Ali Ozhand

Perinatal outcomes based on the institute of medicine guidelines for weight gain in twin pregnancies

Abstract Objective: To estimate the impact of the Institute of Medicine’s (IOM) weight gain recommendations on perinatal outcomes in twin pregnancies. Methods: In this multicenter cohort study, using the 2009 IOM guidelines, we examined pregnancy outcomes in 570 uncomplicated diamniotic twin pregnancies. Subjects were grouped according to pre-pregnancy body mass index. Perinatal outcomes were assessed based on whether maternal weekly weight gain was less than, at, or in excess of the recommended IOM guidelines. Results: In women with a normal pre-pregnancy BMI, patients whose weight gain met the IOM recommendations had a significantly higher mean gestational age at delivery; less prematurity and larger birth weight infants compared to women whose weekly weight gain was less or excess than the recommended IOM guidelines. Similarly, when compared with their low weight gain counterparts, overweight women with appropriate weight gain had improved outcomes including higher mean gestational age at delivery, higher birth weight infants and less prematurity. In obese women, the amount of pregnancy weight gain did not impact perinatal outcomes. Conclusion: Our results confirm that weekly maternal weight gain according to the IOM guidelines results in improved outcomes in twin pregnancies. Importantly, women with a normal or overweight pre-pregnancy BMI whose weekly weight gain was less than recommended, had increased risks of prematurity and lower birth weight infants. Similarly, women with a normal pre-pregnancy BMI whose weekly weight gain was excess than recommended had increased risks of prematurity and lower birth weight infants.

Shortening of atrioventricular delay at increased atrial paced heart rates improves diastolic filling and functional class in patients with biventricular pacing

BackgroundUse of rate adaptive atrioventricular (AV) delay remains controversial in patients with biventricular (Biv) pacing. We hypothesized that a shortened AV delay would provide optimal diastolic filling by allowing separation of early and late diastolic filling at increased heart rate (HR) in these patients.Methods34 patients (75 ± 11 yrs, 24 M, LVEF 34 ± 12%) with Biv and atrial pacing had optimal AV delay determined at baseline HR by Doppler echocardiography. Atrial pacing rate was then increased in 10 bpm increments to a maximum of 90 bpm. At each atrial pacing HR, optimal AV delay was determined by changing AV delay until best E and A wave separation was seen on mitral inflow pulsed wave (PW) Doppler (defined as increased atrial duration from baseline or prior pacemaker setting with minimal atrial truncation). Left ventricular (LV) systolic ejection time and velocity time integral (VTI) at fixed and optimal AV delay was also tested in 13 patients. Rate adaptive AV delay was then programmed according to the optimal AV delay at the highest HR tested and patients were followed for 1 month to assess change in NYHA class and Quality of Life Score as assessed by Minnesota Living with Heart Failure Questionnaire.Results81 AV delays were evaluated at different atrial pacing rates. Optimal AV delay decreased as atrial paced HR increased (201 ms at 60 bpm, 187 ms at 70 bpm, 146 ms at 80 bpm and 123 ms at 90 bpm (ANOVA F-statistic = 15, p = 0.0010). Diastolic filling time (P < 0.001 vs. fixed AV delay), mitral inflow VTI (p < 0.05 vs fixed AV delay) and systolic ejection time (p < 0.02 vs. fixed AV delay) improved by 14%, 5% and 4% respectively at optimal versus fixed AV delay at the same HR. NYHA improved from 2.6 ± 0.7 at baseline to 1.7 ± 0.8 (p < 0.01) 1 month post optimization. Physical component of Quality of Life Score improved from 32 ± 17 at baseline to 25 ± 12 (p < 0.05) at follow up.ConclusionsIncreased heart rate by atrial pacing in patients with Biv pacing causes compromise in diastolic filling time which can be improved by AV delay shortening. Aggressive AV delay shortening was required at heart rates in physiologic range to achieve optimal diastolic filling and was associated with an increase in LV ejection time during optimization. Functional class improved at 1 month post optimization using aggressive AV delay shortening algorithm derived from echo-guidance at the time of Biv pacemaker optimization.

First-Trimester Sonographic Prediction of Obstetric and Neonatal Outcomes in Monochorionic Diamniotic Twin Pregnancies

The purpose of this study was to investigate whether discordant nuchal translucency and crown‐rump length measurements in monochorionic diamniotic twins are predictive of adverse obstetric and neonatal outcomes.

Polymorphisms in hormone metabolism and growth factor genes and mammographic density in Norwegian postmenopausal hormone therapy users and non-users

IntroductionMammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD. Dense breast tissue is characterized by increased stromal tissue and (to a lesser degree) increased numbers of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between MD and 340 tagging single nucleotide polymorphisms (SNPs) from about 30 candidate genes in hormone metabolism/growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004.MethodsWe assessed MD on 2,036 postmenopausal women aged 50 to 69 years using a computer-assisted method (Madena, University of Southern California) in a cross-sectional study. We used linear regression to determine the association between each SNP and MD, adjusting for potential confounders. The postmenopausal women were stratified into HT users (EPT and estrogen-only) and non-users (never HT).ResultsFor current EPT users, there was an association between a variant in the prolactin gene (PRL; rs10946545) and MD (dominant model, Bonferroni-adjusted P (Pb) = 0.0144). This association remained statistically significant among current users of norethisterone acetate (NETA)-based EPT, a regimen common in Nordic countries. Among current estrogen-only users (ET), there was an association between rs4670813 in the cytochrome P450 gene (CYP1B1) and MD (dominant model, Pb = 0.0396). In never HT users, rs769177 in the tumor necrosis factor (TNF) gene and rs1968752 in the region of the sulfotransferase gene (SULT1A1/SULT1A2), were significantly associated with MD (Pb = 0.0202; Pb = 0.0349).ConclusionsWe found some evidence that variants in the PRL gene were associated with MD in current EPT and NETA users. In never HT users, variants in the TNF and SULT1A1/SULT1A2 genes were significantly associated with MD. These findings may suggest that several genes in the hormone metabolism and growth factor pathways are implicated in determining MD.

Variation in Inflammatory Cytokine/Growth-Factor Genes and Mammographic Density in Premenopausal Women Aged 50–55

Background Mammographic density (MD) has been found to be an independent risk factor for breast cancer. Although data from twin studies suggest that MD has a strong genetic component, the exact genes involved remain to be identified. Alterations in stromal composition and the number of epithelial cells are the most predominant histopathological determinants of mammographic density. Interactions between the breast stroma and epithelium are critically important in the maturation and development of the mammary gland and the cross-talk between these cells are mediated by paracrine growth factors and cytokines. The potential impact of genetic variation in growth factors and cytokines on MD is largely unknown. Methods We investigated the association between 89 single nucleotide polymorphisms (SNPs) in 7 cytokine/growth-factor genes (FGFR2, IGFBP1, IGFBP3, TGFB1, TNF, VEGF, IL6) and percent MD in 301 premenopausal women (aged 50 to 55 years) participating in the Norwegian Breast Cancer Screening Program. We evaluated the suggestive associations in 216 premenopausal Singapore Chinese Women of the same age. Results We found statistically significant associations between 9 tagging SNPs in the IL6 gene and MD in Norwegian women; the effect ranged from 3–5% in MD per variant allele (p-values = 0.02 to 0.0002). One SNP in the IL6 (rs10242595) significantly influenced MD in Singapore Chinese women. Conclusion Genetic variations in IL6 may be associated with MD and therefore may be an indicator of breast cancer risk in premenopausal women.

Short-term neonatal outcomes in diamniotic twin pregnancies delivered after 32 weeks and indications of late preterm deliveries.

OBJECTIVE We sought to compare neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth and determine the indications of LPTB. STUDY DESIGN We performed a retrospective cohort study. MPTB was defined as delivery between 32(0/7) and 33(6/7) weeks and LPTB between 34(0/7) and 36(6/7) weeks. The composite neonatal adverse respiratory outcome was defined as respiratory distress syndrome and/or bronchopulmonary dysplasia. The composite neonatal adverse nonrespiratory outcome included early onset culture-proven sepsis, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia. LPTB cases were categorized as spontaneous (noniatrogenic), evidence-based iatrogenic, and non-evidence-based (NEB) iatrogenic. RESULTS Of the 747 twin deliveries during the study period, 453 sets met the inclusion criteria with 22.7% (n = 145) MPTB, 32.1% (n = 206) LPTB, and 15.9% (n = 102) term births. Compared with term neonates, the composite neonatal adverse respiratory outcome was increased following MPTB (relative risk [RR] 24; 95% confidence interval [CI] 3.0 to 193.6) and LPTB (RR 13.7; 95% CI 1.8 to 101.8). Compared with term neonates, the composite neonatal adverse nonrespiratory outcome was increased following MPTB (RR 22.3; 95% CI 3.9 to 127.8) and LPTB (RR 5.5; 95% CI 1.1 to 27.6). Spontaneous delivery of LPTB was 63.6% (n = 131/206) and the rate of iatrogenic delivery was 36.4% (n = 75/206). The majority, 66.6% (n = 50/75), of these iatrogenic deliveries were deemed NEB, giving a total of 24.2% (50/206) NEB deliveries in LPTB group. CONCLUSION Our data demonstrate a high rate of late preterm birth among twin pregnancies, with over half of nonspontaneous early deliveries due to NEB indications. Although our morbidity data will be helpful to providers in counseling patients, our finding of high NEB indications underscores the need for systematic evaluation of indications for delivery in LPTB twin deliveries. Furthermore, this may lead to more effective LPTB rate reduction efforts.

Does Early Second-Trimester Sonography Predict Adverse Perinatal Outcomes in Monochorionic Diamniotic Twin Pregnancies?

To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second‐trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes.

Abstract 2286: Short term reduction in mammographic density predicts survival in breast cancer.

Back ground: Identification of the factors that predict response to treatment in breast cancer patients early after diagnosis is important in guiding the treatment strategy. High mammographic density (MD) is a risk factor for breast cancer. However no study has examined the association between change in MD and death in breast cancer survivors. We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting risk of death from breast cancer and all causes. Methods: We evaluated the relationship between reduction in MD and risk of death from all causes within the Health, Eating, Activity, and Lifestyle (HEAL) Study. In a prospective observational study, we studied 403 women diagnosed with primary invasive breast carcinoma between 1995 and 1998 and followed until death or September 2009. We collected mammograms and prognostic, demographic, and lifestyle factors as well as treatments at the time of diagnosis and two years after the diagnosis was made. Mammograms were digitized and MD was measured on cranio-caudal (CC) images of the unaffected breast using a computer assisted program developed at the University of Toronto. MD reduction (MDR) was evaluated based on two mammograms; the first was taken 12 months before diagnosis, and the second approximately 24 months after diagnosis. MDR was defined as the difference between the MD of these two images (% MDR = % preMD -% postMD). Reduction in MD was categorized into a binary variable as women who had a MDR ≥5% compared to those with less than 5% reduction in MD. Cox proportional hazards models were used to estimate the Hazard ratios and 95% confidence intervals. Results: Breast cancer patients with 5% or more reduction in MD were younger (mean age was 55.7 compared to 58.9), more likely to be premenopausal at diagnosis (36.7% compared to 24.0%), and more likely to have a history of oral contraception (73.9% compared to 63.3%). Women with MDR ≥5% were 49% less likely to die from any cause after adjustment for age, BMI, estrogen receptor status, progesterone receptor status, menopausal status at baseline, smoking, stage, tamoxifen use, chemotherapy, radiation therapy, and study center (HR=0.51 CI: 0.3-0.86). The results were stronger when we restricted the analysis to women who were premenopausal at diagnosis. When we restricted the analysis to women who had taken tamoxifen a similar direction was observed but the results were not statistically significant. Conclusion: Result from our data suggests that reduction in mammographic density few years after breast cancer diagnosis may be used as a predictor of overall survival. Citation Format: Ali Ozhand, Roberta Mckean-Cowdin, Leslie Bernstein, Rachel Ballard-Babash, Anne McTiernan, Kathy B. Baumgartner. Short term reduction in mammographic density predicts survival in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2013-2286

Abstract A87: The association between polymorphisms in hormone metabolism and growth factor genes and mammographic density in Norwegian postmenopausal women

Mammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD, and is known to increase breast cancer risk possibly through increased proliferation of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between mammographic density and 340 SNPs (singular nucleotide polymorphisms) from about 30 putative genes in hormone metabolism / growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004. We assessed mammographic density on 2040 postmenopausal women aged 50–69 years using a computer assisted method (Madena, University of Southern California). We ran multiple regressions models (dominant and additive), adjusting for age, body mass index (BMI) with and without adjustments for multiple comparisons (the number of SNPs per gene). We stratified the postmenopausal women into current, past and never EPT users. For postmenopausal current EPT users there was an association between a variant in the prolactin gene (rs10946545) and MD (dominant model p=0.0002). This association was also present in women who were currently using norethisterone acetate (NETA) based EPT, a regimen common in Nordic countries. In past EPT users, we found that two variants in the catechol-O-methyltransferase gene (COMT; rs2239395 and rs5992500) were associated with MD (dominant model p=0.0112), but the association was no longer significant when we adjusted for multiple tests. Among current estrogen only users, there was an association between a variant in the cytochrome P450 gene (CYP1B1; rs4670813) and MD in current estrogen only users (dominant model p=0.0028). We also found an association between a variant in the vascular endothelial growth factor gene (VEGF; rs833052) and MD for current users of high dose NETA EPT (dominant model p=0.0021), while in low dose NETA EPT users a variant in the tumor necrosis factor gene (TNF; rs4947324) was associated with MD (dominant model p=0.0007). We found some evidence that variants in the prolactin and COMT genes were associated with MD in current or past EPT users. We also found associations between genetic variants in TNF and MD in low dose NETA users, and between variants in VEGF and MD in high dose NETA users. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A87.