Long-Term Morbidity and Mortality in Children After In Utero Exposure to Maternal Cancer
Iben Katinka GreiberJakob Hansen ViuffLone StorgaardMona Aarenstrup KarlsenØjvind LidegaardAnders Pretzmann MikkelsenLene MellemkjærCristel Sørensen Hjortshøj
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PURPOSE In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero. METHODS This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis. RESULTS Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy. CONCLUSION Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.To compare the survival outcomes of patients over 85 years of age with bladder cancer.We used data collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier (KM) curves were generated for overall survival with 95% confidence intervals (CIs). Cox proportional hazard models were used to estimate the hazard ratios among cases in different groups.Of the 9,321 patients who met the inclusion criteria, 6,703 (71.9%) were men and 2,618 (28.1%) were women, with a mean (standard deviation) age of 88.68 (3.216) years. The median follow-up time of this cohort was 18 months. In the low-grade non-muscle-invasive bladder cancer (LG NMIBC) group, our analysis showed that no further treatment led to a better prognosis after the first transurethral bladder tumor resection (TURBT). In the high-grade NMIBC (HG NMIBC) cohort, major therapy was correlated with better OS in univariable and multivariable analyses [hazard ratio (HR) 0.450; 95% CI: 0.351-0.577]. Trimodal therapy gave a better prognosis in the muscle-invasive bladder cancer (MIBC) cohort (HR 1.395; 95% CI: 1.147-1.697). In addition, none of the county factors were risk factors for prognosis in multivariable analysis.Minor and major therapies do not have a better prognosis after TURBT in LG NMIBC. Major therapy has better oncological outcomes in LG NMIBC and MIBC than minor therapy. Trimodal therapy leads to longer OS in MIBC. In addition, none of the county factors were risk factors for prognosis.
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To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators.The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression.443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts.All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.
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Background and objectives Sedentary behavior is associated with increased mortality in the general population. Whether replacing sedentary behavior with low- or light-intensity activities confers a survival benefit in the general or CKD populations is unknown. Design, setting, participants, & measurements This observational analysis of the 2003–2004 National Health and Nutrition Examination Survey examined the associations of low- and light-intensity activities with mortality. On the basis of the number of counts/min recorded by an accelerometer, durations of sedentary (<100/min), low (100–499/min), light (500–2019/min), and moderate/vigorous (≥2020/min) activity were defined and normalized to 60 minutes. The mortality associations of 2 min/hr less sedentary duration in conjunction with 2 min/hr more (tradeoff) spent in one of the low, light, or moderate/vigorous activity durations while controlling for the other two activity durations were examined in multivariable Cox regression models in the entire cohort and in the CKD subgroup. Results Of the 3626 participants included, 383 had CKD. The mean sedentary duration was 34.4±7.9 min/hr in the entire cohort and 40.8±6.8 in the CKD subgroup. Tradeoff of sedentary duration with low activity duration was not associated with mortality in the entire cohort or the CKD subgroup. Tradeoff of sedentary duration with light activity duration was associated with a lower hazard of death in the entire cohort (hazard ratio, 0.67; 95% confidence interval, 0.48 to 0.93) and CKD subgroup (hazard ratio, 0.59; 95% confidence interval, 0.35 to 0.98). Tradeoff of sedentary duration with moderate/vigorous activity duration had a nonsignificant lower hazard in the entire cohort and CKD subgroup. Conclusions Patients with CKD are sedentary nearly two thirds of the time. Interventions that replace sedentary duration with an increase in light activity duration might confer a survival benefit.
Subgroup analysis
Sedentary lifestyle
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Approximately 80% of patients with Crohn's disease will require surgery. Surgery for Crohn's disease is not curative, and recurrence is typical. In this cohort study, based on nationwide Danish registries, we examined the association between postoperative treatment with anti-tumor necrosis factor α (anti-TNF-α) agents and reoperation.The association was examined in cohort 1 = patients not treated with anti-TNF-α agents within 6 months before operation, cohort 2 = patients treated with anti-TNF-α agents within 6 months before operation. Within both cohorts, we defined postoperative exposure to anti-TNF-α agents as at least 1 treatment within 6 months after the first operation and the reference cohorts were those not treated. Patients were followed from 6 months after operation and until 5 years. We used Cox proportional-hazards regression to compute adjusted hazard ratios with 95% confidence intervals.In cohort 1, 31 (1.3%) were treated with anti-TNF-α agents within 6 months after operation and compared with those not treated, the adjusted hazard ratio of reoperation among those treated with anti-TNF-α agents was 3.53 (95% confidence interval: 1.61-7.72). In cohort 2, 63 (16.3%) were treated with anti-TNF-α agents within 6 months after operation, and the corresponding adjusted hazard ratio of reoperation was 2.16 (95% confidence interval: 1.11-4.18).Our data suggest that anti-TNF-α treatment within 6 months after the first operation is not associated with a reduction in the need for subsequent operation. Uncontrolled confounding might have influenced our results, and, furthermore, future studies are warranted to clarify whether our study population is different from populations most often associated with postoperative anti-TNF-α treatment.
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-The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development.-We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups.-During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92-1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40-4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.
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Iodine deficiency in pregnancy is a common problem in the United States and parts of Europe, but whether iodine deficiency is associated with increased pregnancy loss has not been well studied. The LIFE study provided an excellent opportunity to examine the relationship between iodine status and pregnancy loss because women were monitored prospectively to ensure excellent ascertainment of conceptions. The LIFE study, a population-based prospective cohort study, monitored 501 women who had discontinued contraception within two months to become pregnant; 329 became pregnant, had urinary iodine concentrations measured on samples collected at enrollment, and were followed up to determine pregnancy outcomes. Of the 329, 196 had live births (59.5%), 92 (28.0%) had losses, and 41 (12.5%) withdrew or were lost to follow up. Urinary iodine concentrations were in the deficiency range in 59.6% of the participants. The risk of loss, however, was not elevated in the mildly deficient group (hazard ratio 0.69, 95% confidence interval 0.34, 1.38), the moderately deficient group (hazard ratio 0.81, 95% confidence interval 0.43, 1.51), or the severely deficient group (hazard ratio 0.69, 95% confidence interval 0.32, 1.50). Iodine deficiency, even when moderate to severe, was not associated with increased rates of pregnancy loss. This study provides some reassurance that iodine deficiency at levels seen in many developed countries does not increase the risk of pregnancy loss.
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In Brief OBJECTIVE: To estimate the risk of stillbirth in a second pregnancy when previous stillbirth, preterm, and small-for-gestational age (SGA) births occurred in the previous pregnancy. METHODS: This was a population-based cohort study in New South Wales Australia from 2002 to 2006. Singleton births in a first pregnancy were linked to a second pregnancy using data from the New South Wales Midwives Data Collection and the New South Wales Perinatal Death Database. Deaths were classified according to the Perinatal Mortality Classifications of the Perinatal Society of Australia and New Zealand. Crude and adjusted hazard ratios were estimated using a proportional hazards model. RESULTS: Delivery of an SGA newborn in the first pregnancy was associated with increased risks of stillbirth in a second pregnancy (hazard ratio 1.73, 95% confidence interval [CI] 1.15–2.60) and risk was further increased with prematurity (hazard ratio 5.65, 95% CI 1.76–18.12). Stillbirth in a first pregnancy had a nonsignificant association with stillbirth in the second pregnancy (hazard ratio 2.03, 95% CI 0.60–6.90). For women aged 30–34 years, the absolute risk of stillbirth up to 40 completed weeks of gestation was 4.84 per 1,000 among women whose first pregnancy was a stillbirth and 7.19 per 1,000 among women whose first pregnancy was preterm and SGA. CONCLUSION: Delivering an SGA and preterm neonate in a first pregnancy is associated with greater risks for stillbirth in a second pregnancy than delivering a previous stillbirth. All factors merit improved surveillance in a subsequent pregnancy, and research should address underlying factors common to all three outcomes. LEVEL OF EVIDENCE: II Risks of stillbirth in a second pregnancy are greater when the previous neonate was small for gestational age and preterm compared with a previous stillbirth.
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Background A beneficial effect of metformin on heart failure requires confirmation. Methods and Results Patients with new-onset type 2 diabetes mellitus during 1999 to 2005 were enrolled from Taiwan's National Health Insurance database and followed up from January 1, 2006, until December 31, 2011. Main analyses were conducted in an unmatched cohort (172 542 metformin ever users and 43 744 never users) and a propensity score matched-pair cohort (matched cohort I, 41 714 ever users and 41 714 never users). Hazard ratios were estimated by Cox hazard regression incorporated with the inverse probability of treatment weighting using the propensity score in the unmatched cohort and by naïve method in the matched cohort I. Results showed that the respective incidence rates of heart failure hospitalization in ever users and never users were 304.25 and 864.31 per 100 000 person-years in the unmatched cohort (hazard ratio, 0.350; 95% CI, 0.329-0.373) and were 469.66 and 817.01 per 100 000 person-years in the matched cohort I (hazard ratio, 0.571; 95% CI, 0.526-0.620). A dose-response pattern was consistently observed while estimating hazard ratios for the tertiles of cumulative duration of metformin therapy. Findings were supported by another propensity score-matched cohort created after excluding 10 potential instrumental variables in the estimation of propensity score (matched cohort II). An approximately 40% lower risk was consistently observed among ever users in different models derived from the matched cohorts I and II, but models from the matched cohort II were less subject to model misspecification. Conclusions Metformin use is associated with a lower risk of heart failure hospitalization.
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