Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review.

Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABAA receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABAA and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression.

Amniotic fluid index as a predictor of adverse perinatal outcome in the HELLP syndrome.

OBJECTIVE: To evaluate the prognostic value of an amniotic fluid index (AFI) < or = 5 cm for an adverse perinatal outcome in pregnancies with the syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP syndrome). STUDY DESIGN: A prospective, observational study of patients with the HELLP syndrome. An ultrasound estimate of amniotic fluid volume was obtained on admission. Adverse intrapartum outcomes included amnioinfusion for variable decelerations and/or indicated abdominal/vaginal operative delivery for nonreassuring fetal heart rate changes. Maternal characteristics and perinatal outcome parameters were compared AFI < or = vs. > 5 cm. Statistical analysis was performed using chi2 analysis, Student's t test and receiver-operator characteristic curve (ROC) analysis. RESULTS: Between January 1996 and February 1999, 120 patients were enrolled. Twenty-six (22%) had an AFI < or = 5 cm. This group did not differ from that with AFI > 5 cm regarding the severity of the HELLP syndrome, admission-to-delivery interval (p = 0.354), variable decelerations in labor (p = 0.06), Apgar score of < 7 at 5 minutes (p = 0.361), cesarean delivery for nonreassuring fetal status (p = 1.0) or significant fetal acidosis (pH < 7.0 [p = 0.2101). ROC analysis revealed no AFI measurement between 0 and 16 cm that was useful for identifying the compromised fetus. CONCLUSION: Antepartum/intrapartum performance of AFI in patients with the HELLP syndrome is a poor prognostic test for subsequent fetal compromise.

Postpartum intravenous dexamethasone for severely preeclamptic patients without hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome: a randomized trial.

OBJECTIVE: We compared maternal outcomes for patients with severe preeclampsia who were managed postpartum with or without adjunctive intravenous dexamethasone. METHODS: This study was a randomized, blinded placebo-controlled clinical trial comparing the use of dexamethasone postpartum (10 mg-10 mg-5 mg-5 mg intravenously every 12 hours) with a saline control in patients with severe preeclampsia. The Student t and chi(2) tests were used for data analysis, with P < .05 considered significant. RESULTS: Data from 157 patients (77 patients receiving dexamethasone, 80 patients receiving placebo) who were treated during 2000-2003 were analyzed. Demographics, diagnostic criteria, baseline laboratory values, and postpartum outcomes were similar between groups. Although dexamethasone-treated patients had fewer returns (6.5% compared with 11.3%) to the labor/delivery/recovery unit for uncontrolled hypertension than control patients, no significant differences were found in blood pressure, antihypertensive requirements, laboratory values, length of hospitalization, interval urine output at 48 hours postpartum, or major maternal morbidity. Two control patients developed hemolysis, elevated liver enzymes, low platelets syndrome. CONCLUSION: Adjunctive use of intravenous dexamethasone for postpartum patients with severe preeclampsia does not reduce disease severity or duration. LEVEL OF EVIDENCE: I.

Predictability of intrapartum and neonatal outcomes with the amniotic fluid volume distribution: a reassessment using the amniotic fluid index, single deepest pocket, and a dye-determined amniotic fluid volume.

OBJECTIVE: The purpose of this study was to establish whether ultrasound-estimated or dye-determined amniotic fluid distribution (upper compared with lower quadrant) is predictive of perinatal outcome. STUDY DESIGN: Amniotic fluid distribution as measured by the amniotic fluid index, single deepest pocket, and dye-determined volumes was ascertained and correlated with intrapartum and neonatal outcomes. RESULTS: Between January 1997 and January 2001, 135 women (70 upper-greater and 65 lower-greater) participated in this prospective observational study. The sum of the amniotic fluid index (P =.309), single deepest pocket (P =.168), and dye-determined amniotic fluid volume (P =.368) for the upper-greater compared with the lower-greater groups were similar. Decelerations in labor (P =.597), late decelerations (P =.999), cesarean deliveries for fetal distress (P =.413), and umbilical cord pH < 7.2 were similar (P =.647) CONCLUSION: Ultrasound-estimated and dye-determined amniotic fluid volumes are similar between upper-greater and lower-greater groups, and intrapartum/neonatal outcomes are not affected by the amniotic fluid distribution.

Postpartum seizure prophylaxis: using maternal clinical parameters to guide therapy.

OBJECTIVE: To use individual patient clinical parameters to signal cessation of postpartum magnesium sulfate seizure prophylaxis for the spectrum of pregnancy-related hypertensive disorders. METHODS: This was a prospective study using clinical symptoms (absence of headache, visual changes, epigastric pain) and signs (sustained blood pressure less than 150/100 without need for acute antihypertensive therapy, spontaneous diuresis more than 100 mL per hour for no less than 2 hours) to signal cessation of intravenous magnesium sulfate postpartum in gravidas diagnosed with preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome. Laboratory assessments (including proteinuria) were not used as criteria for drug discontinuation. RESULTS: Five hundred three patients were enrolled and classified according to American College of Obstetricians and Gynecologists criteria (mild preeclampsia, severe preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome). Maternal age, gestational age, and hours of magnesium therapy before delivery were not statistically different among groups. There was no significant difference in the duration of postpartum magnesium sulfate therapy among groups with the median duration of therapy 4 hours (range 2-77 hours). No eclamptic seizures occurred after magnesium discontinuation. Thirty-eight patients (7.6%) required reinstitution of magnesium therapy for 24 hours because of exacerbation of blood pressure (sustained blood pressure more than 160/110) associated with headache or visual changes. CONCLUSION: Clinical criteria, when compared with arbitrary protocols, can be used successfully to shorten the duration of postpartum magnesium sulfate administration for seizure prophylaxis in patients with pregnancy-related hypertensive disorders.

Pregnancy after classic cesarean delivery.

OBJECTIVE: To describe maternal and perinatal outcomes after a prior classic cesarean delivery. METHODS: A retrospective review was performed including all patients from 1990-2000 whose most recent pregnancy was preceded by classic cesarean delivery. RESULTS: During the 11-year period, there were 37,863 deliveries and 157 patients (0.4%) underwent classic cesarean operations. In the next pregnancy, one case of uterine rupture (0.6%, 95% confidence interval 0.1, 3.5) occurred at 29 weeks without preterm labor and resulted in fetal death. The prevalence of asymptomatic dehiscence was 9% (95% confidence interval 5, 15). There was no significant difference between patients with uterine dehiscence (n = 15) and patients with intact uteri (n = 141) with regard to maternal demographics, duration of labor, cervical dilatation at time of surgery, transfusion of packed red cells, bowel injury, postpartum endometritis, wound breakdown, thrombophlebitis, or umbilical arterial pH less than 7.00 (P >.05). Duration of labor, cervical dilatation, and gestational age at repeat cesarean delivery were poor predictors for uterine rupture or dehiscence. CONCLUSION: Among patients with prior classic cesarean delivery, uterine rupture and dehiscence are neither predictable nor preventable. One in four patients will experience some form of maternal morbidity. Uterine rupture, although infrequent, can be fatal to the fetus. Uterine dehiscence, however, does not increase neonatal or peripartum maternal morbidity.

Cervical ripening and induction of labor with misoprostol, dinoprostone gel, and a Foley catheter: a randomized trial of 3 techniques.

OBJECTIVE: The purpose of this study was to compare the efficacy of 3 different techniques of cervical ripening and induction. STUDY DESIGN: Patients who required cervical ripening and induction were randomized to one of 3 groups: (1) supracervical Foley catheter and intravaginal dinoprostone gel, (2) supracervical Foley catheter and 100 microg oral doses of misoprostol, or (3) serial 100-microg oral doses of misoprostol. Intravenous oxytocin was administered when a protraction disorder of labor was identified. RESULTS: There were 339 women randomized. There was no significant difference in the time from first intervention to delivery in the 3 groups (P =.546). In each group, a similar percentage of women required oxytocin (P =.103). The rates of cesarean delivery were equivalent among the groups (P =.722). Rates of tachysystole were high but statistically equivalent among the 3 groups. There were no significant differences in Apgar scores or umbilical artery pH. CONCLUSION: Oral 100 microg serial doses of misoprostol, with or without the use of a supracervical Foley catheter, were equivalent to the use of a supracervical Foley catheter and serial 4-mg doses of dinoprostone gel for cervical ripening and the induction of labor.