Cytokine production by cord blood mononuclear cells stimulated with cows milk proteins in vitro: interleukin-4 and transforming growth factor beta-secreting cells detected in the CD45RO T cell population in children of atopic mothers.

BACKGROUND: Food antigens from the maternal circulation may sensitize fetal T cells in utero and be an important determinant in the development of food allergy. METHODS: Here we have examined the spontaneous and recall response to cow's milk proteins of cord blood mononuclear cells (CBMC) of newborn children, using single cell ELISPOT assays. RESULTS: In term newborns, confirming previous studies, the spontaneous cytokine response of CBMC is dominated by IL-4, IL-5, IL-10, and as shown here for the first time, TGF-beta. For TGF-beta only, the response of samples from infants of atopic mothers was significantly lower than samples from infants of non-atopic mothers. In vitro stimulation of CBMC with bovine serum albumin, casein and beta-lactoglobulin resulted in a significant increase of all cytokine-secreting cells, again dominated by T helper type 2 (Th2) cytokines. There was a clear tendency for samples from infants of atopic mothers to have lower Th2 responses than samples from infants of non-atopic mothers, which was particularly significant for both IL-4 and TGF-beta. Spontaneous cytokine secreting cells were virtually absent in cord blood from infants < 34 weeks gestation, as were cows milk protein-induced responses, although they were readily detectable in samples from infants aged > 34 weeks. To explore whether the cytokine secreting cells were in the naive CD4+ CD45RA population or memory CD4+ CD45RO T cells, these subsets were purified by positive and negative selection and tested for spontaneous and cows milk protein-induced cytokine responses. Strikingly, although the responses were small, the CD45RO+ cells from children of atopic mothers showed significant spontaneous and antigen-specific IL-4 and TGF-beta responses, whereas the same population from infants of non-atopic mothers showed virtually no response. In addition CD45RA+ cells from infants of mothers with maternal atopy showed decreased IL-4 and TGF-beta responses, especially the latter. CONCLUSIONS: The cows milk antigen-specific IL-4 and TGF-beta responses preferentially seen in the memory cell subset of infants with a maternal history of atopy strongly suggests Th2 skewing to dietary antigens in utero.

[Changes in breast feeding behavior in Styria 1994 and 2000]. / Anderungen des Stillverhaltens in der Steiermark in den Jahren 1994 und 2000.

Aim of this study was to examine breast feeding behaviour in Styria, Austria in the years 1994 and 2000. Differences were documented and possibilities for better support were outlined. 1994 106 and 2000 60 mothers were questioned about breast feeding behaviour of the last child after delivery of a newborn in our hospital. The social status of the parents, breast feeding duration and frequency, problems while breast feeding and contraception were documented. The mothers were also asked about the breast feeding behaviour they planed for the newborn. 1994 83% and 2000 88% of the mothers breast fed their babies for at least 1 month. The average breast feeding duration increased from 4.8 months in 1994 to 5.3 months in 2000. The frequency of breast feeding also increased. Low social status was correlated with shorter breast feeding duration. Support for breast feeding was used by 53% of the mothers in 1994 and by only 28% of the mothers in 2000. 27% of the mothers wish to breast-feed the newborn longer than the last child in 2000. Breast feeding duration has increased in Styria, Austria from 1994 to 2000. Since mothers want to breast feed even longer, support to breast feeding mothers should be offered as often as possible.

[Routine examination of the term newborn infant]. / Die Routineuntersuchung des reifen Neugeborenen.

The routine examination of healthy term newborn infants on the postnatal ward has at least three goals: diagnosis of a primarily inapparent, yet severe disorder (e.g. acyanotic malformation of the heart), detection of minor, benign abnormalities (e.g. deformed feet) and minor birth lesions (e.g. cephalhematoma, clavicular fracture). Since such findings may cause concern, they are discussed with the parents. Many minor problems such as postural deformities are self limited or can be managed by the mother. A severe disease is detected only rarely. Certain findings should give rise to special investigations (e.g. preauricular tags--urinary tract malformation, hearing impairment).

[Virus infections in pregnancy--neonatal management]. / Virusinfektionen in der Schwangerschaft--neonatales Management.

We report on the most important viral infections in pregnancy. The importance of these infections is based on severe consequences for foetus, neonate and mother herself. New tests, e.g. direct virus detection assays, improved the security of diagnosis. We emphasize the management of viral infected neonates including own experiences.

Risk factors and determinants of neurodevelopmental outcome in cystic periventricular leucomalacia.

UNLABELLED: The aim of the study was to determine risk factors for the development of cystic periventricular leucomalacia (PVL) and to correlate ultrasound findings with neurodevelopmental outcome. By means of a retrospective case-control study (matched for gestational age, birth weight, sex, and year of birth) and a cohort analysis of all preterm infants with cystic PVL documented by ultrasound scans hospitalised at a local tertiary care centre between 1988 and 1998, 98 preterm infants with a gestational age ranging from 26 to 35 weeks were diagnosed as having cystic PVL. The mean day of diagnosis of periventricular echodensities was 3 +/- 2 days (range 1-11 days), and of cystic PVL 21 +/- 8 days (range 2-47 days). Of 79 infants (1988-1997) eligible for neurodevelopmental follow-up (91%), hemi-, di-, or tetraplegia was diagnosed in 61 (77%), normal mental outcome in 22 (28%), associated visual disorders in 41 (52%) and seizure disorders in 12 (15%) infants. Significant risk factors associated with the development of cystic PVL were premature rupture of membranes, chorioamnionitis, and hyperbilirubinaemia (odds ratios 4.665, 6.026, and 2.460 respectively). Subgroup analysis according to gestational age (26-28, 29-32, 33-35 weeks) revealed similar results despite spontaneous labour (26-28 weeks; odds ratio 4.808) and pre-eclampsia (33-35 weeks; odds ratio 3.517). Multiple pregnancy was associated with a twofold increased risk (odds ratio 2.075). The white matter damage probably accounted for the significantly higher prevalence of apnoeas (P < 0.001) and neonatal seizures (P < 0.001). Cysts located bilateral or parieto-occipital were associated with a higher risk of cerebral palsy (odds ratios 6.933 and 4.327 respectively). Solely anterior located cysts were associated with normal neurological outcome. Increasing size of the cysts was associated with increasing risk of cerebral palsy with a cut-off value of 10 mm (odds ratio 3.300 and above) and all infants with cysts of more than 20 mm diameter had cerebral palsy. CONCLUSION: The high prevalence of premature rupture of the membranes and chorioamnionitis further supports the role of intra-uterine infection in the pathogenesis of periventricular leucomalacia. The overall prognosis of cystic periventricular leucomalacia is poor.

Screening and diagnosis of congenital cytomegalovirus infection: a 5-y study.

Although cytomegalovirus infection is the most common infection transmitted via the placenta, there are no guidelines for routine screening to detect children congenitally infected with cytomegalovirus. From 1993 to 1997, maternal serum and cord vein blood of newborns was screened for HCMV-IgM (n = 21,183). Urine was examined for HCMV-excretion during the first postnatal week to prove HCMV infection in children who expressed HCMV-IgM in cord vein blood (n = 13) or who were born to mothers positive for HCMV-IgM in the serum (n = 234), or when both cord vein blood and maternal serum were positive for HCMV-IgM (n = 6). Congenital HCMV infection was detected in 17 newborns. To determine the incidence of congenital HCMV infection, only those mother/child pairs were selected in whom serum and cord vein blood were investigated (n = 5967 mother/child pairs). In this group 13 newborns were infected. The observed incidence for congenital HCMV infection is 0.21%. It is concluded that that this screening programme will detect those children at risk for congenital HCMV infection. These children have to be examined for virus excretion in the urine. Although the observed incidence is only 0.21%, congenital HCMV infection is a problem that can no longer be neglected because of its long-term sequelae.

[Prolongation of a bi-amniotic twin pregnancy after premature rupture of fetal membranes and umbilical cord prolapse of the first twin during the 23rd week of pregnancy]. / Prolongation einer biamniotischen Zwillingsschwangerschaft nach vorzeitigem Blasensprung und Nabelschnurvorfall des ersten Zwillings mit 23 Schwangerschaftswochen.

A 41-year old woman had a premature rupture of the membranes of the first twin with prolapse of the umbilical cord and the left foot in the 24th gestational week (23 + 4). The treatment consisted of bed rest in the Trendelenburg position, antibiotic prophylaxis and glucocorticoids for lung maturation. After 7 days the first twin was delivered vaginally from breech position. He died 10 hours later due to intraventricular hemorrhage. Tocolysis was administered and the umbilical cord was ligated and cut as high as possible. Seven days later a premature rupture of the membranes of the second twin and a prolapse of the fetal hand occurred. The second twin (birth weight 750 g) was delivered by cesarean section in the 26th gestational week (25 + 4) and survived without neurologic sequelae. Prolongation of pregnancy after a very premature delivery of the first twin of a biamniotic twin pregnancy can improve the neonatal outcome.

Reaction of term newborns with prolonged postnatal dyspnoea to early oxygen, mask continuous positive airway pressure, and volume expansion: a prospective, randomised, clinical trial.

UNLABELLED: In a prospective, randomised, open trial 103 term newborns with persisting dyspnoea, tachypnoea and/or cyanosis were treated with oxygen for 5-10 min and then with oxygen plus mask continuous positive airway pressure (CPAP) for another 5-15 min. Cases with overt prenatal or intrapartum obstetric pathology had been excluded from the study. Forty-one infants (40%) responded to this procedure within 10-25 min. The remaining 62 infants (60%) were randomly allocated to one of three forms of further treatment: continuation of mask CPAP for 20 min (group A, n = 24), volume expansion with 9 ml of 3 ml albumin, 3 ml glucose, and 3 mEq of sodium bicarbonate (group B, n = 24), or volume expansion with 4.5 ml albumin and 4.5 ml glucose (group C, n = 14). There was no statistical difference in birth weight, gestational age or Apgar scores at 1 and 5 min between the infants of the groups. Time to normalisation of symptoms was significantly shorter in the volume expansion groups (B: 45 +/- 41 min, range 20-180, and C: 80 +/- 72 min, range 20-210) than in the mask CPAP group (A; 224 +/- 256 min, range 30-1200, P = 0.02). There were statistical differences in umbilical cord and capillary pH values among the infants of the three groups, but the response to therapy was not related to the degree of acidaemia. Thirty-four infants (33%) who did not respond were admitted to a special care unit for further examination (group A: 21/24, group B: 7/24; group C: 6/14). Of these, 23 had no abnormal findings, 8 infants had radiological signs of transitory respiratory distress, and 1 had a non-tension pneumothorax. Septicaemia was found in two infants. No infant was intubated. At discharge all 103 infants did well. CONCLUSION: Incremental application of simple primary care procedures including volume expansion (with or without alkali) in term newborns with persisting postnatal tachypnoea and dyspnoea helps avoid overtreatment and unnecessary separation from the mothers in most cases and reliably selects infants who need close monitoring or special treatment.

[Neonatal hyperthyroidism caused by TSH receptor antibodies in maternal autoimmune hyperthyroidism]. / Neonatale Hyperthyreose durch TSH-Rezeptor-Antikörper bei mütterlicher Autoimmunhyperthyreose.

Between July 1993 and December 1994 five term infants of mothers with Graves' disease were hospitalised at the Frühgeburtenstation of the Univ.-Frauenklinik Graz. Four Mothers had elevated TSH-receptor-antibody (TRAb)--levels during pregnancy, one had normalised TRAb-titers. In one case hyperthyroidism was first diagnosed during pregnancy. Three newborns had elevated TRAb-titers; in one of them thyrotoxicosis was diagnosed clinically and biochemically at the second day of life, one newborn had mild hyperthyroidism with tachycardia at the end of the first week of life and one newborn was asymptomatic by immediately initiated therapy. The two other newborns had normal thyroid hormone and antibody levels and no symptoms or signs of hyperthyroidism. The cases are reported and discussed in detail and our overall approach to diagnosis and treatment of neonatal hyperthyroidism in case of maternal Graves' disease will be given.

Vagal response to feeding tube insertion in preterm infants: has the key been found?

We prospectively studied the vagal response to feeding tube insertion in eight healthy preterm infants, on three occasions in each infant during the first three weeks of life. Heart rate, oxygen saturation, respiration and cerebral blood flow velocities were assessed before, during and immediately after insertion of an orogastric feeding tube. The whole procedure was recorded on video. The duration and quality of tube insertion and the behaviour of the infant were evaluated from the recordings. Twenty-one measurements in eight infants were evaluated. The heart-rate decrease observed immediately after tube insertion correlated significantly with the duration of tube insertion, the quicker the manipulation, the greater the heart-rate decrease (P = 0.000). The maximal decrease of oxygen saturation after tube insertion correlated with the degree of heart rate deceleration (P = 0.009). Significant alterations of the flow velocities were observed only when the heart rate fell below 80 beats/min. We speculate that such episodes of bradycardia can be avoided by carefully inserting the feeding tube over a period of at least 15 s.

Necrotizing enterocolitis prophylaxis: oral antibiotics and lyophilized enterobacteria vs oral immunoglobulins.

We conducted a prospective randomized trial to compare the efficacy of oral gentamicin versus oral IgA-IgG for the prophylaxis of necrotizing enterocolitis (NEC); 200 newborns considered at high risk for NEC were assigned to group A (oral IgA-IgG, n = 100) or group B (oral Gentamicin, n = 100). NEC was diagnosed in 13 cases in group A and in 1 case in group B between the 3rd and 16th days of life. Surgical treatment was necessary in 3 cases (2 in group A). All infants survived. We conclude that oral gentamicin is more effective than oral IgA-IgG in the prevention of NEC in infants at high risk.

[The Graz SIDS Risk Questionnaire: prospective study of 6,000 infants]. / Der SIDS-Risikofragebogen Graz (SRFB): Prospektive Anwendung bei 6000 Säuglingen.

In a prospective study (1988-1990) the SIDS risk questionnaire SRFB was applied to 6000 infants born in the Department of Obstetrics, University Hospital Graz. In all infants at an increased statistical risk for SIDS a standardized intervention including pediatric and polysomnographic investigations was performed. As a result the SIDS incidence decreased from an average of 1.92 per thousand lifeborns (1984-1988) to 0.83 per thousand lifeborns (1989-1990) in our test group, which means a striking reduction of the SIDS incidence by 57%. In addition to this effect, the intensified information of parents and physicians about possible signs of an increased risk for SIDS lead to a general reduction of SIDS in Styria.

[Transverse fetal position syndrome--a combination of congenital skeletal deformities in the newborn infant]. / Das "Schräglagesyndrom"--eine Kombination typischer angeborener Skelettdeformierungen beim Neugeborenen.

We describe a pattern of connatal postural deformities observed in approximately 0.6% of otherwise healthy, mature newborn infants. It comprises unilateral flattening of the skull (dolichocephalus), ipsalateral mandibular hypoplasia and torticollis, deviation of the septum nasi, pes calcaneovalgus on one and pes adductus supinatus on the other side. The deformities occur in four distinct combinations attributable to the prenatal lie of the fetus: dorsoanterior or dorsoposterior, left or right oblique lie. The deformities respond well to manipulative therapy.

[Normal values for free thyroxine, free triiodothyronine, reverse triiodothyronine, thyrotropin, thyroglobulin and thyroxine-binding globulin in umbilical cord blood of healthy mature newborn infants]. / Normwerte für freies Thyroxin, freies Trijodthyronin, reverse Trijodthyronin, Thyreotropin, Thyreoglobulin und Thyroxin-bindendes Globulin im Nabelschnurblut gesunder reifer Neugeborener.

The venous cord blood levels of free thyroxine (fT4), free triiodothyronine (fT3), reverse triiodothyronine (rT3), thyrotropin (TSH), thyroglobulin (TG) and thyroxine binding globulin (TBG) were studied in 56 mature and healthy newborns. Newborns with a gestational age less than 37 or more than 42 weeks, a delivery by forceps or cesarian section, a birth-weight less than 2500 g, a pH-value of the cord-artery blood less than 7.15, an Apgar-value after 1 minute less than 7 were excluded from the study. All mothers were non-smokers. The values of fT4 were 18.66 +/- 4.18 pmol/L, of fT3 were 1.59 +/- 0.75 pmol/L, of fT3 were 2152 +/- 666 pg/ml, of TSH were 7.83 +/- 4.49 mU/ml, of TG were 44.61 +/- 23.84 ng/ml, and of TBG were 25.61 +/- 5.42 micrograms/ml. A weak negative correlation was found between the TG-value and the pH-value of the cord-artery blood (r = -0.27, y = 191.55 - 22.82.x, p less than 0.05), and between the fT4 values and the gestational age (r = -0.34, y = 67.53-1.22.x, p = 0.01). The rT3-values were positively correlated to the gestational age (r = 0.29, y = -4571 + 167.x, p less than 0.03).

[Routine examination of the mature newborn infant. Incidence of frequent "minor findings"]. / Routineuntersuchung des reifen Neugeborenen. Inzidenz häufiger "kleiner Befunde".

From 1st January to 31st August 1989 2,248 healthy, mature infants were delivered at the Department of Obstetrics and Gynaecology in Graz, Austria. They were routinely examined on day 1 and before discharge from hospital on day 4. Attention was paid to the presence or absence of minor abnormalities such as skin lesions, eruptions or rashes, cephalhaematoma, tongue tie, undescended testis, increased physiological jaundice, heart murmurs, talipes calcaneo-valgus, hip click, fracture of the clavicle and other common abnormalities and limb deformities. 20.9% of the investigated babies had no such findings whatsoever. In 79.1% of the subjects with one or more abnormalities, minor lesions due to birth trauma dominated with 24.2%, followed by postural deformities of the lower extremities in 20.5% and hip clicks and/or asymmetric skin-folds in 12.9%. Dislocation of the hip, however, was found in only 17%. Elevated serum bilirubin levels were noted in 33.0%, and in many of the jaundiced infants bruising or haematoma due to birth trauma was evident. Traumatic lesions were much rarer in infants delivered by caesarean section than in infants born vaginally.