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1.  Emergency department visits during an Olympic gold medal television broadcast 
Open Medicine  2011;5(2):e112-e119.
Background
Practice pattern variations are often attributed to physician decision-making with no accounting for patient preferences.
Objective
To test whether a mass media television broadcast unrelated to health was associated with changes in the rate and characteristics of visits for acute emergency care.
Design
Time-series analysis of emergency department visits for any reason.
Subjects
Population-based sample of all patients seeking emergency care in Ontario, Canada.
Measures
The broadcast day was defined as the Olympic men’s gold medal ice hockey game final. The control days were defined as the 6 Sundays before and after the broadcast day.
Results
A total of 99 447 visits occurred over the 7 Sundays, of which 13 990 occurred on the broadcast day. Comparing the broadcast day with control days, we found no significant difference in the hourly rate of visits before the broadcast (544 vs 537, p = 0.41) or after the broadcast (647 vs 639, p = 0.55). In contrast, we observed a significant reduction in hourly rate of visits during the broadcast (647 vs 783, p < 0.001), equal to an absolute decrease of 409 patients, a relative decrease of 17% (95% confidence interval 13–21), or about 136 fewer patients per hour. The relative decrease during the broadcast was particularly large for adult men with low triage severity. The greatest reductions were for patients with abdominal, musculoskeletal or traumatic disorders.
Conclusion
Mass media television broadcasts can influence patient preferences and thereby lead to a decrease in emergency department visits.
PMCID: PMC3148000  PMID: 21915235
2.  Maternal and neonatal separation and mortality associated with concurrent admissions to intensive care units 
Background:
Concurrent admission of a mother and her newborn to separate intensive care units (herein referred to as co-ICU admission), possibly in different centres, can magnify family discord and stress. We examined the prevalence and predictors of mother–infant separation and mortality associated with co-ICU admissions.
Methods:
We completed a population-based study of all 1 023 978 singleton live births in Ontario between Apr. 1, 2002, and Mar. 31, 2010. We included data for maternal–infant pairs that had co-ICU admission (n = 1216), maternal ICU admission only (n = 897), neonatal ICU (NICU) admission only (n = 123 236) or no ICU admission (n = 898 629). The primary outcome measure was mother–infant separation because of interfacility transfer.
Results:
The prevalence of co-ICU admissions was 1.2 per 1000 live births and was higher than maternal ICU admissions (0.9 per 1000). Maternal–newborn separation due to interfacility transfer was 30.8 (95% confidence interval [CI] 26.9–35.3) times more common in the co-ICU group than in the no-ICU group and exceeded the prevalence in the maternal ICU group and NICU group. Short-term infant mortality (< 28 days after birth) was higher in the co-ICU group (18.1 per 1000 live births; maternal age–adjusted hazard ratio [HR] 27.8, 95% CI 18.2–42.6) than in the NICU group (7.6 per 1000; age-adjusted HR 11.5, 95% CI 10.4–12.7), relative to 0.7 per 1000 in the no-ICU group. Short-term maternal mortality (< 42 days after delivery) was also higher in the co-ICU group (15.6 per 1000; age-adjusted HR 328.7, 95% CI 191.2–565.2) than in the maternal ICU group (6.7 per 1000; age-adjusted HR 140.0, 95% CI 59.5–329.2) or the NICU group (0.2 per 1000; age-adjusted HR 4.6, 95% CI 2.8–7.4).
Interpretation:
Mother–infant pairs in the co-ICU group had the highest prevalence of separation due to interfacility transfer and the highest mortality compared with those in the maternal ICU and NICU groups.
doi:10.1503/cmaj.121283
PMCID: PMC3519169  PMID: 23091180
3.  Association between waiting times and short term mortality and hospital admission after departure from emergency department: population based cohort study from Ontario, Canada 
Objective To determine whether patients who are not admitted to hospital after attending an emergency department during shifts with long waiting times are at risk for adverse events.
Design Population based retrospective cohort study using health administrative databases.
Setting High volume emergency departments in Ontario, Canada, fiscal years 2003-7.
Participants All emergency department patients who were not admitted (seen and discharged; left without being seen).
Outcome measures Risk of adverse events (admission to hospital or death within seven days) adjusted for important characteristics of patients, shift, and hospital.
Results 13 934 542 patients were seen and discharged and 617 011 left without being seen. The risk of adverse events increased with the mean length of stay of similar patients in the same shift in the emergency department. For mean length of stay ≥6 v <1 hour the adjusted odds ratio (95% confidence interval) was 1.79 (1.24 to 2.59) for death and 1.95 (1.79 to 2.13) for admission in high acuity patients and 1.71 (1.25 to 2.35) for death and 1.66 (1.56 to 1.76) for admission in low acuity patients). Leaving without being seen was not associated with an increase in adverse events at the level of the patient or by annual rates of the hospital.
Conclusions Presenting to an emergency department during shifts with longer waiting times, reflected in longer mean length of stay, is associated with a greater risk in the short term of death and admission to hospital in patients who are well enough to leave the department. Patients who leave without being seen are not at higher risk of short term adverse events.
doi:10.1136/bmj.d2983
PMCID: PMC3106148  PMID: 21632665
4.  Analysis of Observational Studies in the Presence of Treatment Selection Bias: Effects of Invasive Cardiac Management on AMI Survival Using Propensity Score and Instrumental Variable Methods 
Context
Comparisons of outcomes between patients treated and untreated in observational studies may be biased due to differences in patient prognosis between groups, often because of unobserved treatment selection biases.
Objective
To compare 4 analytic methods for removing the effects of selection bias in observational studies: multivariable model risk adjustment, propensity score risk adjustment, propensity-based matching, and instrumental variable analysis.
Design, Setting, and Patients
A national cohort of 122 124 patients who were elderly (aged 65–84 years), receiving Medicare, and hospitalized with acute myocardial infarction (AMI) in 1994–1995, and who were eligible for cardiac catheterization. Baseline chart reviews were taken from the Cooperative Cardiovascular Project and linked to Medicare health administrative data to provide a rich set of prognostic variables. Patients were followed up for 7 years through December 31, 2001, to assess the association between long-term survival and cardiac catheterization within 30 days of hospital admission.
Main Outcome Measure
Risk-adjusted relative mortality rate using each of the analytic methods.
Results
Patients who received cardiac catheterization (n=73 238) were younger and had lower AMI severity than those who did not. After adjustment for prognostic factors by using standard statistical risk-adjustment methods, cardiac catheterization was associated with a 50% relative decrease in mortality (for multivariable model risk adjustment: adjusted relative risk [RR], 0.51; 95% confidence interval [CI], 0.50–0.52; for propensity score risk adjustment: adjusted RR, 0.54; 95% CI, 0.53–0.55; and for propensity-based matching: adjusted RR, 0.54; 95% CI, 0.52–0.56). Using regional catheterization rate as an instrument, instrumental variable analysis showed a 16% relative decrease in mortality (adjusted RR, 0.84; 95% CI, 0.79–0.90). The survival benefits of routine invasive care from randomized clinical trials are between 8% and 21 %.
Conclusions
Estimates of the observational association of cardiac catheterization with long-term AMI mortality are highly sensitive to analytic method. All standard risk-adjustment methods have the same limitations regarding removal of unmeasured treatment selection biases. Compared with standard modeling, instrumental variable analysis may produce less biased estimates of treatment effects, but is more suited to answering policy questions than specific clinical questions.
doi:10.1001/jama.297.3.278
PMCID: PMC2170524  PMID: 17227979
5.  Metabolic Syndrome features and risk of neural tube defects 
Background
Maternal obesity and pre-pregnancy diabetes mellitus, features of the metabolic syndrome (MetSyn), are individual risk factors for neural tube defects (NTD). Whether they, in combination with additional features of MetSyn, alter this risk is not known. We evaluated the risk of NTD in association with maternal features of the MetSyn.
Methods
We used a population-based case-control study design in the province of Ontario, Canada. Cases and controls were derived from women who underwent antenatal maternal screening (MSS) at 15 to 20 weeks' gestation. There were 89 maternal cases with, and 434 controls without, an NTD-affected singleton pregnancy. Maternal features of MetSyn were defined by the presence of pre-pregnancy diabetes mellitus, body weight ≥ 90th centile among controls, non-white ethnicity and/or serum highly sensitive C-reactive protein (hsCRP) ≥ 75th centile of controls. Since hsCRP naturally increases in pregnancy, analyses were performed with, and without, the inclusion of hsCRP in the model.
Results
Mean hsCRP concentrations were exceptionally high among study cases and controls (6.1 and 6.4 mg/L, respectively). When hsCRP was excluded from the model, the adjusted odds ratios for NTD were 1.9 (95% confidence interval 1.1–3.4) in the presence 1 feature of MetSyn, and 6.1 (1.1–32.9) in the presence of 2 or more features. When hsCRP was included, the respective risk estimates were attenuated to 1.6 (0.88–2.8) and 3.1 (1.2–8.3).
Conclusion
We found about 2-fold and 6-fold higher risk for NTD in the presence 1, and 2 or more features, of the metabolic syndrome, respectively. It is not clear whether this risk is altered by the presence of a high serum hsCRP concentration.
doi:10.1186/1471-2393-7-21
PMCID: PMC2039731  PMID: 17880716
6.  Taking ACE inhibitors during early pregnancy 
Canadian Family Physician  2007;53(9):1439-1440.
QUESTION I knew that angiotensin-converting enzyme (ACE) inhibitors were risky to use during late pregnancy because they can cause renal shutdown in the fetus. Recently I heard of a study that claimed first-trimester exposure (when many patients still are unaware of their pregnancies) can also cause major malformations. Is this proven?
ANSWER A recent study did suggest an increased risk of malformations after first-trimester exposure to ACE inhibitors among women treated for hypertension. We believe this study had serious limitations that preclude drawing any conclusions at present.
PMCID: PMC2234619  PMID: 17872870
7.  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.
doi:10.1503/cmaj.061174
PMCID: PMC1891122  PMID: 17576979
8.  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.
doi:10.1503/cmaj.061680
PMCID: PMC1863534  PMID: 17485694
9.  Adverse perinatal outcomes associated with homelessness and substance use in pregnancy 
Background
Women who are homeless during pregnancy may be exposed to poor nutrition, violence and substance use, yet the health status of their newborn infants has not been systematically evaluated. We undertook a study to provide preliminary estimates of the risk of adverse perinatal outcomes among Canadian women who are homeless or marginally housed during pregnancy, and the effect of concomitant substance use.
Methods
We conducted a retrospective cohort study at a single downtown hospital from October 2002 to December 2004, involving women who, during pregnancy, were homeless or underhoused (n = 80), substance users (n = 59) or neither (n = 3756). We noted neonatal measures such as birth weight and gestational age; the main study outcomes were preterm birth before 37 weeks' gestation, birth weight less than 2000 g and small for gestational age at birth.
Results
Homelessness or inadequate housing was associated with an odds ratio (adjusted for maternal age, gravidity and being a current smoker of tobacco) of 2.9 (95% confidence interval [CI] 1.4–6.1) for preterm delivery, 6.9 (95% CI 2.4–20.0) for infant birth weight under 2000 g and 3.3 (95% CI 1.1–10.3) for delivery of a newborn small for gestational age. Adjusted odds ratios for substance use during pregnancy were similar. In the combined presence of an underhoused or homeless state and maternal substance use, the adjusted risk estimates were 5.9 (95% CI 1.9–18.5), 16.6 (95% CI 3.5–79.3) and 5.6 (95% CI 1.1–28.7), respectively.
Interpretation
Homelessness and maternal substance use may reduce neonatal well-being through prematurity and low birth weight.
doi:10.1503/cmaj.050406
PMCID: PMC1197161  PMID: 16157725
10.  Maternal ethnicity and risk of neural tube defects: a population-based study 
Background
Maternal body mass and the presence of diabetes mellitus are probable risk factors for neural tube defects (NTDs). The association between maternal ethnicity and the risk of NTDs remains poorly understood, however.
Methods
We performed a retrospective population-based study and included all women in Ontario who underwent antenatal maternal screening (MSS) at 15 to 20 weeks' gestation between 1994 and late 2000. Self-declared maternal date of birth, ethnicity and weight and the presence of pregestational diabetes mellitus were recorded in a standardized fashion on the MSS requisition sheet. NTDs were detected antenatally by ultrasonography or fetal autopsy and postnatally by considering all live and stillborn affected infants beyond 20 weeks' gestation. The risk of open NTD was evaluated across the 5 broad ethnic groups used for MSS, with white ethnicity as the referent.
Results
Compared with white women (n = 290 799), women of First Nations origin (n = 1551) were at increased associated risk of an NTD-affected pregnancy (adjusted odds ratio [OR] 5.2, 95% confidence interval [CI] 2.1–12.9). Women of other ethnic origins were not at increased associated risk compared with white women (women of Asian origin [n = 75 590]: adjusted OR 0.9, 95% CI 0.6–1.3; black women [n = 25 966]: adjusted OR 0.6, 95% CI 0.3–1.1; women of “other” ethnic origin [n = 10 009]: adjusted OR 0.1, 95% CI 0.02–0.9).
Interpretation
The associated risk of NTD-affected pregnancies was higher among women of First Nations origin than among women of other ethnic origins. The mechanisms for this discrepancy should be explored.
doi:10.1503/cmaj.1040254
PMCID: PMC509047  PMID: 15313993
11.  Increased blood product use among coronary artery bypass patients prescribed preoperative aspirin and clopidogrel 
Background
The administration of antiplatelet drugs before coronary artery bypass graft surgery (CABG) is associated with an increased risk of major hemorrhage and related surgical reexploration. Little is known about the relative effect of combined clopidogrel and aspirin on blood product use around the time of CABG. We evaluated the associated risk between the combined use of aspirin and clopidogrel and the transfusion of blood products perioperatively.
Methods
We retrospectively studied a cohort of 659 individuals who underwent a first CABG, without concomitant valvular or aortic surgery, at a single large Canadian cardiac surgical centre between January 2000 and April 2002. The four study exposure groups were those prescribed aspirin (n = 105), clopidogrel (n = 11), the combination of both (n = 46), or neither drug (n = 497), within 7 days prior to CABG. The primary study outcome was the excessive transfusion of blood products during CABG and up to the second post-operative day, defined as ≥ 2 units of packed red blood cells (PRBC), ≥ 2 units of fresh frozen plasma, ≥ 5 units of cryoprecipitate or ≥ 5 units of platelets. Secondary outcomes included the mean number of transfused units of each type of blood product.
Results
A greater mean number of units of PRBC were transfused among those who received clopidogrel alone (2.9) or in combination with aspirin (2.4), compared to those on aspirin alone (1.9) or neither antiplatelet drug (1.4) (P = 0.001). A similar trend was seen for the respective mean number of transfused units of platelets (3.6, 3.7, 1.3 and 1.0; P < 0.001) and fresh frozen plasma (2.5, 3.1, 2.3, 1.6; P = 0.01). Compared to non-users, the associated risk of excessive blood product transfusion was highest among recipients of aspirin and clopidogrel together (adjusted OR 2.2, 95% CI 1.1–4.3). No significant association was seen among lone users of aspirin (adjusted OR 1.0, 95% CI 0.6–1.6) or clopidogrel (adjusted OR 0.7, 95% CI 0.2–2.5), compared to non-users.
Conclusions
While combined use of aspirin and clopidogrel shortly before CABG surgery may increase the associated risk of excess transfusion of blood products perioperatively, several study limitations prevent any confident conclusions from being drawn. Beyond challenging these findings, future research might focus on the value of both intraoperative monitoring of platelet function, and the effectiveness of antifibrinolytic agents, at reducing the risk of postoperative bleeding.
doi:10.1186/1471-2261-3-3
PMCID: PMC162165  PMID: 12769833
Coronary artery bypass surgery; antiplatelet; aspirin; clopidogrel; transfusion; hemorrhage; critical care
12.  Use of antihypertensive medications in pregnancy and the risk of adverse perinatal outcomes: McMaster Outcome Study of Hypertension In Pregnancy 2 (MOS HIP 2) 
Background
Uncertainty remains about the potential harmful effects of antihypertensive therapy on the developing fetus, especially for beta-blockers (βb).
Methods
We prospectively enrolled all singleton women with a blood pressure ≥ 140/90 mm Hg during pregnancy. The main analysis included 1948 women with all forms of hypertension and compared the use of βb drugs, non-βb drugs or a combination of both, to no treatment. The primary study outcome was a composite of the diseases of prematurity, need for assisted ventilation for greater than 1 day, or perinatal death. A sub-group analysis evaluated the four treatment options among 583 singleton women with chronic hypertension before 20 weeks gestation.
Results
In the main analysis, no association was observed between βb use and the primary composite outcome [adjusted odds ratio (OR) 1.4, 95% CI 0.9–2.2], while an association was seen with non-βb therapy (OR 5.0, 95% CI 2.6–9.6) and combination therapy (OR 2.9, 95% CI 1.8–4.7). In the sub-group of 583 women with hypertension before 20 weeks, use of a non-βb drug (OR 4.9, 95% CI 1.7–14.2) or combination therapy (OR 2.9. 95% CI 1.1–7.7) was significantly associated with the primary composite outcome, while βb monotherapy was not (OR 1.4, 95% CI 0.6–3.4).
Conclusions
Maternal use of antihypertensive medications other than βbs was associated with both major perinatal morbidity and mortality, while βb monotherapy was not. The combined use of βb and non-βb medications demonstrated the strongest association. Before definitive conclusions can be drawn, a large multicentre randomized controlled trial is needed to address the issues of both maternal efficacy and fetal safety with the use of one or more antihypertensive agents in pregnancy.
doi:10.1186/1471-2393-1-6
PMCID: PMC60658  PMID: 11737873
13.  Genetics University of Toronto Thrombophilia Study in Women (GUTTSI): genetic and other risk factors for venous thromboembolism in women 
Background
Women may be at increased risk for venous thromboembolism (VTE) as compared with men. We studied the effects of genetic and biochemical markers of thrombophilia in women, in conjunction with other established risk factors for VTE.
Method
The present retrospective case-control study was conducted in a thrombosis treatment programme at a large Toronto hospital. The cases were 129 women aged 16-79 years with objectively confirmed VTE. Age-matched control individuals were women who were free of venous thrombosis. Neither cases nor control individuals had known cardiovascular disease. Participants were interviewed regarding personal risk factors for VTE, including smoking, history of malignancy, pregnancy, and oestrogen or oral contraceptive use. Blood specimens were analyzed for common single nucleotide polymorphisms of prothrombin, factor V and methylenetetrahydrofolate reductase (MTHFR; C677T, A1298C and T1317C), and the A66G polymorphism for methionine synthase reductase (MTRR).Fasting plasma homocysteine was also analyzed.
Results
Women with VTE were significantly more likely than female control individuals to carry the prothrombin polymorphism and the factor V polymorphism, or to have fasting hyperhomocysteinaemia. Homozygosity for the C677T MTHFR gene was not a significant risk factor for VTE, or were the A1298C or T1317C MTHFR homozygous variants. Also, the A66G MTRR homozygous state did not confer an increased risk for VTE.
Conclusion
Prothrombin and factor V polymorphisms increased the risk for VTE in women, independent from other established risk factors. Although hyperhomocysteinaemia also heightens this risk, common polymorphisms in two genes that are responsible for homocysteine remethylation do not. These findings are consistent with previous studies that included both men and women.
doi:10.1186/cvm-2-3-141
PMCID: PMC56202  PMID: 11806787
case-control study; deep vein thrombosis; factor V gene; folate; genetics; homocysteine; methionine synthase reductase; methylenetetrahydrofolate reductase; prothrombin gene; pulmonary embolism; risk; thrombophilia; venous thromboembolism; women's health
14.  Major Radiodiagnostic Imaging in Pregnancy and the Risk of Childhood Malignancy: A Population-Based Cohort Study in Ontario 
PLoS Medicine  2010;7(9):e1000337.
In a record-linkage study, Joel Ray and colleagues examine the association between diagnostic imaging during pregnancy and later childhood cancers.
Background
The association between fetal exposure to major radiodiagnostic testing in pregnancy—computed tomography (CT) and radionuclide imaging—and the risk of childhood cancer is not established.
Methods and Findings
We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario's universal health care–linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26–1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25–1.80).
Conclusions
Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In industrialized countries, childhood cancer (any form of cancer in a child aged 14 years or under) remains a major cause of death. With the exception of a few known risk factors, such as acquired genetic predisposition to cancer, which accounts for about 10% of all childhood cancers, the etiology of most childhood cancer remains unknown. There is thought to be an association between exposure to ionizing radiation in pregnancy and the subsequent risk of development of cancer in the exposed mother's child, but the evidence base to support this association is conflicting. For example, studies examining maternal exposure to plain radiographs in pregnancy and subsequent childhood cancer are inconsistent. Furthermore, although their use has dramatically increased over the past two decades, little is known about the cancer risk related to certain types of radiodiagnostic tests, such as CT and radionuclide imaging, both of which expose the fetus to considerably higher doses of radiation than plain radiographs administered at the same anatomical level.
Why Was This Study Done?
Many women could be exposed to major radiodiagnostic tests, such as those used in emergency situations, before they are aware that they are pregnant, as almost 50% of pregnancies are unplanned. This situation means that it is important to determine the subsequent cancer risk to any child exposed to maternal radiodiagnostic tests before birth.
What Did the Researchers Do and Find?
The researchers conducted a retrospective population-based cohort study of women who delivered a live infant in Ontario, Canada between April 1, 1992 and March 31, 2008. The basis of the research was an anonymized database for the whole province of Ontario, where universal health care, including prenatal care and radiodiagnostic testing, is available to all residents. Database characteristics allowed the researchers to link maternal radiation exposure (a major radiodiagnostic test performed on the mother up to one day before her delivery date) in a specific (index) pregnancy to a subsequent malignancy in the child. After birth, maternal-infant pairs were only followed up if the infant was delivered at term, weighed 2,500 g or more, and survived for at least 30 days.
The researchers were able to follow up 1,835,517 maternal-child pairs. The overall rate of exposure to major radiodiagnostic testing in pregnancy was 3.0 per 1,000 and occurred at an estimated mean gestational age of 15.7 weeks. A total of four childhood cancers occurred in the exposed group and 2,539 cancers in the unexposed group corresponding to a crude hazard ratio of 0.69, which did not significantly change after adjustments were made for potential confounding factors, such as maternal age, sex, and the presence of any chromosomal or congenital anomalies in the infant. The overall prevalence of childhood cancer following exposure to CT or radionuclide imaging in pregnancy is under 0.07%, giving an incidence rate of 1.13 per 10,000 person-years.
What Do These Findings Mean?
These findings can help inform clinicians and mothers about the risk of childhood malignancy following major radiodiagnostic testing in pregnancy. The absolute risk appears to be low, while the relative risk is not materially higher than that of unexposed controls. However, as the upper confidence limit of the relative risk of malignancy may be a maximum of 1.8 times that of an unexposed pregnancy, the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic cannot be excluded. Because this finding means that a very slight risk may exist, beta hCG testing should continue to be done in all potentially pregnant women before undergoing major radiodiagnostic testing, and lead apron shielding used in all women of reproductive age, whether or not known to be pregnant. In addition, nonradiation-emitting imaging, such as MRI and ultrasonography, should be considered first, when clinically appropriate. However, some pregnant women will still be faced with the decision to undergo CT or nuclear imaging because the test is clinically warranted. The findings of this study suggest that when clinically indicated, major radiodiagnostic testing in pregnancy should be performed, along with brief counseling to help lessen the anxiety experienced by an expectant mother before and after the birth of her child.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000337.
For information for patients and caregivers on radiodiagnostic testing, see The Royal College of Radiologists
The National Cancer Institute provides information about childhood cancer
CureSearch for Children's Cancer provides additional information about research into childhood cancer
doi:10.1371/journal.pmed.1000337
PMCID: PMC2935460  PMID: 20838660

Results 1-14 (14)