Marian J. Vermeulen

Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population.

Background: Low maternal vitamin B12 status may be a risk factor for neural tube defects (NTDs). Prior studies used relatively insensitive measures of B12, did not adjust for folate levels, and were conducted in countries without folic acid food fortification. In Canada, flour has been fortified with folic acid since mid-1997. Methods: We completed a population-based case–control study in Ontario. We measured serum holotranscobalamin (holoTC), a sensitive indicator of B12 status, at 15 to 20 weeks’ gestation. There were 89 women with an NTD and 422 unaffected pregnant controls. A low serum holoTC was defined as less than 55.3 pmol/L, the bottom quartile value in the controls. Results: The geometric mean serum holoTC levels were 67.8 pmol/L in cases and 81.2 pmol/L in controls. There was a trend of increasing risk with lower levels of holoTC, reaching an adjusted odds ratio of 2.9 (95% confidence interval = 1.2–6.9) when comparing the lowest versus highest quartile. Conclusions: There was almost a tripling in the risk for NTD in the presence of low maternal B12 status, measured by holoTC. The benefits of adding synthetic B12 to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered. It remains to be determined what fraction of NTD cases in a universally folate-fortified environment might be prevented by higher periconceptional intake of B12.

Greater maternal weight and the ongoing risk of neural tube defects after folic acid flour fortification.

OBJECTIVE: Maternal obesity is likely a risk factor for neural tube defects (NTDs). By late 1997, it became mandatory in Canada that all refined wheat flour be fortified with folic acid. Because overweight women may consume greater quantities of refined wheat flour, we questioned whether their risk of NTD changed after flour fortification. METHODS: A retrospective population-based study was conducted between 1994 and late 2000. We included all Ontarian women who underwent antenatal maternal screening at 15 to 20 weeks of gestation. Self-declared maternal date of birth, ethnicity, current weight, and the presence of pregestational diabetes mellitus were recorded in a standardized fashion on the maternal screening requisition sheet. The presence of NTDs was systematically detected both antenatally and postnatally. The risk of open NTD was evaluated across maternal weight quartiles and deciles, and an interaction between greater maternal weight and the presence of flour fortification was tested using multiple logistic regression analysis. RESULTS: A total of 292 open NTDs were detected among 420,362 women. The adjusted odds ratio (OR) for NTD was 1.2 (95% confidence interval [CI] 1.1–1.3) per 10-kg incremental rise in maternal weight. Comparing the highest with the lowest quartile of maternal weight, the adjusted OR for NTD was 2.6 (95% CI 1.8–4.0). A similar finding was observed for the highest compared with lowest weight deciles (adjusted OR 3.3, 95% CI 1.7–6.2). The interaction between elevated maternal weight and the presence of folic acid flour fortification was of borderline significance (P = .09). Before fortification, greater maternal weight was associated with a modestly increased risk of NTD (adjusted OR 1.4, 95% CI 1.0–1.8); after flour fortification, this effect was more pronounced (adjusted OR 2.8, 95% CI 1.2–6.6). CONCLUSION: These data emphasize the higher risk of NTD associated with increased maternal weight, even after universal folic acid flour fortification. Beyond periconceptional folic acid use, consideration should be given to testing whether prepregnancy weight reduction is an independent means of preventing NTD. LEVEL OF EVIDENCE: II-2

Folic acid food fortification is associated with a decline in neuroblastoma

Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known.

Missed Diagnosis of Subarachnoid Hemorrhage in the Emergency Department

Background and Purpose— Subarachnoid hemorrhage (SAH) can be devastating, yet its initial presentation may be limited to common symptoms and subtle signs, potentially leading to misdiagnosis. Little is known about population rates of misdiagnosis of SAH, or hospital factors that may contribute to it. We estimated the population-based rate of missed SAH among emergency department (ED) patients and examined its relationship with hospital characteristics. Methods— We studied persons admitted with a nontraumatic SAH to all Ontario hospitals over 3 years (April 2002 to March 2005). SAH was defined as missed if the patient had an ED visit related to the SAH (based on a prespecified definition) in the 14 days before admission. We examined the association between hospital teaching status and missed SAH and explored whether annual ED volume of SAH or CT availability explained this association. Results— Of 1507 patients diagnosed with SAH, 5.4% (95% CI, 4.3 to 6.6) had a missed diagnosis. The risk was significantly higher among patients triaged as low acuity (odds ratio 2.65; 95% CI, 1.46 to 4.80), as well as in nonteaching hospitals (adjusted odds ratio 2.12; 95% CI, 1.02, 4.44). Neither ED SAH volume nor on-site CT availability explained the effect of teaching status. Conclusions— About 1 in 20 SAH patients are missed during an ED visit. Lower acuity patients are at higher risk of misdiagnosis, suggesting the need for heightened suspicion among patients with minimal clinical findings. The risk is also greater in nonteaching hospitals, but this is not explained by the annual volume of SAHs seen in the ED or access to CT.

Results of the Recent Immigrant Pregnancy and Perinatal Long-term Evaluation Study (RIPPLES)

Background: People who immigrate to Western nations may experience fewer chronic health problems than original residents of those countries, which raises concerns about long-term environmental or lifestyle factors in those countries. We tested whether the “healthy immigrant effect” extends to the risk of placental dysfunction during the short interval of pregnancy. Methods: We conducted a population-based retrospective cohort study of data for 796 105 women who had a first documented obstetric delivery in Ontario between 1995 and 2005. Recency of immigration was determined for each woman as the time from her enrolment in universal health insurance to her date of delivery, classified as less than 3 months, 3–5 months, 6–11 months, 12–23 months, 24–35 months, 36–47 months, 48–59 months and 5 years or more (the referent). The primary composite outcome was maternal placental syndrome (defined as a diagnosis of pre-eclampsia or eclampsia, placental abruption or placental infarction). Results: The mean age of the women was 28.8 years. Maternal placental syndrome occurred in 45 216 women (5.7%). The risk of this outcome was lowest among the women who had immigrated less than 3 months before delivery (3.8%) and highest among those living in Ontario at least 5 years (6.0%), for a crude odds ratio (OR) of 0.62 (95% confidence interval [CI] 0.54–0.71). After adjustment for maternal age, income status, pre-existing hypertension, diabetes mellitus, multiple gestation and receipt of prenatal ultrasonography, the risk of maternal placental syndrome was correlated with the number of months since immigration in a gradient manner (OR, 95% CI): less than 3 months (0.53, 0.47–0.61), 3–5 months (0.68, 0.61–0.76), 6–11 months (0.67, 0.63–0.71), 12–23 months (0.69, 0.66–0.73), 24–35 months (0.75, 0.70–0.79), 36–47 months (0.75, 0.70–0.80) and 48–59 months (0.82, 0.77–0.87). Interpretation: There was a progressively lower risk of maternal placental syndromes associated with recency of immigration. The “healthy immigrant effect” may extend to common placental disorders, diminishes with the duration of residency and underscores the importance of nongenetic determinants of maternal health accrued over a brief period.

Association between folic acid food fortification and congenital orofacial clefts

By January 1998, most of Canadas cereal grain products were being fortified with folic acid. Among 336963 women who underwent antenatal maternal serum screening, the prevalence of orofacial clefts did not change from before (1.15 per 1000) to after (1.21 per 1000) food fortification (prevalence ratio, 1.06; 95% confidence interval, 0.86-1.30).

Heart failure and dysrhythmias after maternal placental syndromes: HAD MPS Study

Background Maternal placental syndromes (MPS)—gestational hypertension, pre-eclampsia and placental abruption/infarction—are more prevalent in women with features of the metabolic syndrome (MetSyn). Both MPS and the MetSyn predispose to left ventricular impairment and sympathetic dominance after delivery. Whether this translates into a higher risk of heart failure (HF) and cardiac dysrhythmias is not known. Objective To determine the risk of new onset of HF and dysrhythmias among women after a prior MPS-affected pregnancy. Methods A retrospective cohort study was carried out of 1 130 764 individual women with a delivery in Ontario between 1992 and 2009, excluding those with cardiac or thyroid disease 1 year before delivery. The risk of a composite outcome of a hospitalisation for HF or an atrial or ventricular dysrhythmia was compared in women with and without MPS, starting 1 year after delivery. Results 75 242 individuals (6.7%) experienced a MPS. After a median duration of 7.8 years, the composite outcome occurred in 148 women with MPS (2.54 per 10 000 person-years) and 1062 women without MPS (1.28 per 10 000 person-years) (crude HR=2.00, 95% CI 1.68 to 2.38). The mean age at composite outcome was 37.8 years. The HR was 1.61 (95% CI 1.35 to 1.91) after adjustment for demographic characteristics, diabetes, obesity, dyslipidaemia and drug dependence or tobacco use, as well as coronary artery disease or thyroid disease >1 year after delivery. The adjusted HRs were minimally reduced by further adjusting for chronic hypertension (1.51, 95% CI 1.26 to 1.80) and were higher in women with MPS plus preterm delivery and poor fetal growth (2.42, 95% CI 1.25 to 4.67). Conclusions Women with MPS are at higher risk of premature HF and dysrhythmias, especially when perinatal morbidity is present.

Reduction in Clostridium difficile infection rates after mandatory hospital public reporting: findings from a longitudinal cohort study in Canada.

A population-based study conducted by Nick Daneman and colleagues in Ontario, Canada reports on the association between population reporting of hospital infection rates and a reduction in population burden of Clostridium difficile colitis.

Effect of widespread restrictions on the use of hospital services during an outbreak of severe acute respiratory syndrome

Background: Restrictions on the nonurgent use of hospital services were imposed in March 2003 to control an outbreak of severe acute respiratory syndrome (SARS) in Toronto, Ont. We describe the impact of these restrictions on health care utilization and suggest lessons for future epidemics. Methods: We performed a retrospective population-based study of the Greater Toronto Area (hereafter referred to as Toronto) and unaffected comparison regions (Ottawa and London, Ont.) before, during and after the SARS outbreak (April 2001–March 2004). We determined the adjusted rates of hospital admissions, emergency department and outpatient visits, diagnostic testing and drug prescribing. Results: During the early and late SARS restriction periods, the rate of overall and medical admissions decreased by 10%–12% in Toronto; there was no change in the comparison regions. The rate of elective surgery in Toronto fell by 22% and 15% during the early and late restriction periods respectively and by 8% in the comparison regions. The admission rates for urgent surgery remained unchanged in all regions; those for some acute serious medical conditions decreased by 15%–21%. The rates of elective cardiac procedures declined by up to 66% in Toronto and by 71% in the comparison regions; the rates of urgent and semi-urgent procedures declined little or increased. High-acuity visits to emergency departments fell by 37% in Toronto, and inter-hospital patient transfers fell by 44% in the circum-Toronto area. Drug prescribing and primary care visits were unchanged in all regions. Interpretation: The restrictions achieved modest reductions in overall hospital admissions and substantial reductions in the use of elective services. Brief reductions occurred in admissions for some acute serious conditions, high-acuity visits to emergency departments and inter-hospital patient transfers suggesting that access to care for some potentially seriously ill patients was affected.

Evaluating the effect of clinical decision units on patient flow in seven Canadian emergency departments.

OBJECTIVES To evaluate the effect of emergency department (ED) clinical decision units (CDUs) on overall ED patient flow in a pilot project funded in 2008 by the Ontario Ministry of Health and Long-Term Care (MOHLTC). METHODS A retrospective analysis of unscheduled ED visits at seven CDU pilot and nine control sites was conducted using administrative data. The authors examined trends in CDU utilization and compared outcomes between pilot-CDU and control sites 1 year prior to implementation, with the first 18 months of CDU operation. Sites that were unsuccessful in their applications for CDU program funding served as controls. Outcomes included ED length of stay (LOS), admission rates, and ED revisit rates. RESULTS At CDU sites, roughly 4% of ED patients were admitted to CDUs. The presence of a pilot-CDU was independently associated with a small reduction in ED LOS for all low-acuity patients (-0.14 hour, 95% confidence interval [CI]=-0.22 to -0.07) and nonadmitted patients (-0.11 hour, 95% CI=-0.16 to -0.07). A small independent effect on absolute hospital admission rate for all high-acuity patients (-0.8%, 95% CI=-1.5% to -0.03%) and moderate-acuity patients (-0.6%, 95% CI=-1.1% to -0.2%) was also observed. Pilot-CDUs were not associated with changes in ED revisit rates. CONCLUSIONS With only 4% of ED patients admitted to CDUs, the potential for efficiency gains in these EDs was limited. Nonetheless, these findings suggest small improvements in the operation of the ED through CDU implementation. Although marginal, the observed effects of CDU operation were in the desired direction of reduced ED LOS, reduced admission rate, and no increase in ED revisit rate.