RESUMEN
BACKGROUND: Antenatal corticosteroid administration is a critical fetal intervention, and the use of a rescue protocol is now standard practice. Rescue antenatal corticosteroid may improve overall accuracy of antenatal corticosteroid administration timing, but this observation and its effect on the initial course is unknown. OBJECTIVE: We sought to compare the accuracy of antenatal corticosteroid administration before and after the implementation of a rescue antenatal corticosteroid protocol. STUDY DESIGN: We performed a retrospective cohort study of patients who received a minimum of 1 dose of antenatal corticosteroid from 2006-2012 at the University of Washington Medical Center with the use of the University of Washington Medical Center Pharmacy Database. For inclusion, subjects were required to be admitted, receive the initial antenatal corticosteroid course at 24-34 weeks gestation, and deliver at University of Washington Medical Center. We designated 2 groups that were based on when rescue antenatal corticosteroid became standard practice at University of Washington Medical Center: before rescue antenatal corticosteroid (2006-2008) and after rescue antenatal corticosteroid (2009-2012). Primary outcome was delivery within any optimal antenatal corticosteroid window, which was defined as 48 hours to 7 days after the first dose or third dose. We also compared delivery within the optimal window of the initial and rescue antenatal corticosteroid courses independently and assessed antenatal corticosteroid timing by the indication for delivery. Chi squared and independent sample t-tests were used to compare results. RESULTS: From 2006-2012, 1356 women met inclusion criteria, 601 before and 755 after rescue antenatal corticosteroid. The study groups demonstrated similar demographics, with the exception of more white women in the group after rescue antenatal corticosteroid (47% vs 60%; P < .01) and delivered at comparable gestational ages (32.7 vs 32.6 weeks; P = .59). Availability of a second course did not increase total subjects who delivered within any optimal window (26.5% vs 28.5%; P = .41). Frequency of delivery within the initial course optimal window did not change after the introduction of the rescue course protocol (26.1% vs 26.4%; P = .92). Similarly, of the 73 subjects who received rescue antenatal corticosteroid, 24.7% delivered in the optimal window of the second course. Delivery within the optimal window varied by indication for antenatal corticosteroid, with highest accuracy among maternal indications (41.2% in any optimal window), followed by preterm premature rupture of membranes (32.1%). Lowest administration accuracy was among women with antenatal cervical shortening and advanced cervical dilation; only 2.8% and 6.3% delivered within the optimal window, respectively. Furthermore, for women with antenatal cervical shortening, the mean gestational age of delivery was 35.1 weeks, and the median interval from antenatal corticosteroid administration to delivery was 55 days (interquartile range, 34-72 days). CONCLUSIONS: The opportunity for a second course of antenatal corticosteroid did not improve the number of women who delivered within any optimal antenatal corticosteroid window. Administration timing was similar for the initial course and the rescue course, with approximately one-quarter of women delivering within the optimal antenatal corticosteroid window. These findings likely reflect the few circumstances in which rescue antenatal corticosteroid is useful and the poor predictability of preterm birth. Future focus should be aimed at tools to predict the timing of preterm birth to optimize antenatal corticosteroid administration.
Asunto(s)
Corticoesteroides/administración & dosificación , Parto Obstétrico , Enfermedades del Prematuro/prevención & control , Adulto , Protocolos Clínicos , Esquema de Medicación , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Atención Perinatal , Embarazo , Nacimiento Prematuro , Atención Prenatal , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Our objective was to determine if progesterone pretreatment could ameliorate the detrimental effects of lipopolysaccharide (LPS)-induced inflammation on cortical neurogenesis. Timed pregnant mouse dams (n = 8) were given intraperitoneal injections of progesterone (42 mg/kg) or vehicle on embryonic day 17.5. Two hours later, mice were given intraperitoneal LPS (140 µg/kg) or vehicle. Mice were sacrificed 16 hours later on embryonic day 18. Two-color immunofluorescence was performed with primary antibodies T-box transcription factor 2 (Tbr2), ionized calcium binding adapter molecule 1 (Iba1), cleaved caspase 3 (CC3), and 5-bromo-2'-deoxyuridine (BrdU). Cells were counted, and statistical analysis was determined using analysis of variance and Tukey-Kramer method. The Tbr2 intermediate neural progenitor cell density decreased after LPS exposure (P = .0022). Pre-exposure to progesterone statistically increased Tbr2 intermediate neural progenitors compared to LPS treatment alone and was similar to controls (P = .0022). After LPS exposure, microglia displayed an activated phenotype, and cell density was increased (P < .001). Cell death rates were low among study groups but was increased in LPS exposure groups compared to progesterone alone (P = .0015). Lipopolysaccharide-induced systemic inflammation reduces prenatal neurogenesis in mice. Pre-exposure with progesterone is associated with increased neurogenesis. Progesterone may protect the preterm brain from defects of neurogenesis induced by inflammation.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/embriología , Encefalitis/embriología , Neurogénesis/efectos de los fármacos , Progesterona/administración & dosificación , Animales , Proliferación Celular/efectos de los fármacos , Encefalitis/inducido químicamente , Femenino , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/fisiologíaRESUMEN
Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P < .001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.