Ambarina S. Faiz

Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies

Objective: Several clinical and epidemiologic studies have reported disparate data on the prevalence rate as well as risk factors associated with placenta previa - a major cause of third-trimester bleeding. We performed a systematic literature review and identified 58 studies on placenta previa published between 1966 and 2000. Study design: Each study was reviewed independently by the two authors and was scored (on the basis of established criteria) on method of diagnosis of placenta previa and on quality of study design. We extracted data on the prevalence rate of placenta previa, as well as associations with various risk factors from each study. A meta-analysis was then performed to determine the extent to which different risk factors predispose women to placenta previa. Results: Our results showed that the overall prevalence rate of placenta previa was 4.0 per 1000 births, with the rate being higher among cohort studies (4.6 per 1000 births), USA-based studies (4.5 per 1000 births) and hospital-based studies (4.4 per 1000 births) than among case-control studies (3.5 per 1000 births), foreign-based studies (3.7 per 1000 births) and population-based studies (3.7 per 1000 births), respectively. Advancing maternal age, multiparity, previous Cesarean delivery and abortion, smoking and cocaine use during pregnancy, and male fetuses all conferred increased risk for placenta previa. Strong heterogeneity in the associations between risk factors and placenta previa were noted by study design, accuracy in the diagnosis of placenta previa and population-based versus hospital-based studies. Conclusion: Future etiological studies on placenta previa must, at the very least, adjust for potentially confounding effects of maternal age, parity, prior Cesarean delivery and abortions.

Age and the prevalence of bleeding disorders in women with menorrhagia.

OBJECTIVE: A study was conducted to evaluate the frequency and types of hemostatic defects occurring in adolescent and perimenopausal-age women diagnosed with menorrhagia. METHODS: A total of 115 women with a physician diagnosis of menorrhagia, including 25 adolescent women, 25 perimenopausal-age women, and 65 women between the ages of 20 and 44, underwent comprehensive hemostatic testing for possible bleeding disorders. Frequencies of bleeding disorders were calculated and compared. RESULTS: Forty-seven percent of women were found to have hemostatic abnormalities, including platelet dysfunction, von Willebrand’s disease, and coagulation factor deficiencies. Adolescents and perimenopausal-age women with menorrhagia were just as likely to have hemostatic abnormalities as were women aged 20 to 44. CONCLUSION: These results demonstrate that underlying bleeding disorders are frequently found in adolescent, postadolescent reproductive age, and perimenopausal-age women presenting with menorrhagia and suggest that women with menorrhagia should be considered for further hemostatic evaluation. LEVEL OF EVIDENCE: II-2

Development of a screening tool for identifying women with menorrhagia for hemostatic evaluation

OBJECTIVE A study was conducted to develop a short, easy to administer screening tool useful for stratifying women with unexplained menorrhagia for hemostatic testing for underlying bleeding disorders. STUDY DESIGN One hundred forty-six women with a physician diagnosis of menorrhagia underwent comprehensive hemostatic testing for the diagnosis of bleeding disorders, including von Willebrand disease, platelet dysfunction, and coagulation factor deficiencies. A 12 page questionnaire of bleeding symptoms was administered. Bleeding symptoms with high predictive values for laboratory hemostatic abnormalities were combined and used as single variables to calculate sensitivity, specificity, and positive and negative predictive values in order to develop a short screening tool to identify females for testing and evaluation. RESULTS A combination of 8 questions in 4 categories resulted in a sensitivity of 82% (95%CI 75-90) for bleeding disorders. Adding a pictorial blood assessment chart score > 100 increased the sensitivity of the screening tool to 95% (95%CI 91-99). CONCLUSION These results demonstrate the feasibility of a simple questionnaire based screening tool to identify females for testing and evaluation for bleeding disorders.

Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time

Summary.  Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrands deficiency and platelet function defects, are prevalent in women presenting with menorrhagia. The objective of this study was to determine the utility of the platelet function analyser (PFA‐100) and bleeding time (BT) as initial screening tests for underlying bleeding disorders in women with menorrhagia. In this study, 81 women with a physician diagnosis of menorrhagia underwent PFA‐100 testing, BT and comprehensive haemostatic testing. The effectiveness of the PFA‐100 and BT as screening tools in women with menorrhagia was assessed using results of haemostatic testing for von Willebrands disease (VWD) and platelet dysfunction. In women presenting with menorrhagia, the PFA‐100 had a sensitivity 80%, specificity 89%, positive predictive value (PPV) 33%, negative predictive value (NPV) 98% and efficiency 88% for VWD. For platelet aggregation defects, the PFA‐100 closure time had a sensitivity 23%, specificity 92%, PPV of 75%, NPV of 52% and efficiency 55%. The data suggest that the PFA‐100 may be useful in stratifying women with menorrhagia for further von Willebrand testing; however, neither the PFA‐100 nor the BT tests are effective for purposes of classifying women for standard platelet aggregometry testing in women presenting with menorrhagia.

Ambient Air Pollution and the Risk of Stillbirth

The purpose of the present study was to examine the risk of stillbirth associated with ambient air pollution during pregnancy. Using live birth and fetal death data from New Jersey from 1998 to 2004, the authors assigned daily concentrations of air pollution to each birth or fetal death. Generalized estimating equation models were used to estimate the relative odds of stillbirth associated with interquartile range increases in mean air pollutant concentrations in the first, second, and third trimesters and throughout the entire pregnancy. The relative odds of stillbirth were significantly increased with each 10-ppb increase in mean nitrogen dioxide concentration in the first trimester (odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.03, 1.31), each 3-ppb increase in mean sulfur dioxide concentration in the first (OR = 1.13, 95% CI: 1.01, 1.28) and third (OR = 1.26, 95% CI: 1.03, 1.37) trimesters, and each 0.4-ppm increase in mean carbon monoxide concentration in the second (OR = 1.14, 95% CI: 1.01, 1.28) and third (OR = 1.14, 95% CI: 1.06, 1.24) trimesters. Although ambient air pollution during pregnancy appeared to increase the relative odds of stillbirth, further studies are needed to confirm these findings and examine mechanistic explanations.

Evaluation of a screening tool for bleeding disorders in a US multisite cohort of women with menorrhagia.

OBJECTIVE The purpose of this study was to determine the usefulness of a simple screening tool for bleeding disorders in a multisite population of women with menorrhagia. STUDY DESIGN Women with menorrhagia between the ages of 18 and 50 years from 6 geographically diverse US centers underwent hemostatic testing for bleeding disorders, complete blood cell count, and ferritin. A questionnaire that contained all elements of the 8-question screening tool was administered. Sensitivity of the screening tool, a screening tool with a pictorial blood assessment chart (PBAC) score of >185, and a screening tool with serum ferritin were calculated for hemostatic disorders. RESULTS Two hundred and seventeen women who were identified with a PBAC score of ≥100 participated in the study. The sensitivity of the screening tool was 89% for hemostatic defects, and sensitivity increased to 93% and 95% with a serum ferritin level of ≤20 ng/mL and a PBAC score of >185, respectively. CONCLUSION This study confirms the usefulness of a short screening tool for the stratification of women with menorrhagia for hemostatic evaluation.

Does ambient air pollution trigger stillbirth

Objective: We previously reported an increased risk of stillbirth associated with increases in trimester-specific ambient air pollutant concentrations. Here, we consider whether sudden increase in the mean ambient air pollutant concentration immediately before delivery triggers stillbirth. Methods: We used New Jersey linked fetal death and hospital discharge data and hourly ambient air pollution measurements from particulate matter ⩽2.5 mm (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2) monitors across New Jersey for the years 1998–2004. For each stillbirth, we assigned the concentration of air pollutants from the closest monitoring site within 10 km of the maternal residence. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of stillbirth associated with interquartile range (IQR) increases in the mean pollutant concentrations on lag day 2 and lag days 2 through 6 before delivery, and whether these associations were modified by maternal risk factors. Results: The relative odds of stillbirth increased with IQR increases in the mean concentrations of CO (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.05–1.37), SO2 (OR = 1.11, 95% CI = 1.02–1.22), NO2 (OR = 1.11, 95% CI = 0.97–1.26), and PM2.5 (OR = 1.07, 95% CI = 0.93–1.22) 2 days before delivery. We found similar associations with increases in pollutants 2 through 6 days before delivery. These associations were not modified by maternal risk factors. Conclusion: Short-term increases in ambient air pollutant concentrations immediately before delivery may trigger stillbirth.

Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction

Summary.  Intranasal desmopressin (IN‐DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN‐DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN‐DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18–45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri‐phosphate (ATP) release pre‐IN‐DDAVP and 60‐min post‐IN‐DDAVP. Eight of eleven women underwent platelet function analyzer (PFA‐100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post‐treatment. IN‐DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN‐DDAVP resulted in elevated VWF levels and shortened PFA‐100 closure time with significant inverse correlation between shortening of PFA‐100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag (P = 0.02), VWF:RCo (P = 0.04) and FVIII:C (P = 0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN‐DDAVP in women with menorrhagia and platelet dysfunction.

Differences in thrombotic risk factors in black and white women with adverse pregnancy outcome

INTRODUCTION Black women have an increased risk of adverse pregnancy outcomes and the characteristics of thrombotic risk factors in this population are unknown. The objective of this study was to examine the racial differences in thrombotic risk factors among women with adverse pregnancy outcomes. METHODS Uniform data were collected in women with adverse pregnancy outcomes (pregnancy losses, intrauterine growth restriction (IUGR), prematurity, placental abruption and preeclampsia) referred to Thrombosis Network Centers funded by the Centers for Disease Control and Prevention (CDC). RESULTS Among 343 white and 66 black women seen for adverse pregnancy outcomes, protein S and antithrombin deficiencies were more common in black women. The prevalence of diagnosed thrombophilia was higher among whites compared to blacks largely due to Factor V Leiden mutation. The prevalence of a personal history of venous thromboembolism (VTE) did not differ significantly by race. A family history of VTE, thrombophilia, and stroke or myocardial infarction (MI) was higher among whites. Black women had a higher body mass index, and a higher prevalence of hypertension, while the prevalence of sickle cell disease was approximately 27 fold higher compared to the general US black population. CONCLUSIONS Thrombotic risk factors differ significantly in white and black women with adverse pregnancy outcomes. Such differences highlight the importance of considering race separately when assessing thrombotic risk factors for adverse pregnancy outcomes.

Trends and risk factors of stillbirth in New Jersey 1997–2005

Introduction: The purpose of this study was to examine the trends in the rates of stillbirth by race and ethnicity and to determine the risk factors of stillbirth. Methods: We used New Jersey data (1997–2005) for live births and fetal deaths. Cox proportional hazards model was used to estimate the risk of stillbirth associated with maternal risk factors and pregnancy complications. Results: The rate of stillbirth was 4.4/1000 total births (3.4 for white and 7.9 for black non-Hispanics and 4.4 for Hispanics/1000 total births). The rates of stillbirth decreased from 3.8 in 1997 to 2.7/1000 total births in 2005 for white non-Hispanics but remained unchanged for other race/ethnicity groups. Adjusted relative risks for the risk factors associated with stillbirth were 1.3 (95% CI, 1.2–1.4) for maternal age ≥ 35 years, 1.9 (95% CI, 1.7–2.1) for black non-Hispanics, 2.8 (95% CI, 2.4–3.3) for no prenatal care, 40.2 (95% CI, 36.9–43.9) for placental abruption, 5.3 (95% CI, 3.4–8.2) for eclampsia, 3.5 (95% CI, 2.8–4.3) for diabetes mellitus and 1.7 (95% CI, 1.3–2.2) for preeclampsia. Conclusion: There was a decline in the rate of stillbirth but there were persistent racial disparities with the highest rates of stillbirth for black non-Hispanics.