A history of cesarean section and future maternal long-term risk for neoplasms: a population-based cohort study.

OBJECTIVE: Mode of delivery has long-term implications on the mother, including recent data regarding the level of transmission of fetal microchimeric cells (FMc) and their possible effect on cancer development. We aimed to evaluate the association between cesarean section (CS) and future risk for neoplasms. STUDY DESIGN: A population-based cohort analysis comparing the long-term risk for neoplasms between patients that delivered only by CS to those that delivered only vaginally (VD). Neoplasms were pre-defined based on ICD-9 codes. Deliveries occurred between the years 1991-2017 in a tertiary medical center. Kaplan-Meier survival curves were used to compare the cumulative incidence of neoplasms and Cox proportional hazards models were constructed to control for confounders. RESULTS: During the study period 105,992 patients met the inclusion criteria; 14150 (13.4%) of patients had only CS and 91842 (86.6%) had VD (comparison group). The CS group had significantly higher incidence of benign and malignant neoplasms (4.73 per 1000 patient-years versus 3.88 per 1000 patient-years, OR = 1.26, 95% CI 1.16-1.37; p = 0.001; 2.19 per 1000 patient-years of follow up versus 1.93 per 1000 patient-years, OR = 1.16, 95% CI 1.03-1.31; p = 0.013). Specifically, the CS group had higher incidence of uterine cancer (1.2 versus 0.06 per 1000 patient-years, OR = 1.97, 95% CI 1.14-3.39; p = 0.013). The cumulative incidence of benign, malignant and uterine neoplasms was significantly higher in the CS group (Log rank test p = 0.001; 0.036 and 0.014; respectively). Importantly, no significant association was found with breast and ovarian malignancies." When performing a Cox regression model controlling for confounders, the risk for malignancy-related hospitalizations remained significant (adjusted HR = 1.22, 95% CI 1.01-1.48; p = 0.031) but not for uterine cancer (adjusted HR = 1.6, 95% CI 0.9-2.8; p = 0.103). CONCLUSION: Our findings provide support to linkage between delivery by cesarean section and future maternal malignancy.

Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]. Half the patients had previous echocardiographic studies available for comparison. RESULTS: The average PLD treatment duration was 23.6 ± 10.8 months (range 13-57), accumulating dose of 1387 ± 483 mg (range 780-2538 mg). The study group had a normal LVEF both by 2D-echo (60 ± 5%, range 50-67) and 3D echo (58 ± 5%, range 46-63). Two patients (14%) were found to have minimally reduced ejection fraction by 2D and 3D echo (50%/46% and 51%/49%, respectively) that did not meet the current definition of CTX. For the seven patients who had consecutive echocardiography studies, the average LVEF remained stable between studies (59 ± 7, 60 ± 9 and 58 ± 10.5% for the latest study, previous, p < 0.79, and most remote study p < 0.9); No change was found in average left ventricular/right ventricular global longitudinal strain as well: -20.8 ± 4.6% at the latest study and -19.3 ± 2.6% for the previous (p < 0.51). CONCLUSION: No prevalent or incident cases of cardiotoxicity were found despite prolonged treatment with large cumulative doses of PLD, adding to previous reports on shorter treatment duration.

Fertility Treatments in Women Who Become Pregnant and Carried to Viability, and the Risk for Long-Term Maternal Cardiovascular Morbidity.

Objective The objective of this study was to investigate whether patients who undergo fertility treatments (ovulation induction or in vitro fertilization) have an increased risk for future maternal cardiovascular morbidity. Design A population-based study compared the incidence of long-term cardiovascular morbidity in a cohort of women with and without a previous exposure to fertility treatments. Deliveries occurred during a 25-year period, with a mean follow-up of 11.7 years. Women with known cardiovascular disease and congenital cardiovascular malformations diagnosed before the index pregnancy and multiple pregnancies were excluded. Results During the study period, 99,291 patients met the inclusion criteria; 4.1% (n = 4,153) occurred in patients with exposure to fertility treatments. Patients with exposure to fertility treatments did not have higher rates of cardiovascular morbidity. Using a Kaplan-Meier survival curve, patients with an exposure to fertility treatments had no higher cumulative incidence of cardiovascular hospitalizations. Using a Cox proportional hazards model, adjusted for confounders such as preeclampsia, diabetes mellitus, and obesity, exposure to fertility treatments remained unassociated with cardiovascular hospitalizations (adjusted hazard ratio = 1.1; 95% confidence interval, 0.9-1.3; p = 0.441). Conclusion In our population, during a mean follow-up period of 11.7, results showed no increased risk for cardiovascular morbidity in women undergoing fertility treatments.

The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up.

OBJECTIVE: To investigate whether an association exists between a history of fertility treatments and future risk of female malignancies. STUDY DESIGN: A population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of fertility treatments including in vitro fertilization (IVF) and ovulation induction (OI). Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Excluded from the study were women with known genetic predisposition for malignancies or known malignancies prior to the index pregnancy. Female malignancies were divided into specific types including ovarian, uterine, breast and cervix. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazard models were used to estimate the adjusted hazard ratios (HRs) for female malignancy. RESULTS: During the study period, 106,031 women met the inclusion criteria; 4.1 % (n = 4363) occurred in patients following fertility treatments. During the follow-up period, patients with a history of IVF treatments had a significantly increased risk of being diagnosed with ovarian and uterine cancer as compared to patients after OI and patients with no history of fertility treatments. Cox proportional hazard models were constructed for ovarian and uterine cancer separately, controlling for confounders such as maternal age and obesity. A history of IVF treatment remained independently associated with ovarian and uterine cancer (adjusted HR 3.9; 95 % CI 1.2-12.6; P = 0.022 and adjusted HR 4.6; 95 % CI 1.4-14.9; P = 0.011; respectively). CONCLUSION: IVF treatments pose a significant risk of subsequent long-term ovarian and uterine cancer.

Is there an association between a history of placental abruption and long-term maternal renal complications?

OBJECTIVE: To investigate whether patients with a history of placental abruption have an increased risk for subsequent maternal long-term morbidity. STUDY DESIGN: A population-based study compared the incidence of long-term renal morbidity in cohort of women with and without a history of placental abruption. Deliveries occurred during a 25-year period, with a mean follow-up duration of 11.2 years. Renal morbidity included kidney transplantation, chronic renal failure, hypertensive renal disease, etc. RESULTS: During the study period 99 354 deliveries met the inclusion criteria; 1.8% (n = 1807) occurred in patients with a diagnosis of placental abruption. Patients with placental abruption did not have higher cumulative incidence of renal related hospitalizations, using Kaplan-Meier survival curve. During the follow-up period patients with a history of placental abruption did not have higher rate of renal morbidity (0.2% versus 0.1%; OR 1.8; 95% CI 0.6-4.8; p = 0.261). When performing a Cox proportional hazards model, adjusted for confounders such as parity and diabetes mellitus, a history of placental abruption was not associated with renal related hospitalizations (adjusted HR, 1.6; 95% CI, 0.6-4.2; p = 0.381). CONCLUSION: Placental abruption, even though considered a part of the "placental syndrome" with possible vascular etiology, is not a risk factor for long-term maternal renal complications.