The role of viscoelastic hemostatic assays for postpartum hemorrhage management and bedside intrapartum care.

Viscoelastic hemostatic assays are point-of-care devices that assess coagulation and fibrinolysis in whole blood samples. These technologies provide numeric and visual information of clot initiation, clot strength, and clot lysis under low-shear conditions, and have been used in a variety of clinical settings and subpopulations, including trauma, cardiac surgery, and obstetrics. Emerging data indicate that these devices are useful for detecting important coagulation defects during major postpartum hemorrhage (especially low plasma fibrinogen concentration [hypofibrinogenemia]) and informing clinical decision-making for blood product use. Data from observational studies suggest that, compared with traditional formulaic approaches to transfusion management, targeted or goal-directed transfusion approaches using data from viscoelastic hemostatic assays are associated with reduced hemorrhage-related morbidity and lower blood product requirement. Viscoelastic hemostatic assays can also be used to identify and treat coagulation defects in patients with inherited or acquired coagulation disorders, such as factor XI deficiency or immune-mediated thrombocytopenia, and to assess hemostatic profiles of patients prescribed anticoagulant medications to mitigate the risk of epidural hematoma after neuraxial anesthesia and postpartum hemorrhage after delivery.

Severe cholestasis-associated coagulopathy diagnosed by routine screening: a case report.

Recent case reports suggest an association between severe intrahepatic cholestasis of pregnancy and fat-soluble vitamin deficiencies, including vitamin K deficiency. Screening for coagulopathy and fat-soluble vitamin deficiency has been proposed as a possible strategy to identify pregnancies at additional risk of adverse outcomes and allow for earlier risk-reducing iatrogenic preterm delivery. This report highlights a case of routine screening that resulted in the detection of subclinical coagulopathy that allowed for earlier intervention and delivery of a healthy neonate at 34 weeks of gestation. Further prospective studies are needed to determine the clinical use of routine screening in detecting coagulopathy and fat-soluble vitamin deficiency in cases of severe cholestasis.

Association of Myomectomy With Anti-Müllerian Hormone Levels and Ovarian Reserve.

OBJECTIVE: To assess whether open and minimally invasive myomectomy are associated with changes in postoperative ovarian reserve as measured by serum anti-müllerian hormone (AMH) level. METHODS: This prospective cohort study included patients who were undergoing open abdominal myomectomy that used a tourniquet or minimally invasive (robot-assisted or laparoscopic) myomectomy that used vasopressin. Serum AMH levels were collected before the procedure and at 2 weeks, 3 months, and 6 months after surgery. The mean change in AMH level at each postsurgery timepoint was compared with baseline. The effect of surgical route on the change in AMH level at each timepoint was assessed by using multivariable linear regression. A subanalysis evaluated postoperative changes in AMH levels among the open myomectomy and minimally invasive myomectomy groups individually. RESULTS: The study included 111 patients (mean age 37.9±4.7 years), of whom 65 underwent open myomectomy and 46 underwent minimally invasive myomectomy. Eighty-seven patients contributed follow-up data. Serum AMH levels declined significantly at 2 weeks postsurgery (mean change -0.30 ng/mL, 95% CI -0.48 to -0.120 ng/mL, P=.002). No difference was observed at 3 months or 6 months postsurgery. On multiple linear regression, open myomectomy was significantly associated with a decline in AMH level at 2 weeks postsurgery (open myomectomy vs minimally invasive myomectomy: ß=-0.63±0.22 ng/mL, P=.007) but not at 3 months or 6 months. Subanalysis revealed a significant decline in mean serum AMH levels in the open myomectomy group at 2 weeks (mean change -0.46 ng/mL, 95% CI -0.69 to -0.25 ng/mL, P<.001) postsurgery but not at three or 6 months. In the minimally invasive myomectomy group, no significant differences in mean AMH levels were detected between baseline and any postoperative timepoint. CONCLUSION: Myomectomy is associated with a transient decline in AMH levels in the immediate postoperative period, particularly after open surgery in which a tourniquet is used. Anti-müllerian hormone levels returned to baseline by 3 months after surgery, indicating that myomectomy is not associated with a long-term effect on ovarian reserve, even with the use of a tourniquet to decrease blood loss. FUNDING SOURCE: This study was funded in part by a Roche Diagnostics Investigator-Initiated Study Grant.

Perioperative dexamethasone with neuraxial anesthesia for scheduled cesarean delivery and neonatal hypoglycemia.

OBJECTIVE: While the use of dexamethasone for cesarean delivery to prevent post-operative nausea and vomiting has become routine, the impact on fetal glucose metabolism is unknown. We aim to examine whether perioperative dexamethasone administration prior to scheduled non-labor cesarean delivery is associated with neonatal hypoglycemia. STUDY DESIGN: Multi-institution retrospective cohort study of singleton, full-term, non-anomalous pregnancies delivered by scheduled non-labor cesarean delivery with neuraxial anesthesia from 2013 to 2019. The exposure was intravenous dexamethasone after neuraxial anesthesia placement. Primary outcome was neonatal hypoglycemia and secondary outcomes included low Apgar, umbilical artery pH < 7.1, NICU admission, and meconium-stained amniotic fluid. A subgroup analysis was performed on pregnancies complicated by diabetes (both gestational and pre-gestational). Multivariate regression adjusting for baseline differences and potential confounders was used to the determine the strength of association between dexamethasone and adverse outcomes. RESULTS: Of the 4991 women in the study, 2719 (54.5%) received dexamethasone. Compared to non-receipt, women receiving dexamethasone were older, more likely to be White, non-Hispanic, have private insurance, and less likely to have diabetes. Perioperative dexamethasone receipt was not associated with neonatal hypoglycemia (adjusted OR 0.90, 95% CI 0.71-1.14). In a subgroup analysis of the 466 (9.3%) pregnancies complicated by pre-gestational and gestational diabetes, 219 (47.0%) received dexamethasone and receipt was associated with a significantly increased rate of neonatal hypoglycemia (adjusted OR 1.96, 95% CI 1.28-3.00). No significant associations were found between perioperative dexamethasone and other outcomes. CONCLUSIONS: Dexamethasone administration after neuraxial anesthesia placement for scheduled non-labor cesarean delivery is associated with altered neonatal glucose metabolism only in pregnancies complicated by diabetes.

Severe fat-soluble vitamin deficiency suspected secondary to intrahepatic cholestasis of pregnancy: A case report.

Intrahepatic cholestasis is the most common hepatobiliary complication of pregnancy. Worsening cholestasis, measured by total bile acid levels, has been associated with an increased incidence of adverse fetal outcomes; however, maternal morbidity remains rare. This report highlights a case of severe fat-soluble vitamin deficiency suspected to be secondary to severe cholestasis. Active management with weekly vitamin supplementation and close outpatient follow-up resulted in the delivery of a 32-week healthy neonate. We propose consideration of screening for fat-soluble vitamin deficiency for patients whose pregnancy is complicated by severe cholestasis or early-onset cholestasis.

Impact of fibrinogen and prothrombin complex concentrate on clotting time in a model of obstetric hemorrhage.

STUDY OBJECTIVE: Determine the impact of varying doses of fibrinogen concentrate and 4-factor prothrombin complex concentrate on clotting time as measured by thromboelastometry in an in-vitro model of dilutional coagulopathy. DESIGN: In-Vitro Study. SETTING: Tertiary academic center. PATIENTS: 31 healthy term singleton gestation patients. INTERVENTIONS: Blood was analyzed and diluted 95% with crystalloid. Washed red blood cells were added to simulate red blood cell transfusion. Two levels of fibrinogen repletion were then added to samples to simulate fibrinogen repletion in massive transfusion. Finally, 4-factor prothrombin complex concentrate (10 U/kg, 15 U /kg, or 25 U/kg) adjusted for body weight and estimated blood volume was added. MEASUREMENTS: Samples were analyzed by thromboelastometry, and the main outcome was a FIBTEM clotting time > 80s. MAIN RESULTS: FIBTEM clotting times were prolonged after dilution. After repletion with fibrinogen and prothrombin complex concentrates 7/31 (22.5%) of samples had a prolonged FIBTEM clotting time (> 80s) in the 50% fibrinogen repletion arm and 0 (0%) had a prolonged clotting time in the 100% fibrinogen repletion arm. FIBTEM clotting times approached their baseline levels at each dose of prothrombin complex concentrate. Median clotting time in the 100% fibrinogen repletion arm was under 80s prior to the administration of prothrombin complex concentrate. CONCLUSIONS: Commonly cited doses for prothrombin complex concentrates in hemorrhage might be too high for the obstetric patient. After fibrinogen correction alone, several samples required no further correction, highlighting the importance of frequent testing at the point of care. Limitations of this study include the in vitro study design and ability to directly apply findings to patient care. Further studies are needed to elucidate the ideal dose of prothrombin complex concentrate for obstetric hemorrhage. TWEETABLE ABSTRACT: Fibrinogen concentrate and low dose 4-factor PCC corrected coagulopathy in in-vitro obstetric hemorrhage.

The relationship between INTEM/HEPTEM coagulation time ratio and heparin plasma concentration in obstetric patients: an exploratory in vitro investigation.

PURPOSE: Unfractionated heparin continues to be one of the main agents used for thromboprophylaxis in obstetrics, which can complicate the placement of neuraxial anesthetics. In this study, we explored the relationship between a point-of-care coagulation test (thromboelastometry) and plasma heparin concentrations in vitro. METHODS: We obtained blood from consenting obstetric patients with uncomplicated pregnancies in their third trimester who were not in labour and had a specific hematocrit range. Blood was processed and analyzed. We added increasing amounts of unfractionated heparin to samples from 0 to 0.3 U·mL-1 in 0.05 U·mL-1 increments to simulate increasing doses of unfractionated heparin. We performed INTEM and HEPTEM testing in parallel with activated partial thromboplastin time (aPTT) testing. We created a model of the relationship between heparin concentration and the INTEM/HEPTEM coagulation time (IH CT) ratio using nonlinear regression. A similar model for aPTT was also created. RESULTS: Seventy-seven patients were included in the study. Only one concentration of heparin was added to blood samples of each patient. At a concentration of 0.05 U·mL-1, the IH CT ratio was less than or equal to 1.1 in 9/11 (82%) samples. Activated partial thromboplastin time was not prolonged (> 35 sec) until a concentration of 0.1 U·mL-1 heparin was added. In all samples, the IH CT ratio was prolonged at a concentration ≥ 0.2 U·mL-1 as measured by thromboelastometry; however, at no concentration of heparin was aPTT prolonged in all samples. CONCLUSION: The point-of-care IH CT ratio may be useful in identifying the presence of little to no heparin activity. Further research is needed to determine if this ratio can predict heparin activity in vivo.

RéSUMé: OBJECTIF: L'héparine non fractionnée demeure l'un des principaux agents utilisés pour la thromboprophylaxie en obstétrique, ce qui peut compliquer la mise en place d'anesthésiques neuraxiaux. Dans cette étude, nous avons exploré la relation entre un test de coagulation au chevet de la patiente (thromboélastométrie) et les concentrations plasmatiques d'héparine in vitro. MéTHODE: Nous avons obtenu du sang de patientes obstétricales consentantes ayant des grossesses non compliquées au cours de leur troisième trimestre qui n'étaient pas en travail et dont l'hématocrite était dans une plage spécifique. Le sang a été traité et analysé. Des quantités croissantes d'héparine non fractionnée ont été ajoutées à des échantillons de 0 à 0,3 U·mL−1 en incréments de 0,05 U·mL−1 pour simuler des doses croissantes d'héparine non fractionnée. Des tests INTEM et HEPTEM ont été réalisés en parallèle avec des tests de temps de thromboplastine partielle activée (aPTT). Un modèle de la relation entre la concentration d'héparine et le ratio temps de coagulation INTEM/HEPTEM (IH CT) a été créé en utilisant une régression non linéaire. Un modèle similaire pour l'aPTT a également été créé. RéSULTATS: Soixante-dix-sept patientes ont été incluses dans l'étude. Une seule concentration d'héparine a été ajoutée aux échantillons de sang de chaque patiente. À une concentration de 0,05 U·mL−1, le ratio IH CT était inférieur ou égal à 1,1 dans 9/11 échantillons (82 %). L'aPTT n'a pas été prolongé (> 35 sec) jusqu'à ce qu'une concentration d'héparine de 0,1 U·mL−1 soit ajoutée. Dans tous les échantillons, le ratio IH CT a été prolongé à une concentration ≥ 0,2 U·mL−1 telle que mesurée par thromboélastométrie; cependant, dans tous les échantillons, aucune concentration d'héparine n'a prolongé l'aPTT. CONCLUSION: Le ratio IH CT au chevet de la patiente peut être utile pour identifier la présence d'une activité d'héparine faible ou nulle. D'autres recherches sont nécessaires pour déterminer si ce ratio peut prédire l'activité héparinique in vivo.

The effects of hemodilution on coagulation in term parturients: an in vitro study utilizing rotational thromboelastometry.

OBJECTIVE: To examine the impact of hemodilution on components of blood coagulation using rotational thromboelastometry (ROTEM®) in term parturients. METHODS: This is a prospective, observational pilot study including 35 healthy, parturients at term (≥37 weeks) without history of bleeding or clotting disorder or on medication affecting coagulation. Venous blood samples were collected and divided into specimen tubes to generate varying degrees of hemodilution with Plasma-Lyte (0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%). ROTEM® was performed to assess for coagulation changes. RESULTS: EXTEM (extrinsically activated assay) clotting time (CT) became prolonged at 65% hemodilution and above, and the median CT was in the coagulopathic range (>80 s) at a dilution of 80%. FIBTEM (extrinsically activated assay with platelet inhibitor) amplitude at 5 min (A5) began to diminish at 35% hemodilution, with the median A5 in the coagulopathic range (<12 mm) at 55% hemodilution. The area under the curve (AUC) for EXTEM and FIBTEM consistently declined as hemodilution increased. Greater decreases in FIBTEM AUC were seen compared to EXTEM AUC, with the ratio of FIBTEM:EXTEM AUC at each dilution demonstrating a statistically significant difference from baseline. CONCLUSION: All thromboelastometry values demonstrated a hypocoagulable trend as hemodilution increased. However, the samples analyzed by the FIBTEM assay trended toward a coagulopathy at a lower degree of hemodilution compared to the EXTEM assay. As FIBTEM tests analyze the role of fibrinogen in hemostasis and EXTEM tests analyze the role of platelets, our findings suggest that platelets may be able to withstand higher degrees of hemodilution before impairing hemostasis compared to fibrinogen. These findings support the growing body of literature that in early stages of severe obstetric hemorrhage, the prioritization of fibrinogen replacement may be critical in preventing further coagulopathy.

Exposure to biologic therapy and associated maternal and neonatal outcomes in pregnancies complicated by inflammatory bowel disease.

BACKGROUND: There is growing evidence that biologic therapy is safe in pregnancies complicated by inflammatory bowel disease and that its use outweighs the risk of worsening disease activity, which is associated with adverse pregnancy outcomes. To our knowledge, there are limited data regarding the use of biologic therapy and the associated maternal adverse effects such as the risk of hypertensive outcomes, postoperative complications, and infectious risk. OBJECTIVE: Our objective was to evaluate a variety of obstetrical complications including maternal infectious outcomes, hypertensive outcomes, other adverse maternal outcomes including postoperative complications, venous thromboembolism, and postpartum hemorrhage; we also evaluated the neonatal outcomes associated with biologic use in pregnancies affected by inflammatory bowel disease. STUDY DESIGN: This was a retrospective cohort study including patients with inflammatory bowel disease who were pregnant and delivered at our institution. The maternal demographics and the incidence of maternal and neonatal outcomes were compared among groups on the basis of biologic exposure using the chi-square or Fisher exact test for categorical variables and the t test or Mann-Whitney test for continuous variables. Multivariable logistic regression analysis was performed on composite outcomes adjusting for age, disease activity, maternal obesity, history of cesarean delivery, and history of corticosteroid use in pregnancy. The statistical significance was defined as P<.05. RESULTS: A total of 322 patients who were pregnant, had inflammatory bowel disease, and delivered at our institution from 2012 to 2019, were included for analysis. Of these, 112 (34%) were on biologics during pregnancy. The patients in the biologic group had significantly lower body mass indices than the patients in the nonbiologic group (median body mass index, 22.4 vs 24.0, respectively; P=.04), and they were less likely to be multiparous (41% vs 59%, respectively; P=.003). In addition, more patients in the biologic group were likely to have Crohn disease with previous inflammatory bowel disease surgery (33% vs 20%, respectively; P=.01); otherwise, the 2 groups had similar baseline characteristics. Maternal infectious and hypertensive outcomes occurred significantly more frequently in the biologic group than the nonexposed group (22% vs 7%; P=.0003 and 19% vs 8%; P=.003, respectively). This remained statistically significant in multivariable logistic regression models. Specifically, maternal infectious and hypertensive outcomes occurred significantly more frequently in the patients on a single-agent antitumor necrosis factor treatment than the patients on no inflammatory bowel disease medication (24% vs 6%; P=.002; 22% vs 6%; P=.004), which remained statistically significant in multivariable logistic regression models. There was no difference in the neonatal adverse outcomes between the 2 groups. CONCLUSION: Our data suggest an association between antepartum biologic use- specifically antitumor necrosis factor alpha therapy-and an increased risk of maternal infectious and hypertensive outcomes. This increased risk may be related to underlying disease activity and the same should be incorporated into a discussion with the patient. However, the discussion must be balanced with the important benefit of optimal disease control associated with biologic use in patients being treated for IBD.

The impact of crystalloid versus colloid on coagulation as measured by thromboelastometry in term parturients: an in vitro study.

OBJECTIVE: A pilot study to examine the impact of crystalloid versus albumin hemodilution in vitro on coagulation using thromboelastometry in pregnant patients. METHODS: This prospective, observational pilot study included seventy-six pregnant patients at term (≥37 weeks) without history of bleeding or clotting disorder or on anticoagulation. Blood was collected and diluted with either Plasma-Lyte or albumin at the following levels: 0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%. Thromboelastometry was performed to assess for coagulation changes. RESULTS: There was a small, statistically significant difference in the FIBTEM A5 between the Plasma-Lyte and albumin samples. However, the predicted probability of coagulopathy, using FIBTEM A5 less than 12 mm, was not different between the groups at any dilution. There was no difference in EXTEM clotting time at low-moderate levels of hemodilution. At dilutions above 40%, the albumin group had a significantly greater prolongation in clotting time compared to the Plasma-Lyte group. CONCLUSION: When albumin is used at low-moderate levels of hemodilution in vitro in parturients there is no additional risk of coagulopathy compared to hemodilution with crystalloid. Given that colloids are frequently used to restore intravascular volume during massive hemorrhage, these results support that during early stages of hemorrhage, albumin may not contribute to additional coagulopathy beyond that of hemodilution, although further in vivo studies are needed.

Baseline parameters for non-activated rotational thromboelastometry tests with and without heparinase in healthy pregnant women at term gestation.

OBJECTIVE: To determine the normal values for non-activated thromboelastometry parameters among pregnant women. DESIGN: Prospective, observational study. SETTING: Tertiary care hospital. PATIENTS: Non-laboring women at term gestation without history of bleeding or clotting disorder or anticoagulation use. INTERVENTIONS: Venous blood samples were collected and ROTEM® was performed using NATEM and NaHEPTEM assays. MEASUREMENTS: Reference ranges were derived by calculating 2.5 and 97.5 percentiles for the following parameters: clotting time (CT), clot formation time (CFT), amplitude at 10 (A10) and 20 min (A20), alpha angle, maximum clot firmness (MCF), and lysis index at 30 (LI30) and 60 min (LI60). The NATEM/NaHEPTEM CT ratio was calculated to determine the baseline ratio in term pregnant women. MAIN RESULTS: 146 women were screened and 120 were enrolled. The median age was 34 years [31-36], median gestational age was 39.1 weeks [38.3-39.3], and median parity was 1 [0-2]. Median pre-delivery platelet and hematocrit levels were within the normal ranges. The reference ranges for NATEM parameters were: CT (232-759 (s)), CFT (69-243 (s)), alpha angle (50-77 (°)), A10 (44-69 (mm)), A20 (54-75 (mm)), MCF (57-77 (mm)), LI30 (100-100 (%)), LI60 (90-100 (%)). The reference ranges for NaHEPTEM parameters were: CT (224-717 (s)), CFT (66-210 (s)), alpha angle (53-77 (°)), A10 (44-67 (mm)), A20 (55-73 (mm)), MCF (58-74 (mm)), LI30 (99-100 (%)), LI60 (90-100 (%)). The NATEM to NaHEPTEM CT ratio reference range was 0.73-1.3. CONCLUSIONS: This study is the first to our knowledge to report reference ranges for non-activated ROTEM® tests with and without heparinase in non-laboring term pregnant women. These reference ranges may serve as a baseline comparison and may be useful for future research on anticoagulation management in pregnancy.

Monitoring of COVID-19-Associated Coagulopathy and Anticoagulation with Thromboelastometry.

INTRODUCTION: Thrombosis occurs frequently in COVID-19. While the exact mechanism is unclear, 3 processes seem to play important roles in sepsis-related thrombosis and mortality: tissue factor expression on circulating monocytes and microparticles, hypercoagulability (increased clot firmness), and hypofibrinolysis. Rotational thromboelastometry is a point-of-care viscoelastic technique that uses the viscoelastic properties of blood to monitor coagulation. Using various assays, viscoelastometry could monitor this triad of changes in severely ill, COVID-19-positive patients. Similarly, with the increased incidence of coagulopathy, many patients are placed on anticoagulants, making management more difficult depending on the agents utilized. Viscoelastometry might also be used in these settings to monitor anticoagulation status and guide therapy, as it has in other areas. CASE PRESENTATION: We present a case series of 6 patients with different stages of disease and different management plans. These cases occurred at the height of the pandemic in New York City, which limited testing abilities. We first discuss the idea of using the NaHEPTEM test as a marker of tissue factor expression in COVID-19. We then present cases where patients are on different anticoagulants and review how viscoelastometry might be used in a patient on anticoagulation with COVID-19. CONCLUSION: In a disease such as COVID-19, which has profound effects on hemostasis and coagulation, viscoelastometry may aid in patient triage, disease course monitoring, and anticoagulation management.

A Three-Year Analysis of the Impact of a Student-Run Gynecology Clinic on Access to Reproductive Health Care for Uninsured Women in East Harlem.

The East Harlem Health Outreach Partnership (EHHOP) is a medical student-run and attending-supervised clinic that provides primary care to predominantly Spanish-speaking, uninsured patients living in East Harlem, New York. In 2010, the clinic launched a Women's Health Clinic (WHC), to offer comprehensive gynecologic and reproductive healthcare under the guidance of faculty gynecologists. In this cross-sectional study, we analyzed WHC data from January 2018 to March 2021. Over this period, 59 individual patients were seen over 39 clinical sessions through a total of 164 clinical encounters staffed by 43 medical students and 19 faculty preceptors from the Department of Obstetrics and Gynecology at Mount Sinai. The most common reasons for referral to the EHHOP WHC were abnormal uterine bleeding, contraception counseling, and management of abnormal Pap smears; the most common procedures performed were Pap smears, long-acting reversible contraception placements and removals, and colposcopies. We discuss the critical role that student-run, physician-supervised reproductive health clinics play in reducing disparities in gynecologic care for uninsured women.

Atypical Hemolytic-Uremic Syndrome Following Obstetric Hemorrhage in the Setting of Fetal Demise and Placenta Accreta: A Case Report.

Multiple disease processes can contribute to coagulopathy in the setting of intrauterine fetal demise. A 34-year-old woman with multiple prior uterine surgeries presented for dilation and evacuation of a fetal demise at 17 weeks. Her case was complicated by significant hemorrhage and coagulopathy requiring massive transfusion and hysterectomy. She developed atypical hemolytic-uremic syndrome postoperatively. Pathology identified a focal placenta accreta. While not known to present together, fetal demise, placenta accreta, and atypical hemolytic-uremic syndrome can occur in the same patient with an overlapping presentation. Early hematology consultation is recommended in the setting of ongoing hemolysis and renal dysfunction.

Thromboelastometry-guided neuraxial anesthesia in a parturient with severe thrombocytopenia due to large granular lymphocytic leukemia.

Severe thrombocytopenia (platelet count <50 000/µl) in pregnancy is uncommon and is generally considered a contraindication to neuraxial anesthesia. We present a case of a parturient who presented with severe thrombocytopenia secondary to bone marrow failure. After receiving platelet and cryoprecipitate transfusions to correct coagulopathy as verified by thromboelastometry, neuraxial anesthesia was safely utilized.

Are Women with a History of Low PAPP-A at Risk for Adverse Perinatal Outcomes in a Subsequent Pregnancy?

OBJECTIVE: To determine if patients with a history of low pregnancy-associated plasma protein A (PAPP-A) in an initial pregnancy are at higher risk for adverse obstetric outcomes in a subsequent pregnancy. STUDY DESIGN: This was a retrospective cohort study in patients who underwent first trimester screening for PAPP-A in two consecutive pregnancies. Two groups were examined: patients who had low PAPP-A in the first pregnancy followed by normal PAPP-A in the second pregnancy and patients who had recurrent low PAPP-A. Maternal and neonatal outcomes were compared between the groups, with the primary outcome being intrauterine growth restriction (IUGR) or preeclampsia. RESULTS: A total of 124 patients were included, representing 248 pregnancies. Ninety-two (74.2%) patients had normal PAPP-A in the second pregnancy, and 32 (12.9%) patients had recurrent low PAPP-A. Patients with recurrent low PAPP-A had a higher rate of IUGR or preeclampsia compared with patients with normal PAPP-A in the second pregnancy but this was not significantly different (12.5 vs. 10.9%, p = 0.51). There were no significant differences for all other outcomes. CONCLUSION: Among patients with a history of low PAPP-A, patients with normal PAPP-A in the subsequent pregnancy have a similar risk of adverse neonatal outcomes compared with patients with recurrent low PAPP-A.

Maternal clinical disease characteristics and maternal and neonatal outcomes in twin and singleton pregnancies with severe preeclampsia.

OBJECTIVE: Based on anecdotal observations, there is concern that severe preeclampsia leads to greater morbidity and mortality for mothers and neonates of twin pregnancies than for mothers and neonates of singleton pregnancies. Because few studies have been done, this study compared maternal disease characteristics and maternal/neonatal clinical outcomes of twin and singleton pregnancies complicated by severe preeclampsia. STUDY DESIGN: An historical cohort study of patients hospitalized at the Mount Sinai Hospital in New York City, NY, USA, from 2006 to 2010, compared 63 twin and 339 singleton pregnancies complicated by severe preeclampsia via chart review. Women were analyzed in two groups: hospitalized ≤34 weeks gestational age (GA) and hospitalized >34 weeks GA. Univariable analysis (using Chi-square test, Fisher's Exact test, Student's t-test, or Wilcoxon Rank-Sum test, as appropriate) then multivariable analysis (using multivariable linear regression or multivariable logistic regression, as appropriate) compared maternal disease characteristics and maternal/neonatal clinical outcomes in twin and singleton pregnancies. RESULTS: Women with twins were older [mean age 34.9 years (standard deviation (SD) 7.9 years) vs. 29.4 years (SD 7.4 years), P-value<.001] and women with singletons had a higher prevalence of chronic hypertension (21% vs. 8%, P=.02) and higher prevalence of history of preeclampsia (13% vs. 2%, P=.006). Women with twins were admitted for severe preeclampsia at an earlier gestational age (GA) [median twin 34.9 weeks GA (interquartile range, IQR, 32.7, 36.1) vs. median singleton 37.1 weeks GA (IQR 35.0, 38.9), P<.001]. Among women presenting ≤34 weeks GA (27 twins; 108 singletons), women with singletons had a higher mean systolic blood pressure (BP) (181.1 vs. 163.5, P<.001), higher mean diastolic BP (108.4 vs. 100.1, P=.002), and higher prevalence of headache (56% vs. 30%, P=.02). Among women presenting >34 weeks GA (36 twins; 231 singletons), women with singletons had a higher prevalence of headache (54% vs. 28%, P=.004). CONCLUSION: Mothers and neonates of twin pregnancies complicated by severe preeclampsia do not appear to have greater morbidity and mortality compared to mothers and neonates of singleton pregnancies complicated by severe preeclampsia.

Risk factors for new-onset late postpartum preeclampsia in women without a history of preeclampsia.

OBJECTIVE: Risk factors for the development of new-onset late postpartum preeclampsia (LPP) in women without any history of preeclampsia are not known. Because identification of women who are at risk may lead to an earlier diagnosis of disease and improved maternal outcomes, this study identified risk factors (associated patient characteristics) for new-onset LPP. STUDY DESIGN: A case-control study of 34 women with new-onset LPP and 68 women without new-onset LPP after normal delivery, who were matched on date of delivery, was conducted at Mount Sinai Hospital, New York, NY. Data were collected by chart review. Exact conditional logistic regression identified patient characteristics that were associated with new-onset LPP. RESULTS: New-onset LPP was associated with age ≥40 years (adjusted odds ratio, 24.83; 95% confidence interval [CI], 1.43-infinity; P = .03), black race (adjusted odds ratio, 78.35; 95% CI, 7.25-infinity; P < .001), Latino ethnicity (adjusted odds ratio, 19.08; 95% CI, 2.73-infinity; P = .001), final pregnancy body mass index of ≥30 kg/m(2) (adjusted odds ratio, 13.38; 95% CI, 1.87-infinity; P = .01), and gestational diabetes mellitus (adjusted odds ratio, 72.91; 95% CI, 5.52-infinity; P < .001). As predictive tests for new-onset LPP, the sensitivity and specificity of having ≥1 of these characteristics was 100% and 59%, respectively, and the sensitivity and specificity of having ≥2 was 56% and 93%, respectively. CONCLUSION: Older age, black race, Latino ethnicity, obesity, and a pregnancy complicated by gestational diabetes mellitus all are associated positively with the development of new-onset LPP. Closer observation may be warranted in these populations.