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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.

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 PLA2group-I and group-II concentrations were significantly elevated. Although BAL fluid catalytic activity of PLA2was 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.

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 Po2above 8 kPa and arterial Pco2below 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.

Antenatal corticosteroid therapy (ACT) has many beneficial effects on preterm infants. The cellular mechanisms of action of ACT includeß-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, p < 0.05). Plasma cAMP concentrations were similar in the two groups. Antihypertensive treatment of the mother was associated with low plasma cAMP(p < 0.001), 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 ß-adrenoceptor signaling after ACT.

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 µg/1.73 m2) and the low-dose ACTH tests (1 µg/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.

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Animal studies have suggested a possible role of ET-1 in alveolar hypoxia. ET-1 may be of pathophysiological significance in the fetal as well as in the maternal circulation in pregnancies complicated with hypertension. ET-1 has been shown to induce a dose-related constriction in vitro of strips of ductus arteriosus from mature fetal lambs. It has also been shown to contract human umbilical vessels at extremely low concentrations. Its role in the newborn infant is not known.In the present study we measured plasma ET-1 levels in preterm and term infants soon after birth as well as in healthy infants and children of different ages. ET-1 was determined by a commercial radioimmunoassay kit (RIK 6071, Peninsula Laboratories Europe Ltd).The plasma levels of ET-1 were as follows (mean, range, pg/ml): preterm (<2A h) 26.8, 11.6-49.2 (n=9); term (<24 h) 19.9, 10.0-39.9 (n=10); 3 mo to 1 y 14.8, 10.2-26.6 (n=13); 2 y to 15 y 8.2, 2.9-16.7 (n=29). Preterm and term infants have relatively high plasma ET-1 levels. In the newborn infant ET-1 is a circulating hormone with possible physiological and pathophysiological roles.

BPD is an important cause of late morbidity in preterm infants with RDS. We investigated the development of BPD in 216 neonates weighing less than 1500 g during a 6-y period. The criteria for BPD and severity of RDS were defined. The results are shown in the table.In infants with BW =1250 g only one infant of 75 developed BPD. Incidence of PDA was higher in infants with BPD than without BPD (p<0.001). Six infants of 25 with BPD died during their first year of life. Nine infants had some degree of developmental sequelae and 10 infants were considered healthy at one year of age.

In the neonate, the role of ANP in the regulation of fluid balance is not clear. We assessed the relation of ANP in preterm infants to renal function and PDA on days 2 and 5. P-ANP was measured by RIA; Gl (<30 wk, n=11) and G2 (30-34 wk, n=12). PDA was assessed on day 2. P-ANP was higher in G1 than in G2 (p<0.01) and decreased by day 5 (p<0.02). A negative correlation between P-ANP and GA was found (day 2: r=-0.54, p< 0.01; day 5: r=-0.45, p<0.05). No correlation between P-ANP and CCror UNPV was found. Infants with PDA had higher P-ANP than infants without PDA in G1 (p<0.02), but not in G2. Preterm infants are able to release huge amounts of ANP postnatally. The high P-ANP concentrations seen postnatally do not directly correlate to the renal regulation of sodium and water balance.