X-ray exposure in utero and school performance: a population-based study of X-ray pelvimetry.

AIM: To investigate the association between exposure to ionising radiation from pelvimetric examinations in utero and school performance. MATERIAL AND METHODS: This was a population-based cohort study comprising 46,066 children born in the county of Östergötland, Sweden, from 1980 through 1990. Through record linkage between Swedish registers, children exposed in utero to X-ray pelvimetry examination were compared to other children born in the same county during the study period, as well as to their unexposed siblings. Outcome variable was primary school grades, expressed in centiles and calculated through linear regression. RESULTS: In the univariate analysis, children exposed to X-ray pelvimetry in utero had higher school grades compared to unexposed children (point estimate 3 centiles, 95% confidence interval [CI]: 1.5 to 4.6). When sex, mother's education and income, birth order, and birth position were included in the analysis; however, the difference was reduced and the association was no longer statistically significant (PE 1.4, 95% CI: -0.1 to 2.8). Comparing exposed children with their siblings showed no statistical difference in univariate analysis or in multivariate analysis. CONCLUSION: No suggestion was found of a negative effect on school performance from in utero exposure of diagnostic X-ray pelvimetry.

Increased stomach cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend<0.001), with an OR of 20.5 (3.7-114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5-2.5; 14 cases and 23 controls). CONCLUSIONS: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

Pancreatic cancer risk after treatment of Hodgkin lymphoma.

BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.

Risk of treatment-related esophageal cancer among breast cancer survivors.

BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Starting time for induction of labor and the risk for night-time delivery.

OBJECTIVE: To analyze if starting time for labor induction affected the risk of night-time delivery, and to evaluate to what extent the risk was influenced by Bishop score at start of induction, mode of induction, and parity. METHOD: A retrospective cohort study of women who delivered at Danderyd Hospital, Stockholm, Sweden, 2002-2006, comprising 1940 women induced by Dinoprostone (PGE(2)) or transcervical balloon catheter (BARD). Risks for night-time delivery were calculated as absolute risk and Odds Ratios by unconditional logistic regression using induction of labor in the morning as reference. RESULTS: For nulliparae with Bishop score 0-3 induced by BARD, odds ratios for night-time delivery were 0.42 (95% C.I. 0.19-0.93) and 0.09 (95% C.I. 0.02-0.47) when inductions started in the afternoon and evening, respectively, compared to inductions starting in the morning For multiparae, however, the risk of night-time delivery was highest if induction started in the evening. Compared to inductions started in the morning, odds ratios for night-time delivery were 3.53 (95% C.I. 2.57-4.83) and 8.49 (95% C.I. 4.45-16.19) for induction starting in the afternoon and evening, respectively. CONCLUSION: Starting time of labor induction affects the risk of giving birth at night. For nulliparae induced by BARD, starting the induction in the evening instead of during the day may reduce the number of night-time deliveries substantially. For multiparae, however, our data suggest that induction of labor should take place in the morning.

Large fetal size in early pregnancy associated with macrosomia.

OBJECTIVE: To assess if fetal size at the time of ultrasound dating examination is associated with the risk of macrosomia and complications associated with macrosomia. METHODS: This was a retrospective cohort study of 19 377 singleton pregnancies dated in gestational weeks 16-20 during the period 1998-2004 at Danderyd Hospital, Stockholm, Sweden. Obstetric outcome was assessed through linkage to the Swedish Medical Birth Register. RESULTS: When fetuses were > or = 7 days larger than expected at dating, compared with the expected size according to last menstrual period, there was a 59% increase in the risk of birth weight > or = 4500 g and a 145% increase in the risk of birth weight > or = 5000 g (odds ratio (OR), 1.59; 95% CI, 1.12-2.24 and OR, 2.45; 95% CI, 1.22-4.90, respectively). For a birth weight of > or = 4000 g the risk estimate was 1.19 (95% CI, 0.96-1.47). CONCLUSION: Fetuses that are larger than expected in the second trimester have an increased risk of macrosomia. This emphasizes that fetal size in early pregnancy is not only a function of gestational duration, but also of fetal growth. However, only a limited proportion of all infants born macrosomic can be identified as such at the time of ultrasound dating.

Amount drained at ultrasound-guided thoracentesis and risk of pneumothorax.

BACKGROUND: It has been suggested that no upper limit of the fluid amount drained is necessary when performing ultrasound-guided thoracentesis, but the risk of pneumothorax when large amounts of fluid are drained has not been studied in detail. PURPOSE: To study the amount of drained fluid at ultrasound-guided thoracentesis and the subsequent risk of pneumothorax. MATERIAL AND METHODS: Prospectively collected information on all ultrasound-guided thoracenteses performed at a county hospital between 2004 and 2006 was evaluated. In total, 735 thoracenteses in 471 patients were included. Chest radiographs performed within 14 days after thoracentesis were identified to obtain cases of pneumothorax and cases treated with tube thoracostomy. Data were analyzed by logistic regression. The study was approved by the regional research ethics committee. RESULTS: There was a steep increase in risk for pneumothorax when large amounts of fluid were drained. Compared to a thoracentesis of 0.8-1.2 l, drainage of 1.8-2.2 l was associated with a more than threefold increase in risk for pneumothorax (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.28-11.2), and after drainage of 2.3 l or more, the increase in risk was almost sixfold (OR 5.7, 95% CI 1.30-24.7). The association between the amount drained and the risk of pneumothorax was even more pronounced for pneumothoraces requiring tube thoracostomy (P for trend <0.0001). Nine of 11 tube thoracostomies occurred after thoracenteses of 1.8 l or more. CONCLUSION: Our study suggests that drainage of large amounts of fluid at ultrasound-guided thoracentesis is a risk factor for pneumothorax.

Being born too small, too early, or both: does it matter for risk of hypertension in the elderly?

BACKGROUND: Low birth weight is an often-reported risk factor for high blood pressure later in life. This study investigates the selective contributions of preterm birth and poor fetal growth to later risk of hypertension. METHODS: A total of 250,000 Swedish birth records from 1925 through 1949 were examined. All subjects born with a gestational duration below 35 weeks and/or a birth weight < or =2,000 g (girls) or < or =2,100 g (boys) were included, as well as an equal number of controls. This yielded a cohort of 6,269 subjects, of which 2,502 were born at <35 weeks of gestation, and 1,226 subjects had a birth weight < or =2,000 g (girls) or < or =2,100 g (boys). The main outcome measure was diagnosis of hypertension in the Swedish Hospital Discharge Register from 1987 through 2006. RESULTS: There were 838 cases of hypertension in the cohort. Birth weight was negatively associated with hypertension (P for trend = 0.0005). This effect was explained by poor fetal growth: when compared with subjects with a normal fetal growth, those born small for gestational age had a 54% increase in risk of hypertension. In contrast, there was no association between gestational duration and hypertension. CONCLUSION: For those born in the first half of the twentieth century, the association between low birth weight and adult hypertension is due to poor fetal growth and not due to preterm birth.

Expected day of delivery from ultrasound dating versus last menstrual period--obstetric outcome when dates mismatch.

OBJECTIVE: To analyse the association between fetal size at time of dating ultrasound and risk for preterm delivery and small-for-gestational-age (SGA) birth and to evaluate if timing of ultrasound, that is before 14 weeks of gestation or after 16 weeks affects this association. DESIGN: Retrospective cohort study. SETTING: Ultrasound departments of Ultragyn, Stockholm, Sweden. POPULATION: A total of 28,776 singleton pregnancies dated between 1998 and 2004. METHODS: Obstetric outcome was assessed through linkage of the cohort to the Swedish Medical Birth Register. MAIN OUTCOME MEASURES: Risks of preterm delivery, low birthweight for gestational age, pre-eclampsia, asphyxia, respiratory distress, instrumental delivery, caesarean section, and postterm birth were calculated for the groups dated early and late. RESULTS: When the expected date of delivery was postponed after ultrasound dating by 7 days or more, there was an increased risk for preterm delivery and pre-eclampsia in the late dating group (OR 1.49, 95% CI 1.27-1.73 and OR 1.27, 95% CI 1.02-1.60, respectively) but not in the early dating group. In both dating groups, there was an increased risk for SGA birth (OR 1.77, 95% CI 1.13-2.78 and OR 2.09, 95% CI 1.59-2.73, respectively) There was no increased risk for any of the other diagnoses. CONCLUSION: Our study gives further support to the notion that intrauterine growth restriction may be present as early as the first trimester. Accordingly, our study also suggests that surveillance of pregnancies with postponed estimated date of delivery may provide means for increased detection of fetal growth restriction.

Preterm birth, birth weight, and subsequent risk of female breast cancer.

We have previously found an increased risk of breast cancer among women born preterm. To confirm or refute the results, an enlarged study was conducted. The results from this study do not confirm the initial findings and suggest that preterm birth can be ruled out as a risk factor for breast cancer.

Maternal pregnancy estriol levels in relation to anamnestic and fetal anthropometric data.

In epidemiologic studies of perinatal exposures, birth weight has been proposed as a proxy variable for intrauterine estrogen exposure. To assess the validity of this assumption, we performed analyses of the association between estriol levels in 188 women in the 17th, 25th, 33rd, and 37th weeks of pregnancy and the birth weights of their infants. We found a general increase in mean cumulative estriol dose with increasing birth weight category throughout pregnancy. In late pregnancy, mean pregnancy estriol level of mothers of infants in the highest birth weight category (>4,500 gm) was twice as high as that of mothers of infants in the lowest category (<2,500 gm), 775 nmol/liter and 392 nmol/liter, respectively. Smoking lowered the maternal estriol levels by 20% or more throughout pregnancy. With smoking and birth weight included in a regression analysis, maternal age, placental weight, and infant ponderal index did not add any explanatory power to the model. Our data suggest that, on an aggregate level, birth weight can be used as a proxy variable of intrauterine estriol exposure.

Sickness in pregnancy and sex of child.

We report a female predominance among the offspring of mothers with hyperemesis gravidarum.

Elevation of cyclosporin A blood levels during carvedilol treatment in renal transplant patients.

In a consecutive study of 21 renal transplant patients suffering from chronic vascular rejection (CVR) we added the beta-receptor-blocking drug carvedilol to their regular medication. The purpose was to investigate possible pharmacokinetic interactions between carvedilol and cyclosporine (CsA), since carvedilol will soon be used in clinical trials in renal transplant patients with CVR. On the first day of the study the patients received 6.25 mg of carvedilol added to their daily medication. The dose was increased stepwise to 50 mg while the doses of other beta-blocking drugs were decreased. The goal was to exchange atenolol with carvedilol at a ratio of 2:1 when substituting atenolol with carvedilol. The patients' blood pressure was the final determinant of the dose of carvedilol. The trough levels of CsA were measured on days 1, 14, 30, 90 and 180. It was found that the blood levels of CsA increased when carvedilol was introduced. Thus, the doses of CsA had to be reduced in order to keep the blood levels within the therapeutic range. At 90 d, the daily doses of CsA had been reduced from 3.7 +/- 0.3 to 3.0 +/- 0.2 mg/kg BW (p < 0.001). The present results suggest an interaction between carvedilol and CsA that demands a 20% average reduction of CsA doses to maintain the CsA blood levels within the therapeutic range. However, the interaction shows a great interindividual variation, calling for careful monitoring of the CsA blood levels.