Pregnancy-associated Hypertensive Disorders Research Articles

P-676 Obstetric and perinatal outcomes in women with Turner Syndrome: A systematic review and meta-analysis

Abstract Study question What is the pooled risk of adverse obstetric and neonatal outcomes in pregnancies in women with Turner Syndrome (TS)? Summary answer TS women experience high rates of adverse outcomes. Risks are increased in egg donation pregnancies and multiple pregnancies compared to singleton spontaneous pregnancies. What is known already TS affects 1 in 2,000 live female births. The 2017 ‘Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome’ acknowledges women with TS are at increased risk of adverse obstetric and perinatal outcomes. Several retrospective cohort studies reporting obstetric and neonatal outcomes in TS pregnancies have been published in recent years. However, these studies are often limited to a single centre cohort, within one country and thus increasing risk of bias. Overall pooled risk estimates for each outcome have yet to be reported. Study design, size, duration A prospectively registered systematic review and meta-analysis was conducted and reported in line with PRISMA guidelines. Overall pooled rates of each outcome Is reported with 95% confidence interval. Pooled risk ratios comparing spontaneous and egg donation pregnancies are also reported. A comparative meta-analysis reports on dichotomous outcomes using summary risk ratio (RR) with 95%CI and on continuous outcomes using weighted mean difference (WMD) with 95%CI. Publication bias was assessed using the Newcastle-Ottawa Scale. Participants/materials, setting, methods A comprehensive literature search was undertaken. Eligibility screening was conducted by 2 independent reviewers. Studies were limited to English language with no time limit. Case reports were excluded. 30 studies reporting obstetric or perinatal outcomes in pregnancies of women with TS were included in the analysis. Outcome data was extracted and tabulated using a standard proforma. Main results and the role of chance 1724 pregnancies were included. Pooled risks: Obstetric outcomes: caesarean section (62.8%)(95%CI:57-76%), pregnancy-associated hypertensive disorders (21%)(95%CI:13-29%), pre-eclampsia (10%)(95%CI:6-14%),gestational diabetes mellitus (6.0%)(95%CI:4-8%), aortic dissection (1.1%)(95%CI:0-2%), intrahepatic cholestasis of pregnancy (4.6%)(95%CI:0-7%), post-partum haemorrhage (17.9%)(95%CI:-3-37%), and maternal mortality (0.3%)(95%CI:0-1%). Perinatal outcomes: prematurity (14.1%)(95%CI:8-18%), low birthweight (25.1%)(95%CI:12-23%), and perinatal mortality (1.2%)(95%CI:0-1%). Egg-donation pregnancies yield significantly higher rates of: caesarean section (82.8% vs. 55.7%) (RR1.49) (95% CI:1.27-1.76), pregnancy-associated hypertensive disorder (33.0% vs 12.9%: p=0.001), pre-eclampsia (16.9% vs 8.2%: p=0.0023), gestational hypertension (17.9% vs 0.0%: p=0.082), low-birthweight (43.0% vs 1.9%: p<0.001) and preterm birth (17.5% vs 0.0%: p<0.001) than spontaneous pregnancies. Multiple pregnancies resulted in high rates of prematurity (70.0%), low birth-weight (73.3%) and pregnancy-associated hypertensive disorders (60.9%). Limitations, reasons for caution Most studies were retrospective and included cases from many years ago so may not be reflective of current obstetric practice and improved care. Most studies were geographically clustered in Europe and North America. Estimations of risk may therefore not be generalisable to other ethnicities and middle and lower income countries Wider implications of the findings This study quantifies the risk of adverse outcomes in pregnancies in women with TS. Risk is increased further in egg donation pregnancies and strategies should aim to screen and prevent complications, particularly hypertensive disorders of pregnancy. Multiple pregnancy should be avoided through use of single embryo transfer. Trial registration number N/a

548 Fetal growth trajectories in women with chronic hypertension and superimposed pregnancy-associated hypertensive disorders

548 Fetal growth trajectories in women with chronic hypertension and superimposed pregnancy-associated hypertensive disorders

Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy.

Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity. Differential gene expression analysis followed by Time Course Gene Set Analysis (TcGSA) was conducted on publicly available high throughput sequencing transcriptomic data sets. Mutational load analysis was carried out on peripheral mononuclear blood cells from healthy pregnant individuals and individuals with preeclampsia. Thirty mitochondrial differentially expressed genes (mtDEGs) were detected in the maternal cell-free circulating transcriptome, whereas nine were detected in placental transcriptome from pregnancies with PIH. In PIH pregnancies, maternal mitochondrial dysregulation was associated with pathways involved in inflammation, cell death/survival, and placental development, whereas fetal mitochondrial dysregulation was associated with increased production of extracellular vesicles (EVs) at term. Mothers with preeclampsia did not exhibit a significantly different degree of mtDNA mutational load. Our findings support the involvement of maternal mitochondrial dysregulation in the pathophysiology of PIH and suggest that mitochondria may mediate maternal-fetal interactions during healthy pregnancy.NEW & NOTEWORTHY This study identifies aberrant maternal and fetal expression of mitochondrial genes in pregnancies with gestational hypertension and preeclampsia. Mitochondrial gene dysregulation may be a common etiological factor contributing to the development of de novo hypertension in pregnancy-associated hypertensive disorders.

Beta-Blockers in Pregnancy: Clinical Update

The aim of this review was to determine the anticipated benefits and adverse effects of beta-blockers in pregnant women with hypertension. The other issue was to assess the possible adverse effects of beta-blockers for their babies and provide current consensus recommendations for appropriate selection and individualized antihypertensive treatment with beta-blockers in pregnancy-associated hypertension. Hypertensive disorders of pregnancy are a major cause of maternal and fetal morbidity, with consequences later in life. Certain beta-blockers are useful for ameliorating hypertension in pregnancy and may have a protective role in endothelial dysfunction. However, some aspects of beta-blocker use in pregnancy are contentious among providers. Evidence on their safety, although well documented, is variable, and recent research reveals areas of controversy. Besides intrauterine growth restriction, other neonatal and obstetric complications remain a concern and should be explored thoroughly. Attention is necessary when treating pregnancy-associated hypertensive disorders with beta-blockers. Specific beta-blockers are considered safe in pregnancy, although the associated effects in the fetus are not clearly known and evidence is lacking for many safety outcomes, other than intrauterine growth restriction. Nevertheless, beta-blockers with specific indications in pregnancy under individualized selection and monitoring may confer substantial improvements in pregnant women with hypertension.

Are pregnancy-associated hypertensive disorders so sweet?

Worldwide, one in seven pregnancies is complicated by some form of diabetes, with a rising trend. Additionally, hypertension is one of the main causes of morbidity and mortality for both the pregnant woman and the fetus and also contributes to premature birth. In a cohort study of pregnant women with diabetes, which was recently published in this journal, at least 84.5% of the subjects had hypertension. This rate of hypertension might be among the highest reported thus far. In the medical literature, approximately 20% of women with diabetes during pregnancy have various pregnancy-associated hypertensive disorders. Racial/ethnic differences, apparently, were not implicated in this elevated rate of hypertension: Although black and Hispanic women have a twofold higher rate of hypertension in pregnancy compared to white women, 75% of the subjects in the study in question were white. Thus, the impressive finding delivered by this large study, merits additional clarifications.

Complement Activation Drives Progression of Pre-Eclampsia to HELLP Syndrome

Background: Pre-eclampsia is a hypertensive disorder of pregnancy that affects about 5% of all pregnancies; however, its pathogenesis remains poorly understood. About 1% of pre-eclampsia cases will progress to a severe form termed HELLP syndrome characterized by Hemolysis, Elevated Liver enzymes, and Low Platelet counts. We have previously shown that abnormal activation of complement is a driver of disease in a subset of patients with HELLP syndrome (Vaught et al. 2016 and 2018). Based on these studies, we proposed that germline variants in complement regulatory genes predispose to HELLP in the setting of pregnancy, a complement amplifying event. However, whether complement dysregulation correlates to disease severity in HELLP syndrome is unclear. In addition, the contribution of complement activation to the onset or severity of pre-eclampsia remains unknown. We hypothesized that patients with pre-eclampsia harboring complement gene variants are at increased risk for progression to HELLP syndrome and worse maternal and fetal outcomes due to dysregulation of the complement system.Methods: In this prospective cohort study, patients with the pregnancy-associated hypertensive disorders including HELLP or pre-eclampsia were enrolled after diagnostic validation with the Tennessee and ACOG classification criteria, respectively. In total, 24 women with HELLP and 42 women with pre-eclampsia were enrolled and followed through their hospital course and compared with 47 healthy normotensive pregnant women. Both maternal and fetal clinical outcomes were recorded. Delivery before estimated gestational age < 23 weeks was considered previable, and intra-uterine fetal death (IUFD) was characterized as death of the fetus in utero during the pregnancy. Targeted sequencing of 13 genes known to regulate the alternative complement pathway was performed, and non-synonymous, heterozygous germline variants with a minor allele frequency less than 0.01 were identified. A functional assay for complement activation, the modified Ham assay (mHam), was performed in a subset of cases with available serum samples. The mHam is based on the principle that a cell line lacking surface complement regulators is susceptible to complement mediated cell death; non-viable cells > 20.5% is considered a positive test.Results: The frequency of rare germline variants in the HELLP cohort was 45.8%, comparable to a well-established complement mediated disease (aHUS, Table 1). By comparison, the frequency of germline variants in the pre-eclampsia and control cohort was 28.6% and 23.4%, respectively. Of the 14 patients with sera available to perform the mHam, 57% of HELLP syndrome patients had a positive mHam as compared to 0% of the controls (p = incalculable). Among patients with HELLP syndrome, those with a complement gene variant were more likely to have a poor clinical outcome compared to those without a variant. Specifically, 3/11 patients with variants versus 1/13 patients without variants were diagnosed at a previable stage and/or experienced IUFD (p = 0.19). There was no difference in the rate of HELLP onset after 28 and 34 weeks between the two groups. Notably, when comparing the cohort of HELLP patients harboring variants to the cohort without, patients with variants had higher rates of acute renal failure, hypoxia, and ICU care, but a lower frequency of blood transfusions (Table 2).Conclusion: Patients with HELLP syndrome harbor rare germline variants in complement genes at a greater frequency than controls (p = 0.05) and a similar frequency to aHUS, a known complement mediated disease. HELLP syndrome patients also carry mutations at a higher frequency than women with pre-eclampsia (p = 0.16) who have a similar rate of variants as controls. This suggests that complement gene variants predispose to progression of pre-eclampsia to HELLP syndrome where the gene variant and pregnancy provide a first and second ‘hit’ similar to other complement disorders. Patients with rare complement-associated variants are also more likely more susceptible to severe disease manifestations. [Display omitted] DisclosuresChaturvedi: UCB: Other: Advisory board participation; Sanofi Genzyme: Other: Advisory board member; Alexion: Other: Advisory board member; Dova: Other: Advisory board member; Argenx: Other: Advisory board member.

Long-Term Effects of Late Gestation in Utero Hypoxic Stress on Mood Disorders: Sex and Age Differences

Abstract Introduction: In utero insults have been linked with increased fear and anxiety in progeny. In utero hypoxic stress is associated with a multitude of gestational complications such as pregnancy-associated hypertensive disorders and intrauterine growth restriction. Maternal hypertension during pregnancy is also associated with increased mood and anxiety disorders in progeny. However, it is unknown if these associations are due to in utero hypoxic stress. We hypothesized that exposure to late gestational hypoxia will have a long-term impact on anxiety in progeny. Methods: Timed pregnant female Long-Evans rats were exposed to five days (gestational days: 15-20) of chronic intermittent hypoxia (CIH) or room air (normoxia - 21% O2) for 8 hours during their sleep phase. Each CIH cycle was 6 min of 3 min hypoxia (10% O2) and 3 min normoxia (21% O2) for a total of 10 CIH cycles/hour. At weaning (PND 28), progeny was pair-housed with a conspecific of same sex and similar weight. To examine mood and anxiety disorders, we quantified anxiety-related behaviors (time spent in the center of open field arena, marble burying test, social and anti-social behaviors with conspecifics) along with quantifying food intake and circulating sex hormone levels during puberty (postnatal day, PND 40-45) and young adulthood (PND 60-65) in male and female progeny. Results: Gestational CIH did not impact circulating sex hormones or food intake, regardless of sex or age of progeny. However, gestational CIH increased anxiety related behaviors in pubertal females. These effects of gestational CIH on anxiety in pubertal females were not maintained, as these behaviors resolved in young adulthood. Gestational CIH did not impact male progeny, regardless of age. Conclusion: Exposure to CIH during gestation resulted in increased anxiety related behaviors in pubertal female progeny. In utero hypoxia during late gestation may temporarily increase the risk for mood and anxiety disorders in pubertal females.

Stroke in women: Is it different?

In the last decades, there has been great progress in the field of stroke. With the introduction of acute therapies (intravenous thrombolysis and intra-arterial treatment), the outcome after stroke has improved significantly. Better prevention, improved acute therapy, and acute rehabilitation improved the morbidity and mortality rate after stroke. Gender differences in risk factors and epidemiology have been known for a long time, but lately attention to gender differences in stroke has increased. The aim of this mini-review is to demonstrate gender disparities in stroke with a focus on epidemiology, specific risk factors (gender-specific and unspecific), and outcomes. The influence of some risk factors for stroke is stronger in women (atrial fibrillation and hypertension) and there are risk factors exclusive to women such as pregnancy, pregnancy-associated hypertensive disorders, oral contraceptives, and hormonal replacement treatment. Data on the impact of other risk factors are inconsistent. The worse outcome after a stroke is mainly caused by demographic characteristics in women. Specific gender research is needed to better understand gender disparities in stroke to improve prevention strategies and treatment for women.

Effects of low-molecular-weight heparin and aspirin in recurrent pre-eclampsia: A stratified cohort study.

To evaluate the effects of low-molecular-weight heparin (LMWH) combined with low-dose aspirin (LDA) in pregnant women with a history of pregnancy-related hypertensive disorders. In the current retrospective stratified cohort study, 33 women with previous hypertensive disorders of pregnancy treated with LMWH and LDA were compared with 37 control women who did not undergo LMWH or LDA treatment. Rates of pre-eclampsia recurrence, placental abruption, and other adverse outcomes for the fetuses and pregnant women were compared in the two groups. The pre-eclampsia recurrence rates were 12/33 (36.4%) in the LMWH+LDA group and 28/37 (75.7%) in the control group (P<0.01). In stratified cohort analysis, pregnant women with a history of early-onset pre-eclampsia, a body mass index of at least 24 (calculated as weight in kilograms divided by the square of height in meters), and aged less than 35years benefited from LMWH+LDA treatment. In women with chronic hypertension or a history of placental abruption there was no protective effect. There were no significant differences in other adverse outcomes such as placental abruption and small size for gestational age in fetuses or pregnant women in the two groups. Administration of LMWH+LDA only lowered the risk of pre-eclampsia recurrence in subgroups of pregnant women with a history of pregnancy-associated hypertensive disorders.

Fetal growth patterns in pregnancy-associated hypertensive disorders: NICHD Fetal Growth Studies

Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.

Does pregnancy interval after laparoscopic sleeve gastrectomy affect maternal and perinatal outcomes?

Background: Obesity is a global health epidemic and is associated with many maternal and neonatal complications. Laparoscopic sleeve gastrectomy (LSG) is among the surgical treatments for obesity. The appropriate timing of pregnancy following LSG remains controversial and few studies have evaluated this public health issue.Objective: To evaluate the effect of pregnancy timing after LSG on maternal and perinatal outcomes.Study design: We performed a retrospective observational study of 23 pregnant women who underwent LSG at a tertiary hospital in Turkey. Women who became pregnant within 18 months of undergoing LSG were included in the early pregnancy after LSG group, and those who became pregnant after 18 months were included the late pregnancy after LSG group. Maternal and perinatal outcomes were evaluated, including gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders, preterm birth, mode of delivery, small and large for gestational age births (small for gestational age (SGA), large for gestational age (LGA)), birth injury, and congenital malformations.Results: Body mass index (BMI) at conception was higher in the early pregnancy after LSG group than in the late pregnancy after LSG group (30.48 versus 27.25, respectively; p = .03). Pregnancy interval after LSG did not impact maternal–fetal complications or mode of delivery. After a 75 g oral glucose tolerance test (OGTT) for GDM, 75% (n = 6) of the early pregnancy group presented with early dumping syndrome, compared to only 13.3% (n = 2) of the late pregnancy after LSG group (p = .009).Conclusions: LSG may reduce obesity-related gestational complications, such as GDM and LGA. The interval between LSG and conception did not impact maternal or neonatal outcomes. Screening for GDM can result in dumping syndrome in pregnancies after LSG.

New Models of Pregnancy-Associated Hypertension

Pregnancy-associated hypertensive disorders are leading causes of maternal and fetal mortality. These include: pre-pregnancy hypertension that persists throughout gestation (chronic/preexisting hypertension), de novo hypertension that is diagnosed after 20 weeks of gestation and resolves after birth (gestational hypertension), de novo hypertension that is diagnosed after 20 weeks of gestation with or without proteinuria and end-organ damage (preeclampsia and eclampsia), and chronic hypertension with superimposed preeclampsia during gestation. Preeclampsia is the most severe form of these disorders. Animal models have been developed by employing surgical, genetic, and pharmacological approaches in order to recapitulate the maternal symptoms of preeclampsia and other hypertensive disorders of pregnancy. The scope of this brief review is to present an up-to-date synthesis of our knowledge of experimental models of pregnancy-associated hypertensive disorders. Novel models, defined in this review as characterized within the last 5 years, will be described and critically discussed. In this review, we will also discuss established experimental models of pregnancy-associated hypertensive disorders in the context of their contribution to new advances in our knowledge about the pathophysiology of these disorders and potential therapeutics. Emphasis will be placed on animal models of preeclampsia; however, models of other hypertensive disorders in pregnancy will also be reviewed.

Maternal and perinatal outcomes after bariatric surgery: a Spanish multicenter study.

Bariatric surgery (BS) has become more frequent among women of child-bearing age. Data regarding the underlying maternal and perinatal risks are scarce. The objective of this nationwide study is to evaluate maternal and perinatal outcomes after BS. We performed a retrospective observational study of 168 pregnancies in 112 women who underwent BS in 10 tertiary hospitals in Spain over a 15-year period. Maternal and perinatal outcomes, including gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders (PAHD), pre-term birth cesarean deliveries, small and large for gestational age births (SGA, LGA), still births, and neonatal deaths, were evaluated. Results were further compared according to the type of BS performed: restrictive techniques (vertical-banded gastroplasty, sleeve gastrectomy, and gastric banding), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD). GDM occurred in five (3 %) pregnancies and there were no cases of PAHD. Women whose pregnancies occurred before 1 year after BS had a higher pre-gestational body mass index (BMI) than those who got pregnant 1 year after BS (34.6 ± 7.7 vs 30.4 ± 5.3 kg/m(2), p = 0.007). In pregnancies occurring during the first year after BS, a higher rate of stillbirths was observed compared to pregnancies occurring after this period of time (35.5 vs 16.8 %, p = 0.03). Women who underwent BPD delivered a higher rate of SGA babies than women with RYGB or restrictive procedures (34.8, 12.7, and 8.3 %, respectively). Pregnancy should be scheduled at least 1 year after BS. Malabsorptive procedures are associated to a higher rate of SGA births.

Increased risk of rheumatoid arthritis in women with pregnancy complications and poor self-rated health: a study within the Danish National Birth Cohort

This study assessed the suggested association between pregnancy-associated hypertensive disorders, hyperemesis and subsequent risk of RA using a cohort with information about pre-pregnancy health. Self-reported information on pre-pregnancy health, pregnancy course, gestational hypertension, pre-eclampsia and hyperemesis was available from 55 752 pregnant women included in the Danish National Birth Cohort. Information about pregnancy-related factors and lifestyle was obtained by interviews twice during pregnancy and at 6 months post-partum. Women were followed for RA hospitalizations identified in the Danish National Patient Register. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Women with RA and non-specific musculoskeletal problems at the time of pregnancy were excluded. On average, women were followed for 11 years after childbirth and 169 cases of RA were identified. The risk of RA was increased in women with pre-eclampsia (n = 11, HR = 1.96, 95% CI 1.06, 3.63), a poor self-rated pregnancy course (n = 32, HR = 1.63, 95% CI 1.11, 2.39) and fair or poor self-rated pre-pregnancy health (fair health: n = 86, HR = 1.52, 95% CI 1.11, 2.09; poor health: n = 14, HR = 3.24, 95% CI 1.82, 5.76). Hyperemesis was not associated with risk of RA. We confirmed the previously suggested increased risk of RA in women with pre-eclampsia and also found an inverse association between self-rated pre-pregnancy health and risk of RA. These results suggest that the clinical onset of RA is preceded by a prolonged subclinical phase that may interfere with women's general well-being and pregnancy course or that some women carry a shared predisposition to pre-eclampsia and RA.

Maternal Cardiovascular Risk Profile After Placental Abruption

The prevalence of premature cardiovascular diseases (CVD) is increased in women with a history of maternal placental syndromes, including pregnancy-associated hypertensive disorders (eg, preeclampsia), fetal growth restriction, and placental abruption. Whereas previous studies have shown a high prevalence of CVD risk factors after pregnancies complicated by preeclampsia, this has not been studied for women with a history of placental abruption. To explore the association of placental abruption with CVD risk factors after delivery, we compared 75 women with a history of placental abruption with a control group of 79 women with uneventful pregnancies at 6 to 9 months postpartum for the presence of common CVD risk factors. In a subanalysis, data were stratified according to the presence or absence of concomitant hypertensive disease and further adjusted for potential confounders. Women with previous placental abruption had significantly higher mean systolic blood pressure, body-mass index, fasting blood glucose, C-reactive protein, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as compared with controls with only uneventful pregnancies. In the subanalysis, all differences remained significant for women with a history of placental abruption only (ie, without concomitant gestational hypertension), except for the associations with low-density lipoprotein-cholesterol and diastolic and systolic blood pressure. Most likely, the identified CVD risk factors predispose to placental abruption and development of premature CVD later in life.

OS014. Which first-line drug to control severe hypertension in pregnancy? A pilot study

Severe hypertension is a common complication in pregnancy-associated hypertensive disorders and there is no clear consensus on which first-line antihypertensive drug to use in this setting. To determine the efficacy and safety of four antihypertensive drugs (two intravenous and two oral) in pregnant women with severe hypertension. Pilot prospective randomised study. pregnant women with a gestational age >24weeks and admitted in the Obstetrics Department with severe hypertension defined as systolic blood pressure (SBP) ⩾165mmHg and/or diastolic blood pressure (DBP) ⩾105mmHg. The women were randomised in 4 groups to receive:-20mg intravenous labetalol;-5mg intravenous hydralazine;-10mg oral nifedipine tablets ;-10mg sublingual nifedipine. Treatment was repeated every 20mn until target SBP and DBP were reached (⩽150/⩽95mmHg). The primary endpoint was the time needed to achieve effective blood pressure control. Treatment failure was defined as the unability to reach the target BP within one hour. After giving informed consent, 41 pregnant women admitted with severe hypertension were randomised. Mean age was 35 years (SD 3.5), 65% were nulliparous and mean SBP and DBP at admission were 176 (SD 16) and 105 (SD 12)mmHg, respectively. Success to achieve target BP was reached in all patients within the oral 10mg nifedipine group (11 patients), in all but one patients with the 10mg sublingual group (12 patients), and only in 5 out of 9 patients and 6 out of 9 patients within the labetalol and hydralazine groups. They were only one hypotension (defined as SBP <120mmHg) in the two groups with intravenous drugs and 3 and 5 in the oral and sublingual nifedipine groups. These results indicate that oral nifedipine seems more effective than intravenous labetalol or hydralazine to reach BP control in pregnant patients with severe hypertension. A large scale randomized trial comparing oral nifedipine versus these commonly used intravenous antihypertensive drugs should be implemented in order to determine whether oral nifedipine is a more effective treatment in this population.

PP056. Placental growth factor is a better predictor of preterm birth than uterine or umbilical artery doppler in hypertensive disorders of pregnancy

Diagnosis of the presence of disease and prediction of the rate of progression of disease in women with hypertensive disorders of pregnancy remains a clinical problem. Adequate placentation and placental development are important for normal pregnancy. We determined whether PlGF is a better predictor of delivery before 34+0 and 37+0 weeks than uterine artery and umbilical artery doppler. One hundred and four women presenting before the completed 34th week of pregnancy with hypertensive disorders of pregnancy were enrolled into the study. Final diagnosis was chronic hypertension (N=24), gestational hypertension (N=21), pre-eclampsia (N=24), HELLP-syndrome (N=15), superimposed preeclampsia (N=20). Blood draw occurred before the 34th week of pregnancy at the time of investigation for expedited delivery or expectant management. Plasma was analysed for PlGF by the Alere Triage® PlGF assay using fluorescently-labelled monoclonal antibodies against PlGF. A positive PlGF test was defined as below the 5th centile of normal healthy pregnancy. Of the 104 pregnant women, the level of PlGF was abnormal in 23 of 24 (96%) women with IUGR, compared to 10 of 24 (42%) and 14 of 24 (58%) for uterine artery doppler and umbilical artery doppler, respectively. In the case of pre-eclampsia, the level of PlGF was abnormal in 50 of 59 (85%), compared to 15 of 59 (25%) and 25 of 56 (45%) for uterine artery doppler and umbilical artery doppler, respectively. Forty four (42%) women required medical delivery before 34+0 weeks gestation and 68 (65%) before 37+0 weeks gestation (see Table). PlGF detected a higher number of women requiring early delivery than doppler. The new Triage® PlGF test provides useful information to inform clinical decisions in pregnancy-associated hypertensive disorders, before the 34th completed gestational week.

Subclinical Thyroid Disease and the Incidence of Hypertension in Pregnancy

To estimate the possibility of long-term effects of subclinical thyroid dysfunction on hypertension and other cardiovascular-related conditions during pregnancy. This is a secondary analysis of a prospective prenatal population-based study in which serum thyroid-function analytes were measured from November 2000 through April 2003. Women with evidence of overt thyroid disease were excluded. The remaining women were classified as being euthyroid, having subclinical hyperthyroid, or having subclinical hypothyroid, and the frequency of pregnancy-associated hypertensive disorders was compared between these groups. Pregnancy outcomes in 24,883 women were analyzed for pregnancy hypertension, classified as gestational hypertension, mild preeclampsia, or severe preeclampsia. The incidence of hypertensive disorders were compared between the three cohorts. The overall incidences of hypertension in pregnancy were 6.2%, 8.5%, and 10.9% in the subclinical hyperthyroid, euthyroid, and subclinical hypothyroid groups, respectively, and were found to be significant when unadjusted (P=.016). After adjusting for confounding factors, there was a significant association between subclinical hypothyroidism and severe preeclampsia (adjusted odds ratio 1.6, 95% confidence interval 1.1-2.4; P=.03). Women with subclinical hypothyroidism identified during pregnancy have an increased risk for severe preeclampsia when compared with euthyroid women. II.

Maternofetal Cardiovascular Complications in Turner Syndrome After Oocyte Donation: Insufficient Prepregnancy Screening and Pregnancy Follow-up Are Associated With Poor Outcome

The life expectancy of girls with Turner syndrome (TS) is reduced, primarily due to the well-known cardiovascular complications, including cardiovascular malformations, early-onset hypertension, coronary ischemia, and aortic dissection and rupture. The use of recombinant hGH treatment and successful oocyte donation (OD) in ovarian insufficiency has improved the quality of life of girls with TS. With the increasing use of OD during in vitro fertilization in recent years among TS women, pregnancy is now possible, but these patients appear to be at substantial risk for adverse maternofetal outcome. Limited data from case reports and other small studies on TS women suggest that there is an increased frequency of maternal deaths due to the rupture of the aortic root as well as a high frequency of pregnancy-related hypertension. Pregnancies in TS women should be considered as high risk. Specific recommendations made by French Medical Societies for TS pregnancies include pregravid cardiac evaluation, aggressive treatment when indicated, and careful follow-up. This multicenter retrospective study investigated the maternofetal outcome of TS pregnancies achieved with OD. All pregnancies were ≥20 weeks of gestation. Data were obtained from reproductive technology centers affiliated with the French Study Group for Oocyte Donation and included 93 pregnant TS patients with ongoing pregnancies who had received OD between 1991 and 2009. Less than 38% of the 93 patients had received pregravid cardiac screening evaluation (including echocardiography [33.3%, n = 31] and thoracic magnetic resonance imaging [4.3%, n = 4]. Among the 82 patients with complete outcome data in this study, 31 (37.8%) developed pregnancy-associated hypertensive disorders (PAHD), including 54.8% (17/31) with PE and 4 with severe preeclampsia or eclampsia. The rate of prematurity was high (38.3%) and was primarily correlated with PAHD (P = 0.01). PAHD were related to a high rate of intrauterine growth retardation and severe intrauterine growth retardation (27.5 and 13.7%, respectively). One case of eclampsia resulted in fetal demise at 23 weeks of gestation. There was an increased risk of maternal death due to aortic dissection or rupture after delivery by cesarean section in 2 patients (2.2%, 4/93). An absolutely normal maternofetal outcome occurred in only 40.2% of the TS pregnancies. These findings show that pregnancies obtained by OD in TS are at risk for maternal death due to aortic dissection and rupture, and require management according to specific recommendations for pregravid cardiac evaluation, aggressive treatment for hypertension and other cardiovascular problems, and careful follow-up.

Materno-Fetal Cardiovascular Complications in Turner Syndrome after Oocyte Donation: Insufficient Prepregnancy Screening and Pregnancy Follow-Up Are Associated with Poor Outcome

Context: Recombinant human GH treatment and oocyte donation (OD) have improved the quality of life in women with Turner syndrome (TS). However, life expectancy is reduced, mainly due to cardiovascular complications. Pregnancy may itself increase that risk and be associated with hazardous materno-fetal outcome. Objective: The objective of this study was to evaluate the materno-fetal outcome of ongoing pregnancies beyond 20 wk of gestation obtained by OD in TS. Design: This was a multicenter retrospective study including all assisted reproductive technology centers affiliated with the French Study Group for Oocyte Donation. Results: Among 93 patients, only 37.6% were prescreened with echocardiography or thoracic magnetic resonance imaging. Maternal outcome was dominated by 37.8% of pregnancy-associated hypertensive disorders including preeclampsia in 54.8% and severe eclampsia in four patients. Prematurity occurred in 38.3% and was correlated with PAHD (P = 0.01). The frequency of in utero growth retardation was 27.5%. One fetal demise was linked to eclampsia. Two patients died from aortic rupture after cesarean section in a context of aortic root dilatation. Only 40% of pregnancies were associated with an absolutely normal materno-fetal outcome. Conclusions: OD pregnancies in TS who have not been managed following recent specific recommendations were at high risk for maternal death by aortic dissection and for preeclampsia and its complications (fetal distress and in utero growth retardation). These recommendations include previous echocardiography, thoracic magnetic resonance imaging, and overnight blood pressure monitoring associated with a tight follow-up during pregnancy. Until future assessment of these recent recommendations, pregnancies obtained in TS after OD must be still considered as very high-risk pregnancies.