717: Physiological insulin resistance of pregnancy leads to increased glucose uptake rat pups

SMFM Abstracts

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PHYSIOLOGICAL INSULIN RESISTANCE OF PREGNANCY LEADS TO INCREASED GLUCOSE UPTAKE RAT PUPS FRANCINE EINSTEIN1, HYE HEO1, LINGGUANG CUI1, DEREK M. HUFFMAN1, RADHIKA H. MUZUMDAR1, NIR BARZILAI1, 1Albert Einstein College of Medicine, Bronx, New York OBJECTIVE: While insulin resistance (IR) of pregnancy is commonly believed to be a necessity to support offspring, no in vivo evidence has supported this theory. Using a tool to modulate IR in pregnant rats, we tested the impact of improved insulin sensitivity on placenta and pups in vivo. STUDY DESIGN: We studied 3 groups of age-matched SD rats: 1)Pregnant (Day 19) non-obese, glucose tolerant (P; n⫽6), 2)Pregnant rats(Day 19) which had visceral fat surgically removed 1 month prior to mating(PVF-; n⫽6) and 3)NonPregnant (NP; n⫽6). We used a model of pre-conception surgical removal of visceral fat (previously shown to improve insulin sensitivity based on glucose infusion rate during hyperinsulinemic clamp) as a tool to improve insulin action in pregnancy. A bolus of 2-[U-14C]deoxyglucose (20 ␮Ci) was administered over 30 minutes before the end of hyperinsulinemic-euglycemic clamp to determine tissue glucose uptake. During this clamp all rats were exposed to similar insulin levels, plasma samples for 2-[U-14C]deoxyglucose-specific activity were obtained at 10min intervals and tissue samples of hid-limb muscle, visceral fat, placenta and pups were collected after the clamp. RESULTS: Glucose uptake in muscle was greater in NP compared to P (27.6⫾4 v 13.5⫾3.4 ug/g/min, p⬍0.05) and intermediate in VF- (23.8⫾6.3 ug/g/min, p⫽NS compared to other groups) demonstrating variation in insulin action. Placental uptake was similar in P and VF- (70.2⫾10.3 v 67.6⫾12.3 ug/g/min, p⫽NS), but fetal uptake was almost doubled in P compared VF- (69.9⫾7.3 v 39.5⫾9.8 ug/g/min, p⬍0.05). The percentage of total body glucose uptake into the fetal/ placental unit is much larger than that into muscle (P 63.0 v 6.1% and VF- 48.6 v 9.3%, respectively). CONCLUSION: IR in pregnancy is a determining factor in glucose uptake to the fetus, but not placenta. Yet, the degree of IR required for adequate, but not excessive fetal growth has yet to be determined as well as if maternal IR increases fetal risk for development of diabetes later in life.

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0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.748

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PROSPECTIVE EVALUATION OF INCIDENCE OF DELAYED VILLOUS MATURATION IN NON DIABETIC AND PRE-GESTATIONAL DIABETIC PREGNANCIES MARY HIGGINS1, NOIRIN RUSSELL1, EOGHAN MOONEY2, FIONNUALA MCAULIFFE1, 1University College Dublin, National Maternity Hospital, Dublin, Ireland, Ireland, 2Pathology, National Maternity Hospital, Dublin, Ireland, Ireland OBJECTIVE: Pre-gestational Diabetes (PGDM) affects less than 1% of the population but is a significant cause of maternal and neonatal morbidity and mortality. Previously we performed a retrospective study showing an increased incidence of delayed villous maturation (DVM) in a PGDM population; DVM is a placental diagnosis with increased risk of perinatal mortality. This study aimed to prospectively study the incidence of DVM in a non diabetic (ND) population compared to PGDM, and its correlation with clinical markers. STUDY DESIGN: With institutional ethics approval the placentas of women with ND and PGDM pregnancies who consented to the study underwent detailed histopathological examination, blinded to the patient groups. RESULTS: 77 ND women and 74 PGDM women consented to the study. Birth weight in infants of diabetic mothers was higher (3650g (2635-4875g) vs. 3440 (2140-4950g); p⬍0.01) and these infants were more likely to be admitted to the NICU (35% vs. 2%; p⬍0.01). The incidence of DVM in the PGDM group was higher than that in the ND group (21/74 (28.4%) vs. 11/77 (14.3%) p⫽0.02; RR 1.98). In the PGDM group clinical and ultrasound markers were compared between the DVM group (n⫽21) and the non DVM group (n⫽53). There was no difference in glycaemic control (HbA1c, fructosamine) or ultrasound findings such as liquor volume, middle cerebral artery pulsatility index, or MCA to Umbilical artery (UA) ratio. Umbilical artery PI was lower at 30 weeks in the DVM group (0.88 vs. 1.00, p⫽0.03) though this did not continue at 33 (0.86 vs. 0.95, p⫽NS) or 36 weeks (0.85 vs. 0.92, p⫽NS). CONCLUSION: DVM, a placental finding with an increased risk of perinatal mortality, is increased in PGDM population 28% compared to non diabetic controls 14%. The presence of DVM may explain the increased perinatal mortality and morbidity seen in PGDM pregnancies. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.750

FIRST TRIMESTER PLACENTAL PROTEIN-13 (PP-13)-RELATIONSHIP WITH MATERNAL CHARACTERISTICS AHMET BASCHAT1, YAEL INNA GRIMPEL2, OZHAN TURAN3, JODIE MARTIN4, JEROME KOPELMAN1, CHUKA JENKINS5, ROBERT ATLAS1, IDO KUHNREICH6, CHRISTOPHER HARMAN1, HAMUTAL MEIRI7, MIRIAM BLITZER1, 1University of Maryland, Baltimore, Department of OB/GYN and Reproductive Sciences, Baltimore, Maryland, 2Diagnostic Technologies, Yoqneam, Israel, Israel, 3University of Maryland at Baltimore, Baltimore, Maryland, 4University of Maryland, Baltimore, Washington, District of Columbia, 5Harbor Hospital Medical Center, Baltimore, Maryland, 6 Technostat, Kfar saba, Israel, Israel, 7Diagnostic Technologies Limited, Yokneam, Israel, Israel OBJECTIVE: PP-13 is a new maternal serum marker that shows potential as a screening test for early detection of patients at risk for pre-eclampsia. Romero et al recently demonstrated the impact of historic cofounders on predictive quality. Aim of this study was to clarify clinically relevant relationships between PP-13 and several 1st trimester maternal/placental factors. STUDY DESIGN: Serum samples from prospectively enrolled patients between 11-14 weeks were analyzed for PP-13 using an ELISA assay. The PP-13 levels were correlated to maternal race, parity, smoking, body mass index (BMI), mean arterial blood pressure (MAP) and uterine and umbilical Doppler parameters. RESULTS: In 170 consecutive patients PP-13 levels ranged from 8-537 ng/ml. Levels showed a minimal (nonsignificant) increase with gestational age and were not correlated with maternal age, race (African American (AA) or Caucasian (C)) and parity. Negative correlations were identified with BMI (Pearson ⫺0.26, p⫽0.001) and MAP (⫺0.16, p⫽0.03). BMI correlations were stronger in AA than C ethnicity (Pearson ⫺0.33, p⬍0.0001, and ⫺0.27, p⬍0.05). While caffeine had no impact, smoking significantly decreased PP-13 (27 vs. 64 ng/ml; Mann Whitney p⬍0.001). No relationship was idenitified with uterine and umbilical blood flow resistance.

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PRIOR OBSTETRICAL HISTORY AS A PREDICTOR OF CURRENT 17HYDROXYPROGESTERONE USE CARLA RANSOM1, JEANNETTE CHIN1, HILARY ROEDER2, TAMMY SINCLAIR1, PHILIPS HEINE3, HAYWOOD BROWN1, AMY MURTHA1, 1Duke University, Durham, North Carolina, 2Duke University Medical Center, North Carolina, 3 Duke University, North Carolina OBJECTIVE: Randomized trials of 17-hydroxyprogesterone caproate (17P) show an unexpectedly high rate of preterm delivery (PTD) in placebo compared to 17P (55 vs. 36%). We sought to determine if gestational age at prior delivery influences the decision to receive 17P in the current gestation. STUDY DESIGN: Retrospective cohort study of women eligible for 17P at Duke Obstetrics Clinic (1/07-6/08). Subjects were identified by medical record review. Socio-demographic and clinical characteristics were obtained. Data were analyzed using t-test, Mann-Whitney and chi square where appropriate. RESULTS: Of the 106 eligible subjects, 82 (77.4%) were offered 17P. Thirty four (41.5%) of the 82 subjects offered 17P declined. There were no significant sociodemographic differences between subjects that accepted or declined 17P. The median GA of the most recent PTD was lower in those subjects who accepted 17P compared to those who declined (28.0 vs. 34.6 wks, p⫽0.004). Gestational age of the earliest PTD as well as delivery GA of the current gestation was not significantly different when subjects that accepted 17P were compared to those that declined (28 vs. 32 g, p⫽0.08 and 36 vs. 38 wks, p⫽0.14, respectively). When subjects offered 17P were compared to those not offered 17P the median GA of the most recent delivery and the earliest prior preterm delivery was significantly lower (30.2 vs. 36.0 wks, p⫽0.004 and 29.5 vs. 32.5 wks, p⫽0.04, respectively) The GA at delivery in the current pregnancy was not different when subjects not offered 17P were compared to those that were offered and either accepted or declined (37.5 vs. 36.7 wks, p⫽0.5). CONCLUSION: Women who received 17P had a history of prior PTD that was 2 weeks earlier than women not accepting 17P. Prior obstetric history, namely GA at PTD, may influence both providers and patients to discuss and/or accept 17P. However, 17P did not significantly increase the GA in the current gestation in this study. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.751

CONCLUSION: First trimester PP-13 levels show significant relationships with maternal risk factors for subsequent placental dysfunction. These relationships appear independent of placental vascular characteristics suggesting an independent role for PP-13 as a 1st trimester screening biomarker for placental development. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.749

Supplement to DECEMBER 2008 American Journal of Obstetrics & Gynecology

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