Comparison of evoked arousability in breast and formula fed infants.

BACKGROUND: Currently, there is no consistent evidence that breast feeding reduces the risk for sudden infant death syndrome (SIDS). Arousal from sleep is believed to be an important survival mechanism that may be impaired in victims of SIDS. Previously it has been shown that arousability is impaired by the major risk factors for SIDS such as prone sleeping and maternal smoking. AIMS: To establish whether arousability was altered by method of feeding, and whether breast fed infants would have lower arousal thresholds. METHODS: Forty three healthy term infants were studied using daytime polysomnography on three occasions: 2-4 weeks post-term, 2-3 months post-term, and 5-6 months post-term. Multiple measurements of arousal threshold (cm H(2)O) in response to nasal air jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS) while infants slept supine. Arousal thresholds and sleep period lengths were compared between formula fed and breast fed infants at each age. RESULTS: Arousal thresholds were not different between breast fed and formula fed infants in QS. However, in AS breast fed infants were significantly more arousable than formula fed infants at 2-3 months of age. There was no difference between groups of infants when sleep period length was compared at any study. CONCLUSIONS: Breast fed infants are more easily aroused from AS at 2-3 months of age than formula fed infants. This age coincides with the peak incidence of SIDS.

Effects of maternal tobacco smoking, sleeping position, and sleep state on arousal in healthy term infants.

OBJECTIVES: To investigate whether a history of maternal tobacco smoking affected the maturation of arousal responses and whether sleeping position and infant age alters these relations. DESIGN: Healthy term infants (13 born to mothers who did not smoke and 11 to mothers who smoked during pregnancy) were studied using daytime polysomnography on three occasions: (a) two to three weeks after birth, (b) two to three months after birth, and (c) five to six months after birth. Multiple measurements of arousal threshold in response to air jet stimulation were made in both active sleep (AS) and quiet sleep (QS) when infants slept both prone and supine. RESULTS: Maternal smoking significantly elevated arousal threshold in QS when infants slept supine at 2-3 months of age (p<0.05). Infants of smoking mothers also had fewer spontaneous arousals from QS at 2-3 months in both prone (p<0.05) and supine (p<0.001) sleeping positions. In infants of non-smoking mothers, arousal thresholds were elevated in the prone position in AS at 2-3 months (p<0.01) and QS at 2-3 weeks (p<0.05) and 2-3 months (p<0.001). CONCLUSIONS: Maternal tobacco smoking significantly impairs both stimulus induced and spontaneous arousal from QS when infants sleep in the supine position, at the age when the incidence of sudden infant death syndrome is highest.

The prone sleeping position impairs arousability in term infants.

OBJECTIVE: To investigate whether the prone sleeping position impaired arousal from sleep in healthy infants and whether this impairment was related to cardiorespiratory variables, temperature, or age. STUDY DESIGN: Healthy term infants (n = 24) were studied with daytime polysomnography on 3 occasions: 2 to 3 weeks after birth, 2 to 3 months after birth, and 5 to 6 months after birth. Multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both active sleep and quiet sleep when infants slept prone at 2 to 3 weeks and 2 to 3 months, but not at 5 to 6 months. These increases were independent of any sleep position-related change in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation, or heart rate. CONCLUSIONS: The prone position significantly impairs arousal from both active sleep and quiet sleep in healthy term infants. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory variables or body temperature. Decreased arousability from sleep in the prone position provides an important insight into its role as a risk factor for sudden infant death syndrome.

Apnoea of prematurity and arousal from sleep.

The incidence of sudden infant death syndrome (SIDS) has been found to be consistently higher in preterm and low birth weight infants than in infants born at term and this increase is inversely related to gestational age. The incidence and severity of apnoea of prematurity, are also inversely related to gestational age. The aim of this study was to investigate whether a neonatal history of apnoea/bradycardia affected the maturation of arousal responses. Twenty-five premature infants were studied. A perinatal risk score was determined for each infant and infants were divided into those with a neonatal history of apnoea/bradycardia (n=16) and those without (n=9). All infants were studied using daytime polysomnography on three occasions: (a) a preterm study around 36 weeks gestation, (b) within 3 weeks of term, and (c) 2-3 months post-term. Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). Arousal thresholds were elevated in apnoeic infants compared to control infants in both AS (P<0.05) and QS (P<0.001) at the term study and in QS at 2-3 months post-term (P<0.01). In addition, arousal thresholds were positively correlated with perinatal risk score in both sleep states, in all studies, with the exception of AS at 2-3 months when all infants were readily arouseable. We conclude that a history of prematurity with neonatal apnoea has a persisting effect on decreasing arousabilty from sleep and these infants may be at increased risk for SIDS.

Unusual respiratory response to oxygen in an infant with repetitive cyanotic episodes.

High inspired oxygen concentrations have recently been recommended to control Cheyne-Stokes respiration in adults, with the intention of averting periodic apnea and its attendant arterial desaturation. We report a case study on an infant presenting with recurrent apnea and cyanosis in which oxygen treatment led to a gross form of respiratory instability we call episodic breathing, in which a breathing phase of 60 to 90 s alternated with an apnea lasting up to 60 s. When oxygen was discontinued, a profound arterial desaturation developed before breathing recommenced and restored oxygen levels. We propose that episodic breathing is an unusual respiratory pattern that involves the central chemoreceptors and results from the ventilatory threshold (the central PCO(2) at which breathing starts) lying considerably above the apneic threshold (the central PCO(2 )at which breathing stops). This feature predisposes to lengthy periods of hyperpnea alternating with lengthy periods of apnea. We suggest that when the case infant returned to air during episodic breathing, termination of apnea was entirely dependent upon carotid body activity, which reached a sufficient level to restart breathing only when arterial desaturation was severe. We conclude that oxygen therapy involves potential risks when employed to treat respiratory disorders involving unstable breathing patterns in the infant.

Effects of prematurity on arousal from sleep in the newborn infant.

The incidence of sudden infant death syndrome has been found to be consistently higher in preterm and low birth weight infants than in infants born at term. Failure to arouse from sleep is one possible mechanism for sudden infant death syndrome. This study compared the arousal responses to nasal air-jet stimulation in a longitudinal study between groups of healthy preterm and term infants. Preterm infants (n = 9) were born at 31-35 wk gestation with normal birth weights for gestational age and studied on three occasions: a preterm study at 36 wk, at 2-3 wk post-term, and at 2-3 mo post-term. Term infants (n = 22) were born at 37-42 wk and were studied at 2-3 wk and 2-3 mo post-term. Arousal thresholds were determined in both active sleep (AS) and quiet sleep (QS). In preterm infants, there was no state-related difference in arousal thresholds at either the 36 wk or 2-3 wk study; however, at 2-3 mo, arousal threshold was significantly greater in QS than AS (p < 0.05). In contrast, in term infants, arousal thresholds were significantly elevated in QS compared with AS at both 2-3 wk and 2-3 mo (p < 0.001). Arousal thresholds in AS were not different between the two groups of infants, with both groups of infants remaining readily arousable. However, in QS at 2-3 mo, arousal thresholds were significantly lower in the preterm infants (p < 0.05). This study has demonstrated that arousability is altered by gestational and postnatal age. The lower arousability that characterizes QS in term infants regardless of age is not evident in preterm infants until 2-3 mo post-term age.

Immunization has no effect on arousal from sleep in the newborn infant.

OBJECTIVE: To investigate arousal from sleep in infants before and after triple antigen immunization (DTP). METHODOLOGY: Arousal thresholds were determined in both active sleep (AS) and quiet sleep (QS) the day before and the day following the first DTP immunisation in 14 infants. Arousal was induced using a pulsatile puff of air delivered alternately to the nostrils of the infant. RESULTS: Arousal threshold was significantly higher in QS compared to AS in both studies (P < 0.001). Mean arousal threshold in the pre immunization study was not different from that in the post immunization study in either sleep state. Core temperature and heart rate measured at the time of stimulus delivery were both significantly elevated in the post immunisation study (P < 0.001). Sleep duration and number of awakenings from sleep were unaffected by immunization. CONCLUSION: The first triple antigen immunisation has no effect on arousal from sleep in either AS or QS in this group of infants.

Dynamic changes in arousal threshold during sleep in the human infant.

Failure to arouse from sleep is a possible mechanism leading to sudden infant death. Using a controlled pulsatile air jet applied alternately to the nostrils we have made multiple measures of arousal threshold both between and within sleep states. Infants (n = 22) born at term were studied at 2-3 wk postterm (mean age 13 d, range 9-17 d, study 1) and again at 2-3 mo postterm (mean age 78 d, range 56-98 d, study 2). Arousal threshold (stimulus driving pressure, cm H2O) was determined in both active sleep (AS) and quiet sleep (QS). At both ages arousal threshold in QS was significantly higher (251 +/- 24 and 298 +/- 35) than in AS (163 +/- 19 and 144 +/- 29) (p < 0.001). In a morning sleep period, the first and second QS epochs were compared in each baby. In both study 1 and study 2, respectively, arousal thresholds were significantly higher in the second QS epoch (270 +/- 34 and 497 +/- 100) than in the first QS epoch (198 +/- 29 and 252 +/- 69) (p < 0.05 and p < 0.02). There was a significant correlation in individual infants between arousal thresholds in the two states at both ages (p < 0.005 and p < 0.007, respectively). Regression analysis showed no correlation between the length of time the infant had been in a particular sleep state and the arousal threshold in either state in study 1 or in AS in study 2; however, arousal threshold increased significantly (p < 0.01) with time in QS in study 2. This study has expanded on previous findings that arousability is sleep state-dependent by demonstrating that arousability in QS is also altered by the length of time that the infant has been asleep.

Changes in the temporal structure of periodic breathing with postnatal development in preterm infants.

The progressive decrease in the periodic cycle duration (PCD) of periodic breathing with postnatal age in term infants has been previously reported by a number of authors and is thought to be associated with peripheral chemoreceptor maturation. We hypothesized that a similar decrease should be observed in preterm infants. Therefore, in this study we measured the changes in PCD with postnatal age in a small group of preterm (n = 4) infants followed longitudinally (36 afternoon nap studies) over the first 6 mo postnatally. PCD declined in these infants from 17.1 +/- 3.3 s (mean +/- 2 SD) at 9 d to 9.8 +/- 3.2 s (mean +/- 2 SD) at 105 d. The regression slope was -0.072 s/d. Beyond 105 d there was no change in PCD up to 6 mo postnatally. We found no significant difference between active and quiet sleep. These results are similar to results previously published in term infants but apparently contradict recent data on a group of preterm infants. Possible reasons for this discrepancy are discussed. By examining long epochs of periodic breathing in these infants we also identified characteristic changes in PCD and V/A ratio, defined as the duration of the ventilatory period divided by the duration of the apneic interval. V/A ratio fell from the start of an epoch from 1.21 +/- 0.08 (mean +/- SEM) to a minimum of 0.62 +/- 0.03 and then increased again to 0.8 +/- 0.05 at the end of the epoch.(ABSTRACT TRUNCATED AT 250 WORDS)

Forehead and forearm skin blood flows in newborn infants measured by laser Doppler flowmetry: short-term variability and relationship to sleep states.

Laser doppler flowmeters were used to measure blood flow in the skin of the forehead and volar surface of the forearm of infants at 2-9 days of age, and at 8-12 weeks of age. At both ages mean skin blood flow was higher during active sleep compared to quiet sleep. In infants up to 9 days of age, mean skin blood flow was higher in forehead skin compared to forearm skin. Skin blood flow was highly variable at both recording sites, and was significantly higher and more variable during active compared to quiet sleep in the forehead, but not in the forearm. The results indicate that recordings of skin blood flow over at least two cycles of active and quiet sleep are needed to describe the normal variation with sleep state. The factors which regulate forehead and forearm skin blood flows may differ in importance between the two sites, perhaps reflecting the different thermoregulatory importance of cutaneous blood flow in the forehead and forearm.

Circadian rhythms in sleep and wakefulness and in salivary melatonin and cortisol concentrations in mothers of term and preterm infants.

We compared the effects of the demands of term and preterm infants on the daily rhythms of sleep and wakefulness and salivary melatonin and cortisol concentrations in mothers for up to 5 months after either birth (term group) or arrival of the infant home (preterm group). Although there were relatively small differences between the term and preterm groups in the daily patterns of infant sleep-wake behavior, there were more marked differences in the maternal sleep-wake parameters. During the first 8 weeks after the arrival of the infant home, the mothers of preterm infants had significantly less time asleep and fewer sleep bouts per 24 hours than did the mothers of term infants. The mothers of preterm infants spent a significantly longer proportion of each night awake (30-40%) for the first 8 weeks than did the mothers of the term infants (20-30%). There was also a significant difference between the term and preterm groups in the effect of time of day on maternal salivary melatonin concentrations. In the term group, maternal melatonin concentrations were higher at night (10 p.m.-6 a.m.) than at any other time of day. In contrast, in the preterm group maternal melatonin concentrations between 10 p.m. and 6 a.m. were only higher than those measured between 6 a.m. and 2 p.m. Salivary cortisol concentrations were significantly higher in the mothers of preterm infants than in the mothers of term infants throughout the 10-week study period, but the peak in salivary cortisol concentrations occurred between 2 a.m. and 10 a.m. in both the term and preterm groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of circadian sleep-wake rhythms in preterm and full-term infants.

We have compared the roles of neurologic maturity and environmental time cues in the development of the entrained circadian sleep-wake rhythm in the preterm and term human infant. The preterm infants (n = 19) spent some time after birth in a hospital nursery with no environmental time cues, whereas the term infants (n = 22) were exposed from birth to a cyclical light and dark environment with one major caregiver. The circadian sleep-wake rhythm in the preterm infants entrained after a similar time of exposure to an environment with daily time cues but at an earlier postconceptional age when compared with the term group. We conclude, therefore, that it is the length of exposure to environmental time cues, rather than neurologic maturity, that determines the entrainment of the circadian rhythm of sleep and wakefulness in the human infant.

Role of lung fluid volume in growth and maturation of the fetal sheep lung.

We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control.

Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep.

This study has examined left (LV) and right ventricular (RV) myocardial morphometry in perfusion-fixed hearts of late-gestation sheep fetuses, neonatal lambs, and adult sheep. During development, myocyte size, intercapillary distance, and myocyte myofibrillar and mitochondrial volume densities increased, whereas capillary density, the myocyte-to-capillary ratio, and the myocyte matrix volume density decreased. RV myocytes were larger than LV myocytes in cross section in fetuses and 4-day-old lambs. LV and RV myocytes were of similar size in 7-day-old lambs. LV and RV myocytes were of larger in older lambs and adult sheep. Differences between LV and RV myocyte volume densities of myofibrils, mitochondria, and matrix were also observed in fetuses and young lambs. As well, variation in capillary size and density was apparent between ventricles in the fetal and neonatal periods. We conclude that, in the sheep heart, 1) LV and RV morphometric differences exist during fetal and postnatal development, 2) fetal LV and RV myocardial morphometry is consistent with an RV dominance in utero, 3) rapid growth of LV and RV myocytes occurs in the perinatal period, and 4) the relative size of LV and RV myocytes does not reflect a postnatal LV dominance until between 1 and 4 wk after birth.

Fetal lung growth in laryngeal atresia and tracheal agenesis.

Three cases of airway obstruction in fetuses born at 21, 32 and 40 weeks gestation are reported. The first had laryngeal atresia, cystic dysplastic kidneys, oligohydramnios and immense fluid-filled lungs. The second had upper tracheal agenesis, a tracheo-oesophageal fistula, a cystic dysplastic horseshoe kidney, oligohydramnios and normal-sized lungs. The third had a pin-hole mucosal tract through an otherwise atretic larynx, normal kidneys, no oligohydramnios and normal-sized lungs. Lung weight:body weight ratios, radial alveolar or radial canalicular counts and point-counting of sections of lungs in cases 1 and 2 show that laryngeal or tracheal obstruction may prevent or reduce the pulmonary hypoplasia associated with renal dysplasia, and in cases 2 and 3, that grossly enlarged, hyperplastic lungs may not be seen unless obstruction is complete.

Effect of changing lung liquid volume on the pulmonary circulation of fetal lambs.

During fetal life the lung develops as a liquid-filled structure with low blood flow compared with postnatal life. We studied the effects of liquid expansion of the fetal lung by measuring vascular conductance in perfused lungs in situ and arterial diameters in excised lungs of fetal lambs. Pulmonary vascular conductance invariably rose as the lung was deflated from its initial volume; maximal deflation to residual volume increased conductance 122%. With reexpansion, conductance fell progressively, culminating in cessation of flow at lung volumes of twice the initial volume. These changes persisted after vagotomy and thoracic sympathectomy and therefore were mechanical in character. Lung expansion from residual volume initially expanded 300- to 500-micron arteries but compressed arteries greater than 1,500 micron. Further expansion reduced the caliber of all arteries. Thus increasing lung liquid volume progressively constricts the pulmonary circulation in the fetus. Because the fetal pulmonary vascular resistance-lung volume relationship differs from that of the U-shaped form found in adult lungs, concepts based on the adult pulmonary circulation are not appropriate for liquid-filled fetal lungs.

An improved perfusion technique for fixation of sheep myocardium.

Although sheep have been widely used as models in the study of cardiac physiology, corresponding morphologic and morphometric data are scanty. For meaningful correlation of morphometric data with physiological information, it is desirable that fixation of the heart occur under controlled conditions. This paper describes a technique for in situ, retrograde aortic perfusion fixation of sheep myocardium under conditions of controlled pressure and minimal wastage of fixative. This is achieved by the application of snares around the brachiocephalic trunk and aortic arch, which are tightened at the start of the perfusion. These isolate the ascending aorta and the coronary vasculature from the remainder of the circulation and allow fixation of the whole heart at a controlled pressure. The method produces good fixation and contrast for transmission electron microscopy and is applicable to late-gestation fetuses, lambs, and adult sheep.

Cluster microvilli in coronary endothelium.

Examination of cardiac vascular endothelium with scanning electron microscopy, and transmission electron microscopy of previously scanned tissue, revealed several regions of the coronary venous system that contained 'cluster' microvilli. These consisted of 2-15 microvillous projections that emanated radially from a common base or were grouped into a fan-like arrangement. Although rare, these clusters, when present, were widely distributed over the endothelial cell surface.

Computerised nutritional data management in neonatal intensive care.

We report a minicomputer based recording, reporting, and research system for patient data management in the neonatal intensive care unit (NICU). It is moderately priced, transportable, and independent of a central computer. It requires only a desk top and standard power supply, and successfully meets the medical documentation, communication, and research needs of the NICU. The first phase of programme development has enabled us to process growth and nutritional data from infants on complex parenteral and enteral nutrition. The system is well suited to medical users and provides a practical interactive data management system with many potential applications in the NICU.