- Email: [email protected]
401: Smoking and preterm birth: A novel effect of 17 alpha-hydroxyprogesterone caproate (17OHP-C)
Poster Session II RESULTS: IL-6 levels in UtSMC treated with DMSO+TNF-a (positive control) were approximately 9-fold higher than a matched DMSOonly negative control (419.1 vs. 45.5 pg/mL). Relative to the TNF-a positive control, IL-6 was significantly reduced after pre-treatment with HPC (302.3 pg/mL, 74%, p¼0.012), 16a-OHP (299.5 pg/mL, 78%, p¼0.006), and 6b-OHP (295.4 pg/mL, 77%, p¼0.005), but not P4 (344.9 pg/mL, 87%, p¼0.38), E2 (407.4 pg/mL, 107%, p¼0.44), or E2/P4 (258.6 pg/mL, 85%, p¼0.41). CONCLUSION: TNF-a stimulated IL-6 production was significantly reduced only by HPC, 16a-OHP, and 6b-OHP, but not by progesterone. Progesterone metabolites may decrease the ability of TNF-a mediated inflammation in human UtSMC to progress to uterine contractility.
ajog.org median maternal serum t-cfDNA than those with preterm PROM [median 338.5 ng/ml (0-3565 ng/ml) vs. median 812 ng/ml (2034132 ng/ml), respectively, p¼0.001], and those with preterm labor [median 496 ng/ml (0-3563 ng/ml), p¼0.042]. Women in the preterm PROM group had a higher median serum t-cfDNA compared to those with preterm labor, but this difference did not reach statistical significance (p¼0.051). No differences were observed in the preterm parturition groups between women who eventually delivered preterm or at term (p¼0.742). The rate of elevated maternal serum t-cfDNA concentrations was higher in the preterm PROM (42.9%) group than the preterm non-labor group (5.6%) (p¼0.011). CONCLUSION: 1) Preterm parturition is associated with an increase in maternal serum t-cfDNA concentration; and 2) Decidual activation, a prominent feature in preterm PROM, may contribute to the marked elevation in t-cfDNA observed specifically in these patients.
401 Smoking and preterm birth: A novel effect of 17 alphahydroxyprogesterone caproate (17OHP-C) Kent Heyborne1,2, Amanda A. Allshouse2 1
Denver Health, Denver, CO, 2University of Colorado, Aurora, CO
OBJECTIVE: Maternal cigarette smoking is linked to preterm birth
400 Maternal total cell-free DNA in different phenotypes of the preterm parturition syndrome-preterm labor and preterm PROM Neta Benshalom-Tirosh1, Dan Tirosh1, Amos Douvdevani1, Majdi Imterat1, Salvatore A. Mastrolia2, Reut Riff1, Ruthy Beer-Weisel1, Vered Klaitman1, Shirley Greenbaum1, Alexander Alioshin1, Gal Rodavsky1, Annachiara Basso2, Offer Erez1 1
Soroka University Medical Center, Beer Sheva, Israel, 2Azienda OspedalieroUniversitaria Policlinico di Bari, School of Medicine, University of Bari “Aldo Moro”, Bari, Italy
OBJECTIVE: To determine whether the concentrations of circulating total cell-free DNA (t-cfDNA) in maternal serum, measured by a simple rapid fluorescent assay, are associated with the two phenotypes of spontaneous preterm parturition syndrome (preterm labor and preterm PROM). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) term non-labor (n¼21); 2) term labor (n¼15); 3) preterm non-labor (n¼18); 4) preterm labor (n¼25); and 5) preterm PROM (n¼14). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold stain, without prior DNA extraction and amplification. Elevated maternal serum tcfDNA concentrations were defined as a cutoff>850 ng/ml. Nonparametric statistics were used for analysis. RESULTS: In both non-labor groups, t-cfDNA concentrations correlated significantly with gestational age at sample collection (rho¼0.52, p<0.001). In the term groups, the median t-cfDNA concentrations did not differ between women with and without labor (p¼0.68). Women in the preterm non-labor group had a lower
(PTB) and other adverse pregnancy outcomes. Despite cessation counseling many women continue to smoke. It is unknown if available PTB prevention strategies might reduce smoking-related PTB. We examined the ability of 17OHP-C to modify the increase in PTB related to smoking. STUDY DESIGN: Secondary analysis of the MFMU Prevention of Recurrent PTB by 17OHP-C (Meis) Trial where women with a prior history of spontaneous PTB (sPTB) were randomized to 17OHP-C vs. placebo in a 2:1 ratio. Smoking status was recorded at study entry (median 19w, 16-21w). The effect of 17OHP-C on the smokingrelated odds of PTB (all PTB, sPTB or PPROM-PTB <37w or <35w) was estimated in logistic regression, adjusted for demographic and clinical characteristics known to impact PTB (>1 prior PTB, education, BMI, race, alcohol/drug use, infection). Resulting adjusted odds ratios (aOR) and 95% CI are reported. RESULTS: Of 463 subjects in the original study, 459 women with complete data were included in this analysis (100 smokers, 359 nonsmokers). Smokers were significantly more likely to be white, less educated, have alcohol or illicit drug use or >1 prior PTB; all of these variable were included in the multivariable analysis as above. Not surprisingly, in the placebo group, smokers had significantly higher odds of PTB <35w than non-smokers (aOR 2.73, CI 1.116.74) with a trend towards increases in other PTB outcomes: aOR PTB <37w 2.17, CI 0.84-5.63; aOR sPTB <37w 1.99, CI 0.82-4.86, aOR sPTB <35w 2.45, CI 0.94-6.87 (Figure). In contrast, in the 17OHP-C group, smokers did not have higher odds of PTB than nonsmokers. This effect modification was significant for PTB <37w and < 35w and sPTB < 37w; marginally for sPTB < 35w; but not for PPROM-PTB (Figure). Observed crude rates of PTB according to smoking status and randomization are shown in the Table. CONCLUSION: In this secondary analysis of women with prior PTB, 17OHP-C appears to block smoking’s effect on PTB. 17OHP-C warrants investigation as a PTB prevention strategy for women who are unable or unwilling to stop smoking. This finding may also provide insights into mechanisms of both smoking-related PTB and 17OHP-C PTB prevention.
S220 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
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with an acute reaction to stress or depressive disorder, not otherwise classified were not at significant increased risk of PTB (Figure). CONCLUSION: Women with mental illness were at increased risk of PTB. Risks ranged between 20 and 100% higher than women without a mental illness and risks persisted across most subgroups. Although it cannot be determined from these data whether specific treatments for mental illness contribute to risk for PTB, the fact that elevated risks of similar magnitude are seen across many different diagnoses suggests that the maternal mental illness itself may confer risk.
% PTB
Outcome
17OHPC % PTB Smoker Nonsmoker
p
Placebo % PTB Smoker Nonsmoker
p
PTB < 37w
33
37
0.57 70
51
0.07
PTB < 35w
19
21
0.74 50
26
0.02
sPTB < 37w 19
23
0.42 50
31
0.06
sPTB < 35w 11
13
0.84 33
15
0.04
402 Risk of preterm birth among pregnant Medi-Cal participants with mental illness Rebecca Baer1, Christina D. Chambers1, Laura L. Jelliffe-Pawlowski2 1
University of California San Diego, La Jolla, CA, 2University of California San Francisco, San Francisco, CA
OBJECTIVE: To examine risk of preterm birth (PTB) among Medi-Cal
(California’s low-income health insurance) participants with a diagnosed mental illness. STUDY DESIGN: The study population was drawn from singleton live births in California from 2007 through 2011 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and hospital discharge records. The sample was restricted to women who delivered between 20 and 44 weeks gestation, paid for their delivery using Medi-Cal and where the infant had no major malformations. Cases included women with an ICD-9 code for mental illness in their hospital discharge record in the year before or after delivery (n ¼ 10,853). Controls were randomly selected at a 1:4 ratio among women without a mental illness ICD-9 code (n ¼ 43,312). Odds ratios (OR) and their 95% confidence intervals (CI) were calculated for PTB (< 37 weeks), adjusting for made for race/ethnicity, maternal age, body mass index, mother’s education, WIC enrollment, smoking, previous preterm birth, hypertension, infection and drug or alcohol abuse. RESULTS: Women with any mental illness were at 20% increased risk of a preterm birth compared with women without a mental illness (adjOR 1.2, 95% CI 1.1 to 1.3). Among the specific mental illnesses, women schizophrenic disorders and personality disorders were at the highest risk of PTB (adjORs 1.8 and 2.0, respectively). Women
403 Population-based estimation of the preterm birth rate in malawi: making every birth count Kathleen M. Antony1, R. Alan Harris1, Judy Levison1, Bertha Banda2, Grace Chiudzu2, Andrew Chigano2, Rose Chirwa2, Mary Nyondo2, Ellina Marko2, Susan Ramin1, Susan Raine1, Michael Belfort1, Henry Phiri3, Peter N. Kazembe2, Kjersti M. Aagaard1 1
Baylor College of Medicine, Houston, TX, 2Baylor Malawi Center of Excellence, Kamuzu Central Hospital, Lilongwe, Malawi, 3Kamuzu Central Hospital, Lilongwe, Malawi
OBJECTIVE: Worldwide, preterm birth (PTB) is the leading cause of childhood mortality, accounting for 15.4% of the 6.3 million children who died in their first 5 years of life in 2013. Malawi has the highest rate of PTB in the world, with estimates ranging from 16.8% to 24.7%. However, these numbers result from studies with notable potential for bias. The objective of this study was to perform a population-based estimation of the PTB rate in Malawi using active surveillance of rural and urban villages, and both local health centers
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ajog.org median maternal serum t-cfDNA than those with preterm PROM [median 338.5 ng/ml (0-3565 ng/ml) vs. median 812 ng/ml (2034132 ng/ml), respectively, p¼0.001], and those with preterm labor [median 496 ng/ml (0-3563 ng/ml), p¼0.042]. Women in the preterm PROM group had a higher median serum t-cfDNA compared to those with preterm labor, but this difference did not reach statistical significance (p¼0.051). No differences were observed in the preterm parturition groups between women who eventually delivered preterm or at term (p¼0.742). The rate of elevated maternal serum t-cfDNA concentrations was higher in the preterm PROM (42.9%) group than the preterm non-labor group (5.6%) (p¼0.011). CONCLUSION: 1) Preterm parturition is associated with an increase in maternal serum t-cfDNA concentration; and 2) Decidual activation, a prominent feature in preterm PROM, may contribute to the marked elevation in t-cfDNA observed specifically in these patients.
401 Smoking and preterm birth: A novel effect of 17 alphahydroxyprogesterone caproate (17OHP-C) Kent Heyborne1,2, Amanda A. Allshouse2 1
Denver Health, Denver, CO, 2University of Colorado, Aurora, CO
OBJECTIVE: Maternal cigarette smoking is linked to preterm birth
400 Maternal total cell-free DNA in different phenotypes of the preterm parturition syndrome-preterm labor and preterm PROM Neta Benshalom-Tirosh1, Dan Tirosh1, Amos Douvdevani1, Majdi Imterat1, Salvatore A. Mastrolia2, Reut Riff1, Ruthy Beer-Weisel1, Vered Klaitman1, Shirley Greenbaum1, Alexander Alioshin1, Gal Rodavsky1, Annachiara Basso2, Offer Erez1 1
Soroka University Medical Center, Beer Sheva, Israel, 2Azienda OspedalieroUniversitaria Policlinico di Bari, School of Medicine, University of Bari “Aldo Moro”, Bari, Italy
OBJECTIVE: To determine whether the concentrations of circulating total cell-free DNA (t-cfDNA) in maternal serum, measured by a simple rapid fluorescent assay, are associated with the two phenotypes of spontaneous preterm parturition syndrome (preterm labor and preterm PROM). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) term non-labor (n¼21); 2) term labor (n¼15); 3) preterm non-labor (n¼18); 4) preterm labor (n¼25); and 5) preterm PROM (n¼14). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold stain, without prior DNA extraction and amplification. Elevated maternal serum tcfDNA concentrations were defined as a cutoff>850 ng/ml. Nonparametric statistics were used for analysis. RESULTS: In both non-labor groups, t-cfDNA concentrations correlated significantly with gestational age at sample collection (rho¼0.52, p<0.001). In the term groups, the median t-cfDNA concentrations did not differ between women with and without labor (p¼0.68). Women in the preterm non-labor group had a lower
(PTB) and other adverse pregnancy outcomes. Despite cessation counseling many women continue to smoke. It is unknown if available PTB prevention strategies might reduce smoking-related PTB. We examined the ability of 17OHP-C to modify the increase in PTB related to smoking. STUDY DESIGN: Secondary analysis of the MFMU Prevention of Recurrent PTB by 17OHP-C (Meis) Trial where women with a prior history of spontaneous PTB (sPTB) were randomized to 17OHP-C vs. placebo in a 2:1 ratio. Smoking status was recorded at study entry (median 19w, 16-21w). The effect of 17OHP-C on the smokingrelated odds of PTB (all PTB, sPTB or PPROM-PTB <37w or <35w) was estimated in logistic regression, adjusted for demographic and clinical characteristics known to impact PTB (>1 prior PTB, education, BMI, race, alcohol/drug use, infection). Resulting adjusted odds ratios (aOR) and 95% CI are reported. RESULTS: Of 463 subjects in the original study, 459 women with complete data were included in this analysis (100 smokers, 359 nonsmokers). Smokers were significantly more likely to be white, less educated, have alcohol or illicit drug use or >1 prior PTB; all of these variable were included in the multivariable analysis as above. Not surprisingly, in the placebo group, smokers had significantly higher odds of PTB <35w than non-smokers (aOR 2.73, CI 1.116.74) with a trend towards increases in other PTB outcomes: aOR PTB <37w 2.17, CI 0.84-5.63; aOR sPTB <37w 1.99, CI 0.82-4.86, aOR sPTB <35w 2.45, CI 0.94-6.87 (Figure). In contrast, in the 17OHP-C group, smokers did not have higher odds of PTB than nonsmokers. This effect modification was significant for PTB <37w and < 35w and sPTB < 37w; marginally for sPTB < 35w; but not for PPROM-PTB (Figure). Observed crude rates of PTB according to smoking status and randomization are shown in the Table. CONCLUSION: In this secondary analysis of women with prior PTB, 17OHP-C appears to block smoking’s effect on PTB. 17OHP-C warrants investigation as a PTB prevention strategy for women who are unable or unwilling to stop smoking. This finding may also provide insights into mechanisms of both smoking-related PTB and 17OHP-C PTB prevention.
S220 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
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with an acute reaction to stress or depressive disorder, not otherwise classified were not at significant increased risk of PTB (Figure). CONCLUSION: Women with mental illness were at increased risk of PTB. Risks ranged between 20 and 100% higher than women without a mental illness and risks persisted across most subgroups. Although it cannot be determined from these data whether specific treatments for mental illness contribute to risk for PTB, the fact that elevated risks of similar magnitude are seen across many different diagnoses suggests that the maternal mental illness itself may confer risk.
% PTB
Outcome
17OHPC % PTB Smoker Nonsmoker
p
Placebo % PTB Smoker Nonsmoker
p
PTB < 37w
33
37
0.57 70
51
0.07
PTB < 35w
19
21
0.74 50
26
0.02
sPTB < 37w 19
23
0.42 50
31
0.06
sPTB < 35w 11
13
0.84 33
15
0.04
402 Risk of preterm birth among pregnant Medi-Cal participants with mental illness Rebecca Baer1, Christina D. Chambers1, Laura L. Jelliffe-Pawlowski2 1
University of California San Diego, La Jolla, CA, 2University of California San Francisco, San Francisco, CA
OBJECTIVE: To examine risk of preterm birth (PTB) among Medi-Cal
(California’s low-income health insurance) participants with a diagnosed mental illness. STUDY DESIGN: The study population was drawn from singleton live births in California from 2007 through 2011 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and hospital discharge records. The sample was restricted to women who delivered between 20 and 44 weeks gestation, paid for their delivery using Medi-Cal and where the infant had no major malformations. Cases included women with an ICD-9 code for mental illness in their hospital discharge record in the year before or after delivery (n ¼ 10,853). Controls were randomly selected at a 1:4 ratio among women without a mental illness ICD-9 code (n ¼ 43,312). Odds ratios (OR) and their 95% confidence intervals (CI) were calculated for PTB (< 37 weeks), adjusting for made for race/ethnicity, maternal age, body mass index, mother’s education, WIC enrollment, smoking, previous preterm birth, hypertension, infection and drug or alcohol abuse. RESULTS: Women with any mental illness were at 20% increased risk of a preterm birth compared with women without a mental illness (adjOR 1.2, 95% CI 1.1 to 1.3). Among the specific mental illnesses, women schizophrenic disorders and personality disorders were at the highest risk of PTB (adjORs 1.8 and 2.0, respectively). Women
403 Population-based estimation of the preterm birth rate in malawi: making every birth count Kathleen M. Antony1, R. Alan Harris1, Judy Levison1, Bertha Banda2, Grace Chiudzu2, Andrew Chigano2, Rose Chirwa2, Mary Nyondo2, Ellina Marko2, Susan Ramin1, Susan Raine1, Michael Belfort1, Henry Phiri3, Peter N. Kazembe2, Kjersti M. Aagaard1 1
Baylor College of Medicine, Houston, TX, 2Baylor Malawi Center of Excellence, Kamuzu Central Hospital, Lilongwe, Malawi, 3Kamuzu Central Hospital, Lilongwe, Malawi
OBJECTIVE: Worldwide, preterm birth (PTB) is the leading cause of childhood mortality, accounting for 15.4% of the 6.3 million children who died in their first 5 years of life in 2013. Malawi has the highest rate of PTB in the world, with estimates ranging from 16.8% to 24.7%. However, these numbers result from studies with notable potential for bias. The objective of this study was to perform a population-based estimation of the PTB rate in Malawi using active surveillance of rural and urban villages, and both local health centers
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S221