Preterm labor biomarker discovery in serum using 3 proteomic profiling methodologies.

OBJECTIVE: The aim of this study was to identify changes in protein expression in normal pregnancy compared with preterm labor by using 3 proteomic methods. STUDY DESIGN: Serum was collected from 25 nonpregnant (n = 5) and pregnant women at 24-40 weeks' gestation (n = 20) who had preterm labor resulting in preterm delivery (n = 5), preterm labor with term delivery (n = 5), term labor resulting in delivery (n = 5), or at term with contractions (n = 5). Undepleted serum was used for surface-enhanced laser desorption ionization and immune-depleted serum for matrix-assisted laser desorption ionization and 2-dimensional electrophoresis. RESULTS: Surface-enhanced laser desorption ionization identified significantly different peaks between preterm labor resulting in preterm delivery vs term labor resulting in delivery and preterm labor resulting in preterm delivery vs preterm labor with term delivery using 4 surfaces. In preterm labor resulting in preterm delivery vs preterm labor with term delivery, a peak of 7783.2 m/z was significantly up-regulated and at 3164 m/z down-regulated on 3 surfaces. By using 2-dimensional electrophoresis, protein 5364 was significantly different between preterm labor resulting in preterm delivery and term labor resulting in delivery. In preterm labor resulting in preterm delivery, 6 proteins showed decreasing trend and 1 showed increasing trend vs preterm labor with term delivery. Matrix-assisted laser desorption ionization showed a striking difference at 55,000 m/z between preterm labor resulting in preterm delivery and term labor resulting in delivery. CONCLUSION: Surface-enhanced laser desorption ionization identified 2 proteins fulfilling the criteria of putative biomarkers. Biomarker identification may aid in identifying women with preterm labor who will deliver preterm.

Diagnosis and management of atypical preeclampsia-eclampsia.

Preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets syndrome are major obstetric disorders that are associated with substantial maternal and perinatal morbidities. As a result, it is important that clinicians make timely and accurate diagnoses to prevent adverse maternal and perinatal outcomes associated with these syndromes. In general, most women will have a classic presentation of preeclampsia (hypertension and proteinuria) at > 20 weeks of gestation and/or < 48 hours after delivery. However, recent studies have suggested that some women will experience preeclampsia without > or = 1 of these classic findings and/or outside of these time periods. Atypical cases are those that develop at < 20 weeks of gestation and > 48 hours after delivery and that have some of the signs and symptoms of preeclampsia without the usual hypertension or proteinuria. The purpose of this review was to increase awareness of the nonclassic and atypical features of preeclampsia-eclampsia. In addition, a stepwise approach toward diagnosis and treatment of patients with these atypical features is described.

The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the obstetric triage and emergency department: lessons from 4 tertiary hospitals.

OBJECTIVE: We report a series of occurrences of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) in pregnancy that emphasizes early diagnosis. STUDY DESIGN: Fourteen pregnancies with TTP (n = 12) or HUS (n = 2) were studied. Analysis focused on clinical and laboratory findings on examination, initial diagnosis, and treatment. RESULTS: There were 14 pregnancies in 12 patients; 2 cases of TTP were diagnosed as recurrent. Five women were admitted to the emergency department (ED), and 7 patients were admitted to an obstetrics triage. Patients who were evaluated by an obstetrician were treated initially for hemolysis, elevated liver enzymes and low platelets syndrome/preeclampsia, whereas patients who were seen in the ED had a diagnosis that is commonplace in the ED (panic attack, domestic violence, gastroenteritis). Latency from the onset of symptoms to diagnosis ranged from 1-7 days. Plasmapheresis treatments in early gestation resulted in favorable maternal-neonatal outcome. Maternal and perinatal mortality rates were 25% each. CONCLUSION: TTP/HUS is a challenging diagnosis in obstetric triage and ED areas. We propose a management scheme that suggests how to triage patients for early diagnosis in pregnancy.

The coexistence of gestational hypertension and diabetes: influence on pregnancy outcome.

Gestational hypertension (GHTN) and gestational diabetes mellitus (GDM) are both insulin resistance states. Perinatal outcome of GHTN or GDM alone are well established, but their combined effect on pregnancy outcome is underinvestigated. Our objective was to determine if pregnancies complicated by GHTN/GDM have higher rates of morbidity. We identified nulliparous women with singleton pregnancies delivering at 37 to 40 weeks of gestation from 1995 to 2004 from a database. Outcomes of pregnancies complicated by GHTN only, GDM only, or combined GHTN/GDM were compared with controls. Data analysis included the Mann-Whitney U test, the Kruskal-Wallis H test, and analysis of variance. Multivariate analysis was used to adjust for confounders. Of 14,880 patients, there were 11,349 controls, 2604 GHTN, 728 GDM, and 199 GHTN/GDM. After controlling for covariates, GHTN significantly increased cesarean section (C/S) rate (odd ratio [OR], 1.62; confidence interval [CI], 1.47 to 1.78), rates of admittance to the neonatal intensive care unit (NICU), and birth of large for gestational age (LGA) infants. GDM significantly increased C/S (OR, 1.42; CI 1.21 to 1.66), rates of NICU admission (OR, 1.32; CI, 1 to 1.75), birth of LGA (OR, 1.51; CI 1.14 to 1.98), and macrosomic infants (OR, 1.53; CI, 1.12 to 2.08). Rates of LGA infants (OR, 1.85; CI, 1.19 to 2.86) and C/S (OR, 2.03; CI, 1.52 to 2.71) were significantly increased with GHTN/GDM. We concluded that GHTN or GDM is associated with increased rates of adverse outcomes. Their coexistence further increases adverse perinatal outcomes.

HELLP syndrome: an atypical presentation.

HELLP syndrome without proteinuria or hypertension is rare. We present the case of a 33-year-old primigravid who initially was diagnosed with pulmonary embolism. The patient was readmitted with a diagnosis of subcapsular hematoma and eventually diagnosed with HELLP syndrome with a sequela of hepatic rupture.

Postpartum headache: is your work-up complete?

OBJECTIVE: Headache is a common finding in the postpartum period, and there are limited data describing the cause and treatment of women with postpartum headache. Our objective was to describe our experience with women who were hospitalized for postpartum headache and to develop a management algorithm for these women. STUDY DESIGN: Data for 95 women with headache >24 hours after delivery from 2000-2005 were reviewed retrospectively. Maternal assessment included an evaluation for benign and serious causes of headache that included preeclampsia, dural puncture, and neurologic lesions. Neurologic imaging were performed on the basis of initial neurologic findings and clinical course. Outcomes that were studied included cause, a need for cerebral imaging, neurologic findings, maternal complications, and long-term follow-up evaluations. RESULTS: The mean onset of headache was 3.4 days (range, 2-32 days) after delivery. Tension-type/migraine headache was the most common cause (47%). Preeclampsia/eclampsia and spinal headache comprised 24% and 16% of cases, respectively. Anesthesia evaluation was required in 15 patients because of suspected spinal headache; blood patch was required in 12 of these patients. Cerebral imaging was performed in 22 patients because of focal neurologic deficits and/or failure to respond to initial therapy; 15 of these women (68%) had abnormal findings. Ten patients had serious cerebral pathologic findings, such as hemorrhage, thrombosis, or vasculopathy. There were no deaths; 2 women had minor residual neurologic damage on follow-up evaluation. CONCLUSION: The evaluation of persistent headaches that develop >24 hours after delivery must be performed in a stepwise fashion and requires a multidisciplinary approach. Preeclampsia should be considered initially in women with hypertension and proteinuria. Normotensive women should be evaluated initially for tension-type/migraine headache or spinal headache. Patients with headache that is refractory to usual therapy and patients with neurologic deficit require cerebral imaging to detect the presence of life-threatening causes.

Thrombophilia and adverse maternal-perinatal outcome: controversies in screening and management.

A recent review of the literature on thrombophilia and adverse pregnancy outcome reveals contradictory findings. There are retrospective and prospective studies that recommend testing for genetic and acquired markers of thrombophilia for those with the enumerated adverse pregnancy outcome. Based on our review, routine screening for thrombophilias in women with a history of adverse pregnancy outcome (preeclampsia, abruptio placenta, intrauterine growth restriction, and fetal loss) is not justified. Based on data from observational studies and few randomized trials with inadequate number of subjects, there is consensus that women with true antiphospholipid antibody syndrome should receive low-dose aspirin plus adjusted-dose heparin in subsequent pregnancies. Some authors also recommend heparin prophylaxis in subsequent pregnancies in women with genetic thrombophilia with previous adverse pregnancy outcome. However, this recommendation is not based on randomized trials. Hence, a randomized double-blind, controlled trial is urgently needed to evaluate the benefit of heparin during pregnancy in women with a history of adverse pregnancy outcome in association with genetic thrombophilia.

Thrombophilia and adverse maternal-perinatal outcome.

A recent review of the literature on thrombophilia and adverse pregnancy outcome (APO) reveals contradictory findings. We have limited our review of literature mostly to the most recent decade. On the basis of our review, screening for thrombophilias with a history of APO (preeclampsia, abruptio placenta, intrauterine growth restriction, and fetal loss) is not clear. There are retrospective and prospective studies that recommend testing for genetic and acquired markers of thrombophilia for those with the enumerated APO. The rationale for such recommendation is to use heparin prophylaxis in subsequent pregnancies. However, this recommendation is not based on randomized trials. Hence, a randomized double-blinded controlled trial is urgently needed to evaluate the benefit of heparin during pregnancy in women with a history of APO in association with thrombophilia.

Preeclampsia: Diagnosis and management of the atypical presentation.

Preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome remain as major obstetric problems that plague a large percentage of women resulting in an equally large percentage of maternal and perinatal morbidities. It is important that a clinician makes the most accurate diagnosis possible to prevent these adverse maternal and perinatal outcomes. In general, most women will have a classical presentation of preeclampsia (hypertension and proteinuria) at >20 weeks gestation and <48 hours postpartum. However, recent studies have suggested that some women will develop preeclampsia without the classical findings. The purpose of this review is to increase awareness of the non-classical and atypical features of preeclampsia, eclampsia, and HELLP syndrome and their respective management. Atypical cases are those that develop before 20 weeks, beyond 48 hours postpartum and those that present with some of the signs and symptoms of preeclampsia without the usual hypertension or proteinuria. By formulating a rational stepwise approach towards diagnosis, we may prevent the costly consequence of a missed diagnosis and its eventual possible fatalities.

Tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks of gestation: a randomized controlled pilot study.

OBJECTIVE: The purpose of this study was to determine whether intravenous magnesium sulfate (MgSO4) followed by oral nifidepine tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks' gestation reduces neonatal hospital stay. STUDY DESIGN: Fifty-four women between 32 0/7 and 34 6/7 weeks with preterm labor were randomized to receive either MgSO4 and oral nifidepine (n = 24) or no tocolysis (n = 30). All women received betamethasone and prophylactic antibiotics. The primary outcome was total neonatal hospital stay. Data were analyzed using Chi-square and Mann Whitney U test. RESULTS: The 2 groups had similar mean cervical dilation and gestational age at enrollment. There were no statistically significant differences in total neonatal hospital stay (5.8 +/- 7.2 days; median of 3 days in the no tocolysis vs. 7.5 +/- 8.6 days; median of 3 days in the tocolysis group), rate of preterm delivery (57% vs. 75%) or need for oxygen supplementation (7% vs. 21%, p < 0.23). The neonatal complications were similar in each group. CONCLUSION: Tocolysis after 32 weeks gestation does not reduce neonatal hospital stay.