Hospitalization vs. outpatient care in the management of triplet gestations.

OBJECTIVE: To compare the course and outcome of triplet gestations under a preventive care strategy that includes hospitalization, surveillance, bed rest, and daily specialized care from the beginning of the second trimester, with pregnancies managed according to the Croatian standard outpatient care protocol for multiplets. METHODS: A retrospective study of 79 triplet pregnancies. Preventive hospitalization from the beginning of the second trimester, with complete bed rest and all necessary interventions, was chosen by 55 women (Group I). The remaining 24 women (Group II) elected the standard outpatient protocol for multiple pregnancies. Outpatient management with prophylactic bed rest was initiated at home as soon as the multiple pregnancy was diagnosed. After 28 weeks of gestation, all outpatients were hospitalized until delivery irrespective of symptoms. RESULTS: There was no difference between the groups regarding maternal age, race, pre-pregnancy weight and height, weight gain during the first 24 weeks of pregnancy, or the proportion of pregnancies achieved with assisted reproductive technology. Four out of 55 women (7.2%) from Group I and 4 out of 24 women (12.5%) from Group II had monochorionic triplet pregnancies (P=n.s.). Nulliparity was more frequent in Group I than in Group II (P=0.006). Elective cesarean delivery was significantly more frequent in Group I (46 out of 55 gestations, 72.7%) than in Group II (9 out of 24 gestations, 37.5%), P=0.024. Gestational age at delivery and mean birth weight were significantly higher in Group I than in Group II (P<0.001). Deliveries up to 28 weeks of pregnancy were infrequent in Group I (P=0.02). Thirty-three gestations in Group I (60%) and 6 (25%) in Group II had a duration of 33-36 weeks (P<0.001). Two out of 55 triplet gestations in Group I (3.6%) and 4 out of 24 in Group II (16.7%) ended in spontaneous abortion (P=0.053). The survival of the three triplets was more frequent in Group I than in Group II (P=0.048). For gestations reaching 24 weeks or more, the fetal and perinatal death rate was significantly lower in Group I (P<0.001). In Group I the intrauterine death rate for fetuses weighing 1500 g or less was also significantly lower (P=0.007), and the early neonatal death rate was almost half (15.8 vs. 28.9%, P=0.157). There were no differences in other pregnancy complications between the two groups except significantly more frequent preterm premature rupture of membranes and preterm labor requiring parenteral tocolysis in Group II (P=0.042 and 0.036, respectively), and significantly more frequent fetal growth retardation in Group I (P<0.001). CONCLUSION: Preventive hospitalization offers a better outcome for triplets even though prolonged hospitalization and all other procedures necessary to achieve optimal pregnancy outcome are also offered in the Croatian standard outpatient care protocol for multiplet pregnancies.

Antenatal predictors of the neurologic sequelae at 3 years of age: a multivariate analysis.

OBJECTIVE: To study the association between fetal blood flow abnormalities and the occurrence of long-term neurologic sequelae. STUDY DESIGN: Umbilical, aortic and middle cerebral artery blood flow parameters were obtained by Doppler examination and retrospectively analyzed in 128 high-risk singleton pregnancies, followed by neurologic examination of the surviving children at 3 years of age. Traditional parameters of neurologic outcome (Apgar scores, intrauterine growth retardation (IUGR), umbilical artery pH and base deficit, gestational age, birth weight, newborn encephalopathy, mode of delivery, fetal heart rate, neurosonographic examination) were included as possible confounding factors. Mann-Whitney U-test, Student's t-test, analysis of variance or Fisher's exact test, where applicable, were used for the univariate analysis. A stepwise logistic regression procedure was conducted to test the independent association of selected perinatal risk factors on neurological outcome. Statistical significance was assumed at P<0.05. RESULTS: Eighteen out of 114 surviving children suffered neurologic illness at 3 years of age. Four children had major neurologic dysfunction and the remaining 14 suffered minor or mild form of the disease. Although blood flow parameters and various perinatal parameters did not differ significantly between the group of children with major neurologic dysfunction and healthy children, aortic resistance index showed an independent association with occurrence of minor or mild neurologic disabilities. CONCLUSION: Antenatal evaluation of the aortic blood flow might be an important predictive variable for permanent neurologic disturbances.

Pregnancy outcome in renal transplant recipients.

OBJECTIVE: To correlate pregnancy outcome with complications in pregnancy and transplantation-to-pregnancy interval in renal transplant recipients in Croatia. METHOD: Data on 23 pregnancies after prepregnancy stabilization of blood pressure and normalization of graft function were retrospectively analyzed. RESULT: The mean interval between transplantation and conception was 3.1 years. Primary renal disease was chronic glomerulonephritis in 7, chronic pyelonephritis in 7 and agenesis of right kidney and stenosis of left renal artery in 1 patient. There were 10 term and 5 preterm deliveries, 6 induced and 2 spontaneous abortions. The mean gestational age was 38.1 weeks and the mean newborn birthweight was 3015 g. The prematurity rate was 21.7%. Patients with arterial hypertension in pregnancy, elevated serum creatinine level and bacteriuria, as well as those with conception occurring less than 2 years after transplantation, had a higher rate of therapeutic and spontaneous abortions, preterm deliveries and low birth weight infants. CONCLUSION: The interval between transplantation and conception, as well as allograft function during pregnancy, seem to be of great importance for successful obstetric outcome in renal transplant patients.

Pheochromocytoma with negative urinalysis in pregnancy.

We present a rare case of adrenal pheochromocytoma in pregnancy, with serial 24-h urine specimen collections showing normal concentrations of catecholamine metabolites. The diagnosis was based on clinical presentation, abdominal ultrasound, and magnetic resonance imaging, and was confirmed on post-operative pathohistological examination. Clinical suspicion of pheochromocytoma in pregnancy should be sufficient to implement adequate therapeutic measures, regardless of urine catecholamine concentrations.

Maternal neonatal outcome in quadruplet and quintuplet versus triplet gestations.

OBJECTIVE: Examination and comparison of the natural histories of triplet versus quadruplet and quintuplet gestations. STUDY DESIGN: A retrospective study of sixty-four multifetal pregnancies (fifty-two sets of triplets, nine sets of quadruplets and three sets of quintuplets) cared for during past 12 years in our department. Quintuplets and quadruplets were compared with triplet pregnancies according to gestational age, birthweight, pregnancy complications and perinatal outcome. Student's t-test, Fisher exact test and chi2 test were used for statistical analysis, considering P value of <0.05 as statistically significant. RESULTS: Although mean gestational age at delivery between triplets and higher order gestations was not significantly different, birthweight of quadruplets and quintuplets was significantly lower. Pregnancy complications, including intrauterine growth retardation, were equally distributed between the groups. Early neonatal and perinatal mortality were significantly higher in quadruplets and quintuplets than in triplets. Surprisingly, survival of growth retarded fetuses was better than survival of their eutrophic counterparts. The spontaneous loss rate was 11.5% for entire triplet gestation and 16.7% for quadru- and quintuplet pregnancies. CONCLUSIONS: As the spontaneous loss rate of triplets and higher order pregnancies observed in our study is quite similar to pregnancy loss rate caused by multifetal pregnancy reduction, conservative management of multifetal pregnancies in specialised tertiary centers seems to be a prudent solution.

The triple-marker test in predicting fetal aneuploidy: a compromise between sensitivity and specificity.

OBJECTIVE: to review the contribution of unconjugated estriol in Down's syndrome detection, and influence of maternal age, cut-off choice, and population specificity on the balance between triple-marker test sensitivity and specificity. STUDY DESIGN: Prenatal karyotyping was performed in 2833 pregnant women, 73% of them over the age of 34. Duration of gestation was determined by ultrasound in 98% of women. Prior to amniocentesis, the serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol were evaluated and corrected for weight. The risk of trisomy 21 was calculated for the first 986 subjects using default medians, and for 1847 by our population-specific medians. The cut-off was initially 1:300 at term, but the 1:100 and 1:200 risks were also tested. Down syndrome risk was calculated with alpha-fetoprotein and human chorionic gonadotropin combination as well. Linear logistic regression model was performed to test the ability of aneuploidy markers to classify patients into normal and trisomic groups. RESULTS: There were twelve cases of Down's syndrome, seven of trisomy 18, four of trisomy 13, and one trisomy 22. Four cases of aneuploidy (16.7%) referred to women younger than 35. With the cut-off risk of 1:300, detection rate was 87.5% and specificity 63.3%, and with 1:100, 66.7% and 79.5%, respectively. The sensitivity for Down's syndrome was from 75% for cut-off=1:100 to 92% for cut-off=1:300, while detection of other trisomies was less successful (58% and 83%, respectively). Exclusion of unconjugated estriol MoM from the risk calculations reduced detection rate by 33% and improved specificity by 4% independently of cut-off choice. Linear logistic regression analysis showed that only unconjugated estriol was able to correctly classify patients between normal and trisomy 21 (p=0.011, odds ratio=1.445), and normal and trisomy 18 (p=0.0023, odds ratio=1.96) groups. CONCLUSIONS: The unconjugated estriol significantly contributes in Down's syndrome detection with cost of slightly reduced specificity. The 1:300 risk caused an unfavorable compromise between sensitivity and specificity. A higher cut-off, 1:100, would indicate performance of amniocentesis in women aged 39 years and older, and in those aged 35-39 only after the screen-positive result.

Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) in Croatia.

We report on the prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase in 20 at-risk pregnancies (16 salt-wasting and 4 simple virilizing families). We have diagnosed 3 affected fetuses (2 males and 1 female), 3 healthy homozygotes (2 males and 1 female), and 14 healthy heterozygotes (7 females and 7 males). These data were collected over 4 years. In 16 fetuses, the diagnosis was made with measurements of 17-hydroxyprogesterone (17-OHP) and delta-4-androstenedione (delta) in amniotic fluid (AF), human leukocyte antigen (HLA) typing of amniotic cells, as well as karyotypes between the 16th and 18th weeks of gestation. In 4 fetuses, DNA analysis of amniotic cells was also performed. In 3 pregnancies in which affected fetuses were suspected (on the basis of HLA typing and measurements of 17-OHP and delta concentrations in AF), the fetuses were electively aborted between the 17th to 19th weeks of gestation by parental decision. In all aborted fetuses, diagnosis was confirmed with HLA typing, autopsy findings of hyperplastic adrenal glands, and ambiguous genitalia in female fetuses. Postnatal diagnosis was confirmed in healthy fetuses with HLA typing and serum measurements of 17-OHP concentrations, and in 4 of them with DNA analysis. In 3 of the 4 families, DNA analyses revealed the following mutations: in Family 1, the index case mutation was Intron 2, Exon 3/Exon 6, and the fetus was Normal/Exon 6; in Family 2, the index case mutation was Ex1 Int2 Ex3/ Int2, and the fetus was Ex1 Int2 Ex3/Normal; and in Family 3, the index case mutation was Ex8(356)/Ex8(356), and the fetus was Ex8(356)/ Normal. We also report one case of prenatal diagnosis and treatment. Dexamethasone 0.5 mg BID (20 micrograms/kg/d) was given starting at 6th week of gestation. Prenatal diagnosis suggested, but did not prove, that the female fetus was a heterozygote as the fetus lacked the paternal mutation Ex8(318). No mutation was found in the mother. The fetus, the mother, and the affected sib shared a haplotype, further suggesting heterozygosity. The unaffected status was confirmed postnatally.

Possible influence of expatriation on perinatal outcome.

BACKGROUND: In order to test the hypothesis of possible influence of environmental stress on the length of gestation the data on deliveries in the Maternity Unit, Zagreb University School of Medicine in three six months periods; May-October 1991 (active war in Croatia), May-October 1990 (pre-war period), and the same period in 1992 are analysed. METHODS: Deliveries of 7845 women from free areas of Croatia (non-displaced population) and deliveries from 712 women from occupied areas of Croatia, as well of 593 Croatian refugees from Bosnia and Herzegovina and Serbia (expatriated population) were compared. The duration of pregnancy, fetal weight, immediate neonatal condition, mode of delivery and perinatal outcome in non-displaced and expatriated population were compared using chi-square test in statistical analysis. RESULTS: During 1992 and 1991, there was a slight increase in total number of deliveries in comparison to 1990. The number of deliveries by displaced women more than doubled. The incidence of major pregnancy complications was almost the same for both groups in all three time periods. The two populations were comparable regarding their age, parity and previous obstetric history. Slight increase in preterm delivery rate (7.7% in l990, 8.7% in 1991 and 9.4% in 1992), and a subsequent slight decrease in birth weight was found in all women. There was no significant change in the proportion of growth-retarded newborns. Expatriated women both in 1990 and in 1991 delivered twice as often prematurely in comparison to non-displaced women (17.5% and l4.3% deliveries), respectively. Birth weight of their infants was significantly more often under 2500 grams. Slight increase in overall perinatal mortality was observed. Perinatal mortality in the experiated population was significantly higher than in the non-displaced population. Increase in perinatal mortality could be attributed exclusively to increase in prematurity rate. CONCLUSION: Our results support the concept of possible influence of stress, fear, exile and inadequate antenatal surveillance on the length of gestation.

Antenatal fetal demise in multiple gestation--the outcome of surviving fetus at one to four years of age.

The outcome of 26 multifetal pregnancies with single fetal demise after 12 weeks of pregnancy cared for at the University Medical School of Zagreb from 1986 to 1991 is presented. Growth retardation of dead and surviving infant and pathohistological findings consistent with reduced uterine blood flow to cotyledonary space was the most frequent complication, irrespective of the type of placentation. Perinatal infection was the most frequent neonatal complication. Neonatal asphyxia was observed in only one infant. The outcome at 1-4 years of age was perfect in 14 out of 15 surviving infants for whom data are available. An early diagnosis of multifetal pregnancy, based essentially on ultrasonography and appropriate monitoring of the mother and the survivor, with cesarean delivery carried out at first signs of imminent asphyxia, is the best guarantee for a favorable outcome.

[The effect of chronic kidney disease on the course and outcome of pregnancy]. / Utjecaj kronicnih bubreznih bolesti na tijek i ishod trudnoce.

In order to estimate the effect of renal disease on the pregnancy, and the effect of pregnancy on the natural course of renal disease, the course and outcome of the 37 pregnancies was analyzed in gravidas with chronic renal disease. The women were cared for between 1978 and 1990 at the Department of Obstetrics, School of Medicine University of Zagreb. Analysis of the results in this article is retrospective. Thirty-six pregnancies finished by vaginal or cesarean delivery or by abortion, while one pregnancy was ectopic and ended by laparotomy during the 20th week. There were 31 live births from 36 fetuses (86.1%), 5 stillbirths (13.19%), of which 2 pregnancies ended in fetal death (abortion). In addition, there were 6 instances of neonatal death (8.3%). Twenty-five percent of pregnancies finished before 37 weeks of gestation. In 6 of 34 (17.6%) deliveries amniotic fluid was meconium stained, and 5 of 31 (16.1%) infants were born hypoxic. There were 29 percent of growth retarded liveborn fetuses. Perinatal mortality was 167/1000. Renal insufficiency was noted in 12 of 37 (32.4%) pregnancies, 54% of pregnant women had hypertension, 8.1% hyperkalemia, 78.4% were anemic, 27% had significant bacteriuria and 21.6% overt pyelonephritis. There was one case of acute deterioration in renal function that required hemodialysis, and one case of preeclampsia. Renal insufficiency or hypertension reduce drastically the chances for a successful outcome of pregnancy in gravidas with kidney disorders. However renal insufficiency in the presence of hypertension, carries even poorer prognosis, with perinatal mortality of 428/1000.

[Maternal and fetal monitoring during labor]. / Nadzor majke i ceda u porodu.

By use of cardiotocography, as screening method, and by fetal acid-base status estimation, it is possible, nowdays, to assess fetal oxygenation during every labor, allowing that way to recognize jeopardized fetus, and to undertake termination of labor on time. Fetal intrapartal mortality in Croatia has been declining for years. In 1985 fetal intrapartal mortality was 1.2%, in 1988 1.0% and in 1990 only 0.6%. At the Department of Obstetrics and Gynecology School of Medicine University of Zagreb fetal intrapartal mortality dropped from 3.3% in period from 1963 to 1967 to 0.6% in 1990. Increase in proportion of caesarean section deliveries, as well as increase in number of CTG equipments on our disposal is roughly parallel to this decline in intrapartal and perinatal mortality. In 1972 in only 4% of maternity hospitals there were more than 6% caesarean section deliveries, whereas in 1990 even in 26% of them the proportion of caesarean section deliveries exceeded 10%. In 1985 we were in need for 29 CTG equipments, and in 1990 for only 19. The decrease in perinatal, intrapartal and early neonatal mortality must be put in connection with increase in proportion of caesarean section deliveries and with increase in CTG's on disposal. On the contrary, fetal mortality during pregnancy has not changed for years and is between 4.7 and 5.7%. In spite of clearly improved perinatal outcome, this points to still not adequate antenatal surveillance with inadequate screening of high risk pregnancies.

[Pregnancy outcome after early amniocentesis]. / Ishod trudnoce nakon rane amniocenteze.

The indications, karyotype, and outcome of 1812 pregnancies following midtrimester amniocentesis (eACZ/as) performed from 1977 to 1989 are presented, especially regarding the risk of pathologic karyotypes and spontaneous abortion. There were 37 pathologic karyotypes (trisomy 21 in 24 pregnancies). The spontaneous abortion rate following amniocentesis was 2.8% although it was almost halved after direct ultrasound guidance had been introduced (1.87% versus 3.66%). In gravidas with previous spontaneous abortion, the preterm delivery rate and spontaneous abortion rates following rACZ were significantly increased. There is a progressive increase of the spontaneous abortion rate after eACZ with the number of previous spontaneous abortions; 5.83% when there was only 1 previous spontaneous abortion, 7.83% when there were 2, and 8.75% when there were 3 or more spontaneous abortions. Previous spontaneous abortions do not increase the risk of chromosomal aberration. In women aged 37 years or more the risk of trisomy 21 is 0.69%, aged 38 years 1.55% and over 39 years 0.44%. The risk is rapidly increasing after 40 years of age (2.25%). The proportion of pathologic karyotypes in these age groups was significantly higher in comparison to younger women. The age limit of 37-38 years as the indication of a possible appearance of mid-trimester ACZ is discussed.

[T lymphocyte subpopulations in women with spontaneous abortions]. / Subpopulacije T limfocita u zena sa spontanim pobacajima.

Investigations were carried out to observe changes in the functional T-lymphocyte activity, as well as the presence of single T-lymphocyte subpopulations in the first trimester of pregnancy in 10 pregnant women with recurrent abortions in their previous pregnancies, compared to 8 healthy pregnant women in the first trimester and 20 of them in the third trimester of pregnancy, and in 30 healthy nonpregnant women at the fertile age. The functional T-lymphocyte activity (PHA-test) was decreased in pregnant women with recurrent abortions (54 +/- 0.99) and in healthy pregnant women (56 +/- 2.50) compared to healthy nonpregnant women (76 +/- 4.80). The total number of lymphocytes in the first trimester was decreased in the investigated group (22 +/- 5.38) and also in healthy pregnant women (25 +/- 1.55) in relation to nonpregnant women (33 +/- 3.15). The percentage of T-lymphocytes was similar (59 +/- 4.32 and 58 +/- 1.96 in relation to 80 +/- 2.80). Helper T-lymphocytes (T-4) were significantly decreased in the investigated group (28 +/- 4.25) compared to the group of healthy pregnant women in the first trimester (32 +/- 1.60) and healthy nonpregnant women (55 +/- 2.37). Suppression T-lymphocytes (T-8) were significantly increased in the investigated group (30 +/- 3.11) in relation to healthy pregnant women in the first trimester (25 +/- 2.45) and to healthy nonpregnant women (23 +/- 1.95). The ratio of helper T-lymphocytes and suppression T-lymphocytes (T4:T8) was significantly lower in pregnant women with recurrent abortions compared to healthy pregnant women in the first trimester and to healthy nonpregnant women.

[Pregnancy outcome after conization]. / Ishod trudnoce nakon konizacije.

The outcome of pregnancy in 68 women with previously made conisation of the uterine cervix is presented. As a control group were 68 pregnancies which were the first in the protocol following the examined ones. Of 68 women of observed group there were 45 (66.2%) term deliveries, 10 (14.7%) preterm deliveries, and 13 (19.1%) spontaneous abortions, while in women of control group the results were 52 (76.5%), 6 (8.8%) and 10 (14.7%) respectively. This did not represent a statistical significance (chi 2 = 1.89; p less than 0.05). In the first desired pregnancy after conisation 43 (63.2%) women were resting in bed and taking medicaments, 20 (29.4%) had cervical cerclage, while in women of the control group there were 14 (20.6%) and 5 (7.4%), respective what represents statistically significant difference (chi 2 = 25.4; p less than 0.01; chi 2 = 11.3; df = 1, p less than 0.01). Of 43 women of observed group with resting and medicaments in pregnancy 33 (76.7%) had term deliveries, 8 (18.6%) preterm deliveries and 2 (4.7%) spontaneous abortions, while in 25 women without resting and no medicaments, the results were 13 (52%), 11 (44%), 1 (4%) respectively. This represents statistical significant difference (chi 2 = 4.42; p less than 0.05). In the control group of 54 women without resting and no medicaments, there were 45 (83.3%) term deliveries, 3 (5.6%) preterm deliveries and 6 (11.1%) spontaneous abortions, while in 25 women after conisation and no resting there were 13 (52%), 11 (44%), 1 (4%) respectively. This represents a statistical significance (chi 2 = 8.59; p less than 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)

[Electromyography of the uterus in monitoring pregnancies with symptoms of premature labor]. / Pouzdanost elektromiografije uterusa u pracenju trudnoca sa simptomima prijevremenog porodaja.

Characteristics of uterine muscle action potentials in 100 gravidas with symptoms of preterm labor or imminent abortion (presence of contractions with cervical changes) from 18th till the 32nd weeks of pregnancy are analysed. Twenty four gravidas with uncomplicated pregnancy were monitored electromyographically from the 20th weeks until term, once a week. There was low electrical activity in uncomplicated pregnancies up to 7 days before labor. A similar trend was observed in pregnancies that were finished before term. But, in symptomatic pregnancies finished preterm, the index of uterine muscle electrical activity (expressed in the percentage of voltage plus frequency) was continuously, although not significantly, above the values in symptomatic and asymptomatic term pregnancies. In only 2 out of 18 (11.1%) before term terminated pregnancies and in 45 out of 82 (54.9%) in term accomplished pregnancies, was electrical silence was registered during clinical symptoms (p less than 0.01). In preterm accomplished pregnancies, higher voltages and more frequent occurrence of biphasic and polyphasic spikes were registered (p less than 0.05), although the single parameter was of no prognostic significance. With a successful tocolytic treatment, the index of uterine muscle electrical activity was significantly reduced (from 57.16 to 20.86, t = 2.52, p less than 0.02) and was similar to that registered in symptomatic term pregnancies subjected to no tocolytic treatment. Although intravenous tocolysis was shown diminish voltage and frequency, in preterm delivered pregnancies no reduction in electrical activity was observed. Uterine electromyography could be used as a predictor of successful or unsuccessful tocolytic treatment.

[Peroral and intracervical administration of prostaglandin E2 for stimulation of term labor in premature rupture of fetal membranes]. / Peroralna i intracervikalna primjena prostaglandina E2 u stimulaciji rocnog poroda kod prijevremenog prsnuca vodenjaka.

The outcome of stimulation of labour in 219 primiparous patients with more than 6 hours following a premature rupture of the membranes, and with an ripe cervix, without the established labour, was analysed according to the mode of treatment. One hundred and thirty eight (138) women received PGE2 peroral tablets, 14 intracervical PGE2 gel, and 67 oxytocin intravenously. There were 73.2% vaginal deliveries in the group that received PGE2 per os, 77.5% in the group that received oxytocin, and 92.9% in the group that was given intracervical gel. The differences were significant. The cervix remained unripe in 9.4% patients that received PGE2 perorally, in 14.9% of those that received oxytocin, while in the gel group it became favourable in all parturients. Uterine polisistoly was encountered in 10.9% labours after peroral stimulation, in 7.1% in the gel group and in 1.5% in the oxytocin group, and perinatal asphyxia in 16.7%, 7.1% and 13.4%, respectively. When too frequent, especially if combined with oxytocin and given to patients with a moderately favourable cervix, peroral stimulation predisposes to uterine polisitoly. Intracervical application of PGE2 gel is the method of choice in primigravid patients with a premature rupture of the membranes and the unripe cervix (Bishop score O). In gravidas with a more favourable cervix (Bishop score 4-6) the administration of oxytocin is acceptable with less complications. In those with a moderately favourable cervix (Bishop score 1-4) the gel application proved to be preferable, although stimulation could be carried out as well.

HLA and red blood group antigens in pregnancy disorders.

Total of 356 women with various types of pregnancy disorders as well as their husbands were classified in four groups regarding the type of the disorder as follows: 1. Recurrent spontaneous abortions (RSA) of unknown etiology (N = 105) and RSA - primary aborters only (N = 84); 2. Blighted ovum (N = 80); 3. Rh immunization in pregnancy (N = 90); 4. ABO immunization in pregnancy (N = 47). Two groups of couples were used as controls: 1. Couples randomly taken from forensic medicine cases of paternity evaluation (N = 104); 2. Couples having two or more children with HLA immunization in pregnancy (N = 78). The couples from all groups were typed for red blood group antigens of ABO, Rhesus, MNSs, Kell, Duffy, Lewis, Kidd and P systems and also for HLA antigens. Significantly higher frequency of antigen HLA-A9 was found in women with RSA (corr. p = 0.0003) and in women with pregnancy disorders caused by Rh immunization (corr. p = 0.0136). In couples with RSA the degree of HLA compatibility was significant (p = 0.0048) and the reactivity of spouses in MLR was significantly decreased (p = 0.0001). Significantly, more low responders in MLR were also found among the women with RSA as compared to the controls (p = 0.0217). Two possible pathologic mechanisms may explain the association between HLA antigens and RSA: 1. immunological defects which are linked to HLA-D/DR region causing malfunction of immunosuppressive mechanisms during pregnancy; 2. endocrinological defect which is linked to HLA region as 21-OH hydroxylase deficiency gene.