique et multivitamines d'ordonnance comptant 5,0 mg d'acide folique. (III) Recommandations 1. Les femmes devraient se voir conseiller de maintenir un régime alimentaire santé riche en folate; la mise en œuvre d'une supplémentation en acide folique / multivitamines s'avère cependant requise pour leur assurer l'obtention des taux érythrocytaires de folate qui sont associés à l'octroi d'une protection maximale contre les anomalies du tube neural. (III-A) 2. Toutes les femmes en âge de procréer (12-45 ans) qui sont toujours fertiles (la grossesse demeure possible) devraient se voir offrir, dans le cadre de leurs consultations gynécologiques de dépistage (renouvellement de la contraception, test de Pap, examen gynécologique annuel), des services de counseling au sujet des avantages de l'acide folique administré sous forme d'une supplémentation multivitaminique, et ce, qu'elles envisagent ou non de connaître une grossesse. Puisqu'un si grand nombre de grossesses se manifestent de façon inattendue, cette recommandation s'applique à toutes les femmes qui pourraient devenir enceintes. (III-A) 3. La supplémentation en acide folique est peu susceptible de masquer la carence en vitamine B12 (anémie pernicieuse). La tenue d'explorations (examen ou épreuves de laboratoire) n'est pas requise avant la mise en œuvre d'une supplémentation en acide folique chez les femmes exposées à des risques d'anomalies du tube neural (ou d'autres anomalies congénitales sensibles à l'acide folique) primaires ou récurrentes qui envisagent une grossesse. Il est recommandé que l'acide folique soit administré sous forme de multivitamines comptant également 2,6 µg/jour de vitamine B12, de façon à atténuer toutes les préoccupations (même celles qui sont théoriques). (II-2A) 4. Les femmes exposées à des RISQUES ÉLEVÉS (pour lesquelles une dose d'acide folique supérieure à 1 mg s'avère indiquée) qui prennent des multivitamines contenant de l'acide folique devraient être avisées de respecter les consignes d'utilisation du produit en question et de ne pas prendre plus d'une dose quotidienne de supplément multivitaminique; ces femmes devraient plutôt prendre des comprimés additionnels ne contenant que de l'acide folique pour obtenir la dose requise. (II-2A) 5. Pendant au moins les deux à trois mois précédant la conception, tout au long de la grossesse et pendant de quatre à six semaines à la suite de l'accouchement (ou tant et aussi longtemps que se poursuit l'allaitement), les femmes qui sont exposées à un FAIBLE RISQUE d'anomalie du tube neural ou d'autres anomalies congénitales sensibles à l'acide folique et qui comptent un partenaire masculin également exposé à un faible risque doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément multivitaminique oral quotidien contenant 0,4 mg d'acide folique. (II-2A) 6. À partir d'au moins trois mois avant la conception, les femmes qui sont exposées à un RISQUE MODÉRÉ d'anomalie du tube neural ou d'autres anomalies congénitales sensibles à l'acide folique et qui comptent un partenaire masculin également exposé à un risque modéré doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément multivitaminique oral quotidien contenant 1 mg d'acide folique. Ces femmes devraient poursuivre l'utilisation de cette posologie jusqu'à l'atteinte d'un âge gestationnel de 12 semaines. (1-A) À partir de 12 semaines d'âge gestationnel, tout au long du reste de la grossesse et pendant de quatre à six semaines postpartum (ou tant et aussi longtemps que se poursuit l'allaitement), la supplémentation quotidienne utilisée devrait être composée d'une multivitamine contenant de 0,4 à 1,0 mg d'acide folique. (II-2A) 7. Pendant au moins trois mois avant la conception et jusqu'à l'atteinte d'un âge gestationnel de 12 semaines, les femmes qui sont exposées à un RISQUE ÉLEVÉ ou accru d'anomalie du tube neural et qui comptent un partenaire masculin présentant des antécédents personnels d'anomalie du tube neural (ou encore en présence d'antécédents personnels ou familiaux de grossesse affectée par une anomalie du tube neural chez l'un ou l'autre des partenaires) doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément oral quotidien de 4 mg d'acide folique. À partir de 12 semaines d'âge gestationnel, tout au long du reste de la grossesse et pendant de quatre à six semaines postpartum (ou tant et aussi longtemps que se poursuit l'allaitement), la supplémentation quotidienne utilisée devrait être composée d'une multivitamine contenant de 0,4 à 1,0 mg d'acide folique. (I-A) Le même régime alimentaire et de supplémentation devrait être respecté en présence d'antécédents personnels ou familiaux de grossesse affectée par une anomalie du tube neural chez l'un ou l'autre des partenaires. (II-2A).

Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants.

BACKGROUND: Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. METHODS: Spectroscopy data were obtained from 99 very preterm infants (born ≤32 wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LCModel. Multiple regression was used to examine the association of metabolite ratios with focal noncystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. RESULTS: Within 2 wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5 min after birth. CONCLUSION: Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures.

A prospective comparison of intestinal sonography and abdominal radiographs in a neonatal intensive care unit.

BACKGROUND: No study reported in the literature comprehensively compares findings on neonatal abdominal radiographs with sonography. OBJECTIVE: To compare the findings on abdominal radiographs and sonograms in infants in intensive care, to better understand how the various intestinal gas patterns on radiographs relate to the spectrum of appearances on sonography and, second, to evaluate the ability of sonography to differentiate necrotizing enterocolitis from other intestinal pathology. MATERIALS AND METHODS: We prospectively evaluated sonograms and radiographs, blinded to the other modality and to clinical information. Patients' charts were reviewed by a third blinded reader and used as a reference standard for diagnosis. We made associations between sonographic findings, radiographic intestinal gas patterns and clinical diagnoses. RESULTS: We included 75 infants with gestational ages between 23 weeks and 41 weeks. Sonographic abnormalities were present in infants with all radiographic intestinal gas patterns, including normal patterns. We only saw absent intestinal perfusion and fluid collections on sonography (suggesting intestinal necrosis and sealed perforation) in infants with intestinal dilatation with elongation on radiographs. Separation of intestinal loops on radiographs was most commonly caused by reasons other than intestinal wall thickening. Increased intestinal echogenicity or free fluid with echoes on sonography correlated with a diagnosis of necrotizing enterocolitis, whereas anechoic free fluid correlated with absence of necrotizing enterocolitis. CONCLUSION: Sonography is complementary to radiographs in infants with suspected intestinal pathology, with a spectrum of appearances seen on each modality. Some sonographic findings either strongly suggest necrotizing enterocolitis or supply evidence against this diagnosis.