Israel Medical Association Journal

Innate and adaptive immune response dysregulations are equally involved in the induction of autoimmunity. Toll-like receptors play a leading role in the activation of innate immune cells, thus priming auto-reactive T cells. Th17 cells and related cytokines are widely involved in many immune-mediated diseases such as rheumatoid arthritis. Thus, the recent introduction of anti-IL-17  therapies should be further evaluated. Janus kinase inhibitors and Fc receptor-targeting drugs are some of the new therapeutic strategies that are being implemented when old classical therapies lack sufficient beneficial outcomes

Background: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities.

Objectives: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19.

Methods: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March–April 2020 (during the COVID-19 outbreak) with March–April of the preceding year, 2019.

Results: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods.

Conclusions: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients

Background: The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.

Objectives: To assess perinatal complications in offspring of women with GDM and PGDM.

Methods: The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.

Results: In the study period 2015–2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P < 0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.

Conclusions: Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks

Background: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM.

Objectives: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach.

Methods: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA).

Results: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts.

Conclusions: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

Background: Admission to an intensive care unit (ICU) is an objective marker of severe maternal morbidity (SMM).

Objectives: To determine the prevalence of obstetric ICU admissions in one medical center in Israel and to characterize this population.

Methods: In this retrospective study the files of women coded for pregnancy, birth, or the perinatal period and admission to the ICU were pulled for data extraction (2005–2013).

Results: During the study period, 111 women were admitted to the ICU among 120,279 women who delivered babies (0.09%). Their average age was 30 ± 6 years, most were multigravida, a few had undergone fertility treatments, and only 27% had complicated previous pregnancies. Most pregnancies (71.2%) were uneventful prior to admission. ICU admissions were divided equally between direct (usually hemorrhage) and indirect (usually cardiac disease) obstetric causes.

Conclusions: The indications for obstetrics ICU admission correlated with the proximate causes of maternal arrest observed worldwide. While obstetric hemorrhage is often unpredictable, deterioration of heart disease is foreseeable. Attention should be directed specifically toward improving the diagnosis and treatment of maternal heart disease during pregnancy in Israel.

Background: Complete hydatidiform mole and a co-existing normal fetus (CHMCF) is associated with a high complication rate. A possible association with assisted conception might increase the prevalence of CHMCF.

Objectives: To study the potential association between assisted conception and the risks of CHMCF.

Methods: Case series at a single university hospital from 2008 to 2018 are presented and contrasted with data from a comprehensive literature review (1998–2018). Cases were identified from the institutional database that matched the sonographic criteria for CHMCF. A literature review showed comparable cases.

Results: None of the three pregnancies presented in this article resulted in a viable fetus, all were aborted. One of the three patients needed chemotherapy due to gestational trophoblastic neoplasia (GTN). A literature search identified 248 reported cases in which 22 fetuses (9%) reached term, 88/248 (35%) progressed to GTN, and 25/120 (21%) were conceived following assisted conception. From 2008 until 2018 at our medical facility, there were 3144 twin pregnancies of which 1667 (53%) were conceived using assisted conception. In our cohort, there was no statistical trend for assisted conception as an etiological factor for CHMCF.

Conclusions: No association between assisted conception and the risk for CHMCF was established at our hospital, although approximately one-quarter of all reported CHMCF pregnancies are attributed to assisted conception technology. However, these data are not always reported, making it difficult to draw definitive conclusions.

Background: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia.

Objectives: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages.

Methods: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia.

Results: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05).

Conclusions: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Rheumatic diseases commonly affect women of childbearing age, when women may be contemplating pregnancy or they discover an unplanned pregnancy. Therefore, specific issues about pregnancy planning and management are commonly encountered in patients during these times. Knowledge of the effect of pregnancy on disease activity is important for counseling. This review summarizes recent data on the course of different rheumatic diseases during pregnancy and the postpartum period. Rheumatoid arthritis and systemic lupus erythematosus are the most commonly investigated diseases. Data are increasing about spondyloarthritis. Sparse data are available for other rheumatic diseases. Despite the differences in these diseases and the various courses these disease take during pregnancy, a common feature is that active maternal disease in the months prior to conception increases the risk of flares during pregnancy, which in turn can lead to adverse pregnancy outcomes. Therefore, maternal and fetal health can be optimized if conception is planned when disease is inactive so that a treatment regimen can be maintained throughout pregnancy.

Background: Rheumatic mitral stenosis (MS) is a relatively rare diagnosis in the developed countries and its treatment during pregnancy is challenging due to hemodynamic changes. With the demographic changes due to recent waves of immigration an increase in the prevalence of rheumatic heart disease is expected.

Objective: To evaluate maternal and neonatal complications in patients with mitral stenosis.

Methods: During the years 2006–2017, 22 women who underwent 31 pregnancies were followed at the Sheba Medical Center in Israel. We collected on regarding hemodynamic changes and their clinical course. MS was classified as mild, moderate, or severe according to mitral valve area by echocardiography. Maternal and fetal adverse events were evaluated according to severity of MS and compared by Poisson regression modeling.

Results: MS was severe in 7 pregnancies (22.6%), moderate in 9 (29%), and mild in 15 (48.4%). Twenty patients were managed conservatively and 2 underwent a successful percutaneous mitral balloon valvuloplasty (PBMVP) during pregnancy. All pregnancies ended with a liveborn neonate and with no maternal mortality. Peak and mean mitral pressure gradients increased during pregnancy from 13.3 ± 5.3 to 18.6 ± 5.1 mmHg and from 5.9 ± 2.3 to 9.6 ± 3.4 mmHg respectively (P < 0.05). Eight pregnancies (25.8%) were complicated by pulmonary congestion, 2/15 (13.3%) with mild MS, 2/9 (22.2%) with moderate, and 4/7 (57.1%) with severe MS. The adverse event rate was higher among patients with severe MS compared with moderate and mild MS [hazard ratio (HR) 3.15, 95% confidence interval (95%CA) 1.04–9.52 and HR 4.06, 95%CI 1.4–11.19 respectively, P < 0.05]. Nine of 31 deliveries were vaginal; 6 of 22 cesarean sections (27.3%) were performed for cardiac indications.

Conclusions: The number of total adverse events were higher among patients with severe MS. Patients with moderate and mild MS should be treated attentively, but good obstetric and maternal outcome can be expected.

Background: Ptyalism gravidarum (PG) is a condition of hypersalivation that affects pregnant women early in gestation. Symptoms include massive saliva volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation, significant emotional distress, and social difficulties.

Objectives: To examine maternal and fetal characteristics and pregnancy outcomes of patients with PG.

Methods: Patients diagnosed with PG in our clinic during the years 2001–2016 were identified and contacted. Demographic data were extracted from patient charts and clinical and outcome data was collected via telephone interviews.

Results: The incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%) with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not increase the risk. Of the mothers presenting with PG, 37% had a positive family history for this condition. There was no associated increase in the rate of fetal or maternal complications. Two women reported a resolution of the symptoms immediately following hypnosis with acupuncture treatment.

Conclusions: Although PG represents an unpleasant mental and physical condition, it does not pose any specific risk to the health of the mother or increase adverse perinatal outcomes for the fetus. Alternative medicine could play a role in the treatment of PG.

Background: Abnormal gestational weight gain (GWG) has been associated with adverse outcomes for mothers and their offspring.

Objectives: To compare the achievement of recommended GWG and lifestyle factors in women with high-risk versus normal-risk pregnancies.

Methods: Pregnant women hospitalized in a gynecological and obstetrics department and pregnant women who arrived at a community clinic for a routine checkup were interviewed and completed questionnaires relating to weight gain and lifestyle factors (e.g., smoking, diet, exercise). Recommended GWG was defined by the American Congress of Obstetricians and Gynecologists (ACOG).

Results: GWG higher than ACOG recommendations was reported by 52/92 women (57%) with normal pregnancies and by 43/86 (50%) with high-risk pregnancies. On univariate analysis, characteristics associated with greater GWG were: current or past smoking, age > 40 years, pre-gestational body mass index (BMI) > 25 kg/m², low fruit intake, and high snack intake. High-risk pregnancies were associated with pre-gestational BMI > 25 kg/m² (48% vs. 27%, P = 0.012), consumption of vitamins (84% vs. 63%, P = 0.001), avoidance of certain foods (54% vs. 21%, P = 0.015), receiving professional nutritionist consultation (65% vs. 11%, P = 0.001), and less physical activity (9% vs. 24%, P = 0.01).

Conclusions: A minority of pregnant women met the recommended GWG. No difference was noted between normal and high-risk pregnancies. High-risk population tended to have a less healthy lifestyle. Counseling to follow a healthy, balanced diet should be recommended, regardless of pregnancy risk, with particular attention to women at high risk of extra weight gain.