Prior Preeclampsia Research Articles

Intraabdominal fat, insulin sensitivity, and cardiovascular risk factors in postpartum women with a history of preeclampsia

Women who develop preeclampsia have a higher risk of future cardiovascular disease and diabetes compared to women who have uncomplicated pregnancies. We hypothesized that women with prior preeclampsia would have increased visceral adiposity that would be a major determinant of their metabolic and cardiovascular risk factors. We compared intraabdominal fat (IAF) area, insulin sensitivity index (SI), fasting lipids, low-density lipoprotein relative flotation rate, and brachial artery flow-mediated dilatation in 49 women with prior preeclampsia and 22 controls who were at least 8 months postpartum and matched for age, parity, body mass index, and months postpartum. Women were eligible if they did not smoke tobacco, use hormonal contraception, have chronic hypertension, or have a history of gestational diabetes. The groups were similar for age (mean ± SD: prior preeclampsia 33.4 ± 6.6 vs control 34.6 ± 4.3 years), parity (median: 1 for both), body mass index (26.7 ± 5.9 vs 24.0 ± 7.3 kg/m(2)), and months postpartum (median [25th-75th percentile]: 16 [13-38] vs 16.5 [13-25]). There were no significant differences in IAF area and SI. Despite this, women with preeclampsia had lower high-density lipoprotein (46.0 ± 10.7 vs 51.3 ± 9.3 mg/dL; P < .05), smaller/denser low-density lipoprotein relative flotation rate (0.276 ± 0.022 vs 0.289 ± 0.016; P = .02), higher systolic (114.6 ± 10.9 vs 102.3 ± 7.5 mm Hg) and diastolic (67.6 ± 7.5 vs 60.9 ± 3.6 mm Hg; P < .001) blood pressures, and impaired flow-mediated dilatation (4.5 [2-6.7] vs 8.8 [4.5-9.1] percent change, P < .05) compared to controls. In a subgroup analysis, women with nonsevere preeclampsia (n = 17) had increased IAF (98.3 [60.1-122.2]) vs 63.1 [40.1-70.7] cm(2); P = .02) and decreased SI (4.18 [2.43-5.25] vs 5.5 [3.9-8.3] × 10(-5) min(-1)/pmol/L; P = .035) compared to the controls, whereas women with severe preeclampsia (n = 32) were not different for IAF and SI. IAF was negatively associated with SI and positively associated with cardiovascular risk factors even after adjusting for the matching variables and total body fat. Women with prior preeclampsia have an atherogenic lipid profile and endothelial dysfunction compared to matched control subjects despite having similar adiposity and insulin sensitivity, suggesting that there are mechanisms separate from obesity and insulin resistance that lead to their cardiovascular risk factors. Visceral adiposity may have a role in contributing to these risk factors in the subgroup of women who have preeclampsia without severe features.

Prediction of small-for-gestational-age neonates: screening by fetal biometry at 35-37 weeks.

To investigate the value of fetal biometry at 35-37 weeks' gestation in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE). This was a screening study in singleton pregnancies at 35-37 weeks' gestation, comprising 278 that delivered SGA neonates with a birth weight < 5th percentile and 5237 cases unaffected by SGA, PE or gestational hypertension. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors and Z-scores of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) or estimated fetal weight (EFW) had a significant contribution to the prediction of SGA neonates. Multivariable logistic regression analysis demonstrated that the likelihood of delivering a SGA neonate with a birth weight < 5th percentile decreased with maternal weight and height, and in parous women the risk increased with a longer interpregnancy interval. The risk was higher in women of Afro-Caribbean and South Asian racial origins, in cigarette smokers, nulliparous women and in those with history of SGA, with or without prior PE. Combined screening by maternal characteristics and history with EFW Z-scores at 35-37 weeks predicted 89% of SGA neonates with birth weight < 5th percentile delivering < 2 weeks following assessment, at a 10% false-positive rate (FPR). The respective detection rate for the prediction of SGA neonates delivering ≥ 37 weeks' gestation was 70%. The performance of screening by a combination of Z-scores of fetal HC, AC and FL was similar to that achieved by the EFW Z-score. Combined testing by maternal characteristics and fetal biometry at 35-37 weeks could identify, at a 10% FPR, about 90% of pregnancies that subsequently deliver SGA neonates within 2 weeks of assessment and 70% of those that deliver ≥ 37 weeks.

Sympathetic Neural Activity During Early Pregnancy in Women with Prior Gestational Hypertension and Preeclampsia

Background Sympathetic overactivity likely plays a role in the primary manifestation of gestational hypertension and preeclampsia, and may contribute to the substantially-elevated risk for recurrence in women with a history of the disorders. We tested the hypothesis that women with a history of hypertensive pregnancy would have augmented neural activity prior to and during the early phase of a subsequent pregnancy. Methods: Healthy women with (HP+; n= 8) and without (CON; n = 8) a history of hypertensive pregnancy were tested prior to (PRE, mid-luteal phase) and during EARLY (4-8 weeks) pregnancy. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, and muscle sympathetic nerve activity (MSNA) were measured during 6 min of supine rest, followed by 6 min of 60° head-up tilt (HUT). Results: There were no group differences in supine or HUT HR, SBP, or DBP at either PRE or EARLY. Supine and HUT MSNA tended to be higher in HP+ compared to CON during PRE (p = 0.098). During EARLY, supine MSNA increased from PRE in both groups (p < 0.001) and tended to be greater in HP+ than CON (28 ± 9 vs. 20 ± 9 bursts·min-1; p = 0.11); however, HP+ women had an attenuated increase in MSNA from supine to HUT (ΔMSNA: 15 ± 7 vs. 26 ± 9 bursts·min-1; p = 0.014). Conclusions Despite similar hemodynamic responses, HP+ women appear to have elevated MSNA at rest but attenuated sympathetic responses to upright tilt during early pregnancy, compared to healthy women. A “ceiling” effect (a reduced sympathetic reserve during tilting) and/or decreased sympathetic baroreflex sensitivity may be the underlying mechanism(s).

5-Methyl-tetrahydrofolate in prevention of recurrent preeclampsia

Objective: To evaluate the efficacy of 5-methyl-tetrahydrofolate (5-MTHF) supplementation in prevention of recurrent preeclampsia.Methods: Retrospective cohort of women who received daily oral 5-MTHF 15 mg supplementation as prophylactic treatment since first trimester for recurrent preeclampsia were compared with women who did not. All asymptomatic singleton gestations with prior preeclampsia (in the previous pregnancy) were included. Women with chronic hypertension were excluded. The primary outcome was the incidence of preeclampsia.Results: Three hundred and three singleton gestation met the inclusion criteria: 157 received 5-MTHF, while 146 did not (control group). Women who received 5-MTHF had a significantly lower incidence of recurrent overall preeclampsia (21.7% versus 39.7%; odds ratio (OR) 0.57, 95% confidence interval (CI) 0.25, 0.69), severe preeclampsia (3.2% versus 8.9%; OR 0.44, 95% CI 0.12–0.97) and early-onset preeclampsia (1.9% versus 7.5%; OR 0.34, 95% CI 0.07–0.87) compared to control. The intervention group delivered about 10 d after the control and had higher birth weight.Conclusion: This retrospective study showed that women with prior preeclampsia who received daily oral 5-MTHF 15 mg supplementation had a significantly lower incidence of overall preeclampsia, severe preeclampsia and early-onset preeclampsia. Randomized controlled trials are needed to confirm our findings.

Early initiation of low-dose aspirin for reduction in preeclampsia risk in high-risk women: a secondary analysis of the MFMU High-Risk Aspirin Study.

Early initiation of low-dose aspirin (LDA) may reduce preeclampsia risk. We sought to determine whether LDA was beneficial when initiated <17w0d, within a trial of high-risk women enrolled <26w0d. Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin study, including women enrolled <17w0d, randomized to LDA (60 mg day(-1)) or placebo with chronic hypertension (CHTN, n=186), diabetes (n=191) or prior preeclampsia (n=146). The primary outcome was preeclampsia at any time in pregnancy, secondary outcomes were early preeclampsia (<34w0d), late preeclampsia (⩾34w), small for gestational age (SGA; neonatal birthweight <10th %) and composite (early preeclampsia or SGA). Outcomes were compared by exact Χ(2)-tests. Baseline characteristics were similar between treatment groups. Aspirin was associated with a lower rate of late-onset preeclampsia ⩾34w (17.36% vs 24.42%, P=0.047), with a 41% reduction in women with CHTN (18.28% vs 31.18%, P=0.041). There were no other significant differences in the outcome. Aspirin initiated <17w0d reduced the risk for late-onset preeclampsia by 29% supporting the practice of early initiation of aspirin in high-risk women.

Placenta previa and the risk of delivering a small-for-gestational-age newborn.

To evaluate whether there is an association between placenta previa and delivery of a small-for-gestational-age (SGA) newborn and to quantify the contribution of individual risk factors for SGA that are associated with placenta previa stratified by maternal parity. A cross-sectional study using the Finnish Medical Birth Register during 2000-2010. All singleton births (N=596,562) were included; major congenital anomalies were excluded. An association between SGA (less than 2 standard deviations below the mean) and placenta previa was modeled by parity-specific unadjusted and adjusted statistical models. Placenta previa complicated 625 of 249,476 singleton births among nulliparous women (2.50/1,000) and 915 of 347,086 singleton births among multiparous women (2.64/1,000). Among nulliparous women, the most common risk factor for placenta previa was in vitro fertilization; placenta previa was not associated with an increased prevalence of SGA controlling for maternal age, smoking, in vitro fertilization, socioeconomic status, and preeclampsia (adjusted odds ratio [OR] 0.81, 95% confidence interval [CI] 0.57-1.17). Among multiparous women, placenta previa was associated with a twofold increased risk of SGA controlling for maternal age, parity, prior preterm birth, prior caesarean delivery, prior SGA newborn, prior preeclampsia, smoking, in vitro fertilization, socioeconomic status, and preeclampsia (adjusted OR 2.08, 95% CI 1.50-2.89). Furthermore, only one-fourth of the association between SGA and placenta previa could be explained by controlling for risk factors clustering with placenta previa among multiparous women. Placenta previa is associated with impaired fetal growth in multiparous but not nulliparous women. II.

The BRAzil MAGnesium (BRAMAG) trial: a randomized clinical trial of oral magnesium supplementation in pregnancy for the prevention of preterm birth and perinatal and maternal morbidity.

BackgroundPreterm birth is the leading cause of infant mortality globally, including Brazil. We will evaluate whether oral magnesium citrate reduces the risk of placental dysfunction and its negative consequences for both the fetus and mother, which, in turn, should reduce the need for indicated preterm delivery.Methods/DesignWe will complete a multicenter, randomized double-blind clinical trial comparing oral magnesium citrate 150 mg twice daily (n = 2000 women) to matched placebo (n = 1000 women), starting at 121/7 to 206/7 weeks gestation and continued until delivery. We will include women at higher risk for placental dysfunction, based on clinical factors from a prior pregnancy (e.g., prior preterm delivery, stillbirth or preeclampsia) or the current pregnancy (e.g., chronic hypertension, pre-pregnancy diabetes mellitus, maternal age > 35 years or pre-pregnancy maternal body mass index > 30 kg/m2). The primary perinatal outcome is a composite of preterm birth < 37 weeks gestation, stillbirth > 20 weeks gestation, neonatal death < 28 days, or SGA birthweight < 3rd percentile. The primary composite maternal outcome is preeclampsia arising < 37 weeks gestation, severe non-proteinuric hypertension arising < 37 weeks gestation, placental abruption, maternal stroke during pregnancy or ≤ 7 days after delivery, or maternal death during pregnancy or ≤ 7 days after delivery.DiscussionThe results of this randomized clinical trial may be especially relevant in low and middle income countries that have high rates of prematurity and limited resources for acute newborn and maternal care.Trial registrationClinicalTrials.gov Identifier NCT02032186, registered December 19, 2013.

Prediction of preeclampsia utilizing the first trimester screening examination

To derive a prediction rule for preeclampsia and early onset preeclampsia requiring delivery <34 weeks using first trimester maternal, ultrasound, and serum markers. Prospective cohort study of women enrolled at first trimester screening. Maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women with preeclampsia and normal outcome. The prediction rule was derived by Lasso logistic regression analysis. In 2441 women, 108 (4.4%) women developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log pregnancy-associate pregnancy protein-A multiples of the median were primary risk factors. Prediction rules for preeclampsia/early preeclampsia had an area under the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49% sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive rate. First trimester prediction rules using parameters currently available at first trimester screening identify a significant proportion of women with subsequent preeclampsia.

Implications of sleep-disordered breathing in pregnancy

The objective of the study was to examine the relationship between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort. This was a planned analysis of a prospective cohort designed to estimate the prevalence and trends of SDB in high-risk pregnant women. We recruited women with a body mass index of 30 kg/m(2) or greater, chronic hypertension, pregestational diabetes, prior preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea hypopnea index of 5 or greater and further grouped into severity categories: mild SDB (5-14.9), moderate SDB (15-29.9), and severe SDB (≥30). Pregnancy outcomes (preeclampsia, gestational diabetes, preterm birth, infant weight) were abstracted by physicians blinded to the SDB results. Of the 188 women with a valid early pregnancy sleep study, 182 had complete delivery records. There was no relationship demonstrated between SDB exposure in early or late pregnancy and preeclampsia, preterm birth less than 34 weeks, and small-for-gestational-age (<5%), or large-for-gestational-age (>95%) neonates. Conversely, SDB severity in early pregnancy was associated with the risk of developing gestational diabetes (no SDB, 25%; mild SDB, 43%; moderate/severe SDB, 63%; P= .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8). This study suggests a dose-dependent relationship between SDB in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight were demonstrated.

263: Longitudinal changes in cerebral blood flow and brain structure in healthy nulliparous women (NP) and those with prior preeclampsia (PRE)

263: Longitudinal changes in cerebral blood flow and brain structure in healthy nulliparous women (NP) and those with prior preeclampsia (PRE)

First trimester maternal characteristics, Doppler parameters and serum analytes after preeclampsia

Objective: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy. Methods: A total of 1283 parous patients were prospectively enrolled at 9–14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia. Results: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors. Conclusion: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.

Risk of future cardiovascular disease in women with prior preeclampsia: a focus group study

BackgroundA history of preeclampsia is a risk factor for the future development of hypertension and cardiovascular disease (CVD). The objective of this study was to assess, in women with prior preeclampsia, the level of knowledge regarding the link between preeclampsia and CVD, motivators for and barriers to lifestyle change and interest in a lifestyle modification program to decrease CVD risk following a pregnancy complicated by preeclampsia.MethodsTwenty women with a history of preeclampsia participated in 5 phone-based focus groups. Focus groups were recorded, transcribed, and analyzed. Qualitative content analysis was used to identify common themes across focus groups. Consensus was reached on a representative set of themes describing the data.ResultsWomen with prior preeclampsia were in general unaware of the link between preeclampsia and future CVD but eager to learn about this link and motivated to achieve a healthy lifestyle. Major perceived barriers to lifestyle change were lack of time, cost of healthy foods and family responsibilities. Perceived facilitators included knowledge of the link between preeclampsia and CVD, a desire to stay healthy, and creating a healthy home for their children. Women with prior preeclampsia were interested in the idea of a web-based program focused on lifestyle strategies to decrease CVD risk in women.ConclusionsWomen with prior preeclampsia were eager to learn about the link between preeclampsia and CVD and to take steps to reduce CVD risk. A web-based program to help women with prior preeclampsia adopt a healthy lifestyle may be an appropriate strategy for this population.

Recurrence of Preeclampsia in Northern Tanzania: A Registry-Based Cohort Study

ObjectivePreeclampsia occurs in about 4 per cent of pregnancies worldwide, and may have particularly serious consequences for women in Africa. Studies in western countries have shown that women with preeclampsia in one pregnancy have a substantially increased risk of preeclampsia in subsequent pregnancies. We estimate the recurrence risks of preeclampsia in data from Northern Tanzania.MethodsA prospective cohort study was designed using 19,811 women who delivered singleton infants at a hospital in Northern Tanzania between 2000and2008. A total of 3,909 women were recorded with subsequent deliveries in the hospital with follow up through 2010. Adjusted recurrence risks of preeclampsia were computed using regression models.ResultsThe absolute recurrence risk of preeclampsia was25%, which was 9.2-fold (95% CI: 6.4 - 13.2) compared with the risk for women without prior preeclampsia. When there were signs that the preeclampsia in a previous pregnancy had been serious either because the baby was delivered preterm or had died in the perinatal period, the recurrence risk of preeclampsia was even higher. Women who had preeclampsia had increased risk of a series of adverse pregnancy outcomes in future pregnancies. These include perinatal death (RR= 4.3), a baby with low birth weight (RR= 3.5), or a preterm birth (RR= 2.5). These risks were only partly explained by recurrence of preeclampsia.ConclusionsPreeclampsia in one pregnancy is a strong predictor for preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies in Tanzania. Women with previous preeclampsia may benefit from close follow-up during their pregnancies.

Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women

Objective: Chronic hypertension, pregestational diabetes mellitus, history of prior preeclampsia and obese nulliparity are maternal conditions associated with increased preeclampsia risk. Whether altered maternal angiogenic factor levels allow for prediction of pending disease is unclear. Our objective was to evaluate angiogenic factors for early preeclampsia prediction in high-risk women.Methods: Serial serum specimens were collected from 157 women at high preeclampsia risk and 50 low-risk controls between 23 and 36 weeks gestation in 3 windows (23–27.6, 28–31.6, and 32–35.6 weeks) in a two-center observational cohort. Soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) were measured by ELISA.Results: Multivariate parsimonious logistic regression analyses using backward elimination for prediction of early-preeclampsia (diagnosed < 34 weeks) found the best-fitting model included the predictors (1) sFlt1 measured in the second window (28–31.6 weeks) with AUC 0.85, sensitivity 67% and specificity 96% and (2) sFlt1 measured in the first window (23–27.6 weeks) and sEng change between first and second window with AUC 0.91, sensitivity 86% and specificity 96%.Conclusions: Two-stage sampling screening protocol utilizing sFlt1 and sEng is promising for prediction of preeclampsia diagnosed before 34 weeks. Larger studies are needed to confirm these findings.

A History of Prior Preeclampsia As a Risk Factor for Preterm Birth

The objectives of this study are to evaluate the frequency and type of preterm birth (PTB) in women with prior preeclampsia and to compare neonatal outcomes between spontaneous PTB (SPTB) and medically indicated PTB (IPTB) groups. A secondary analysis of data in women with prior preeclampsia enrolled in a multicenter randomized trial for preeclampsia prevention. Delivery indications were categorized as SPTB and IPTB. Primary outcomes were rates of SPTB and IPTB by gestational age (GA). The rates of composite respiratory morbidity and neonatal intensive care unit (NICU) admission were compared between the PTB groups. Of the 606 pregnancies studied, 142 (23%) pregnancies were delivered at < 37 weeks: 67 (47%) pregnancies were caused by SPTB and 75 (53%) pregnancies were caused by IPTB. Of those who delivered preterm, 89 (63%) were in the late preterm period. The overall rate of the composite neonatal morbidity was 23%. The rates of composite neonatal morbidity, NICU admission, and perinatal death were not different between the groups. The frequency of small for gestational age (SGA) infants was higher in the IPTB group as compared with the SPTB group (21.3 vs. 1.4%, p = 0.01). Women with prior preeclampsia are at high risk for PTB (SPTB and IPTB), particularly late PTB, as well as increased risk for SGA.

Gestational angiogenic biomarker patterns in high risk preeclampsia groups

Several conditions are associated with increased preeclampsia (PE) risk. Whether altered maternal angiogenic factor levels contribute to risk in these conditions is unknown. Our objective was to compare angiogenic biomarker patterns in high-risk pregnancies and low-risk controls. We conducted a planned secondary analysis of a 2-center observational study of angiogenic biomarkers in high-risk women. A total of 156 pregnant women with a PE risk factor and 59 low-risk controls were studied. Serial maternal serum samples were collected during 3 gestational windows: 23-27 weeks, 28-31 weeks, and 32-35 weeks. Soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay. Geometric mean angiogenic biomarker levels and angiogenic ratio (sFlt1+ sEng):PlGF were compared with low-risk controls for each risk group, at each gestational window. Gestational biomarker patterns differed in PE risk groups as compared with low-risk controls. Women with multiple gestations had markedly higher sFlt1 and sEng at all gestational windows. Women with prior PE had higher sFlt1 and angiogenic ratio, and lower PlGF, from 28 weeks onward. Women with chronic hypertension had significantly higher angiogenic ratio for all 3 gestational windows, but differences disappeared when women with PE were excluded. Obese and nulliparous women had significantly lower PlGF, but no differences in the angiogenic ratio. High-risk groups have altered angiogenic biomarker patterns compared with controls, suggesting that altered production or metabolism of these factors may contribute to PE risk, particularly in women with multiple gestations and prior PE.

619: A history of prior preeclampsia is a major risk factor for preterm birth

major risk factor for preterm birth Brendan Connealy, Carlos Carreno, Benjamin Kase, Laura Hart, Sean Blackwell, Baha Sibai University of Texas Health Science Center Houston, Obstetrics, Gynecology, and Reproductive Sciences, Houtson, TX OBJECTIVE: Women with prior preeclampsia are considered at increased risk for adverse pregnancy outcomes (recurrent preeclampsia, fetal growth restriction, abruptio placentae). Limited data exists to describe an association between prior preeclampsia and spontaneous preterm birth (SPTB). Our objective is to evaluate the frequency of SPTB in women with prior preeclampsia and describe neonatal outcomes in these infants compared those with indicated preterm birth (IPTB). STUDY DESIGN: This is a secondary analysis of data in women with prior preeclampsia enrolled in a multicenter randomized trial of low dose aspirin for preeclampsia prevention. Inclusion criteria were women with history of prior preeclampsia, and live fetus. Women with preexisting medical disorders were excluded. Indications for delivery were categorized as SPTB (PTL or PPROM) and IPTB. Primary outcomes were rates of SPTB and IPTB by GA. Composite respiratory morbidity and NICU admission were compared between groups. Chi square and t test were used to establish a difference between the study groups. RESULTS: Of the 606 pregnancies studied, 142 (23%) delivered at 37 weeks. Of those delivered preterm, 47% were due to SPTB and 53% were IPTB. The table below summarizes the frequency of PTB by subtype and GA. There were no significant differences in rates of SPTB or IPTB, or in the rates of composite neonatal morbidity, between the GA groups. There were 14 perinatal deaths (2.3%): of which the majority (13) were at 34 weeks. Additionally, there were no differences in NICU admission between the groups. CONCLUSION: Women with prior preeclampsia have a substantially high rate of preterm birth with almost half being spontaneous and nearly two-thirds occurring in the late preterm. We recommend that prior preeclampsia should be considered a risk factor for both IPTB and SPTB with the potential for early intervention to improve perinatal outcome. 620 Timing of adverse neonatal outcomes in pregnancies complicated by preeclampsia and small for gestational age births in a cohort of high-risk pregnancies Cande Ananth, Jaclyn Coletta-Lucas, Ronald Wapner Columbia University Medical Center, Department of Obstetrics and Gynecology, New York, NY OBJECTIVE: In a group of high-risk women with underlying medical conditions predisposing to preeclampsia and small for gestational age (SGA), the timing of delivery is often based on a worsening maternal condition. We evaluated the risk of adverse neonatal outcomes in early intervention compared to spontaneous delivery. STUDY DESIGN: We performed a secondary analysis of data from the Maternal-Fetal Medicine Units network of a randomized controlled trial of aspirin to prevent preeclampsia in high-risk women (those with chronic hypertension, insulin-dependent diabetes mellitus and women with previous preeclampsia). The trial resulted in no benefit of aspirin on the risk of preeclampsia. We examined risks of adverse composite neonatal outcomes (perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, patent ductus arteriosus, pulmonary hypertension, neonatal seizures, admission to the neonatal intensive care unit and 5-minute Apgar 5) in relation to preeclampsia and small for gestational age (SGA, birthweight 10% for gestational age). Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression models after adjusting for potential confounders. RESULTS: Of the 1,787 women in the high-risk trial, the overall risk of composite neonatal outcome was 29.3%. The risk of composite outcome was higher in the SGA-only and preeclampsia (with or without SGA) groups, but this association was evident only at preterm gestations (Table). Among infants that were SGA (only), the risk of neonatal morbidity was dramatically higher among women that had a spontaneous rather than indicated preterm birth. CONCLUSION: In a group of women at high-risk for preeclampsia, appropriately timed obstetrical interventions at preterm gestations, relative to spontaneous preterm birth, is associated with reduced risk of neonatal morbidity.

Pre-eclampsia and pregnancy-induced hypertension are associated with severe diabetic retinopathy in type 1 diabetes later in life

To investigate whether pre-eclampsia (PE) or pregnancy-induced hypertension (PIH) predicts the development of severe diabetic retinopathy (SDR) in type 1 diabetes. Altogether, 203 women with type 1 diabetes who were followed during pregnancy were re-examined within the Finnish Diabetic Nephropathy Study. After excluding patients with pre-pregnancy hypertension and those who had had laser treatment or whose retinopathy was graded as proliferative at the index pregnancy, 158 were prospectively studied. As a surrogate marker for SDR, retinal laser photocoagulation was used. The time from pregnancy to SDR (N=21) or follow-up was 16years (interquartile range, 11-19). HbA1c was repeatedly measured both during pregnancy and follow-up. Women with prior PE (26% vs. 6%, P=0.003) or PIH (24% vs. 6%, P=0.008) had more often incident SDR during follow-up compared to those with normotensive pregnancy. The hazard ratios (HR) remained associated with the progression to SDR after adjustment for duration of diabetes and diabetic nephropathy in a Cox regression analysis [PE: 3.5 (95% CI 1.1-10.9); P=0.03 and for PIH: 3.2 (1.1-9.8); P=0.04]. The association between PIH and incident SDR did not change after inclusion of mean HbA1c, measured during pregnancy (all 3 trimesters) and serial HbA1c measurements during follow-up, 3.5 (1.1-11.8; P=0.03). However, in a similar model, the HR for PE was no more significant 2.0 (0.6-6.8; P=NS). The results suggest that women with type 1 diabetes and a hypertensive pregnancy have an increased risk of severe diabetic retinopathy later in life.

OP09.04: Maternal ophthalmic artery Doppler: novel parameter to predict early‐onset pre‐eclampsia in the first trimester of pregnancy

Objectives: To evaluate the utility of sequential measurement of the uterine artery (UtA) resistances in both the 11–14 weeks scan (1T) and the 19–22 weeks scan (2T) for the prediction of preeclampsia (PE) in a high-risk population. Methods: Prospective observational study of 155 singleton pregnancies at high risk for PE (at least having one major risk factor: prior PE, chronic hypertension, pregestational diabetes mellitus, chronic renal disease, BMI >30, autoimmune disorders or thrombophilia). Pregnancies with abnormal karyotype or incomplete outcome were excluded. Measurement of mean UtA pulsatility index (UtA-PI) was performed at 1T and 2T and statistical comparisons were established between unaffected gestations and those who developed either late PE (gestational age at delivery ≥34 weeks) or early PE ( 1.8 in the 2T developed PE (2 late, 4 early) (OR 13.9; 95% CI 3.2–59.8), and 5/14 (36%) pregnancies with mean UtA-PI in the 2T > mean UtA-PI in the 1T developed PE (2 late, 3 early) (OR 8.2; 95% CI 2.1–33.0). Conclusions: When applied to high-risk women, UtA Doppler screening proved to be ineffective for the prediction of late PE and showed a modest performance for the prediction of early PE, especially in the 1T. However, very high UtA resistances in the 2T as well as the increase of the UtA resistances between 1T and 2T are associated with a highly increased risk of developing PE in high-risk women. OP09.04 Maternal ophthalmic artery Doppler: novel parameter to predict early-onset pre-eclampsia in the first trimester of pregnancy

Bloody mess

Women with positive antiphospholipid antibodies may present with severe preeclampsia, fetal growth restriction (FGR), fetal demise, and recurrent miscarriage.1Ziakas P.D. Pavlou M. Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss A systematic review and meta-analysis.Obstet Gynecol. 2010; 115: 1256-1262Crossref PubMed Scopus (137) Google Scholar, 2Branch D.W. Silver R.M. Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way.Lupus. 2010; 19: 446-452Crossref PubMed Scopus (28) Google Scholar In addition, these women are at increased risk of arterial and venous thrombosis.3American College of Obstetricians and GynecologistsACOG practice bulletin no. 118.Antiphospholipid syndrome. January 2011; Google Scholar As a result, testing for these antibodies is increasing in women with such complications and those with positive tests for lupus anticoagulant, anticardiolipin, or anti-B2 glycoprotein I are considered to have the antiphospholipid antibody syndrome (APS). Once APS is diagnosed, the essential question is whether any treatment, beyond counseling and close observation in subsequent pregnancy, is necessary. During the past 2 decades, several authors suggested using heparin with or without aspirin to improve pregnancy outcome in women with APS.2Branch D.W. Silver R.M. Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way.Lupus. 2010; 19: 446-452Crossref PubMed Scopus (28) Google Scholar, 3American College of Obstetricians and GynecologistsACOG practice bulletin no. 118.Antiphospholipid syndrome. January 2011; Google Scholar There are no randomized trials evaluating the benefits of such therapy in women with prior severe preeclampsia, FGR, or fetal demise. There are 9 randomized or pseudorandomized trials evaluating heparin with aspirin, aspirin alone, or a placebo in patients with recurrent miscarriage and APS. The results of these trials are inconsistent.4Miyakis S. Lockshin M.D. Atsumi T. et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome.J Thromb Haemost. 2006; 4: 295-306Crossref PubMed Scopus (4921) Google Scholar Of interest, the rate of live birth in the placebo subjects (n = 28) ranged from 85% to 100%; in the aspirin-only subjects (n = 207), the rate was 42-90%; in the unfractionated heparin-plus-aspirin subjects (n = 113), the rate was 31-85%; and in the low-molecular-weight heparin-plus-aspirin subjects (n = 111), it was 69-84%. In 2006, the laboratory criteria for APS have been revised,5Laskin C.A. Spitzer K.A. Clark C.C. et al.Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled Hep ASA trial.J Rheumatol. 2009; 36: 279-287Crossref PubMed Scopus (271) Google Scholar and thus, there are currently no randomized trials evaluating the benefits of heparin and aspirin in women with recurrent miscarriage and true APS. A recent American College of Obstetricians and Gynecologists practice bulletin on APS does not support screening for anticardiolipin antibodies in patients with severe preterm preeclampsia or FGR but recommends screening those patients with 1 fetal loss or 3 or more recurrent embryonic losses. It also recommends the prophylactic use of heparin and aspirin in subsequent pregnancies in such women. However, such recommendation is not evidence based. Because the potential benefits of treatment are uncertain, screening such women is very costly and is associated with anxiety, and treatment is associated with side effects that can be severe. At present, data from relevant literature suggest that the association of anticardiolipin antibodies with recurrent miscarriage and placental insufficiency is weak at best. There are no evidence-based studies to indicate that treatment with prophylactic doses of heparin plus aspirin are beneficial. Thus, there is an urgent need for a multicenter trial with adequate sample size. Such trials will hopefully provide conclusive evidence-based treatment to replace recommendations based on personal bias.