Band 31, Heft 2

Objective: To compare the perinatal outcome and placental morphology of twins conceived by assisted reproductive technologies (ART) or natural conception (NC). Methods: The present retrospective study included 88 twin pairs. Methods of ART included in vitro fertilization, intrauterine insemination, embryo transfer and induced ovulation. Placental morphology was described by chorionicity, amnionicity, placental weight, umbilical cord insertion and the number of cord vessels. Perinatal outcomes included maternal age, gestational age, birth weight (BW), BW discordance and mode of delivery. Results: The mothers of ART twins were 4 years older than NC mothers. ART twins delivered 2.2 weeks earlier than NC twins. The BW of ART twins A and B were less than NC twins A and B. There was no difference in the proportion of discordant twins in either group. Dichorionic diamniotic (DD) placentas accounted for the majority of placentas in both groups. There were no monochorionic-monoamniotic placentas in ART pairs, but there were 2.9% in NC pairs. Mode of conception had no effect on placental weight in DD or monochorionic-diamniotic twins in either group except for larger DD fused placentas in the ART group. Conclusion: ART twin pairs were delivered at an earlier gestational age at lower birth weights to older mothers predominantly by cesarean section. This perinatal outcome was not reflected by placental morphology.

Objective: The purpose of this study was to determine the effect of birth weight discordance (BWD) and prematurity on twin neonatal outcome by measuring Apgar scores and blood glucose concentrations at birth. Methods: This was a retrospective cross-sectional study. All twins born at NY Methodist Hospital between January 1998 and December 2001 were eligible. Excluded were fetal deaths, maternal systemic disease, maternal infections, major neonatal malformations, neonates with birth weight < 500 g and multiple gestation greater than 2. BWD was defined as intrapair difference in birth weight expressed as percentage of the larger twin greater than 20% and prematurity as gestation of less than 37 weeks. Hypoglycemia was defined as blood glucose concentration < 40 mg/dl. Results: There were 75 (48%) preterm and 80 (52%) term twin pairs. Nineteen (12%) of the preterm and 15 (9.6%) of the term showed BWD. Mean Apgar scores at 1 and 5 minutes were higher for the term twins as expected. Neither prematurity nor hypoglycemia was present predominantly in BWD twins. Twelve of the preterm and six of the term BWD twins showed evidence of hypoglycemia. Conclusion: Hypoglycemia in the early hours of postnatal life is relatively common in preterm BWD twins. Blood glucose measurement using reagent strips is an efficient way of monitoring blood glucose concentrations in these infants.

Aims: To determine the impact of antenatal suspicion of esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) on neonatal outcome. Methods: Retrospective review of all neonates with EA who received prenatal care including fetal ultrasound and delivery at our institution from 1990–2001. Cases with suspected EA on prenatal ultrasound (hydramnios and/or an absent stomach bubble) were identified. Neonatal outcome variables for the group suspected antenatally and the group diagnosed postnatally were compared. Mann Whitney U and Fischer exact tests were used in analysis. Results: Twenty-two patients met inclusion criteria. Nine cases (40.9%) had prenatal ultrasound findings associated with EA/TEF. There was no statistically significant difference in the incidence of preterm delivery, intrauterine growth restriction, respiratory distress syndrome, additional anomalies or neonatal death, birth weight, requirement for preoperative and postoperative mechanical ventilation or length of hospital stay between the prenatally suspected and postnatally diagnosed groups. There were two neonatal demises: one had trisomy 18 and one was born prematurely at 29 weeks. Conclusions: In our experience, prenatal detection of ultrasound findings associated with EA/TEF does not affect neonatal outcome or identify a group at increased risk for neonatal morbidity and mortality. Our favorable outcomes, with or without prenatal suspicion, may reflect the comprehensive care readily available at a tertiary care facility. Larger series need to be studied to exclude the possibility of a type II error.

Aims: To determine the frequency and clinical significance of microbial invasion of the amniotic cavity at the time of delivery in preterm infants. Methods: Prospective cohort study during June 2001 and January 2002. Preterm infants < 33+6 weeks of gestation who had amniotic fluid and placental tissue sampled for culture during cesarean section were included. Results: Of a total of 80 neonates, 42 had negative culture results, 22 had growth of Ureaplasma urealyticum, and 16 had growth of other pathogens. Isolation of Ureaplasma urealyticum was associated with a decreased risk of developing hyaline membrane disease after birth but a more than 20 times increased risk of developing chronic lung disease. Patients with growth of other pathogens had a significantly higher mortality than patients with negative culture results. Conclusions: Isolation of microorganisms from the amniotic cavity at birth is associated with an adverse outcome of the preterm infant. In the light of extremely small numbers of positive blood cultures in preterm infants after birth, we consider it reasonable to recommend routine culturing of amniotic cavity tissues/fluid obtained during cesarean section in order to increase the identification rate of pathogens potentially involved in the pathogenesis of perinatal infections.

Objective: The purpose was to determine the effect of vaginal pessaries in patients at risk for spontaneous preterm birth (SPB). Study Design: Transvaginal sonography (TVS) was longitudinally performed to measure cervical length (CL) in 258 singleton at risk for SPB and 282 twin pregnancies. Pairs with or without treatment were matched for gestational age and the CL at examination. Results: In 4 singleton and 7 twin pregnancies the CL was < 15 mm before 24 weeks, the mean interval between pessary insertion and delivery was 13+2 and 12+5 weeks respectively. For the matched control analysis, 12 pairs with singleton and 23 pairs with twin pregnancies were compared. For singleton pregnancies, the mean interval between TVS and delivery was 99 (70–134) days in the treatment and 67 (2–130) days in the control group (p = 0.0184), the mean gestational age at delivery was 38 (36+6–41) and 33+4 (26–38) weeks respectively (p = 0.02). For twin pregnancies, the interval was 85 (43–129) days in the treatment and 67 (21–100) days in the control group (p = 0.001), gestational age at delivery was 35+6 (33–37+4) and 33+2 (24+4–37+2) respectively (p = 0.02). Within singleton pregnancies with pessary, there was no SPB < 36 weeks compared to 6/12 cases in the control group (p < 0.001). Within twin pregnancies, the rates were 8/23 cases with SPB < 36 weeks but none < 32 weeks, compared to 12/23 cases with SPB < 36 weeks and 7/23 cases < 32 weeks in the control group (p < 0.001). Conclusions: Insertion of a vaginal pessary may be a cost-effective preventive treatment in patients at risk for SPB. Prospective controlled trials are needed.

Our purpose was to examine the hypothesis that corticosteroids, when administered intramuscularly, can enhance the labor process and reduce the time interval between the induction and the active phase. A randomized, controlled study was conducted on 66 women with gestational age of 41 weeks and over and favorable cervix (bishop score ≥ 7). The study group (n = 32) received 10mg of dexamethasone phosphate intramuscularly in two doses at an interval of 12 hours, and the day after the enrolling administration intravenous oxytocin was given. The control group (n = 33) received only intravenous oxytocin 24 hours after enrolling. The number of patients to enter the active phase of labor was significantly higher in the study group than in the control group (n = 33 [100%] vs n = 29 [87.9%], p < 0.039). The mean time interval between induction of labor and the active phase was significantly shorter in the study group than in the control group (1.7±1.5 hours vs 4±1.7, P < 0.0001), and the mean of oxytocin dose was significantly lower in the study group (1.15±1.5u vs 4.16±2.5u, P < 0.0001). Induction of labor with the use of intramuscularly injected dexamethasone phosphate reduced the time interval between the induction of labor and the active phase.

Objective: To evaluate the effect on perinatal outcome of replacing glucose measurements for the diagnosis of gestational diabetes mellitus in central laboratories with those obtained by portable glucose meter. Study design: Simultaneously, venous blood samples were taken at the 100-g glucose tolerance test, and finger capillary blood glucose levels were also measured with a portable glucose meter in 180 pregnant patients. Patient management was according to the venous plasma glucose results. Following deliveries, the women were reallocated to diagnostic groups by both methods of measurements and by using the same cutoff values, and the outcome data were compared. Results: By using glucose values obtained by portable glucose meters instead of the results attained in the central laboratory, more women were diagnosed with gestational diabetes (33 vs 25) and the perinatal outcome was comparable. Conclusions: Obstetricians have to identify glucose intolerance during pregnancy in order to prevent macrosomia and its perinatal complications. These goals can be achieved with at least the same efficacy by performing the 100-g glucose tolerance test with a portable glucose meter as with current laboratory methods. Such an approach is time and resource saving and more convenient for both patients and health providers.

Objective: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with “ parvo biovar ” and those with “ T960 biovar ”. Study design: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. Results: 1) The “ parvo biovar ” was detected in 82% (63/77) and “ T960 biovar ” was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for “ parvo biovar ” and in 50% (7/14) of cases with positive for “ T960 biovar ”; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. Conclusions: 1) The “ parvo biovar ” is more frequently isolated from amniotic fluid of preterm gestations than the “ T960 biovar ”; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.

Aims: To study the relationship between the expression levels of cytokine/receptor genes in placenta and the pathogenesis of pre-eclampsia. Methods: The study was performed to compare the mRNA contents of cytokine (receptor) superfamily genes in placentas from 5 patients with pre-eclampsia and 5 strictly matched normal pregnancies. A complementary DNA microarray representing over 220 cytokine-associated genes was employed to complete the detection. Results: It was shown that, among the 221 kinds of cytokine-associated genes, 162 of those including 22 interleukin/interleukin receptor genes presented with a difference of over two times in pre-eclamptic placentas compared to normal placentas. Most of the 22 interleukin/interleukin receptor genes were shown to be highly expressed in preeclamptic placenta, while the expression of IL-2 receptor (IL-2Rα, GenBank: X01057) gene in preeclamptic placenta was comparatively lower than that in normal placenta. Furthermore, some tumor necrosis factor (TNF)/receptor superfamily genes, including TNF (GenBank: X02910), TNF ligands (Gen-Bank: U03398, U37518, AF053712, AF055872) and TNF receptors (GenBank: X60592, X63717, M83554, AF016266, AF016267, U81232) were also shown to be highly expressed in pre-eclamptic placenta. Besides interleukin and tumor necrosis factor (receptor) gene superfamily, the mRNA levels of another 39 cytokine and 15 cytokine receptor genes showed a two-fold difference between pre-eclamptic and normal placental tissues. Additionally, most of the genes were up-regulated in pre-eclamptic placenta. Conclusions: The up-regulation of cytokine-associated genes including interleukin and TNF (receptor) superfamily expression in placenta might be intensively related to the pathogenesis of pre-eclampsia.

Aims. Chorangiomas are rare hamartomatous lesions. Possible correlations between their occurrence and the progression of a pregnancy have been objects of discussions for quite some time. Methods. In a retrospective study 22439 unselected placentas were examined for incidences of chorioangiomas, morphological features and accompanying clinical characteristics. Results. Chorangiomas occur in 0,61% of pregnancies, they are mainly microscopically small, and 55% of them are localized subchorial. The rate of their occurrence rises almost linearly with maternal age; chorangiomas are found most often in women who are over 30 years old. Hypertension and diabetes are found more often in combination with chorangiomas than they are in otherwise normal pregnancies. In 72% of all cases girls were born; in 33% we also observed malfunctions in the maturation processes of the placental parenchyma, in particular arrested and delayed maturation of the villi. Premature births occur approximately three times more often in chorioangioma pregnancies than in normal ones. Chorangiomas are often found in primipara and twin pregnancies.

Aims. Chorioangiomas are benign tumors of the hemochorial placenta. They are malformations or hamartomas, formed as a result of defective angiogenesis. They are of clinical importance due to their association with premature placental release and pre-eclampsia. Methods. Since a link has been established in neoplasias between tumor growth and an increased expression of angiogenic growth factors, 136 samples of chorioangiomas and 136 samples of tumor-free placental tissue were examined in terms of proliferation rate and expression of the growth factors angiopoietin-1 and -2, the angiopoietin-receptor Tie-2, PDGF and the PDFG β-receptor. Results. The chorioangiomas exhibited differing proliferation rates, whereas tumor-free placental tissue barely proliferated at all. Angiopoietin expression was—morphologically—considerably higher within the chorioangiomas than in the comparison placentas; morphological amounts of the Tie-2 receptor were identical in all samples. Expression of PDGF and its receptor was the same for chorioangiomas and tumor-free placentas. Conclusions. According to this study and the current literature in the field of hamartomas and some neoplasia, we can assume that increased growth factor expression plays a role in the formation of chorioangiomas, since it stimulates proliferation in a wide variety of cell compartments.

Preterm newborn infants are especially susceptible to Gram-negative sepsis that is associated with a lethality of up to 40%. Aims: We tested whether polymorphonuclear leukocytes (PMN) from preterm infants exhibit an impaired antibacterial response upon stimulation with lipopolysaccharide (LPS) from Escherichia coli when compared to full term newborns or adults. Methods: We studied the effect of LPS on the expression of the surface proteins CD11b and CD14 and the secretion of elastase by PMN from preterm infants, term infants and adults ex vivo . Results: We found a significantly reduced antibacterial activity of PMN from preterm infants upon stimulation with LPS as indicated by low surface expression of the adhesion molecule CD11b and the reduced secretion of PMN elastase. LPS-induced CD11b expression was dependent on binding of LPS to the surface protein CD14 as CD14 antibodies inhibited LPS dependent CD11b upregulation. Furthermore CD14 expression was lower on PMN from preterm infants than from adults. In addition, CD14 independent upregulation of CD11b in response to tumor necrosis factor (TNF-α), N-formyl peptides (FMLP) and phorbol ester (PMA) was impaired. Conclusion: PMN from preterm infants are distinctly hyporesponsive to LPS, which may explain the predisposition of these children to invasive disease due to gramnegative bacteria.

Critical fetal organs are preferentially supplied with oxygenated blood from the umbilical vein (UV) by way of the ductus venosus (DV). Under normal conditions a significant part of UV-blood flows steadily forward through the left portal vein (LPV). Blood flow through the LPV could reverse, however, in cases of absent or reversed enddiastolic flow in the umbilical arteries. We tested when fetal blood flow reversal occurs by studying 28 cases with pathological flow in the umbilical artery. In the LPV we observed normal nonpulsatile forward flow in 9 cases, pulsatile forward flow in 10 cases, and reversed flow in 9 cases. Reverse flow in the LPV correlated significantly with an elevated resistance index of the umbilical arteries. This reversal could have major physiological implications: Deoxygenated blood may be added via the LPV to the blood shifted through the DV and ultimately reach critical fetal organs. In extremis there could be a waterhose effect, whereby more blood flows through the DV than the UV that supplies it. The LPV is thus the watershed of the venous circulation of the fetus.