462: First trimester maternal vitamin D status and the risk for spontaneous preterm birth

2
Variable Adjusted Odds Ratio 95% Confidence Interval Gestational age (days) 0.93 0.929-0.936 .......................................................................................................................................................................................... Received antenatal corticosteroids 0.58 0.49-0.69 .......................................................................................................................................................................................... Small for gestational age (P10) 3.02 2.41-3.79 .......................................................................................................................................................................................... Male infant 1.33 1.15-1.53 .......................................................................................................................................................................................... Multiple birth 0.78 0.66-0.91 .......................................................................................................................................................................................... Caucasian race/ethnicity 1.39 1.16-1.67 .......................................................................................................................................................................................... Hypertension/preeclampsia 0.97 0.81-1.18 .......................................................................................................................................................................................... Delivery in 3rd level hospital 0.84 0.72-0.98 .......................................................................................................................................................................................... No admission to an Neontal Intensive Care Unit 2.27 1.89-2.72 .......................................................................................................................................................................................... Non cephalic presentation 1.17 1.01-1.35 .......................................................................................................................................................................................... Parity 0 0.88 0.74-1.04 .......................................................................................................................................................................................... Parity 1 1.00 .......................................................................................................................................................................................... Parity 2 1.06 0.84-1.32 .......................................................................................................................................................................................... 460 The association of stress biomarkers with placental inflammation Ann Borders 1 , Linda Ernst 1 , Kaitlin Wolfe 1 , Jane Holl 1 , William Grobman 1 1 Northwestern University Feinberg School of Medicine, Chicago, IL OBJECTIVE: Preterm birth has been associated with chronic stress, though the biologic mechanisms remain unclear. Preterm birth also has been associated with chronic placental inflammation. The objec- tive of this study was to assess the association between maternal stress biomarkers collected in the 2 nd and 3 rd trimesters with placental inflammation. STUDY DESIGN: African-American and Caucasian pregnant women were recruited at an urban university hospital between May 2008 and July 2009. Blood samples, collected between 14 to 22 weeks and 28 to 32 weeks, were analyzed for serum Epstein-Barr Virus (EBV) anti- body, C-Reactive Protein (CRP), CRH, and ACTH. Placentas were collected at the time of delivery and underwent pathologic evaluation for both acute and chronic inflammation (including chronic villitis, chronic deciduitis, chronic decidual perivasculitis, and chronic chorioamnionitis). RESULTS: 114 (58 Caucasian and 56 African-American) women were recruited. Mean EBV, ACTH and CRH values were not significantly different in patients with chronic placental inflammation. Both sec- ond and third trimester mean maternal CRP levels, however, were significantly higher in patients with chronic villitis in the placenta (2 nd trimester: 16.8 4.3 vs. 9.0 1.1, p0.02; 3 rd trimester: 18.3 4.5 vs. 8.4 1.4, p0.01). Patients with CRP levels in the top quartile were significantly more likely to show any chronic inflammatory lesion in the placenta (40% vs. 18%, p0.04) than those in the lower quartiles. Acute placental inflammation was not significantly associated with EBV, ACTH, CRH or CRP levels. Patients with any chronic placental inflammation had a significantly lower mean birth weight (3600 565 vs. 3126 667, p .01). CONCLUSIONS: Maternal CRP levels are elevated in women whose pla- centas have chronic inflammation and chronic placental inflamma- tion is associated with lower birth weight. These data suggest a rela- tionship between chronic stress, placental inflammation, and pregnancy outcomes that requires further study. 461 Using item response theory to optimize measures of chronic stress in pregnancy Ann Borders 1 , Jin-Shei Lai 1 , Kaitlin Wolfe 1 , Jie Peng 1 , Kwang-Youn Kim 1 , Jane Holl 1 , William Grobman 1 1 Northwestern University Feinberg School of Medicine, Chicago, IL OBJECTIVE: Although multiple studies have shown an association be- tween stress and preterm birth, these findings are inconsistent. This inconsistency may be related to the diversity of survey tools used to measure stress. The present study utilized Rasch analysis, a form of Item Response Theory, to evaluate psychometric properties of multi- ple measures of stress and condense them based on underlying core domains. STUDY DESIGN: African-American and Caucasian pregnant women were recruited at an urban university hospital between May 2008 and July 2009. Equal numbers of women were enrolled by race. In addi- tion, each of these groups was constructed to ensure a similar socio- economic distribution by health insurance status. Self-reported stress was measured using 96 items from 8 existing scales from 14 to 22 weeks of gestation. Multidimensional scaling (MDS) was used to ex- plore underlying factors by estimating Euclidean distances among items. Rasch analysis was used to evaluate unidimensionality of items (criteria: fit index 1.4) within each factor identified by MDS. RESULTS: 114 (58 Caucasian and 56 African-American) pregnant women were enrolled. Equal proportions of Caucasian and African American women had Medicaid versus private insurance, and mean income levels did not differ by race. MDS results indicate that the surveys could be reduced to 31 and 46 questions and grouped into two factors: Factor 1 (perceived stressors) and Factor 2 (buffers of stress). Both factors had excellent internal consistency defined by alpha 0.9. Caucasian women reported significantly higher buffers of stress (p .045), as did women who had private insurance (p .001), a planned pregnancy (p .01), and a domestic partner (p.001). CONCLUSIONS: These data suggest that self-reported stress measures in pregnancy can be reduced into two groups of questions which can be classified as perceived stressors and buffers of stress. Future studies should investigate whether item-reduced measure of maternal stress can be reproduced in other populations as well as associated with biologic measures of stress and pregnancy outcomes. 462 First trimester maternal vitamin D status and the risk for spontaneous preterm birth Arthur Baker 1 , Sina Haeri 1 , Carlos Camargo 2 , Alison M Stuebe 1 , Kim Boggess 1 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, 2 Massachusetts General Hospital, Boston, MA OBJECTIVE: Vitamin D deficiency in pregnancy is common and may play a role in adverse pregnancy outcomes. Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. Vitamin D is important in immune tolerance and in supporting placental im- plantation. Preterm birth rates are higher for pregnancies concieved in winter when maternal vitamin D stores are typically lower. Our objective was to assess whether first trimester maternal vitamin D deficiency is associated with an elevated risk of spontaneous preterm birth. STUDY DESIGN: We conducted a nested case-control study in a cohort of 4,225 women. All women who delivered at the University of North Carolina-Chapel Hill between November 2004 and July 2009 and had provided blood at 11-14 weeks for routine genetic screening were eligible. Fourty women with spontaneous preterm birth (23 0/7 and 34 6/7 weeks) were matched by race/ethnicity to 120 women with uncomplicated term (37 weeks) birth. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D] using liquid chromatography-tandem mass spectrometry. Vitamin D defi- ciency was defined as 25(OH)D 50 nmol/L. RESULTS: Maternal demographics were similar between the groups. The mean (SD) concentration of 25(OH)D in this study was 90 26 nmol/L. The prevalence of first trimester maternal 25(OH)D defi- ciency was low both among women later experiencing a spontaneous preterm birth or term birth (8% vs. 7%, respectively; P0.90). The prevalence of vitamin D sufficiency (defined as 25(OH)D 75 nmol/L) was high in both groups (73%). CONCLUSIONS: In a cohort of women with a high prevalence of optimal levels of serum 25(OH)D, vitamin D status was not associated with spontaneous preterm birth. Studies in pregnant populations where www.AJOG.org Doppler Assessment, Fetus, Neonatology, Prematurity Poster Session III Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology S185

Transcript of 462: First trimester maternal vitamin D status and the risk for spontaneous preterm birth

Page 1: 462: First trimester maternal vitamin D status and the risk for spontaneous preterm birth

w

J

thtb

rdos

8stAEi5

cttp

m

K

t

wAisfBC.p

pcscb

a

A

N

pbipiodb

T

l

www.AJOG.org Doppler Assessment, Fetus, Neonatology, Prematurity Poster Session III

VariableAdjusted OddsRatio

95% ConfidenceInterval

Gestational age (days) 0.93 0.929-0.936..........................................................................................................................................................................................

Received antenatal corticosteroids 0.58 0.49-0.69..........................................................................................................................................................................................

Small for gestational age (P10) 3.02 2.41-3.79..........................................................................................................................................................................................

Male infant 1.33 1.15-1.53..........................................................................................................................................................................................

Multiple birth 0.78 0.66-0.91..........................................................................................................................................................................................

Caucasian race/ethnicity 1.39 1.16-1.67..........................................................................................................................................................................................

Hypertension/preeclampsia 0.97 0.81-1.18..........................................................................................................................................................................................

Delivery in 3rd level hospital 0.84 0.72-0.98..........................................................................................................................................................................................

No admission to an NeontalIntensive Care Unit

2.27 1.89-2.72

..........................................................................................................................................................................................

Non cephalic presentation 1.17 1.01-1.35..........................................................................................................................................................................................

Parity 0 0.88 0.74-1.04..........................................................................................................................................................................................

Parity 1 1.00..........................................................................................................................................................................................

Parity 2� 1.06 0.84-1.32..........................................................................................................................................................................................

460 The association of stress biomarkersith placental inflammation

Ann Borders1, Linda Ernst1, Kaitlin Wolfe1,ane Holl1, William Grobman1

1Northwestern University Feinberg School of Medicine, Chicago, ILOBJECTIVE: Preterm birth has been associated with chronic stress,hough the biologic mechanisms remain unclear. Preterm birth alsoas been associated with chronic placental inflammation. The objec-ive of this study was to assess the association between maternal stressiomarkers collected in the 2nd and 3rd trimesters with placental

inflammation.STUDY DESIGN: African-American and Caucasian pregnant womenwere recruited at an urban university hospital between May 2008 andJuly 2009. Blood samples, collected between 14 to 22 weeks and 28 to32 weeks, were analyzed for serum Epstein-Barr Virus (EBV) anti-body, C-Reactive Protein (CRP), CRH, and ACTH. Placentas werecollected at the time of delivery and underwent pathologic evaluationfor both acute and chronic inflammation (including chronic villitis,chronic deciduitis, chronic decidual perivasculitis, and chronicchorioamnionitis).RESULTS: 114 (58 Caucasian and 56 African-American) women wereecruited. Mean EBV, ACTH and CRH values were not significantlyifferent in patients with chronic placental inflammation. Both sec-nd and third trimester mean maternal CRP levels, however, wereignificantly higher in patients with chronic villitis in the placenta (2nd

trimester: 16.8 � 4.3 vs. 9.0 � 1.1, p�0.02; 3rd trimester: 18.3 � 4.5 vs..4 �1.4, p�0.01). Patients with CRP levels in the top quartile wereignificantly more likely to show any chronic inflammatory lesion inhe placenta (40% vs. 18%, p�0.04) than those in the lower quartiles.cute placental inflammation was not significantly associated withBV, ACTH, CRH or CRP levels. Patients with any chronic placental

nflammation had a significantly lower mean birth weight (3600 �65 vs. 3126 � 667, p� .01).

CONCLUSIONS: Maternal CRP levels are elevated in women whose pla-entas have chronic inflammation and chronic placental inflamma-ion is associated with lower birth weight. These data suggest a rela-ionship between chronic stress, placental inflammation, andregnancy outcomes that requires further study.

461 Using item response theory to optimizeeasures of chronic stress in pregnancy

Ann Borders1, Jin-Shei Lai1, Kaitlin Wolfe1, Jie Peng1,wang-Youn Kim1, Jane Holl1, William Grobman1

1Northwestern University Feinberg School of Medicine, Chicago, ILOBJECTIVE: Although multiple studies have shown an association be-

ween stress and preterm birth, these findings are inconsistent. This s

Supplem

inconsistency may be related to the diversity of survey tools used tomeasure stress. The present study utilized Rasch analysis, a form ofItem Response Theory, to evaluate psychometric properties of multi-ple measures of stress and condense them based on underlying coredomains.STUDY DESIGN: African-American and Caucasian pregnant womenwere recruited at an urban university hospital between May 2008 andJuly 2009. Equal numbers of women were enrolled by race. In addi-tion, each of these groups was constructed to ensure a similar socio-economic distribution by health insurance status. Self-reported stresswas measured using 96 items from 8 existing scales from 14 to 22weeks of gestation. Multidimensional scaling (MDS) was used to ex-plore underlying factors by estimating Euclidean distances amongitems. Rasch analysis was used to evaluate unidimensionality of items(criteria: fit index �1.4) within each factor identified by MDS.RESULTS: 114 (58 Caucasian and 56 African-American) pregnant

omen were enrolled. Equal proportions of Caucasian and Africanmerican women had Medicaid versus private insurance, and mean

ncome levels did not differ by race. MDS results indicate that theurveys could be reduced to 31 and 46 questions and grouped into twoactors: Factor 1 (perceived stressors) and Factor 2 (buffers of stress).oth factors had excellent internal consistency defined by alpha �0.9.aucasian women reported significantly higher buffers of stress (p �

045), as did women who had private insurance (p � .001), a plannedregnancy (p � .01), and a domestic partner (p�.001).

CONCLUSIONS: These data suggest that self-reported stress measures inregnancy can be reduced into two groups of questions which can belassified as perceived stressors and buffers of stress. Future studieshould investigate whether item-reduced measure of maternal stressan be reproduced in other populations as well as associated withiologic measures of stress and pregnancy outcomes.

462 First trimester maternal vitamin D statusnd the risk for spontaneous preterm birth

Arthur Baker1, Sina Haeri1, Carlos Camargo2,lison M Stuebe1, Kim Boggess1

1University of North Carolina at Chapel Hill, Chapel Hill,C, 2Massachusetts General Hospital, Boston, MA

OBJECTIVE: Vitamin D deficiency in pregnancy is common and maylay a role in adverse pregnancy outcomes. Spontaneous pretermirth is a major cause of perinatal morbidity and mortality. Vitamin D

s important in immune tolerance and in supporting placental im-lantation. Preterm birth rates are higher for pregnancies concieved

n winter when maternal vitamin D stores are typically lower. Ourbjective was to assess whether first trimester maternal vitamin Deficiency is associated with an elevated risk of spontaneous pretermirth.

STUDY DESIGN: We conducted a nested case-control study in a cohortof 4,225 women. All women who delivered at the University of NorthCarolina-Chapel Hill between November 2004 and July 2009 and hadprovided blood at 11-14 weeks for routine genetic screening wereeligible. Fourty women with spontaneous preterm birth (�23 0/7 and�34 6/7 weeks) were matched by race/ethnicity to 120 women withuncomplicated term (�37 weeks) birth. Banked maternal serum wasused to measure maternal 25-hydroxyvitamin D [25(OH)D] usingliquid chromatography-tandem mass spectrometry. Vitamin D defi-ciency was defined as 25(OH)D �50 nmol/L.RESULTS: Maternal demographics were similar between the groups.

he mean (SD) concentration of 25(OH)D in this study was 90 � 26nmol/L. The prevalence of first trimester maternal 25(OH)D defi-ciency was low both among women later experiencing a spontaneouspreterm birth or term birth (8% vs. 7%, respectively; P�0.90). Theprevalence of vitamin D sufficiency (defined as 25(OH)D �75nmol/L) was high in both groups (73%).CONCLUSIONS: In a cohort of women with a high prevalence of optimalevels of serum 25(OH)D, vitamin D status was not associated with

pontaneous preterm birth. Studies in pregnant populations where

ent to JANUARY 2011 American Journal of Obstetrics & Gynecology S185

Page 2: 462: First trimester maternal vitamin D status and the risk for spontaneous preterm birth

p

K

N

ta

tcigctGfi

tw38ts9v

wNoPw

b

T

t

v

s

M

M

(as

tw1aawbe

Poster Session III Doppler Assessment, Fetus, Neonatology, Prematurity www.AJOG.org

vitamin D deficiency is more prevalent are needed to determine therole of vitamin D in spontaneous preterm birth.

463 Fetal fibronectin as a predictor of spontaneousreterm birth in triplet gestations

Ashley Roman1, Cara Pessel2, Nathan Fox1, Chadlauser1, Daniel Saltzman1, Andrei Rebarber1

1Maternal Fetal Medicine Associates, PLLC, New York,Y, 2NYU School of Medicine, New York, NY

OBJECTIVE: To assess the diagnostic accuracy of vaginal fetal fibronec-in (fFN) sampling for predicting preterm birth (PTB) in asymptom-tic women with triplet gestations.

STUDY DESIGN: An historical cohort of patients carrying triplet gesta-ions between 1998 and 2010 was identified from a single practice byhart review. All patients were screened with fFN testing without us-ng a speculum at 2-3 week intervals from 22 weeks to 32 weeks ofestation. A fetal fibronectin concentration of 50 ng/ml or greater wasonsidered to be positive. Physicians and patients were not blinded tohe results. The primary outcome was gestational age at delivery.roups were compared using Fisher Exact test with significance de-ned as p�0.05.

RESULTS: There were 56 pregnancies that met criteria for inclusion. Aotal of 182 fFN tests were performed; 8% of tests were positive. fFNas significantly associated with SPTB (Table). For delivery prior to0 weeks’ gestation, the test had a sensitivity of 75%, a specificity of5%, a positive predictive value (PPV) of 46%, and a negative predic-ive value (NPV) of 95% (p�0.0001). For delivery within 3 weeks of aingle fFN assessment, the test had a sensitivity of 53%, a specificity of6%, a positive predictive value of 53%, and a negative predictivealue of 96% (p�0.0001).

CONCLUSIONS: The presence of vaginal fFN is significantly associatedith preterm birth in triplet gestations. fFN testing maintains a highPV of greater than or equal to 95% for identifying patients at low riskf PTB in triplet gestations Furthermore, fFN testing also has a highPV for both delivery within 3 weeks of testing and PTB prior to 30eeks.

Risk of PTB by fFN result in triplet gestations

fFN negative fFN positive p-value

PTB�28 weeks 2.3% 25.5% � 0.0001..........................................................................................................................................................................................

PTB�30 weeks 4.7% 46.2% 0.0002..........................................................................................................................................................................................

PTB�32 weeks 14.6% 60% 0.06..........................................................................................................................................................................................

PTB within 2 weeks of test 3.0% 27.7% � 0.0001..........................................................................................................................................................................................

PTB within 3 weeks of test 4.2% 53% � 0.0001..........................................................................................................................................................................................

464 The kinetics of matrix metalloproteinase-9 inhibitiony magnesium sulfate in fetal cord plasma

Brad M. Dolinsky1, Danielle L Ippolito1, Craig M. Zelig1, Deborahinnemore1, Jonathan D Stallings1, Peter G. Napolitano1

1Madigan Army Medical Center, Tacoma, WAOBJECTIVE: Magnesium sulfate (MgSO4) therapy in preterm labormay decrease the risk of adverse neuro-developmental outcomes, asdemonstrated in several clinical trials. The specific biologic mecha-nism of this is poorly understood. Matrix metalloproteinase-9(MMP-9), a zinc (Zn��) dependent enzyme, is thought to play a key role inthe breakdown of the blood-brain-barrier in adults with sepsis. Wehave previously demonstrated that in vitro addition of magnesiumsulfate to cord plasma inhibits MMP-9 activity through a post-trans-lational mechanism. Our objective was to determine whether MgSO4

attenuates MMP-9 activity by inhibiting Zn�� mediated activation incord plasma.STUDY DESIGN: We collected umbilical cord plasma from five unla-bored, term patients. Cord plasma was pretreated with ZnCl and

2

varying doses of MgSO4 approximating cord blood levels measured in r

S186 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2

the BEAM trial (unpublished data). MMP-9 was isolated from cordplasma by immunoaffinity and chemically activated. Kinetics ofMMP-9 activation were measured by Activity ELISA over 48 hours.RESULTS: Based on our kinetic curves, MgSO4 inhibits Zn�� activa-ion of MMP-9 in cord plasma. Initially MgSO4 potentiates Zn��

activation of MMP-9. This peaks at 3.5 hours after which MMP-9activity is inhibited. Using one-way ANOVA, the activity levels ofMMP-9 were decreased with MgSO4 and Zn�� compared to Zn��

alone at hour ten (1.254 �/� .02 AU vs 1.319 �/� .0004 AU p�.01).The most pronounced attenuation of MMP-9 activity was observed inMgSO4 doses consistent with the third and fourth quartiles levels de-scribed in BEAM (figure).CONCLUSIONS: MgSO4 inhibits Zn�� activation of MMP-9 in our initro model after 3.5 hours. The duration and timing of MgSO4 ther-

apy may have a significant impact on the inhibition of MMP-9 incord plasma. Our data suggest a novel mechanism of action forMgSO4inhibition of MMP9, and may be useful when designing trialsto optimize treatment.

465 Does first trimester crown to rump length predictpontaneous preterm delivery? A matched-cohort study

Brenda Kazemier1, Jolande Vis1, Emily Kleinrouweler1,artijn Oudijk2, Joris van der Post1, Ben Willem Mol1

1Academic Medical Center, Amsterdam, 2Universityedical Center Utrecht, Utrecht

OBJECTIVE: It has been suggested that a short crown to rump lengthCRL) is associated with preterm delivery. (Mook-Kanamori, D. O., etl 2010) We assessed the association between first trimester CRL andpontaneous preterm birth.

STUDY DESIGN: We performed a retrospective matched-cohort studyamong women with a spontaneous preterm delivery between 24-32weeks (cases) and women with a spontaneous term delivery (con-trols). All women who delivered preterm between 2000 and 2010 in aDutch tertiary hospital with a known reliable first day of their lastmenstrual period and a reliable CRL measurement between 8�0 and13�6 weeks were included as cases. Controls were matched on ma-ternal age, medical indication, parity and previous preterm deliveries.Differences between the measured CRL and the expected CRL basedon the last menstrual period were expressed as multiples of the median(MoM). The MoM of the CRL between the cases and the controls wascompared using a two-sample paired t-test.RESULTS: We included 104 cases and 104 controls. The median gesta-ional age at the CRL measurement was 11�5 (IQR 10�3 to 12�5)eeks in women with a preterm delivery and 11�4 (IQR 9�6 to2�2) weeks in women with a term delivery. The median gestationalge at delivery was 28�6 (IQR 26�2 to 31�0) weeks in women withpreterm delivery and 39�3 (IQR 38�3 to 40�1) weeks in womenith a term delivery. We found no differences in MoM of the CRLetween women with preterm delivery and women with a term deliv-ry (MoM 0.91 (95% CI 0.88 to 0.94) versus 0.95 (95% CI 0.90 to 1.0)

espectively, p�0.21).

011