228: Biochemical markers of bone turnover and bone mineral density during pregnancy in twin...

1
227 Blockade of CD4 T cells prior to placental insult, attenuates hypertension in response to placental ischemia Sarah Novotny 1 , Kedra Wallace 1 , Pushpinder Dhillon 1 , Janae Moseley 1 , Judith Heath 1 , James N Martin Jr 1 , Babbette LaMarca 1 1 University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, MS OBJECTIVE: Preeclampsia is associated with hypertension, proteinuria, chronic immune activation involving activated CD4 T cells, inflam- matory cytokines, and agonistic autoantibodies. Research from our laboratory has shown that hypertension in the chronic placental isch- emia rat model of preeclampsia (RUPP) is associated with CD4T cell activation, inflammatory cytokines, autoantibodies and renal dys- function. Our most recent studies indicate that adoptive transfer of RUPP CD4 T cells into normal pregnant rats causes hypertension and much of the pathophysiology seen in women with preeclampsia. Therefore, we hypothesize that CD4 T cell activation blockade with abatacept (Orencia) would attenuate hypertension in RUPP pregnant rats. STUDY DESIGN: To answer this question four groups of pregnant rats were examined: normal pregnant (NP, n20), Reduced uterine per- fusion pressure (RUPP, n20), NP orencia (NPO; n12) and RUPP orencia (RUPPO; n19). Orencia, abatacept, (250mg/kg) was infused i.v. via jugular catheter over a 20 minute period on day 13 to NP (n31)rats, 19 of which underwent the RUPP surgical proce- dure on day 14, same day as RUPP controls. On day 18 indwelling carotid catheters were inserted into all groups and on day 19 MAP was analyzed, plasma collected for FACS analysis of CD4 T cells, and serum was collected for ELISA. RESULTS: MAP increased from 94 / 2 mmHg in NP rats to 123 / 3 mmHg in RUPP rats. This response was attenuated with CD4 T cell blockade, MAP was 104 / 2 mmHg in RUPPO, and had no effect in the NPO (96 / 2 mmHg). Circulating CD4 T cells increased in RUPPs compared to NP rats, 66% / 3% and 55.5%/ 2.7% respectively (p0.04) but was attenuated in RUPPO rats (54.8 / 2.5%) and was 59 / 4% in NPO. The twofold increase in TNF alpha seen in RUPPs (277 / 47 pg/ml) was decreased to 80 /18 pg/ml in RUPPsO. CONCLUSION: Blockade of CD4 T cells prior to the initial placental insult attenuated hypertension in RUPP rats, indicating the impor- tance of immune activation in the pathophysiology of hypertension in response to placental ischemia. 228 Biochemical markers of bone turnover and bone mineral density during pregnancy in twin pregnancy and singleton pregnancy SiWon Lee 1 , Jae Hyug Yang 2 , Kwang Moon Yang 3 , Jung Yeol Han 2 , June Seek Choi 3 , Hyun Kyeong Ahn 3 , Min Hyuong Kim 3 , Hyun Mee Ryu 2 , Moon Young Kim 2 , Jin Hoon Chung 3 , Yoo Jung Han 3 1 Cheil General Hospital and Women’s Healthcare Center, Obstetrics and Gynecology, Seoul, CT, South Korea, 2 Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Obstetrics and Gynecology, Seoul, CT, Korea, 3 Cheil General Hospital, Obstetrics and Gynecology, Seoul, CT, Korea OBJECTIVE: To examine the influence of twin pregnancy on biochem- ical markers of bone turnover and bone mineral density (BMD) dur- ing pregnancy by comparing with singleton pregnancy. STUDY DESIGN: Between February 2004 and February 2008, we con- ducted a prospective study to show the patterns of changes in bio- chemical markers of bone turnover and bone mineral density (BMD) during pregnancy in twin and singleton pregnancies. Forty-eight twin and 41 singleton pregnant women were included. In both cross-sec- tional and longitudinal studies, ultrasound BMD and serum markers of bone resorption (-Crosslaps) and bone formation (total alkaline phosphatase (ALP), osteocalcin (OC)), total calcium, phosphorus and parathyroid hormone were measured during each trimester of pregnancy. RESULTS: BMD was generally lower in twin pregnancy than in single- ton pregnancy. BMD decreased until second trimester in both groups. However, in the third trimester, BMD started to recover in singleton pregnancy whereas it continued to decrease in twin pregnancy al- though not statistically significant (p0.308). In twin pregnancy, marker of bone resorption (-Crosslaps) was lower in the first trimes- ter and higher in the third trimester compared to singleton pregnancy. Markers of bone formation (ALP, OC) also showed higher levels in the third trimester in twin pregnancy. In cross-sectional study, serum calcium and phosphorus were significantly higher and serum PTH was significantly lower in twin pregnancy than in singleton pregnancy (p0.001). CONCLUSION: In twin pregnancy, BMD was lower and biochemical markers of bone turnover showed generally earlier and larger in- creases during pregnancy signifying higher fetal demand for calcium compared to the singleton pregnancy. Therefore, higher levels of cal- cium and vitamin D supplementation should be recommended for women with twin pregnancy. 229 Changes in biochemical markers of bone turnover and bone mineral density during pregnancy and postpartum in twin pregnancy SiWon Lee 1 , Jae Hyug Yang 2 , Jung Yeol Han 2 , June Seek Choi 3 , Hyun Kyeong Ahn 3 , Min Hyuong Kim 3 , Hyun Mee Ryu 2 , Moon Young Kim 2 , Jin Hoon Chung 3 , Yoo Jung Han 3 1 Cheil General Hospital and Women’s Healthcare center, Obstetrics and Gynecology, Seoul, CT, South Korea, 2 Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Obstetrics and Gynecology, Seoul, CT, Korea, 3 Cheil General Hospital, Obstetrics and Gynecology, Seoul, CT, Korea OBJECTIVE: Twin pregnancy is characterized by high bone metabo- lism. We conducted a prospective study to show the patterns of changes in biochemical markers of bone turnover and ultrasound bone mineral density (BMD) during pregnancy and postpartum in twin pregnancy. STUDY DESIGN: Between August 2007 and February 2009, 48 healthy twin pregnant women were included. We used ultrasound bone den- sitometer to measure BMD which is advantageous to pregnant women. We measured markers of bone resorption (-Crosslaps), bone formation (total alkaline phosphatase (ALP), osteocalcin (OC)), Poster Session I Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology www.AJOG.org S112 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012

Transcript of 228: Biochemical markers of bone turnover and bone mineral density during pregnancy in twin...

227 Blockade of CD4� T cells prior to placental insult,attenuates hypertension in response to placental ischemiaSarah Novotny1, Kedra Wallace1, Pushpinder Dhillon1, JanaeMoseley1, Judith Heath1, James N Martin Jr1, Babbette LaMarca1

1University of Mississippi Medical Center,Obstetrics and Gynecology, Jackson, MSOBJECTIVE: Preeclampsia is associated with hypertension, proteinuria,chronic immune activation involving activated CD4� T cells, inflam-matory cytokines, and agonistic autoantibodies. Research from ourlaboratory has shown that hypertension in the chronic placental isch-emia rat model of preeclampsia (RUPP) is associated with CD4�Tcell activation, inflammatory cytokines, autoantibodies and renal dys-function. Our most recent studies indicate that adoptive transfer ofRUPP CD4� T cells into normal pregnant rats causes hypertensionand much of the pathophysiology seen in women with preeclampsia.Therefore, we hypothesize that CD4� T cell activation blockade withabatacept (Orencia) would attenuate hypertension in RUPP pregnantrats.STUDY DESIGN: To answer this question four groups of pregnant ratswere examined: normal pregnant (NP, n�20), Reduced uterine per-fusion pressure (RUPP, n�20), NP � orencia (NP�O; n�12) andRUPP � orencia (RUPP�O; n�19). Orencia, abatacept, (250mg/kg)was infused i.v. via jugular catheter over a 20 minute period on day 13to NP (n�31)rats, 19 of which underwent the RUPP surgical proce-dure on day 14, same day as RUPP controls. On day 18 indwellingcarotid catheters were inserted into all groups and on day 19 MAP wasanalyzed, plasma collected for FACS analysis of CD4� T cells, andserum was collected for ELISA.RESULTS: MAP increased from 94 �/� 2 mmHg in NP rats to 123�/� 3 mmHg in RUPP rats. This response was attenuated withCD4� T cell blockade, MAP was 104 �/� 2 mmHg in RUPP�O, andhad no effect in the NP�O (96 �/� 2 mmHg). Circulating CD4� Tcells increased in RUPPs compared to NP rats, 66% �/� 3% and55.5%�/� 2.7% respectively (p�0.04) but was attenuated inRUPP�O rats (54.8 �/� 2.5%) and was 59 �/� 4% in NP�O. Thetwofold increase in TNF alpha seen in RUPPs (277 �/� 47 pg/ml) wasdecreased to 80 �/�18 pg/ml in RUPPs�O.CONCLUSION: Blockade of CD4� T cells prior to the initial placentalinsult attenuated hypertension in RUPP rats, indicating the impor-tance of immune activation in the pathophysiology of hypertension inresponse to placental ischemia.

228 Biochemical markers of bone turnover andbone mineral density during pregnancy in twinpregnancy and singleton pregnancySiWon Lee1, Jae Hyug Yang2, Kwang Moon Yang3,Jung Yeol Han2, June Seek Choi3, Hyun Kyeong Ahn3,Min Hyuong Kim3, Hyun Mee Ryu2, Moon YoungKim2, Jin Hoon Chung3, Yoo Jung Han3

1Cheil General Hospital and Women’s Healthcare Center,Obstetrics and Gynecology, Seoul, CT, South Korea, 2Cheil GeneralHospital and Women’s Healthcare Center, Kwandong University Collegeof Medicine, Obstetrics and Gynecology, Seoul, CT, Korea, 3CheilGeneral Hospital, Obstetrics and Gynecology, Seoul, CT, KoreaOBJECTIVE: To examine the influence of twin pregnancy on biochem-ical markers of bone turnover and bone mineral density (BMD) dur-ing pregnancy by comparing with singleton pregnancy.STUDY DESIGN: Between February 2004 and February 2008, we con-ducted a prospective study to show the patterns of changes in bio-chemical markers of bone turnover and bone mineral density (BMD)during pregnancy in twin and singleton pregnancies. Forty-eight twinand 41 singleton pregnant women were included. In both cross-sec-tional and longitudinal studies, ultrasound BMD and serum markersof bone resorption (�-Crosslaps) and bone formation (total alkalinephosphatase (ALP), osteocalcin (OC)), total calcium, phosphorusand parathyroid hormone were measured during each trimester ofpregnancy.RESULTS: BMD was generally lower in twin pregnancy than in single-ton pregnancy. BMD decreased until second trimester in both groups.However, in the third trimester, BMD started to recover in singletonpregnancy whereas it continued to decrease in twin pregnancy al-though not statistically significant (p�0.308). In twin pregnancy,marker of bone resorption (�-Crosslaps) was lower in the first trimes-ter and higher in the third trimester compared to singleton pregnancy.Markers of bone formation (ALP, OC) also showed higher levels in thethird trimester in twin pregnancy. In cross-sectional study, serumcalcium and phosphorus were significantly higher and serum PTHwas significantly lower in twin pregnancy than in singleton pregnancy(p�0.001).CONCLUSION: In twin pregnancy, BMD was lower and biochemicalmarkers of bone turnover showed generally earlier and larger in-creases during pregnancy signifying higher fetal demand for calciumcompared to the singleton pregnancy. Therefore, higher levels of cal-cium and vitamin D supplementation should be recommended forwomen with twin pregnancy.

229 Changes in biochemical markers of bone turnoverand bone mineral density during pregnancyand postpartum in twin pregnancySiWon Lee1, Jae Hyug Yang2, Jung Yeol Han2, June Seek Choi3,Hyun Kyeong Ahn3, Min Hyuong Kim3, Hyun Mee Ryu2,Moon Young Kim2, Jin Hoon Chung3, Yoo Jung Han3

1Cheil General Hospital and Women’s Healthcare center, Obstetrics andGynecology, Seoul, CT, South Korea, 2Cheil General Hospital and Women’sHealthcare Center, Kwandong University College of Medicine, Obstetricsand Gynecology, Seoul, CT, Korea, 3Cheil General Hospital,Obstetrics and Gynecology, Seoul, CT, KoreaOBJECTIVE: Twin pregnancy is characterized by high bone metabo-lism. We conducted a prospective study to show the patterns ofchanges in biochemical markers of bone turnover and ultrasoundbone mineral density (BMD) during pregnancy and postpartum intwin pregnancy.STUDY DESIGN: Between August 2007 and February 2009, 48 healthytwin pregnant women were included. We used ultrasound bone den-sitometer to measure BMD which is advantageous to pregnantwomen. We measured markers of bone resorption (�-Crosslaps),bone formation (total alkaline phosphatase (ALP), osteocalcin (OC)),

Poster Session I Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology www.AJOG.org

S112 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012