Neda Razaz

Trends in Optimal, Suboptimal, and Questionably Appropriate Receipt of Antenatal Corticosteroid Prophylaxis

OBJECTIVE: To conduct a population-based study to assess rates of optimal, suboptimal, and questionably appropriate administration of antenatal corticosteroid (betamethasone or dexamethasone) use. METHODS: All live births in Nova Scotia, Canada, from 1988 to 2012 were included in the study. Temporal trends in optimal (proportion of live births at 24–34 weeks of gestation exposed to antenatal corticosteroids between 24 hours and 7 days before delivery), suboptimal (proportion of live births at 24–34 weeks of gestation exposed to antenatal corticosteroids less than 24 hours or more than 7 days before delivery), and questionably appropriate exposure to antenatal corticosteroids (proportion of live births 35 weeks of gestation or greater exposed to antenatal corticosteroids) were quantified using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 246,459 live births between 1988 and 2012, 2.5% received a partial or a full course of antenatal corticosteroids. The rate of antenatal corticosteroid exposure for neonates born between 28 and 32 weeks of gestation increased from 39.5% in 1988–1992 to 79.3% in 2008–2012, whereas exposure for those born at 33–34 weeks of gestation increased from 14.3 to 49.7%. Optimal antenatal corticosteroid receipt increased from 10% in 1988 to 23% in 2012 (OR 2.7, 95% CI 1.6–4.5), suboptimal administration increased from 7 to 34% (OR 6.7, 95% CI 3.9–11.6), and questionably appropriate administration increased from 0.2% in 1988 to 1.7% in 2012 (OR 7.5, 95% CI 4.9–11.3). Of the women who received antenatal corticosteroids in 2012, 52% delivered at 35 weeks of gestation or greater. CONCLUSION: Temporal increases in optimal exposure to antenatal corticosteroids have been matched by increases in suboptimal and questionably appropriate receipt of antenatal corticosteroids, highlighting the need for accurate preterm delivery prognostic models. LEVEL OF EVIDENCE: II

Multiple sclerosis in men: management considerations

Multiple sclerosis (MS) is a lifelong disease typically affecting individuals in young to middle adulthood. There are recognized sex differences in MS onset and clinical course. MS affects approximately three times more women than men, thus resulting in less attention to the male experience (i.e. diagnosis, management, societal dimensions). Here, we review current scientific evidence on sex differences in MS risk and course, highlight potential sources of bias, and suggest avenues of further inquiry. We then describe what is known about male experiences with MS diagnosis, treatment, and symptom management (particularly mood and sexual function). Finally, we consider ways in which healthcare providers might engage male patients in the broader aspects of living with MS (e.g. familial and societal relationships) to influence their long-term quality of life (QOL). When possible, we draw from published sources to underscore our collective clinical and scientific experiences.

Children and adolescents adjustment to parental multiple sclerosis: a systematic review

BackgroundFamilies are the primary source of support and care for most children. In Western societies, 4 to 12% of children live in households where a parent has a chronic illness. Exposure to early-life stressors, including parenting stress, parental depression and parental chronic disease could lead to harmful changes in children’s social, emotional or behavioural functioning. Little is known about the child living with a parent who has Multiple Sclerosis (MS). We systematically reviewed the literature regarding possible effects of having a parent with MS on the child’s or adolescents psychosocial adjustment.MethodsThe following databases: MEDLINE, PsychInfo, CINAHL, EMBASE, Web of Knowledge, ERIC, and ProQuest Digital Dissertations were searched (from 1806 to December 2012). References from relevant articles were also manually searched. Selected studies were evaluated using the Graphic Appraisal Tool for Epidemiology (GATE).ResultsThe search yielded 3133 titles; 70 articles were selected for full text review. Eighteen studies met inclusion criteria. Fourteen studies employed quantitative techniques, of which 13 were cross-sectional and one was longitudinal. Four studies were both qualitative and cross-sectional in design. Only 2 of 18 studies were rated as having high methodological quality. Overall, eight studies reported that children of MS patients exhibited negative psychosocial traits compared with children of “healthy” parents. Specifically for adolescents, greater family responsibilities were linked to lower social relationships and higher distress. Three studies indicated that parental MS was associated with positive adjustment in children and adolescents, such as higher personal competence, while four found no statistically significant differences.ConclusionAlthough having a parent with MS was often reported to have negative psychosocial effects on children and adolescents, there was a lack of consensus and some positive aspects were also found. However, few high quality studies were identified which makes it difficult to draw evidence-based conclusions at this point. There are potentially important, long-term impacts of early life stressors, such as having a parent with a chronic disease, on subsequent life chances and health, and thus more extensive and higher quality research in this area is greatly needed.

Temporal trends in ankyloglossia and frenotomy in British Columbia, Canada, 2004-2013: a population-based study

BACKGROUND Routine surveillance of congenital anomalies has shown recent increases in ankyloglossia (tongue-tie) in British Columbia, Canada. We examined the temporal trends in ankyloglossia and its surgical treatment (frenotomy). METHODS We conducted a population-based cohort study involving all live births in British Columbia from Apr. 1, 2004, to Mar. 31, 2014, with data obtained from the provinces Perinatal Data Registry. Spatiotemporal trends in ankyloglossia and frenotomy, and associations with maternal and infant characteristics, were quantified using logistic regression analysis. RESULTS There were 459 445 live births and 3022 cases of ankyloglossia between 2004 and 2013. The population incidence of ankyloglossia increased by 70% (rate ratio 1.70, 95% confidence interval [CI] 1.44-2.01), from 5.0 per 1000 live births in 2004 to 8.4 per 1000 in 2013. During the same period, the population rate of frenotomy increased by 89% (95% CI 52%-134%), from 2.8 per 1000 live births in 2004 to 5.3 per 1000 in 2013. The 2 regional health authorities with the lowest population rates of frenotomy (1.5 and 1.8 per 1000 live births) had the lowest rates of ankyloglossia and the lowest rates of frenotomy among cases with ankyloglossia, whereas the 2 regional health authorities with the highest population rates of frenotomy (5.2 and 5.3 per 1000 live births) had high rates of ankyloglossia and the highest rates of frenotomy among cases of ankyloglossia. Nulliparity, multiple birth, male infant sex, birth weight and year were independently associated with ankyloglossia. INTERPRETATION Large temporal increases and substantial spatial variations in ankyloglossia and frenotomy rates were observed that may indicate a diagnostic suspicion bias and increasing use of a potentially unnecessary surgical procedure among infants.

Factors Underlying the Temporal Increase in Maternal Mortality in the United States.

OBJECTIVE To identify the factors underlying the recent increase in maternal mortality ratios (maternal deaths per 100,000 live births) in the United States. METHODS We carried out a retrospective study with data on maternal deaths and live births in the United States from 1993 to 2014 obtained from the birth and death files of the Centers for Disease Control and Prevention. Underlying causes of death were examined between 1999 and 2014 using International Classification of Diseases, 10th Revision (ICD-10) codes. Poisson regression was used to estimate maternal mortality rate ratios (RRs) and 95% confidence intervals (CIs) after adjusting for the introduction of a separate pregnancy question and the standard pregnancy checkbox on death certificates and adoption of ICD-10. RESULTS Maternal mortality ratios increased from 7.55 in 1993, to 9.88 in 1999, and to 21.5 per 100,000 live births in 2014 (RR 2014 compared with 1993 2.84, 95% CI 2.49-3.24; RR 2014 compared with 1999 2.17, 95% CI 1.93-2.45). The increase in maternal deaths from 1999 to 2014 was mainly the result of increases in maternal deaths associated with two new ICD-10 codes (O26.8, ie, primarily renal disease; and O99, ie, other maternal diseases classifiable elsewhere); exclusion of such deaths abolished the increase in mortality (RR 1.09, 95% CI 0.94-1.27). Regression adjustment for improvements in surveillance also abolished the temporal increase in maternal mortality ratios (adjusted maternal mortality ratios 7.55 in 1993, 8.00 per 100,000 live births in 2013; adjusted RR 2013 compared with 1993 1.06, 95% CI 0.90-1.25). CONCLUSION Recent increases in maternal mortality ratios in the United States are likely an artifact of improvements in surveillance and highlight past underestimation of maternal death. Complete ascertainment of maternal death in populations remains a challenge even in countries with good systems for civil registration and vital statistics.

Association Between Pregnancy and Perinatal Outcomes Among Women With Epilepsy

Importance To date, few attempts have been made to examine associations between exposure to maternal epilepsy with or without antiepileptic drug (AED) therapy and pregnancy and perinatal outcomes. Objectives To investigate associations between epilepsy in pregnancy and risks of pregnancy and perinatal outcomes as well as whether use of AEDs influenced risks. Design, Setting, and Participants A population-based cohort study was conducted on all singleton births at 22 or more completed gestational weeks in Sweden from 1997 through 2011; of these, 1 424 279 were included in the sample. Information on AED exposure was available in the subset of offspring from July 1, 2005, to December 31, 2011. Data analysis was performed from October 1, 2016, to February 15, 2017. Main Outcomes and Measures Pregnancy, delivery, and perinatal outcomes. Multivariable Poisson log-linear regression was used to estimate adjusted risk ratios (aRRs) and 95% CIs, after adjusting for maternal age, country of origin, educational level, cohabitation with a partner, height, early pregnancy body mass index, smoking, year of delivery, maternal pregestational diabetes, hypertension, and psychiatric disorders. Results Of the 1 429 652 births included in the sample, 5373 births were in 3586 women with epilepsy; mean (SD) age at first delivery of the epilepsy cohort was 30.54 (5.18) years. Compared with pregnancies of women without epilepsy, women with epilepsy were at increased risks of adverse pregnancy and delivery outcomes, including preeclampsia (aRR 1.24; 95% CI, 1.07-1.43), infection (aRR, 1.85; 95% CI, 1.43-2.29), placental abruption (aRR, 1.68; 95% CI, 1.18-2.38), induction (aRR, 1.31; 95% CI, 1.21-1.40), elective cesarean section (aRR, 1.58; 95% CI, 1.45-1.71), and emergency cesarean section (aRR, 1.09; 95% CI, 1.00-1.20). Infants of mothers with epilepsy were at increased risks of stillbirth (aRR, 1.55; 95% CI, 1.05-2.30), having both medically indicated (aRR, 1.24; 95% CI, 1.08-1.43) and spontaneous (aRR, 1.34; 95% CI, 1.20-1.53) preterm birth, being small for gestational age at birth (aRR, 1.25; 95% CI, 1.13-1.30), and having neonatal infections (aRR, 1.42; 95% CI, 1.17-1.73), any congenital malformation (aRR, 1.48; 95% CI, 1.35-1.62), major malformations (aRR, 1.61; 95% CI, 1.43-1.81), asphyxia-related complications (aRR, 1.75; 95% CI, 1.26-2.42), Apgar score of 4 to 6 at 5 minutes (aRR, 1.34; 95% CI, 1.03-1.76), Apgar score of 0 to 3 at 5 minutes (aRR, 2.42; 95% CI, 1.62-3.61), neonatal hypoglycemia (aRR, 1.53; 95% CI, 1.34-1.75), and respiratory distress syndrome (aRR, 1.48; 95% CI, 1.30-1.68) compared with infants of unaffected women. In women with epilepsy, using AEDs during pregnancy did not increase the risks of pregnancy and perinatal complications, except for a higher rate of induction of labor (aRR, 1.30; 95% CI, 1.10-1.55). Conclusions and Relevance Epilepsy during pregnancy is associated with increased risks of adverse pregnancy and perinatal outcomes. However, AED use during pregnancy is generally not associated with adverse outcomes.

Impact of parental multiple sclerosis on early childhood development: A retrospective cohort study

Background: Exposure to parental chronic illness is associated with several adverse developmental outcomes. Objectives: We examined the association between parental multiple sclerosis (MS) and childhood developmental outcomes. Methods: We conducted a population-based retrospective cohort study in Manitoba, Canada, using linked databases. The outcome was childhood development at 5 years of age, expressed as vulnerability (absent vs. present) on the Early Development Instrument (EDI). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: Children with an MS parent (n=153) were similar to children of unaffected parents (n=876) on all EDI domains. However, mental health morbidity was more common among MS parents compared with non-MS parents 49.5% vs. 35.3%. Among MS parents, mental health morbidity was associated with children’s vulnerability on the social competence (OR, 5.73 [95% CI:1.11–29.58]) and emotional maturity (OR, 3.03 [95% CI:1.03–8.94]) domains. The duration of child’s exposure to parental MS was associated with vulnerability on the physical health domain (OR, 1.49 [95%CI:1.03–2.15]). Conclusion: Parental MS was not associated with adverse early childhood developmental outcomes. However, children of parents with mental health morbidity, and those with longer duration of exposure to parental MS, were at higher risk for early childhood developmental vulnerability.

Maternal Body Mass Index in Early Pregnancy and Risk of Epilepsy in Offspring

Importance There is growing concern about the long-term neurologic effects of prenatal exposure to maternal overweight and obesity. The causes of epilepsy are poorly understood and, in more than 60% of the patients, no definitive cause can be determined. Objectives To investigate the association between early pregnancy body mass index (BMI) and the risk of childhood epilepsy and examine associations between obesity-related pregnancy and neonatal complications and risks of childhood epilepsy. Design, Setting, and Participants A population-based cohort study of 1 441 623 live single births at 22 or more completed gestational weeks in Sweden from January 1, 1997, to December 31, 2011, was conducted. The diagnosis of epilepsy as well as obesity-related pregnancy and neonatal complications were based on information from the Sweden Medical Birth Register and National Patient Register. Multivariate Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% CIs after adjusting for maternal age, country of origin, educational level, cohabitation with partner, height, smoking, maternal epilepsy, and year of delivery. Data analysis was conducted from June 1 to December 15, 2016. Main Outcomes and Measures Risk of childhood epilepsy. Results Of the 1 421 551 children born between January 1, 1997, and December 31, 2011, with covariate information available, 7592 (0.5%) were diagnosed with epilepsy through December 31, 2012. Of these 3530 (46.5%) were female. The overall incidence of epilepsy in children aged 28 days to 16 years was 6.79 per 10 000 child-years. Compared with offspring of normal-weight mothers (BMI 18.5 to <25.0), adjusted HRs of epilepsy by maternal BMI categories were as follows: overweight (BMI 25.0 to <30.0), 1.11 (95% CI, 1.04-1.17); obesity grade I (BMI 30.0 to <35.0), 1.20 (95% CI, 1.10-1.31); obesity grade II (BMI 35.0 to <40.0), 1.30 (95% CI, 1.12-1.50); and obesity grade III (BMI≥40.0), 1.82 (95% CI, 1.46-2.26). The rates of epilepsy were considerably increased for children with malformations of the nervous system (adjusted HR, 46.4; 95% CI, 42.2-51.0), hypoxic ischemic encephalopathy (adjusted HR, 23.6; 95% CI, 20.6-27.1), and neonatal convulsions (adjusted HR, 33.5; 95% CI, 30.1-37.4). The rates of epilepsy were doubled among children with neonatal hypoglycemia (adjusted HR, 2.10; 95% CI, 1.90-2.33) and respiratory distress syndrome (adjusted HR, 2.43; 2.21-2.66), and neonatal jaundice was associated with more than a 50% increased risk of epilepsy (adjusted HR, 1.47; 95% CI, 1.33-1.63). The elevated risk of epilepsy in children of overweight or obese mothers was not explained by obesity-related pregnancy or neonatal complications. Conclusions and Relevance The rates of childhood epilepsy increased with maternal overweight or obesity in a dose-response manner. Given that overweight and obesity are modifiable, prevention of obesity may be an important public health strategy to reduce the incidence of childhood epilepsy.

Five-minute Apgar score as a marker for developmental vulnerability at 5 years of age

Objective To assess the relationship between the 5 min Apgar score and developmental vulnerability at 5 years of age. Design Population-based retrospective cohort study. Setting Manitoba, Canada. Participants All children born between 1999 and 2006 at term gestation, with a documented 5 min Apgar score. Exposure 5 min Apgar score. Main outcome measures Childhood development at 5 years of age, expressed as vulnerability (absent vs present) on five domains of the Early Development Instrument: physical health, social competence, emotional maturity, language and cognitive development, and communication skills. Results Of the 33 883 children in the study, most (82%) had an Apgar score of 9; 1% of children had a score <7 and 5.6% had a score of 10. Children with Apgar scores <10 had higher odds of vulnerability on the physical domain at age 5 years compared with children with a score of 10 (eg, adjusted OR (aOR) for Apgar 9=1.23, 95% CI 1.05 to 1.44). Similarly, children with Apgar scores of <10 were more vulnerable on the emotional domain (eg, aOR for Apgar 9=1.20, 95% CI 1.03 to 1.41). Nevertheless, the Apgar-based prognostic model had a poor sensitivity for physical vulnerability (19%, 95% CI 18% to 20%). Although the Apgar score-based prognostic model had reasonable calibration ability and risk-stratification accuracy for identifying developmentally vulnerable children, classification accuracy was poor. Conclusions The risk of developmental vulnerability at 5 years of age is inversely associated with the 5 min Apgar score across its entire range, and the score can serve as a population-level indicator of developmental risk.

Incidence of Mood or Anxiety Disorders in Children of Parents with Multiple Sclerosis

BACKGROUND Although parental multiple sclerosis (MS) may put children at increased risk for mental health disorders such as anxiety and depression, the incidence and determinants of such disorders have not been examined. METHOD We carried out a retrospective cohort study in British Columbia, Canada, among children of parents with MS and age-matched children of unaffected parents. Cox regression was used to estimate the association between parental MS and mood or anxiety disorders in children. RESULTS The study included 1028 children of MS parents, 4010 children of unaffected parents, and 25 464 child-years of follow-up (median follow-up of 4 years). Mental health morbidity was more common among MS parents vs. unaffected parents (50.4% vs. 33.1%) and among MS-affected mothers vs. unaffected mothers (54.6% vs. 38.0%, P < 0.001). The incidence of child mood or anxiety disorders was 8.3 and 6.3 per 1000 child-years among children of parents with and without MS respectively. Sex of the MS-affected parent modified the relationship between parental MS and mood or anxiety disorders in children (P = 0.04). Compared with children of unaffected mothers, children of mothers affected by MS had higher rates of mood or anxiety disorders (HR 1.7, 95% CI 1.1, 2.4), whereas children of MS-affected fathers did not (HR 0.5, 95% CI 0.2, 1.7). Adjustment for mental health morbidity in mothers diminished the association between maternal MS and child mood or anxiety disorders. CONCLUSION Maternal MS is associated with a higher rate of mood or anxiety disorders in children and this association appeared to be mediated by maternal mental health morbidity.