Anna L.V. Johansson

Reasons for increasing trends in large for gestational age births

OBJECTIVE: To describe the magnitude of change in the proportion of term and postterm (37 completed weeks or more) large for gestational age (LGA) infants between 1992–2001 in Sweden and to examine whether time trends in prevalence of LGA births can be explained by changes in maternal risk factors. METHODS: Using the population-based Swedish Birth Register, we analyzed data from 1992 through 2001 on births of women who delivered live, singleton, term infants without malformations (N = 874,163). Unconditional logistic regression was used to model the odds of LGA birth. RESULTS: Mean birth weight and proportions of LGA births and births 4,500 g or more rose during the period 1992 to 2001. An unadjusted analysis estimated that the risk of LGA birth increased by 23% over 10 years. However, the prevalence of overweight and obesity (body mass index of 25 or greater) increased from 25% to 36%, and the prevalence of smoking decreased from 23% to 11% during the same period. After adjusting trends in all covariates simultaneously, the association between risk of LGA birth and calendar year disappeared. CONCLUSION: The increasing proportions of LGA births over time is explained by concurrent increases in maternal body mass index and decreases in maternal smoking. With the increasing prevalence of overweight among adolescents and young women, the prevalence of LGA infants and associated risks may increase over time. LEVEL OF EVIDENCE II-2

Long-term follow-up of transsexual persons undergoing sex reassignment surgery: Cohort study in Sweden

Context The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the persons body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment. Objective To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons. Design A population-based matched cohort study. Setting Sweden, 1973-2003. Participants All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973–2003. Random population controls (10∶1) were matched by birth year and birth sex or reassigned (final) sex, respectively. Main Outcome Measures Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]). Results The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8–4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8–62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9–8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0–3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls. Conclusions Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group.

Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy

Background. The accuracy of maternal self‐reported smoking information, especially exposure to environmental tobacco smoke, has been questioned. This study aimed to validate self‐reported smoking, smoking cessation, and environmental tobacco smoke exposure in early and late pregnancy, using the biomarker cotinine as the gold standard. Methods. Prospective cohort study of 953 pregnant Swedish women between 1996 and 1998. In‐person interviews and cotinine measurements were performed at 6–12 and 31–34 completed weeks of gestation. All women were asked about nicotine exposures throughout pregnancy, including cigarette smoking, oral snuff, nicotine replacement therapy, and environmental tobacco smoke exposure. Results. The validity of self‐reported daily smoking was high in early and late pregnancy. However, among women reporting smoking cessation before the first interview and between the first and second interviews, 13% and 25% misreported active smoking, respectively. According to cotinine measurements, 22% of non‐smoking women were exposed to environmental tobacco smoke in early pregnancy, and 8% were exposed in late pregnancy. Self‐reported information on environmental tobacco smoke exposure in early and late pregnancy misclassified most exposed women as unexposed. Conclusion. The results of this study indicate that self‐reported smoking information among pregnant women can be trusted. However, among women reporting smoking cessation during pregnancy, the misclassification rate increased with recency of quitting. Environmental tobacco smoke exposure was common among non‐smokers, and the low validity of self‐reported environmental tobacco smoke exposure suggests that future studies on environmental tobacco smoke exposure and risks of pregnancy outcomes may have to rely on biomarker assessments.

Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity

OBJECTIVE: We examined whether an association between preterm birth and risk of autistic disorders could be explained by pregnancy complications or neonatal morbidity. METHODS: This Swedish, population-based, case-control study included 1216 case subjects with autistic disorders who were born between 1987 and 2002 and 6080 control subjects who were matched with respect to gender, birth year, and birth hospital. We assessed associations between gestational age and autistic disorders and adjusted for maternal, birth, and neonatal characteristics. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared with infants born at term, the unadjusted ORs for autistic disorders among very and moderately preterm infants were 2.05 [95% CI: 1.26–3.34] and 1.55 [95% CI: 1.22–1.96], respectively. When we controlled for maternal, pregnancy, and birth characteristics, ORs were reduced to 1.48 [95% CI: 0.77–2.84] and 1.33 [95% CI: 0.98–1.81], respectively. When we also controlled for neonatal complications, ORs were 0.98 [95% CI: 0.45–2.16] and 1.25 [95% CI: 0.90–1.75], respectively. Reductions in risks of autistic disorders related to preterm birth were primarily attributable to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar scores at 5 minutes, and intracranial bleeding, cerebral edema, or seizures in the neonatal period. Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were associated with increased risk of autistic disorders for term but not preterm infants. CONCLUSION: The increased risk of autistic disorders related to preterm birth is mediated primarily by prenatal and neonatal complications that occur more commonly among preterm infants.

Environmental Tobacco Smoke and Risk of Spontaneous Abortion

Background: Studies of exposure to environmental tobacco smoke (ETS) and risk of spontaneous abortion are limited to a few studies of self-reported exposure, and the results have been inconsistent. The aim of this study was to investigate risk of early spontaneous abortion related to ETS and active smoking as defined by plasma cotinine levels. Methods: We conducted a population-based case–control study in Uppsala County, Sweden, between January 1996 and December 1998. Cases were 463 women with spontaneous abortion at 6 to 12 completed weeks of gestation, and controls were 864 pregnant women matched to cases according to the week of gestation. Exposure status was defined by plasma cotinine concentrations: nonexposed, <0.1 ng/mL; ETS-exposed, 0.1–15 ng/mL; and exposed to active smoking, >15 ng/mL. Multivariable analysis was used to estimate the relative risk of spontaneous abortion associated with exposure to ETS and active smoking. Results: Nineteen percent of controls and 24% of cases were classified as having been exposed to ETS. Compared with nonexposed women, risk of spontaneous abortion was increased among both ETS-exposed women (adjusted odds ratio = 1.67; 95% confidence interval = 1.17–2.38) and active smokers (2.11; 1.36–3.27). We could not show a differential effect of exposure to ETS or active smoking between normal and abnormal fetal karyotype abortions. Conclusions: Nonsmoking pregnant women exposed to ETS may be at increased risk of spontaneous abortion. Given the high prevalence of ETS exposure, the public health consequences of passive smoking regarding early fetal loss may be substantial.

Prognosis of Patients With Breast Cancer: Causes of Death and Effects of Time Since Diagnosis, Age, and Tumor Characteristics

PURPOSE The proportion of women living with a diagnosis of breast cancer in developed countries is increasing. Because breast cancer-specific deaths decrease with time since diagnosis, it is important to assess the burden of other causes of death in women diagnosed with breast cancer. METHODS Different causes of death within 10 years from diagnosis were assessed in 12,850 women younger than 75 years of age with stage 1 to 3 breast cancer diagnosed in Stockholm and Gotland regions 1990 to 2006. Flexible parametric survival models were used to estimate hazard ratios over time since diagnosis by tumor characteristics and age at diagnosis. RESULTS The proportion of deaths attributed to breast cancer ranged from 95.0% among women younger than age 45 years at diagnosis to 44.5% among women age 65 to 74 years. The proportions of circulatory system-specific deaths and deaths resulting from other causes increased with older age at diagnosis. Patients with one to three positive lymph nodes were more likely to die as a result of breast cancer during the first 10 years of follow-up compared with women without positive lymph nodes. Women with estrogen receptor (ER) -positive tumors had the same risk of dying as a result of breast cancer 5 years after diagnosis compared with women with ER-negative tumors. CONCLUSION Lymph node negativity is an important long-term predictor of more favorable prognosis. The nature of the relationship between ER status and risk of dying as a result of breast cancer after 5 years of follow-up requires further investigation. Circulatory system diseases are an important cause of death, especially in women diagnosed with breast cancer at an older age.

Helicobacter pylori status in family members as risk factors for infection in children

This study aimed to disentangle the independent contributions of Helicobacter pylori infections in mothers, fathers and siblings to the risk for the infection in the 11-13 years age group. Index children from a cross-sectional Stockholm school survey and their family members completed questionnaires and contributed blood samples. H. pylori serostatus was determined with an enzyme-linked immunosorbent assay and immunoblot. Fifty-four seropositive and 108 seronegative index children were included and 480 out of 548 family members contributed blood. In multivariate logistic regression modelling, having an infected mother (OR 11.6, 95% CI 2.0-67.9) or at least one infected sibling (OR 8.1, 95% CI 1.8-37.3) were risk factors for index child infection, whilst the influence of infected fathers was non-significant. Birth in high-prevalence countries was an independent risk factor (OR 10.4, 95% CI 3.4-31.3). H. pylori infections in mothers and siblings and birth in high-prevalence countries stand out as strong markers of infection risk amongst children in Sweden.

Increased Mortality in Women with Breast Cancer Detected during Pregnancy and Different Periods Postpartum

Background: Because of a continued trend toward postponed childbearing, the incidence of pregnancy-associated breast cancer (PABC) is likely to increase. This study investigated the mortality in women with PABC in relation to when the tumor was detected (during pregnancy, different postpartum periods) and by time since diagnosis, compared with women with non-PABC. Methods: A population-based cohort study of 15,721 Swedish women diagnosed with breast cancer between ages 15 to 44 years, of whom 1,110 (7%) had a PABC (diagnosed during or within two years after pregnancy). Information on outcome and potential confounders was obtained from population-based health registers. Mortality rates and HRs with 95% CIs were estimated. Results: Women with PABC had higher mortality compared with women with non-PABC diagnosed at the same age and calendar period. Among women with PABC, 46% died within 15 years after diagnosis, whereas 34% died among non-PABC patients. The mortality in both groups peaked at around two years after diagnosis, with the highest peak occurring in women diagnosed 4 to 6 months after delivery (HR = 3.8, 95% CI: 2.4–5.9). An increased mortality among women with PABC remained until 10 years after diagnosis. Conclusions: Women with PABC had a poorer prognosis compared with women with breast cancer and no recent birth. The mortality increase was most pronounced in the subgroup of women diagnosed shortly after delivery. Impact: An increased awareness among clinicians may help reduce the mortality in women with PABC, for example, by avoiding undue delays in diagnosis and treatment. Cancer Epidemiol Biomarkers Prev; 20(9); 1865–72. ©2011 AACR.

Hysterectomy and risk of cardiovascular disease: a population-based cohort study.

AIMS Hysterectomy for benign indications is one of the commonest surgical procedures in women, but the association between the procedure and cardiovascular disease (CVD) is not fully understood. In this population-based cohort study, we studied the effects of hysterectomy, with or without oopherectomy, on the risk of later life CVD. METHODS AND RESULTS Using nationwide healthcare registers, we identified all Swedish women having a hysterectomy on benign indications between 1973 and 2003 (n = 184,441), and non-hysterectomized controls (n = 640,043). Main outcome measure was the first hospitalization or death of incident CVD (coronary heart disease, stroke, or heart failure). Occurrence of CVD was determined by individual linkage to the Inpatient Register. In women below age 50 at study entry, hysterectomy was associated with a significantly increased risk of CVD during follow-up [hazard ratio (HR), 1.18, 95% confidence interval (CI), 1.13-1.23; HR, 2.22, 95% CI, 1.01-4.83; and HR, 1.25, 95% CI, 1.06-1.48; in women without oopherectomy, with oopherectomy before or at study entry, respectively, using women without hysterectomy or oopherectomy as reference]. In women aged 50 or above at study entry, there were no significant associations between hysterectomy and incident CVD. CONCLUSIONS Hysterectomy in women aged 50 years or younger substantially increases the risk for CVD later in life and oopherectomy further adds to the risk of both coronary heart disease and stroke.

Socioeconomic factors and risk of esophageal adenocarcinoma: a nationwide Swedish case-control study.

Background: The increase in esophageal adenocarcinoma incidence in developed countries remains unexplained. Although low socioeconomic status (SES) is linked to an increased risk of esophageal squamous cell carcinoma (SCC), the relation with adenocarcinoma is uncertain. Methods: We addressed the importance of various socioeconomic factors in a Swedish population-based case-control study, where 189 and 262 cases of esophageal adenocarcinoma and the gastric cardia, respectively, 167 cases of esophageal SCC, and 820 control participants underwent personal interviews. Our classification of SES was derived from occupational histories. Relative risks were estimated by odds ratios with 95% confidence intervals (95% CI), derived from conditional logistic regression, in crude and adjusted models. Results: The risk of both esophageal adenocarcinoma and SCC increased with decreasing SES; unskilled workers had 3.7-fold (95% CI, 1.7-7.7) and 2.1-fold (95% CI, 1.0-4.7) increased risks, respectively, compared with age- and sex-comparable professionals. Adjustment for reflux symptoms, body mass, and tobacco smoking attenuated the excess risk for esophageal adenocarcinoma, whereas adjustment for Helicobacter pylori infection in a subset of the interviewed participants did not influence the results. Life without a partner was associated with a >2-fold increased risk of both histologic types of esophageal cancer, associations that remained even after multiple adjustments. Conclusions: Esophageal adenocarcinoma and SCC are both linked to low SES and a life without a partner. These associations are only partly explained by established risk factors.