First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study

ObjectivesTo estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women.MethodsWe conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 11⁰ and 13⁶ weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth.ResultsAmong 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log₁₀PlGF MoM, log₁₀AFP MoM and log₁₀UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75–0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%–73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%–37%).ConclusionsThe combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.     

Dalteparin and Low-Dose Aspirin in the Prevention of Adverse Obstetric Outcomes in Women With Inherited Thrombophilia

ObjectiveTo evaluate the benefit of treatment with dalteparin and low-dose aspirin (ASA) in the prevention of obstetric complications in women with inherited thrombophilia.MethodsA retrospective chart review identified women who had had at least one pregnancy complicated by severe early-onset preeclampsia, placental abruption, fetal growth restriction (FGR), or fetal death. The following inherited thrombophilias were included: deficiencies of antithrombin, protein C, or protein S, and mutations of factor V Leiden (G1691A), factor II (G20210A), or methylenetetrahydrofolate reductase C677T.ResultsThe records of 43 women with 110 pregnancies were included in the study. Anticoagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11. Dalteparin alone and ASA alone showed equivalent effects in preventing preeclampsia and FGR. Combined dalteparin and ASA significantly decreased the risk of preeclampsia (odds ratio [OR] 0.80; 95% confidence intervals [CI] 0.70–0.91, P = 0.001) and FGR (OR 0.70; 95% CI 0.60–0.82, P = 0.001).ConclusionData from this retrospective cohort study suggest that combined treatment with dalteparin and ASA decreases the risk of preeclampsia by 20% and the risk of FGR by 30% in women with inherited thrombophilia.     

Effect of early use of low-dose aspirin therapy on late-onset preeclampsia

Objective: Low-dose aspirin (LDA) therapy has been found to be effective in preventing the development of early-onset preeclampsia. However, its effect on late-onset preeclampsia has not been described. Our study was aimed at determining if LDA therapy prescribed from early in pregnancy modified the severity of late-onset preeclampsia.

Materials and methods: A retrospective analysis of all women who were screened for early-onset preeclampsia at 11–13⁺⁶ weeks’ gestation between April 2012 and October 2014 at our institution, and who subsequently developed late-onset preeclampsia. The treatment group consisted of women who were prescribed LDA therapy from early in pregnancy as a result of the screening. The control group consisted of women who did not receive LDA therapy.

Results: The aspirin group was associated with earlier delivery at 38.0 (37.5–38.5) weeks’ gestation versus 39.0 (38.7–39.4) weeks’ gestation for the nonaspirin group (p?p?p?=?.62]. No other significant difference was noted.

Conclusions: There was no difference in the clinical severity of late-onset preeclampsia between women screened as high risk for early-onset preeclampsia and subsequently prescribed LDA during their pregnancy, compared to women found to be at low risk and not prescribed LDA.     

Transabdominal uterine artery Doppler between 11 and 14 weeks of gestation for the prediction of outcome in high-risk pregnancies

Objective.?To assess the value of early transabdominal uterine artery Doppler ultrasound for the prediction of gestational outcomes in pregnancies at high risk for preeclampsia.

Methods.?This was an observational study. Doppler ultrasound of the uterine arteries at 11–14 weeks of gestation was performed in 76 women at high risk for preeclampsia. Abnormal uterine Doppler was defined by the presence of bilateral notching or by a mean resistance index (RI) >0.80. Adverse outcomes evaluated were preeclampsia, fetal growth restriction, placental abruption, intrauterine death, and complications requiring delivery before 34 weeks of gestation.

Results.?Among 76 women, 30 (39%) had abnormal uterine Doppler and 46 (61%) had normal Doppler waveform configuration and RI. Abnormal uterine flow was related to a significantly higher incidence of preeclampsia (17% vs. 0%; p = 0.0041), fetal growth restriction (27% vs. 0%; p = 0.0002), intrauterine death (13% vs. 0%; p = 0.0109), and iatrogenic preterm delivery (20% vs. 2%; p = 0.0086). When the Doppler was normal, the negative predictive value for complications requiring delivery before 34 weeks was 98%.

Conclusions.?Normal impedance to flow in uterine arteries between 11 and 14 weeks of gestation is strongly related to a normal pregnancy outcome in women at high risk for preeclampsia.     

Second Trimester Placental Growth Factor Levels and Placental Histopathology in Low-Risk Nulliparous Pregnancies

ObjectivePlacental growth factor (PlGF) levels are lower at delivery in pregnancies with preeclampsia or fetuses small for gestational age (SGA). These obstetrical complications are typically mediated by placental dysfunction, most commonly related to the specific placental phenotype termed placental maternal vascular malperfusion (MVM). The objective of this study was to determine the relationship between PlGF levels in the second trimester and the development of placental diseases that underlie adverse perinatal outcomes.MethodsWe performed a secondary analysis of the prospective Placental Health Study in unselected healthy nulliparous women (n = 773). Maternal demographic data, Doppler ultrasound measurements, and plasma PlGF levels at 15 to 18 weeks gestation were analyzed for association with pregnancy outcomes and placental pathology following delivery.ResultsLow PlGF levels in the second trimester (<10th percentile; <72 pg/mL) was associated with preterm delivery (<37 weeks; 26% vs. 6%, P < 0.001; unadjusted odds ratio (OR) 5.75, 95% CI 3.2–10.5), reduced mean birth weight (2998 vs. 3320 g, P < 0.001), SGA deliveries (25% vs. 11%, P = 0.001; OR 2.6, 95% CI 1.5–4.6), and preeclampsia (7% vs. 2%, P = 0.02; OR 4.3, 95% CI 1.5-12.8) relative to normal PlGF levels (≥10th percentile; ≥72 pg/mL). Low PlGF was associated with lower mean placental weight (447 vs. 471 g, P = 0.01), aberrant cord insertion (25% vs. 12%, P = 0.001) and a pathologic diagnosis of MVM (18% vs. 11%, P = 0.04; OR 1.9, 95% CI 1.01–3.55) but not with other placental pathologies.ConclusionMVM placental pathology and related adverse perinatal outcomes are associated with low PlGF in the early second trimester for healthy nulliparous women.     

Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas

OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at <37 and <35 weeks of gestation, small-for-gestational-age infant, abruptio placentae, and perinatal death. Data were compared by using chi-square analysis and Wilcoxon rank sum test. RESULTS: The rates of preeclampsia and of severe preeclampsia were significantly higher in the previous preeclamptic group as compared to the nulliparous group (17.9% vs 5.3%, P <.0001, and 7.5% vs. 2.4%, P <.0001, respectively). Women who had recurrent preeclampsia experienced more preterm deliveries before 37 and 35 weeks of gestation than nulliparous women who developed preeclampsia. In addition, among women who developed severe preeclampsia, those with recurrent preeclampsia had higher rates of preterm delivery both before 37 weeks (67% vs 33%, P =.0004) and before 35 weeks of gestation (36% vs 19%, P =.041), and higher rates of abruptio placentae (6.7% vs 1.5%) and fetal death (6.7% vs 1.4%) than did nulliparous women. CONCLUSION: Compared to nulliparous women, women with preeclampsia in a previous pregnancy had significantly higher rates of preeclampsia and adverse perinatal outcomes associated with preterm delivery as a result of preeclampsia.     

Outcomes in patients with early-onset fetal growth restriction without fetal or genetic anomalies

Objective: Early-onset fetal growth restriction is associated with poor pregnancy outcomes, but frequently is due to fetal structural or chromosomal abnormalities. The objective of this study was to determine outcomes in patients with early-onset fetal growth restriction without diagnosed fetal or genetic anomalies and to identify additional risk factors for poor outcomes in these patients.

Methods: This was retrospective cohort study of singleton pregnancies in women with early-onset growth restriction defined as a sonographic estimated fetal weight <10% diagnosed between 16–28 weeks’ gestation. We excluded all women with a fetal structural or chromosomal abnormality diagnosed prenatally. Data on pregnancy characteristics and outcomes were collected and analyzed for estimated fetal weight <10% and ≤5%. A nested case-control study within the cohort of patients with ongoing pregnancies was then performed to identify risk factors associated with poor pregnancy outcome using chi-squared test.

Results: One hundred forty-two patients were identified who met inclusion and exclusion criteria and 20 patients were found to have fetal structural or chromosomal abnormalities. In the remaining 122 patients, the incidence of intrauterine fetal demise was 5.7% and there were high rates of preterm birth <37 weeks (20%), birth weight <10% (59.3%), and gestational hypertension (14.1%). Later gestational age at diagnosis and the presence of echogenic bowel and abnormal initial umbilical artery Dopplers were associated with poor pregnancy outcome (22.56 versus 20.86 weeks, p?=?.046), (17.4 versus 2.2%, OR 9.68, 95%CI 1.65–56.73), and (35.3 versus 0%, OR 4.46, 95%CI 2.65–7.50) respectively.

Conclusions: Patients with early-onset fetal growth restriction with no fetal structural or genetic abnormality have a high risk of poor pregnancy outcomes. Gestational age at diagnosis and certain ultrasound findings are associated with poor pregnancy outcome.     

First-Trimester Uterine Artery Doppler for the Prediction of SGA at Birth: The Great Obstetrical Syndromes Study

Objective

To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).

Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes

IntroductionSoluble fms-like tyrosine kinase 1 (sFLT-1) is an anti-angiogenic factor implicated in the pathogenesis of preterm preeclampsia. We evaluated sFLT-1 expression and placental pathology in pregnancies complicated by small for gestational age (SGA) infants (<10th percentile), without evidence of preeclampsia.MethodsClinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas.ResultsNineteen of 69 placentas showed high sFLT-1 expression. The high sFLT-1 group had higher predelivery median systolic blood pressure (BP); 140 (interquartile range (IQR) 133–152) vs. 126 (118–139) mm Hg (p = 0.003), and median diastolic BP; 87 (78–94) vs. 77.5 (71–86) mm Hg (p = 0.02). Abnormal umbilical Doppler abnormalities were more prevalent; 89.5% vs. 46% (p = 0.001). These pregnancies delivered earlier; 31.9 weeks (28.3–34.7 weeks) vs. 37.1 weeks (33.7–38.7 weeks) (p < 0.001), and infants had lower birthweight; 980 grams (520–1545 grams) vs. 2087.5 grams (1455–2340 grams) (p < 0.001). Placental-weight to fetal-weight ratios, a marker of vascular insufficiency, was increased in the high sFlt-1 group: 0.18 (0.14–0.28) vs 0.15 (0.13–0.18), p = 0.03. Placentas with high sFLT-1 showed more decidual vasculopathy; 42.1% vs. 10.0% (p = 0.005), infarction; 36.8% vs. 14.0% (p = 0.048), distal villous hypoplasia; 78.9% vs. 36.0% (p = 0.001), and fetal thrombotic vasculopathy; 47.4% vs. 16.0% (p = 0.01).DiscussionPlacental sFLT-1 expression is upregulated in approximately 28% of non-preeclamptic pregnancies complicated by SGA infants. These pregnancies showed increased placental vascular pathology, more umbilical Doppler abnormalities, and earlier delivery with lower birthweight. A subgroup of non-preeclamptic fetal growth restriction with upregulated sFlt-1 expression may share a common pathogenic pathway with preterm preeclampsia. This subgroup is worthy of additional study.     

睡前口服小剂量阿司匹林预防高危孕妇子痫前期的发生

目的:探讨小剂量阿司匹林对高危孕妇子痫前期及妊娠诱发的高血压综合征的预防作用。方法:将242例存在子痫前期高危因素暴露的孕13~16周的妇女随机分成阿司匹林处理组(n=120,睡前口服75 mg阿司匹林至分娩)和对照组(n=122,安慰剂替代阿司匹林),随访至妊娠结束后2周,记录子痫及妊娠高血压综合征的发生率。结果:本研究中共失访5例,其中阿司匹林组2例,对照组3例。子痫前期的发生率,阿司匹林组低于对照组(18.6%vs 52.9%),其中轻度子痫前期、早发子痫前期、严重子痫前期的发生率阿司匹林组(11.0%、3.4%、4.2%)均低于对照组(26.9%、12.6%、13.4%)。妊娠诱发高血压的发生率(4.2%vs 16.0%)、宫内发育迟缓发生率(13.6%vs 30.3%)、出生孕周<34周的孕妇比例(4.2%vs 13.4%)、37周前分娩的孕妇比例(18.6%vs 40.3%)、流产比例(2.5%vs 10.1%),阿司匹林组均低于对照组。平均出生体质量(2 890±340 g vs 2 611±479 g)、平均出生孕周(36.8±2.0 vs 35.0±3.1),阿司匹林组大于对照组(P<0.05)。阿司匹林组与对照组在新生儿围产期内死亡率(0.8%vs 1.7%)、胎盘早剥率(6.8%vs 5.0%)、阴道分娩率(43.2%vs 40.3%)之间均无统计学差异(P>0.05)。结论:睡前口服小剂量阿司匹林能使子痫前期高危孕妇受益。     

Neonatal outcome after preterm delivery for preeclampsia

Objective: Our purpose was to determine whether maternal preeclampsia per se has a beneficial effect on neonatal outcome after delivery before 35 weeks.Study design: A matched cohort study design was used. Two hundred twenty-three infants of strictly defined preeclampsia women were matched for gestational age, race, gender, and mode of delivery with infants of normotensive women with preterm labor and delivery. Pregnancies with multiple gestation, premature rupture of membranes, known fetal anomalies, diabetes, or maternal medical disease were excluded. Information was obtained by review of maternal and neonatal charts. Paired categoric and continuous data were compared by McNemar's test and the Wilcoxon signed-rank test, respectively.Results: There was no difference in the incidence of neonatal death (4.5% vs 4.5%, p = 0.82), respiratory distress syndrome (22.0% vs 22.0%, p = 0.88), grades 3 and 4 intraventricular hemorrhage (2.2% vs 2.2%, p = 0.72), grades 2 and 3 necrotizing enterocolitis (5.8% vs 4.0%, p = 0.48), and culture-proved sepsis (9.0% vs 9.0%, p = 0.85). Results were similar when analysis was limited to infants born at ≤ 32 weeks, infants born to mothers with severe preeclampsia, and infants with intrauterine growth restriction.Conclusion: Maternal preeclampsia per se does not have a beneficial effect on the postnatal course] of infants born at 24 to 35 weeks' gestation.     

Preventing preeclampsia and its fetal complications with low-dose aspirin in East Asians and non-East Asians:A systematic review and meta-analysis

Background: Low-dose aspirin can reduce the incidence of preeclampsia and intrauterine growth restriction (IUGR). However, the effects of ethnicity upon low-dose aspirin’s efficacy has not been analyzed. Here, we comparatively evaluated the efficacy of low-dose aspirin in preventing preeclampsia and related fetal complications in East Asian and non-East Asian pregnant women at risk for preeclampsia. Methods: Several databases were searched for randomized controlled trials (RCTs) comparing low-dose aspirin with either placebo or no treatment in pregnant women at risk for preeclampsia. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for preeclampsia and related fetal outcomes were tabulated. Results: Low-dose aspirin significantly reduced preeclampsia risk in both East Asians (OR = 0.20, 95% CI: 0.11–0.35) and non-East Asians (OR = 0.84, 95% CI: 0.77–0.92). Low-dose aspirin significantly reduced IUGR risk in East Asians (OR = 0.36, 95% CI: 0.20–0.67) but not in non-East Asians (OR = 0.85, 95% CI: 0.41–1.77). Low-dose aspirin did not significantly reduce the risk of cesarean section in either East Asians (OR = 0.67, 95% CI: 0.14–3.22) or non-East Asians (OR = 1.01, 95% CI: 0.86–1.19). Conclusions: Low-dose aspirin is effective in reducing preeclampsia risk in both East Asians and non-East Asians and has differential effects in East Asians and non-East Asians with respect to IUGR.     

Screening for adverse perinatal outcomes: uterine artery Doppler,cerebroplacental ratio and estimated fetal weight in low-risk women at term

Objective: To stratify apparently low-risk pregnant women into those who are at risk of adverse perinatal outcomes. Appropriate stratification would allow targeted prenatal and intrapartum management.

Methods: This prospective, observational study included normotensive women with appropriately grown, non-anomalous, singleton pregnancies. Participants underwent fortnightly ultrasounds from 36 weeks’ gestation and intrapartum and neonatal outcomes were recorded. The association between uterine artery pulsatility index (UtA-PI), the cerebroplacental ratio (CPR) and estimated fetal weight (EFW) were explored along with their screening performance for CS-IFC and CNM.

Results: The final cohort included 429 women. As continuous variables, UtA-PI and the CPR were not correlated (rho?=??0.05, p?=?.33). UtA-PI >95^th centile and the CPR <10^th centile were predictive of CS-IFC and CNM, with the highest sensitivity achieved by their combination (33.3%, 95% CI 11.6–55.1) for a false positive rate (FPR) of 15.8% (12.3–19.3). For CNM, the highest sensitivity (28.4%, 95% CI 18.6–38.2) and corresponding FPR (17.0%, 95% CI 13.0–20.9) was achieved by combining UtA-PI 95^th centile, the CPR 10^th centile and EFW 10^th centile. EFW was the weakest of the three predictors.

Conclusion: In this population, UtA-PI 95^th centile and the CPR 10^th centile have modest screening performance for CS-IFC and CNM.     

Utility of Head/Abdomen Circumference Ratio in the Evaluation of Severe Early-Onset Intrauterine Growth Restriction

ObjectiveTo determine whether the predominant phenotype of intrauterine growth restriction (IUGR) is symmetric or asymmetric in severe, early-onset disease due to placental insufficiency.MethodsWe conducted a retrospective chart review of high-risk pregnant women with severe, early-onset IUGR who were delivering at < 33+0 weeks’ gestation at Mount Sinai Hospital from 2001 to 2010. Ultrasound images were reviewed for fetal biometry, amniotic fluid volume, and uterine and umbilical Doppler flow studies within seven days of delivery, and the frequency of head circumference/abdominal circumference ratio ≥ 95th percentile for gestation was determined.ResultsSixty-two of 107 pregnancies (58%) with early-onset IUGR had an elevated HC/AC ratio (≥ 95th percentile), which was more than 10-fold greater than the expected proportion (P < 0.001). High rates of severe preeclampsia (53%), abnormal amniotic fluid (70%), and abnormal uterine artery Doppler studies (78%) indicated placental insufficiency.ConclusionFetuses with severe placental IUGR in the second trimester are more likely to have an asymmetric phenotype. This is in contrast to the current belief that asymmetric IUGR is confined to third trimester IUGR.     

The association between maternal pre-pregnancy body mass index and pregnancy outcomes of preeclampsia

ObjectiveTo evaluate the effects of pre-pregnancy maternal body mass index (BMI) to pregnancy outcomes in patients diagnosed as preeclampsia.Materials and methodsThis was a retrospectively study on women who had been diagnosed as preeclampsia and delivered at Seoul National University Bundang Hospital between June 2017 and March 2020. Multifetal gestation, major fetal anomaly, and fetal death in utero were excluded. A total of 150 singleton pregnancies were included and divided into four groups according to the pre-pregnancy BMI classification: underweight (<18.5 kg/m², n = 6), normal (18.5–22.9 kg/m², n = 66), overweight (23.0–24.9 kg/m², n = 26), and obese (≥25.0 kg/m², n = 52). Pregnancy outcomes including gestational age at delivery, birthweight, and delivery modes were reviewed.ResultsThe rates of preterm birth before 34 weeks of gestation were 67%, 49%, 35%, and 27% for underweight group, normal BMI group, overweight group, and obese group, respectively (p-trend = 0.006). The birthweight of newborn increased significantly as pre-pregnancy BMI increased (p-trend<0.001). The proportions of small for gestational age (SGA) were highest in underweight group and decreased as pre-pregnancy BMI increased (67%, 41%, 42%, and 10% for each group, respectively, p-trend<0.001).ConclusionThe rates of preterm birth before 34 weeks and SGA increased as pre-pregnancy BMI decreased in patients with preeclampsia.Implications for practiceWomen with underweight before pregnancy are at the highest risk for preterm birth and SGA, therefore they need to be monitored more intensively when diagnosed as preeclampsia.     

Impact of early supplementation with low-dose aspirin on functional first trimester parameters in low-risk pregnancies

Introduction: There is recent evidence that prophylaxis with 150?mg of aspirin given before 14–16 weeks significantly reduces preeclampsia rates and may improve pregnancy outcome. We conducted an observational study that investigates the effect of low-dose aspirin initiated early in pregnancy or in preconception on functional parameters assessed at 11–14 weeks.

Materials and methods: We have retrospectively selected 128 pregnant women that presented for the first trimester screening for aneuploidies between 11⁺⁰ and 13⁺⁶ weeks of gestation and received low-dose aspirin before 14 weeks. We excluded cases with an estimated high risk for early preeclampsia (cut-off?>?1:100). This group was matched to 1044 cases that did not receive aspirin in early pregnancy. We have selected for statistical analysis maternal parameters, ultrasound parameters (crown-rump length, nuchal translucency thickness, pulsatility index in uterine arteries – left, right, average and average uterine PI expressed in multiple of median (MoM)), first trimester maternal biochemical markers (free β hCG and PAPP-A expressed in MoM), and the calculated risk for early onset and late onset preeclampsia.

Results: The most common dosages of aspirin were 75?mg (77 cases) and 100?mg (32 cases). The most significant results are within the aspirin group. In the subgroup that received aspirin before 11 weeks (110 cases), irrespective of the dosage, the uterine blood flow is significantly improved (average uterine PI 1.7 compared with 2.22, p?p?>?.05, [(?0.65)???0.02] 95% CI). The estimated risk for both early and late onset preeclampsia in this group is reduced (1:2141 compared with 1:333 for early preeclampsia, p?p?Conclusion: Even though the results are not always statistically significant, they demonstrate that placentation parameters improve with higher doses of aspirin started before 11 weeks.     

Effects of calcium,magnesium, low-dose aspirin and low-molecular-weight heparin on the release of PP13 from placental explants

BackgroundPreeclampsia is one of the leading causes for maternal and fetal morbidity. Attempts to prevent preeclampsia have already been made using low-dose aspirin, low-molecular-weight heparin (LMWH), and calcium supplementation. Magnesium sulphate is used at the time of disease to prevent eclampsia. Here we investigated the effect of these agents on PP13 release from placental explants.MethodsPlacentas harvested after C-section of term or preterm control and preeclampsia cases or first trimester terminations were used to obtain explants. Explants were incubated for 24 h with/without respective agents, harvested, weighed and subjected to PP13 determination in the culture medium and the explant. LDH was used to determine viability. Dose response curves were obtained for each drug. P < 0.05 was considered significant.ResultsExposure to magnesium (0.7–7 g/day) slightly decreased PP13 release from controls, and slightly increased it in preeclampsia and first trimester termination. Calcium (0. 3–6 g/day) showed a tendency to decrease the release in control and preeclampsia, whereas in first trimester release was increased in a bell-shaped manner. Aspirin (0–250 mg/day) tended to decrease the release in controls but increased it in a bell-shaped manner in first trimester and preeclampsia. LMWH showed no effect from 0 to 80 mg/day in controls but tended to decrease PP13 release in preeclampsia and first trimester.ConclusionThis data might point to a beneficial effect of aspirin and calcium supplementation in the first trimester of pregnancy and aspirin at the time of disease, although the interaction with the maternal system still needs to be elucidated.     

Expectant management of severe preterm preeclampsia: a comparison of maternal and fetal indications for delivery

Objective: To examine the delivery indication (maternal or fetal) for patients with preterm preeclampsia and assess whether disease characteristics at presentation are predictive of delivery indication.

Methods: We conducted a retrospective cohort study at a tertiary hospital in Melbourne, Australia (Mercy Hospital for Women). We assessed indication for delivery for participants presenting with preeclampsia from 23⁺⁰ to 32⁺⁶ weeks gestation. We compared baseline disease characteristics, disease features at delivery and postnatal outcomes between those delivered for maternal or fetal indications, or for both maternal and fetal indications.

Results: Two hundred sixty six participants presented with preterm preeclampsia and 108 were eligible for inclusion in our study. More participants were delivered for maternal indications at 65.7% compared to those requiring delivery on fetal grounds at 19.4% or for both indications at 14.8% (p?<?0.0001). Maternal disease characteristics at presentation were similar between groups; however, there was a higher proportion of growth restriction and abnormal Dopplers among those delivered on fetal grounds. Participants delivered on maternal grounds gained less gestation, had higher blood pressure and higher incidence of abnormal liver function tests than those delivering for fetal indications at delivery.

Conclusion: Participants with preterm preeclampsia were predominantly delivered due to maternal disease progression compared to fetal compromise.     

Decreased Pathological Placental Findings in Aspirin-Treated Pregnant Women at Risk of Hypertensive Complications

Objective: The small controlled trials reporting large reductions in the incidence of preeclampsia and intrauterine growth restriction (IUGR) in highrisk pregnant women treated with low-dose aspirin have recently been followed by large clinical trials suggesting less beneficial results. The effect of low-dose aspirin on placental lesions associated with preeclampsia and IUGR has not yet been studied.

Methods: We participated in the large multicenter randomized collaborative low-dose aspirin study in pregnancy (CLASP) trial of low-dose aspirin for the prevention and treatment of preeclampsia and intrauterine growth restriction. As part of this study, we evaluated placentae submitted from 25 women treated with aspirin and 28 with placebo.

Results: More of the pathological findings classically described in preeclampsia and IUGR were demonstrated in the placentae from the placebo group than from the aspirin group (54% vs. 16%, P = 0.02). The placental findings did not correlate with clinical pregnancy outcome or Doppler flow parameters of the fetal umbilical artery in either group.

Conclusions: Our results support the assumption that aspirin may have some inhibitory effect on the uteroplacental circulatory ischemic changes typically occurring in preeclampsia and IUGR.