Preeclampsia in Twin Pregnancies: Incidence and Outcome

Objectives: To confirm the increased incidence of preeclampsia in twin pregnancy and to determine the relationship to zygosity and placentation; to consider the perinatal outcome of twin pregnancies in this condition.

Methods: Retrospective study of all twin pregnancies (n = 2473) identified from the Aberdeen Maternity and Neonatal Databank to women resident in the Grampian Region of Scotland for the period 1950–1995.

Results: The increased relative risk for gestational hypertension, preeclampsia, and eclampsia in twin pregnancies compared to singleton pregnancies has been confirmed as significant both in primiparas and multiparas with little variation in rates over the time period under review. Neither the sex of the offspring nor zygosity influences the incidence of hypertensive disease, whereas preeclampsia is more common in association with monochorionic placentation.

As the birth weight was lower and placental weight greater in MzMc twins compared to either MzDc or DzDc, there was a higher placental index in such cases. No difference in the birth weights of individual twins, the difference in birth weights between the twins, placental weight, or placental index were found in relation to hypertensive disease. Gestation at delivery was earlier in normotensive twin pregnancies than in those women who developed a hypertensive problem. This leads to a higher perinatal death rate and lower survival rate for the babies in normotensive women with a twin pregnancy.

Conclusion: Although gestational hypertension, preeclampsia, and eclampsia all occur more commonly in twin pregnancy, this does not lead to significant growth retardation nor discordant fetal growth and a poor outcome for the twins. Although the incidence of preeclampsia is higher in twin pregnancies with monochorionic placentation, this does not seem to be mediated by deficiencies in placental development as assessed in this study.     

Uterine Doppler velocimetry and placental hypoxic-ischemic lesion in pregnancies with fetal intrauterine growth restriction.

We tested the hypothesis that Doppler velocimetry of the ascending uterine arteries (Ut.DV) in cases of fetal intrauterine growth restriction (IUGR) can reflect the presence of hypoxic-ischaemic lesions of the placenta, and whether this prediction is affected by the maternal blood pressure status.Ut.DV was obtained within 7 days of delivery in 90 consecutive pregnancies with IUGR and in 37 uneventful control pregnancies. Abnormal Ut.DV was defined as an average of a (left and right systolic)/diastolic ratio >2.6 and diastolic notching. After delivery, pathological studies were performed with attention paid to macroscopic and microscopic evidence of hypoxic or ischaemic placental lesions related to uteroplacental vascular pathological features.In patients with IUGR, the total rate of placental lesions was significantly higher in the presence of abnormal Ut.DV compared to the presence of normal Ut.DV (relative risk, 6.35; 95 per cent confidence interval=5.2-7.3). The rate and the severity of these lesions was not significantly different between normotensive and hypertensive pregnancies (87 versus 93 per cent;P =0.2). When Ut.DV was normal, the rate of placental lesions was similar between IUGR cases and control pregnancies (14 versus 8 per cent;P =0.69). The perinatal outcome was not significantly different in any of the normotensive and the hypertensive pregnancies with growth-restricted fetuses and abnormal Ut.DV.The presence of abnormal Doppler velocimetry of the uterine arteries in pregnancies with fetal intrauterine growth restriction is may be in fact an important indicator of hypoxic or ischaemic placental lesions. This abnormal Doppler velocimetry is independent of the maternal blood pressure status.     

Distribution of Placental Grading by Gestational Age

Objective: to describe the ultrasonography-based gestation-specific placental grading distribution in a Chinese population.Methods: ultrasonographic examination of placentae was performed in 5,476 normal pregnancies (more than 95% first births) in five obstetric ultrasound laboratories in Central-South China between January 1, 1992 and December 31, 1993. A gestation-specific placental grading distribution was presented and compared with previous studies.Results: the gestational ages of the patients included in this study ranged from 16 to 40 weeks. The gestation-specific distribution of placental grading showed patterns similar to those observed previously, with grade III placentae starting to occur at 32 weeks and increasing to 32.3 percent at 40 weeks of gestation.Conclusions: the occurrence of grade III placentae is too high in preterm and too low in term pregnancies. Ultrasonographic placental grading alone is not a reliable measure of fetal pulmonary maturity.     

Pregnancy outcome and placental pathology differences in term gestational diabetes with and without hypertensive disorders

Objective: To compare pregnancy outcome and placental pathology in pregnancies complicated by gestational diabetes mellitus (GDM A1 and A2), with and without hypertensive disorders.

Methods: Pregnancy outcome and placental pathology from term deliveries of women complicated with GDM with (GDM?+?H) and without (GDM???H) hypertensive disorders were compared. Results of the GDM?+?H group were compared also with the non-diabetic patients but with hypertensive disorders (non-GDM?+?H). Composite neonatal outcome was defined as one or more of early complications: respiratory distress or need of ventilation support, sepsis, phototherapy, transfusion, seizure, hypoxic-ischemic encephalopathy. Placental lesions were categorized to lesions related to maternal and fetal vascular supply abnormalities, and maternal and fetal inflammatory responses.

Results: Of the 192 women with GDM, the GDM?+?H group (n?=?41) were more obese, p?<?0.001, with higher rate of placental maternal and fetal vascular supply lesions, p?=?0.008, p?=?0.03, respectively, but similar neonatal outcome, compared to the GDM???H (n?=?151) group. Compared to the non-GDM?+?H group (n?=?41), the GDM?+?H group had higher birth weights, similar neonatal outcome and similar rate of placental vascular lesions.

Conclusions: Higher rate of placental maternal and fetal vascular supply lesions express underlying placental pathology in women with diabetes and hypertensive disorders, similar to women without DM and with hypertensive complications.     

Placental abruption: critical analysis of risk factors and perinatal outcomes

Objective.?To investigate risk factors and pregnancy outcome of patients with placental abruption.

Methods.?A population-based study comparing all pregnancies of women with and without placental abruption was conducted. Stratified analysis using multiple logistic regression models was performed to control for confounders.

Results.?During the study period there were 185,476 deliveries, of which 0.7% (1365) occurred in patients with placental abruption. The incidence of placental abruption increased between the years 1998 to 2006 from 0.6 to 0.8%. Placental abruption was more common at earlier gestational age. The following conditions were significantly associated with placental abruption, using a multivariable analysis with backward elimination: hypertensive disorders, prior cesarean section, maternal age, and gestational age. Placental abruption was significantly associated with adverse perinatal outcomes such as Apgar scores?<7 at 1 and 5?min and perinatal mortality. Patients with placental abruption were more likely to have cesarean deliveries, as well as cesarean hysterectomy.Using another multivariate analysis, with perinatal mortality as the outcome variable, controlling for gestational age, hypertensive disorders, etc., placental abruption was noted as an independent risk factor for perinatal mortality.

Conclusions.?Placental abruption is an independent risk factor for perinatal mortality. Since the incidence of placental abruption has increased during the last decade, risk factors should be carefully evaluated in an attempt to improve surveillance and outcome.     

Fetal and uteroplacental flow velocity waveforms and placental grading

Doppler studies were performed on umbilical, fetal internal carotid, and arcuate arteries within 36 to 40 weeks of gestation in 85 women (66 with healthy pregnancies and 18 complicated by growth retardation, and results were analyzed by calculating the pulsatility index. In each case the placenta was examined and graded sonographically. No significant correlation was found between pulsatility index in fetal and uteroplacental vessels and placental grading in normal pregnancies. This suggests that tissue changes responsible for the echogenicity of maturing placenta are not directly related to vascular impedance of the placental vascular bed.     

Maternal complications in women with chronic hypertension: a population-based cohort study

BACKGROUND: The aim of the study was to determine if pregnant women with chronic hypertensive disease have an independent risk for preeclampsia, gestational diabetes or placental abruption. To examine if superimposed preeclampsia in this group of women is related to an increased risk of placental abruption. METHODS: This study is a population-based cohort study using the Swedish Medical Birth Register 1992-98. A population of 681 515 women aged between 15-44 years with singleton pregnancies, excluding women with systemic lupus erythematosus (SLE), diabetes mellitus and chronic renal disease were studied. Among these, 3374 women were diagnosed with chronic hypertensive disease. Multiple logistic regression analysis was performed and the outcome measures of crude and adjusted odds ratios (OR) were presented with 95% confidence intervals (CI). RESULTS: Chronic hypertensive disease is associated with multiparity, age, high body mass index and Nordic ethnicity. After controlling for confounders, chronic hypertensive disease is an independent risk factor for preeclampsia (OR 3.8; 95% CI 3.4-4.3), gestational diabetes (OR 1.8; 95% CI 1.4-2.4) and placental abruption (OR 2.3; 95% CI 1.6-3.4). CONCLUSION: Chronic hypertensive disease is independently associated with an increased incidence of preeclampsia, gestational diabetes and placental abruption.     

Reproductive risk factors,Doppler findings,and outcome of affected births in placental abruption: a population-based analysis

Placental abruption complicates about 1% of all singleton pregnancies and the aim of this study is to assess the reproductive maternal risk factors associated with placental abruption, and the outcome of affected births. We analyze 170 women with singleton pregnancies complicated by placental abruption who gave birth at Kuopio University Hospital from March 1989 to December 1999. The general obstetric population ( n = 22,905) was selected as the reference group and logistic regression analysis was used to identify independent reproductive risk factors. Furthermore, Doppler ultrasonographic results and pregnancy outcome measures in the two groups were also recorded. The incidence of placental abruption was 0.57% in the referral area. Preeclampsia, grand multiparity, velamentous umbilical cord insertion, cigarette smoking, prior fetal demise, advanced maternal age (>35 years), and previous miscarriage were independent risk factors of placental abruption, with adjusted relative risks of 4.39, 3.60, 2.53, 2.46, 2.02, 1.62, and 1.55, respectively. Most cases of placental abruption occur before the onset of labor in low-risk pregnancies and are not predictable with regard to maternal reproductive risk factors. Current antepartum methods of detecting uteroplacental problems, including Doppler ultrasonography, are not effective in prenatal prediction of placental abruption. The outcome of affected births is still poor.     

Outcome of pregnancy in women with hereditary thrombophilia.

OBJECTIVES: The aims of this study are to review the outcome of pregnancy in women with thrombophilia, and investigate the possible beneficial effect of heparin therapy in these women. METHODS: We reviewed the hospital records of 126 women who were referred to the high-risk obstetrical hematology clinic between June 1996 and December 1999. The placental histology and outcome of 39 pregnancies in 24 women with hereditary thrombophilia were studied, and pregnancies which were treated with heparin were compared with those without treatment. RESULTS: An adverse pregnancy outcome occurred in 54% of the pregnancies. All seven miscarriages (18%) occurred in pregnancies that were not treated with heparin. However, heparin treatment did not prevent the development of obstetric complications in later pregnancies (odds ratio=0.955, 95% C.I.=0.255-3.577, Fisher's exact test). Excluding miscarriages, 28% of the placentas had thrombotic lesions, and the pregnancies with placental thrombotic lesions were more likely to have complications than those pregnancies without placental abnormalities (P=0.023, C.I.=1.257-5.197, Fisher's exact test). CONCLUSIONS: Pregnancy complications in cases of hereditary thrombophilia may be related to placental abnormalities. Heparin therapy is likely to be useful in preventing miscarriage in cases of hereditary thrombophilia.     

Plasma human placental lactogen, oxytocinase, and placental phosphatase in normal and toxemic pregnancies.

A total of 625 serum samples were drawn from 400 normal and 225 hypertensive toxemic pregnant women. Each sample was simultaneously assayed for its human placental lactogen (HPL), oxytocinase (O), and placental phosphatase (PP) concentration. In addition, accurate placental and infant birth weights were determined in those cases where the serum sample was obtained within 14 days of delivery. The results showed a significant rise and correlation of each of the three proteins with increasing weeks of gestation. Although the infant birth weight was unrelated to the serum level of the three proteins, both the HPL and O concentrations were significantly correlated with the placental weight in the normal pregnancies. In both types of pregnancies, the concentration of O was significantly related to that of PP and this was also true for HPL and O and HPL and PP. In all instances O was more strongly related than PP. In the toxemic pregnancies there was a higher O and lower PP level than in normal gestations. These data suggest that placental enzyme measurements, especially O, could be clinically helpful in monitoring high-risk pregnancies.     

Villous histomorphometry and placental bed biopsy investigation in Type I diabetic pregnancies

Insulin-dependent diabetes mellitus (Type I) is associated with disregulation of the glucose and oxygen metabolic pathways during pregnancy, both of which affect placental villous development. Term complete placentas and placental bed biopsies, between 37 and 40 weeks, from 12 singleton pregnancies complicated by Type I diabetes were collected following delivery by elective Caesarean section. The controls consisted of 10 term placentas from uncomplicated pregnancies delivered by elective Caesarean section. Villous morphology was investigated using unbiased histomorphometric techniques, in relation to the degree of transformation of the spiral arteries and the presence of fetal macrosomia. A significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast was found in the diabetic group compared to the controls. A significant reduction in the villous membrane specific diffusing capacity was observed between the diabetic and control groups (1.32 vs 1.72 cm3 min(-1)mmHg(-1)kg(-1), P=0.032). A significant increase in the volume of the intermediate and terminal villi, the surface area of the villi and of the fetal capillaries, and the harmonic thickness of the villous membrane was found in the macrosomic subgroup compared to the controls. There were no differences between the hypertensive subgroup with histological evidence of partial transformation of the spiral arteries and the controls. These data indicate that placental development in insulin-dependent diabetic pregnancies is affected differentially when pregnancies complicated by fetal macrosomia are separated from those complicated by maternal hypertensive disorders with partial transformation of the spiral arteries. The reduction in the specific diffusing capacity of the villous membrane may contribute to the fetal hypoxia and increased fetal and neonatal morbidity associated with diabetes.     

Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome

OBJECTIVE: BNip3 and its homologue Nix are pro-apoptotic factors of the Bcl-2-family and are expressed in malignant tumors. In vitro, this expression was shown to be mediated by hypoxia. Recently, it has been shown that placental hypoxia as well as apoptosis are pathogenetic factors for pregnancy-induced hypertensive diseases and intrauterine growth retardation (IUGR). The aim of the study was to analyze placental expression of BNip3 and Nix in pregnancies complicated by preeclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and IUGR. MATERIAL AND METHODS: Placental tissue was sampled from 10 pregnancies each with preeclampsia, HELLP syndrome, IUGR and gestational age-matched controls. The placental expression of BNip3/Nix has been investigated with immunohistochemistry by the use of specific human BNip3/Nix antibodies. RESULTS: In cytotrophoblastic cells, the BNip3 expression was strong in the control placentas, but only mediate in the placentas from pregnancies with preeclampsia, IUGR or HELLP syndrome. The intensity of the Nix staining showed a similar pattern. In the syncytiotrophoblast, there was a weak BNip3 staining observable in the control as well as IUGR samples, whereas BNip3 was undetectable in preeclamptic placentas or those with HELLP syndrome. For Nix, only in the preeclampsia a weak staining was detectable, whereas all other probes were negative. CONCLUSIONS: Our study shows for the first time that the pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta. Pregnancies with placental dysfunction and hypertensive pregnancy disorders with different clinical manifestations are characterized by a significantly decreased expression of BNip3 and Nix. These results suggest that the hypothesis of generally increased placental apoptosis in pregnancy-induced hypertensive disorders caused by disturbed trophoblast invasion has to be partly reconsidered.     

Fetofetal transfusion syndrome in triplet pregnancies: outcome after endoscopic laser surgery

OBJECTIVE: The purpose of this study was to determine the outcome of fetofetal transfusion syndrome in triplet pregnancies after treatment with endoscopic laser ablation of communicating placental vessels. STUDY DESIGN: Cases of severe fetofetal transfusion syndrome that occur in triplet pregnancies and that are treated with endoscopic laser ablation of placental anastomosis were identified from a prospectively collected fetal medicine database. Chorionicity was determined by sonography and classified as dichorionic or monochorionic. Perinatal outcome was obtained in all cases, and long-term follow-up was obtained in all pregnancies that resulted in at least 1 survivor. RESULTS: During a 6-year period, 10 cases of severe fetofetal transfusion syndrome that were treated with endoscopic laser ablation were identified, of which 7 cases were dichorionic and 3 cases were monochorionic. At least 1 fetus survived in all 7 dichorionic pregnancies and in 2 of the 3 monochorionic pregnancies. In the dichorionic pregnancies, 14 of 21 fetuses (66.7%) survived, but in the monochorionic pregnancies only 2 of 9 fetuses (22.2%) survived. CONCLUSION: Endoscopic laser ablation is feasible in triplet pregnancies that are complicated by severe fetofetal transfusion syndrome. The treatment appears to be associated with improved perinatal outcome in dichorionic, but not in monochorionic, triplets, probably because of the technical inability in achieving ablation of all the communicating vessels in monochorionic triplets.     

The effect of placental location on uterine artery flow velocity waveforms

We examined the effect of placental location with regard to flow velocity waveforms in the uterine arteries in 84 control and 28 hypertensive women during the third trimester of pregnancy. The ratio of systolic peak to end-diastolic frequency was obtained with a continuous-wave Doppler device and the placental location was determined by real-time ultrasonography. In both normal and hypertensive pregnancies with unilateral placental location the systolic/diastolic ratio of the ipsilateral uterine artery was significantly lower than the contralateral artery ratio [1.73 +/- 0.35 (systolic/diastolic ratio) versus 2.46 +/- 0.73, p less than 0.001, and 2.38 +/- 1.01 versus 4.04 +/- 1.77, p = 0.0012, respectively]. The physiologic and clinical significance of this finding is discussed.     

The correlation of ultrasonic placental grading and fetal pulmonary maturation in five hundred sixty-three pregnancies

In a previous study, it was suggested that the presence of a grade III placenta correlates 100% with a mature lecithin/sphingomyelin (L/S) ratio and may replace amniocentesis in confirming fetal lung maturity. In this study that hypothesis was tested in 563 pregnancies. All patients underwent amniocentesis and simultaneously had placental grading. The correlations of placental grade with an L/S ration ≥2 were: grade 0, 17%; grade I, 68%; grade II, 91%; grade III, 93%. The correlations of placental grade with the presence of phosphatidylglycerol (PG) were: grade 0, 17; grade I, 41%; grade II, 79%; grade II, 75%. The false positive rates associated with grade III placenta were, therefore, 7% for mature L/S ratio and 25% for PG present; when combined with a biparietal diameter ≥9.0 cm, a grade III placenta incorrectly predicted lung maturity in 8.5%. We conclude that placental grading is not accurate enough to replace amniocentesis as the standard test of fetal pulmonary maturity.     

Useful of cerebral placental ratio in pregnancies complicated by intrauterine growth retardation and it correlation with perinatal outcome

OBJECTIVE: The aim of this study was to asses usefulness of cerebro-placental ratio in the estimation of the intrauterine fetal well being in pregnancies complicated by intrauterine growth retardation and prediction of perinatal outcome. MATERIAL AND METHODS: We investigated 22 pregnant women between 28th and 40th week of pregnancy with IUGR detected by ultrasound examination. 19 pregnant women between 28th and 41st week of pregnancy was control group. We measured parameters blood flow in umbilical arteries and in middle cerebral arteries in both groups. We calculated cerebro placental ratios(CPR, CPP). We divided pregnant women with IUGR int 2 groups depending on correct (CPR, CPP > 1.08) or incorrect (CPR, CPP < 1.08). In both groups we analyzed perinatal outcome. RESULTS: In group pregnancies complicated with IUGR cerebro-placental ratios (CPR and CPP) were statistically significant lower than in control group. (for CPR p < 0.015 and for CPP p < 0.033). Sensitivity of cerebro placental ratio in screening small gestational age fetuses was 59% and specificity 89%. Sensitivity of cerebro placental ratio in predicting adverse perinatal outcome was 85% and specificity was 82%. CONCLUSIONS: Statistically significant decrease of cerebro-placental ratios is observed in pregnancies complicated wit IUGR. Cerebro placental ratio is very useful tool for prediction of adverse perinatal outcome.     

Ultrasound of the placenta: a systematic approach. Part II: functional assessment (Doppler)

Doppler velocimetry is the ideal clinical tool to assess placental performance in high-risk pregnancies. It also has value in predicting later complications and outcome in pregnancies which appear uncomplicated. All three circulations (fetal, placental and maternal) may be interrogated by Doppler technology. In the following review, we present basic physics aspects of Doppler and discuss mainly Doppler investigation of the fetal-placental circulation (umbilical artery, intraplacental circulation) as well as the uterine arteries. The assessment of umbilical blood flow provides information on blood perfusion of the fetal-placental unit. The diastolic blood flow velocity component in umbilical artery increases with advancing gestation. In pregnancies complicated by placental dysfunction, there may be a reduction in the number of functional villi and/or small blood vessels with, as a result, increased impedance, reflected, mainly, by a decrease in end-diastolic velocity. When the resistance increases even more, there is no diastolic forward velocity (absent end-diastolic velocity). Further increase in the resistance causes reversed end-diastolic velocity, which is considered a late step in the cascade of events leading to intrauterine fetal demise. Doppler assessment of the umbilical arteries was found to improve outcome of high-risk pregnancies, and reduce hospital admissions. On the contrary, routine Doppler ultrasound in low risk or unselected populations does not seem to confer benefit on mother or newborn. Uterine artery Doppler is a useful test in predicting pregnancies at high risk of developing complications related to uteroplacental insufficiency. It identifies women who may benefit from increased antenatal surveillance or prophylactic therapy. Three-dimensional power Doppler sonography can provide new insights into placental pathophysiology.     

Comparison of Pregnancy Outcome Between Normotensive and Hypertensive Women with Primary Glomerulonephritis

To examine the effect of pre-existing hypertension en pregnancy outcome, the clinical courses of 105 pregnancies undertaken by 76 wemen (55 normotensive, 21 hypertensive) with a renal biopsy diagnosis of primary glomerulonephritis have been compared. Total foetal loss was similar for both groups (18% Vs 16%) as was perinatal mortality (6% Vs 7%). Prematurity rates of hypertensive and normotensive groups were also similar (24% Vs 15%) but 25% of infants of mothers in the hypertensive group were small for gestational age compared with only 4% in the normotensive group (p<0.05). Blood pressure in excess of 90 mmHg was recorded in 47% of pregnancies in the hypertensive group despite continuation of the patients' prepregnancy anti-hypertensive therapy. This compared with a 23% incidence recorded in the normotensive group. Early hypertension was significantly more common in previously hypertensive patients' pregnancies (28%) than the normotensive group (10%) (p<0.05). Pre-existing hypertension was not a major determinant of foetal outcome in women with primary glomerulonephritis in this series although the incidence of small for gestational age infants and of early pregnancy hypertension was significantly higher if hypertension predated pregnancy Thus, at least in the absence of other risk factors, pre-existing hypertension need not be a contra-indication to pregnancy.     

The effect of caffeine on placental and fetal blood flow in human pregnancy

The effects of maternal ingestion of two cups of coffee were investigated in 20 pregnancies during the last trimester. Maternal serum caffeine and epinephrine concentrations after 30 minutes were significantly elevated as compared with the fasting values (p less than 0.01). The intervillous placental blood flow decreased almost significantly (p less than 0.05). The fetal umbilical vein blood flow was unchanged. In patients with hypertensive pregnancy in the series there was reduced intervillous blood flow initially, and these values did not change after the maternal caffeine intake. The decrease of placental blood supply and increased maternal serum epinephrine levels associated with maternal coffee ingestion may be potential perinatologic risks, and more investigation about caffeine effects in human pregnancy is needed.     

Growth and function of human fetal heart in normal, hypertensive and diabetic pregnancy

Fetal cardiac left and right ventricular dimensions and contractility were measured by echocardiography in late pregnancy in 51 normal, 26 hypertensive and 18 diabetic pregnancies. In relationship with the fetal size, both of the ventricular dimensions, the contractility and left ventricular output were decreased in diabetic cases. In hypertensive pregnancy the relative size of the right ventricle was increased and its contractility decreased, but the function of the left ventricle was no different from normal. These findings may reflect biochemical changes in diabetic myocardium and increased peripheral fetal and placental resistance in hypertensive pregnancy.