- Email: [email protected]
Association of interleukin-1 and interleukin-1 receptor antagonist gene expression and preterm birth
SMFM Abstracts S49 131 THE RELATIONSHIP BETWEEN SELF-REPORTED STRESS AND LOW BIRTH WEIGHT NEONATES IN A LOW-INCOME POPULATION OF WOMEN ANN BRYANT (F)1, WILLIAM GROBMAN1, JANE HOLL3, 1Northwestern LAURA AMSDEN2, University, Obstetrics and Gynecology, Institute for Healthcare Studies, 2 Chicago, Illinois, Northwestern University, Institute for Healthcare Studies, Chicago, Illinois, 3Northwestern University, Pediatrics, Institute for Healthcare Studies, Chicago, Illinois OBJECTIVE: To determine if there is an association between chronic psychosocial stress and low birth weight neonates in low-income women. STUDY DESIGN: Between 1999 and 2004, randomly selected women from the 1998 welfare rolls in 9 Illinois counties were interviewed yearly to evaluate their psychosocial, socioeconomic and health characteristics. Women who gave birth during this period were identified. Using a nested case-control design, responses of those who delivered low birth weight neonates were compared with responses of those who did not. Self-reported stress was assessed as the: (1) external stressors (e.g. life events, economic hardship, food security, hardship obtaining medical care, child with chronic illness, and home crowdedness); (2) enhancers of stress (e.g. depression, mental health, drug or alcohol use); (3) buffers against stress (e.g. social support, community group involvement, church attendance, coping skills); and (4) perceived stress (e.g. perceived economic hardship, self-rated health, perceived neighborhood safety) that occurred in temporal proximity to the delivery. RESULTS: Of the 379 infants born during the study period, 51 (13.5%) were low birth-weight. Bivariate analysis showed that having poor coping skills (p=.001), hardship obtaining appropriate amounts of food (p=.003), a child in the home with a chronic illness (p=.003), and increased crowding in the home (p= .005) were all significantly associated with low birth weight. History of depression in the last year (p=.05) and high levels of perceived economic hardship (p=.05) were reported more often by women with low birth weight infants, however, did not reach statistical significance. CONCLUSION: This study provides evidence that chronic psychosocial stress may be associated with low birth weight neonates in a low-income population of women.
133 ASSOCIATION OF INTERLEUKIN-1 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE EXPRESSION AND PRETERM BIRTH SARAH ELLESTAD (F)1, BRYAN YONISH1, PHILLIP HEINE1, AMY MURTHA1, 1Duke University, Division of Maternal-Fetal Medicine, Durham, North Carolina OBJECTIVE: The inflammatory response plays an important role in the pathophysiology of prematurity. The objective of this investigation was to determine if the expression of interleukin (IL)-1. b and IL-1 receptor antagonist (RA) is different in subjects that deliver preterm compared to subjects that deliver at term. In addition, we sought to determine if the IL-1. b/IL-1 RA ratio was higher in preterm subjects in the presence of chorioamnionitis. STUDY DESIGN: After IRB approval patients admitted to labor and delivery were eligible for enrollment. Cases were defined as women who delivered before 37 weeks gestation after PTL or PPROM. Controls were defined as women who delivered after 37 weeks gestation without PTL or PPROM. Demographic and clinical information were collected prospectively. Placental samples were collected at the time of delivery and stored in RNAlaterÒ (Qiagen Inc., CA) at ÿ80( Celsius. RNA was extracted for quantitative RTPCR using primers specific for IL-1. b and IL-1 RA. Standard curves were generated from known concentrations of each transcript. Placentas were examined for evidence of histologic chorioamnionitis. Data were analyzed using Mann Whitney U and t-test. RESULTS: Thirty-four placental samples were analyzed; 15 preterm cases and 19 term controls. The mean IL-1. b/IL-1 RA ratio was significantly higher for preterm subjects when compared to term subjects (1.380 vs. .709, p!.02). When preterm subjects were analyzed seperately the mean IL-1. b/IL-1 RA ratio for subjects with chorioamnionitis was not different from those without chorioamnionitis (1.546 vs. 1.275, p!.60). Likewise, the mean IL-1. b/IL1 RA ratio for subjects with and without funisitis was not found to be significantly different (1.082 vs. 1.500, respectively, p! .51). CONCLUSION: Preterm labor appears to be associated with a pro-inflammatory state when compared to term labor. These data suggest that even in the absence of infection, inflammation likely plays an important role. Additional investigation is needed to further clarify the relationship between inflammation and preterm labor.
132 PPROM IN SINGLETON VS MULTIPLE GESTATION PREGNANCIES: DURATION OF LATENCY AND PERINATAL OUTCOMES YVONNE CHENG (F)1, NATALI AZIZ1, AARON CAUGHEY1, 1University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California OBJECTIVE: To examine the duration of latency and associated perinatal outcomes in singleton vs multiple gestation pregnancies complicated by preterm premature rupture of the membranes (PPROM). STUDY DESIGN: This is a retrospective cohort study of pregnancies complicated by PPROM between 24 and 34 weeks of gestation. Primary outcome was the duration of latency. Gestational age at time of delivery and perinatal outcomes were examined. Chi-square test was used to evaluate dichomotous outcomes and student t-test for continuous variables. Survival analysis was performed to evaluate latency, with log-rank test for comparison of Kaplan-Meier survival curves. RESULTS: There were 974 singleton and 194 multiple gestation pregnancies (184 twins and 13 triplets) meeting study criteria. Compared to singletons, the odds of having PPROM at an earlier gestational age was higher for multiples (OR=1.68, 95% CI 1.04-2.72). Although the mean duration of latency was longer for singleton compared to multiples (mean latency = 4.34 days for singletons and 2.34 days for multiples, p!0.001), 25% delivered within 2 days and 75% delivered within 4 days of initial PPROM for both groups. There were also no differences in latency duration within 28 days following the initial PPROM by log-rank test (p=0.36, see Figure). There were no differences in perinatal outcomes (chorioamnionitis, 5-minute Apgar score !7, sepsis, respiratory distress syndrome, or admission to the neonatal intensive care unit).
134 PRETERM LABOR AND 17-P: LESSONS FROM A MOUSE MODEL MICHAL ELOVITZ1, MRINALINI CONJEEVARAM2, 1University of Pennsylvania, Philadelphia, Pennsylvania, 2University of Pennsylvania, Department of Obstetrics and Gynecology, Philadelphia, Pennsylvania OBJECTIVE: Based on the recent MFMU clinical trial, ACOG supports the administration of 17-alpha hydroxyprogesterone caproate (17-P) to high risk patients who meet suggested criteria. However, recent surveys indicate that 17P is used beyond these guidelines including its use during acute episodes of preterm labor. Since inflammation/infection is believed to be a contributing factor in many cases of preterm birth (PTB), it is imperative to understand the effect of 17-P in this clinical situation. STUDY DESIGN: Using a mouse model of localized intrauterine inflammation, we investigated the ability of 17-P to prevent inflammation-induced PTB. On day 15 of gestation, dams were randomized to treatment with 17-P or vehicle prior to intrauterine infusion of LPS. All dams were monitored for morbidity and preterm birth. Separate sets of experiments were performed to assess the preterm birth rate at 24 hrs and the number of live pups at term. To determine if prevention of PTB with 17-P resulted in a systemic inflammatory response in the dam, C-reactive protein and cytokine levels were measured in maternal serum by ELISA. RESULTS: 79% (19/24) of dams treated with 17-P prior to intrauterine LPS delivered at least one pup by 24 hrs which was not significantly different from dams treated with LPS alone (n=28, P=0.22). However, treatment with 17-P did result in a significant increased number of dams with pups remaining in the uterine horns at 24 hrs (7/16) than LPS alone (24/28)(P=0.005). Dams treated with 17-P did not deliver any live pups at term. Treatment with 17-P resulted in significant maternal morbidity (46 %, 11/24) including two maternal deaths. CONCLUSION: In the setting of intrauterine inflammation, 17-P decreases the PTB rate but results in significant maternal morbidity. 17-P should not be used in patients suspected of having sub-clinical infection. The mechanisms by which 17-P inhibits preterm birth warrants further investigations so that use of this drug to appropriate populations could be pursued without undue fetal or maternal harm.
PPROM Latnecy Duration: Singleton vs Multiples CONCLUSION: In pregnancies complicated by PPROM, the duration of latency was not different between singleton and multiple gestations. There were no differences in perinatal outcomes.
133 ASSOCIATION OF INTERLEUKIN-1 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE EXPRESSION AND PRETERM BIRTH SARAH ELLESTAD (F)1, BRYAN YONISH1, PHILLIP HEINE1, AMY MURTHA1, 1Duke University, Division of Maternal-Fetal Medicine, Durham, North Carolina OBJECTIVE: The inflammatory response plays an important role in the pathophysiology of prematurity. The objective of this investigation was to determine if the expression of interleukin (IL)-1. b and IL-1 receptor antagonist (RA) is different in subjects that deliver preterm compared to subjects that deliver at term. In addition, we sought to determine if the IL-1. b/IL-1 RA ratio was higher in preterm subjects in the presence of chorioamnionitis. STUDY DESIGN: After IRB approval patients admitted to labor and delivery were eligible for enrollment. Cases were defined as women who delivered before 37 weeks gestation after PTL or PPROM. Controls were defined as women who delivered after 37 weeks gestation without PTL or PPROM. Demographic and clinical information were collected prospectively. Placental samples were collected at the time of delivery and stored in RNAlaterÒ (Qiagen Inc., CA) at ÿ80( Celsius. RNA was extracted for quantitative RTPCR using primers specific for IL-1. b and IL-1 RA. Standard curves were generated from known concentrations of each transcript. Placentas were examined for evidence of histologic chorioamnionitis. Data were analyzed using Mann Whitney U and t-test. RESULTS: Thirty-four placental samples were analyzed; 15 preterm cases and 19 term controls. The mean IL-1. b/IL-1 RA ratio was significantly higher for preterm subjects when compared to term subjects (1.380 vs. .709, p!.02). When preterm subjects were analyzed seperately the mean IL-1. b/IL-1 RA ratio for subjects with chorioamnionitis was not different from those without chorioamnionitis (1.546 vs. 1.275, p!.60). Likewise, the mean IL-1. b/IL1 RA ratio for subjects with and without funisitis was not found to be significantly different (1.082 vs. 1.500, respectively, p! .51). CONCLUSION: Preterm labor appears to be associated with a pro-inflammatory state when compared to term labor. These data suggest that even in the absence of infection, inflammation likely plays an important role. Additional investigation is needed to further clarify the relationship between inflammation and preterm labor.
132 PPROM IN SINGLETON VS MULTIPLE GESTATION PREGNANCIES: DURATION OF LATENCY AND PERINATAL OUTCOMES YVONNE CHENG (F)1, NATALI AZIZ1, AARON CAUGHEY1, 1University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California OBJECTIVE: To examine the duration of latency and associated perinatal outcomes in singleton vs multiple gestation pregnancies complicated by preterm premature rupture of the membranes (PPROM). STUDY DESIGN: This is a retrospective cohort study of pregnancies complicated by PPROM between 24 and 34 weeks of gestation. Primary outcome was the duration of latency. Gestational age at time of delivery and perinatal outcomes were examined. Chi-square test was used to evaluate dichomotous outcomes and student t-test for continuous variables. Survival analysis was performed to evaluate latency, with log-rank test for comparison of Kaplan-Meier survival curves. RESULTS: There were 974 singleton and 194 multiple gestation pregnancies (184 twins and 13 triplets) meeting study criteria. Compared to singletons, the odds of having PPROM at an earlier gestational age was higher for multiples (OR=1.68, 95% CI 1.04-2.72). Although the mean duration of latency was longer for singleton compared to multiples (mean latency = 4.34 days for singletons and 2.34 days for multiples, p!0.001), 25% delivered within 2 days and 75% delivered within 4 days of initial PPROM for both groups. There were also no differences in latency duration within 28 days following the initial PPROM by log-rank test (p=0.36, see Figure). There were no differences in perinatal outcomes (chorioamnionitis, 5-minute Apgar score !7, sepsis, respiratory distress syndrome, or admission to the neonatal intensive care unit).
134 PRETERM LABOR AND 17-P: LESSONS FROM A MOUSE MODEL MICHAL ELOVITZ1, MRINALINI CONJEEVARAM2, 1University of Pennsylvania, Philadelphia, Pennsylvania, 2University of Pennsylvania, Department of Obstetrics and Gynecology, Philadelphia, Pennsylvania OBJECTIVE: Based on the recent MFMU clinical trial, ACOG supports the administration of 17-alpha hydroxyprogesterone caproate (17-P) to high risk patients who meet suggested criteria. However, recent surveys indicate that 17P is used beyond these guidelines including its use during acute episodes of preterm labor. Since inflammation/infection is believed to be a contributing factor in many cases of preterm birth (PTB), it is imperative to understand the effect of 17-P in this clinical situation. STUDY DESIGN: Using a mouse model of localized intrauterine inflammation, we investigated the ability of 17-P to prevent inflammation-induced PTB. On day 15 of gestation, dams were randomized to treatment with 17-P or vehicle prior to intrauterine infusion of LPS. All dams were monitored for morbidity and preterm birth. Separate sets of experiments were performed to assess the preterm birth rate at 24 hrs and the number of live pups at term. To determine if prevention of PTB with 17-P resulted in a systemic inflammatory response in the dam, C-reactive protein and cytokine levels were measured in maternal serum by ELISA. RESULTS: 79% (19/24) of dams treated with 17-P prior to intrauterine LPS delivered at least one pup by 24 hrs which was not significantly different from dams treated with LPS alone (n=28, P=0.22). However, treatment with 17-P did result in a significant increased number of dams with pups remaining in the uterine horns at 24 hrs (7/16) than LPS alone (24/28)(P=0.005). Dams treated with 17-P did not deliver any live pups at term. Treatment with 17-P resulted in significant maternal morbidity (46 %, 11/24) including two maternal deaths. CONCLUSION: In the setting of intrauterine inflammation, 17-P decreases the PTB rate but results in significant maternal morbidity. 17-P should not be used in patients suspected of having sub-clinical infection. The mechanisms by which 17-P inhibits preterm birth warrants further investigations so that use of this drug to appropriate populations could be pursued without undue fetal or maternal harm.
PPROM Latnecy Duration: Singleton vs Multiples CONCLUSION: In pregnancies complicated by PPROM, the duration of latency was not different between singleton and multiple gestations. There were no differences in perinatal outcomes.