Early Severe Preeclampsia Research Articles

Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor

Preeclampsia has been proposed to be an antiangiogenic state that may be detected by the determination of the concentrations of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor (PlGF) in maternal blood even before the clinical development of the disease. The purpose of this study was to determine the role of the combined use of uterine artery Doppler velocimetry (UADV) and maternal plasma PlGF and sVEGFR-1 concentrations in the second trimester for the identification of patients at risk for severe and/or early onset preeclampsia. A prospective cohort study was designed to examine the relationship between abnormal UADV and plasma concentrations of PlGF and sVEGFR-1 in 3348 pregnant women. Plasma samples were obtained between 22 and 26 weeks of gestation at the time of ultrasound examination. Abnormal UADV was defined as the presence of bilateral uterine artery notches and/or a mean pulsatility index above the 95th percentile for the gestational age. Maternal plasma PlGF and sVEGFR-1 concentrations were determined with the use of sensitive and specific immunoassays. The primary outcome was the development of early onset preeclampsia (< or = 34 weeks of gestation) and/or severe preeclampsia. Secondary outcomes included preeclampsia, the delivery of a small for gestational age (SGA) neonate without preeclampsia, spontaneous preterm birth at < or = 32 and < or = 35 weeks of gestation, and a composite of severe neonatal morbidity. Contingency tables, chi-square test, receiver operating characteristic curve, and multivariate logistic regression were used for statistical analyses. A probability value of < .05 was considered significant. (1) The prevalence of preeclampsia, severe preeclampsia, and early onset preeclampsia were 3.4% (113/3296), 1.0% (33/3296), and 0.8% (25/3208), respectively. UADV was performed in 95.4% (3146/3296) and maternal plasma PlGF concentrations were determined in 93.5% (3081/3296) of the study population. (2) Abnormal UADV and a maternal plasma PlGF of < 280 pg/mL were independent risk factors for the occurrence of preeclampsia, severe preeclampsia, early onset preeclampsia, and SGA without preeclampsia. (3) Among patients with abnormal UADV, maternal plasma PlGF concentration contributed significantly in the identification of patients destined to develop early onset preeclampsia (area under the curve, 0.80; P < .001) and severe preeclampsia (area under the curve, 0.77; P < .001). (4) In contrast, maternal plasma sVEGFR-1 concentration was of limited use in the prediction of early onset and/or severe preeclampsia. (5) The combination of abnormal UADV and maternal plasma PlGF of < 280 pg/mL was associated with an odds ratio (OR) of 43.8 (95% CI, 18.48-103.89) for the development of early onset preeclampsia, an OR of 37.4 (95% CI, 17.64-79.07) for the development of severe preeclampsia, an OR of 8.6 (95% CI, 5.35-13.74) for the development of preeclampsia, and an OR of 2.7 (95% CI, 1.73-4.26) for the delivery of a SGA neonate in the absence of preeclampsia. The combination of abnormal UADV and maternal plasma PlGF concentration of < 280 pg/mL in the second trimester is associated with a high risk for preeclampsia and early onset and/or severe preeclampsia in a low-risk population. Among those with abnormal UADV, a maternal plasma concentration of PlGF of < 280 pg/mL identifies most patients who will experience early onset and/or severe preeclampsia.

Infants of women with severe early pre-eclampsia: the effect of absent end-diastolic umbilical artery Doppler flow velocities on neurodevelopmental outcome

Umbilical artery Doppler flow velocity waveform studies were performed over a period of 4 y on 242 women with severe pre-eclampsia before 34 wk gestation. Sixty-eight (28%) had absent end-diastolic umbilical artery Doppler flow velocities. One hundred and ninety-three infants survived to hospital discharge and were followed at 6-monthly intervals until 48 mo of age. Fhe mean corrected developmental quotient was 94 ± 8 at 24 mo of age and 87 ± 9 at 48 mo. Ninety-two percent of the infants had a developmental quotient of >80 at 24 mo and 72% at 48 mo of age. Fhis decline is thought to be due to the impact of social circumstances. Fhere were no differences between the developmental quotients of the infants with normal and those with absent end-diastolic umbilical artery Doppler flow velocities at either 24 or 48 mo of age. At 24 mo of age, infants with absent end-diastolic umbilical artery Doppler flow velocities scored lower in the Performance subscale test (p= 0.03). developmental quotients of infants from poorer socioeconomic backgrounds were significantly lower than those living in more privileged circumstances. At 48 mo, 153 (97%) of the children presented with normal gross motor development. Four infants had cerebral palsy. No differences were noted in the motor outcomes between the infants of women with normal umbilical artery waveforms and those with absent end-diastolic umbilical artery Doppler flow velocities.

Effect of pregnancy on vascular responses in the offsprings of endothelial nitric oxide synthase knockout mice

MEASUREMENTS DAVID CHAFFIN, Society for Maternal-Fetal Medicine, Huntington, WV OBJECTIVE: To evaluate the clinical outcomes of a program to pharmacologically manage hypertensive pregnant patients based on serial measurements of blood pressure, cardiac output (CO), and systemic vascular resistance (SVR) beginning in the second trimester. STUDY DESIGN: Patients were enrolled in the program based on a history of chronic hypertension, type 1 diabetes, chronic renal failure, or early severe preeclampsia. Blood pressure, cardiac output, and systemic vascular resistance were measured using thoracic electrical impedance plethysmography. Patients with hyperdynamic or mixed vasoconstrictive/hyperdynamic measurements at a gestational age of less than 24 weeks were treated with atenolol. Vasodilators were added for SVR >1100 dyne*sec*cm . Patients were followed on a regular basis until 34 weeks’ gestation with medication dosages adjusted to attempt to achieve normal hemodynamics. Patients were managed by referring physicians after 34 weeks. RESULTS: The first 106 patients treated with atenolol enrolled at less than 24 weeks are included in this report. Themean gestational age at enrollment was 16 ± 4 wks. The average mean arterial blood pressure was 99 ± 12 mm Hg. Initial cardiac output was 7.7 ± 1.5 liters/min (normal < 7.6 liters/min) with a range of 4.1 to 12.8 liters/min. Atenolol dosage ranged from 25 mg to 200 mg per day. Additional vasodilators used included hydralazine, nifedipine, and Isordil.Mean gestational age at delivery was 36 ± 3weeks with amean percentile birth weight of 47 (11% less than 10th centile). There were 4 patients delivered at less than 34 weeks for hypertensive complications. Three fetal deaths were due to premature labor at 22 to 23 weeks. 35 patients delivered between 34 and 37 weeks. The average hospital stay for these infants was 3.5 days (2.5 days for term infants). CONCLUSION: Early intervention with atenolol in an at-risk population with abnormal hemodynamics results in a low rate of early hypertensive complications with no increase in growth restriction.

Early onset, severe pre-eclampsia and HELLP syndrome: sex ratio of infants

"Early onset, severe pre-eclampsia and HELLP syndrome: sex ratio of infants." Journal of Obstetrics and Gynaecology, 22(6), p. 636

Infants of Women With Severe Early Pre-Eclampsia: The Effect of Absent End-Diastolic Umbilical Artery Doppler Flow Velocities on Neurodevelopmental Outcome

Umbilical artery Doppler flow velocity waveform studies were performed over a period of 4 y on 242 women with severe pre-eclampsia before 34 wk gestation. Sixty-eight (28%) had absent end-diastolic umbilical artery Doppler flow velocities. One hundred and ninety-three infants survived to hospital discharge and were followed at 6-monthly intervals until 48 mo of age. The mean corrected developmental quotient was 94 +/- 8 at 24 mo of age and 87 +/- 9 at 48 mo. Ninety-two percent of the infants had a developmental quotient of >80 at 24 mo and 72% at 48 mo of age. This decline is thought to be due to the impact of social circumstances. There were no differences between the developmental quotients of the infants with normal and those with absent end-diastolic umbilical artery Doppler flow velocities at either 24 or 48 mo of age. At 24 mo of age, infants with absent end-diastolic umbilical artery Doppler flow velocities scored lower in the Performance subscale test (p = 0.03). The developmental quotients of infants from poorer socioeconomic backgrounds were significantly lower than those living in more privileged circumstances. At 48 mo, 153 (97%) of the children presented with normal gross motor development. Four infants had cerebral palsy. No differences were noted in the motor outcomes between the infants of women with normal umbilical artery waveforms and those with absent end-diastolic umbilical artery Doppler flow velocities.

Expectant management of early onset, severe pre-eclampsia: perinatal outcome.

To evaluate the perinatal outcome of expectant management of early onset, severe pre-eclampsia. Prospective case series extending over a five-year period. Tertiary referral centre. All women (n = 340) presenting with early onset, severe pre-eclampsia, where both mother and the fetus were otherwise stable. Frequent clinical and biochemical monitoring of maternal status with careful blood pressure control. Fetal surveillance included six-hourly heart rate monitoring, weekly Doppler and ultrasound evaluation of the fetus every two weeks. All examinations were carried out in a high care obstetric ward. Prolongation of gestation, perinatal mortality rate, neonatal survival and major complications. A mean of 11 days were gained by expectant management. The perinatal mortality rate was 24/1,000 (> or = 1,000 g/7 days) with a neonatal survival rate of 94%. Multivariate analysis showed only gestational age at delivery to be significantly associated with neonatal outcome. Chief contributors to neonatal mortality and morbidity were pulmonary complications and sepsis. Three pregnancies (0.8%) were terminated prior to viability and only two (0.5%) intrauterine deaths occurred, both due to placental abruption. Most women (81.5%) were delivered by caesarean section with fetal distress the most common reason for delivery. Neonatal intensive care was necessary in 40.7% of cases, with these babies staying a median of six days in intensive care. Expectant management of early onset, severe pre-eclampsia and careful neonatal care led to high perinatal and neonatal survival rates. It also allowed the judicious use of neonatal intensive care facilities. Neonatal sepsis remains a cause for concern.

Infants of women with severe early pre-eclampsia: the effect of absent end-diastolic umbilical artery doppler flow velocities on neurodevelopmental outcome.

Umbilical artery Doppler flow velocity waveform studies were performed over a period of 4 y on 242 women with severe pre-eclampsia before 34 wk gestation. Sixty-eight (28%) had absent end-diastolic umbilical artery Doppler flow velocities. One hundred and ninety-three infants survived to hospital discharge and were followed at 6-monthly intervals until 48 mo of age. The mean corrected developmental quotient was 94 +/- 8 at 24 mo of age and 87 +/- 9 at 48 mo. Ninety-two percent of the infants had a developmental quotient of >80 at 24 mo and 72% at 48 mo of age. This decline is thought to be due to the impact of social circumstances. There were no differences between the developmental quotients of the infants with normal and those with absent end-diastolic umbilical artery Doppler flow velocities at either 24 or 48 mo of age. At 24 mo of age, infants with absent end-diastolic umbilical artery Doppler flow velocities scored lower in the Performance subscale test (p = 0.03). The developmental quotients of infants from poorer socioeconomic backgrounds were significantly lower than those living in more privileged circumstances. At 48 mo, 153 (97%) of the children presented with normal gross motor development. Four infants had cerebral palsy. No differences were noted in the motor outcomes between the infants of women with normal umbilical artery waveforms and those with absent end-diastolic umbilical artery Doppler flow velocities.

Necrotizing enterocolitis in infants born to women with severe early preeclampsia and absent end-diastolic umbilical artery doppler flow velocity waveforms.

The aim of this study was to determine the prevalence of necrotizing enterocolitis (NEC) in infants born to a homogeneous group of women with severe preeclampsia before 34 weeks' gestation and who had absent end-diastolic umbilical artery Doppler flow (AEDF) or normal umbilical Doppler flow velocities (NUFV). A total of 242 infants were entered into the study. The mean birth weight was 1260.5 g (SD = 339) and the mean gestational age 30.5 weeks (SD = 2.0). Sixty-eight (28%) infants had AEDF, 43 (18%) had umbilical artery Doppler flow velocities between the 95th and 99th percentile, and 131 (54%) had NUFV. Forty-one (18%) infants developed NEC, of whom 20 (8%) developed definite and advanced NEC (grade 2 and 3). Of these, 16(80%) had grade 2 and 4(20%) had grade 3. Twenty-one (8%) infants developed suspected NEC (grade 1). The mean onset of grade 1 NEC (7.2 days) occurred significantly earlier than in those with grades 2 and 3 NEC (18.7 and 23.3 days, respectively). Of the 21 infants with grade 1 NEC, 10 (48%) had AEDF and 9 (43%) had NUFV. None of the infants with grades 2 or 3 NEC had AEDF. We conclude that although chronically hypoxemic fetuses born to women with severe early onset preeclampsia and AEDF respond by redistributing blood flow to vital organs and away from the gut; the intestinal compromise is of insufficient magnitude to induce intestinal necrosis or NEC. Enteral feeding, however, should be introduced cautiously in infants with AEDF, as so-called suspected NEC developed significantly more often in these infants.

Acute Oligohydramnios and Deteriorating Fetal Biophysical Profile Associated with Severe Preeclampsia

Acute changes in fetal biophysical profile (BPP) status usually include rapid cessation of all nonessential acute biophysical activities, yet not necessarily an acute decrease in the amniotic fluid volume, or oligohydramnios. A 36-year-old para 3 with early third-trimester severe preeclampsia, mild placental abruption, and fetal growth restriction, with a reassuring BPP of 8/8, was managed expectantly with intravenous magnesium sulfate, hydralazine, and intramuscular corticosteroids. Within 20 h of admission a marked change in the BPP was noted, with a score of 0/8. Amniotic fluid index (AFI), which on admission had been 20.1, progressively became 0, despite a stable normovolemic maternal status. At immediate cesarean, a mildly acidotic and hypoxic fetus was delivered which subsequently did well. This case supports the concept that acute oligohydramnios may develop rapidly in the presence of acute fetal hypoxemia.

Activated protein C resistance and adverse pregnancy outcome

OBJECTIVE: Activated protein C resistance is a genetic disorder that predisposes to thrombosis. Hyperestrogenism strongly increases the risk of thrombosis in affected individuals. Other thrombophilic disorders, such as the antiphospholipid antibody syndrome, have been associated with adverse pregnancy outcome, probably mediated by abnormal clotting in the placental circulation. The purpose of this series is to present clinical and laboratory data on individuals with a poor obstetric history and activated protein C resistance. STUDY DESIGN: Within an 18-month period seven patients with more than five early pregnancy losses, recurrent intrauterine fetal deaths, intrauterine growth restriction, and early severe preeclampsia in association with activated protein C resistance came to our attention. The initial diagnosis was made by activated protein C ratios, and molecular diagnoses of activated protein C resistance genotypes were made by polymerase chain reaction for the factor V Leiden mutation. All patients had an extensive diagnostic workup for known etiologies of the above complications and other thrombophilic disorders. RESULTS: All patients had activated protein C ratios <1.7. Six patients were heterozygous for the Leiden mutation, and one patient was homozygous. A personal or family history of thromboembolism was present in one case and three cases, respectively. The diagnostic workup was otherwise unrevealing. One newborn was diagnosed of bilateral renal vein thrombosis on day 1 of life. CONCLUSIONS: Activated protein C resistance was found in association with extremely poor obstetric outcomes. A family or personal history of thromboembolism was suggestive in many cases. A population-based study is needed to determine the role of activated protein C resistance in adverse pregnancy outcome. (Am J Obstet Gynecol 1997;177:170-3.)

Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correlation with pregnancy outcome. Anti-β2 glycoprotein I antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia

Objective: To evaluate the prevalence in normal pregnancies of anti-β2 glycoprotein I (anti-β2GPI) antibodies, and their association with obstetrical complications. Study design: Prospective study of anti-β2GPI and anticardiolipin (CL) antibodies in 510 healthy pregnant women at 15–18 weeks. According to the results, women were categorized into three groups: group I, negative for both antibodies; group II, positive for anti-β2GPI antibodies; group III, positive for aCL only. The rates of fetal loss, abruptio placentae, preeclampsia-eclampsia, and fetal growth retardation were compared in the three groups. Results: Anti-β2GPI antibodies were found in 20 women (3.9%) and aCL in 8 patients (1.6%). Obstetrical complications were more frequent, even if not significantly different, in group II, 15%, than in group I, 4.1% (difference 10.9%; 95% confidence interval (CI): 1.6–20.2%; p=0.0575), while no complications were seen in group III. Preeclampsia-eclampsia were significantly more frequent in group II (10%) than in group I (0.8%; difference 9.2%; 95% CI: 4.4–14%; p=0.021). The prevalence of fetal growth retardation was not significantly different in the two groups (5% vs. 2%, respectively). Comment: Our findings indicate that anti-β2GPI antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia, even if more conventional antiphospholipid antibodies are not present. This observation suggests that these antibodies should be investigated in such cases, in order to improve the outcome of subsequent pregnancies, as well as in women with a history of early and/or recurrent severe preeclampsia in order to start a prophylactic treatment (i.e. low-dose aspirin or heparin).

Low-Dose Aspirin in High-Risk Pregnancy?

Objectives: To determine the value of low-dose aspirin (100 mg/day) therapy in high-risk pregnancies, and to assess improvement in maternal abnormalities in response to this therapy, we conducted a prospective, randomized, double-blind, placebo-controlled therapeutic study.Methods: One hundred and eight pregnant women with preexisting hypertension (n = 60) or renal disease (n = 28), or a history of early severe preeclampsia (n = 20) in a previous pregnancy, took either aspirin (n = 58) or placebo (n = 50) from 17 to 19 weeks amenorrhea till approximately 37 weeks amenorrhea. The main outcome measures were duration of pregnancy, birth weight, maximum antenatal blood pressure, and maximum antenatal serum uric acid level.Outcome: Median values for the maximum antenatal blood pressure were higher and for birth weight lower in placebo-treated than in aspirin-treated women. Noncompliance with treatment, as assessed by platelet aggregation studies, was high in both groups.Conclusion: There was a small but potentially beneficial effect of aspirin on the development of hypertension and on fetal growth but no effect on overall pregnancy outcome. Noncompliance in both treatment groups may contribute to failure to demonstrate a clearer difference between them, and may partially explain conflicting results of aspirin therapy in the literature.

Perinatal results of hemodynamic and conservative temporizing treatment in severe pre-eclampsia

Objective: To evaluate maternal and perinatal outcome of hemodynamic temporizing management in severe pre-eclampsia. Design: Study group of 57 pre-eclamptic women, gestational age 35 weeks or less, treated with plasma volume expansion and vasodilatation under invasive hemodynamic monitoring, retrospectively matched with a control group treated in another center without volume expansion and invasive monitoring. Results: In both groups pregnancy was prolonged with 10–11 days. Maternal morbidity was low in both groups. No complications of hemodynamic monitoring were observed. Perinatal mortality was not significantly different between the study group (7.1%) and the control group (14.3%). SGA-infants were significantly less frequent in the study group (9%) than in controls (33%). Conclusion: Temporizing treatment of patients with early severe pre-eclampsia, with or without plasma volume expansion and invasive hemodynamic monitoring, may reduce neonatal mortality and morbidity. The difference in birthweight between study group and control group may be an effect of the therapy or may be caused by selection bias. The perinatal outcome in the study group suggests that there may be a subgroup of patients who might benefit from hemodynamic treatment.

Antiphospholipid syndrome in pregnancy: a diagnostic dilemma

To present a case of severe pre-eclampsia in which diagnosis of the antiphospholipid syndrome was made after delivery, and to discuss pointers to the diagnosis. A 32-year-old woman in her second pregnancy presented at 32 weeks' gestation with severe pre-eclampsia. Her persisting severe postpartum illness was investigated. The presence of anticardiolipin antibodies and lupus anticoagulant led to the diagnosis of antiphospholipid syndrome. Induction of labour was successful, with delivery of a healthy baby girl. The patient made a full recovery after treatment with corticosteroids and warfarin. The antiphospholipid syndrome should be considered in cases of severe early pre-eclampsia.