Israel Medical Association Journal

In this article, we offer a brief summary of the report from the Task Force for the Promotion of the Status of Women in Medicine in Israel. The task force, formed by the Israel Medical Association in 2013, published a comprehensive report in May 2015 dedicated to the promotion of equal opportunities for female doctors in the Israeli healthcare system and in the academic world. The aim of this paper is to present the work of the task force and to highlight its main principles and recommendations against the backdrop of the gender revolution in the Israeli healthcare system and worldwide.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Invasive cervical cancer is caused by human papillomavirus (HPV).

Objectives: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.

Methods: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006–2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).

Results: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.

Conclusions: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

Background: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation. 

Objectives: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester.

Methods: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded.

Results: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05). 

Conclusions: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

 

Background: The prevalence of major malformations in the general population is estimated at 5% of all live births. Prenatal diagnosis is an important scientific tool that allows reliable consultation and improves pregnancy outcome. In 2008, congenital malformations were the leading cause of death in Muslim infants and the second cause of death in Jewish infants in Israel. It is known that folic acid consumption prior to pregnancy decreases the rate of several fetal malformations.

Objectives: To assess the folic acid consumption rate and to characterize variables associated with its use among pregnant women attending a rural medical center. 

Methods: A cross-sectional observational study was conducted at our institution. Pregnant women in the second or third trimester of pregnancy or within 3 days postpartum were interviewed. The main variable measured was the use of folic acid. Demographic variables and the rate of prenatal testing were assessed. A secondary analysis of the population that reported no consumption of folic acid was carried out. 

Results: Out of 382 women who participated in the study, 270 (71%) reported consumption of folic acid. Using a multivariate analysis model, we found that maternal education, planning of pregnancy, and low parity were independent predictors of folic acid consumption. Women who were not consuming folic acid tended to perform fewer prenatal tests during pregnancy.

Conclusions: High maternal educational level, planning of pregnancy, and low parity are related to high consumption rates of folic acid. Women who were not taking folic acid performed fewer prenatal tests during pregnancy. 

Background: Pregnant women with acute abdominal pain pose a diagnostic challenge. Delay in diagnosis may result in significant risk to the fetus. The preferred diagnostic modality is magnetic resonance imaging (MRI), since ultrasonography is often inconclusive, and computed tomography (CT) would expose the fetus to ionizing radiation

Objectives: To describe the process in setting up an around-the-clock MRI service for diagnosing appendicitis in pregnant women and to evaluate the contribution of abdominal MR in the diagnosis of acute appendicitis.

Methods: We conducted a retrospective study of consecutive pregnant women presenting with acute abdominal pain over a 6 year period who underwent MRI studies. A workflow that involved a multidisciplinary team was developed. A modified MRI protocol adapted to pregnancy was formulated. Data regarding patients' characteristics, imaging reports and outcome were collected retrospectively. 

Results: 49 pregnant women with suspected appendicitis were enrolled. Physical examination was followed by ultrasound: when positive, the patients were referred for MR scan or surgery treatment; when the ultrasound was inconclusive, MR scan was performed. In 88% of women appendicitis was ruled out and surgery was prevented. MRI diagnosed all cases with acute appendicitis and one case was inconclusive. The overall statistical performance of the study shows a negative predictive value of 100% (95%CI 91.9–100%) and positive predictive value of 83.3% (95%CI 35.9–99.6%).

Conclusions: Creation of an around-the-clock imaging service using abdominal MRI with the establishment of a workflow chart using a dedicated MR protocol is feasible. It provides a safe way to rule out appendicitis and to avoid futile surgery in pregnant women.

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered  in the general population with a reported prevalence of 1% to 5%  However, APS is far more infrequent with a prevalence of 40–50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin.

Objectives: To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels.

Methods: In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. 

Results: Patients’ age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0–20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. 

Conclusions: In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

 

Autoimmune rheumatic diseases (ARD) affect mainly young women during their reproductive years. Fertility is usually not diminished but the time it takes to conceive is usually longer. Factors related to an ARD or to its treatment are responsible for this effect. In addition, contraception counseling is required to prevent negative fetal outcome and exacerbation of disease symptoms. In recent years, advances in therapies, clarification of risk factors for adverse pregnancy outcomes, and a multidisciplinary approach have vastly improved obstetric management, increasing the possibility of successful pregnancy with a high likelihood of favorable outcome.

Objectives: To determine the profile of unsaturated fatty acids in the breast milk of two populations in southern Israel, Jewish and rural tent-dwelling Bedouin women.

Methods: This study involved 48 lactating Israeli mothers, 29 Jewish and 19 Bedouin (16–20 weeks postpartum), whose full-term infants were fed exclusively with breast milk. Total milk lipid extracts were transmethylated and analyzed by using an improved gas chromatographic method.

Results: The breast milk of the Bedouin women contained significantly higher levels of total major saturated fatty acids, lauric acid and palmitic acid (45.2 ± 4.7% vs. 41.0 ± 5.6%, P = 0.005; 5.2 ± 2.1 vs. 6.8 ± 2.0%, P = 0.03; and 22.7 ± 2.4 vs. 20.6 ± 3.8%, P = 0.02) respectively. No difference was found in the myristic acid level between the groups. The level of stearic acid was significantly higher in the Jewish group compared to the Bedouin group (5.7 ± 1.1 vs. 5.1 ± 1.1%, P = 0.04). There was a linear correlation between the levels of C14:0 and C12:0 in the Bedouin and Jewish groups respectively (R = 0.87, R = 0.82, P < 0.001).

Conclusions: Higher levels of saturated fatty acids were measured in the breast milk of Bedouin women, an economically weaker population. The results emphasize the importance of diet among lactating women and its influence on milk quality. 

Background: Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory disease of the aorta and/or its major branches and more frequently affects female patients before menopause. Since persistent inflammation may lead to arterial ischemia, hypertension is an important complication of TA. Objectives: To evaluate gestational results and complications in patients with TA arteritis.

Methods: We conducted a retrospective analysis of the medical records of patients with TA admitted to the high risk pregnancy clinic for women with systemic autoimmune diseases at Hospital Universitário Pedro Ernesto.

Results: From 1998 to 2011 we followed 11 pregnancies in 9 patients with TA; the patients’ age ranged from 17 to 42 years and disease duration from 2 to 28 years. In 7 of the 11 pregnancies, uncontrolled blood pressure occurred before labor and preeclampsia was diagnosed in one. Two deliveries were preterm, one newborn was treated for sepsis and four (36%) had intrauterine growth restriction (IUGR).

Conclusions: Close monitoring improves the perinatal outcomes in patients with TA who are more prone to develop hypertension, preeclampsia and IUGR. Disease activity was not observed in our group of patients during pregnancy. Coordinated care between the obstetric, rheumatologic and cardiologic teams is the ideal setting to follow pregnant women with TA.