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According to previous studies, childhood cancer survivors have an elevated risk for late mental health effects. However, only few studies exist on young adulthood (YA) cancer survivors' mental health outcomes. In our study, we examined first time antidepressant (AD) medication purchases of childhood and YA cancer patients compared to siblings. The first time AD medication purchases of 7,093 cancer patients aged 0-34 years at diagnosis and a sibling cohort (N = 26,882) were retrieved from the Social Insurance Institution of Finland (Kela) since 1.1.1993. Cancer patients diagnosed between 1.1.1994 and 31.12.2004 were identified from the Finnish Cancer Registry and sibling controls via the Population Registry Centre. Statistical analyses were performed via the Cox regression model, and the hazard ratios (HR) were adjusted for age and gender. Increased hazard ratios for AD purchases were found in the younger (0-19 years at cancer diagnosis) [HR 5.2, 95%CI (3.7-7.2)] and older (age 20-34 years at cancer diagnosis) [HR 4.5, 95%CI (3.9-5.2)] cancer patient groups compared to siblings. The gender effect was similar in patients and controls, showing that females have higher risk for AD purchases than males. Males in the younger patient group had highest HR (5.6) for AD purchases compared to siblings. Patients with sarcoma or CNS tumor in the younger age group and leukemia or CNS malignancy in the older age group had the highest risk for AD medication purchases. The frequency and risk for AD purchases has been increasing during recent decades in both cancer patient age groups compared to siblings. Thus, cancer patients' psychological support should be properly assessed already after primary treatment. Certain diagnostic groups as well as female patients may require more psychological support than others.

Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH. Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH. Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro. Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.

UNLABELLED The effects of maternal magnesium sulphate treatment on neonatal mineral status and parathyroid hormone secretory response were studied in 8 exposed and 27 control preterm infants during the first 2 wk of life. Antenatal magnesium sulphate resulted in hypermagnesaemia during the first 3-7 d of life without affecting other serum mineral concentrations. CONCLUSION Early hypermagnesaemia was associated with hypercalciuria during the first 3 d and parathyroid hormone suppression up to the age of 2 wk in the exposed infants.

The Finnish HPV Family Study is a prospective cohort study assessing the dynamics of human papillomavirus (HPV) transmission between parents and infant. Serial genital and oral scrapings from 76 families, including mother, father, and infant, and semen samples were collected over 2 years of follow-up, analyzed by nested PCR, and confirmed by hybridization with 12 high-risk (HR) HPV types. The most common HPV profile was HR HPV in all family members (29%), followed by HPV-positive mother-infant pairs (26%). HPV-positive father-infant pairs were less frequent (11%), and in six (8%) families, only the infant was HR HPV positive. The prevalence of genital HR HPV in the parents ranged from 13 to 25%, and that of oral HPV ranged from 8 to 34%. In the infants, HPV DNA was detected in 15% of the genital and 10% of the oral samples at birth, reaching peaks of 18 and 21%, respectively, at 6 months, and declining to 10% at 24 months. Persistent HPV in the mother was a risk factor for oral HPV in the infant (odds ratio [OR], 5.69; 95% confidence interval [95% CI], 1.5 to 21.3), while oral HPV in the mother at 6 months was a risk factor for genital HR HPV (OR, 6.38; 95% CI, 1.15 to 35.32). No such independent risk could be attributed to subclinical HPV in the father. Persistent maternal cervical HPV and subclinical oral HPV affect the risk of infant HPV. The age of 6 months is a critical point for the infant to acquire or be free of HR HPV DNA.

Neonatal meconium aspiration often produces severe respiratory distress due to an inflammatory pulmonary injury, but the extension of this damaging reaction to the noncontaminated lung regions is still uncertain. To investigate the presence of generalized pulmonary inflammatory response, 31 anesthetized and ventilated neonatal piglets (1-3 d) were studied. Meconium (n = 16) or saline (n = 15) was instilled unilaterally into the right lung, and analysis of the lung tissue or bronchoalveolar lavage (BAL) fluid from both lungs was performed after 12 h. Meconium increased the wet/dry weight ratio, histologic tissue injury score and tissue myeloperoxidase activity as well as BAL fluid total cell count in the contaminated lung. Tumor necrosis factor-alfa concentrations in BAL fluid did not however differ significantly. Furthermore, in the meconium-instilled lungs the tissue and lavage fluid catalytic activity of phospholipase A2 (PLA2) and tissue PLA2 group-I and group-II concentrations were significantly elevated. Although BAL fluid catalytic activity of PLA2 was moderately increased also in the meconium noninstilled lung, significant inflammatory injury in this lung was absent. The results thus indicate that meconium aspiration induces severe local inflammation and lung injury, but significant generalized pulmonary inflammatory damage in the pathogenesis of meconium aspiration syndrome is unlikely.

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.

To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3-13.3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy-related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.

In many very-low-birth-weight (VLBW) infants the ductus arteriosus fails to close spontaneously, and they subsequently develop signs and symptoms of poor tissue perfusion and heart failure. This study evalutes the results of early surgical closure of patent ductus arteriosus (PDA). We retrospectively reviewed the records of all 101 VLBW infants who weighed 1,500 g or less when their PDA was surgically ligated in Turku University Hospital between 1988 and 1998. The mean gestational age at birth was 27.2 weeks and mean birth weight 963+/-239 g. The operation was performed at 12+/-8 days of age; the infants' weight at operation was 969+/-231 g and they were tracheally extubated 11+/-14 days after the operation. The surgery-related mortality was 3% (3/101) and overall mortality 10% (10/101). We conclude that surgical closure of PDA is safe and effective in VLBW infants.

Background: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. Objective: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. Methods: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. Results: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing ( P = .005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 × 10 7 [3.8-22.9 × 10 7 ] vs 3.3 × 10 7 [1.8-6.1 × 10 7 ], P = .04) and tended to have fewer bifidobacteria (1.8 × 10 9 [0.4-7.6 × 10 9 ] vs 6.1 × 10 9 [2.5-14.6 × 10 9 ], P = .11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia ( P = .03). The differences were not detected by bacterial cultivation. Conclusion: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode. (J Allergy Clin Immunol 2001;107:129-34.)

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3′,5′-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.

Background: According to data from animal and in vitro studies, transforming growth factor-β (TGF-β) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. Objective: We sought to ascertain whether TGF-β in breast milk is associated with specific IgA production and atopic disease in human subjects. Methods: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-β1 and TGF-β2 in maternal colostrum, mature milk, and the infants' sera were determined. The enzyme-linked immunospot assay was used to assess the infants' specific IgA production in response to β-lactoglobulin, casein, gliadin, and ovalbumin. Results: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-β1 and TGF-β2 were higher in maternal colostrum, but not in mature milk and infants' serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease ( P = .0008 and P = .015, respectively). The concentration of TGF-β2 was, and that of TGF-β1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells ( P = .048 and P = .076, respectively). Conclusion: TGF-β in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects. (J Allergy Clin Immunol 1999;1251-7.)

The present study was performed to measure the vasoregulatory reactions to dynamic changes in local skin temperature during open bed phototherapy. Periodic thermal stimulation using warm and cool air currents was applied to the skin of ten term infants with physiological jaundice, before and during open bed phototherapy. The reactivity of skin blood flow (SBF) and heart rate was measured using laser Doppler flowmetry and power spectral analysis. The baseline SBF increased significantly by 70% (P = 0.008) during phototherapy without any significant change in skin or rectal temperature. Before phototherapy, the rhythmic (0.08 Hz) thermal skin stimulation increased the oscillations of SBF (from 89 ± 26 au to 213 ± 37 au, P = 0.02) at the stimulation frequency band. This response was further increased (P = 0.03) during phototherapy (from 198 ± 54 au to 658 ± 115 au, P = 0.004). Phototherapy increased SBF in icteric otherwise healthy neonates. The cutaneous vasodilatation augments the cardiovascular responsiveness to thermal stimulation. Conclusions These results suggest that open bed phototherapy does not inhibit the cardiovascular responsiveness to local thermal skin stimulation in healthy term infants.

Factors that direct the immune responsiveness of the newborn beyond the immediate post-natal period are not known. We investigated the influence of mode of delivery and type of feeding on the phagocyte activity during the first 6 months of life. Sixty-four healthy infants (34 delivered vaginally and 30 by elective Caesarean section) were studied at birth and at the ages of 2 and 6 months. Phagocyte functions were studied by measuring the chemiluminescence (CL) activity of whole blood and isolated leucocytes and by investigating the expression of phagocyte receptors (FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16), CR1 (CD35), CR3 (CD11b) and FcαR (CD89)) on neutrophils, monocytes and eosinophils by using receptor-specific MoAbs and immunofluorescence flow cytometry. Infants born by elective Caesarean section had significantly higher CL activity than those delivered vaginally during the entire 6-month follow up. In addition, infants who received formula feeds had significantly higher CL activity at 6 months of age and higher expression of FcγRI-, Fcα- and CR3-receptors on neutrophils than infants exclusively breast-fed. We suggest that stress reaction associated with labour influences the phagocytic activity measured in the cord blood but later during infancy the intraluminal antigens, gut microflora and diet, become important determinants in immune programming of human individuals.

Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization--for example, cesarean delivery and antimicrobial agents. To study the duration of the effect of external factors on intestinal colonization, two groups of infants with different delivery methods were investigated.The fecal flora of 64 healthy infants was studied prospectively. Thirty-four infants were delivered vaginally, and 30 by cesarean birth with antibiotic prophylaxis administered to their mothers before the delivery. The fecal flora was cultured on nonselective and selective media in infants 3 to 5, 10, 30, 60, and 180 days of age. Gastrointestinal signs were recorded daily by the mothers for 2 months.The fecal colonization of infants born by cesarean delivery was delayed. Bifidobacterium-like bacteria and Lactobacillus-like bacteria colonization rates reached the rates of vaginally delivered infants at 1 month and 10 days, respectively. Infants born by cesarean delivery were significantly less often colonized with bacteria of the Bacteroides fragilis group than were vaginally delivered infants: At 6 months the rates were 36% and 76%, respectively (p=0.009). The occurrence of gastrointestinal signs did not differ between the study groups.This study shows for the first time that the primary gut flora in infants born by cesarean delivery may be disturbed for up to 6 months after the birth. The clinical relevance of these changes is unknown, and even longer follow-up is needed to establish how long-lasting these alterations of the primary gut flora can be.

Patterns of long-chain faecal fatty. acids were studied by gas-liquid chromatography in 55 newborn infants in a neonatal intensive care unit. Decreased fractions of fatty acid C16: l 9 and increased fractions of C16:0 and C17 :0 were associated with the occurrence of abdominal distension. Decreased fractions of C16 : 1 9 and C18 : 2 9.1 were associated with diarrhoea. Flatulence was found in infants who had relatively smaller amounts of fatty acids Cl 7 : 0D and Cl 5 : 0 in their faecal samples. The differences in the patterns of faecal fatty acids are due to differences in bacterial flora. The results support the hypothesis that the initial intestinal colonization plays a role in the later gastrointestinal signs of newborn infants.

Improvements in cancer therapy have resulted in an expanding population of early-onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early-onset cancer survivors with a special interest in YA cancer survivors. In a population-based setting, we explored the risk of cardiovascular disease in early-onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5-year survivors were included in our study (N = 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0-19 and 20-34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9-20.4) and 3.6 (95% CI 2.8-4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3-5.1) and 1.7 (95% CI 1.4-2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7-6.5) and 1.8 (95% CI 1.5-2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2-2.6) and 1.4 (95% CI 1.2-1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk-based long-term follow-up of early-onset cancer survivors.

Genetic factors cannot explain the recent rapid increase in the incidence of atopic diseases. The phenomenon has been explained by environmental factors, and there are data for and against the hypothesis that a decline in the pressure of microbial stimulation early in life could be behind the allergy epidemic. Changes have also occurred in maternity care, among them a rise in the caesarean section rate, which could diminish initial microbial exposure and thereby alter T helper 1 cell/T helper-2 cell development and affect the risk of developing atopy. In this study, we sought to establish whether mode of delivery does influence the development of atopic asthma. Finnish 1987 Medical Birth Register (n = 59,927 live births) information was linked between several national health registers to obtain information on asthma and mode of delivery in children registered. The data were adjusted for maternal age, previous deliveries, child's sex, and birth size. Atopy was evaluated in the second study (Turku Birth Cohort), which involved 219 children born by vaginal delivery (n = 106) or caesarean section (n = 113); history of atopic symptoms was established by questionnaire and a clinical examination was conducted, including skin prick testing and determination of total and allergen-specific IgE in serum. The register study showed the cumulative incidence of asthma at the age of seven to be significantly higher in children born by caesarean section (4.2%) than in those vaginally delivered (3.3%), the adjusted odds ratio (OR) for confounding variables being 1.21 (1.08-1.36), p < 0.01. In the second study, significantly more positive allergy tests were reported in questionnaires in the caesarean (22%) than in the vaginal delivery group (11%), OR 2.22 (1.06-4.64), p < 0.01, and a trend toward more positive skin prick reactions was documented at clinical examination; 41% versus 29%, OR 1.31 (0.65-2.65), p = 0.11. In conclusion, these results suggest that caesarean section delivery may be associated with an increased prevalence of atopic asthma.

We hypothesized that the absence of an increase in the Doppler-derived aortopulmonary pressure gradient (APPG) across the ductus arteriosus, which reflects pulmonary artery pressure during the first day of life, can predict clinical complications in preterm infants with neonatal respiratory distress syndrome (RDS) STUDY DESIGN: Twenty-nine healthy preterm infants weighing 2210 +/- 244 gm (mean +/- SEM) and 63 infants with RDS weighing 1645 +/- 86 gm were studied with the Doppler ultrasound technique for measurement of the mean APPG at 2, 24, 48, and 72 hours of age. Of infants with RDS, 67% were treated with synthetic surfactant.Spontaneous closure of the ductus arteriosus on the first day of life led to exclusion of 11 infants with RDS and 17 control subjects from the study. Of the remaining 52 infants with RDS, 26 had an increase in the APPG from 2 to 24 hours of age, and APPG values remained low in the other 26 infants. Neonatal complications appeared more frequently (p0.001) in distressed infants with little change in APPG values (delta APPG) (22/26) than in infants with high delta APPG (6/26). Six of the infants with high delta APPG values (23%) needed medical or surgical closure of the ductus, but no other acute neonatal complications occurred; 14 (54%) of the infants with low delta APPG required ductal closure. Between the ages of 24 and 58 hours, five of the latter 26 infants had severe pulmonary hemorrhage, which was fatal in two cases. Severe (grade III or IV) intraventricular hemorrhage was seen in three infants with RDS and a low delta APPG; one of these infants also had severe pulmonary bleeding. Pneumothorax occurred in six infants with a low delta APPG. Infants without an increase in the APPG value during the first day of life required a significantly higher fraction of inspired oxygen.Noninvasive measurement of the change in APPG during the first day of life may provide a useful method for identifying infants with RDS at high risk of neonatal complications.

Pulsatile changes in intracranial blood volume (transcephalic electrical impedance, delta Z), arterial blood pressure (aBP) and respiration were studied during the first day after birth in 42 neonates with a birth weight of 1040-3850 g and gestational age of 26-36 weeks. The neurological outcome was assessed at 1 year of age to study the predictive ability of delta Z. delta Z, ECG, respirogram and direct aBP were recorded at 8-h intervals. Outcome was adverse in seven infants of whom two died from severe peri-intraventricular haemorrhage. PCO2 was higher (6.2 kPa) in the infants with adverse outcome than in those infants with favourable outcome (5.0 kPa) (P = 0.004). Blood glucose (4.5 vs. 3.3 mmol/l, P = 0.030) and first day administration of fluid (80 vs. 63 ml/kg/day, P = 0.003) behaved, respectively. Of the infants receiving dopamine therapy, 60% had adverse outcome while only 11% of those not receiving dopamine had adverse outcome (P = 0.016). Of the infants with high diastolic blood pressure levels, 32% had adverse outcome, while none with low diastolic blood pressure levels had adverse outcome (P = 0.031). Spectral analysis was used to examine signal variabilities in the frequency domain. During the first 24 h of life, the variabilities of aBP and respiration were equal in all the infants. The high-frequency delta Z signal variability (1.50-4.00 Hz, heart rate level) was found to be lower in the infants with adverse outcome (330 units) than in the infants with favourable outcome (1280 units, P = 0.017). The low delta Z variability allowed us to assume that there is a decrease of pulsatile cerebral blood flow (CBF) in the infants with adverse outcome. We speculate that this may result from the 'no reflow phenomenon', increased tissue pressure due to ischaemia and/or PIVH, the 'brain sparing effect' or constriction of main cerebral arteries due to increased pressure support or metabolic factors (PCO2, glucose). We believe that transcephalic impedance provides a potential cot-side method for monitoring cerebral circulation in the neonatal period with an ability to predict outcome.

Background: Asthma is generally regarded as a disease with strong T H 2-type cytokine expression, whereas in autoimmune disorders, such as coeliac disease (CD), insulin-dependent diabetes mellitus (IDDM), and rheumatoid arthritis (RA), T H 1-type expression is seen. According to the cross-regulatory properties of T H 1 and T H 2 cells, one would assume that these diseases exist in different patient populations. Objective: We sought to test the hypothesis that asthma could exist in children with T H 1-type diseases, such as CD, IDDM, and RA. Methods: Comparison was made of the cumulative incidence of asthma in children with CD, IDDM, or RA by linking Finnish Medical Birth Register data on the whole 1987 birth cohort (n = 60,254 births) with the data of several national health registers to obtain information on the incidences of these diseases during the first 7 years of life. Results: The cumulative incidence of asthma in children with CD (24.6%) or RA (10.0%) was significantly higher than in children without CD (3.4%) or RA (3.4%; P P = .016, respectively). Asthma tended to be more common in children with IDDM than in children without IDDM. Conclusion: These data indicate that the T H 1 and T H 2 diseases can coexist, indicating a common environmental denominator behind the disease processes. (J Allergy Clin Immunol 2001;108:781-3.)

We describe platelet alloimmunization which caused severe thrombocytopenia in a neonate and could only be detected by testing the father's platelets. The platelet-specific antibodies were identified by a monoclonal antibody-immobilized platelet protein assay (MAIPA) using monoclonal antibodies against glycoprotein (GP) IIbIIIa complex (AP2 and 2G12). The previously described alloantigen systems on the GPIIbIIIa complex (HPA 1, HPA 3 or HPA 4) were not responsible for the reaction. In addition the newly described private platelet antigen Sra was not identical to the antigen. The antigen is therefore different from all known platelet alloantigens and was designated Vaa. The antigen was present on the platelets of the affected child. Family studies showed that the platelet antigen was transmitted as an autosomal dominant trait in three generations. No Va (a+) individuals were found in a population study of 250 blood donors, which indicates that the antigen is of low frequency in the Finnish population. The Va antigen was not detectable by immunoblot analysis, which suggests that the epitope may not be a linear peptide structure. The antigen was also destroyed by solubilization of platelets. Thrombin activation of platelets, known to increase the expression of GPIIbIIIa on platelets, did not increase the number of binding sites for anti-Vaa antibodies to the extent observed with anti-HPA 1a binding.

Of the excitatory amino acids, glutamic and aspartic acid were studied in the cerebrospinal fluid of six infants 4–32 hours after a documented episode of severe neonatal asphyxia. Aspartic acid concentration was definitely increased in the cerebrospinal fluid of these patients, whereas glutamic acid concentration varied considerably. Aspartic acid was always increased, even hours after the period of asphyxia, but values were greater in samples taken less than 12 hours after the asphyxial event. The patients with the highest cerebrospinal fluid aspartic acid concentrations had more severe outcomes.

Severe prematurity is a prime factor causing perinatal mortality or morbidity. In Finland 1% of babies are born before 32 completed weeks of pregnancy and 0.9% are delivered with a birth weight of 1500 g or less. Since transport of a baby in utero is preferable to transporting a neonate, approximately 85% of infants below 1000 g and 90% of infants between 1000 to 1499 g are delivered in departments with facilities for neonatal intensive care. The rate of caesarean delivery is approximately 50% in pregnancies between 26 and 28 weeks, while the overall caesarean section rate is 15%. Deaths of low birth weight babies account for 66% of the total perinatal mortality and those of very low birth weight babies 46%. Intrauterine deaths constitute two thirds and neonatal deaths one third of perinatal mortality among very low birth weight babies. In Turku, neonatal survival rate for infants of 500 to 749 g was 61.5% and for infants of 750 to 999 g, 77.3%. In Turku respiratory distress syndrome is one of main complications of prematurity that has led to death in 11.2% of infants in recent years. Of the survivors, 85% have been healthy at the age of two years. The incidence of the bronchopulmonary dysplasia among very low birth weight infants has been 19.7%. In recent years, the incidence of severe brain haemorrhage has been 32% among infants with a birth weight below 1000 g.

Early postnatal pulmonary hemodynamic changes were investigated with Doppler echocardiography in 17 infants with mild or moderate meconium aspiration syndrome (MAS) and 16 healthy infants in a control group. The results indicate that the physiologic adaptation of the pulmonary hemodynamics is delayed in mild and moderate forms of MAS. Thus infants with clinical evidence of MAS need careful cardiovascular monitoring during postnatal circulatory transition.

We studied Malassezia furfur colonization of neonates in the neonatal intensive care unit (NICU) and found that the rate was astonishingly high as compared to the previous studies. In very low birth weight (less than 1,000 g) infants we recorded a colonization rate of 80%, and 4% infants with a birth weight greater than 2,000 g. Under 10 day's hospitalization the rate was 11%, and it was 70% after 20 days spent in the unit. Among the infants with the birth weight less than 1,700 g, antibiotic therapy was recorded as a significant risk factor for colonization. In the infants with a greater birth weight, the colonization rate was independent from the risk factors studied. M. furfur colonization could not be linked with occurrence of any symptoms of signs recorded and colonization by M. furfur was so common in NICU that the predictive value of surveillance cultures is poor.

Knowledge of the sleep state is important in physiological studies since many physiological variables show different properties in different sleep states. The recently developed static charge sensitive bed (SCSB) method allows long-term recordings of body movements, respiration and ballistocardiogram without electrodes attached to the subject. The recordings are easy to carry out and they do not disturb the subject in any way. The recorded variables are basic characteristics of different sleep states. SCSB-recordings and electroencephalography (EEG) based polygraphy as well as blind sleep state scoring were carried out in 8 newborn infants. The positive correlation between SCSB-scoring and EEG-based polygraphy scored by two clinical neurophysiologists was 68.1 and 64.1%. Only in 2% of all epochs was active sleep scored as quiet sleep or vice versa. The results indicate the usefulness of the SCSB method in sleep state scoring of newborn infants.

The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestationor = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (96 h duration) versus early prolonged (96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e.96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group.The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.

OBJECTIVES To examine whether cerebral blood flow variables during the first critical day of life can predict the 1-yr neurologic outcome in ventilated and nonventilated preterm infants. DESIGN Prospective follow-up study. SETTING Neonatal intensive care unit of university central hospital. PATIENTS Forty-nine preterm infants

We assessed by echocardiography the left ventricular systolic and diastolic function in newborn infants of mothers with well-controlled pregestational type 1 or gestational diabetes (IDM) in comparison to normal term neonates.Two-dimensional/M-mode and Doppler transmitral flow velocity measurements were performed in 18 IDM and 26 control infants of non-diabetic mothers (gestational ages 36-40 and 36-41 weeks, respectively) between days 2 and 5 after birth. In the IDM, there were nine mothers with pregestational (White class C or D) and nine mothers with gestational diabetes (White class A or A/B). Peak early and atrial filling velocity, early deceleration time, early acceleration time, early, atrial and total time velocity integrals were used to examine the left ventricular diastolic performance. We also calculated the early/atrial velocity ratio, early/atrial integral ratio and early/total integral ratio. The fractional shortening, fractional shortening area, midwall fractional shortening (mFS), left ventricular mass and indexed left ventricular mass for body surface area (BSA) and birth weight were used in assessment of left ventricular systolic performance.The early deceleration time was longer, resulting in higher early integral and early filling fraction (EFF) in the IDM than in the control infants (p0.01). In the IDM, the fractional shortening was somewhat greater and the left ventricular mass/body surface area ratio was higher than in the control group (p0.05), although the measures of systolic performance were within the normal range. There were no significant differences in the systolic or diastolic function parameters between the gestational and pregestational groups.In the infants of mothers with well-controlled pregestational or gestational diabetes, we found prolonged deceleration time of early left ventricular diastolic filling, probably reflecting an impaired left ventricular relaxation rather than compliance. The mechanism for the findings may be maternal hyperglycemia during the third trimester and subsequent fetal hyperinsulinaemia leading to neonatal cardiac hypertrophy.

To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor.12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed.The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO290% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004).Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.

Objective: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome. Study design: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996–1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models. Results: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores. Conclusion: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22–26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.

To compare postnatal adaptation between Caesarean and vaginal deliveries, by studying sleep states, oxygenation, heart rate and body movements. Another aim was to follow the adaptation of healthy, term, vaginally born babies.Ten vaginally born and 12 neonates born by elective Caesarean section were recorded with a movement sensor (SCSB, static-charge-sensitive bed), electrocardiogram and oximeter. The recordings started 1.5 h after birth and lasted for 12 h. For the vaginal group, another 12 h recording was performed during the third night postpartum.Delivery mode did not affect sleep state distribution. The vaginal group had more oxyhaemoglobin desaturation episodes95% than the Caesarean section group (mean +/- SD: 59 +/- 10% vs 42 +/- 22% of epochs, p = 0.03), especially in active sleep, but baseline saturation was similar (96 +/- 1% vs 95 +/- 3%, p = 0.93). The vaginal group had fewer movements during sleep than the Caesarean section group (movements of 5-10 s: 5 +/- 1 h(-1) vs 10 +/- 3 h(-1), p = 0.0001). During the first 3 d, the amount of sleeping and active sleep increased, whereas wakefulness and quiet sleep decreased. Baseline oxyhaemoglobin saturation and the number of movements of over 5 s increased.Delivery mode did not affect sleep state distribution but, unexpectedly, the vaginal group had more oxyhaemoglobin desaturation events and fewer body movements than the Caesarean section group. These differences during the first postnatal day remain unexplained, but they may reflect stress and pain during labour. After a few days, changes in sleep organization, and increases in oxyhaemoglobin saturation and frequency of body movements were noted in the vaginal group, which may represent recovery and adaptation to extrauterine life.

Background Although citalopram has gained wide acceptance in the treatment of depression and anxiety disorders, its use during pregnancy and lactation has been poorly characterized. The aim of this study was to examine the efficacy and safety of citalopram in relation to concentrations of citalopram and its metabolites during pregnancy and lactation. Methods Eleven mothers taking citalopram and their infants were enrolled in the study, and a control group of 10 women who were not taking medication were prospectively matched for confounding obstetric characteristics at the time of delivery. Plasma and breast milk samples were collected from mother/infant pairs during pregnancy, at delivery, and for up to 2 months after delivery. Trough plasma and breast milk concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram were measured by HPLC. The pregnancy outcome was recorded, and the neurodevelopment of children was monitored for up to 1year. Results Although the citalopram dose of 20 mg to 40 mg once daily resulted in low maternal trough plasma concentrations (range, 46-214 nmol/L) and metabolites during pregnancy, only one subject required an increase of daily dose. The mean didesmethylcitalopram-desmethylcitalopram metabolic ratio was significantly higher during pregnancy (54%, P < .001) than at 2 months after delivery, indicating induction of cytochromeP450 (CYP) 2D6 during pregnancy. At delivery, the trough plasma citalopram, desmethylcitalopram, and didesmethylcitalopram concentrations in the infants were 64%, 66%, and 68% ofthe maternal concentrations, respectively. The citalopram and metabolite concentrations in the milk were 2- to 3-fold higher compared with maternal plasma concentrations, but theinfant citalopram and metabolite plasma concentrations were very low or undetectable. Thedelivery outcome and the neurodevelopment of all infants up to the age of 1 year were normal. Conclusion Even though the sample size was limited, results from this prospective clinical trial suggest uncomplicated pregnancy outcome in mothers using citalopram during pregnancy and minimal exposure of the infants to citalopram during lactation. However, maternal therapeutic drug monitoring of citalopram should be recommended to minimize fetal exposure. Clinical Pharmacology & Therapeutics (2002) 72, 184–191; doi: 10.1067/mcp.2002.126181

We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.

Objective: To examine the influence of antenatally administered magnesium sulfate (MgSO 4 ) and ritodrine on cerebral blood flow and systemic hemodynamics in preterm infants. Design: Prospective, observational study. Setting: Neonatal intensive care unit of a university central hospital. Patients: Fifty-five preterm infants age

In a prospective follow up of 116 high risk infants, a 24 hour behavioural chart on seven consecutive days was analysed at seven and 12 weeks of age. Of children who manifested atopic disease at 2 years, 44/116 (38%), had shown significantly more fussing during the seventh, and colic type cry during the twelfth week than those who remained healthy (72/116, 62%).

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.

Objectives.The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996–1997, and to analyze risk factors associated with poor outcome.Participants and Methods.The study population included all stillborn and live-born ELBW infants (birth weight: Results.A total of 529 ELBW infants (.4% of all newborn infants) were born during the 2-year study. The perinatal mortality of ELBW infants was 55% and accounted for 39% of all perinatal deaths. Of all ELBW infants, 34% were stillborn, 21% died on days 0 through 6, and 3% on days 7 though 28. Neonatal mortality was 38% and postneonatal mortality was 2%. Of the infants who were alive at the age of 4 days, 88% survived. In infants surviving >12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight Conclusion.Our study shows that even with modern perinatal technology and care, intrauterine and early deaths of ELBW infants are common. The outcome of infants born at 22 to 23 GWs was unfavorable, but the prognosis improved rapidly with increasing maturity. The clear regional and hospital level differences detected in survival rates and in short-term outcome of ELBW infants emphasizes that the mortality and morbidity rates should be continuously followed and that differences should be evaluated in perinatal audit procedures. However, before the overall outcome of ELBW infants can be evaluated, the results of long-term follow-up and the effects of a premature birth on the family should be taken into consideration. prematurity, perinatal mortality, neonatal morbidity, extremely low birth weight infants.

AIM—To evaluate the role of intestinal microflora and early formula feeding in the maturation of humoral immunity in healthy newborn infants. STUDY DESIGN—Sixty four healthy infants were studied. Faecal colonisation with Bacteroides fragilis group, Bifidobacterium-like, and Lactobacillus-like bacteria was examined at 1, 2, and 6 months of age, and also the number of IgA-secreting, IgM-secreting, and IgG-secreting cells (detected by ELISPOT) at 0, 2, and 6 months of age. RESULTS—Intestinal colonisation with bacteria from the B fragilis group was more closely associated with maturation of IgA-secreting and IgM-secreting cells than colonisation with the other bacterial genera studied or diet. Infants colonised with B fragilis at 1month of age had more IgA-secreting and IgM-secreting cells/106 mononuclear cells at 2 months of age (geometric mean (95% confidence interval) 1393 (962 to 2018) and 754 (427 to 1332) respectively) than infants not colonised (1015 (826 to 1247) and 394 (304 to 511) respectively); p = 0.04 and p = 0.009 respectively. CONCLUSIONS—The type of bacteria colonising the intestine of newborns and the timing may determine the immunomodulation of the naive immune system.

Magnesium sulphate and ritodrine are commonly used drugs in the prevention of preterm delivery. However, the effects of these treatments on the newborn are controversial. It has previously been suggested that antenatal tocolytic magnesium sulphate decreases the incidence of cerebral palsy, but increases paediatric mortality. On the other hand, antenatal ritodrine treatment has been reported to increase the incidence of neonatal peri-intra-ventricular haemorrhage (PIVH). We investigated the cerebral ultrasonographic findings, neurological outcome and apparent life-threatening events (ALTE) among 63 infants, born before 33 wk of gestation, whose mothers were antenatally treated for premature birth with ritodrine or magnesium sulphate, and for pre-eclampsia with magnesium sulphate. Cerebral ultrasonography was performed during the first week of life and repeated before hospital discharge. The pathological findings were confirmed by a paediatric radiologist. A paediatrician and a physiotherapist performed the neurological follow-up examination of the survivors at 6 mo of age. We found Grade 3-4 PIVH in 15% of the infants exposed to maternal ritodrine treatment, in 9% of the infants whose mothers received tocolytic magnesium treatment, and in none of those exposed to maternal magnesium treatment for pre-eclampsia (p = 0.19). However, no differences were observed in 6-mo development or in the rate of paediatric mortality and ALTE among these three study groups. Because of the retrospective design and the limited number of subjects, the results of this study must be interpreted with caution.

To evaluate the development of intestinal flora in young infants, and especially to estimate the influence of mode of delivery and type of feeding on the establishment of intestinal microflora, faecal flora was studied indirectly by measuring prospectively the faecal bacterial enzyme activities (beta-glucosidase, beta-glucuronidase and urease) in 29 full-term, healthy infants during the first 6 months of life. Mode of delivery had no influence on the faecal enzyme activities. In contrast, infants receiving formula feeds were more often urease positive at 1-2 months of age (70% vs 25%, p=0.043) and had higher median activity of beta-glucuronidase at 6 months of age (0.90 and 0.19 nmoles/mg protein x min, p= 0.0043) than exclusively breast-fed infants. Through indirect methods to measure the development of a faecal microflora our results indicate that the type of milk that infants receive during the first months of life may have an important role in the development of intestinal flora.

Objective. The aim of this study was to investigate sequential neuroradiologic changes in the brains of infants after transient neonatal hypoglycemia. We used magnetic resonance imaging (MRI) and ultrasonography (US) head scans. Methods. Eighteen symptomatic full-term infants whose serum glucose concentrations were ≤45 mg/dL (2.5 mmol/L) without any other diseases were included in the hypoglycemic group. MRI and US head scans were performed at full-term age and at the age of 2 months. The imaging results were compared with the findings of MRI and US scans in 19 healthy normoglycemic term newborn infants at the respective ages. The neurologic outcome was followed in the both groups. Results. MRI or US showed evidence of abnormality in 39% the hypoglycemic infants. MRI detected more abnormalities in the brains than US. Four infants showed patchy hyperintensity lesions either in the occipital periventicular white matter or the thalamus on T1-weighted images. These lesions had a good tendency to recover and only 1 of these infants appeared to be neurologically affected. Of the 19 controls, 10% (2 of 19) had caudothalamic cysts, which were detected both with MRI and US. The relative risk of the hypoglycemic child compared with nonhypoglycemic child, to have any abnormality detected in the brain, was 3.7, with a 90% confidence interval from 1.11 to 12.28. Conclusions. Postnatal full-term MRI and US scans showed abnormalities four times more often after transient neonatal hypoglycemia than in the healthy control group. However, most often lesions were absent 2 months later. The clinical relevance of these abnormal findings remains to be clarified with detailed neurologic examinations and follow-up.

The low-dose ACTH test seems to reveal mild cases of adrenal insufficiency and is beginning to be preferred over the standard ACTH test in the evaluation of adrenal suppression both in infants and in adults. The concentration-time profile of plasma cortisol in infants after a low ACTH dose is obscure. In this crossover study, we compared timing of the peak values in the low-dose and the standard ACTH stimulation tests in preterm and full-term infants. We performed the standard ACTH tests (250 microg/1.73 m2) and the low-dose ACTH tests (1 microg/1.73 m2) on 10 infants (26-40 wk gestational age) and measured serum cortisol concentration at 0, 30, 40, 60, and 120 min by RIA. Nine of the infants had received postnatal glucocorticoid treatment, and most of them had also been treated with dexamethasone antenatally. In the low-dose test, the peak values occurred at 30 or 40 min in 9/10 patients. In the standard-dose test, the peak values occurred at 60 or 120 min in 8/10 patients. These results are comparable with those from adults. According to this study, blood samples for the low-dose ACTH test in infants should be taken before dosing and between 30 and 40 min after dosing.

Antenatal corticosteroid therapy (ACT) has many beneficial effects on preterm infants. The cellular mechanisms of action of ACT include beta-adrenergic receptor-mediated cAMP generation. This study investigated the effects of ACT on sympathoadrenal mechanisms during immediate postnatal adaptation of preterm infants. Plasma epinephrine, norepinephrine, 3,4-dihydroxyphenylglycol, and cAMP were measured within 12 h after birth in 103 preterm infants (gestational age 24-36 wk), who were divided into two groups (non-ACT and ACT group) according to whether the mother had received dexamethasone treatment. Infants in the ACT group had significantly lower concentrations of plasma catecholamines than infants in the non-ACT group; plasma epinephrine was 38% lower, and plasma norepinephrine was 20-40% lower in the ACT group, depending on gestational age (r = -0.37 in the non-ACT group and r = -0.28 in the ACT group, p0.05). Plasma cAMP concentrations were similar in the two groups. Antihypertensive treatment of the mother was associated with low plasma cAMP (p0.001), whereas tocolytic treatment was associated with high plasma cAMP (p = 0.001) of the infant. The results indicate that ACT attenuates the birth-related increase in plasma catecholamines. Still, plasma cAMP levels remain high, which suggests enhanced beta-adrenoceptor signaling after ACT.

Objective: To test the hypothesis with Doppler ultrasound method that the postnatal adaptation of the pulmonary and ductal hemodynamics in infants of diabetic mothers is disturbed. Study Design: Infants of diabetic mothers are prone to respiratory distress caused by characteristic fetal metabolic abnormalities such as hyperglycemia and hyperinsulinemia with subsequent excess fetal growth. However, the postnatal course of the pulmonary and ductal hemodynamics is poorly known in these neonates. The presence of ductal shunting and the mean aortopulmonary pressure difference across the ductus arteriosus reflecting pulmonary artery pressure, as well as the left ventricular output, were serially evaluated with Doppler ultrasound method at 2, 12, 24, 48, and 72 hours of age in 47 infants of diabetic mothers and 37 control neonates of nondiabetic mothers. Results: The infants of diabetic mothers had a higher incidence of patent ductus arteriosus at 12 ( p = 0.03) and 48 hours ( p = 0.006) of life than control infants, but none of the infants of diabetic mothers needed ductal closure. Bidirectional ductal shunting was found more frequently in infants of diabetic mothers than control infants during the first day of life. The mean ductal aortopulmonary pressure difference was significantly higher in the control infants than in infants of diabetic mothers during the first 24 hours of life ( p = 0.002). The mean systemic pressure values were higher in the infants of diabetic mothers than control infants ( p = 0.002), but no significant differences in the left ventricular output were seen between the study groups during the first 3 days of life. Conclusions: The closure of the ductus arteriosus and postnatal decrease in pulmonary artery pressure are delayed in infants of diabetic mothers when compared with control infants during the first days of life. Left ventricular output values in infants of diabetic mothers do not differ from those of the control infants. (J Pediatr 1997;131:545-8)

Severe neonatal aspiration of meconium is frequently complicated by fatal pulmonary hypertension. The protective effect of an i.v. bolus of methylprednisolone on meconium aspiration-induced hypertensive lung injury was studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator settings were adjusted to keep arterial PO2 above 8 kPa and arterial PCO2 below 5 kPa. Meconium insufflation induced a biphasic pulmonary pressor response during the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h) increase in pulmonary artery pressure and inhibited significantly the second phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary vascular resistance. This inhibition of resistance increase was most profound in the postarterial segment of the lung circulation, as determined by pulmonary artery occlusion. Additionally, the methylprednisolone pretreated group demonstrated a significant decrease in venous admixture together with improved oxygenation during the late phase after the insult, and further showed evidence of diminished lung edema formation. Although meconium aspiration-induced fall in blood leukocyte concentration was inhibited by methylprednisolone pretreatment, no histologic difference was found in pulmonary leukocyte sequestration. Our results thus show that in adapted porcine lungs methylprednisolone pretreatment improves oxygenation and attenuates the meconium aspiration-induced pulmonary hypertensive response by preventing the increase in the postarterial resistance.

Objective: We studied the effect of neonatal hypoglycaemia on the local cerebral metabolic rate for glucose (LCMRglc). Materials and methods: Eight newborn infants with neonatal hypoglycaemia were studied. The LCMRglc in the whole brain, in five cerebral regions and in skeletal muscles were quantitated using positron emission tomography (PET) and 2-[ 18 F]Fluoro-2-deoxy- d -glucose (FDG). The PET studies were performed at the age of 5.3 ± 6.2 days during normoglycaemia. The LCMRglc of these infants were compared to the age-adjusted LCMRglc of eight infants with suspected hypoxic-ischaemic brain injury but with normal neurological development. Results: After neonatal hypoglycaemia the age-adjusted LCMRglc in the whole brain was not lower than LCMRglc of the control infants (5.33 ± 0.60 μmol/100 g/min vs. 6.71 ± 0.60 μmol/100 g/min). Also the metabolic rate for glucose (MRglc) in the skeletal muscles was similar in hypoglycaemic and control infants (5.56 ± 2.48 μmol/100 g/min vs. 6.99 ± 2.41 μmol/100 g/min). Conclusion: MRglc in brain and in skeletal muscle seems to be normal after neonatal hypoglycaemia, although larger group of patients with more severe hypoglycaemia are needed to confirm this finding.

Oscillations of skin blood flow and heart rate can be synchronised using external rhythmic thermal stimulation in healthy adults and infants. We examined the effect of thermal stimulation on the cutaneous circulation and heart rate of an anencephalic neonate using cutaneous laser Doppler flowmetry and ECG monitoring. The results suggest that synchronisation of SBF and HR to thermal stimulation can also be induced in an anencephalic newborn.

To investigate whether aspiration of meconium induces a hemodynamic and histologic pulmonary response similar to that frequently seen in experimental acute respiratory distress syndrome, twelve 10-week-old pigs with postnatally adapted lungs were studied. Six 10-week-old pigs received 3 ml/kg 20% human meconium via the endotracheal tube. Six control pigs of the same age were given sterile saline. Ventilator settings were adjusted to keep PaO2 above 8 kPa and PaCO2 below 5 kPa. The pulmonary hemodynamic response to aspiration consisted of two separate hypertensive components. An initial peak in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) was followed by a progressive increase in PAP and PVR in the meconium group, whereas in the saline group these parameters returned to baseline levels. The distribution of PVR, determined by pulmonary artery occlusion, was characterized by an increase in the postarterial resistance immediately after meconium aspiration and a progressive increase in both arterial and postarterial resistance during the later phase. On histological examination, marked neutrophil sequestration was seen in the meconium lungs. In addition, lung edema formation was significantly enhanced in the meconium group, as shown by an increased lung wet/dry weight ratio. Thus, meconium aspiration resulted in a biphasic pulmonary pressor response and severe pulmonary inflammation. This response resembled that of models of experimental acute respiratory distress syndrome following diverse types of precipitating insults; this suggests that similar pathophysiologic mechanisms are elicited and cause similar pulmonary dysfunction following different forms of lung injury.