Pregnancy complications in women with inherited thrombophilia

Objective: The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications. Methods: All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000–2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Results: Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9–10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5–16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3–10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4–15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90–10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age. Conclusion: Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.     

Obstetric implications of fetal inherited thrombophilia in thrombophilic women

ObjectivesThe relationship between fetal thrombophilic polymorphism and adverse pregnancy outcomes is still unclear. The aim of this study is to evaluate if fetal thrombophilia may affect obstetric and perinatal outcomes in thrombophilic women.Study designFrom 2007 to 2011 all patients with a known inherited thrombophilic mutation consecutively admitted to our labor ward at ⩾25 weeks of gestation with a singleton viable pregnancy were considered eligible for the purpose of the study. At the age of 1 year, the infants were tested for inherited thrombophilic mutations. Patients were then divided into two groups according to the presence or absence of any neonatal mutation.Main outcome measuresThe following outcome variables were then compared between the two groups: gestational age at delivery, birth weight, incidence of hypertensive disorders of pregnancy and SGA neonates.ResultsOverall, 67 pregnancies of 49 women were studied. Among them, the G20210A Prothrombin (32/67 or 47.7%) mutation and the Factor V Leiden mutation (31/67 or 46.3%) were the commonest findings, with a single patient presenting both. A thrombophilic mutation was found in 38 mother–infant pairs. The risk of all maternal and perinatal events including the incidence of hypertensive disorders disorders (5/29 or 17.2% vs 6/38 or 15.7% p = 1.00) and of SGA neonates (3/29 or 10.3% vs 7/38 or 18.4%, p = 0.49) was comparable between the two groups irrespective of the associated fetal thrombophilia.ConclusionsOur data suggest that women with inherited thrombophilia carrying a thrombophilic fetus are not at increased risk of adverse pregnancy outcomes.     

Autophagy in the placenta of women with hypertensive disorders in pregnancy

IntroductionAutophagy has not been studied extensively in the human placenta. This study was performed to determine whether autophagy is increased in the placentas of women with hypertensive disorders in pregnancy compared to normotensive pregnancies.MethodsLC3-II and p62 protein expression were examined by quantitative Western blotting analysis in 40 placentas from women not experiencing labor pains. The 40 placentas were from 13, 8, and 19 women with preeclampsia, gestational hypertension, and normal pregnancy, respectively. Hypertensive disorders in pregnancy included preeclampsia and gestational hypertension.ResultsLC3-II expression was significantly increased, while that of p62 was significantly reduced in 21 placentas of women with hypertensive disorders compared to those with normal blood pressure irrespective of the presence or absence of fetal growth restriction (FGR). LC3-II expression was also significantly increased in 13 placentas of women with preeclampsia irrespective of the presence or absence of FGR.DiscussionThe results of this study suggested that autophagy is active in the placenta of hypertensive disorders even in the absence of FGR.     

Fetal human leukocyte antigen-C and maternal killer-cell immunoglobulin-like receptors in cases of severe preeclampsia

IntroductionThe pathogenesis of preeclampsia may involve inadequate trophoblast invasion caused by excessive inhibition of uterine natural killer cells (uNK) by extravillous trophoblast cells (EVT). This may be the result of a combination of maternal killer-cell immunoglobin-like receptor (KIR) AA genotype and fetal human leukocyte antigen-C2 (HLA-C2) genotype. A few studies have reported a significantly increased frequency of the maternal KIR AA/fetal HLA-C2 combination in cases of preeclampsia compared to controls.MethodsStudy subjects were 259 cases of severe preeclampsia/eclampsia and 259 matched pregnant women without preeclampsia or eclampsia. All pregnancies were singleton pregnancies, and mothers were preferentially primigravidae. Blood samples from women and their newborns were obtained from the Danish National Birth Cohort (DNBC) and the Danish Neonatal Screening Biobank. Significant differences in the frequencies of KIR AA and HLA-C2 between cases and controls were investigated.ResultsNo significant difference was observed between cases and controls in the frequency of maternal KIR AA (OR = 0.86, 95%CI = 0.60–1.23, P = 0.41), neither when the fetus carried an HLA-C2 allele (OR = 0.85, 95%CI = 0.52–1.38, P = 0.51), nor when the fetus carried an HLA-C2 allele more than its mother (OR = 0.75, 95%CI = 0.34–1.64, P = 0.47).ConclusionThe Results show no influence of HLA-C/KIR genetic variation on the risk of severe preeclampsia, contrary to what some previous studies have observed. An explanation could be that severe preeclampsia represents a separate pathological entity compared to mild preeclampsia.     

Is thrombophilia a risk factor for placenta-mediated pregnancy complications?

Purpose

To determine if thrombophilia is a risk factor for placenta-mediated pregnancy complications (PMPC) (i.e., preeclampsia, intrauterine growth restriction (IUGR), placental abruption, intrauterine fetal death and recurrent pregnancy loss).

Methods

A 5-year retrospective cohort study. Ongoing pregnancies in women with an antecedent PMPC with thrombophilia were compared with the pregnancies in similar women without thrombophilia. The main outcome measures were mean birth weight deviations, corrected for gestational age, and recurrence of PMPC. Low-molecular-weight heparin (LMWH) was employed for thromboprophylaxis only. Mann?CWhitney??s, Fisher??s and Chi-square tests were employed for comparison.

Results

PMPC recurred in 10/43 (23?%) in the thrombophilia group and in 7/41 (17?%) in the non-thrombophilia group, P?P?Conclusion Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH.     

Thrombophilic risk factors for placental stillbirth

Objectives

To define the characteristics of placental stillbirth and the possible contribution of thrombophilic risk factors.

Study design

A prospective cohort study was performed. Women diagnosed with antenatal stillbirth (>20 weeks) of singleton pregnancies between 2006 and 2008 were referred postpartum for evaluation. Maternal risk factors, fetal, placental and cord abnormalities, and a detailed thrombophilia screening, including inherited and acquired thrombophilia, were evaluated. Fetal autopsy and placental pathology were encouraged.Placental stillbirth was defined as death of a normally-formed fetus with evidence of intrauterine fetal growth restriction, oligohydramnios, placental abruption and/or histological evidence of placental contribution to fetal death. Pregnancy characteristics and thrombophilia profiles were compared between placental and non-placental stillbirth cases.

Results

Sixty-seven women with stillbirth comprised the study group. Placental stillbirth was evident in 33/67 (49.3%). Significantly more women with placental stillbirth were nulliparous, when compared with non-placental stillbirth women (21/33 vs. 9/34, p = 0.002). Mean gestational age was lower for placental, compared with non-placental stillbirth (31.1 ± 6.1 weeks vs. 33.9 ± 4.8 weeks, p = 0.04), as was birth weight. Thirty-six of the 67 women (53.7%) tested positive for at least one thrombophilia. The prevalence of maternal thrombophilia was higher for placental stillbirth women (63.6%), and even higher (69.6%) for women after preterm (<37 weeks) placental stillbirth. Factor V Leiden and/or prothrombin G20210A mutation were much more prevalent in placental versus non-placental stillbirth women (OR 3.06, 95% CI 1.07-8.7).

Conclusions

Placental stillbirth comprises a unique subgroup with specific maternal characteristics. Maternal thrombophilia is highly prevalent, especially in preterm placental stillbirth. This may have implications for the management strategy in future pregnancies in this subgroup.     

Preeclampsia in Jordan: incidence,risk factors,and its associated maternal and neonatal outcomes

Objectives: To estimate the incidence of preeclampsia among Jordanian pregnant women, determine its risk factors and its associated neonatal morbidity and mortality.

Methods: The study is a part of a comprehensive national study of perinatal mortality that was conducted in Jordan. This study included all women who gave birth in the selected hospitals during the study period. Maternal and medical conditions during pregnancy and neonatal outcomes were compared between women who developed preeclampsia and who did not.

Results: This study included a total of 21,928 women. The overall incidence rate of preeclampsia was 1.3%. Obesity (OR?=?2.6) and high blood pressure (OR?=?11.9) were significantly associated with increasing odds of preeclampsia. The risk of preeclampsia was 2.3 times higher in first pregnancies than that in second or more pregnancies. The rates of low birth weight (LBW) delivery (32.5% vs. 8.3%), and prematurity (30.8% vs. 7%), and the neonatal mortality rate (81 vs. 12 per 1000 live births) were significantly higher among women with preeclampsia.

Conclusions: The overall incidence rate of preeclampsia was 1.3%. Preeclampsia was significantly associated with maternal and neonatal morbidity and mortality as well as increasing vaginal operative delivery, cesarean section, LBW, and birth asphyxia.     

Expectant management of severe preeclampsia with severe fetal growth restriction in the second trimester

ObjectiveWe investigated whether women with severe fetal growth restriction (FGR <5th percentile) associated with severe preeclampsia (PE) occurring in the second trimester are candidates for expectant management.Study designThis is a retrospective study involving 33 women who developed severe PE or superimposed PE in the second trimester and were expectantly managed at a tertiary center. They were divided into groups with and without severe FGR on admission (severe FGR (+) group: 17 women; severe FGR (−) group: 16 women) for comparison of the duration of pregnancy prolongation, major maternal complications, and perinatal outcomes. The data are presented as medians (range) or frequencies (percentage).ResultsThe duration of pregnancy prolongation was 10 days in both groups. Major maternal complications occurred in 5 of 17 women (29.4%) in the severe FGR (+) and 5 of 16 (31.3%) in the severe FGR (−) group, showing very similar incidence rates in the 2 groups. The perinatal survival rates were favorable at 82.4% (14/17) in the severe FGR (+) and 100% (16/16) in the severe FGR (−) group.ConclusionRegarding expectant management of severe preeclampsia occurring in the second trimester, there was no difference in the duration of pregnancy prolongation between the groups with and without severe FGR on admission. Because favorable perinatal outcomes can be expected without compromising maternal safety by prolonging pregnancy as expectant management for severe FGR, it was suggested that women with severe FGR are suitable candidates for expectant management.     

Outcomes in an obstetrical population with hereditary thrombophilia and high tobacco use

Objective: The purpose of this study was to examine birth outcomes in women treated or untreated for thrombophilia during pregnancies affected or not by tobacco exposure.

Methods: This was a retrospective cohort study of consecutive women from a single maternal fetal medicine clinic who delivered between January 2009 and December 2013. We compared birth outcomes by four groups of thrombophilia and smoking combinations and then by treated or untreated groups.

Results: Of the 8889 pregnant women in this study, 113 had thrombophilia and 97 received treatment. Thromboprophylaxis included: low molecular weight heparin, aspirin, unfractionated heparin, folic acid, and combinations of these. Smokers with thrombophilia had significantly higher rates of preeclampsia, intrauterine growth restriction, preterm birth (<37?weeks gestation) and low birth weight (all p?≤?.001). Conversely, this group had significantly lower rates of hemolysis, elevated liver enzymes, low platelet count (HELLP syndrome) and placental abruption. Women with thrombophilia who received thromboprophylaxis had lower rates of adverse birth outcomes, reaching significance for preterm birth?<32?weeks gestation (4.3% versus 21.1%, p?=?.026).

Conclusion: Pregnant women who smoke and have thrombophilia may be more likely to experience adverse birth outcomes and receive more benefit from thromboprophylaxis than their nonsmoking counterparts.     

An assessment of predictive value of the biophysical profile in women with preeclampsia using data from the fullPIERS database

IntroductionPre-eclampsia is associated with increased risk to both the mother and fetus. Effective monitoring of the fetal condition is essential to the management of women with pre-eclampsia. The biophysical profile (BPP) is one monitoring tool available to clinicians.Aims and ObjectivesTo compare the BPP test with cardiotocography/non-stress test (CTG/NST) alone for their ability to predict fetal acidemia at birth or a composite adverse perinatal outcome among women with preeclampsia and to estimate the effect of BPP assessment on mode of delivery and birth outcome.MethodsSecondary analysis of a prospective cohort of women with preeclampsia. The predictive ability of the tests was assessed based on sensitivity, specificity, positive and negative likelihood ratios (LR+, LR?). Women assessed with the BPP were compared with matched controls not assessed with the BPP to determine the odds of Cesarean delivery or adverse perinatal outcomes after adjustment for potential confounders.ResultsFive out of 89 women (5.6%) had an abnormal BPP; 18 out of 89 (20.2%) had an abnormal CTG/NST. Fetal acidemia was diagnosed in 13 fetuses (14.6%); composite adverse perinatal outcome in 68 fetuses/infants (76.4%). Both tests had relatively poor predictive performance for both outcomes (LR+ between 2.50 and 3.90 and LR? between 0.64 and 0.93). Assessment with the BPP was positively associated with fetal acidemia (adjusted OR 4.84; 95% CI 1.33–17.66).ConclusionThe BPP and CTG/NST alone were poor predictors of perinatal outcome in this cohort; multiple tests should be considered when assessing fetal risk in women with preeclampsia.     

Recurrence and severity of abnormal pregnancy outcome in patients treated by low-molecular-weight heparin: a prospective pilot study

Objective: This prospective pilot study assesses the recurrence rate and severity of abnormal pregnancy outcome (APO), excluding early pregnancy complications, in pregnant patients, without acquired thrombophilia, treated by prophylactic doses of low-molecular-weight heparin (LMWH), independently from their congenital thrombophilic condition. Methods: We recruited a cohort of 128 pregnant patients with previous APO; 100 of whom with APO and intrauterine growth restriction (IUGR) and 28 with maternal APO only. LMWH treatment was started at recruitment. Composite cross-over recurrence rate IUGR, gestational hypertension, preeclampsia, help syndrome, abruptio placenta were analyzed. The main outcome measure was severe APOs with iatrogenic delivery ≤ 32 weeks of gestation. Results: Median gestational age at LMWH treatment was 20 weeks. Severe APO decreased in treated pregnancies from 45% to 4% (relative risk = 0.3, confidence interval 95% = 0.2–0.8). This value was not significantly different in thrombophilic and nonthrombophilic patients. When severe and minor complications were analyzed altogether, the recurrence rate was 28%. In patients with APO and fetal growth restriction (FGR) in the index pregnancy, newborn weights were significantly better in the treated pregnancy: 1090 g (1035–1145) vs. 850 g (535–1200), p < 0.01. Conclusions: Prophylactic regimen of LMWH significantly reduced the recurrence rate of severe composite APO in pregnancies affected in the index pregnancy by APO and FGR or small for gestational age newborns. This result was independent from the patients’ inherited thrombophilic conditions.     

Low-Molecular-Weight Heparin for the Prevention of Obstetric Complications in Women with Thrombophilias

Objective. To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications.

Methods. The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy.

Results. Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 ± 5.0 weeks and 1175 ± 590 g, respectively, compared to 37.6 ± 2.3 weeks and 2719 ± 526 g, respectively, in the treated pregnancies (p ≤ 0.001).

Conclusions. This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.     

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.     

Carriers of thrombophilic factor among women with preeclampsia (preliminary report)

The aim of this study was to determine whether inherited thrombophilia increases the risk of mild preeclampsia. Twenty five women who developed mild preeclampsia and 49 controls--women with previous uneventful pregnancies, were tested for factor V Leiden, C677T gene variant of methylenetetrahydrofolate reductase (MTHFR), polymorphism 4G/5G in plasminogen activator inhibitor 1 (PAI 1), polymorphism A1/A2 in platelet glycoprotein IIb/Illa (GIPrllb/llla A1/A2). The higher but not significant prevalence of C677T gene variant and polymorphism A1/A2 in women with preeclampsia compared with controls was found: 32% and 12.2%, respectively for cases and controls for both factors, with OR: 3.37 (95% CI 0.883-13.2), p > 0.05. The values of OR and RR for these two thrombophilic factors show that platelet integrin polymorphisms (GIPrIIb/llla A1/A2) and C677T gene variant might be have an important role for development of preeclampsia. The carriage of FVL was with a very small prevalence in women with preeclampsia (8%) as compared to controls (6,1%), with OR: 1.333 (CI 95% 0.143-10.864), p > 0.05. The similar results were found for carriage of polymorphism 4G/5G in PAI-1: gene, respectively 24% u 18.4% in women with preeclampsia as compared to controls, OR: 1.404 (95% CI 0.374-5.14), p > 0.05. The results are not significant, because of the small group of selected patients. Larger case-control study should be executed for the evaluation of impact of inherited thrombophilic factors in the development of mild preeclampsia.     

Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study

ObjectiveTo determine maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus (SLE).MethodsIn a retrospective cohort study using the Nova Scotia Atlee Perinatal Database, 97 pregnancies in women with SLE, with 99 live births, were compared with 211 355 pregnancies in women without SLE and their 214 115 babies. All were delivered in Nova Scotia between 1988 and 2008.ResultsIn women with SLE, gestational age at birth and mean neonatal birth weight were lower (P < 0.001) than in women without SLE. On bivariate analysis, severe preeclampsia, Caesarean section, newborn resuscitation for > 3 minutes, respiratory distress syndrome, assisted ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, mild to moderate intraventricular hemorrhage, retinopathy of prematurity, and congenital heart block in neonates were significantly more frequent in the women with SLE.Logistic regression analysis identified that having SLE increased the risks of Caesarean section (OR 1.8; 95% CI 1.1 to 2.8, P = 0.005), postpartum hemorrhage (OR 2.4; 95% CI 1.3 to 4.3, P = 0.003), need for blood transfusion (OR 6.9; 95% CI 2.7 to 17, P = 0.001), postpartum fever (OR 3.2; 95% CI 1.7 to 6.1, P = 0.032), small for gestational age babies (OR 1.7; 95% CI 1.005 to 2.9, P = 0.047), and gestational age ≤ 37 weeks (OR 2.1; 95% CI 1.3 to 3.4, P = 0.001). Neonatal death was not shown to be more common in women with SLE (RR 3.05; CI 0.43 to 21.44, P = 0.28).ConclusionMothers with SLE have an increased risk of Caesarean section, postpartum hemorrhage, and blood transfusion. They are more likely to deliver premature babies, smaller babies, and babies with congenital heart block.     

Effect of Co-twin Fetal Sex on Fetal Anthropometry and Birth Time in Twin Pregnancies

ObjectiveThis study of twin deliveries aimed to examine the effect of fetal sex and fetal sex of the co-twin on fetal anthropometry and length of gestation.MethodsPregnancies were grouped as male/male, male/female, and female/female. Birth weight, head circumference, body length and delivery time of newborns were compared between unlike-sex and like-sex twin pregnancies.ResultsA total of 1028 pregnant women who met the inclusion criteria were enrolled in the study. Of these pregnancies, 32.6% (n = 335) were male/male, 33.4% (n = 343) were male/female, and 34.0% (n = 350) were female/female. The discordant (male/female) newborns had a higher total birth weight than concordant twins (P = 0.015). Compared with male newborns from male/female twin pregnancies, male newborns from male/male pregnancies were found to be 129 grams heavier, 0.7 cm longer, and had a 0.4 cm larger head circumference (P<0.001, P=0.023, and P = 0.039, respectively). Pregnancies with male/female fetuses had statistically significantly longer gestations than pregnancies with male/male and female/female fetuses (P = 0.003 and P = 0.004, respectively). The shortest mean gestation was observed in the male/male group. Male/male pregnancies had a 1.53 times higher risk of preterm delivery than male/female pregnancies and a 1.51 times higher risk than female/female pregnancies (OR 1.53; 95% CI 1.07–2.19 and OR 1.51; 95% CI 1.06–2.16, respectively).ConclusionsThis study suggests that, in twin pregnancies, birth weight, head circumference, and body length are affected by the sex of the co-twin. Male sex is associated with shorter gestation and male/male twin pregnancies are at higher risk for preterm labour.     

Fetal hydrops and the risk of severe preeclampsia

Objective: To assess the incidence and severity of preeclampsia in pregnancies complicated by fetal hydrops.

Methods: We performed a retrospective cohort study of singleton gestations from 2005 to 2008 in California. The primary predictor was fetal hydrops and the primary outcome was preeclampsia. Selected adverse maternal and neonatal events were assessed as secondary outcomes. Potential confounders examined included fetal anomalies, polyhydramnios, race/ethnicity, nulliparity, chronic hypertension, and gestational or pregestational diabetes mellitus.

Results: We identified 337 pregnancies complicated by fetal hydrops, 70.0% had a concomitant fetal anomaly and 39.8% had polyhydramnios. Compared to the general population, hydrops was associated with an increased risk for severe preeclampsia (5.26 versus 0.91%, p?p?=?.29). In multivariable analysis, fetal hydrops remained an independent risk factor for severe preeclampsia (as adjusted odds ratios (aOR) 3.13, 1.91–5.14). Hydrops was also associated with increased rates of eclampsia, acute renal failure, pulmonary edema, postpartum hemorrhage, blood transfusion, preterm birth, and neonatal death.

Conclusions: We find that fetal hydrops is an independent risk factor for severe preeclampsia. In light of serious concerns for maternal and neonatal health, heightened surveillance for signs and symptoms of severe preeclampsia is warranted in all pregnancies complicated by fetal hydrops.     

Acetylsalicylic Acid for the Prevention of Preeclampsia and Intra-uterine Growth Restriction in Women with Abnormal Uterine Artery Doppler: A Systematic Review and Meta-analysis

BackgroundPreeclampsia is a major global cause of maternal, neonatal and perinatal mortality. From studies of placental pathophysiology in women with preeclampsia, a potentially important role of low-dose acetylsalicylic acid (ASA) in the prevention of preeclampsia was expected, but the results from clinical trials have been disappointing. While recent evidence has shown that uterine Doppler can predict preeclampsia as early as in the first trimester of pregnancy, most clinical trials have evaluated ASA in the second and third trimesters.ObjectivesWe performed a meta-analysis to assess the influence of gestational age at the time of introduction of ASA on the incidence of preeclampsia in women at increased risk, on the basis of abnormal uterine artery Doppler.MethodsComputerized searches of randomized controlled trials were conducted to retrieve studies in which pregnant women at increased risk of preeclampsia had been identified on the basis of abnormal uterine Doppler measurements. The trials compared women who received ASA with a control group. The primary outcome was preeclampsia. Secondary outcomes included severe preeclampsia, gestational hypertension, preterm birth, intrauterine growth restriction, placental abruption, birth weight and gestational age at delivery. Statistical analyses used fixed effects of risk ratio (RR) with the Mantel-Haenszel method and 95% confidence intervals.ResultsNine randomized controlled trials with a total of 1317 women met the inclusion criteria. ASA treatment beginning in early gestation was associated with a greater reduction in the incidence of preeclampsia than treatment beginning in late gestation: ASA treatment started at ≤16 weeks’ gestation resulted in RR 0.48 (95% CI 0.33 to 0.68), at 17–19 weeks RR 0.55 (95% CI 0.17 to 1.76), and at ≥ 20 weeks RR 0.82 (95% CI 0.62 to 1.09). ASA treatment started before 16 weeks was also linked with a significant reduction in the incidence of severe preeclampsia (RR 0.10; 95% CI 0.01 to 0.74), gestational hypertension (RR 0.31; 95% CI 0.13 to 0.78) and IUGR (RR 0.51; 95% CI 0.28 to 0.92).ConclusionASA treatment initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences in women with ultrasonographic evidence of abnormal placentation diagnosed by uterine artery Doppler studies.     

Clinical risk factors for gestational hypertensive disorders in pregnant women at high risk for developing preeclampsia

ObjectivesTo evaluate clinical risk factors for the development of gestational hypertensive disorders in a group of pregnant women at high risk for developing preeclampsia. Secondly we evaluated the incidence and recurrence rate of preeclampsia and pregnancy-induced hypertension.Study designA prospective analysis of data obtained from a cohort study was performed. Pregnant women were included who had at least one of the following risk factors for preeclampsia: previous history of preeclampsia, previous history of HELLP syndrome, chronic hypertension, diabetes mellitus, multiple pregnancy, obesity, or autoimmune disease. Univariate and multivariate logistic regression analyses were used to evaluate the role of clinical characteristics and risk factors in the development of hypertensive disorders.Main outcome measuresDevelopment of gestational hypertensive disorders.ResultsThirty-five percent (36/103) developed a hypertensive disorder. The univariate analysis identified preeclampsia in a previous pregnancy (OR 2.94, 95% CI: 1.25–6.91, p = 0.013) as a significant risk factor. Multivariate logistic regression revealed that a previous history of preeclampsia was the only significant independent risk factor for gestational hypertensive disorders (OR 2.89, 95% CI: 1.17–7.08, p = 0.021). Women with a previous history of PE had the highest incidence rate of 51.4% for hypertensive disorders compared to the incidence rates of other risk factors (20.8%–38.5%).ConclusionA previous history of preeclampsia proves to be a strong independent clinical risk factor for gestational hypertensive disorders in high-risk pregnant women, even in our relatively small cohort study.     

Placental Vascular Sonobiopsy Using Three-dimensional Power Doppler Ultrasound in Normal and Growth Restricted Fetuses

ObjectiveTo investigate placental vascular sonobiopsy using three-dimensional (3D) power Doppler ultrasound to assess placental vascularization in normal and growth restricted fetuses.MethodsPlacental vascular sonobiopsy using 3D power Doppler ultrasound with the VOCAL imaging analysis program was performed on 208 normal fetuses between 12 and 40 weeks of gestation and 13 pregnancies with fetal growth restriction (FGR) at 22–39 weeks' gestation. Only pregnancies with an entirely visualized anterior placenta were included in the study. 3D power Doppler indices related to placental vascularization (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) were calculated in each placenta. Intra- and inter-class correlation coefficients and intra- and inter-observer agreements of measurements were assessed.ResultsA weak linear relationship was found between the gestational age and VI, FI, and VFI, respectively. VI values in 8 of 13 FGR pregnancies (61.5%), FI value in one FGR pregnancy (7.7%) and VFI values of 6 FGR pregnancies (46.2%) were below ?1.5SD of the reference ranges for VI, FI and VFI, respectively. After 32 weeks of gestation, VI, FI, and VFI values in 10 FGR pregnancies were significantly lower compared to 79 normal pregnancies, respectively (P < 0.01). All 3D power Doppler indices (VI, FI and VFI) showed a correlation greater than 0.85, with good intra- and inter-observer agreements.ConclusionOur findings suggest that placental vascular sonobiopsy using 3D power Doppler ultrasound may provide new information on the assessment of placental vascularization in normal and FGR pregnancies, while placental perfusion is reduced in FGR compared to normal pregnancy. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of FGR subjects studied. Further studies involving a larger sample size of FGR pregnancies are needed to confirm the usefulness of placental vascular sonobiopsy using 3D power Doppler ultrasound in clinical practice.