Johannes Egberts

The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal

Objective To determine the proportional reduction per day in the number of fetal and donor red blood cells from the fetal circulation after intrauterine intravascular transfusions.

Theoretical Changes in Neonatal Hospitalisation Costs After the Introduction of Porcine-Derived Lung Surfactant (‘Curosurf’)

SummaryThe aims of this study were to determine the effects of porcine-derived lung surfactant (PLS; ‘Curosurf’) therapy on mortality, periods of care and hospitalisation costs in a model cohort of 1000 premature neonates. In this cohort, 55% of the neonates would develop respiratory distress syndrome (RDS) and this would result in a mortality rate of 35%. The mortality rate among infants without RDS is 19%. Five modes of surfactant therapy were studied: (i) late rescue; (ii) early treatment; (iii) prophylaxis; (iv) multiple-dose treatment; and (v) high multiple-dose treatment.At a 55% incidence of RDS, we found that late rescue and single-dose treatment of severely ill neonates resulted in between 4 and 51 extra survivors, and that multiple-dose treatments increased the number of extra survivors by between 17 and 101. Early treatment and prophylaxis were found to be the most effective strategies, resulting in between 38 and 111 extra survivors. These 2 modes of surfactant therapy were also more effective than the other types of intervention at other incidences of RDS.The introduction of PLS therapy increased the total hospitalisation costs of the cohort of 1000 neonates [71 million Netherlands guilders (NLG) if no patients received surfactant] by 0.8 to 16.0% because of increased survival. Improved survival increased the mean period of intensive care by 0.5 to 12.6% and of nonintensive care by 0.6 to 16.0%, thereby increasing the need for more beds. Costs for PLS ranged from 0.3 to 1.2% of the total hospital costs.The additional costs of PLS therapy per additional survivor, compared with the’ do nothing’ option, ranged from NLG68 034 to NLG136 233, and were lowest with prophylaxis and highest with high multiple-dose treatment. Savings in costs per survivor (0.2 to 4.1 %) and nonsurvivor (5.1 to 23.1 %) were highest with prophylaxis and early treatment, which were found to be the most cost effective of the strategies studied.n

Estimated Costs of Different Treatments of the Respiratory Distress Syndrome in a Large Cohort of Preterm Infants of Less than 30 Weeks of Gestation

Within a model cohort of 1,000 preterm infants of less than 30 weeks of gestation, the incidence and mortality of RDS change if corticosteroids are used prenatally and surfactant prophylactically or therapeutically after birth. Combined pre- and postnatal therapies give the best results: approximately 125 extra survivors. Therapeutic surfactant administration even in combination with prenatal corticosteroids has cost implications because extra intensive care beds (7-11%) are needed. More special care places (12-24%) are required after each type of intervention. The estimated costs per extra survivor are the lowest for prenatal corticosteroid administration. The combination of corticosteroids prenatally and prophylactic surfactant postnatally seems to be most cost-effective because it produces the greatest number of survivors and the lowest number of intensive and high dependency care days in hospital.

A new method to determine the feto-placental volume based on dilution of fetal haemoglobin and an estimation of plasma fluid loss after intrauterine intravascular transfusion

Objectives (1) To calculate the feto‐placental volume (FPV), using the haematocrit (Ht) values and the percentages of fetal haemoglobin (HbF), before and after red blood cell transfusion. (2) To estimate the transfusion‐induced loss of plasma fluid.

Plasma guanosine 3 ',5 '-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome.

High cervical fetal-fibronectin concentrations and birth within 3 days in pregnancies of 41 weeks or more.

To the Editor: Preterm birth has been reported to occur shortly after the appearance of substantial amounts of fetal fibronectin in vaginal and cervical secretions.1,2 Fetal fibronectin, a component of the extracellular matrix of fetal membranes, leaks into the cervix when the interaction between the fetal membranes and the uterine wall weakens. However, if the vaginal fetal-fibronectin concentration remains low at 39 weeks of gestation, then the pregnancy is likely to progress beyond 41 weeks,3 with an increased risk of perinatal morbidity and mortality.4 If the approximate day of parturition could be predicted, it would aid in deciding whether .xa0.xa0.

Cervicovaginal fetal fibronectin concentrations: predictive value of impending birth in postterm pregnancies

OBJECTIVEnTo determine the predictive value of cervicovaginal fetal fibronectin (fFN) concentrations > or =50 ng/ml for spontaneous onset of labour within 3 days in pregnancies of 41 weeks gestation or more.nnnSTUDY DESIGNnIn the Department of Obstetrics, Leiden University Medical Centre, and of the Diaconessen Hospital, Voorburg (The Netherlands), 126 cervicovaginal secretions of fFN, from 80 consenting women between 287 and 304 days gestation were collected. Pregnant women underwent sterile speculum examinations for cervicovaginal sampling from the 41st week onwards. The fFN concentration in these samples was determined with a quantitative solid-phase enzyme-linked immunosorbent assay. Concentrations of <50 ng fFN per ml were characterised as negative test results, meaning that spontaneous delivery would not take place within 3 days, and those of > or =50 fFN ng/ml were taken as positive test results. Sensitivity and specificity of the fFN test were calculated for predicting spontaneous birth. Parametric and nonparametric tests were used for evaluating differences and correlations.nnnRESULTSnSpontaneous delivery took place after 2.5+/-2.5(SD) days with fFN values > or =50 ng/ml and after 4.7+/-3.6 days with fFN concentrations <50 ng/ml (P<0.001). Sensitivity and specificity of the fFN test predicting spontaneous onset of labour within 3 days, were 0.71 [95% confidence interval (CI) 0.58-0.86] and 0.64 (95% CI 0.48-0.78). If fFN > or =50 ng/ml then a spontaneous onset of labour is more likely to occur within 3 days (odds ratio 4.5 (95% CI 1.8-11.3).nnnCONCLUSIONSnThe fFN test does not predict accurately enough whether or not birth will take place within 3 days of sampling. Nevertheless, the higher odds for spontaneous delivery within a few days when the test is positive may be of use in planning adjusted induction of labour.

Development of a human lung surfactant, derived from extracted amniotic fluid

Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates.

Non‐protein‐bound iron and free radical damage in fetuses with rhesus haemolytic disease: influence of intrauterine transfusions

Objectiveu2003 To determine iron‐induced free radical damage in fetal rhesus haemolytic disease (RHD) before and after repeated intrauterine red blood cell transfusions and its relation to hydrops fetalis.

Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia

deliver a smaller baby and thus reduce damage to her pelvis. If the mother increasingly restricts fetal growth as pregnancy progresses, and the fetus fights back by increasing maternal peripheral resistance (thus diverting more blood flow to the placenta), then one would expect a steadily increasing incidence of pre-eclampsia as gestation progresses. This is in fact what we see. This observation leads to the suggestion that all women would develop pre-eclampsia if pregnancy lasted long enough, and that for some women preterm delivery may be protective against pre-eclampsia as well as pelvic damage. However, I agree with Sacks that if the penalty for growing a large baby is removed, then the gene combinations that allow growth (and therefore do not provoke pre-eclampsia) are likely to increase in frequency, and thus the overall incidence of pre-eclampsia would be expected to fall.