Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth.

BACKGROUND: To determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth. METHODS: This retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined. RESULTS: Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95% CI 1.5-8.5)]. CONCLUSIONS: Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.

The association between adolescent obesity and later gestational diabetes in military personnel: A retrospective cohort study.

BACKGROUND: The association between body mass index (BMI) in adolescence and gestational diabetes mellitus (GDM) has not been completely delineated. The purpose of our study was to determine the extent by which adolescent obesity increases the risk for developing GDM later in life. METHODS: A retrospective cohort study including all army personnel pregnancies occurring between the years 2009-2019 was conducted. Adolescent BMI of participants was available using pre-recruitment army records. GDM and other pregnancy outcomes were compared between two groups: adolescent BMI below 30 (comparison group) and that of 30 or more (exposed group). Multivariable models were adjusted for sociodemographic factors. RESULTS: Following exclusion of cases with missing or partial glucose tests, and undocumented BMI, 6877 deliveries were included in the analysis. GDM rates were higher in the exposed group (4.9% vs. 2.9%, p value-0.09). GDM rates were twice as common in the exposed group (4.9% vs. 2.9%, p value-0.09). The multivariable model, adjusted for country of birth, socio-economic class, medical profile score, maternal age, and follow-up time, confirmed an independent association between adolescent obesity and later GDM, with an adjusted odds ratio of 2.22 (CI 1.1-4.5, p value - 0.03). CONCLUSION: Obesity during the adolescent years is independently associated with gestational diabetes later in life.

Policy for reducing unplanned pregnancies and repeat unplanned pregnancies rates in Israeli Defense Force.

Israel has compulsory military service, beginning at the age of 18. Women serve about two years and men for about three years. However, de facto only some of the potential service entrants are recruited. Among women, those who enlist are mainly secular Jews who are unmarried; among men, most of the ultra-Orthodox Jews do not enlist. In addition, only a fraction of the recruits chooses to turn the military service into a career and sign up for additional service as professional military personal (officers and non-commissioned officers). Thus, military personnel are not representative of the general Israeli population, even after controlling for age.The rate of pregnancies among female soldiers (obligatory service) in the Israeli army is low, but almost all pregnancies in this group are unplanned and most result in termination of pregnancy. An unplanned pregnancy carries a direct impact on the service of that female soldier and consequently on the military's routine.In a recent article in the Israel Journal of Health Policy Research (IJHPR), Rottenstreich et al. (IJHPR 7:42, 2018) describe a retrospective cohort study designed to evaluate the prevalence and risk factors for repeated unintended pregnancies among this population of female soldiers.This commentary presents the current IDF policy intended to further reduce unplanned pregnancies and repeat unplanned pregnancies rates. We also suggest additional tools to support evidence-based strategy planning in this field.

Medically indicated late preterm delivery and its impact on perinatal morbidity and mortality: a retrospective population-based cohort study.

Objective: In the last few decades, attention has been focused on morbidity and mortality associated with late preterm delivery (34-36 + 6/7 weeks), accounting for 60-70% of all preterm births. This study is aimed to determine (1) the prevalence of late preterm deliveries (spontaneous and medically indicated) in our population; and (2) the rate of neonatal morbidity and mortality as well as maternal complications associated with the different phenotypes of late preterm deliveries. Study design: This retrospective population-based cohort study, included 96,176 women who had 257,182 deliveries, occurred between 1988 and 2011, allocated into three groups: term (n = 242,286), spontaneous (n = 10,063), and medically indicated (n = 4833) late preterm deliveries. Results: (1) Medically indicated late preterm deliveries were associated with increased maternal morbidity, as well as neonatal morbidity and mortality, in comparison with other study groups (p < .01 for all comparisons); (2) medically indicated late preterm delivery was an independent risk factor for composite neonatal morbidity (low Apgar score at 5', seizures, asphyxia, acidosis) after adjustment for confounding factors (maternal age and ethnicity and neonatal gender) and stratification according to gestational age at delivery; and (3) the proportion of medically indicated late preterm deliveries affected the neonatal mortality rate. Below 35% of all late preterm deliveries, indicated late preterm birth were associated with a reduction in neonatal mortality; however, above this threshold medically indicated late preterm deliveries were associated with an increased risk for neonatal death. Conclusions: (1) Medically indicated late preterm deliveries were independently associated with adverse composite neonatal outcome; and (2) to benefit in term of neonatal outcome from the tool of medically indicated late preterm birth, their proportion should be kept below 35% of all late preterm deliveries, while exceeding this threshold increases the risk of neonatal mortality.

Urine protein-to-creatinine ratio: a point of care for the diagnosis of preeclampsia.

BACKGROUND: The aim of this study was to determine the correlation between the urine protein-creatinine ratio (UPCR) and the 24-hour urine protein excretion test (UPET), and to identify the optimal threshold values of UPCR for the diagnosis of preeclampsia and its severe form. METHODS: This prospective cohort study included 81 hypertensive pregnant patients who had a 24-h UPET and a UPCR tests. Two groups were created using a UPCR cut-off of 23.2 mg/mmol (40 negative UPCR, 41 positive UPCR). RESULTS: Forty-nine patients of were diagnosed with preeclampsia, and 23 of them had a severe disease. There was a significant correlation between UPCR and 24-h UPET. A cut-off UPCR value of 23.2 mg/mmol had an area under the curve (AUC) of 0.27, sensitivity of 89%, specificity 88%, positive predictive value 90%, a positive likelihood ratio (+LR) of 7.41 and a negative likelihood ratio (-LR) of 0.13 for the diagnosis of preeclampsia. UPCR value of 325 mg/mmol had an AUC of 0.841, and a sensitivity of 83%, specificity 81%, positive predictive value 81%, +LR of 4.4 and -LR of 0.2 for the diagnosis of severe preeclampsia. CONCLUSIONS: The UPCR test is highly correlated with the 24-h UPET. We propose a novel and sensitive cut-off for the diagnosis of preeclampsia by UPCR test. The UPCR test can be used for the identification of hypertensive patients with preeclampsia and severe disease.

Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation.

OBJECTIVES: Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. RESULTS: Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). CONCLUSIONS: Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.

LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis.

Placental mediated pregnancy complications such as preeclampsia and fetal growth restriction (FGR) are common, serious, and associated with increased morbidity and mortality. We conducted a systematic review and meta-analysis to determine the effect of treatment with low-molecular-weight heparins (LMWHs) for secondary prevention of these complications in non thrombophilic women. We searched the electronic databases PubMed, Scopus, and Cochrane Library for randomised controlled trials addressing this question. Five studies including 403 patients met the inclusion criteria, 68 developed preeclampsia and 118 FGR. The studies were very heterogeneous in terms of inclusion criteria, LMWH preparation, and dosage. Meta-analyses were performed using random-effect models. The overall use of LMWHs was associated with a risk reduction for preeclampsia (Relative risk (RR) 0.366; 95 % confidence interval (CI), 0.219-0.614) and FGR (RR 0.409; 95 % CI, 0.195-0.932) vs. no treatment. From the data available for analysis it appears that the use of Dalteparin is associated with a risk reduction for preeclampsia (p=0.002) and FGR (p<0.001); while Enoxaparin is associated with risk reduction for preeclampsia (p=0.013) but not for FGR (p=0.3). In spite of the small number of studies addressing the research question, and the high variability among them, our meta-analysis found a modest beneficial effect of LMWH for secondary prevention of preeclampsia and FGR. Further studies are needed to address these questions before a definite conclusion can be reached.

A prior placenta accreta is an independent risk factor for post-partum hemorrhage in subsequent gestations.

OBJECTIVE: The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies. STUDY DESIGN: A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta (n=514); and (2) control group without placenta accreta (n=239,126). RESULTS: (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5-11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0-36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4-13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3-2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26-0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5-1.9) after adjusting for confounders. CONCLUSION: A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients.

Placenta accreta is an independent risk factor for late pre-term birth and perinatal mortality.

OBJECTIVE: This study is aimed to identify the risk factors for the development of placenta accreta (PA) and characterize its effect on maternal and perinatal outcomes. STUDY DESIGN: This population-based retrospective cohort study included all deliveries at our medical center during the study period. Those with placenta accreta (n = 551) comprised the study group, while the rest of the deliveries (n = 239 089) served as a comparison group. RESULTS: The prevalence of placenta accerta is 0.2%. Women with this complication had higher rates of ≥2 previous CS (p < 0.001), recurrent abortions (p = 0.03), and previous placenta accreta [p < 0.001]. The rates of placenta previa and peripartum hemorrhage necessitating blood transfusion were higher in women with placenta accreta than in the comparison group. PTB before 34 and 37 weeks of gestation was more common among women with placenta accreta (p < 0.01), as was the rate of perinatal mortality (p < 0.001). Placenta accreta was an independent risk factor for perinatal mortality (adj. OR 8.2; 95% CI 6.4-10.4, p < 0.001) and late PTB (adj. OR 1.4; 95% CI 1.1-1.7, p = 0.002). CONCLUSION: Placenta accreta is an independent risk factor for late PTB and perinatal mortality.

Corticosteroids in sepsis: a new concept for an old drug.

Sepsis is an inflammatory syndrome caused by infection. Consequently, anti-inflammatory therapy in sepsis has been a subject of extensive research, and corticosteroids have long been used to treat severe infections. However, studies conducted in the 1980s failed to demonstrate any beneficial effects of high dose, short-term steroid therapy in sepsis and this therapy was therefore abandoned in the last decade. Recently, a new concept has emerged with more promising results--low dose, long-term hydrocortisone therapy- and this approach is now being evaluated in the treatment of septic shock. It is supported by the observation that many sepsis patients have relative adrenal insufficiency. Moreover, the anti-inflammatory effects of steroids and their ability to improve reactivity to catecholamines further contribute to their effects in sepsis. Large randomized clinical trials will be required to determine the exact role of corticosteroids in septic shock.

Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes.

Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.