Susan Hosseini Nasab

Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks

The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4–5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.

Catastrophic antiphospholipid syndrome in pregnancy, a diagnosis that should not be missed

Abstract Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure. It is a rare and life-threatening condition that can be easily mistaken with hemolysis elevated liver enzymes low platelets syndrome, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at least three organs or systems, and to have positive antiphospholipid antibody on two occasions (6 weeks apart), and histopathologic confirmation of small vessel occlusion. However, due to similarities in clinical and laboratory findings between CAPS and some other obstetric complications, potential misdiagnosis or delay in diagnosis are common, increasing the risk of adverse maternal and perinatal outcomes. In this review we summarized information presented in previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic criteria, differential diagnosis, and common presentation ranging from malaise, abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We also discussed management in pregnancy and included a detailed algorithm with steps to take. Of note, the most significant reduction in mortality was seen in patients receiving triple therapy which will be discussed in this review.

Same-day confirmation of intrauterine pregnancy failure in women with first- and early second-trimester bleeding

OBJECTIVE To determine if alpha-fetoprotein (AFP) concentration in vaginal blood, in the setting of dissolved fetal tissue, is significantly higher than its concentration in the maternal serum. DESIGN A prospective cohort study. SETTING Medical center. PATIENT(S) Four groups of women were evaluated: 1) with missed/incomplete miscarriage with vaginal bleeding; 2) with threatened miscarriage; 3) with vaginal bleeding during cerclage placement; and 4) undergoing dilation and curettage (D&C). INTERVENTIONS(S) None. MAIN OUTCOME MEASURE(S) In each patient, AFP concentration in the vaginal blood or in the liquid component of the evacuated products of conception (POC; D&C group) was compared with the AFP concentration in the maternal serum. RESULT(S) The median (range) concentration ratios of AFP in vaginal blood (or POC) to AFP in maternal serum were 24.5 (5.1-8,620) and 957 (4.6-24,216) for the missed/incomplete (n = 30) and the D&C (n = 22) groups, respectively, whereas they were only 1.2 (0.4-13.4) and 1.01 (0.7-1.5) for the threatened miscarriage (n = 15) and cerclage (n = 9) groups, respectively. Receiver operating characteristic (ROC) analysis demonstrated 100% sensitivity and 86.7% specificity for the detection of the passage of fetal tissue (ratio 4.3, area under the ROC curve 0.96). CONCLUSION(S) Higher concentrations of AFP in vaginal blood than in maternal serum may indicate the presence of dissolved fetal tissue (i.e., confirming a failed pregnancy).

Effect of partial compliance on the prevention of recurrent preterm birth in women receiving weekly 17 alpha-hydroxyprogesterone caproate injections

Abstract Purpose: To analyze the effect of partial compliance on preterm birth (PTB) prevention among women with previous PTB and receiving 17 alpha-hydroxyprogesterone caproate (17-OHPC). Study Design: This is a secondary analysis of a multicenter trial for the prevention of recurrent PTB. Women with prior PTB were randomly assigned between 15 0/7 and 20 3/7 weeks to weekly injections of either 17-OHPC or placebo. Full 100% compliance (group 1) was compared to 40-80% (group 2). Recurrent PTB rates and odds ratios were calculated. Students t, Chi-square, Wilcoxon Rank-Sum, multivariate logistic regression and Breslow-Day tests were used. Results: Group 1 included 370 women versus 35 in group 2. In each group, the PTB rate was significantly reduced in pregnancies receiving 17-OHPC compared to placebo. The adjusted odds ratio for PTB rate in group 1 was 0.48 (95% CI 0.31–0.75) versus 0.18 (95% CI 0.04–0.92) in group 2. Comparing the homogeneity of both odds ratios, the rates of recurrent PTB prevention in both groups were not statistically different (Breslow–Day test; p= .15). Conclusion: A compliance rate of 40–80% did not significantly reduce 17-OHPC’s efficacy. If confirmed, our findings could lead to a dramatic decrease in costs related to prevention of recurrent PTB.

Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study

Objectives: To explore whether the metabolic switches proceed or succeed the histological changes in precancerous lesions. To validate pyruvate kinase isoform 1 (PKM1) and pyruvate kinase isoform 2 (PKM2) as a histological biomarker to predict the progression of endometrial hyperplasia into invasive cancer status. Methods: The records of 56 patients with a primary diagnosis of complex hyperplasia with atypia after endometrial biopsy were selected and analyzed retrospectively. A set of 3 consecutive sections at 4-μm thickness were cut and studied with immunohistochemical stains. From each case, 2 to 3 fields with a diagnosis of complex hyperplasia with atypia were selected and compared. A single pathologist blinded to the final diagnosis assigned the scoring. Results: Positive immunostaining for PKM1 was observed in 31.25% (10 out of 32) of initial endometrial biopsy with the diagnosis of complex hyperplasia with atypia and final diagnosis of endometrial cancer, while 91.67% (out of 24) of patients with final diagnosis of negative endometrial cancer had endometrial biopsy with positive PKM1 staining (P < .001). Positive immunostaining for PKM2 was observed in 100% of patient with endometrial biopsy result of endometrial hyperplasia with atypia (56 of 56). Conclusions: Lack of staining with PKM1 expression may help to predict the fate of endometrial hyperplasia. The disappearance of this marker is associated with the progression of hyperplasia toward cancer phenotype. Further studies are needed to understand the causes and potential mechanisms for suppressing Pyruvate Kinase Isoform 1 expression in endometrial hyperplasia.

The impact of time of delivery on gestations complicated by preterm premature rupture of membranes: daytime versus nighttime

Abstract Background: Perinatal death, in particular intrapartum stillbirth and short-term neonatal death, as well as neonatal short-term and long-term morbidity have been associated with the time of day that the birth occurs. Indeed, evening and nighttime deliveries were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Impact of shift change, as well as time of day delivery have been extensively studied in the context of maternal and neonatal complications of cesarean delivery, however, no studies were previously performed on timing of delivery and its effect on the outcome of pregnancies complicated by preterm premature rupture of membranes. Objective: Our objective was to compare obstetric, neonatal as well as long-term outcomes between women delivered in the daytime versus nighttime, in singleton gestations whose pregnancies were complicated by preterm premature rupture of membranes. Study design: This was a secondary analysis of a trial of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network “A Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate for the Prevention of Cerebral Palsy.” For this analysis, the time of delivery was divided into the daytime, from 07:01 to 19:00, and the nighttime, from 19:01 to 07:00. Epidemiological, obstetric characteristics as well as neonatal and long-term outcomes were compared between deliveries occurring during the daytime versus the nighttime periods. Inclusion criteria consisted of singleton gestations diagnosed with preterm premature rupture of membranes (PPROM). Multifetal gestations and pregnancies with preterm labor without preterm premature rupture of membranes were excluded. Results: A total of 1752 patients met inclusion criteria, 881 delivering during the daytime, while 871 during the nighttime. There were no differences in demographic maternal variables. There were no differences in the number of patients receiving steroids and the doses of steroids. Antibiotic prophylaxis was also equal in both groups. Postpartum endometritis, chorioamnionitis, and the latency to delivery were also equivalent between both the groups. Cesarean delivery for distress was the only different outcome, more prevalent in daytime deliveries (157 (44.7%) versus 108 (35.9%) of the nighttime ones p = .02). Neonatal adverse outcomes as well as long-term outcomes were similar between the two groups. Conclusions: In the setting of delivery at a tertiary care center, and in the era of universal use of steroids, and latency antibiotics for the management of preterm premature of membranes, there is no marked difference in pregnancy, neonatal as well as long-term outcomes for infants delivered in the daytime versus nighttime.

Adverse pregnancy outcomes in deliveries prior to, at and beyond 39 weeks; low- and high-risk women

Abstract Background: Hypertensive disorders are associated with maternal and neonatal complications. Though they are more common in women with history of prior preeclampsia, they can occur in uncomplicated pregnancies. Objective: To determine the proportion of adverse pregnancy outcomes in deliveries prior to or at ≥39 weeks, in uncomplicated singleton nulliparous women (low-risk), as well as women with history of preeclampsia in a prior gestation (high-risk). Study design: This was a secondary analysis from the multicenter trials of low dose aspirin for preeclampsia prevention in low and high-risk pregnancies. The proportion of adverse pregnancy outcomes including hypertensive disorders in pregnancy, small for gestational age, placental abruption, neonatal intensive critical unit admission, and respiratory distress syndrome were evaluated in the two groups. Adverse pregnancy outcomes were stratified by gestational age at delivery (<39 weeks and ≥39 weeks). Descriptive statistics were performed, and results reported as percentages. Results: Three thousand twenty-one pregnancies were included in the low risk group, and 600 in the high risk one. In the low risk group 362 (12%) had hypertensive disorders, with 58% occurring at ≥39 weeks. In the low risk group, the rate of small for gestational age was of 5.9%, placental abruption 0.4%, neonatal intensive care unit admission 9%, and respiratory distress syndrome 3.5%. Sixty percent of all small for gestational age, 31% of all placenta abruptions, 44% of all neonatal intensive care unit admissions and 33% of respiratory distress syndrome cases, occurred at ≥39 weeks in the low risk group. In contrast in the high risk group, 197 (33%) patients developed a hypertensive disorder, with 35.5% occurring at ≥39 weeks. The overall rate of small for gestational age was 9.2%, abruption 2%, neonatal intensive care unit admission 15.5%, and respiratory distress syndrome 5%. In this group, 24% of all small for gestational age, 8.3% of all placental abruptions, 16% of all neonatal intensive care unit admissions and 3% of respiratory distress syndrome cases, were at ≥39 weeks. Conclusions: We found that in low-risk women, the majority of hypertensive disorders occur at ≥39 weeks, whereas in women with prior preeclampsia the majority develops at <39 weeks. Moreover, a third of all placental abruption occurred at or beyond 39 weeks in the low risk group. Our findings suggest that in low-risk women, a policy of delivery at 39 weeks may prevent most of the adverse outcome that occurs beyond that gestational age cutoff.

Caesarean Delivery Surgical Site Infection: What are Expected Rates and Potentially Modifiable Risk Factors?

OBJECTIVE This study sought to determine baseline Caesarean delivery (CD) surgical site infection (SSI) rates in various patient subgroups and to identify potentially modifiable and non-modifiable risk factors for SSI. METHODS This is a secondary analysis of a multicentre CD registry. Women who underwent CD were divided into SSI versus no SSI. SSI was defined as an infection that occurred in the part of the body where the surgery took place, within 30 days of surgery. Clinical characteristics and potential risk factors were compared between groups. RESULTS Of 57 182 women, 3696 (6.5%) had SSI. SSI rates were higher in primary versus repeat CD (9.7% vs. 4.2%; P <0.001), and in CD after labour vs. no labour (9.5% vs. 3.8%; P <0.001). After adjustment for confounding factors, low transverse CD (adjusted OR [aOR] 0.7 [0.6-0.9]), CD performed between 7 pm and 7 am (aOR 0.9 [0.83-0.98]), primary CD (aOR 0.5 [0.5-0.6]), and intrapartum antibiotics (aOR 0.3 [0.1-0.4]) were associated with a decreased in the rate of SSI. Black race (aOR 1.9 [1.7-2.1]), tobacco use (aOR 1.4 [1.2-1.6]), increasing American Society of Anesthesiologists category (aOR 1.3 [1.1-1.6]), vertical skin incision (aOR 1.2 [1.1-1.3], emergency CD (aOR 1.3 [1.1-1.5]), and postpartum transfusion (aOR 2.7 [2.1-3.6]) were associated with an increase in the rate of SSI. CONCLUSION This study estimates the CD SSI rates in different subgroups and serves as a baseline for future trials designed to develop preventive guidelines and protocols.

Composite neonatal and maternal morbidities with small- versus appropriate- for gestational age among uncomplicated obese women undergoing repeat cesarean delivery

Abstract Purpose: Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10–89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD). Study design: This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, > 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus <30 kg/m2. CNM included respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, seizure, or death; CMM included transfusion, hysterectomy, operative injury, coagulopathy, thromboembolism, pulmonary edema, or death. Multivariate logistic regression was used to control for confounding factors. Results: Of 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p < .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19–3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02–0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03–4.59). Conclusions: SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials.

A Simple and Fast Approach to Confirm Pregnancy Failure in First Trimester Bleeding [8Q]

INTRODUCTION: A failing pregnancy may present with vaginal bleeding and the passage of fetal tissue. Alpha-fetoprotein (AFP) concentration in fetal serum is at least 1000 times higher than it is in maternal serum. The objective of this study was to determine if vaginal blood mixed with fetal tissue has a relatively higher concentration of AFP than vaginal blood in the case of a threatened abortion. METHODS: The study group was women with incomplete abortion or with missed abortion that started to have vaginal bleeding. The control group was women with threatened abortion (ie, not passing fetal tissue and with a fetal heartbeat). In each group, every womans maternal serum AFP concentration was compared to the AFP concentration in the vaginal blood. Values were expressed as mean±SEM. Paired t test was used. RESULTS: In the study group (17 women), the mean AFP concentration in blood sampled from the vagina was 17,043±11,048 ng/mL vs 11±2.7 ng/mL in the maternal serum (P<.001). In the control group (9 women), the mean AFP concentration in the blood sampled from the vagina was 71 ± 18 ng/mL vs 112 ± 32 ng/mL in the maternal serum (P=.1). In the study group, the AFP concentration in the vaginal blood was 8–8,620 times higher than in the maternal serum, whereas in the control group the ratio was around 1 (range 0.37–1.36). CONCLUSION: AFP concentration in vaginal blood that is at least 8 times higher than AFP concentration in maternal serum may indicate a passage or dissolving fetal tissue (ie, pregnancy failure).