Zoltán Papp

MATERNAL AND NEONATAL OUTCOME OF PREECLAMPTIC PREGNANCIES: THE POTENTIAL ROLES OF FACTOR V LEIDEN MUTATION AND 5,10 METHYLENETETRAHYDROFOLATE REDUCTASE

Objective To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women.Study Design One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates.Results Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90–20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24–6.48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia.Conclusion Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

Apoptosis in Various Organs of Preterm Infants: Histopathologic Study of Lung, Kidney, Liver, and Brain of Ventilated Infants

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL). Twenty-four autopsy cases were studied histologically to detect the apoptotic ratio, which was performed on the basis of hematoxylin and eosin staining and validated by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) reaction. Elevated apoptotic ratio was found in stages II, III, and IV of bronchopulmonary dysplasia (BPD) among alveolar and bronchiolar cells. The apoptotic activity was very low in stage I of BPD. High apoptotic ratio was detected in hypoxic injuries of the central nervous system (CNS) of preterm infants. Features of apoptosis were present in proximal and excreting tubules of the kidney. Significant elevation of apoptotic activity may play a role in the development of BPD, ischemic brain lesions, and renal failure.

β2-adrenergic receptor gene polymorphisms and pregnancy outcome

Abstract Aims: The association between alleles at two loci of the polymorphic β2-adrenergic receptor (β2AR) gene and pregnancy outcome was determined. Methods: In a case-control study, buccal swabs obtained from 159 mother-infant pairs after a preterm or term birth were analyzed by gene amplification and endonuclease digestion for polymorphisms at codons 16 and 27 of the β2AR gene. Results: Homozygosity for allele A at codon 16 (Arg-16) occurred in 26 (20.5%) of 127 mothers with a term birth and in none of the mothers who had a spontaneous preterm birth (p = 0.002). Conversely, 24 of 32 (75.0%) mothers with a spontaneous preterm birth, as compared to 58 of 127 (45.7%) mothers with term births, were Arg-16/allele G (Gly-16) heterozygotes (p = 0.003). There was no relation between pregnancy outcome and infant genotype at codon 16 or maternal or infant genotypes at codon 27. The alleles at codon 16 and 27 were in linkage disequilibrium and the combinations of Arg-16-Gln-27 homozygosity (p = 0.04) and Arg-16/Gly-16-Gln homozygous (p = 0.01) were associated with a decreased and increased rate of spontaneous preterm birth, respectively. Conclusion: At codon 16 of the β2-AR gene, maternal Arg-16 homozygosity protects against, and Gly-16 predisposes to spontaneous preterm birth.

Hypogastric artery ligation for severe hemorrhage in obstetric patients

Abstract Ligation of the hypogastric arteries (HAL) was first introduced into surgery by the end of the 19th century to control intractable hemorrhage from the uterus of women with advanced cervical cancer. At present, HAL is one in a spectrum of operative methods to control life-threatening postpartum hemorrhage before hysterectomy. Bilateral ligation of the internal iliac artery does not result in complete blockage of but to a significant decrease in blood supply to the female pelvic organs. Soon after ligation three previously existent collateral circulations will develop. Due to the smaller caliber of these arteries, the arterial pulse and pulse pressure are virtually eliminated. The effectiveness of HAL in avoiding hysterectomy for postpartum hemorrhage has been reported in up to 50% of cases. HAL has no adverse effect on subsequent fertility or pregnancy outcome, however, assessment for intrauterine fetal growth restriction is recommended. This safe and effective procedure should be taught during obstetric and gynecologic training.

Factors Influencing Parental Decision Making in Prenatal Diagnosis of Sex Chromosome Aneuploidy

OBJECTIVE: To evaluate factors influencing parental decisions toward continuing or terminating a pregnancy with prenatal diagnosis of sex chromosome aneuploidy. METHODS: We reviewed the records of patients with fetuses with sex chromosome aneuploidy between 1990 and 2001. A questionnaire survey of women who chose to terminate such pregnancies was designed to examine aspects of their decision-making process. RESULTS: Forty-nine of 89 pregnancies with sex chromosome aneuploidy were terminated (termination rate 0.55; 95% confidence interval 0.45–0.65). Pregnancies with abnormal ultrasound findings (14/16, 87%), with 45,X or 47,XXY karyotypes (26/36, 72%), and with nonmosaic karyotypes (30/48, 63%) were terminated significantly more often than pregnancies with normal ultrasound findings (35/73, 48%; P < .01), with 47,XXX or 47,XYY karyotypes (4/12, 33%; P < .05), and with mosaic karyotypes (5/25, 20%; P = .01). There was a trend (P = .136) toward a lower rate of termination from 67% to 36% across time, with a significant decrease from 67% to 7% in pregnancies with 47,XXX; 47,XYY; and mosaic karyotypes (P < .01), and no change in cases with 45,X and 47,XXY karyotypes (67% compared with 69%; P = 1.0). Abnormal sexual development and infertility were the greatest parental concerns related to termination. CONCLUSION: Fear of having a child with abnormal sexual development or infertility remains the major determinant of parental decision toward terminating pregnancy, resulting in consistently high termination rates across time in pregnancies with 45,X and 47,XXY karyotypes. In cases with 47,XXX; 47,XYY; and mosaic karyotypes, the declining termination rate across time is a consequence of recent studies reporting normal sexual development and fertility. LEVEL OF EVIDENCE: II-2

Light baryons in a constituent quark model with chiral dynamics

Abstract It is shown from rigorous three-body Faddeev calculations that the masses of all 14 lowest states in the N and Δ spectra can be described within a constituent quark model with a Goldstone-boson-exchange interaction plus linear confinement between the constituent quarks.

Prenatal detection of trisomy 21 and 18 from amniotic fluid by quantitative fluorescent polymerase chain reaction.

Prenatal diagnosis of fetal trisomies is usually performed by cytogenetic analysis on amniotic fluid. This requires lengthy laboratory procedures and high costs, and is unsuitable for large scale screening of pregnant women. An alternative method, which is both rapid and inexpensive and suitable for diagnosing trisomies even from single fetal cells, is the fluorescent polymerase chain reaction using polymorphic small tandem repeats (STRs). In this paper we present the preliminary results of a larger study comparing parallel prenatal diagnoses of trisomies 21 and 18 using cytogenetics with quantitative fluorescent polymerase chain reaction using STR markers. The results obtained by the two techniques were concordant in all cases. This is the first study reporting significant numbers of prenatal diagnoses using the quantitative fluorescent polymerase chain reaction. We believe that further studies on greater numbers of samples will determine the absolute reliability of this technique. These results also provide a model for diagnosis of trisomy from single fetal cells isolated from maternal blood.

Genetic Amniocentesis in Multiple Pregnancy

Objectives: Second-trimester genetic amniocentesis is the most frequently used invasive prenatal diagnostic technique. Several reports have been published about the effect of genetic amniocentesis on fetal loss in multiple pregnancies over the past two decades. Here we analyze our experience with genetic amniocentesis in multiple pregnancies over the past 10 years. Methods: Details of 184 multiple pregnancies were processed in all cases in whom genetic amniocentesis was performed in women who presented at our department since 1990. The outcomes of 175 cases (95.1%) out of 184 genetic amniocenteses were available to us. As a control group, we followed up the outcome of 300 twin pregnancies in which no genetic amniocenteses were performed. Results: We found that the proportion of spontaneous losses in multiple pregnancies between the 18th and the 24th gestational weeks was 2.39%, whereas if genetic amniocentesis was performed the loss rate before the 24th week was 3.87%. The perinatal mortality rate was 10.03/1,000 in the group who underwent amniocentesis, while it was 10.52/1,000 in the group without amniocentesis. Conclusions: Our results suggest that the genetic amniocentesis performed in multiple pregnancies slightly increased (1.48%) the fetal loss rate until the 24th week. Beyond 5 weeks after the procedure, no consequent fetal loss should be expected. In our study the intervention did not have any undesired effect on perinatal mortality rates.

Massive obstetric hemorrhage.

Abstract Massive obstetric haemorrhage is a major cause of maternal death and morbidity; abruption of the placenta, placenta praevia and postpartum haemorrhage being the main causes of haemorrhages. A delay in the correction of hypovolaemia, diagnosis and treatment of defective coagulation and/or surgical control of bleeding are the avoidable factors in most maternal deaths caused by haemorrhage. The main goal is to maintain effective circulating intravascular volume by prompt and adequate replacement of blood, crystalloids or fresh-frozen plasma through more than one intravenous line (it might be necessary to pump blood under pressure) with constant monitoring of the pulse rate and the arterial blood pressure. The rapid correction of hypovolaemia with crystalloids and red cells is the first priority, followed by blood component therapy. Oxytocin and prostaglandin will correct uterine atony, and appropriate surgical intervention is required for traumatic bleeding. Ligation of the uterine arteries, ovarian arteries and hypogastric arteries will usually control uterine bleeding and arterial embolization is also effective. Hysterectomy should also be considered in severe cases. All gynecologists should be able to perform without delay the operative maneuvers which are necessary to control the bleeding, including hypogastric artery ligation, or even emergency hysterectomy. This topic may have received little attention because it is perceived as being associated with maternal morbidity rather than mortality in developed countries; it is only recently that the extent and importance of postnatal maternal morbidity has been recognized.

Prenatal diagnosis and pathoanatomy of iniencephaly

The authors discuss the diagnostic criteria of iniencephaly based on data from the literature and eleven additional, new cases. The most important differential diagnostic problems involve anencephaly with spinal retroflexion and the Klippel‐Feil syndrome. Ultrasound indicated cranio‐spinal alterations while amniotic fluid AFP estimation and exfoliative cytology substantiated abnormal closure of the neural tube, thus comprising helpful means for prenatal diagnosis of iniencephaly. The authors emphasize the need for median‐sagittal sectioning through the spinal column for accurate evaluation of vertebral abnormalities. This, together with close observation of the occiput and the foramen magnum, helps the precise diagnosis of iniencephaly and once regularly applied will most likely result in more frequent recognition of this developmental abnormality.