Volume 32, Issue 3

In the last ten years, the body of scientific knowledge concerning the use of antenatal pharmacologic magnesium sulfate (MgSO 4 ) has become substantially larger. Several randomized controlled trials have provided compelling evidence that MgSO 4 is the drug of choice for maternal seizure prophylaxis in toxemia. In contrast, the recent Cochrane Systematic Review, as well as other studies, have shown there is no evidence basis for the use of MgSO 4 for tocolysis. Furthermore, when tocolyticstrength doses of MgSO 4 are employed, there is an excess risk for total pediatric mortality (Cochrane Systematic Review and our own previous work). It is conceivable, nonetheless, that low doses of MgSO 4 , when used as prophylaxis in some selected cases of preterm labor, may ultimately be shown to be neuroprotective for a relatively small number of children. Unfortunately, the indiscriminate use of high-dosage MgSO 4 for attempted tocolysis in preterm labor is much more likely to cause harm than do good.

Background: Prevention of congenital toxoplasmosis is most often based on the results of a serological screening program in pregnant women followed by prenatal and postnatal treatment of women and their newborns when infection is already established during pregnancy or on cord blood (secondary prevention). Little effort has been made to study primary prevention of toxoplasmosis during pregnancy. Objective: To assess the possibilities of two different programs aimed at preventing the acquisition of toxoplasmosis during pregnancy. Methods: During the first study period (1979–1982) the natural incidence of toxoplasmosis in pregnancy was studied in 2986 pregnant women. In the second study period (1983–1990) the incidence of toxoplasmosis was studied in 8300 women. During this period, seronegative women received a written list of recommendations on how to avoid a toxoplasma infection during pregnancy. In the third study period (1991–2001) the incidence of toxoplasmosis was studied in 16541 women. During this period, the prevention campaign consisted of a leaflet explaining a) toxoplasmosis as a disease and b) what measures should be taken to avoid toxoplasmosis during pregnancy. The third part of the campaign involved a reiteration of these recommendations during antenatal classes held around mid-gestation. The impact of the two prevention programs was studied by measuring the seroconversion rate in seronegative women. Results: Twenty of 1403 seronegative women in the first period (1.43%), 19 of 3605 women in the second period (0.53%) and 8 of 8492 in the third period (0.09%) seroconverted during pregnancy. The first prevention campaign reduced the seroconversion rate by 63% (p<0.05 OR 2.729 95% CI 1.452–5.084). The second prevention program resulted in a reduction rate of 92% compared to the seroconversion rate in the first period (p<0.0001 OR 15.34 95% CI 6.741–34.89). Conclusion: Promotion of simple measures is very effective in the prevention of toxoplasmosis during pregnancy. Primary prevention should not only be based on education about preventive measures given by physicians, but these guidelines should be reiterated during antenatal classes and leaflets distributed containing written recommendations on the nature of the disease and its avoidance.

Aim: To evaluate the impact of the rate of multiple pregnancies and congenital malformations on perinatal mortality. Methods: The study is based on data from the perinatal audit in Vejle County Denmark. Fetal deaths with gestational age ≥22 weeks and deaths in livebirths within the first 28 days after birth were included in the calculated perinatal mortality. Total number of births was 30,181 and 252 pregnancies and 268 fetuses/infants were evaluated. The study period was 1995–2000. There was no routine ultrasound screening for congenital malformations in the county, though midtrimester ultrasound was used to assess gestational age. Results: Perinatal mortality was 8.9 per 1000 births with no significant change over time. Rate of multiple pregnancies was 1.94% ranging from 1.81% during the first 3 years to 2.06% for the last 3 years (not significant). Fetuses and infants from multiple pregnancies contributed 18% of all deaths. Perinatal mortality for single births was 7.6 per 1000 births and for multiple births 42.2/1000 (P<0.0001). The distribution of gestational age for single and multiple births was highly significant (P<0.0001) with 67% of multiple pregnancies with GA <28 weeks compared to 26% of single pregnancies. Nineteen percent of all deaths were caused by congenital malformations and the majority of these were potentially detectable by ultrasound investigation. Conclusions: The increasing rate of multiple pregnancies makes it difficult to see improvements in perinatal mortality. Calculated from the perinatal mortality in single and multiple pregnancies in Vejle County assisted conceptions contribute with an an excess of 45 perinatal deaths per year in Denmark. The difference between countries in rate of multiple pregnancies and in prenatal ultrasound screening recommendations for malformations makes it difficult to compare perinatal mortality.

Aims: Our aim was to evaluate the efficacy of maintenance oral nifedipine in pregnant women initially treated with intravenous ritodrine plus verapamil for preterm labor. Methods: The study included 73 patients with preterm labor with intact membranes. Patients were randomized to receive either maintenance oral nifedipine therapy (n=37) administered 20 mg every six hours or no treatment (controls, n=36) after discontinuation of acute intravenous tocolysis. Results: Compared to the control group, the mean±SD time gained from initiation of maintenance therapy to delivery (26.65±18.89 vs. 16.14±12.91 days, p =0.007) and the gestational age at delivery (37.03±2.06 vs. 35.1±3 weeks, p =0.003) were higher in the nifedipine maintenance therapy group. The proportion of patients who required one or more courses of subsequent intravenous therapy and perinatal outcomes were similar in the maintenance therapy and control groups. Conclusions: The gestational age and time gained from initiation of maintenance therapy to delivery were longer in women receiving oral maintenance tocolysis with nifedipine. However, maintenance therapy did not decrease the recurrence of preterm labor episodes or improve perinatal outcomes.

Hypercoagulability leading to placental thrombosis has been implicated in severe pregnancy complications. We compared the perinatal outcome in women with severe preeclampsia, intrauterine growth retardation (IUGR) and severe abruptio placentae and multiple acquired and inherited thrombophilias (study group, n=22) to matched women with similar complications and single thrombophilia (control group, n=22). Gestational age at delivery and birth weight were significantly lower in the study group compared to the control group (p<0.01) and among the study women with severe preeclampsia and IUGR. Severe pregnancy complications may occur earlier during pregnancy and more seriously affect perinatal outcome in women with multiple thrombophilias.

Aims: To assess the reproducibility of 3D power Doppler study of placental vascularization in order to establish its methodological bases for its further application in normal and pathological pregnancies. Methods: A prospective study was carried on 30 normal singleton pregnancies from 14 to 40 weeks. To evaluate placental vascularization 3D power Doppler was applied to obtain a “placental biopsy”. The spherical volume acquired was analyzed using the VOCAL imaging program. Two consecutive measurements were taken from each patient by a single observer, obtaining a total of 60 datasets. Placental volume (PV), Mean Gray (MG), Vascularization Index (VI), Flow Index (FI) and Vascularization Flow Index (VFI) were calculated. Intra-class correlation coefficient (ICC) and intra-observer agreement was evaluated. Results: PV and MG presented an ICC of 0.98 and 0.94 respectively, with differences approaching zero. All 3D power Doppler vascular indices (VI, FI and VFI) showed a correlation greater than 0.85, with a better intra-observer agreement for the flow indices (FI and VFI). Conclusions: Placental vascular biopsy through 3D power Doppler is a new and simple tool to routinely study placental vascularization in human pregnancy. Our results provide the validation of the technique demonstrating a good reproducibility of the 3D power Doppler parameters when applied to the study of the placental vascular tree in normal pregnancies.

The problem of preterm deliveries has worsened in developed countries over the past decade. To evaluate whether multiple deliveries had an impact on this development, we analyzed the data of the Berlin Perinatal Survey from 1993–1999 for 206,308 deliveries. The prevalence of preterm deliveries was fairly constant during this period, and the proportion of preterm deliveries in the case of multiples remained constant. But the prevalence of preterm neonates increased significantly in Berlin due to an increased prevalence of multiple births. There was a significant increase of mothers aged over 30, of German nationality, and with preceding infertility treatment, while the prevalence rates of nearly all other risk factors for prematurity decreased over time. The risk of infertility treatments resulting in multiple deliveries increased in these years. On average, infertility treatment led to an about 10 times higher risk of producing multiples than singletons OR (95% Cl) of 9.6 (8.6–10.6).

Aims: The purpose of the present study was to compare fetal and neonatal outcomes with amniotic fluid erythropoietin (EPO) levels obtained in the antepartum period in pregnancies complicated by preeclampsia, pregnancy-induced hypertension or chronic hypertension. Methods: Erythropoietin concentrations were measured in amniotic fluid within 2 days before delivery and in cord blood at birth in 75 hypertensive women and in 23 healthy controls delivered by cesarean section before labor contractions. Erythropoietin levels did not influence clinical decisions. Results: Amniotic fluid erythropoietin levels correlated highly significantly with cord plasma EPO levels and were significantly higher in pregnancies complicated by hypertension than in control pregnancies. Umbilical arterial pH, acid-base and blood gas values at birth were not different from controls. Both cord plasma and amniotic fluid erythropoietin levels correlated with cord blood pH, acidbase and blood gas values at birth in the study group. Newborn infants admitted to the newborn intensive care unit had significantly higher fetal erythropoietin levels and were more acidotic, hypoxemic and hypoglycemic than infants admitted to the normal care nursery. Conclusions: Our findings suggest that elevated amniotic fluid erythropoietin levels are markers of chronic or subchronic fetal hypoxia and are associated with neonatal morbidity in pregnancies complicated by hypertension.

Aims: During pregnancy, the placenta produces a variety of steroid hormones and proteins. Several of these substances have been shown to exert immunomodulatory effects. Progesterone is thought to mediate some of these effects by regulating uterine responsiveness. The aim of this study was to clarify the effect of amniotic fluid transferrin and its N-glycans on the release of progesterone by first trimester trophoblast cells in vitro . Methods: Cytotrophoblast cells were prepared from human first trimester placentae by trypsin-DNAse dispersion of villous tissue followed by a percoll gradient centrifugation and depletion of CD45 positive cells by magnetic cell sorting. Trophoblasts were incubated with varying concentrations (50–300 μg/ml) of transferrin from human amniotic fluid and serum as well as with N-glycans obtained from amniotic fluid transferrin. Culture supernatants were assayed for progesterone by enzyme-immunometric methods. Results: The release of progesterone increased in amniotic fluid transferrin- and N-glycan-treated trophoblast cell cultures compared to untreated trophoblast cells. There was no stimulating effect of serum transferrin on the progesterone production of trophoblast cells. Conclusions: The results suggest that amnion-transferrin and especially its N-glycans modulate the endocrine function of trophoblasts in culture by up regulating progesterone secretion.

Aims: To investigate the incidence of severe fetal-to-maternal transfusion after delivery and to identify risk factors. Material and methods: In a prospective study at the Department of Obstetrics, Charité, Campus Virchow- Klinikum, Berlin, Germany, we analyzed the incidence of severe fetal-to-maternal transfusion (>10 ml) and fetalto- maternal hemorrhage (>25 ml) in Rh D-negative pregnant women after delivery of Rh D-positive infants. 942 women were included in the study and Kleihauer-Betke tests were performed. The results were compared to perinatal data. Results: Fetal-to-maternal hemorrhage occurred in 13 cases out of 942 (incidence of 1.3%) and severe fetalto- maternal transfusion in 61 cases (6.5%). In all of the cases with fetal-to-maternal hemorrhage, mothers were compatible with their infants in ABO-system. The incidence of fetal-to-maternal transfusion and its severe form was significantly higher in twin pregnancies (7/21 cases and 5/21 cases respectively, 33.3% and 23.8%) than in singleton pregnancies (22.5% and 5.9%, P<0.001). All other factors, such as maternal age, parity, ethnicity, mode of delivery, presentation, duration of first and second stage of labor, CTG, or Apgar score were not associated with an increased risk of severe fetal-to maternal transfusion. Conclusions: Twin pregnancy is the only independent risk factor for severe fetal-to-maternal transfusion. ABO-incompatibility between mother and infant seems to be protective against Rh D-alloimmunization.

Aims: To assess the influence that fetal head position has on induction, labor and delivery outcome for both mother and baby. Methods: During a one month period, in November 1999, all women attending for a post-dates scan were enrolled as the study population. In total, 91 women formed our study population for analysis of data. The sonographic, induction and labor details of all women were recorded on a dedicated data sheet. As well as documenting the maternal age, parity, liquor volume (mm) and BPS, the position of the fetal head was noted by the sonographer as occipitoanterior, occipitotransverse or occipitoposterior. All women had gestation confirmed by ultrasound early during the course of their pregnancy. Maternal, ultrasonographic, induction and labor variables were correlated with fetal head presentation at scan. Results: There was no positive correlation found between fetal head position at the term plus 12 scan and associated induction, labor or delivery complications in the 91 women studied. Conclusions: Our study shows no positive correlation between fetal head position and induction, labor or delivery complications.

Objective: To study changes in uteroplacental and fetal circulation after maternal exercise in appropriate-for-gestational- age fetuses (AGA) and intrauterine-growth-retarded fetuses (IUGR). Materials and method: 33 women with an uncomplicated course of pregnancy and ten women with IUGR were examined. Physical stress was caused through a bicycle ergometer with 1.25 W/kg maternal weight. Doppler examinations were performed in the umbilical artery, fetal aorta, middle cerebral and in the uterine artery. Fetal heart rate was documented by monitoring. Maternal lactate and glucose levels as well as maternal blood pressure and heart rate were recorded. Results: No significant changes after cycling could be observed in umbilical and uterine vessels either in the normal pregnancies or in pregnancies with IUGR. In contrast, in the fetal aorta an increase of the RI was recorded in both groups (an increase of 16% [P<0.01] and 18% [P<0.05], respectively for AGA and IUGR cases). In cerebral arteries a decrease of the RI was observed after cycling in both groups (a decrease of 24% [P<0.01] and 13% [P<0.05], respectively for AGA and IUGR cases). In AGA fetuses the RI of the aorta and middle cerebral artery returned to pre-test level by the 18 th minute of examination. In IUGR fetuses the RI of the aorta and middle cerebral artery did not return to pre-test levels at the end of the test. Fetal heart rate remained unchanged in both groups. Maternal blood pressure and heart rate increased during the exertion phase but returned to initial values at the end of the test. A 21% and 24% (for AGA and IUGR groups respectively) reduction of maternal glucose values after exercise was observed (P<0.001). Lactate values doubled in both groups after exercise (P<0.001). Conclusion: From the results obtained we conclude that maternal exercise does not significantly alter uterine and umbilical perfusion in AGA and IUGR pregnancies, suggesting an absence of change in the uterine vascular bed resistance. However, submaximal maternal exercise was followed by fetal cerebral vasodilatation and an increase of resistance in the fetal aorta that was more evident in IUGR fetuses. This might be due to slight fetal hemoglobin desaturation in those cases.

Aims: To investigate the relationship between fetal weight and leptin levels in maternal serum, amniotic fluid and umbilical cord. Methods: Forty pregnant women presenting for antenatal care at early weeks of gestation were enrolled for the study. Maternal and cord blood samples for leptin measurement were obtained at birth. Amniotic fluid samples were recovered by amniotomy performed during labor. Maternal body mass index and placental weight were also recorded. Leptin measurement was carried out using the ELISA method. Spearman's correlation test was used for comparison of non-parametric data. Results: Leptin concentration in venous cord blood correlated significantly with birth weight and placental weight whereas maternal serum and amniotic fluid leptin levels did not show correlation with birth weight. There were no significant correlations between leptin levels in maternal serum, cord blood and amniotic fluid. Conclusion: We conclude that lack of correlation between leptin levels in mother, cord and amniotic fluid suggest that these compartments may be non-communicating separate units or have different mechanisms regulating leptin synthesis or degradation, and that leptin in maternal blood and amniotic fluid may not have a direct effect on fetal growth but rather a different role in pregnancy.

Objective: To evaluate the role of intrauterine smoke exposure and other variables on the development of bronchopulmonary dysplasia (BPD) in infants with birth weight <1500 g (VLBW). Methods: This case-control study investigated 277 VLBW infants (141 cases, 136 controls) admitted at birth to neonatal intensive care unit and survived to discharge. A retrospective telephone interview provided detailed parental information supplementing clinical data. Logistic regression assessed the effects of birth weight <1000 g, gestational age <30 weeks (GA<30), respiratory distress syndrome (RDS), neonatal mechanical ventilation >7 days (MV>7), patent ductus arteriosus (PDA), intrauterine smoke exposure ≥3 months (ISE), and of parental history of asthma on BPD (oxygen dependency at 28 days with characteristic radiographic abnormalities) occurrence. Results: Including all variables, only GA<30, RDS and MV>7 were significantly associated with BPD. ISE did not contribute significantly to this model (odds ratio wORx 1.94; 95% confidence interval 0.88–4.26). Excluding iatrogenic variable MV>7, GA<30, RDS, PDA and ISE (OR 2.21; 95% confidence interval 1.03–4.76) were significantly associated with BPD. Analyzing GA as a continuous variable, the OR was 0.63 for each additional week. Conclusions: Prolonged mechanical ventilation, RDS and low gestational age were the major BPD determinants. Intrauterine smoke exposure seems to influence independently BPD development.

Background: Phenobarbital is one of the oldest, cheapest and easily available cerebroprotective drugs for the hypoxic brain. However, its potential and various actions have not been fully explored. Aim: To evaluate the effects of Phenobarbital on levels of oxidants and anti-oxidants in term and near term neonates with hypoxic ischemic encephalopathy. Methods: Design–randomized controlled trial. Setting–tertiary care referral perinatal centre. Procedure–asphyxiated neonates (gestation ≥34 weeks) with HIE were randomized to receive Phenobarbital 20 mg/kg IV within first six hours of life or to control group. CSF levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and blood levels of vitamins A and E were estimated at 10–12 hours of age. Results: CSF levels of MDA, SOD, GPx and blood levels of vitamins A and E were significantly lower in the Phenobarbital group (p<0.001). There was a trend towards lower levels of CSF MDA, SOD, GPx and blood vitamins A and E in babies with normal outcome as compared to babies with adverse outcome (death or neurologically abnormal at discharge). Conclusion: Phenobarbital in the dose of 20 mg/kg IV given within 6 hours of life in term and near-term neonates with HIE, was associated with a decrease in lipid peroxides, anti-oxidant enzymes and anti-oxidant vitamins.

Aim: To test the hypothesis that preterm infants who develop new type of bronchopulmonary dysplasia BPD have higher cord blood sE-selectin levels and neutrophil counts in the tracheal aspirate at birth than those who do not. Methods: The relationship between cord blood sE-selectin levels and neutrophil counts in the tracheal aspirate at birth and the development of BPD was examined in 30 preterm infants. Levels of sE-selectin and neutrophil counts were measured by specific immunoassay and by cytospin analysis. Results: Median cord blood levels of sE-selectin and neutrophil counts in the tracheal aspirate at birth were higher in preterm infants who developed BPD than in those who did not (P<0.01 for each). These differences persisted significantly after adjusting for the effects of gestational age and the presence of histologic chorioamnionitis and patent ductus arteriosus PDA (P<0.01 for each). Conclusion: Fetal pulmonary inflammation, as measured by increased cord blood levels of sE-selectin and neutrophil counts in the tracheal aspirate at birth, may be a risk factor for the development of new BPD in preterm infants. These results support the hypothesis that the lung injury responsible for new BPD in preterm infants can begin in the prenatal period and could be associated with a fetal pulmonary inflammation.

Background: Congenital biliary atresia is suspected to originate from prenatal biliary duct inflammation of unknown etiology. Objective: Based on clinical grounds, we aimed to establish a hypothesis on the primary cause of inflammation, and to suggest a causal treatment modality. Case report: History. A 28 years old Turkish woman had lost her first child aged two years from congenital biliary atresia (parents second degree cousins). After a miscarriage, in her otherwise uneventful third pregnancy sonography at 34 wks revealed echogenic material in the fetal gallbladder. Nine days later the gallbladder was completely filled with sludge. Chemical inflammation was suspected, and birth was induced at 36+3 weeks in order to allow for surgical flushing of the bile duct. Neonatal clinical chemistry was insuspicious. There was no spontaneous resolution of the sludge within the first 24 hours of life. A trial of medical treatment with intermittent iv secretin (0.03 CU/kg/h) and iv coeruletid (60 ng/kg/h) was started. Within 24 hours, sludge had resolved. Conclusions: We hypothesize that dysmaturation may lead to insufficient induction/production/activity of intrinsic gut hormones resulting in prenatally impaired bile flow, or even inspissated bile. Familial occurrence suggests a genetic defect. Exogenous hormone therapy might be an appropriate treatment modality.