Maternal pregestational diabetes and risk of acute lymphoblastic leukemia in the offspring: A population-based study in Northern Italy.

INTRODUCTION: This population-based study aims to evaluate the association between maternal pregestational diabetes and risk of acute lymphoblastic leukemia (ALL) in the offspring. METHODS: All 241,958 children born in three Northern Italy provinces 1998-2010 were followed from birth until first cancer diagnosis (National Childhood Cancer Register), age 15 years, or 31 December 2017. We computed hazard ratio (HR) and 95% CI of ALL in relation to the presence of maternal diabetes through Cox proportional regression models. RESULTS: We observed 145 cases of ALL, with a higher incidence in children born to women with pregestational diabetes compared to the others (12.4 vs 4.6). Adjusted hazard ratio of ALL was 2.6 (CI, 0.6-10.5) for maternal diabetes. DISCUSSION: We estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.

Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy.

Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1 : 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies.

Validity of hospital discharge records to identify pregestational diabetes in an Italian population.

AIMS: In recent years, the prevalence of pregestational diabetes (PGDM) and the concern about the possibility of adverse pregnancy outcomes in affected women have been increasing. Routinely collected health data represent a timely and cost-efficient approach in PGDM epidemiological research. This study aims to evaluate the reliability of hospital discharge (HD) coding to identify a population-based cohort of pregnant women with PGDM and to assess trends in prevalence in two provinces of Northern Italy. METHODS: We selected all deliveries occurred in the period 1997-2010 with ICD-9-CM codes for PGDM in HD record and we matched up to 5 controls from mothers without diabetes. We used Diabetes Registers (DRs) as the gold standard for validation analysis. RESULTS: We selected 3800 women, 653 with diabetes and 3147 without diabetes. The agreement between HD records and DRs was 90.7%, with K=0.58. We detected 350 false positives and only 1 false negative. Sensitivity was 99.3%, specificity 90.0%, positive predictive value 46.4% and negative predictive value 99.9%. Of the false positives, 48.6% had gestational diabetes and 2.3% impaired glucose tolerance. After the validation process, PGDM prevalence decreased from 4.4 to 2.0 per 1000 deliveries. CONCLUSIONS: Our results show that HD facilitate detection of almost all PGDM cases, but they also include a large number of false positives, mainly due to gestational diabetes. This misclassification causes a large overestimation of PGMD prevalence. Our findings require accuracy evaluation of ICD-9-CM codes, before they can be widely applied to epidemiological research and public health surveillance related to PGDM.

Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study.

A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories.

Risk of birth defects associated with maternal pregestational diabetes.

Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.

Building a population-based diabetes register: an Italian experience.

AIMS: To describe the methodology used to set up the Reggio Emilia (northern Italy) Diabetes Register. The prevalence estimates on December 31st, 2009 are also provided. METHODS: The Diabetes Register covers all residents in the Reggio Emilia province. The register was created by deterministic linkage of six routinely collected data sources through a definite algorithm able to ascertain cases and to distinguish type of diabetes and model of care: Hospital Discharge, Drug Dispensation, Biochemistry Laboratory, Disease-specific Exemption, Diabetes Outpatient Clinics, and Mortality databases. Using these data, we estimated crude prevalence on December 31st, 2009 by sex, age groups, and type of diabetes. RESULTS: There were 25,425 ascertained prevalent cases on December 31st, 2009. Drug Dispensation and Exemption databases made the greatest contribution to prevalence. Analyzing overlapping sources, more than 80% of cases were reported by at least two sources. Crude prevalence was 4.8% and 5.9% for the whole population and for people aged 18 years and over, respectively. Males accounted for 53.6%. Type 1 diabetes accounted for 3.8% of cases, while people with Type 2 diabetes were the overriding majority (91.2%), and Diabetes Outpatient Clinics treated 75.4% of people with Type 2 diabetes. CONCLUSION: The Register is able to quantify the burden of disease, the first step in planning, implementing, and monitoring appropriate interventions. All data sources contributed to completeness and/or accuracy of the Register. Although all cases are identified by deterministic record linkage, manual revision and General Practitioner involvement are still necessary when information is insufficient or conflicting.

Maternal exposure to magnetic fields from high-voltage power lines and the risk of birth defects.

The issue of adverse human health effects due to exposure to electromagnetic fields is still unclear, and congenital anomalies are among the outcomes that have been inconsistently associated with such exposure. We conducted a population-based, case-control study to examine the risk of congenital anomalies associated with maternal exposure to magnetic fields (MF) from high-voltage power lines during pregnancy in a community in northern Italy. We identified 228 cases of congenital malformations diagnosed in live births, stillbirths, and induced abortions among women living in the municipality of Reggio Emilia during the period 1998-2006, and a reference group of healthy newborns was matched for year of birth, maternal age, and hospital of birth. We identified maternal residence during early pregnancy and used Geographic Information System to determine whether the residences were within geocoded corridors with MF ≥0.1 µT near high-voltage power lines, then calculated the relative risk (RR) of congenital anomalies associated with maternal exposure. One case and 5 control mothers were classified as exposed, and the RR associated with MF ≥0.1 µT was 0.2 (95% CI: 0.0-2.0) after adjusting for maternal education. While small or moderate effects may have gone undetected due to low statistical power, the results of this study overall do not provide support for major effects of a teratogenic risk due to exposure to MF during early pregnancy.

Risk of congenital anomalies around a municipal solid waste incinerator: a GIS-based case-control study.

BACKGROUND: Waste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator and risk of birth defects in a northern Italy community, using Geographical Information System (GIS) data to estimate exposure and a population-based case-control study design. By modelling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998-2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first three months of pregnancy to geocode cases and controls. RESULTS: Among women residing in the areas with medium and high exposure, prevalence of anomalies in the offspring was substantially comparable to that observed in the control population, nor dose-response relations for any of the major categories of birth defects emerged. Furthermore, odds ratio for congenital anomalies did not decrease during a prolonged shut-down period of the plant. CONCLUSION: Overall, these findings do not lend support to the hypothesis that the environmental contamination occurring around an incineration plant such as that examined in this study may induce major teratogenic effects.

The epidemiology of amyotrophic lateral sclerosis in Reggio Emilia, Italy.

Incidence and mortality rates of amyotrophic lateral sclerosis (ALS) vary between countries, and in some studies appear to increase over time. We performed a study to assess ALS incidence in a northern Italy area over a 10-year period. We identified the new cases of probable or definite ALS diagnosed among residents in Reggio Emilia province between 1996 and 2005 using several sources of data, such as death certificates, clinical records, hospital discharge registers and drug prescriptions. A total of 94 newly-diagnosed patients were identified. The average standardized incidence in the period was 2.0 and 1.0 cases/100,000/year, using the Italian and the world population, respectively, as reference. There was no variation in rates over time. Incidence was 1.3 in males and 0.8 in females. No cases were observed in patients under 35 years of age. Incidence increased after the age of 55 years, reaching a peak in the group aged 70-74 years and declining thereafter. We concluded that ALS incidence in this population was similar to that observed in other Italian regions and European countries, and no variation was identified during the study period.