Pieter E. Treffers

Enhanced thrombin generation in normal and hypertensive pregnancy.

We investigated the plasma levels of thrombin-antithrombin III complexes in women with uncomplicated pregnancy, patients with preeclampsia, gestational hypertension, and nonpregnant control subjects. In addition, we measured the coagulation inhibitors antithrombin III, protein C, and protein S. In normal pregnancy we observed a progressive increase in plasma thrombin-antithrombin III levels, and a decrease in protein S levels. In preeclampsia we observed increased thrombin-antithrombin III levels, reduced antithrombin III and protein C levels, and no further reduction of protein S compared with normal pregnancy. These new methods provide solid evidence for a prethrombotic state in normal pregnancy, especially in preeclampsia.

Ovarian Tumors in Pregnancy

Abstract. The results of 90 pregnancies complicated by an ovarian tumor are analysed. On this basis it seems advisable to follow a ‘wait‐and‐see’ policy until the 16th week. Tumors persisting into the second trimester can best be extirpated between the 16th and 20th week. Ovarian tumors present after the first trimester can lead to serious complications. However, an ovarian tumor discovered in the second half of pregnancy calls for temporization of treatment. Ce‐sarean section at term with simultaneous extirpation of the tumor is the treatment of choice.

Management of premature rupture of membranes: The risk of vaginal examination to the infant

Presented are the results over a 4-year period of the conservative management of cases of premature rupture of the membranes. Perinatal mortality in infants delivered more than 24 hours after rupture of the membranes is not higher than that in infants delivered within 24 hours of rupture of the membranes, if these results are based on pregnancies of comparable gestational age. Two independent factors influence the risk of infection: the duration of gestation, and the interval between vaginal examination and delivery. If corrections are made for these two factors, there appears to be no clear correlation between the incidence of infection and the period of time the membranes have been ruptured. Conservative management is justified if vaginal examination is avoided until delivery within 24 hours is expected to occur.

Epidemiological observations of thrombo-embolic disease during pregnancy and in the puerperium, in 56,022 women

During a 28‐year period the incidence of thrombosis and pulmonary embolism (TE) in pregnancy remained practically equal (0.7‰), the incidence of puerperal TE was higher (2.3‰) but decreased during the last 7 years. Puerperal TE was influenced by age, mode of delivery, hypertension and prophylactic anticoagulant therapy. TE during pregnancy was not noticeably correlated with age and hypertension. TE during pregnancy and in the puerperium are closely related diseases, but their epidemiological characteristics are apparently distinct. Both are associated with a high rate of preterm deliveries and a high perinatal mortality rate.

Long-term follow-up in patients with a history of (H)ELLP syndrome

OBJECTIVE To provide long-term follow-up data on women with a history of hemolysis, elevated liver enzymes, and low platelets [(H)ELLP] syndrome regarding the risk of recurrence in subsequent pregnancies and disease in later life. METHODS All women admitted to the Academic Medical Centre between January 1984 and January 1996 with (H)ELLP syndrome and a living singleton fetus in utero were included. Women with known preexisting diseases were excluded. The (H)ELLP syndrome was defined as elevated liver enzymes (serum aspartate aminotransferase or serum alanine aminotransferase >or= 50 U/L) and low platelet count (< 100 x 10(9)/L). Those patients with hemolysis (LDH >or= 600 U/L) were classified as HELLP, the remaining ones were classified as ELLP. The participants were asked to fill out a questionnaire regarding their general health and their own obstetric and medical history and that of their first-and second-degree relatives. RESULTS One hundred sixteen (94%) of 123 women responded; 4 women had died. The median age of the group was 36.0 years at completion of the questionnaire; the median interval after the index pregnancy was 5.7 years (3-12.9). The incidence of hypertension requiring medical treatment was three times higher than in a reference population of Dutch women between 20 and 40 years old. The need for psychological support was frequent. Thirty-nine patients (34%) refrained from further pregnancies. Twenty-nine percent of the first subsequent pregnancies were complicated by gestational hypertension (GH), but only 2% had (H)ELLP syndrome. Birth weight was, on average, 1385 g higher and gestational age at delivery 5 weeks later in the first subsequent pregnancy irrespective of a recurrence of GH. A family history of cardiovascular disease or preeclampsia was common in the total group; however, this did not influence the recurrence rate. Multiparity, gestational age at delivery <30 weeks, and birth weight <1000 g in the index pregnancy increased the risk of recurrence of GH in the first subsequent pregnancy significantly. CONCLUSIONS (H)ELLP syndrome is a severe complication of pregnancy that has not only short-term but also long-term sequelae.

Jejunal atresia related to the use of methylene blue in genetic amniocentesis in twins

Objective To calculate the incidence of jenunal atresia in newborns in The Netherlands. To study the relation between the occurrence of jejunal atresia and genetic amniocentesis to determine a possible iatrogenic cause for the unexpected high incidence of this anomaly in twins.

Placental-type plasminogen activator inhibitor in preeclampsia.

The present cross-sectional study in patients with preeclampsia and gestational hypertension and in gestational age-matched controls was undertaken to investigate further the fibrinolytic system in these conditions. In preeclampsia we observed increased levels of total plasminogen activator inhibitor (p less than 0.001) but low levels of placental-type plasminogen activator inhibitor (p less than 0.05) compared with controls. The levels of placental-type plasminogen activator inhibitor were even more reduced (p less than 0.002) in pregnancies with a poor fetal outcome. It is concluded that placental-type plasminogen activator inhibitor does not contribute to the increased levels of total plasminogen activator inhibitor activity in preeclampsia. Placental-type plasminogen activator inhibitor levels correlated significantly with birth weight and placenta weight and may therefore reflect placental function.

Antithrombin III levels in preeclampsia correlate with maternal and fetal morbidity

In 57 patients with pregnancy-induced or aggravated hypertension, antithrombin III levels correlated inversely with maternal morbidity. Morbidity was determined by the maximal diastolic blood pressure, disturbance of renal and liver function, and thrombocytopenia. Antithrombin III levels and platelet counts correlated inversely with the degree of placental infarction. Proteinuria (grams per 24 hours) was most predictive of fetal outcome, which was considered to be either favorable if a healthy baby could be discharged with its mother or unfavorable in case of perinatal death or a prolonged stay in the neonatal intensive care unit. Plasma antithrombin III and serum glutamic oxaloacetic transaminase levels, in that order, augmented the number of correct predictions. Antithrombin III inhibits blood coagulation by forming irreversible complexes with activated clotting enzymes, notably with factor Xa and thrombin. Evidence is presented which suggests that antithrombin III levels in preeclampsia are depressed as a result of increased consumption in the maternal vascular tree, rather than decreased synthesis or increased urinary loss.

Second-trimester placental volume measurement by ultrasound: Prediction of fetal outcome

A prospective study evaluated sonographic second-trimester placental volume measurements in the prediction of fetal outcome. A parallel section scan method was used. Abnormal fetal outcome could be predicted with a sensitivity and specificity of approximately 90%. Evidence is given that fetal growth retardation is preceded by abnormal placental development in the first half of pregnancy. To a large extent, fetal birth weight and outcome are results of placental development and the ability of the placenta to meet the growing needs of the fetus as determined by its intrinsic growth potential.

Risks of midtrimester amniocentesis; assessment in 3000 pregnancies

Summary. The obstetric outcome of 3000 pregnancies with midtrimester amniocentesis was followed in all but one patient. Thirty pregnancies ended in fetal death or abortion within 3 weeks after amniocentesis. Chronologically 23 of these occurred in the first series of 1500 pregnancies and the remaining seven fetal deaths/abortions within 3 weeks after amniocentesis occurred in the second series of 1500 pregnancies. Fetal loss within 3 weeks after amniocentesis was apparently related to the experience of the obstetrician and to the use of modern ultrasound guidance. It is concluded that the risk of fetal death after midtrimester amniocentesis is approximately 0.5%, if only experienced obstetricians using modern techniques are involved.