[Need for blood transfusion in premature infants in 2 Dutch perinatology centres particularly determined by blood sampling for diagnosis]. / Bloedtransfusiebehoefte bij prematuren in 2 Nederlandse perinatologische centra sterk bepaald door bloedafname voor diagnostiek.

OBJECTIVE: Determination of factors related to the need for transfusion in premature infants. DESIGN: Descriptive. METHOD: The need for transfusion in premature infants was determined in 2 academic centres: University Medical Center Utrecht and Leiden University Medical Center, The Netherlands. The data had been acquired in another study. The factors under study were: hospital, pregnancy duration, birth weight, gender, time of clamping of the umbilical cord, total volume of blood sampled for diagnostic purposes, number of days of mechanical ventilation, total duration of admission and duration of the admission to the Neonatal Intensive care unit. Both hospitals followed the national interdisciplinary practice guideline 'Blood transfusion'. RESULTS: The total volume ofsampled blood for diagnosis, the duration of the mechanical ventilation and the admission period were related to a greater need for transfusion. On the other hand, the chance of transfusions diminished with longer pregnancy duration or increased birth weight. The difference in need for blood transfusion between both centres was significant. The total volume of transfused erythrocytes showed a strong correlation with the volume sampled for diagnostic procedures. CONCLUSION: Anaemia in neonates is strongly related to the amount of blood taken for diagnostic procedures. Alternatives for blood transfusions in premature infants, and consequently for the reduction of the number of donors per child, are to be sought in delayed clamping of the umbilical cord, use of erythropoietin and use ofautologous umbilical cord blood.

Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment.

AIM: The incidence of necrotizing enterocolitis (NEC) strongly increased in an neonatal intensive care unit (NICU) in 1997 and 1998 compared with previous years, which coincided with increased incidence of nosocomial sepsis. Specific risk factors related to this NICU and a possible relationship between NEC and nosocomial sepsis were studied retrospectively, including all patients with NEC since 1990 and matched controls. METHODS: Clinical and bacteriological data from the period before the development of NEC and a similar period for the controls were collected retrospectively and corrected for birthweight and gestational age. Statistical analysis was performed by a stepwise regression model. RESULTS: Data of 104 neonates with NEC and matched controls were analysed. The median day of onset of NEC was 12 d (range 1-63 d). Significant risk factors for NEC were: insertion of a peripheral artery catheter [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.3-3.9] and a central venous catheter (OR 5.6, 95% CI 3.1-10.1), colonization with Klebsiella sp. (OR 3.4, 95% CI 1.5-7.5) and Escherichia coli (OR 2.1, 95% CI 1.0-4.5), and the occurrence of sepsis, in particular due to coagulase-negative staphylococci (OR 2.6, 95% CI 1.4-5.1). The risk for NEC was decreased after the early use (< 48 h after birth) of amoxicillin-clavulanate and gentamicin (OR 0.3, 95% CI 0.2-0.6). CONCLUSION: Insertion of central venous and peripheral arterial catheters is positively associated with NEC, as is colonization with the Gram-negative bacilli Klebsiella and E. coli and the occurrence of sepsis, particularly due to coagulase-negative staphylococci. Early treatment with amoxicillin-clavulanate and gentamicin is negatively associated with NEC and may be protective against NEC.

[Four infants with congenital cystic malformation of the lung: different routes of diagnosis and forms of management]. / Vier zuigelingen met congenitale cysteuze longafwijkingen: gedifferentieerde diagnostiek en behandeling.

In four neonates, two boys and two girls, congenital cystic malformation of the lung was diagnosed. Two cases were diagnosed during prenatal ultrasound investigation. One of the patients recovered by a wait-and-see policy, one after antibiotic treatment and two following surgical removal of the diseased lung sections. Congenital pulmonary cysts are rare; congenital cystadenomatoid malformation (CCAM) is the most prevalent form. The most common presentation of CCAM is respiratory distress immediately following birth. Some children are asymptomatic at birth, but present with recurrent respiratory infections later in childhood. With the increasing use of antenatal ultrasound, an increasing number of cystic lung lesions are diagnosed antenatally. The prognosis of these mostly asymptomatic lesions is not clear and indications for prenatal and postnatal interventions must be determined by a multidisciplinary approach. Recently, malignant pulmonary tumours were found to be associated with CCAM. This finding necessitates long-term follow-up, even of asymptomatic CCAM lesions.

Precarious acrocentric short arm in prenatal diagnosis: no chromosome 14 polymorphism, but trisomy 17p.

Precarious acrocentric short arm in prenatal diagnosis: no chromosome 14 polymorphism, but trisomy 17p: We report on a girl with multiple congenital abnormalities and a prenatally diagnosed 46,XX,14p+ de novo karyotype. Fluorescence in situ hybridization (FISH) demonstrated that the extra material on the short arm of chromosome 14 was not just a polymorphism, but that it originated from chromosome 17. The phenotypic findings of this patient with pure trisomy 17p are compared with those of ten previously published cases.

Right ventricular function in respiratory distress syndrome and subsequent partial liquid ventilation. Homeometric autoregulation in the right ventricle of the newborn animal.

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.

New developments in neonatology: less severe retinopathy of prematurity?

PURPOSE: To determine the effects of surfactant replacement therapy (SRT), high-frequency oscillatory ventilation (HFOV), and general improvements in quality of care on the incidence of severe retinopathy of prematurity (ROP). METHODS: Retrospective comparison of the incidence and severity of ROP in two groups of preterm infants admitted to our neonatal intensive care unit (NICU) in two consecutive 5-year periods (1986-1995) and screened for ROP. During the second study period, natural surfactant was introduced in the treatment of respiratory distress syndrome (RDS) and HFOV was used for treatment of respiratory insufficiency of any origin. The effects of these developments and general improvements on the incidence of severe ROP were analyzed with stepwise logistic regression. RESULTS: The overall incidence of ROP from 1986-1990 was not significantly different from the incidence of ROP from 1991-1995. The incidence of severe ROP (ROP stage 3 or greater) was significantly lower in the second period (15.7% versus 6.4%, P=.015). For infants <1000 g, the incidence of overall ROP was increased significantly during the second study period (47.6% versus 60.1 %, P=.045), although the incidence of severe ROP remained unchanged. Only SRT was associated with a decreased risk for severe ROP; HFOV and general improvements in quality of care had no influence on the outcome. In patients with RDS, the incidence of severe ROP decreased significantly during the second period. CONCLUSION: Of the recent new developments in neonatology, only SRT was associated with a decreased risk for severe ROP.

[Elective cesarean section is preferred after the completion of a minimum of 38 weeks of pregnancy]. / Electieve sectio caesarea bij voorkeur na minimaal 38 complete zwangerschapsweken.

OBJECTIVE: To determine the frequency of neonatal respiratory morbidity following elective caesarean delivery at term and to identify prognostic factors for this morbidity. DESIGN: Retrospective. SETTING: Academic Hospital Utrecht/Wilhelmina Children's Hospital Neonatal Intensive Care Unit, Utrecht, the Netherlands. METHOD: All elective caesarean deliveries in the Academic Hospital Utrecht from the period 1990-1995 were studied. Also, neonates were included who were admitted for intensive neonatal care because of respiratory insufficiency following elective caesarean delivery in the region surrounding Utrecht. An elective caesarean delivery was defined as a delivery performed after 37 weeks of gestation without any complicating factor that might influence the timing of delivery. Prognostic factors for neonatal morbidity after caesarean delivery were identified by multivariate logistic regression analysis. RESULTS: During 1990-1995, 272 elective caesarean deliveries after 37 weeks of gestation were performed that fulfilled the inclusion criteria; 5.1% of the neonates were admitted to the medium care unit because of respiratory problems. The relative risk of respiratory morbidity after delivery by caesarean section with a gestational age of 39-42 weeks compared with a gestational age of 37-38 weeks, was 0.14 (95% confidence interval: 0.03-0.64; p < 0.001). Male sex was a cofactor. Nine neonates of whom 8 (90%) had a gestational age of less than 39 weeks were admitted to the intensive care unit. CONCLUSION: Most of neonatal respiratory morbidity could have been avoided by postponement of the at-term elective caesarean section until a certain gestational age of at least 38 complete weeks. An elective caesarean section should not be performed before that period.

[Increase in perinatal referral to regional centers of premature birth in The Netherlands: comparison 1983 and 1993]. / Toename van perinatale verwijzing naar regionale centra bij vroeggeboorte in Nederland: vergelijking van 1983 en 1993.

OBJECTIVE: To determine changes in referral of preterm newborns. DESIGN: Descriptive. SETTING: Foundation for Perinatal Epidemiology the Netherlands, Leiden. METHODS: Data regarding hospital of birth, referral, need of intensive care and mortality of the infants < 32 weeks and (or) < 1500 g birth weight born in 1993 from the National Neonatology Register were supplemented with data from a questionnaire for hospitals not included in the register. The data were compared with those of similar infants from the 'Project on preterm and small for gestational age', born in 1983. RESULTS: In 1983, 61% of the preterm infants were treated in a perinatal centre: 39% were not referred. In 1993 these numbers were 89% and 11%, respectively. The contribution of antenatal referral increased from 29% to 47% while that of postnatal referral decreased from 41% to 25%. Mortality decreased from 25.4% in 1983 to 14.3% in 1993. CONCLUSION: Regionalization of high risk perinatal care resulted in concentration of care for preterm infants. At the same time, in-hospital mortality decreased by almost 50%.

Total energy expenditure in infants with bronchopulmonary dysplasia is associated with respiratory status.

UNLABELLED: Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 +/- 13 days) and nine matched controls (36 +/- 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 +/- 9 vs 63 +/- 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min-1]; r2 = 0.82, P < 0.001), and was the single most significant determinant of Ee. CONCLUSION: Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD.

Less severe retinopathy of prematurity induced by surfactant replacement therapy.

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.

Survival of a neonate after myocardial infarction complicated by late mitral regurgitation.

A neonate born with a normal heart developed acute myocardial infarction at 12 days of age. Trivial mitral regurgitation secondary to fibrosis of posteromedial papillary muscle progressed to heart failure at 6 months of age. Mitral valve annuloplasty improved her condition.

Surfactant replacement therapy: a new risk factor in developing retinopathy of prematurity?

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8; P = 0.29). The ROP prevalence in the treatment group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3-20.7, P = 0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.

[Chylothorax in the neonatal period]. / Chylothorax in de neonatale periode.

The data of 11 infants with chylothorax in the neonatal period, seven with congenital chylothorax and 4 infants with iatrogenic chylothorax are reported. Chylothorax in the neonatal period may cause birth asphyxia and serious respiratory problems. Among the infants with congenital chylothorax diagnosis can be established before birth by ultrasound technique, followed by optimal resuscitation to prevent asphyxia. In most of the cases, conservative treatment with continuous drainage and total parenteral nutrition is sufficient.

Maternal antibodies against fetal blood group antigens A or B: lytic activity of IgG subclasses in monocyte-driven cytotoxicity and correlation with ABO haemolytic disease of the newborn.

IgG antibodies against blood group antigens A or B (anti-A/B) are able to sensitize erythrocytes for destruction in an antibody-dependent cell-mediated (ADCC) assay with monocytes as effector cells. The activity of maternal IgG anti-A/B in this test was compared with clinical signs of haemolytic disease of the newborn (HDN). When the ADCC was negative (less than 10% of the sensitized cells lysed), signs of increased red-cell destruction in the children were never observed. In three cases with a strongly positive ADCC (greater than 45% lysis), the children were severely affected and needed more than one exchange transfusion. In the cases with greater than 10% but less than 45% lysis in the ADCC, there was no clear correlation between the result of the ADCC and the degree of lysis in the newborn infants. In these cases, the degree of lysis of the red cells of the infant was shown to be strongly influenced by the number of A/B antigens per red cell. There was a direct correlation between the degree of lysis in the ADCC and the titre of IgG3 anti-A/B in the sera. There was comparable activity of maternal IgG anti-A/B in the ADCC test in the 32nd week of pregnancy and at the moment of delivery.

What is the best predictor of the severity of ABO-haemolytic disease of the newborn?

In 80 newborn infants ABO-incompatible with their mothers, the lysis-inducing effect of the maternal IgG anti-A or anti-B antibodies in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay and the antigen density of A or B antigens on the red cells of the children were measured. On the basis of the results, the children were divided into two groups--24 children in whom increased haemolysis was to be expected, and 56 children in whom it was not. Signs of haemolysis and serological features of ABO haemolytic disease of the newborn (ABO-HDN) were compared in these two groups and a control group of 120 ABO-compatible infants. The effect of the maternal antibodies in the ADCC assay, the titres of maternal IgG anti-A or anti-B antibodies, the results of the direct antiglobulin test on the red cells in the cord blood, and the titre of IgG anti-A or anti-B antibodies in the serum of the infants were compared for their ability to predict the severity of ABO-HDN. This was also done for the combination of the ADCC assay results plus the A or B antigen density and the direct antiglobulin test plus the titre of maternal IgG anti-A or anti-B antibodies. The ADCC assay with maternal serum was the most sensitive assay to predict ABO-HDN, and the combination of the ADCC assay with A or B antigen density determination the most specific test.

Complement is not activated in ABO-haemolytic disease of the newborn.

We studied the lysis in vitro of group A red cells by IgG anti-A. IgG anti-A, which strongly lysed A red cells from adults, did not lyse A red cells from cord blood, if fresh cord serum from a child with blood group AB was used as a source of complement. In cases of haemolytic disease of the newborn due to A-O or B-O antagonism with a positive direct antiglobulin test with anti-IgG serum, the red cells did not react with anti-complement sera. Apparently, complement is also not activated in vivo in case of A-O haemolytic disease of the newborn.