Jens B. Grogaard

Increased survival rate in very low birth weight infants (1500 grams or less): No association with increased incidence of handicaps

The incidence of major handicaps was studied in a selected high-risk population of 1919 very low birth weight (less than or equal to 1500 gm) infants born between 1976 and 1985. Seventy-four percent of these infants were discharged alive. We have handicap information on 632 infants who have been followed for up to 7 years of age; 462 were evaluated at 18 months or later. Patients lost to follow-up represent 55% of the eligible population, but inpatient morbidity factors were available for the entire population and were used to calculate synthetic estimates of handicap rates. The overall incidence of severe major handicaps at 18 months was 18.0% (83/462). Cerebral palsy was found in 7.6%, and 6.5% were mentally retarded (IQ less than or equal to 70). Severe retinopathy of prematurity was present in 5.5%, and 5.4% of the infants had neurosensory hearing loss. Thirty-one infants (6.7%) had more than one handicap, the most common combination being cerebral palsy and mental retardation. Outcome of infants grouped by 250 gm birth weight intervals was compared for two periods (1976 to 1980, and 1981 to 1985); the numbers of survivors in each birth weight group increased during the second period, especially in the 500 to 750 gm and the 751 to 1000 gm groups. The observed incidence of major handicaps decreased from the first 5-year period to the second 5-year period (p less than 0.001). The largest decreases in the observed proportion handicapped occurred in the two lowest birth weight groups. The incidence of multiple handicaps also dropped; again, the two lowest birth weight groups showed the largest decrease. We conclude that an increased survival rate of very low birth weight infants need not be associated with an increased incidence of major handicaps.

Respiratory Syncytial Virus Infection Reinforces Reflex Apnea in Young Lambs

ABSTRACT: To evaluate the effect of respiratory syncytial virus (RSV) infection on reflex apnea clicited by application of water on the laryngeal mucosa, 11 healthy, term lambs were chronically instrumented at 2 wk of age. Six lambs were inoculated with bovine RSV, and five lambs were mock-infected. The lambs were studied awake and unsedated before and 4, 8, 14, and 21 d after infection. RSV infection was associated with slight rhnorrhea and with moderately increased tracheal mucous discharge. There was an average increase of 0.5°C in body temperature. Arterial pH, PO2, and PCO2 remained within the normal range. The ventilatory response to laryngeal chemostimulation measured as the percentage of decrease in ventilation from control was significantly (p < 0.05) larger among the infected animals when compared with controls on d 4 and 8. There were no differences in indices of respiratory drive (airway occlusion pressure and mean inspiratory flow), ventilatory response to hypoxia (0.10 fraction of inspired O2), or hypercarbia (0.03 fraction of inspired O2). We speculate that RSV infection alters the sensitivity of the laryngeal chemoreceptors so that a prolonged or even fatal apnea may result from stimulation of these receptors. These results may be relevant to the pathogenesis of sudden infant death syndrome associated with RSV infection.

Prolonged hypoxemia enhances and acute hypoxemia attenuates laryngeal reflex apnea in young lambs.

ABSTRACT: To determine the influence of an altered carotid body function on the laryngeal chemoreflex (LCR) response, reflex apnea was induced by laryngeal water stimulation during normoxia or acute hypoxia in unanesthetized awake lambs in which the ventilatory response to acute hypoxia was attenuated by prolonged postnatal hypoxemia. Prolonged hypoxemia (H) was induced in seven lambs for 12 d after birth through exposure to 0.10 fraction of inspired oxygen. Five control lambs were kept in 0.21 fraction of inspired oxygen. Studies were performed repeatedly during the first 7 wk after birth. The ventilatory response to LCR stimulation, expressed as a percent decrease in minute ventilation, was tested in 0.21, 0.14, and 0.10 fraction of inspired oxygen. H after birth resulted in a markedly increased inhibition of ventilation in response to LCR stimulation and postponed the age-related decrease in LCR response. A potential failure to recover from apnea occurred only in the H lambs, and in these lambs there was a significantly greater requirement for mechanical ventilation after LCR stimulation. Acute hypoxemia preceding LCR stimulation significantly attenuated the ventilatory response in both control and H lambs, with a stronger effect in the H lambs. There was no difference between the two groups in heart rate response to LCR stimulation. Acute hypoxemia significantly augmented reflex bradycardia in the H lambs. These results show that there is a relationship between H immediately after birth—which is known to delay resetting of carotid chemoreceptors—and augmented ventilatory inhibition in response to LCR stimulation. They do not confirm the theory that acute hypoxia reinforces reflex apnea.

Effects of Carotid Body Maturation and Terbutaline on the Laryngeal Chemoreflex in Newborn Lambs

ABSTRACT. The response to laryngeal chemoreflex (LCR) water stimulation was compared in unanesthetized awake 4- to 10-day-old preterm and 2- to 4-wk-old term lambs before and after infusion of a β-adrenergic agonist, terbutaline, given pre- and postcarotid body denervation (CBD). Ventilation decreased more in response to LCR stimulation post-CBD in the older lambs. CBD did not change the respiratory response to LCR stimulation in the younger lambs. LCR stimulation resulted in less bradycardia post-CBD in both groups. Terbutaline significantly attenuated the LCR response in the older lambs pre-CBD but not post-CBD. LCR respiratory response was not changed in the younger lambs when terbutaline was infused, pre- or post-CBD. Compared to wakefulness, the LCR response in preterm lambs was greater in sleep not associated with arousal. If arousal occurred, LCR response during sleep did not differ from that during wakefulness. The incidence of arousal decreased markedly after CBD, suggesting that arousal is modified by the carotid bodies. It is concluded that the carotid bodies modify the reflex response to LCR stimulation in 2- to 4-wk-old lambs. During the 1st postnatal wk, preterm Iambs have a reduced carotid body function during wakefulness and, therefore, a decreased hypoxic ventilatory response and increased respiratory response to LCR stimulation. The attenuating effect of terbutaline on LCR response is partially related to mature carotid body function.

DETECTION OF INTRAVENTRICULAR HEMORRHAGE (IVH) BY TRANSCEPHALIC IMPEDANCE (TCZ) IN PREMATURE INFANTS

ABSTRACT. Transcephalic impedance was measured serially in 45 preterm infants <1500 g birth weight in order to test the method for the early detection of intraventricular hemorrhage. TCZ increased in all seventeen (38%) infants who developed IVH diagnosed by CT‐scan or autopsy. Five of 8 infants monitored 4‐8 weeks following confirmed IVH developed hydrocephalus documented by repeat CT‐scans; all 5 were discovered early by the TCZ‐method 2‐3 weeks before physical findings or an increasing head circumference indicated the possibility of hydrocephalus. TCZ appears to be a useful non‐invasive clinical guide to the occurrence and course of IVH in the newborn.

Increased Survival Rate in Very Low Birth Weight Infants (1500 Grams or Less): No Association with Increased Incidence of Handicaps

The incidence of major handicaps was studied in a selected high-risk population of 1919 very low birth weight (less than or equal to 1500 gm) infants born between 1976 and 1985. Seventy-four percent of these infants were discharged alive. We have handicap information on 632 infants who have been followed for up to 7 years of age; 462 were evaluated at 18 months or later. Patients lost to follow-up represent 55% of the eligible population, but inpatient morbidity factors were available for the entire population and were used to calculate synthetic estimates of handicap rates. The overall incidence of severe major handicaps at 18 months was 18.0% (83/462). Cerebral palsy was found in 7.6%, and 6.5% were mentally retarded (IQ less than or equal to 70). Severe retinopathy of prematurity was present in 5.5%, and 5.4% of the infants had neurosensory hearing loss. Thirty-one infants (6.7%) had more than one handicap, the most common combination being cerebral palsy and mental retardation. Outcome of infants grouped by 250 gm birth weight intervals was compared for two periods (1976 to 1980, and 1981 to 1985); the numbers of survivors in each birth weight group increased during the second period, especially in the 500 to 750 gm and the 751 to 1000 gm groups. The observed incidence of major handicaps decreased from the first 5-year period to the second 5-year period (p less than 0.001). The largest decreases in the observed proportion handicapped occurred in the two lowest birth weight groups. The incidence of multiple handicaps also dropped; again, the two lowest birth weight groups showed the largest decrease. We conclude that an increased survival rate of very low birth weight infants need not be associated with an increased incidence of major handicaps.

112: POSTNATAL CHRONIC HYPOXIA CHANGES THE OXYGEN SENSITIVITY IN THE CAROTID BODIES

The ventilatory response to acute hypoxia is mediated mainly by the carotid body (CB) chemoreceptors. These are active in the last trimester of the fetal lamb. The normal rise in PaO2 occurring at birth silences the CB during the first postnatal days before the postnatal reset of O2 sensitivity has occurred. We hypothesized that the postnatal reset mechanism of the CB oxygen sensitivity can be reversed by longterm exposure to hypoxia. Minute ventilation (Vmin) was studied in 6 lambs at 2 weeks of age during normoxia and during hypoxia (FiO2 0.14). The results were compared to Vmin after 8 days in chronic hypoxia (FiO2 0.14). Vmin decreased 53% during chronic hypoxic exposure compared to Vmin prior to hypoxia. The acute hypoxic ventilatory response to a change in FiO2 from 0.21 to 0.14 was decreased compared to that prior to chronic hypoxia (+3% vs +53%, p 0.002). The hypoxic ventilatory response after chronic hypoxia corresponds to our previously reported hypoxic ventilatory response to CB denervated lambs. We conclude that the decreased hypoxic ventilatory response demonstrated is due to a reversal of the CB oxygen sensitivity. This finding might have implications for the ability to abort apnea in infants at a time period when CB is an important factor in the control of breathing.