Pharmacologic venous thromboembolism prophylaxis for preterm prelabor rupture of membranes.

BACKGROUND: Pregnant patients with preterm prelabor rupture of membranes may experience prolonged hospitalization, which is an indication for pharmacologic venous thromboembolism prophylaxis according to certain international guidelines. The proportion of patients who deliver unexpectedly and within a period during which pharmacologic prophylaxis would be expected to impact coagulation is unknown. OBJECTIVES: To estimate the proportion of patients with preterm prelabor rupture of membranes who would deliver within 12 hours of typical dosing of pharmacologic venous thromboembolism prophylaxis if administered routinely for antepartum admissions >72 hours. STUDY DESIGN: This is a retrospective cohort study from a database including patients admitted for expectant management of preterm prelabor rupture of membranes January 2011-September 2020. The outcome of the study was the proportion of patients who remained undelivered 72 hours after admission and experienced an unplanned delivery potentially within 12 hours of enoxaparin administration. We evaluated patients undelivered after 72 hours due to international recommendations to initiate venous thromboembolism prophylaxis in hospitalized patients after 72 hours. Unplanned delivery was defined as onset of spontaneous labor or other indication for immediate delivery. Timing of delivery was analyzed based on usual timing of enoxaparin administration daily at approximately 8 am and the recommendation to withhold regional anesthesia until 12 hours after a prophylactic dose. RESULTS: 1381 deliveries were identified as preterm prelabor rupture of membranes out of the 49,322 deliveries in our database. 139 cases were included after the following exclusions: delivery >35 weeks (N=641), rupture of membranes >34 weeks (N=145), delivery <72 hours after admission (N=409), insufficient data (N=35), and duplicates (N=12). Sixty of the 139 (43%) had an unplanned delivery, while 33 of these (24% of total) occurred within 12 hours of enoxaparin administration. CONCLUSION: A quarter of patients admitted for preterm prelabor rupture of membranes had an unplanned delivery within 12 hours of typical enoxaparin dosing. This cohort may experience harm (ineligibility for regional anesthesia, risks of general anesthesia, increased risk of bleeding) if given routine pharmacologic venous thromboembolism prophylaxis. Risk/benefit considerations should be discussed with patients in considering pharmacologic versus mechanical prophylaxis during prolonged hospitalization for preterm prelabor rupture of membranes.

Hepatic encephalopathy precipitated by preeclampsia in the setting of cirrhosis: A case report.

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications. A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved promptly post-delivery. Preeclampsia can trigger acute hepatic dysfunction, including hepatic encephalopathy, in the setting of previously compensated preexisting liver disease. Recognizing this association has important implications for management and treatment.

Gestational hypertension and "severe" disease: time for a change.

Our understanding and management of gestational hypertension and its variants are substantially hindered by a reliance on antiquated terminology and on practice recommendations based largely on tradition rather than outcomes-based evidence. Unsurprisingly, gestational hypertension remains a major contributor to maternal and neonatal morbidity and mortality rates, with little improvement seen over the past half century except as it relates to better newborn care. Reliance on a binary classification of vastly disparate types and degrees of organ dysfunction (severe or not severe) and the use of nonphysiological and largely arbitrary gestational age cutoffs are particularly problematic. If this situation is to improve, it will be necessary to abandon current misleading terminology and non-evidence-based traditional practice patterns and start again, building on management approaches validated by outcomes-based data.

Management of a Novel Autoimmune Disease, COPA Syndrome, in Pregnancy.

Background: COPA syndrome is a rare autoimmune disease, demonstrating an autosomal dominant inheritance pattern with variable penetration that occurs more frequently in females than males. This disease manifests in childhood as pulmonary hemorrhage, arthritis, and renal disease. Case: We present a case of obstetric management of a 20-year-old nulligravida patient with a diagnosis of COPA syndrome. Her case was further complicated by multiple antepartum admissions for hypoxemia and a complex psychosocial history of substance use. On her first antepartum admission, rheumatology recommended management with hydroxychloroquine, inhaled corticosteroids (budesonide), and bronchodilators (albuterol inhaler) as needed. On admission for induction of labor, she was again noted to have oxygen desaturations. A chronic thrombus was noted on computed tomography (CT), and a multidisciplinary team was recommended against Valsalva. Thus, she had a primary cesarean delivery. Her postpartum course was only remarkable for improved oxygenation status. Conclusion: Management of COPA syndrome should be performed by a multidisciplinary team including maternal-fetal medicine, rheumatology, and pulmonology specialists. Traditionally, COPA syndrome is treated with immunomodulator therapy often used to treat autoimmune syndromes. However, many of these medications are not well studied or contraindicated in pregnancy. Preconception counseling is recommended both to ensure pregnancy safe medications being prescribed and to provide information on the genetic inheritance of this disease. At time of entry to care, patients should have a baseline work-up including a radiographic imaging, complete blood count, complete metabolic panel, lactate dehydrogenase, and a 24-hour urine protein collection for baseline. Although thought to be rare, COPA syndrome has an autosomal dominance pattern of inheritance with variable penetrance that is more common in females. Thus, incidence of COPA syndrome in pregnancy will likely increase in the future. Further case studies are warranted to optimize management of patients with COPA syndrome in pregnancy.

Cerebral perfusion pressure and autoregulation in eclampsia-a case control study.

BACKGROUND: Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. OBJECTIVE: This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. STUDY DESIGN: This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. RESULTS: We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). CONCLUSION: Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.

Accuracy of Ultrasound to Predict Neonatal Birth Weight Among Fetuses With Gastroschisis: Impact on Timing of Delivery.

OBJECTIVES: To determine the accuracy of ultrasound estimation of fetal weight among fetuses with gastroschisis and how the diagnosis of fetal growth restriction (FGR) affects the timing of delivery. METHODS: This was a retrospective cohort study including all fetuses with a diagnosis of gastroschisis at our institution from November 2012 through October 2017. We excluded multiple gestations, pregnancies with major structural or chromosomal abnormalities, and those for which prenatal and postnatal follow-up were unavailable. Performance characteristics of ultrasound to predict being small for gestational age (SGA) were calculated for the first and last ultrasound estimations of fetal weight. RESULTS: Our cohort included 75 cases of gastroschisis. At the initial ultrasound estimation, 15 of 58 (25.9%) fetuses met criteria for FGR; 48 of 70 (68.6%) met criteria at the time of the last ultrasound estimation (median, 34.7 weeks). Cesarean delivery was performed for 37 of 75 (49.3%), with FGR and concern for fetal distress as the indication for delivery in 17 of 37 (45.9%). Only 6 of 17 (35.3%) of the neonates born by cesarean delivery for an indication of FGR and fetal distress were SGA. The initial ultrasound designation of FGR corresponded to SGA at birth in 8 of 15 (53.3%), whereas the last ultrasound estimation corresponded to SGA in 17 of 48 (35.4%). The initial ultrasound estimation agreed with the last ultrasound estimation before delivery with the diagnosis of FGR in 13 of 15 (86.7%). CONCLUSIONS: Ultrasound in the third trimester was sensitive but had a low positive predictive value and low accuracy for the diagnosis of SGA at birth for fetuses with gastroschisis. A large proportion of fetuses were born by cesarean delivery with indications related to FGR or fetal concerns.

Pregnancy and Lactation in a 67-Year-Old Elderly Gravida following Donor Oocyte In Vitro Fertilization.

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum course was uncomplicated, and she was able to successfully breastfeed for six months and resume prepregnancy activity. For comparison, we analyzed deliveries among gravidae > 45 years of age from our institutional obstetrical database (2011-2018). This case represents the eldest gravidae identified in the literature and illustrates the potential for a relatively uncomplicated perinatal course with successful lactation. This case may enable other providers to counsel elderly patients on anticipated outcomes inclusive of ability to breastfeed.

Diagnostic Imaging and Outcomes for Nonobstetric Surgery During Pregnancy.

A surgical disease occurring during pregnancy can present a diagnostic dilemma due to the desire to make a timely and accurate diagnosis within the constraints of limiting radiation exposure to the fetus. However, required diagnostic imaging should be pursued when indicated and attempts made to minimize the radiation dose by utilizing abdominal shielding and low-dose protocols when feasible. When surgery is indicated due to disease processes, treatment should not be altered or delayed due to pregnancy as the evidence for adverse pregnancy outcomes including early pregnancy loss and preterm delivery are overall of low quality due to substantial confounding by the disease process itself.

Peripartum Outcomes Before and After Hurricane Harvey.

OBJECTIVE: To evaluate the association between Hurricane Harvey landfall with maternal and neonatal morbidity. METHODS: Using an institutional perinatal database from two hospitals in Houston, Texas, women with nonanomalous singletons delivering after 24 weeks of gestation between August 2011 and June 2018 were included. To evaluate the possible association of hurricane landfall with pregnancy outcomes, gravid women delivering within 280 days (40 weeks of gestation) on or after August 25, 2017 (the day of hurricane landfall) were categorized as exposed, and women who delivered before August 25, 2017, were the reference group. Composite maternal morbidity included any of the following: hypertensive disorders of pregnancy, chorioamnionitis, endometritis, blood transfusion, peripartum hysterectomy, maternal critical care admission, pulmonary edema, or maternal death. Composite neonatal morbidity included any of the following: 5-minute Apgar score 3 or less, respiratory distress syndrome, use of ventilator or continuous positive airway pressure, suspected newborn sepsis, seizure, stillbirth, or neonatal death. Adjusted odds ratios (aORs) were calculated after correcting for possible confounders identified on univariate analysis. Disruption in outcome trends were measured in time series analyses. RESULTS: Of 40,502 deliveries in our database, 29,179 (72%) met the inclusion criteria, with 3,842 (13.2%) delivering within 280 days of Hurricane Harvey landfall. Women delivering after Hurricane Harvey were on average less likely to be obese and more likely to be older, Caucasian, married, have a household income higher than $75,000, a high school education, and private insurance. However, compared with the cohort of gravid patients who delivered before Hurricane Harvey, composite maternal morbidity increased by 27% (11.5% vs 14.7%, aOR 1.27, 95% CI 1.14-1.42) after the storm. Composite neonatal morbidity increased by 50% (7.8% vs 11.9%, aOR 1.52, 95% CI 1.34-1.71). In time series analyses, we observed a significant shift in composite maternal morbidity specific to women of low socioeconomic status (estimate 2.87, P=.028). CONCLUSION: Despite having fewer at-risk baseline characteristics, gravid patients delivering after landfall by Hurricane Harvey had a significantly higher likelihood of adverse outcomes as did their neonates.

Characterization of precursor lesions in the endometrium and fallopian tube epithelium of early-stage uterine serous carcinoma.

To determine if selected cases of uterine serous carcinoma (USC) arise from tubal rather than endometrial epithelium. Bilateral fallopian tubes from 38 women with pure USC were entirely submitted for histopathologic examination using the protocol Sectioning and Extensively Examining the FIMbria (SEE-FIM). Non-neoplastic endometrium was extensively sampled. Immunohistochemistry for p53 was performed on all paraffin blocks of fallopian tube and non-neoplastic endometrium. Endometrial intraepithelial carcinoma (EIC) was present in 22 cases (58%). Endometrial p53 foci were identified in 3 patients. There were 11 cases (29%) with fallopian tube involvement; 9 of 11 had tubal wall invasion or lymphatic involvement without serous tubal intraepithelial carcinoma (STIC) and were, therefore, classified as metastatic from the endometrium. STIC was identified in 3 patients (8%). There were 3 cases with tubal p53 foci in non-neoplastic epithelium. EIC was present in 58% of patients, further supporting EIC as a precursor lesion to USC. STIC was present in 8%, suggesting that the fallopian tube may in fact represent the primary lesion in a minority of patients with USC. This finding may account for the early multifocal disease distribution observed in these patients.

Decision-to-incision time and neonatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the proportion of emergent cesarean deliveries accomplished within 30 minutes, the mean time from decision-to-incision or delivery, and differences in neonatal outcomes in deliveries accomplished within 30 minutes compared to beyond 30 minutes. DATA SOURCES: Electronic databases (Ovid MEDLINE and EMBASE and www.clinicaltrials.gov) were searched from inception to January 2013. METHODS OF STUDY SELECTION: Eligible studies reported decision-to-incision time or delivery time intervals for nonelective cesarean deliveries. Both emergent and urgent deliveries (also known as category 1 and category 2 deliveries) were included. Two reviewers independently identified studies for inclusion. TABULATION, INTEGRATION, AND RESULTS: Out of 737 reports identified in the primary search, 34 studies (22,936 women) met eligibility criteria. Seventy-nine percent (95% confidence interval [CI] 61-97%) of category 1 deliveries and 36% (95% CI 24-48%) of category 2 deliveries were achieved within 30 minutes, with significantly shorter time in category 1 compared to category 2 deliveries (21.2 compared with 42.6 minutes; P<.001). In the 13 studies that included neonatal outcomes, there was a higher risk of overall 5-minute Apgar score less than 7 (odds ratio [OR] 3.10; 95% CI 1.93-4.96) and umbilical artery pH level less than 7.10 (OR 3.40; 95% CI 2.38-4.87) in cases involving shorter delivery intervals. However, analyses limited to category 1 deliveries did not show a statistically greater risk of Apgar score less than 7 (OR 0.69; 95% CI 0.11-4.51) or umbilical artery pH level less than 7.10 (OR 1.10; 95% CI 0.28-4.40) with shorter delivery intervals. There was no difference by delivery interval in admission to neonatal intensive care units or special newborn units (OR 1.23; 95% CI 0.90-1.68). CONCLUSION: Delivery within 30 minutes was not achieved in a substantial proportion of cases. The clinical significance of failing to achieve this standard remains uncertain.

Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas.

Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2-targeted treatment in a small series of women with recurrent HER2-amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2-overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2-targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.

Spontaneous rectus sheath hematoma pregnancy: case report and review of the literature.

Rectus sheath hematoma (RSH) is a rare, but important potential cause of acute upper abdominal pain in pregnancy. We report a patient with history of hemolysis, elevated liver enzymes, low platelets syndrome who presented with upper abdominal pain, hypotension, elevated hepatic transaminase levels, and a visibly enlarging right costal margin mass at 33 weeks' gestation. She underwent emergent cesarean delivery and upper abdominal exploration with findings of a large hematoma involving the entire right rectus sheath. The current case illustrates that the diagnosis of an RSH in pregnancy can be difficult as its presentation can mimic many common causes of abdominal pain seen outside of pregnancy, as well as many specific to pregnancy. Review of the published cases from the past 20 years shows that correct diagnosis remains difficult in pregnancy despite advances in diagnostic imaging. Although management of an RSH outside of pregnancy is frequently conservative, it is very often treated surgically in pregnant patients and often leads to preterm delivery.