Daniel J Faucher

Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?

Objective:To compare risk-adjusted changes in outcomes of preterm infants <29 weeks gestation born in 1996 to 1997 with those born in 2006 to 2007.Study Design:Observational retrospective comparison of data from 15 units that participated in the Canadian Neonatal Network during 1996 to 1997 and 2006 to 2007 was performed. Rates of mortality and common neonatal morbidities were compared after adjustment for confounders.Result:Data on 1897 infants in 1996 to 1997 and 1866 infants in 2006 to 2007 were analyzed. A higher proportion of patients in the later cohort received antenatal steroids and had lower acuity of illness on admission. Unadjusted analyses revealed reduction in mortality (unadjusted odds ratio (UAOR): 0.83, 95% confidence interval (CI): 0.63, 0.98), severe retinopathy (UAOR: 0.68, 95% CI: 0.50 to 0.92), but increase in bronchopulmonary dysplasia (UAOR: 1.61, 95% CI: 1.39 to 1.86) and patent ductus arteriosus (UAOR: 1.22, 95% CI: 1.07 to 1.39). Adjusted analyses revealed increases in the later cohort for bronchopulmonary dysplasia (adjusted odds ratio (AOR): 1.88, 95% CI: 1.60 to 2.20) and severe neurological injury (AOR: 1.49, 95% CI: 1.22 to 1.80). However, the ascertainment methods for neurological findings and ductus arteriosus differed between the two time periods.Conclusion:Improvements in prenatal care has resulted in improvement in the quality of care, as reflected by reduced severity of illness and mortality. However, after adjustment of prenatal factors, no improvement in any of the outcomes was observed and on the contrary bronchopulmonary dysplasia increased. There is need for identification and application of postnatal strategies to improve outcomes of extreme preterm infants.

Urinary arginine vasopressin: pattern of excretion in the neonatal period

ABSTRACT. The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (μU/ mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n =13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (>200 μU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of ˜400 mosmol/kg at urinary AVP levels <200 μU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.

Vasopressin and Catecholamine Secretion during Metabolic Acidemia in the Ovine Fetus

ABSTRACT: It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AYP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2 and/or pHa; however, the components of these “stresses,” i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 ± 4 (mean ± SD) days gestation with 1 M NH4C1, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 ± 0.01 to 7.04 ± 0.05 (p<0.05) during NH4C1 and did not return to control levels until 24 h later. AVP increased from 2.85 ± 0.23 to 5.26 ± 1. 1 1 μU/ml (p<0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, p = 0.001); however, after stopping NH4C1, AVP returned to baseline levels although pHa remained <7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p<0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable.

Fetal Tracheal Occlusion in Lambs with Congenital Diaphragmatic Hernia: Role of Exogenous Surfactant at Birth

Fetal tracheal occlusion (TO) has been used to reverse the lung hypoplasia associated with congenital diaphragmatic hernia (CDH). However, TO has a detrimental effect on type II pneumocyte function and surfactant production. Previously, we have shown that in surgically created CDH lambs, TO improved markedly the response to resuscitation even though the lungs remain surfactant deficient. The goal of this investigation was to assess the effects of exogenous surfactant administered at birth to CDH lambs with or without fetal TO during 8 h of resuscitation. Lambs were divided into five groups: CDH, CDH+surfactant (SURF), CDH+TO, CDH+TO+SURF, and nonoperated controls. A left-sided CDH was created in fetal lambs at 80 d gestation. TO was performed at 108 d, and the lambs were delivered by hysterotomy at 136 d. Bovine lipid extract surfactant was administered before the first breath and again at 4 h of life. All CDH+SURF lambs, but only three of five CDH lambs, survived up to 8 h. When compared with the corresponding nonsurfactant-treated group, surfactant-treated CDH and CDH+TO lambs did not demonstrate improved alveolar-arterial oxygen gradients, pH, or Pco2. In fact, in the CDH+TO group, surfactant treatment significantly worsened ventilation efficiency as measured by the ventilation efficiency index. The observed improvement in pulmonary compliance secondary to surfactant treatment was not significant. This investigation demonstrates that prophylactic surfactant treatment at birth does not improve gas exchange or ventilation efficiency in CDH lambs with or without TO.

Effects of Acute Hypercapnia on Maternal and Fetal Vasopressin and Catecholamine Release

Although fetal asphyxia, i.e. hypoxemia, acidosis, and hypercapnia, increases plasma arginine vasopressin (AVP) >40-fold, hypoxemia and metabolic acidosis occurring independently cause only 5-fold and 2-fold increases, respectively. To determine the effects of hypercapnia on AVP release, we examined the effects of acute hypercapnia on AVP secretion in six pregnant sheep and their fetuses at 135 ± 4 d (x ± SD), exposing the ewe successively to room air, 30% O2, 30% O2 plus 10% CO2, 30% O2, and room air, and monitoring uterine blood flow, as well as maternal and fetal mean arterial pressure, heart rate, arterial blood gases, and plasma AVP and catecholamines. Oxygen exposure had no effect on the ewe or fetus. During O2 plus CO2 exposure, the ewes and fetuses developed hypercapnia in the absence of hypoxia, arterial CO2 tension increasing to 8.38 ± 0.87 kPa (62.9 ± 6.5 mm Hg) and 10.0 ± 0.61 kPa (75.2 ± 4.6 mm Hg) (p < 0.001), respectively, at 30 min of exposure. Although fetal heart rate and mean arterial pressure were unchanged, maternal values rose 61 and 30% (p < 0.001), respectively. At 30 min of O2 + CO2 exposure, maternal norepinephrine increased from 2.23 ± 0.74 to 8.52 ± 3.97 nmol/L (p = 0.15) and fetal epinephrine increased from 0.27 ± 0.10 to 2.271 ± 0.90 nmol/L (p = 0.01); plasma AVP was not significantly increased in the ewe or fetus, although levels rose from ∼45 to 127 ± 48 and 137 ± 64 pmol/L (p = 0.10), respectively. Hypercapnia alone is not a major determinant of AVP secretion in the mother or fetus; thus, the marked rise in fetal AVP secretion observed during asphyxial insults may reflect interaction between the effects of hypercapnia and hypoxemia.

EFFICACY OF EARLY SYSTEMIC AND INHALED CORTICOSTEROID THERAPY IN THE PREVENTION OF CHRONIC LUNG DISEASE OF PREMATURITY. |[bull]| 2005

We conducted a double-blind, randomized controlled trial to assess the efficacy of a combination of prophylactic systemic dexamethasone (SD) and nebulized budesonide (NB) in reducing the incidence and severity of chronic lung disease (CLD) in VLBW infants at risk. Fifty-nine ventilator-dependent infants < 30 wks and ≤ 1500 g were assigned to receive either steroids(S) or saline placebo as of 7 d of age. The S group (n=30, GA=25.8±1.6 wks, BW=731±144 g) received SD 0.25 mg/kg twice daily for 3 days, followed by NB 500 μg twice daily for 18 days. Control infants (n=29, GA=25.9±1.8 wks, BW=796±199 g) received systemic and inhaled saline.

1591 SODIUM (Na) BALANCE (B) IN THE GROWING PRETERM

Negative NaB and hyponatremia have been reported for growing preterm infants. It has been suggested that less Na is required when fluid therapy is restricted. To examine this, we have measured NaB(total intake-urinary excretion/24hrs), serum Na and potassium(K) concentrations, and urinary aldosterone (U-A) in 11 neonates(BW=1378±43g; GA=30.6±0.5wks) during 1st and 3rd wks of life. (Mean ± SEM; *p<°0.05).Maximum wt. change(Δ) from birth was -13.5±1.4% at 8.4±0.8d. Adequate growth, positive NaB and normal serum Na can be achieved in rapidly growing preterm infants receiving moderate Na intake when fluid therapy is not excessive. The increase in U-A from 1 to 3wks was associated with a decrease in the U Na/K ratio. U Na/K did not correlate with U-A during the 1st wk(r=-0.10) but did during the 3rd wk(r=-0.43). We conclude that an appropriate renal tubular response to A was evident by the 3rd wk of life in these infants.

Ontogeny of Plasma, CSF and Brainstem ACTH in Piglets: Effects of Hypoxia and Anesthesia

This study was designed to assess the postnatal maturation of adrenocorticotropin (ACTH) levels in piglets under basal conditions and in response to single, acute stressors. ACTH levels were measured by radioimmunoassay in plasma, cerebrospinal fluid (CSF) and in a dorsal medullary slice containing the nucleus tractus solitarii (dmscNTS) of young and older piglets (1.5-6 and 35-43 days old, respectively) under the following experimental conditions: (1) normoxia (both groups); (2) hypoxia, 10% O2/N2 for greater than or equal to 30 min (both groups); (3) sham anesthesia, i.p. saline in normoxia (young group); (4) anesthesia, 25 mg/kg i.p. pentobarbital in normoxia (young group), and (5) anesthesia combined with hypoxia (young group). During normoxia, ACTH levels in young, as compared to older piglets, were higher in CSF (p less than 0.01) and plasma (0.05 less than p less than 0.10) and not different in dmscNTS. Hypoxia produced no ACTH changes in CSF, increased ACTH in plasma of young (p = 0.03) and older piglets (p = 0.09), and decreased ACTH in dmscNTS of older (p = 0.01) and young piglets (p = 0.07). As compared to sham anesthesia, anesthesia did not alter any ACTH levels. Combined hypoxia and anesthesia increased ACTH levels in plasma when compared to normoxia (p less than 0.05), sham anesthesia (p less than 0.05) or anesthesia alone (p less than 0.05), but not when compared to hypoxia alone. We conclude that neonatal swine have high basal ACTH levels and mount significant plasma ACTH responses to a single, acute hypoxic stressor. The presence of ACTH in the region of the NTS supports its possible role as a neuromodulator in the brain.

SURVIVAL AT THE BORDERLINE OF VIABILITY (22-24 WEEKS). 1484

With parental informed consent 38 of 49 infants of 22-24 weeks have been treated intensively at our institution during 1990-94. Of the 49, 17 (35%) survived. Mean weights were 650g (survivors) and 539g (deaths). Survival rates were higher at 24 than 22 weeks (53% vs 23%), with higher Apgar scores (53% vs 16%), and when a full course of steroids was given (63% vs 21%). Survival was not influenced by route of delivery, nor by infant sex.

ARGIMIME YASUPRESSIN (AP): A INDUCED ACTH SECRETION IN THE FETUS

The “stress” hormone AVP has been shown in vivo and in vitro to directly stimulate ACTH secretion and to potentiate the effects of corticotropin releasing factor (CRF) in adult animals. A similar role for AVP in fetal secretion of ACTH during “stress” is unclear; therefore, we have studied the effect of continuous 30min infusions of AVP (12mU/min) on the secretion of ACTH in chronically instrumented late gestation fetal sheep (n=10, 130-141d) while continuously monitoring heart rate (HR) and mean arterial pressure (MAP). Arterial blood samples were obtained prior to, 15 and 30min during, and 60min postinfusion for measurements of PO2, PCO2, pH, hematocrit (Hct), AVP, and ACTH. As expected, at 30min HR fell from 167±6 (X±SE) to 115±7bpm* and MAP rose from 52±2 to 66±3mmHg*, both returning to control levels 30min postinfusion. PaO2, pHa, and Hct were unchanged; PaCO2 fell from 42±1.0 to 37±1.3mmHg*. Plasma levels of AVP rose from 2.3±0.2 to 85±7.5* and 89±11* pg/ml at 15 and 30min, respectively, while plasma levels of ACTH rose from 18±2.4 to 28±3.7 and 43±8.0*pg/ml, respectively, an increase of 150±45% at 30min; both returned to control levels at 60min postinfusion. Neither the preinfusion values nor the AVP-induced rise in plasma ACTH at 30min were significantly related to changing gestational age; however, there was a trend for the 30min %ΔACTH to fall. As in adult animals, AVP acts as a CRF, thereby suggesting an important role for this peptide hormone in modulating and coordinating the cardiovascular and hormonal responses observed during fetal “stress.” *n<0.05.