Volume 28, Issue 1

The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. As of 1999, there are data of three randomized controlled trials involving a total of 210 infants below 33 weeks of gestation. None of the trials was able to demonstrate a benefit of iNO with respect to mortality or chronic lung disease. We performed a meta-analysis of the three published trials. Of 111 infants receiving iNO, 44 deaths were observed, compared to 40 of 99 control infants (p = 0.91). The odds ratio in favor of iNO was 0.97 (95% confidence interval 0.54–1.75). There was also no significant difference for treatment failure, defined as death or chronic lung disease (iNO: 32 of 111 infants versus control: 34 of 99, p=0.39, odds ratio 0.77, 95% confidence interval 0.41–1.45). The rates of intracranial hemorrhage were similar in both groups (35 of 111 infants receiving iNO vs 25 of 99 controls, p=0.33, odds ratio 1.37, 95% confidence interval 0.69–2.74) ). We conclude that the use of inhaled nitric oxide may improve oxygenation but not survival in preterm infants with severe hypoxemic respiratory failure.

Aims: Transverse cerebellar diameter has been described as a tool to check for gestational age, but there are no available studies that attempt to determine differences in transverse cerebellar diameter between groups of different ethnic origin. The present study was undertaken to check for differences in ultrasound-measured transverse cerebellar diameter between pregnant women of autochthonous Belgian origin and migrant women from Morocco and Turkey. Methods: A prospective cross-sectional study was performed. Patients were pregnant women presenting between 17 and 40 weeks of gestational age. Only uncomplicated singleton pregnancies with a known date of the last menstrual period confirmed by first trimester ultrasound were included. The father of the child had to be of the same ethnic origin as the mother. Polynomial regression was fitted for the three different ethnic groups. Results: The transverse cerebellar diameter was obtained in 471 singleton fetuses, including 333 Belgian, 69 Moroccan and 69 Turkish. F-tests on the residual sums of squares of different fits demonstrated significant effects of ethnicity on the regression of the measurement versus gestational age ( P < 0.00005). In a third order polynomial regression model the second order coefficient was significantly higher and the third order coefficient was significantly lower for the Moroccan group. Conclusion: The transverse cerebellar diameter is not independent of the ethnic origin of the patient. When using the transverse cerebellar diameter for the evaluation of fetal growth or for dating a pregnancy, care should be taken to rely on charts appropriate for the ethnic group, as demonstrated here for Moroccan fetuses.

Objective: To compare the outcome of induction of labor and patient's preferences using a protocol with the first dose of prostaglandin E 2 endocervical gel in the evening versus a protocol with the first dose in the morning. Design: We performed a randomized trial comparing administration of prostaglandin E 2 endocervical gel in the morning with administration of prostaglandin E 2 gel in the evening, followed if necessary by a second dose being given after six hours if labor had not started or the cervix was still unripe. Formal induction of labor by amniotomy and oxytocin infusion was performed the morning after the initial prostaglandin E 2 dose. Patients' preferences were assessed using a questionnaire that was completed after delivery. Setting: Tertiary care hospital in the Netherlands with 1,600 deliveries per year. PARTICIPANTS: One-hundred and twenty-six women with viable singleton pregnancies at term who had induction of labor with prostaglandins. Main outcome measures: Time of delivery (daytime, evening or night) and patient's satisfaction. Results: Fifty-eight women were allocated for administration of gel in the morning, whereas 68 had their gelin the evening. Administration of gel in the evening did not significantly reduce delivery between 23.00 hours and 08.00 hours, although there was a reduction in delivery between 23.00 hours and 08.00 hours in nulliparae.None of the multiparous women delivered between 18.00 hours and 23.00 hours after induction of labor in the evening.The relative risk for delivery by vacuum or forceps was increased after allocation of gel in the evening (4.2;95% confidence limits 1.4 to 13). Patient's preferences favored administration of gel in the morning. Conclusions: There was no benefit in starting induction of labor with prostaglandin E 2 in the evening, compared with starting in the morning.

Aims: A single course of prenatal corticosteroid reduces the mortality and morbidity of preterm birth. Repeated courses of prenatal corticosteroids are widely prescribed despite a lack of safety data. Repeated corticosteroids delay myelination in the ovine central nervous system at the time of preterm delivery but with catch-up at term. We aimed to evaluate their effect in the peripheral nervous system. Methods: Thirty date-mated ewes were administered either saline, a single injection of betamethasone, or four injections of betamethasone between 104 and 124 day's gestation, with delivery on day 125 or 145 (term = 150 days). Sciatic nerves were dissected and fixed in modified Karnovsky's fixative and prepared for light and electron microscopy to determine the proportion of myelinated axons and mean axon diameter. Results: Repeated, but not single, corticosteroid administration resulted in significant decreases in the total cross-sectional and fascicle-containing areas of the sciatic nerve, and in the mean diameter of myelinated and unmyelinated axons. Deficits persisted at term. The proportion of myelinated axons was unaffected. Conclusion: Repeated prenatal corticosteroids have the capacity to affect the growth of peripheral nerve axons in sheep. Documentation of their effects in human pregnancy await randomized trials.

Objective: To assess if fetal examination is feasible by endoscopy in the late first-early second trimester. Setting: Tertiary referral center for high risk obstetrics and genetics. Patients and Methods: Patients (total number 9) submitted to pregnancy termination for social reason (7) or for chromosomal abnormality (2) between 10 and 14 weeks of pregnancy. Visualisation of the foetus by a transabdominally introduced endoscope (19 gauge) under local anaesthesia. Step by step examination of the foetal contour and double check of the recordings by a senior Pathologist. Results: Patients complained no serious discomfort. Visualisation was accomplished in all cases with ease and the images were judged satisfactory by the Pathologist. Fetal examination was found easier at 10–12 weeks of gestation rather than at 13–14 weeks. Discussion: Endoscopy is a simple and well tolerated procedure, which enables precise visualization of external fetal anatomy as early as the first trimester of gestation. Therefore it can be proposed before surgical termination of pregnancy.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9% , C4: 45.1% , C3: 56.2% ). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (r s = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%–3.0 %) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

The aim of this study was to ascertain the incidence of preterm delivery, the associated etiological factors and consequent perinatal mortality in an Irish obstetrical population. All deliveries between 24 + 0 and 36 + 6 weeks of gestation that occurred during the five year period 1992–1996 were included in the study. The overall group of preterm deliveries was also analyzed separately as an early preterm group (24 + 0 – 31 + 6 weeks gestation) and a late preterm group (32 + 0 –36 + 6 weeks gestation). The overall incidence of preterm delivery was 5.5% (n = 683) with 1% (n = 122) occurring in the early preterm group and 4.5% (n = 561) in the late preterm group. The etiological factors contributing to preterm delivery in our population together with their frequency of occurrence in both early and late preterm groups are outlined. Spontaneous unexplained preterm delivery, multiple pregnancy, and hypertensive disorders of pregnancy were the commonest etiological factors for preterm delivery. The perinatal mortality rate (PMR) was 57 per 1000 (n = 39) in the preterm group overall with a 213/1000 PMR in the early preterm group and a 23/1000 PMR in the late preterm group.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used 18 F-labelled 6-fluoro- L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2–5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO 2 was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO 2 ) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO 2 to the inspired gas. Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO 2 remained unchanged throughout the as phyxial period. Despite this, brain tissue pO 2 was reduced from 19 ± 4 mm Hg to 6 ± 3 mm Hg ( p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product ( PS ) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA ( k 3 ) was, however, significantly increased (p < 0.01). This increase of the AADC activity is associated with reduced brain tissue pO 2 . Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.

Premature closure of the foramen ovale, 4-chamber cardiac hypertrophy, and renal vein/vena cava thrombosis were found at autopsy of a stillborn dizygotic twin at 36 weeks gestational age. Review of the original prenatal sonograms showed features suggestive of early closure of the foramen ovale. Homozygosity for the 5,10 methylene tetrahydrofolate reductase mutation was shown only in the affected twin after the parents were found to be heterozygous for the mutation. The difference in outcome of the twins following prenatal treatment with beta mimetics and corticosteroids for preterm labor may be related to the added susceptibility factor for thromboembolism associated with presumed hyperhomocysteinemia in the proband which was not shared by the surviving healthy twin. The role of premature closure of the foramen ovale and prenatal treatment are discussed but remain uncertain.

Absence of the ductus venosus is a rare vascular anomaly. We report a late onset of a hydrops fetalis seen in a fetus at 34 completed weeks of gestation. A persistence of the cranial parts of the left and right umbilical veins and of the paired cranial vitelline veins with an absent ductus venosus led to a bilateral hydrothorax, ascites and skinedema. Postnatally the hydrops resolved within 7 days most probably due to the change from the fetal to the adult circulation. The abnormal venous system was confirmed by angiography. Agenesis of the ductus venosus can manifest in two different morphologic patterns: The umbilical vein drains exclusively into the left branch of the intrahepatic portal vein or the umbilical vein drains into the inferior vena cava or directly into the right atrium by-passing the liver completely. In both patterns, the preferential direction of the flow towards the foramen ovale is not present. While the first pattern leads to hyperperfusion of the liver parenchyma, the latter would result in reduced perfusion and oxygenation. Our findings suggest that agenesis of ductus venosus might induce hydrops fetalis. We conclude, that in every case of hydrops fetalis the venous system should be evaluated by ultrasonography prenatally and/or immediately postnatally.