os084. maternal haemodynamics at 11–13 weeks of gestation and adverse pregnancy outcomes

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References [1] Silveira PP, Portella AK, Goldani MZ, Barbieri MA. Developmental origins of health and disease (DOHaD). J Pediatr (Rio J) 2007;83(6):494–504. [2] Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 2007;27:363–88. [3] Silveira PP, Portella AK, Goldani MZ, Barbieri MA. Developmental origins of health and disease (DOHaD). J Pediatr (Rio J) 2007;83(6):494–504. [4] Barker DJ. Human growth and cardiovascular disease. Nestle Nutr Workshop Ser Pediatr Program 2008;61:21–38. doi:10.1016/j.preghy.2012.04.083 OS083. Fetal growth and maternal vascular function in early pregnancy C. Iacobaeus, G. Jörneskog, T. Kahan, M. Thorsell, E. Andolf * (Department of Clinical Sciences, Karolinska Insitutet, Danderyds Hospital, Danderyd, Sweden) Introduction: Increasing evidence indicates that the rate of fetal growth is partly determined already in the first half of pregnancy. A number of authors have reported that if the fetus is smaller than expected at dating, the risk for a small for gestational age fetus increases. Objectives: To investigate if maternal vascular function in early pregnancy reflects fetal growth in the first trimester. Methods: Fifty healthy women with singleton viable preg- nancies were included in the study that were recorded the ultrasound department of UltraGyn Stockholm, Sweden for ultrasound dating in gestational week 11–14 . Of these, 25 women had their estimated date of delivery postponed 7 days at ultrasound dating compared to last menstrual per- iod in gestational week 11–14. As controls 25 women were fetal size were in accordance with the last menstrual period (defined as expected date of delivery moved less than six days) were recruited. The dating examinations were per- formed by specially trained midwives. To assess gestational age, biparietal diameter was used. Exclusion criteria were the use of oral contraceptives within three months before conception, uncertain date of the last menstrual period, irregular menstrual periods, fetuses that were 21 days lar- ger or smaller than expected, and fetal anomalies. Women that smoked were also excluded. Blood pressure was measured in the upper arm in a con- ventional way. The central blood pressure was calculated with a validated algorithm. Changes in skin microcirculation were measured using laser Doppler fluxmetri (LDF). Both endothelial dependent dilatation using assessment of acetyl- choline (Ach) and local warming of skin to 44C for maximum micro vascular hyperaemia (MMH) and non endothelial dila- tation using assessment of sodium nitroprusside (SNP) was examined. Results: Fetuses that were smaller than expected at ultra- sound dating compared to last menstrual period at gesta- tional week 11–14, had an increased change in maximum micro vascular hyperaemia (p = 0.034). There was no signif- icant correlation between ACh-response (p = 0.59) and SNP- response (p = 0.23). No differences were seen in blood pressure. Conclusion: In the first trimester, changes in vascular function might reflect important adaptations that are required to facilitate normal fetal growth. This was high- lighted by the findings of a positive correlation between fetal growth at 11–14 weeks gestation and changes in endo- thelial dependent microcirculation.. Vascular function of these women will be followed longi- tudinally during pregnancy and related to obstetric out- come. If changes in microcirculation in the first trimester correlates to an increased risk for complications such as hypertensive disorders during pregnancy or intrauterine growth restriction this gives new insights into the early phase of these complications. Disclosure of interest None declared. doi:10.1016/j.preghy.2012.04.084 OS084. Maternal haemodynamics at 11–13 weeks of ges- tation and adverse pregnancy outcomes A. Khalil 1,* , R. Akolekar 2 , A. Syngelaki 3 , M. Elkhouli 3 , K. Nicolaides 4 ( 1 Fetal medicine unit, Institute for Women’s Health, University College London, United Kingdom, 2 Department of Fetal Medicine, University College London and King’s College Hospital, United Kingdom, 3 Fetal Medicine Unit, King’s College Hospital, United Kingdom, 4 Fetal medicine Unit, University College London and King’s College Hospital, United Kingdom) Introduction: Women who develop adverse pregnancy outcomes are at increased risk of cardiovascular disease. In individuals with cardiovascular disorders there is increased central aortic systolic blood pressure (SBPAo) and arterial stiffness. Objectives: The hypothesis is that increased SBPAo and arterial stiffness are apparent before the clinical onset of adverse pregnancy outcomes. Methods: This was a prospective study in singleton preg- nancies at 11 +0 –13 +6 weeks’ gestation. Pulse wave velocity (PWV), augmentation index (AIx) and SBPAo were mea- sured. At the same visit, we recorded maternal characteris- tics and medical history and performed combined screening for aneuploidies. We also measured the uterine artery Doppler pulsatility index (PI). The study outcomes included preeclampsia (PE), gestational hypertension (GH), gestational diabetes (GDM), small for gestational age (SGA) and preterm delivery (PTD). The diagnosis of PE and GH was made according to the guidelines of the International Society for the Study of Hypertension in Pregnancy. The neo- nate was considered SGA if the birth weight was less than the 5th percentile for gestation at delivery. The diagnosis of GDM was made if the fasting plasma glucose level was at least 6 mmol/L or the plasma glucose level 2 h after oral administration of 75 g glucose was 7.8 mmol/L or more (WHO). We compared these parameters in those that devel- oped PE (n = 181), GDM (n = 105), GH (n = 137), SGA (n = 337), PTD prior to 37 weeks’ gestation (n = 354) with Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 175–239 223

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References

[1] Silveira PP, Portella AK, Goldani MZ, Barbieri MA. Developmentalorigins of health and disease (DOHaD). J Pediatr (Rio J)2007;83(6):494–504.

[2] Waterland RA, Michels KB. Epigenetic epidemiology of thedevelopmental origins hypothesis. Annu Rev Nutr 2007;27:363–88.

[3] Silveira PP, Portella AK, Goldani MZ, Barbieri MA. Developmentalorigins of health and disease (DOHaD). J Pediatr (Rio J)2007;83(6):494–504.

[4] Barker DJ. Human growth and cardiovascular disease. Nestle NutrWorkshop Ser Pediatr Program 2008;61:21–38.

doi:10.1016/j.preghy.2012.04.083

OS083. Fetal growth and maternal vascular function inearly pregnancyC. Iacobaeus, G. Jörneskog, T. Kahan, M. Thorsell, E. Andolf *

(Department of Clinical Sciences, Karolinska Insitutet,Danderyds Hospital, Danderyd, Sweden)

Introduction: Increasing evidence indicates that the rate offetal growth is partly determined already in the first half ofpregnancy. A number of authors have reported that if thefetus is smaller than expected at dating, the risk for a smallfor gestational age fetus increases.

Objectives: To investigate if maternal vascular function inearly pregnancy reflects fetal growth in the first trimester.

Methods: Fifty healthy women with singleton viable preg-nancies were included in the study that were recorded theultrasound department of UltraGyn Stockholm, Sweden forultrasound dating in gestational week 11–14 . Of these, 25women had their estimated date of delivery postponed �7 days at ultrasound dating compared to last menstrual per-iod in gestational week 11–14. As controls 25 women werefetal size were in accordance with the last menstrual period(defined as expected date of delivery moved less than sixdays) were recruited. The dating examinations were per-formed by specially trained midwives. To assess gestationalage, biparietal diameter was used. Exclusion criteria werethe use of oral contraceptives within three months beforeconception, uncertain date of the last menstrual period,irregular menstrual periods, fetuses that were � 21 days lar-ger or smaller than expected, and fetal anomalies. Womenthat smoked were also excluded.

Blood pressure was measured in the upper arm in a con-ventional way. The central blood pressure was calculatedwith a validated algorithm. Changes in skin microcirculationwere measured using laser Doppler fluxmetri (LDF). Bothendothelial dependent dilatation using assessment of acetyl-choline (Ach) and local warming of skin to 44C for maximummicro vascular hyperaemia (MMH) and non endothelial dila-tation using assessment of sodium nitroprusside (SNP) wasexamined.

Results: Fetuses that were smaller than expected at ultra-sound dating compared to last menstrual period at gesta-tional week 11–14, had an increased change in maximummicro vascular hyperaemia (p = 0.034). There was no signif-icant correlation between ACh-response (p = 0.59) and SNP-response (p = 0.23). No differences were seen in bloodpressure.

Conclusion: In the first trimester, changes in vascularfunction might reflect important adaptations that arerequired to facilitate normal fetal growth. This was high-lighted by the findings of a positive correlation betweenfetal growth at 11–14 weeks gestation and changes in endo-thelial dependent microcirculation..

Vascular function of these women will be followed longi-tudinally during pregnancy and related to obstetric out-come. If changes in microcirculation in the first trimestercorrelates to an increased risk for complications such ashypertensive disorders during pregnancy or intrauterinegrowth restriction this gives new insights into the earlyphase of these complications.

Disclosure of interest

None declared.

doi:10.1016/j.preghy.2012.04.084

OS084. Maternal haemodynamics at 11–13 weeks of ges-tation and adverse pregnancy outcomesA. Khalil 1,*, R. Akolekar 2, A. Syngelaki 3, M. Elkhouli 3,K. Nicolaides 4 (1 Fetal medicine unit, Institute for Women’sHealth, University College London, United Kingdom,2 Department of Fetal Medicine, University College Londonand King’s College Hospital, United Kingdom, 3 FetalMedicine Unit, King’s College Hospital, United Kingdom,4 Fetal medicine Unit, University College London and King’sCollege Hospital, United Kingdom)

Introduction: Women who develop adverse pregnancyoutcomes are at increased risk of cardiovascular disease. Inindividuals with cardiovascular disorders there is increasedcentral aortic systolic blood pressure (SBPAo) and arterialstiffness.

Objectives: The hypothesis is that increased SBPAo andarterial stiffness are apparent before the clinical onset ofadverse pregnancy outcomes.

Methods: This was a prospective study in singleton preg-nancies at 11+0–13+6 weeks’ gestation. Pulse wave velocity(PWV), augmentation index (AIx) and SBPAo were mea-sured. At the same visit, we recorded maternal characteris-tics and medical history and performed combinedscreening for aneuploidies. We also measured the uterineartery Doppler pulsatility index (PI). The study outcomesincluded preeclampsia (PE), gestational hypertension (GH),gestational diabetes (GDM), small for gestational age (SGA)and preterm delivery (PTD). The diagnosis of PE and GHwas made according to the guidelines of the InternationalSociety for the Study of Hypertension in Pregnancy. The neo-nate was considered SGA if the birth weight was less thanthe 5th percentile for gestation at delivery. The diagnosisof GDM was made if the fasting plasma glucose level wasat least 6 mmol/L or the plasma glucose level 2 h after oraladministration of 75 g glucose was 7.8 mmol/L or more(WHO). We compared these parameters in those that devel-oped PE (n = 181), GDM (n = 105), GH (n = 137), SGA(n = 337), PTD prior to 37 weeks’ gestation (n = 354) with

Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 175–239 223

unaffected controls (n = 6,766). Multiple regression analysiswas used to examine which maternal characteristics pro-vided a significant contribution in the prediction of AIx-75,PWV and SBPAo. Each value was expressed as a multipleof the median (MoM) after adjustment for those characteris-tics. Pearson correlation analysis was used to examine theassociation between log10AIx-75 MoM, log10PWV MoM,log10 SBPAo MoM, log10uterine artery PI MoM and log10-

PAPP-A MoM with gestational age at delivery.Results: In the PE group there was an increase in AIx-75

(1.13, IQR 0.96–1.33 MoM vs 1.00, IQR 0.87–1.16 MoM,p < 0.0001), PWV (1.11, IQR 0.97–1.17 MoM vs 1.00, IQR0.90–1.12 MoM, p < 0.0001), and SBPAo (1.09, IQR 1.02–1.20 MoM vs. 1.00, IQR 0.94–1.08 MoM, p < 0.0001). In thosethat subsequently developed GH, compared to unaffectedcontrols, there was no significant difference in the uterineartery PI, PAPP–A or PWV but AIx–75 and SBPAo wereincreased (p < 0.0001). In the GDM group there was anincrease in PWV (1.06, IQR 0.96–1.19 MoM vs. 1.00, IQR0.90–1.13 MoM, p = 0.001) and SBPAo (1.03, IQR 0.98–1.14vs. 1.00, IQR 0.94–1.08, p < 0.0001), but no significant differ-ence in the AIx–75 (1.02, IQR 0.89–1.22 MoM vs. 1.00, IQR0.87–1.17 MoM, p = 0.118). Compared to women who hadterm delivery, women who had iatrogenic PTD had signifi-cantly higher AIx–75 (1.08, IQR 0.91–1.27 MoM vs. 1.00,IQR 0.86–1.16 MoM, p < 0.001) and SBPAo (1.06 MoM, IQR0.98–1.15 vs. 1.00, IQR 0.93–1.07, p < 0.001).

Conclusion: A high proportion of women who develop PE,GDM or iatrogenic PTD have increased SBPAo and arterialstiffness that is apparent from the first trimester of pregnancy.

Disclosure of interest

None declared.

doi:10.1016/j.preghy.2012.04.085

OS085. Decreased maternal circulating PLGF is a signifi-cant predictor of length of pregnancy in women withhypertensive disorders of pregnancyN. Gullai *, B. Stenczer, A. Molvarec, Z. Veresh, B. Nagy,J. Rigo Jr (First Dept. of Obstetrics and Gynecology,Semmelweis University, Budapest, Hungary)

Introduction: Diagnosis of the presence of disease and pre-diction of the rate of progression of disease in women withhypertensive disorders of pregnancy remains a clinical prob-lem. Better methods are needed to determine the magnitudeof risk to support patient counseling and clinicalmanagement.

Objectives: To investigate whether the level of free PlGF isa significant predictor of length of pregnancy in women withhypertension.

Methods: In this case-control study a single sample wastaken between the 22nd and 34th completed gestationalweeks from 130 pregnant women with a final diagnosis of:pre-eclampsia (PE), HELLP-syndrome, superimposed pre-eclampsia (SIPE), chronic hypertension (CHT), gestationalhypertension (GHT), and normal healthy pregnancy (Con-trol). Plasma was analysed for PlGF using the Triage� PlGFassay (Alere, San Diego). A positive PlGF test was definedas below the 5th centile of normal healthy pregnancy. Haz-ard ratios for length-of-pregnancy were calculated for apositive PlGF test in a multivariate Cox proportional hazardsmodel adjusting for two covariates, the gestational age atsample collection and a final diagnosis of proteinuric hyper-tension (PE, HELLP, and SIPE).

Results: Median PlGF concentration was significantlylower in women with hypertension than in controls. Womenwith proteinuric hypertension had the lowest levels of PlGF.

A positive PlGF test predicted delivery before 35 weeks in93.7% women, and delivery before 37 weeks in 90.5%women. A positive PlGF test was associated with a signifi-cantly higher risk of imminent delivery.

PlGF was a significant and independent predictor ofwomen destined to deliver early because of maternal or fetalcomplication (adjusted Hazard Ratio of 3.43, 95%CI of 1.97 to5.98).

Conclusion: A positive PlGF test is significant predictor oflength of pregnancy, independent of other diagnostic crite-ria. PlGF has the potential to identify increased risk withoutthe limitation of non-specificity which exists with otherdiagnostic parameters.

Disclosure of interest

None declared.

doi:10.1016/j.preghy.2012.04.086

OS086. Methylation status of the HOXA13 promoterregion in placental tissue of pregnancies complicated byearly onset severe preeclampsiaM.P. Rambaldi *, A. Pieralli, S. Ottanelli, C. Serena, S. Simeone,G. Mello, F. Mecacci (Obstetric and gynecology – High riskpregnancy unit, AOU Careggi, Florence, Italy)

Introduction: Compromised placental function and mor-phology found in early onset preeclampsia as well as a mod-ified phenotype of the fetus may derive from a deviation in

Group N Median 25th% 75th% ⁄p-value

Control 27 331 163 633 n/aGHT 18 168 28 527 0.0199CHT 25 64 13 145 0.0000PE 23 12 12 12 0.0000HELLP 20 12 12 12 0.0000SIPE 17 16 12 53 0.0000

224 Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 175–239