- Email: [email protected]
106: Women receiving 17P hospitalized for preterm labor at <34 weeks benefit from daily perinatal nursing surveillance
SMFM Abstracts
www.AJOG.org 104
HEME OXYGENASE IN HUMAN MYOMETRIAL CELLS AND TISSUE JAMIE MURPHY, MARTIN SLODZINSKI, Johns Hopkins University, Anesthesiology and Critical Care Medicine, Baltimore, Maryland OBJECTIVE: Heme oxygenase 1 (HO-1) has been extensively studied as an inducible stress response protein essential to heme metabolism. HO-1 may also be present in other systemic tissues and may in fact be inducible by non-heme substrates such as heavy metals, endotoxin, heat shock, inflammatory cytokines, and prostaglandins. Little is known regarding HO-1 and human myometrium. We postulate that HO-1 is critical for myometrial homeostasis and is instrumental in maintaining gravid uterine quiescence. STUDY DESIGN: With IRB approval, human myometrial tissue was obtained from the lower uterine segment of pregnant women undergoing cesarean delivery for pre-term and term labor. A western blot analysis was performed using polyclonal rabbit antibody (1:2000) to identify the presence of HO-1. Ratiometric imaging of intracellular calcium and isometric myometrial tissue force were measured in response to oxytocin and the competitive HO-1 inhibitor zinc protoporphyrin IX (PPN-9) and bilirubin. RESULTS: HO-1 is expressed in term and preterm human myometrial tissue. In primary cultured human myocytes, PPN-9 (10uM, 5minutes) inhibition of HO-1 irreversibly increased intracellular calcium. This increase was prevented if bilirubin (100uM) was applied with the PPN-9. In isometric myometrial contractions, PPN-9 (1nM)increased the amplitude and rate of contraction compared with controls. H202 (10uM-1mM) increased the amplitude of contraction in the PPN-9 more than the control tissue. Bilirubin partially abolished the H202 increase in amplitude. CONCLUSION: While extensive research has been performed regarding the function of HO-1 in heme degradation, HO-1 physiology is unexplored in human myometrium. Our investigation demonstrates that HO-1 is present within gravid myometrium and influences myometrial intracellular calcium homeostasis and myometrial tissue contractibility.
106
GA at PTL GA at delivery SPTD ⬍37 SPTD ⬍35 SPTD ⬍32
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.115
105
17 ALPHA-HYDROXYPROGESTERONE CAPROATE PROLONGS GESTATION AMONG PATIENTS WHOSE PREVIOUS DELIVERY WAS VERY PRETERM CHARLES RITTENBERG1, SCOTT SULLIVAN1, AMELIA ROWLAND1, THOMAS HULSEY1, MYLA EBELING1, MONIKA BATREJA1, ROGER NEWMAN1, 1Medical University of South Carolina, Charleston, South Carolina OBJECTIVE: To determine the efficacy of 17 alpha-hydroxyprogesterone caproate (17P) in reducing preterm birth (PTB) based on the gestational age (GA) of the patient’s immediately preceeding delivery. STUDY DESIGN: Using our institutional perinatal database, we identified all women with a PTB since 2000 with a subsequent index pregnancy in which they either received 17P (n⫽66) or did not (n⫽269). We performed a multi-variable logistic regression analysis to compare index pregnancy outcomes based on GA of the preceeding viable delivery. For both deliveries, GA was categorized as ⬍33, 33⫹0 to 35⫹6, and ⬎⫽36⫹0 wks. Mean GA, birth weight, and rate of NICU admissions were also analyzed. Chi-square analysis was used with significance at the p⬍0.05 level. RESULTS: Maternal demographic characteristics were similar between the groups. The majority of the 17P group had failed to reach 33 wks in the preceeding pregnancy (46/66, 70%). Among these, 74% (34/46) reached 36 wks in the index pregnancy compared to only 53% (68/129) of the untreated patients whose prior delivery was ⬍33 wks. [RR 1.4 (95% CI 1.1&endash;1.7), p⫽0.01] When adjusted for maternal age and race, the 17P group was still significantly more likely to achieve 36 wks gestation. In spite of a similar mean GA (36.2 v. 35.6 wks, p⫽.23), infants born to the 17P group were heavier (2713 v. 1843 g, p⬍.0001) and had fewer NICU admissions (10.9 v. 43.7%, p⬍.0001). CONCLUSION: 17P appears to be effective for prolonging gestation among women whose immediately preceeding delivery was less than 33 weeks gestational age. Among all women with a history of PTB, 17P is associated with increased birth weight and fewer NICU admissions. Results of multi-variable logistic regression analysis GA of previous viable birth
AOR for delivery ⬎⫽36⫹0 in 17P group
95% CI
p-value
⬍33 wks 33⫹0–35⫹6 ⬎⫽36 wks
2.25 2.51 0.76
1.05–4.83 0.57–11.01 0.39–1.48
0.04 0.22 0.42
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.116
WOMEN RECEIVING 17P HOSPITALIZED FOR PRETERM LABOR AT <34 WEEKS BENEFIT FROM DAILY PERINATAL NURSING SURVEILLANCE CHARLES RITTENBERG1, SCOTT SULLIVAN1, NIKI ISTWAN2, DEBBIE RHEA2, GARY STANZIANO2, ROGER NEWMAN1, 1 Medical University of South Carolina, Charleston, South Carolina, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To compare pregnancy outcomes of women hospitalized for preterm labor (PTL) while receiving 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent spontaneous preterm delivery (SPTD) prescribed daily versus weekly perinatal nursing surveillance. STUDY DESIGN: Singleton gestations with a history of SPTD enrolled into an outpatient 17P administration program at ⬍27 weeks= gestation were identified from a database (n⫽1177). Women hospitalized for PTL at ⬍34 weeks (n⫽379) were selected for analysis. All patients received weekly home nursing visits for 17P administration. Among these patients, 99 were also prescribed daily perinatal nursing surveillance (dPNS) including home uterine activity monitoring. Patients receiving daily surveillance (n⫽99) were matched by Medicaid status and gestational age at onset of PTL to women receiving weekly surveillance (n⫽280) yielding 83 matched pairs. Primary outcome was SPTD ⬍35 weeks. McNemar=s chi-square, Wilcoxon Rank Sum and paired t test statistics were used to assess 2-sided significance at the p⬍0.05 level. RESULTS: Among patients receiving 17P who were hospitalized for PTL, those also prescribed dPNS following hospitalization had significantly lower rates of SPTD ⬍32 and ⬍35 weeks while rates of SPTD ⬍37 weeks were similar. Maternal characteristics were similar between the groups including age, race, number of prior SPTD, smoking, cerclage, and GA at 17P initiation. Daily assessment (n ⫽ 83)
Weekly assessment (n ⫽ 83)
p-value
95% CI
28.2 ⫾ 3.9 35.2 ⫾ 3.3 59.0% 24.1% 9.6%
28.2 ⫾ 4.0 33.9 ⫾ 4.5 61.4% 49.4% 24.1%
0.027 0.855 0.001 0.017
⌬ ⫽ ⫹1.3 (0.16, 2.5) OR ⫽ 0.250 (0.17, 0.33) OR ⫽ 0.294 (0.207, 0.381)
CONCLUSION: Women receiving prophylactic 17P hospitalized for PTL before 34 weeks appear to benefit from the addition of daily perinatal nursing surveillance. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.117
107
LATE PRETERM ELECTIVE CESSATION OF TOCOLYSIS RESULTS IN AN INCREASED INCIDENCE OF ADVERSE NEONATAL OUTCOMES IN SINGLETON PREGNANCIES ANDREI REBARBER1, JANE CLEARY-GOLDMAN1, NIKI ISTWAN2, DEBBIE RHEA2, GARY STANZIANO2, DANIEL SALTZMAN1, 1Maternal Fetal Medicine Associates, New York, New York, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To compare neonatal outcomes, rates of preterm delivery (PTD) and nursery charges in singleton pregnancies where elective discontinuation (DC) of tocolytic treatment (TX) occurred at 33-36 weeks= gestation. STUDY DESIGN: Singleton pregnancies prescribed an outpatient preterm labor surveillance program and continuous subcutaneous terbutaline tocolytic TX were identified from a database. Non-hospitalized patients discontinuing TX at 33-36 weeks= gestation without subsequent indicated delivery or stillbirth were included for analysis. Nursery charges were modeled at $500/per day for Regular nursery, $1500/per day for Intermediate care nursery, and $2500/per day for NICU. Pregnancy outcomes and charges were compared for each gestational week at stop of TX group compared to the successive week. RESULTS: Pregnancy outcomes and estimated charges for 4,253 singleton pregnancies receiving tocolytic TX stratified by gestational week at TX DC are presented below. 1 ⫽ p⬍0.05 vs previous week, adjusted for multiple comparisons. Week of TX DC PTD ⬍37 (%) Delivered within 7 days of TX DC (%) NICU admission (%) Low birth weight (%) Nursery days Total nursery charges ($)
33 weeks (n ⫽ 207)
34 weeks (n ⫽ 528)
35 weeks (n ⫽ 1371)
36 weeks (n ⫽ 2147)
75.4 53.6
71.6 47.5
62.41 55.11
43.21 63.11
44.0
26.31
15.01
9.21
53.6
32.2
1
15.41
8.01
7.4 ⫾ 7.1 4 (1–38) 14,884 ⫾ 19.250
4.2 ⫾ 4.4 2 (1–30)1 6,850 ⫾ 11,500
3.3 ⫾ 5.0 2 (1.98)1 4,408 ⫾ 12,807
2.7 ⫾ 2.9 2 (1–56)1 2,579 ⫾ 7,166
4000 (500–95,000)
1000 (500, 75,000)1
(500, 245,000)1
(500, 140,000)1
CONCLUSION: Early tocolytic DC leads to a high incidence of late preterm birth, with significantly greater rates of NICU admission and low birth weight, and significantly higher nursery charges. As late preterm birth is known to be associated with both short- and long-term neonatal morbidities, tocolytic TX should be continued through 36 weeks. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.118
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S43
www.AJOG.org 104
HEME OXYGENASE IN HUMAN MYOMETRIAL CELLS AND TISSUE JAMIE MURPHY, MARTIN SLODZINSKI, Johns Hopkins University, Anesthesiology and Critical Care Medicine, Baltimore, Maryland OBJECTIVE: Heme oxygenase 1 (HO-1) has been extensively studied as an inducible stress response protein essential to heme metabolism. HO-1 may also be present in other systemic tissues and may in fact be inducible by non-heme substrates such as heavy metals, endotoxin, heat shock, inflammatory cytokines, and prostaglandins. Little is known regarding HO-1 and human myometrium. We postulate that HO-1 is critical for myometrial homeostasis and is instrumental in maintaining gravid uterine quiescence. STUDY DESIGN: With IRB approval, human myometrial tissue was obtained from the lower uterine segment of pregnant women undergoing cesarean delivery for pre-term and term labor. A western blot analysis was performed using polyclonal rabbit antibody (1:2000) to identify the presence of HO-1. Ratiometric imaging of intracellular calcium and isometric myometrial tissue force were measured in response to oxytocin and the competitive HO-1 inhibitor zinc protoporphyrin IX (PPN-9) and bilirubin. RESULTS: HO-1 is expressed in term and preterm human myometrial tissue. In primary cultured human myocytes, PPN-9 (10uM, 5minutes) inhibition of HO-1 irreversibly increased intracellular calcium. This increase was prevented if bilirubin (100uM) was applied with the PPN-9. In isometric myometrial contractions, PPN-9 (1nM)increased the amplitude and rate of contraction compared with controls. H202 (10uM-1mM) increased the amplitude of contraction in the PPN-9 more than the control tissue. Bilirubin partially abolished the H202 increase in amplitude. CONCLUSION: While extensive research has been performed regarding the function of HO-1 in heme degradation, HO-1 physiology is unexplored in human myometrium. Our investigation demonstrates that HO-1 is present within gravid myometrium and influences myometrial intracellular calcium homeostasis and myometrial tissue contractibility.
106
GA at PTL GA at delivery SPTD ⬍37 SPTD ⬍35 SPTD ⬍32
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.115
105
17 ALPHA-HYDROXYPROGESTERONE CAPROATE PROLONGS GESTATION AMONG PATIENTS WHOSE PREVIOUS DELIVERY WAS VERY PRETERM CHARLES RITTENBERG1, SCOTT SULLIVAN1, AMELIA ROWLAND1, THOMAS HULSEY1, MYLA EBELING1, MONIKA BATREJA1, ROGER NEWMAN1, 1Medical University of South Carolina, Charleston, South Carolina OBJECTIVE: To determine the efficacy of 17 alpha-hydroxyprogesterone caproate (17P) in reducing preterm birth (PTB) based on the gestational age (GA) of the patient’s immediately preceeding delivery. STUDY DESIGN: Using our institutional perinatal database, we identified all women with a PTB since 2000 with a subsequent index pregnancy in which they either received 17P (n⫽66) or did not (n⫽269). We performed a multi-variable logistic regression analysis to compare index pregnancy outcomes based on GA of the preceeding viable delivery. For both deliveries, GA was categorized as ⬍33, 33⫹0 to 35⫹6, and ⬎⫽36⫹0 wks. Mean GA, birth weight, and rate of NICU admissions were also analyzed. Chi-square analysis was used with significance at the p⬍0.05 level. RESULTS: Maternal demographic characteristics were similar between the groups. The majority of the 17P group had failed to reach 33 wks in the preceeding pregnancy (46/66, 70%). Among these, 74% (34/46) reached 36 wks in the index pregnancy compared to only 53% (68/129) of the untreated patients whose prior delivery was ⬍33 wks. [RR 1.4 (95% CI 1.1&endash;1.7), p⫽0.01] When adjusted for maternal age and race, the 17P group was still significantly more likely to achieve 36 wks gestation. In spite of a similar mean GA (36.2 v. 35.6 wks, p⫽.23), infants born to the 17P group were heavier (2713 v. 1843 g, p⬍.0001) and had fewer NICU admissions (10.9 v. 43.7%, p⬍.0001). CONCLUSION: 17P appears to be effective for prolonging gestation among women whose immediately preceeding delivery was less than 33 weeks gestational age. Among all women with a history of PTB, 17P is associated with increased birth weight and fewer NICU admissions. Results of multi-variable logistic regression analysis GA of previous viable birth
AOR for delivery ⬎⫽36⫹0 in 17P group
95% CI
p-value
⬍33 wks 33⫹0–35⫹6 ⬎⫽36 wks
2.25 2.51 0.76
1.05–4.83 0.57–11.01 0.39–1.48
0.04 0.22 0.42
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.116
WOMEN RECEIVING 17P HOSPITALIZED FOR PRETERM LABOR AT <34 WEEKS BENEFIT FROM DAILY PERINATAL NURSING SURVEILLANCE CHARLES RITTENBERG1, SCOTT SULLIVAN1, NIKI ISTWAN2, DEBBIE RHEA2, GARY STANZIANO2, ROGER NEWMAN1, 1 Medical University of South Carolina, Charleston, South Carolina, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To compare pregnancy outcomes of women hospitalized for preterm labor (PTL) while receiving 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent spontaneous preterm delivery (SPTD) prescribed daily versus weekly perinatal nursing surveillance. STUDY DESIGN: Singleton gestations with a history of SPTD enrolled into an outpatient 17P administration program at ⬍27 weeks= gestation were identified from a database (n⫽1177). Women hospitalized for PTL at ⬍34 weeks (n⫽379) were selected for analysis. All patients received weekly home nursing visits for 17P administration. Among these patients, 99 were also prescribed daily perinatal nursing surveillance (dPNS) including home uterine activity monitoring. Patients receiving daily surveillance (n⫽99) were matched by Medicaid status and gestational age at onset of PTL to women receiving weekly surveillance (n⫽280) yielding 83 matched pairs. Primary outcome was SPTD ⬍35 weeks. McNemar=s chi-square, Wilcoxon Rank Sum and paired t test statistics were used to assess 2-sided significance at the p⬍0.05 level. RESULTS: Among patients receiving 17P who were hospitalized for PTL, those also prescribed dPNS following hospitalization had significantly lower rates of SPTD ⬍32 and ⬍35 weeks while rates of SPTD ⬍37 weeks were similar. Maternal characteristics were similar between the groups including age, race, number of prior SPTD, smoking, cerclage, and GA at 17P initiation. Daily assessment (n ⫽ 83)
Weekly assessment (n ⫽ 83)
p-value
95% CI
28.2 ⫾ 3.9 35.2 ⫾ 3.3 59.0% 24.1% 9.6%
28.2 ⫾ 4.0 33.9 ⫾ 4.5 61.4% 49.4% 24.1%
0.027 0.855 0.001 0.017
⌬ ⫽ ⫹1.3 (0.16, 2.5) OR ⫽ 0.250 (0.17, 0.33) OR ⫽ 0.294 (0.207, 0.381)
CONCLUSION: Women receiving prophylactic 17P hospitalized for PTL before 34 weeks appear to benefit from the addition of daily perinatal nursing surveillance. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.117
107
LATE PRETERM ELECTIVE CESSATION OF TOCOLYSIS RESULTS IN AN INCREASED INCIDENCE OF ADVERSE NEONATAL OUTCOMES IN SINGLETON PREGNANCIES ANDREI REBARBER1, JANE CLEARY-GOLDMAN1, NIKI ISTWAN2, DEBBIE RHEA2, GARY STANZIANO2, DANIEL SALTZMAN1, 1Maternal Fetal Medicine Associates, New York, New York, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To compare neonatal outcomes, rates of preterm delivery (PTD) and nursery charges in singleton pregnancies where elective discontinuation (DC) of tocolytic treatment (TX) occurred at 33-36 weeks= gestation. STUDY DESIGN: Singleton pregnancies prescribed an outpatient preterm labor surveillance program and continuous subcutaneous terbutaline tocolytic TX were identified from a database. Non-hospitalized patients discontinuing TX at 33-36 weeks= gestation without subsequent indicated delivery or stillbirth were included for analysis. Nursery charges were modeled at $500/per day for Regular nursery, $1500/per day for Intermediate care nursery, and $2500/per day for NICU. Pregnancy outcomes and charges were compared for each gestational week at stop of TX group compared to the successive week. RESULTS: Pregnancy outcomes and estimated charges for 4,253 singleton pregnancies receiving tocolytic TX stratified by gestational week at TX DC are presented below. 1 ⫽ p⬍0.05 vs previous week, adjusted for multiple comparisons. Week of TX DC PTD ⬍37 (%) Delivered within 7 days of TX DC (%) NICU admission (%) Low birth weight (%) Nursery days Total nursery charges ($)
33 weeks (n ⫽ 207)
34 weeks (n ⫽ 528)
35 weeks (n ⫽ 1371)
36 weeks (n ⫽ 2147)
75.4 53.6
71.6 47.5
62.41 55.11
43.21 63.11
44.0
26.31
15.01
9.21
53.6
32.2
1
15.41
8.01
7.4 ⫾ 7.1 4 (1–38) 14,884 ⫾ 19.250
4.2 ⫾ 4.4 2 (1–30)1 6,850 ⫾ 11,500
3.3 ⫾ 5.0 2 (1.98)1 4,408 ⫾ 12,807
2.7 ⫾ 2.9 2 (1–56)1 2,579 ⫾ 7,166
4000 (500–95,000)
1000 (500, 75,000)1
(500, 245,000)1
(500, 140,000)1
CONCLUSION: Early tocolytic DC leads to a high incidence of late preterm birth, with significantly greater rates of NICU admission and low birth weight, and significantly higher nursery charges. As late preterm birth is known to be associated with both short- and long-term neonatal morbidities, tocolytic TX should be continued through 36 weeks. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.118
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S43