Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.

BACKGROUND: There is a robust association between altered angiogenic factor concentrations, which includes placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women with suspected preeclampsia at <35 weeks gestation, however, remains to be clarified. OBJECTIVE: The purposes of this study were to examine the relationship between placental growth factor and time to delivery in women at <35 weeks gestation with signs or symptoms of preeclampsia and to compare the performance of placental growth factor to other clinical markers for prediction of time to delivery in preeclampsia. STUDY DESIGN: Women with signs or symptoms of preeclampsia between 20.0 and 35.0 weeks gestation were enrolled in a prospective, observational study at 24 centers. Blood was collected at presentation for placental growth factor, and subjects were evaluated and treated according to local protocols. Clinical outcomes were obtained, and all final diagnoses were adjudicated by an independent expert panel according to 2013 American College of Obstetricians and Gynecologists' Hypertension in Pregnancy criteria. Placental growth factor was measured retrospectively on the Alere, Inc, triage platform. A normal placental growth factor was defined as >100 pg/mL; the assay's limit of detection is 12 pg/mL. Two-by-2 tables were constructed for comparison of test outcomes that included negative predictive value; time-to-delivery was analyzed by survival curves and Cox regression. RESULTS: Seven hundred fifty-three subjects were enrolled; 538 (71%) had a final diagnosis of preeclampsia; 542 (72%) delivered at <37 weeks gestation, and 358 (47%) delivered at <34 weeks gestation. Among the 279 women (37%) with a normal placental growth factor at presentation, the negative predictive value for preeclampsia delivered within 14 days or within 7 days was 90% and 93%, respectively. Compared with women with normal placental growth factor, women with placental growth factor ≤100 pg/mL have a hazard ratio of 7.17 (confidence interval, 5.08-10.13) in Cox regression for time to delivery after adjustment for both gestational age at enrollment and the final diagnosis of preeclampsia. The placental growth factor levels of normal (>100 pg/mL), low (12-100 pg/mL), and very low (<12 pg/mL) have well-separated distributions of time to delivery, with median values of 45, 10, and 2 days, respectively. Subjects with placental growth factor ≤100 pg/mL have a perinatal death rate of 5.7% and a small-for-gestational-age rate of 51.7%; subjects with placental growth factor >100 pg/mL have a perinatal death rate of 0% (no observations in this cohort) and an a small-for-gestational-age rate of 16.8%. CONCLUSION: In women with suspected preeclampsia at <35.0 weeks gestation, a low placental growth factor was correlated strongly with preterm delivery independent of a diagnosis of preeclampsia or gestational age at presentation, whereas a normal placental growth factor was associated with pregnancy prolongation, even in patients who ultimately had a final diagnosis of preeclampsia. This suggests that placental growth factor levels are superior to clinical markers in the prediction of adverse pregnancy in women with suspected preeclampsia.

Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes. STUDY DESIGN: This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 34(0/7) weeks of gestation or documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women. RESULTS: From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of stay. CONCLUSION: Compared with placebo, weekly 17OHP-C injections did not prolong pregnancy or reduce perinatal morbidity in patients with PROM in this trial.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Removal versus retention of cerclage in preterm premature rupture of membranes: a randomized controlled trial.

OBJECTIVE: The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. STUDY DESIGN: A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. RESULTS: The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). CONCLUSION: Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention.

The rates of abnormal glucose challenge tests and gestational diabetes in women receiving 17α-hydroxyprogesterone caproate.

We compared the rates of abnormal 1-hour glucose challenge tests (GCT) and gestational diabetes (GDM) between women receiving 17α-hydroxyprogesterone caproate (17-P) and women who did not receive 17-P to determine if the effect varies based on the number of doses received or in a group of high-risk obese women. We performed a secondary analysis of a prospective cohort study where women with a history of a previous preterm delivery in the antecedent pregnancy followed at a high-risk clinic were offered 17-P. GCT was performed after the initiation of 17-P, and doses given prior to testing were recorded. Rates of abnormal GCT and GDM were compared between those receiving 17-P ( N = 67) and controls ( N = 140). Mean glucose values (112.4 versus 111.3, P = 0.8), rate of abnormal GCT (23.9% versus 20%, adjusted odds ratio 1.45, 95% confidence interval 0.7 to 3.0), and rate of GDM (6% versus 8.6%, adjusted odds ratio 1.21, 95% confidence interval 0.3 to 4.5) were similar between groups. In this prospective study, 17-P administration to women at risk of recurrent preterm delivery did not significantly affect glucose tolerance.

Indications for delivery and short-term neonatal outcomes in late preterm as compared with term births.

OBJECTIVE: The objective of the study was to evaluate the indications for late preterm birth and compare outcomes by gestational age among late preterm (34-36 weeks) and term (> or = 37 weeks) neonates at our institution. STUDY DESIGN: This was a retrospective analysis of delivery indications and short-term neonatal outcomes in women who delivered at the University Hospital between January 1, 2005 and Dec. 31, 2006. Data were analyzed using chi(2), Student's t-test, analysis of variance, and post hoc Tukey tests. RESULTS: One hundred forty-nine late preterm (n = 49 for 34, n = 50 for 35, n = 50 for 36 weeks) and 150 term infants (n = 50 for 37, n = 50 for 38, n = 50 for 39 weeks or longer) were evaluated. Differences among groups (ie, 34 vs 35 vs 36 vs 37, etc) as well as combinations of differences between 2 groups (ie, 34-36 weeks vs > or = 37 or > or = 38 weeks) were analyzed. Spontaneous labor and/or rupture of membranes were the most common indications for late preterm delivery (92%). Compared with term, late preterm infants had longer hospital stays (5 days vs 2.4 days; P < .001) and higher rates of neonatal intensive care unit (NICU) admissions (56% vs 4%; P < .001), feeding problems (36% vs 5%; P < .001), hyperbilirubinemia (25% vs 3%; P < .001), and respiratory complications (20% vs 5%; P < .001). Neonatal complications were minimal at 38 weeks or longer. CONCLUSION: Rates of neonatal intensive care unit admission, length of stay, and neonatal morbidities are significantly higher in late preterm as compared with term births.

Long-term maternal and subsequent pregnancy outcomes 5 years after hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.

OBJECTIVE: To evaluate subsequent pregnancy outcome and impact of gestational age at onset of HELLP on long-term prognosis after HELLP over an average follow-up of 5 years STUDY DESIGN: One hundred twenty-eight patients with a history of HELLP filled out questionnaires and sent their medical records. Hemolysis, elevated liver enzymes, and low platelets data were stratified according to gestational age at onset of HELLP < or =28 weeks and >28 weeks. RESULTS: Fifty-three patients had subsequent pregnancies with 24% complicated by HELLP and 28% by preeclampsia. During follow-up, 33% of the patients had new onset hypertension develop, 32% had depression develop, 26% had anxiety develop, and 2.4% required dialysis. There was no significant difference in long-term outcome between comparison groups. CONCLUSION: Patients with a history of HELLP are at increased risk for preeclampsia and HELLP as well as long-term morbidities as depression and chronic hypertension. Gestational age at the onset of HELLP could be a predictor for long-term outcome.

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.

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.

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length.

OBJECTIVE: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

Cervical dilatation on presentation for preterm labor and subsequent preterm birth.

We sought to determine the risk of preterm (< 32 weeks) delivery as it relates to cervical dilatation at presentation of an initial preterm labor admission episode. We retrospectively reviewed the records of all patients presenting with preterm contractions at 22 to 32 weeks' gestation. Multiple regression was used to analyze the relationship between the interval from initial preterm labor admission episode to delivery and cervical dilatation at presentation. Logistic regression analysis was used to identify variables associated with preterm birth. Mean gestational age on admission for preterm labor episode was 28.1 +/- 2.9 weeks. With a cervical dilatation of 0 to 1 cm, 6% of the women delivered within 48 hours, 20% delivered at < 32 weeks, and 38% delivered at < 35 weeks. With cervical dilatation of 6 to 10 cm, 89% delivered in < 24 hours, 11% between 24 and 48 hours, 94% delivered at < 32 weeks, and 100% delivered at < 35 weeks. Time from admission for initial preterm labor episode to delivery was inversely associated with cervical dilatation. Variables associated with preterm birth at < 32 weeks' gestation were cervical dilatation ( P < 0.0001), gestational age ( P < 0.0001), and effacement ( P < 0.0001) at presentation. In women who experience preterm contractions, cervical dilatation on admission is inversely related to interval to delivery. However, women with cervical dilatation of 0 to 1 cm are still at significant risk for preterm delivery: 19/94 (20%) at < 32 weeks' gestation and 40/104 (38%) at < 35 weeks' gestation.

Cervical Pessary versus Expectant Management for the Prevention of Delivery Prior to 36 Weeks in Women with Placenta Previa: A Randomized Controlled Trial.

Objective This multicenter randomized controlled trial compared cervical pessary (CP) versus expectant management (EM) in women with placenta previa between 22.0 and 32.0 in prolonging gestation until ≥ 36.0 weeks' gestation. Study Design This study took place from November 2016 to June 2018. Women were randomized to receive either the Bioteque CP or EM. The pessary was removed at ≥ 36.0 weeks unless indicated. The primary outcome was gestational age (GA) at delivery, with secondary outcomes including need for transfusion, number and duration of antepartum admissions, type of delivery, and neonatal outcomes. A total of 140 patients were needed to show a 3-week prolongation of pregnancy in the pessary group; however, the trial was stopped early due to budgetary issues. Results Of the 33 eligible women, 17 were enrolled. Although not statistically significant, the mean GA at delivery in the CP group was greater than women in the EM group (36.5 ± 1.23 vs. 36.0 ± 2.0; p = 0.1673). The number and duration of antepartum admissions was greater in the EM group (2.7 ± 0.58 vs. 16.0 ± 22.76 days; p = 0.1264) as well. Conclusion Although the study was underpowered to determine the primary outcome, safety and feasibility of CP in pregnancies complicated with previa were demonstrated.

Expectant management of severe preeclampsia at less than 27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.

OBJECTIVE: The objective of the study was to determine perinatal outcome and maternal morbidities based on gestational age (GA) at the onset of expectant management in severe preeclampsia at less than 27 weeks. STUDY DESIGN: This was a retrospective analysis of outcome in patients with severe preeclampsia. Forty-six patients (51 fetuses) with severe preeclampsia at less than 27 weeks were studied. Corticosteroids were administered beyond 23 weeks. Perinatal and maternal complications (a composite maternal morbidities including HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, pulmonary edema, eclampsia, and renal insufficiency were analyzed. RESULTS: Four patients had multifetal gestations (1 triplet, 3 twins). Median days of prolongation was 6 (range 2-46). Overall perinatal survival was 29 of 51 (57%). Birthweights of 27 (53%) were less than 10%, and 18 (35%) were less than 5%. There were no perinatal survivors in those with a GA less than 23 weeks, at 23 to 23 6/7 weeks, 2 of 10 (20%) survived, and both reached 26 weeks at delivery. For those at 24 to 24 6/7, 25 to 25 6/7, and 26 to 26 6/7 weeks, the perinatal survival rates were 5 of 7 (71%), 13 of 17 (76%), and 9 of 10 (90%), respectively; but rates of respiratory complications were high. There were no maternal deaths, but overall maternal morbidity was 21 of 46 (46%), but was 9 of 14 (64%) in those at less than 24 weeks. CONCLUSION: Perinatal outcome in severe preeclampsia in the midtrimester is dependent on GA at onset of expectant management and GA at delivery. Given the high maternal morbidity and extremely low perinatal survival in expectant management at less than 24 weeks, termination of pregnancies should be offered after extensive counseling.

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.

Does peripartum infection increase the incidence of cerebral palsy in extremely low birthweight infants?

OBJECTIVES: This study was undertaken to determine the perinatal predictors of cerebral palsy in extremely low birthweight infants (<1000 g). STUDY DESIGN: A case control study of infants with birthweight of less than 1000 g (19 with cerebral palsy and 38 controls) who survived beyond 18-22 months of corrected age was performed. Outcome variables included maternal demographics, obstetric complications, and neonatal outcome (gestational age at delivery, birthweight, Apgar scores, intrauterine growth restriction, respiratory distress syndrome, intraventricular hemorrhage, and neonatal sepsis). Data analysis consisted of t tests, chi2, and analysis of variance when appropriate. RESULTS: There were no significant differences between cerebral palsy and control groups with regard to mode of delivery, Apgar scores, preeclampsia, antenatal vaginal bleeding, or the use of magnesium sulfate. However, male gender (odds ratio 3.70; 95% CI 1.05-12.5), primigravid status (odds ratio 5.52; 95% CI 1.67-18.3), early neonatal sepsis (odds ratio 12.9; 95% CI 2.94-57.2) and chorioamnionitis, both clinical and histologic (odds ratio 3.71; 95% CI 1.16-11.9) were significantly associated with the development of cerebral palsy. The strong association between cerebral palsy and chorioamnionitis, as well as early neonatal sepsis, remain significant after adjustment for primigravid status and male gender. CONCLUSION: In extremely low birthweight infants, cerebral palsy was strongly associated with chorioamnionitis, early neonatal sepsis, male gender, and primigravid status.

Prophylaxis with 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery: does gestational age at initiation of treatment matter?

OBJECTIVE: The purpose of this study was to determine effectiveness of 17 alpha-hydroxyprogesterone caproate (17 P) prophylaxis by gestational age (GA) at 17 P initiation. STUDY DESIGN: Singleton gestations with > or = 1 preterm birth (PTB) treated with 17 P prophylaxis for recurrent preterm birth before 27 weeks were identified from a data base. Data were stratified by GA at 17 P initiation (16-20.9 [n = 599] weeks and 21-26.9 [n = 307] weeks) and number of PTB (1, 2, > 2). Outcome variables were PTB at < 37, < 35, and < 32 weeks. RESULTS: No significant differences were found in gestational age at delivery or rates of recurrent PTB < 37, < 35, and < 32 weeks between those women initiating 17 P at 16-20.9 weeks or 21-26.9 weeks, or when stratified by number of prior preterm deliveries. CONCLUSION: Initiation of 17 P prophylaxis at 21-26.9 weeks is as effective as initiation at 16-20.9 weeks of gestation.

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.

The pattern of change in the lecithin/sphingomyelin ratio in patients with preterm premature rupture of membranes between 24 and 34 weeks' gestation.

OBJECTIVE: To report the pattern of change in the lecithin/sphingomyelin (L/S) ratio in patients with preterm premature rupture of membranes (PPROM) between 24 and 34 weeks' gestation. STUDY DESIGN: L/S was determined prospectively using transvaginally and transabdominally collected amniotic fluid from patients with PPROM between 24 and 34 weeks' gestation. Samples were collected prospectively on admission and every 48 to 96 hours until L/S was > or =2.0. All patients received intramuscular betamethasone weekly. RESULTS: Fifty-five patients were included in the study. One hundred twenty-seven samples were collected transvaginally and nine were collected transabdominally. Cox regression analysis showed that a higher initial L/S value and more advanced gestational age were associated with accelerated lung maturation. Among patients at > or =29 weeks' gestation with an initial L/S of > or =1.5 and <2.0 (n=17), 15 of 17 (88%) reached L/S > or = 2 at a mean of 3.1 +/- 1.7 days (range 1.0 to 7.0 days). With an initial L/S of > or =1.0 and <1.5 (n=16), 14 of 16 (88%) patients reached L/S > or =2 at a mean of 4.1 +/- 1.9 days (range 1.7 to 7.0 days). With an initial L/S of <1.0 (n=11), 6 of 11 (54%) patients reached L/S > or =2 at a mean of 5.0 +/- 1.6 days (range 4.7 to 6.8 days). CONCLUSION: Our data document a dramatic acceleration of fetal lung maturation among patients with PPROM at > or = 29 weeks.

Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety.

Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants. Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence. Two recent double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (IM 17OHP-C) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery. However, it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural, racial and genetic differences play a role in patient's response to supplemental progesterone. In addition the patient's acceptance of such recommendation is also in question. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety.