Eosinophil activation in preterm infants with lung disease.

AIM: We investigated the role of eosinophils in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Fifteen preterm infants with BPD were compared to 13 preterms with respiratory distress syndrome (RDS) and to 16 healthy preterms. We assessed total eosinophil and neutrophil counts in venous blood samples and the levels of the eosinophilic activity markers eosinophilic cationic protein (ECP) and the cellular surface antigen (CD9). RESULTS: The eosinophil count was greater in BPD compared with RDS and healthy infants (1414 vs. 797 and 471 cells per microlitre, respectively, p = 0.03). ECP levels were elevated (34 vs. 12.8 and 9.8 microg/L, respectively, p = 0.002) and CD9 levels reduced (75 vs. 94 and 86 mean fluorescence intensity units, respectively, p = 0.01) in BPD compared with RDS and healthy infants, suggesting eosinophilic activation in BPD. These findings were not solely explained by differences between gestational age or birth weight of the different groups. ECP levels were positively correlated with the duration of oxygen supplementation in the BPD group. The eosinophil count fell promptly after steroid treatment was commenced in the BPD group. CONCLUSION: The findings suggest that BPD is linked to eosinophil activation, which might contribute to the pathogenesis.

Discordant twin growth in utero and differences in blood pressure and endothelial function at 8 years of age.

OBJECTIVE: Low birth weight is associated with increased prevalence of hypertension and cardiovascular disease in adults. The aim of this study was to evaluate genetic and intrauterine environmental contributions to blood pressure (BP) and vascular functions in twins with discordant growth in utero. SUBJECTS: We studied 31 twin pairs (21 monozygous and nine dizygous), mean age 8 years) with large within-pair differences in birth weight. Among the monozygous pairs, nine had suffered from twin-to-twin-transfusion syndrome (TTTS). METHODS: Apart from BP, we determined diameters and elasticity of the carotid artery and abdominal aorta with ultrasonography, and endothelial function in skin vessels with a laser Doppler technique, before and after transdermal delivery of acetylcholine and nitroglycerin. RESULTS: Eight of 62 twin subjects had a systolic BP above the 90th percentile in a North-American reference population. Among these, seven/eight were monozygous with a history of poor fetal growth and/or TTTS. In monozygous twin pairs without TTTS, systolic BP and pulse pressure were higher and vascular endothelial function was impaired in the lower birth weight twin. In the TTTS group, the lighter twin had a narrower carotid artery but there was no within-pair difference in arterial elasticity. Pre-eclampsia during the index pregnancy enhanced within-pair differences in BP but abolished within-pair differences in endothelial function. CONCLUSIONS: Severe fetal growth retardation contributes to higher BP, arterial narrowing and endothelial dysfunction in childhood. Pre-eclampsia may act both as an effect modifier and confounder of these associations.

Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study.

AIM: Antiepileptic drugs (AEDs) are known teratogens. Some specificity between different AEDs has been noted in the literature. The aim was to compare the teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy. METHODS: Infants exposed to AEDs (n = 1398) in early pregnancy were identified from the Swedish Medical Birth Registry. The number of infants with congenital malformations and exposed to AED was compared with the expected number estimated from all infants born (n = 582656). RESULTS: 90% (1256) of the AED exposed children were exposed to AEDs in monotherapy, 56% were exposed to CBZ and 21% to VPA. The odds ratio (OR) for having a malformation in the AED exposed group was 1.86 [95% confidence interval (95% CI) 1.42-2.44]. Exposure to VPA in monotherapy compared with CBZ in monotherapy gave OR = 2.51 (95% CI 1.43-4.68) for a neonatal diagnosis of malformations. However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups. CONCLUSION: There was a small increase in the risk of having a major malformation after exposure to AEDs in monotherapy. Exposure to VPA seems to carry a higher risk than exposure to CBZ.

Psychomotor development in preschool children exposed to antiepileptic drugs in utero.

UNLABELLED: The aim of this study was to assess psychomotor development with the Griffiths' test in preschool children exposed to antiepileptic drugs (AED) in utero. The study sample consisted of 76 children exposed to AED in utero and 71 unexposed children. The children (exposed and unexposed) have since birth been included in a population-based longitudinal follow-up study of children born to women with meticulously treated epilepsy during pregnancy, initiated in 1985. In total, 67 exposed and 66 unexposed children were tested with the Griffiths' test, which consists of 6 subsets: locomotor function, personal and social behaviour, hearing and speech, eye and hand coordination, performance, and practical reasoning. There was no significant difference in the global scores of the Griffiths' test between the two groups of children. Children exposed to phenytoin in utero (n = 16) showed a significant but subtle reduction in the scores for locomotor development compared with the unexposed children (mean scores: 98 vs 106: 95% confidence interval for the difference in mean scores: -14.0 to -0.4). There was no such difference for the children exposed to carbamazepine in utero (n = 35). The exposed children had significantly fewer siblings (p < 0.01). A significant number of the mothers with AED treatment had no higher level of education than compulsory school (p < 0.01). No other differences in socioeconomic status were observed between the groups. CONCLUSION: The subtle delay in locomotor development evaluated with the Griffiths' test at 4.5-5 y of age in children exposed to phenytoin may indicate a subtle influence on psychomotor development, which may be more obvious at school age: thus, larger studies and further follow-up are warranted.

Early discharge of preterm infants followed by domiciliary nursing care: parents' anxiety, assessment of infant health and breastfeeding.

UNLABELLED: The aim of this study was to evaluate the effect of early discharge of preterm infants, followed by domiciliary nursing care, on the parents' anxiety, their assessment of infant health and breastfeeding. Seventy-five families including 88 preterm infants who were physiologically stable but in need of further special care, such as gavage feeding, were allocated to an early discharge group (EDG) that was offered home visits (n = 40), or to a control group offered standard neonatal care (CG) (n = 35). Seventy families (37 in the EDG and 33 in the CG) completed the study to the 1-y follow-up. Data were collected by means of questionnaires on three occasions: in the EDG, at hospital discharge, on completion of the domiciliary care programme and after 1 y, and in the CG at the corresponding points in time, which were during hospitalization, at hospital discharge and after 1 y. No statistical differences were observed between the groups in emotional well-being, except that mothers in the EDG had a lower level of situational anxiety at the time of hospital discharge compared with CG mothers whose infants remained in hospital. One year after the birth, the EDG mothers said they had felt better prepared to take responsibility for the care of their babies after completion of the domiciliary care programme, in contrast to CG mothers. However, no statistical differences were observed in the recollection of anxiety, confidence in handling the baby and periods of mental imbalance. No statistical difference was observed in breastfeeding rates between the groups. Fathers in the EDG group tended to perceive their babies as being healthier, compared with CG fathers. CONCLUSION: Early discharge of preterm infants followed by domiciliary nursing care did not seem to have any major effect on the parents' anxiety and their assessment of infant health.

Body dimensions of infants exposed to antiepileptic drugs in utero: observations spanning 25 years.

PURPOSE: To investigate the influence of maternal antiepileptic drug (AED) treatment on pregnancy duration, birth weight, body length, head circumference, and intrauterine growth in infants exposed in utero to antiepileptic drugs in Sweden between 1973-1997, with 963 singleton infants. METHODS: Data collected from (a) 1973-1981 (record linkage between a hospital discharge register and a medical birth register); (b) 1984-1995 (prospectively collected information in one defined catchment area with two delivery hospitals); and (c) 1995-1997 (medical birth register data). Observed numbers of infants below a defined size for body measurements compared with expected numbers calculated from all births in Sweden after stratification for year of birth, maternal age, parity, and education or smoking habits in early pregnancy. Standard deviation scores estimated with same stratification procedures. RESULTS: Fraction of monotherapy exposures increased from approximately 40% to approximately 90% from 1973 to 1997. Significantly increased numbers of infants with small body measurements found in exposed group. Negative influence on body dimensions decreased over time. More marked effects found in infants exposed to polytherapy. In monotherapy, only infants exposed to carbamazepine consistently showed reduction in body dimensions. Significant effect on gestational age in girls and on number of small for gestational age (<2 SD) in boys. CONCLUSIONS: Polytherapy with antiepileptic drugs and negative influence on body dimensions decreased. In monotherapy, only carbamazepine has a negative influence on body dimensions in this study.

Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome.

Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.

Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study.

The aim of this study was to assess psychomotor development, using Griffiths' test, and the incidence of minor anomalies at birth in children who had been exposed to antiepileptic drugs (AEDs) in utero. The study sample comprised 100 children of mothers who were treated with AEDs during pregnancy and 100 matched control children. Women with epilepsy were recruited from a pregnant urban population (450 000 inhabitants). The lowest possible dose of the fewest AEDs to maintain seizure control was used. Drug levels were controlled on a monthly basis. The children were assessed at 9 months of age. The study children had a significant increase in the number of minor anomalies (31 compared with 18 control children; odds ratio 2.4, CI 1.15 to 5.02, P=0.02 McNemars test), and an increased number of facial anomalies after carbamazepine exposure (11 compared with six control children). Drug exposure did not influence the Griffiths' score at 9 months of age. Even a meticulous AED treatment strategy during pregnancy increases the number of minor anomalies. However, treatment with AEDs does not necessarily influence short-term psychomotor development.

Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs.

PURPOSE: To prospectively study the incidence of structural and/or functional ophthalmological abnormalities in the offspring to an unselected population of women with epilepsy, subjected to a well controlled antiepileptic drug (AED) treatment during pregnancy. METHODS: Forty-three children prenatally exposed to antiepileptic drugs and 47 controls were included. Blinded ophthalmological examinations including fundus photography were performed at a median age of 7 years and 4 months. RESULTS: No major eye anomalies were found except in one child in the exposed group who had nystagmus and low vision. The visual acuity was lower in the eye with lowest acuity among the exposed children (p < 0.05). No other significant difference was found between the two groups. CONCLUSION: The results suggest that a well-controlled treatment with AEDs, preferably monotherapy, during pregnancy does not have any major adverse effects on the development of the eye and ophthalmological functions.

Early discharge of preterm infants needing limited special care, followed by domiciliary nursing care.

The aim of this study was to evaluate the effect of early discharge, followed by domiciliary nursing care, on infant health and utilization of health services in preterm infants still in need of special care (mainly gavage feeding). In total, 88 infants who were physiologically stable, but in need of further special care such as gavage feeding, were allocated to an early discharge group (EDG = 45 infants) and offered home visits by a nurse backed up by a neonatologist, or to a control group offered standard neonatal care (CG = 43 infants). Infants in the EDG spent 30.6 d (mean) in hospital after birth compared with 46.3 d in the CG (p = 0.003). On average, the domiciliary nurse spent 10.4 h with each family in the EDG, including a median number of 5 home visits, scheduled telephone contact and travelling time. The infants had a mean of 1.7 scheduled visits and 0.4 unscheduled visits to the neonatal ward. The domiciliary nurse received a mean of 0.9 telephone calls from the parents. When the period of domiciliary care in the EDG (post-conceptional age 35.9-38.7 wk) was compared with the corresponding time in hospital in the CG (post-conceptional age 35.6-38.6 wk), no statistical differences were observed in infant health, surgical procedures or medication. However, a reduced incidence of respiratory infections was observed in the EDG (6 versus 16 infants; p = 0.02). Nine infants in the EDG were re-hospitalized. The two groups did not differ in the numbers of rehospitalizations and non-elective contacts with the health services during the first year after discharge. In conclusion, early discharge of preterm infants still requiring special care, followed by domiciliary nursing care, was associated neither with an increased utilization of health services after discharge, nor with infant morbidity after discharge. More information on safety is needed before widespread early discharge can be advocated.

[Epilepsy and pregnancy. Balancing between risks to the mother and child]. / Epilepsi och graviditet. En balansgång mellan risker för mor och barn.

Pregnancy may be especially problematic for the epileptic woman, obstetric complications tend to be more frequent, and seizure control and the pharmacokinetics of anticonvulsants may be affected. The risk of seizures is particularly high during labour and delivery-almost 10-fold higher than at other times during pregnancy. As uncontrolled generalised tonic-clonic seizures may be hazardous to both gravida and fetus, the use of anticonvulsants to prevent their occurrence is to be recommended during pregnancy even though all anticonvulsant drugs are potential teratogens. There is a 2- to 3-fold increase in the risk of birth defects in conjunction with fetal exposure to these drugs. Although the mechanisms mediating the teratogenic effects have not been identified, interference with folate metabolism, formation of toxic metabolites and drug-induced fetal hypoxia have been suggested. Despite the incompleteness of our knowledge, some recommendations can be made for the management of pregnant women with epilepsy. Pre-pregnancy counselling is important. Epileptic women contemplating pregnancy need to be informed of the pros and cons, and any major change in anticonvulsant therapy should be made before conception. Monotherapy is preferable, using the drug appropriate to seizure type and epilepsy syndrome at the lowest dosage and serum level that protects against tonic-clonic seizure. The clinical situation needs to be assessed and drug levels need to be monitored more frequently during pregnancy than otherwise. Patients on anticonvulsant treatment during pregnancy also need to be informed of the possibility of antenatal diagnosis. The use of new anticonvulsant drugs during pregnancy represents a particular challenge, since available clinical data may be insufficient to indicate their teratogenic potential Such a drug should be used in pregnancy only if essential to obtain seizure control. Moreover, the outcome of all such pregnancies needs to be carefully documented.

The Stockholm birth centre trial: maternal and infant outcome.

OBJECTIVE: To compare an in-hospital birth centre with standard maternity care regarding medical interventions and maternal and infant outcome. BACKGROUND: The birth centre care was characterised by comprehensive antenatal, intrapartum and postpartum care with the same team of midwives, restricted use of medical technology, and discharge within 24 h after birth. METHODS: Of 1860 women meeting low risk medical criteria in early pregnancy and interested in birth centre care, 928 were randomly allotted birth centre care and 932 standard maternity care. Data were collected mainly from hospital records, and analysis was by intention-to-treat. RESULTS: Of the women in the birth centre group, 13% were transferred antenatally and 19% intrapartum. No statistical differences were observed in maternal morbidity or in perinatal mortality, neonatal morbidity, Apgar score or infant admissions to neonatal care. Perinatal mortality, defined as intrauterine death after 22 weeks of gestation and infant death within seven days of birth, occurred in eight cases (0.9%) in the birth centre group and in two cases (0.2%) in the standard care group (OR 4.04, 95% CI 0.80 to 39.17; P = 0.11). Subgroup analysis showed that a larger proportion of first-born babies in the birth centre group (15.6%) were admitted for neonatal care than in the standard care group (9.5%) (P = 0.003), whereas the converse was the case for the newborns of multiparous women: 4.7% and 8.4%, respectively (P = 0.04). The overall rates of operative delivery (e.g. caesarean section, vacuum extraction and forceps), 11.1% in the birth centre group and 13.4% in the standard care group, did not differ statistically (P = 0.12), but obstetric analgesia, induction, augmentation of labour and electronic fetal monitoring were less frequently used in the birth centre group. Labour was 1 h longer in the birth centre group. CONCLUSION: Birth centre care was associated with less medical interventions than standard care without any statistically significant differences in health outcomes. However, the excess of perinatal deaths and of morbidity in primigravidas' infants in the birth centre group gives cause for concern and necessitates further studies.

Antiepileptic drug treatment during pregnancy and neonatal screening results.

Many antiepileptic drugs induce hepatic metabolic enzymes and thus enhance metabolism of steroid and thyroid hormones. Antiepileptic drugs readily cross the placenta and the foetal liver is metabolically active. We therefore evaluated the neonatal screening results of TSH and 17-hydroxyprogesterone in 34 study children and their matched controls. There were no statistically significant differences in the results between the groups.

Inhibition of cerebrospinal fluid formation by omeprazole.

Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.

Early postnatal development of transport functions in the rabbit choroid plexus.

The development of transport functions in the rabbit choroid plexus was followed postnatally up to 2 months after birth. The activity of ouabain-sensitive Na+, K+-ATPase in newborn rabbit choroid plexus composes about one-fourth (lateral and third ventricle) to one-half (fourth ventricle) of the activity in the adult animal, and it increases markedly within the first 3 weeks of early life. A similar profile of postnatal changes is observed for the capacity to take up and accumulate the organic base choline, which is about three to five times higher for the adult rabbit than for the newborn animal. This coincides with the maturation of the epithelial cells as well as with the development of the sympathetic nerve supply in the choroid plexus. The results suggest that energy-dependent translocation systems influenced by local sympathetic nerves in the choroid plexus, at the interface between blood and CSF, have a functional role shortly after birth.