Jennifer J. McIntosh

The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention.

Preterm birth remains a major cause of neonatal death and short and long-term disability in the US and across the world. The majority of preterm births are spontaneous and cervical length screening is one tool that can be utilized to identify women at increased risk who may be candidates for preventive interventions. The purpose of this document is to review the indications and rationale for CL screening to prevent preterm birth in various clinical scenarios. The Society for Maternal-Fetal Medicine recommends (1) routine transvaginal cervical length screening for women with singleton pregnancy and history of prior spontaneous preterm birth (grade 1A); (2) routine transvaginal cervical length screening not be performed for women with cervical cerclage, multiple gestation, preterm premature rupture of membranes, or placenta previa (grade 2B); (3) practitioners who decide to implement universal cervical length screening follow strict guidelines (grade 2B); (4) sonographers and/or practitioners receive specific training in the acquisition and interpretation of cervical imaging during pregnancy (grade 2B).

Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura

UNLABELLED Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. CONCLUSIONS With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children.

Syndromes of thrombotic microangiopathy associated with pregnancy

When a pregnant or postpartum woman presents with sudden and severe microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, three syndromes that require urgent care must be considered: (1) preeclampsia with severe features/hemolysis, elevated liver function tests, low platelets (PE/HELLP) syndrome; (2) thrombotic thrombocytopenic purpura (TTP); and (3) complement-mediated thrombotic microangiopathy (C-TMA; also referred to as atypical hemolytic-uremic syndrome). The distinction among these three syndromes is often unclear because they share multiple clinical features. Overlap between PE/HELLP syndrome and the other two syndromes is also apparent from the fact that pregnancy can be a trigger for both TTP and C-TMA both before and after delivery and also the increased frequency of PE/HELLP syndrome in women who have recovered from TTP. When diagnostic criteria for PE/HELLP syndrome are present, management of hypertension and delivery is curative. Absence of improvement or actual progression of MAHA, thrombocytopenia, and kidney function abnormalities after delivery requires consideration of TTP and C-TMA. Minimal kidney involvement with severe thrombocytopenia suggests TTP and the need for treatment with plasma exchange; progressive kidney injury (in the absence of a cause for acute tubular necrosis) suggests C-TMA and the need for anti-complement treatment. We describe how we use these criteria to evaluate and manage pregnant/postpartum women with MAHA and thrombocytopenia.

Difficulties in establishing routine amniocentesis for preterm labor evaluation

After a recent practice change implementing amniocentesis into the evaluation of preterm labor (PTL) or preterm premature rupture of membranes (PPROM), actual performance of the procedure was tracked. Fifty-nine patients were admitted with these diagnoses. Twenty-three patients (39%) were offered amniocentesis and 36 patients (61%) were not offered amniocentesis as part of the clinical protocol. Seven (30%) patients of those offered an amniocentesis underwent the procedure. The predominant reasons for not performing an amniocentesis were patient refusal and provider discomfort. In conclusion, implementation of amniocentesis to evaluate for subclinical infection/inflammation in the setting of PTL or PPROM proved difficult, as only 7 of 59 (11.9%) patients admitted with these diagnoses actually received an amniocentesis.

Multiple myeloma presenting as hypercalcemic pancreatitis during pregnancy.

BACKGROUND: Multiple myeloma is typically a disease found in older women and is a rare diagnosis in pregnancy. CASE: A 22-year-old woman, gravida 1 para 0, at 32 3/7 weeks of gestation presented with nausea, vomiting, and rib and back pain. She was hypertensive, anemic, thrombocytopenic, and in acute renal insufficiency, with hypercalcemia and laboratory parameters indicative of pancreatitis. She was admitted to the obstetric intensive care unit with working diagnoses of preeclampsia, pancreatitis, nephrolithiasis, and renal insufficiency. She ultimately was delivered because of declining clinical status, and multiple myeloma eventually was diagnosed as the underlying cause of her myriad of problems. CONCLUSION: Multiple myeloma is unusual during pregnancy. However, in patients with significant and unexplained hypercalcemia, malignancy should remain high on the differential diagnosis.

Assessing the quality of evidence for preterm labor tocolytic trials

Objective: To assess the quality of tocolysis randomized controlled trials (RCTs) and to determine trial factors contributing to better quality evidence. Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, MEDLINE In-Process, EMBASE and CINAHL were searched for terms “preterm labor,” “tocolytic” or “obstetric labor, premature” up to 1 August 2009.Data regarding study design, characteristics, number of participants and outcomes reported were extracted by at least two review authors. Study quality was assigned using the Cochrane Collaboration Handbook methodology and categories. Trends for quality over time, the impact of study size and the individual drugs compared were analyzed for impact on overall quality of trials. Results: Of the 3197 titles initially identified, 89 RCTs of tocolytic therapy were reviewed. Of the six quality areas, 10 (11.2%) trials satisfied all areas, while only one trial (1.1%) met one area. The mean number of adequate areas was 4.1 ± 1.2. Overall, 52 (58.4%) of the trials achieved high-quality categorization. Controlling for multiple trial factors, the trial continent and decade were significant predictors of overall trial quality. Conclusion: The majority of tocolysis RCTs are of high quality. Larger trials, more recent trials and placebo-controlled trials were associated with higher quality scores.

Platelet counts in women with normal pregnancies: A systematic review

The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3,039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000‐264,000/µL); second trimester, 238,000/µL (95% CI, 222,000‐253,000/µL); third trimester, 224,000/µL (95% CI, 213,000‐235,000/µL); delivery, 237,000/µL (95% CI, 209,000‐264,000/µL); 4‐8 weeks postpartum, 247,000/µL (95% CI, 207,000‐287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross‐sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy.

362: The impact of fetal anomalies on contemporary labor patterns

• The most significant trends were observed in the preterm nulliparous and multiparous groups • Labor curves for these groups indicate labor progressed more slowly for patients with pregnancies affected by fetal anomalies (Figures 1,2) • The median traverse times from 4cm to complete dilation • Preterm nulliparous patients • 5.2 hours in the control and 6.6 hours in the anomaly group (p<0.05). • Preterm multiparous • 5.2 hours in the control and 6.2 hours for the anomaly group (p<0.05) • Labor proceeds at a slower rate for patients with pregnancies affected by fetal anomalies in preterm nulliparous and multiparous groups. • This slower rate should be considered while caring for these patients in labor. RESULTS BACKGROUND

PLATELET SEQUESTRATION AND CONSUMPTION IN THE PLACENTAL INTERVILLOUS SPACE CONTRIBUTE TO LOWER PLATELET COUNTS DURING PREGNANCY

ment of CD19 MPAL and to establish its efficacy in controlling this rare type of acute leukemia. Although the survival of patients with MPAL has improved in recent years, primarly due to incorporation of allo-HSCT into treatment, the overall prognosis remains poor. The risk of death from MPAL is 59% and 26% higher than for ALL and AML, respectively. In the absence of prospective clinical trials, MPAL treatment is guided by retrospective studies and is based on ALL regimens. Given high relapse rates with chemotherapy, targeted approaches may improve outcomes. B/myeloid MPAL blasts express CD19. In this report, we aimed to study the efficacy of blinatumomab in the treatment of two patients with CD19 MPAL. The clinical hypothesis was that treatment of these patients with CD19 MPAL with blinatumomab, along with a tyrosine kinase inhibitor for Ph(+) disease in the first patient, would result in the achievement of sustained MRD-negative CR and maintenance of MRD-negative CR in the first and second patient, respectively. Our patients had short periods of myelosuppression and few adverse events, which led to overall improved functional status after therapy. Both patients were able to proceed to allo-HSCT, thus far resulting in sustained MRD-negative clinical remissions. The poor outcomes of R/R MPAL with chemotherapy underscore the need for a prospective clinical study of targeted therapy in this patient population. We suggest that blinatumomab is an excellent candidate for this purpose.