Bengt Haglund

Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden

Aims/hypothesisIn the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study.MethodsWe followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted the occurrence of malignancies. Seven different nationwide registers were used to obtain information on insulin exposure, outcome and possible confounders; these were linked using the unique personal identity number assigned to every Swedish resident.ResultsAfter adjustment for age and, when appropriate, sex, users of insulin glargine alone (no other types of insulin), compared with users of types of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31–3.03) for breast cancer, 0.93 (95% CI 0.61–1.40) for gastrointestinal cancer, 1.27 (95% CI 0.89–1.82) for prostate cancer and 1.07 (95% CI 0.91–1.27) for any type of malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at birth of first child, cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 (95% CI 1.29–3.00). The 95% CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin.Conclusions/interpretationIn Sweden, during 2006 and 2007, women using insulin glargine alone (no other types of insulin) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine. This result may be due to a random fluctuation; the possibilities for examining validity are limited, and no statistically significant results were obtained for any other individual cancer site or for the outcome ‘all malignancies’. No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study.

Cigarette Smoking as a Risk Factor for Sudden Infant Death Syndrome: A Population-Based Study.

Risk factors for sudden infant death syndrome (SIDS) were examined in a prospective study based on Swedish births between 1983 and 1985. All infants surviving the first week of life were included (279,938). The overall rate of SIDS was 0.7 per 1,000 first week survivors. Elevated relative risks were associated with low maternal age, multiparity, maternal smoking, and male infants. Smoking doubled the risk and a clear dose-response relation by amount smoked was observed. Maternal smoking also seemed to influence the time of death, as infants of smokers died at an earlier age. In countries like Sweden, smoking may be the single most important preventable risk factor for sudden infant death syndrome.

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Design Population based cohort study using data from the national health registers. Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants More than 1.6 million infants born after gestational week 33. Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Teenage pregnancies and risk of late fetal death and infant mortality.

Objective To estimate the effect of low maternal age on late fetal death and infant mortality and to estimate the extent of any increase in infant mortality attributable to higher rates of preterm birth among teenagers.

The incidence of adverse events in Swedish hospitals: a retrospective medical record review study

Objectives To estimate the incidence, nature and consequences of adverse events and preventable adverse events in Swedish hospitals. Design A three-stage structured retrospective medical record review based on the use of 18 screening criteria. Setting Twenty-eight Swedish hospitals. Population A representative sample (n = 1967) of the 1.2 million Swedish hospital admissions between October 2003 and September 2004. Main Outcome Measures Proportion of admissions with adverse events, the proportion of preventable adverse events and the types and consequences of adverse events. Results In total, 12.3% (n = 241) of the 1967 admissions had adverse events (95% CI, 10.8–13.7), of which 70% (n = 169) were preventable. Fifty-five percent of the preventable events led to impairment or disability, which was resolved during the admission or within 1 month from discharge, another 33% were resolved within 1 year, 9% of the preventable events led to permanent disability and 3% of the adverse events contributed to patient death. Preventable adverse events led to a mean increased length of stay of 6 days. Ten of the 18 screening criteria were sufficient to detect 90% of the preventable adverse events. When extrapolated to the 1.2 million annual admissions, the results correspond to 105 000 preventable adverse events (95% CI, 90 000–120 000) and 630 000 days of hospitalization (95% CI, 430 000–830 000). Conclusions This study confirms that preventable adverse events were common, and that they caused extensive human suffering and consumed a significant amount of the available hospital resources.

Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

Abstract Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses. Design: Population based cohort study. Subjects: 1 026 249 pregnancies without congenital malformations. Setting: Sweden 1983-92. Main outcome measure: Late fetal death rate. Results: Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women ≥175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers. Conclusions: Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants—for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension. Key messages Small for gestational age fetuses are at increased risk of late fetal death regardless of the underlying determinants The effect of birthweight ratio on risk of late fetal death is modified by underlying determinants, except maternal age Regardless of birthweight ratio the rates of late fetal death are higher among women aged 35 years or older compared with younger women In pregnancies of extremely small for gestational age fetuses lower rates of late fetal death are associated with a maternal age of less than 35 years, short maternal stature, multiple births, and hypertensive disorders In pregnancies with non-malformed fetuses late fetal death rates are increased in smokers, in multiple births, and in women with severe pre-eclampsia.

The risk of maternal ischaemic heart disease after gestational hypertensive disease

Objective  The aim of this study was to investigate whether the risk of developing ischaemic heart disease (IHD) later in life increases with severity and recurrence of gestational hypertensive disease.

Sinistrality—a side-effect of prenatal sonography: A comparative study of young men

Although ultrasound during pregnancy is used extensively, there is little published on adverse fetal effects. We undertook a cohort study including men born in Sweden from 1973 to 1978 who enrolled for military service. We estimated relative risks for being born left-handed according to ultrasound exposure in fetal life using logistic regression analysis. Eligible for the study were 6,858 men born at a hospital that included ultrasound scanning in standard antenatal care (exposed) and 172,537 men born in hospitals without ultrasound scanning programs (unexposed). During the introduction phase (1973 to 1975) there was no difference in left-handedness between ultrasound exposed and unexposed (odds ratio = 1.03, 95% confidence interval (CI) = 0.91 to 1.17). When ultrasonography was offered more widely (1976 to 1978), the risk of left-handedness was higher among those exposed to ultrasound compared with those unexposed (odds ratio = 1.32, 95% CI = 1.16 to 1.51). We conclude that ultrasound exposure in fetal life increases the risk of left-handedness in men, suggesting that prenatal ultrasound affects the fetal brain.

Deliveries, mothers and newborn infants in Sweden, 1973-2000: Trends in obstetrics as reported to the Swedish medical Birth Register

Introduction.  The aim of this report is to present descriptive data from the Swedish Medical Birth Register (MBR) reflecting trends in obstetric and neonatal practices over three decades.

Teenage childbearing and long-term socioeconomic consequences: a case study in Sweden.

CONTEXT Whether long-term socioeconomic problems experienced by many teenage mothers are a reflection of preexisting disadvantage or are consequences of teenage motherhood per se remains unclear. METHODS National data on all women born in Sweden from 1941 to 1970 who were younger than age 30 when they first gave birth (N=888,044) were analyzed. The outcome measures, assessed during adulthood, were employment status, socioeconomic status, educational attainment, single motherhood, family size, receipt of disability pension and dependence on welfare. Multiple logistic regression techniques were used to adjust for maternal birth cohort and for socioeconomic background of the womans family. RESULTS Compared with Swedish women who first gave birth at ages 20-24, those who were teenage mothers had significantly increased odds of each unfavorable socioeconomic outcome in later life, even after the data were adjusted for family socioeconomic situation and maternal birth cohort. For example, teenage motherhood was positively associated with low educational attainment (odds ratios of 1.7-1.9, depending on the specific age during adolescence when the woman gave birth), with single living arrangements (odds ratios, 1.5-2.3), with high parity (odds ratios, 2.6-6.0), with collecting a disability pension (odds ratios, 1.6-1.9) and with welfare dependency (odds ratios, 1.9-2.6). These trends were usually linear, with the highest odds ratios corresponding to women who had had their first child at the youngest ages. CONCLUSIONS A longitudinal analysis of record-linkage data from Sweden supports the view that childbearing during adolescence poses a risk for socioeconomic disadvantage in later life--even for adolescents from relatively comfortable backgrounds and for those who studied beyond elementary school.