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Our aim was to evaluate programs promoting bed sharing on maternity wards and determining ways to reduce these risks. Members of the National Association of Medical Examiners were contacted requesting information on deaths of healthy infants while bed sharing on maternity wards. Fifteen deaths and three near deaths are reported. One or more factors that increase the risk of bed sharing were present in all cases. Accidental suffocation was deemed the most likely cause of these incidents. Cases of infant deaths and near deaths while bed sharing on maternity wards are under reported. The ‘Baby Friendly’ (BF) initiative in maternity hospitals to promote breastfeeding is endorsed by the American Academy of Pediatrics and the US Center for Disease Control and Prevention. The BF initiative encourages prolonged skin-to-skin contact and bed sharing. Education of mothers and more efficient monitoring should significantly reduce the risk of maternity ward bed sharing.

Autoresuscitation (AR) is a highly conserved response among mammals, which allows survival from transient extreme hypoxia. During hypoxia, bradycardia, and hypoxic gasping develop after a brief period of hyperactivity. Normally, AR occurs if oxygen is restored during the gasping period where an initial heart rate increase is rapidly followed resumption or eupneic breathing. Humans and other mammals can survive multiple immediately repeated AR. A defective AR capacity has been implicated in Sudden Infant Death Syndrome. We had reported earlier that inbred strains of mice such as BALB/cJ could survive a characteristic number of immediately repeated AR trials, but that SWR/J mice failed to AR from a single hypoxic episode. We now report that strains closely related to SWR/J, FVB/N and SJL/J exhibit partial resuscitation defects relative to BALB/cJ or other mouse strains, establishing a genetic basis for variation in AR failure. The AR trial phenotype of BALB/cJ x SWR/J intercross F(1) and F(2) mice was consistent with BALB/cJ dominance and a discrete number of loci. Genome-wide mapping conducted with 60 intercross F(2) animals linked two loci to the number of AR trials survived, including one sex-specific locus with male expression, consistent with the observed 50% male bias for Sudden Infant Death Syndrome in humans. A locus carried on SWR/J chromosome 10 seems to be particularly important in AR failure and was confirmed in a partial consomic line. These results establish a genetic basis for AR failure phenotype in mice, with relevance to Sudden Infant Death Syndrome.

Laryngeal closure following hypoxic gasps has been documented, but its efficacy in improving autoresuscitation capacity is unknown. We studied SWR/J mice who normally cannot autoresuscitate and the C57/BLJ strain who can. We evaluated the effects of elevated end-inspiratory lung volume immediately following a gasp. We compared upper airway-intact mice with tracheostomized mice in which the vocal cords are bypassed. We used the techniques of repeated autoresuscitate trials to test autoresuscitation capability. Both SWR/J and C57/BLJ mice could maintain elevated lung volume immediately after a gasp (breath holding). Such breath holding increased autoresuscitation ability in C57/BLJ mice but did not in SWR/J mice. In SWR/J mice, the duration of the breath holds was less than that in the C57/BLJ mice. These findings indicate that gasp-associated breath holding improves autoresuscitation capability during repeated autoresuscitation trials. Also, they show that SWR/J mice have a deficiency in central nervous system mechanisms regulating glottic closure during hypoxic gasping.

Rebreathing may impair ventilation and lead to sudden death among sleeping infants. To estimate the potential for rebreathing imposed by an infant's sleep microenvironment, we developed a mechanical model to assess the rate of CO2 dispersal away from an infant's face. We compared the mechanical model results with changes in arterial blood gases of rabbits. The rabbits breathed into the same microenvironments used for the model studies. In the rabbits, rebreathing (documented by capnometry) caused hypercarbia and in some cases death. The mechanical model consisted of the mannequin head positioned as in the rabbit studies and connected to a 100-ml syringe filled with CO2. CO2 was washed out of the system using 30-ml “breaths” (rate = 15/min). The half times (t1/2) for CO2 dispersal served to quantify the rebreathing potential of 16 items of bedding. The t1/2 values correlated with increments in the rabbits' arterial PCO2 (r = 0.789). The threshold for the increase in the rabbits' arterial PCO2 corresponded to t1/2 values of > or = 18.7 s; the 90% point for lethality in the rabbit model was 28.1 s. The mechanical model was also used to show the independent effects of softness and porosity of bedding on its rebreathing potential. By describing the potential for rebreathing within bedding, the mechanical model should be useful in future quantitative studies of infants' respiratory adaptation to sleep microenvironments.

Dr. Paviotti and his associates are to be commended for developing a program that intends to improve newborn infant safety while promoting mother–infant contact and breast feeding.1 I agree on the need to prove the effectiveness of this protocol as in my report a few infants, who died, had awake mothers and room visitors at the time. The scheduled observations may prove valuable, but an infant can become dangerously hypoxic when its airway is obstructed for only a few minutes. I agree that bed sharing should be discouraged.

Recurrent laryngeal nerve injury during patent ductus ligation: can this common complication be reduced?

To examine whether the prone sleeping position may increase the risk for sudden infant death syndrome (SIDS), particularly in infants unused to prone sleep.A 3-year (1987-1990) case-control study.Nationwide study in New Zealand.Four hundred eighty-five infants who died of SIDS and 1800 controls.Infants were classified as unaccustomed to prone if their usual sleep position was nonprone and they were placed prone for the last sleep. Secondary prone was used to describe infants placed nonprone but found prone.Infants usually and last placed nonprone were at the lowest risk for SIDS (odds ratio [OR], 1.0); those usually and last placed prone were at increased risk (adjusted OR, 4.6; 95% confidence interval, 3.4-6.3). Risk was greatly increased among infants unaccustomed to the prone position (adjusted OR, 19.3; 95% confidence interval, 8.2-44.8). These infants accounted for 8% (31/ 386) of all SIDS deaths. Ninety percent (28/ 31) of infants in this group were found prone, and 71% (20/28) of those found prone were found with their faces turned down into bedding-a position in which asphyxia has been implicated as a mechanism of death. In addition, 138 infants who died of SIDS were last placed nonprone. Forty-seven infants (34%) in this group were found prone (secondary prone), and 60% (28/47) of those found prone were found with their faces turned down into the bedding. This group accounted for 12% of all SIDS deaths. Most of these infants (91% [43/47]) were usually placed nonprone.Infants placed supine to sleep were at the lowest risk of SIDS, which supports the recommendation that this is the preferred sleeping position for healthy infants. In New Zealand, 20% of SIDS deaths involved lack of experience with the prone sleeping position. Our findings suggest the possibility that an infant's competence in escaping from potentially lethal situations during prone sleep (eg, the face-down position) may be impaired by inexperience in prone sleeping. Great caution should be exercised in placing infants unaccustomed to the prone sleeping position in the prone position.

The mucosa covering the interarytenoid space at the entrance to the larynx contains specialized nerve endings (receptors) that are stimulated when a fluid comes into contact with the mucosal surface. These receptors mediate several aspiration preventive reflex responses, which include swallowing, cessation of breathing, airway constriction or closure, and coughing. The laryngeal receptors are more sensitive to water than to saline, and therefore the combined reflex response to receptor stimulation is termed the "laryngeal chemoreflex." This reflex can be activated during regurgitation of gastric contents into the pharynx, in which case the several components of the reflex serve to prevent intrapulmonary aspiration of gastric fluid. In certain infants a hyperactive laryngeal chemoreflex may cause episodic prolonged apnea. Such reflex-mediated apnea has been implicated in several kinds of prolonged infantile apnea, including apea of prematurity, gastric regurgitation-related apnea, and apnea associated with upper respiratory infection.

Severe hypoxia produces a state of neural depression known as hypoxic coma in which reflex activity is believed to be absent but from which spontaneous recovery (“autoresuscitation”) still can occur. We evaluated the swallowing reflex during hypoxic coma by employing mechanical and chemosensory stimuli. BALB/c mice were given 97% N2-3% CO2 to breathe. At onset of coma, a 0.05-ml bolus of saline or water was infused into the pharynx. Unlike mechanical stimulation (sham infusion), fluid infusion usually was followed by rapid swallowing, more so with water than with saline. This model allowed examination of interactions among swallowing, hypoxic gasping, airway fluid removal, and autoresuscitation. Compared with sham infusion, saline and water reduced gasping rate equally. Saline, however, prolonged the process of autoresuscitation more than did water, an effect possibly related to an observed increased retention of saline in the airway. Occasionally, mice failed to swallow after infusions, in which case airway obstruction during gasping and autoresuscitation failure was repeatedly observed. These studies suggest that the swallowing component of the laryngeal chemoreflex is present during hypoxic coma and that swallowing facilitates autoresuscitation when upper airway fluid is present.

To determine whether rebreathing of expired air is a plausible lethal mechanism of sudden death in infants sleeping face down on sheepskins.Case reports of infants who died on sheepskins combined with a controlled study of effects of their respiratory microenvironment at death.Research laboratory.Rabbits used experimentally to assist in simulation of an infant's respiratory microenvironment. Rabbits breathed into sheepskin through the airway of an infant mannequin.None.Rebreathing of expired air was documented by carbon dioxide analysis of airway gas. Arterial blood gas analysis showed hypoxemia, hypercarbia, and acidosis in all experimental rabbits but not in controls. Rebreathing expired air was lethal for three of four experimental rabbits.Infants sleeping prone on a sheepskin, with their faces straight down, experience potentially lethal rebreathing of expired air. Avoidance of the prone position would markedly reduce the risk of rebreathing expired air. The pronounced decrease in sudden infant death syndrome in southern New Zealand that followed a campaign to eliminate prone sleeping may have been attributable to reduced fatal rebreathing, as deaths of infants sleeping face down on sheepskins were common before the campaign.

Mechanisms underlying failure of autoresuscitation from hypoxic apnea were investigated. Failure was induced by repeated exposure to hypoxia. The influence of maturation was studied in adults, weanlings, and 10- and 5-day-old mice. Mice successful at autoresuscitation (BALB/c) as well as those prone to autoresuscitation failure (SWR weanlings) were studied. Hypoxic apnea was induced with 97% N2–3% CO2, and 21% O2 was given at its onset; electrocardiogram and ventilation were recorded. Hypoxic exposure was repeated if autoresuscitation (recovery of eupnea) occurred. Autoresuscitation failure (death) was induced in all mice. Young BALB/c mice tolerated more trials than older mice. SWR weanlings frequently failed to autoresuscitate on the initial exposure and tolerated fewer repeat trials overall than age-matched BALB/c mice. Induced autoresuscitation failure in all mice appeared to be unrelated to gasping regulation, because both gasp number and amplitude were similar during the failed trial and the previous successful trial. In most mice, failure was associated with absent recovery of heart rate during gasping. In BALB/c mice in particular, this persistent bradycardia was usually due to heart block, which occurred in 95% of failed trials. In addition, heart block occurred with increasing frequency on later successful trials, but conversion to sinus rhythm always preceded successful autoresuscitation. Heart block was also frequent in SWR mice and had similar consequences. BALB/c mice exposed to continuous anoxia survived longer than SWR mice, indicating increased endurance of components of the autoresuscitation mechanism not directly related to the ventilatory function of gasping (e.g., cardiovascular components).(ABSTRACT TRUNCATED AT 250 WORDS)

We unknowingly "screened" all NICU infants for elevated levels of serum benzyl alcohol (Bz-OH) over a three-month period. The fortuitous "screening" procedure resulted from the interference by Bz-OH with a routine blood CO2 assay used for all infants; validity was proved by (1) replication of the interference pattern with Bz-OH or benzoic acid; (2) confirmation of elevated benzoic acid levels in serum in two of the four screening positive infants tested but not in control infants, and (3) disappearance of the interference patterns when Bz-OH solutions were discontinued in affected infants. Screened Bz-OH-positive infants were compared to screened negative control infants, matched for weight (less than 1000 g), severity of RDS (on respirators), exposure to Bz-OH, and survival for longer than 48 hours. Intraventricular hemorrhage (IVH), metabolic acidosis appearing prior to IVH, and mortality were increased in Bz-OH-positive infants (P less than .05 in each case); hyperbilirubinemia and thrombocytopenia were not. Gasping respirations were not a major symptom. It is concluded that Bz-OH poisoning was a major cause of morbidity and mortality in NICU infants weighing less than 1000 g at birth during the three-month screening period. A retrospective review of patient records covering a 16-month period showed significant improvement in the survival rate of infants weighing less than 1000 g following the discontinuation of Bz-OH solutions.

The upper airway is vulnerable to collapse from negative intraluminal pressures during inspiration. The tongue muscles, the genioglossi and geniohyoids, by contracting during inspiration, appear to function to resist this collapse. This study supports the hypothesis that two cervical strap muscles, the sternohyoid and sternothyroid, have a similar function. First, phasic inspiratory electromyographic activity was recorded from the sternohyoid and sternothyroid muscles of nine anesthetized rabbits during tidal breathing. Furthermore, each muscle showed a progressive increase in electromyographic activity with airway occlusion. Second, in eight rabbits, by determining the amount of negative pressure required to collapse the upper airway (airway closing pressure determination), it was shown that upper airway stability improved with electrical stimulation of either the paired sternohyoid or sternothyroid muscles. In addition, in 12 freshly killed rabbits, mechanical tension, mimicking the contraction of either the sternohyoid or sternothyroid, improved airway stability. Finally, observations of the pharyngeal lumen utilizing a fiber-optic endoscope, revealed concentric narrowing of the oro- and nasopharynx when airway pressure was lowered and concentric widening when tension was increased in the sternohyoid or sternothyroid muscles. These findings support the hypothesis that phasic inspiratory contraction of the sternohyoid and sternothyroid muscles functions to resist pharyngeal airway collapse due to negative intraluminal pressures.

Tonic and phasic inspiratory genioglossus (GG) electromyographic activity (EMG) was recorded from 13 anesthetized rabbits during unstimulated breathing. Integrated GG EMG peaked earlier in inspiration and presented a more rounded contour than integrated diaphragmatic (DIA) EMG. Spontaneous augmented deep inspirations (sighs) showed a biphasic pattern in both GG and DIA EMGs. Hyperventilation abolished phasic inspiratory activity in the GG before the DIA, suggesting that the GG has a higher CO2 apneic point. Hypercapnia increased both EMGs; however, GG EMG increased more, as a percent of base line, than did DIA EMG. Oxygen breathing decreased GG more than DIA EMG; sodium cyanide injection and brief nitrogen breathing increased GG more than DIA EMG; carotid body denervation abolished these responses. Vagotomy abolished the Hering-Breuer inflation-inhibition reflex in both muscles, and tactile, visual, and auditory stimulation increased GG more than DIA EMG. Thus, the GG responses to chemoreceptor input and to nonspecific respiratory stimuli are qualitatively similar but quantitatively different from DIA responses. The relevance to mixed and obstructive apnea is discussed.

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.

The ability of the extrathoracic airway (ETA) to remain open when exposed to negative pressure was investigated in rabbits. Postmortem, the ETA collapsed at -6.3 +/- 0.6 cmH2O whereas, during airway occlusion maneuvers in lightly anesthetized animals, it remained patent at pressures as low as -80 cmH2O. This discrepancy suggested that a neuromuscular mechanism maintains ETA patency. Four findings indicated that the genioglossus and geniohyoid muscles, which pull the tongue and hyoid bone anteriorly, help maintain ETA patency: 1) anterior movement of the hyoid bone increased the negative pressure at which the ETA collapsed postmortem, 2) ETA closure during occluded inspirations occurred after 12th nerve section abolished electromyographic activity in these muscles and 3) after deep anesthesia depressed such activity, and 4) closing pressure was linearly related to peak integrated electromyograms of the two muscles. After 12th nerve section, ETA closing pressure became more negative with progressive asphyxia greatly exceeding postmortem closing pressure, which suggests that other muscles also help maintain ETA patency. Blood gas tensions, respiratory system mechanoreceptors, and depth of anesthesia appear to influence genioglossus and geniohyoid activity.

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.

To learn how increased cervical adipose tissue might affect upper airway function, we studied effects of mass loading on upper airway dimensions, stability, and resistance. Eight rabbits were studied (anesthetized and postmortem) using lard-filled bags to simulate cervical fat accumulation. Additionally, a handheld device was used to apply measured loads at localized sites along the airway. Upper airway resistance and closing pressure (a reflection of airway stability) were determined before and after loading. Endoscopy revealed concentric narrowing of the pharynx during loading in anesthetized and postmortem preparations. Upper airway resistance was increased by mass loads, with larger loads having greater effects. Loading caused decreased airway stability as reflected by closing pressures. The area over the thyrohyoid membrane was more vulnerable to mass loading than adjacent areas. Because mass loading of the upper airway causes changes in its configuration and function similar to those seen in obstructive sleep apnea syndrome (OSA), we speculate that such loading may contribute to the pathogenesis of OSA associated with obesity.

A nasal flowmeter suitable for preterm infants is described. It is made from a commercially available nasal cannula and 400-mesh stainless steel screen. Low dead space (0.35 ml) and low resistance (1.3 cmH2O . 100 ml-1 . s) are advantages. Light weight and compact design have eliminated the need for extensive restraint of the subject. Also, the investigator need not hold the flowmeter in place. These features make accurate measurement of respiratory airflow and tidal volume possible during polygraphic monitoring studies lasting several hours.

A 46-year-old man with Behçet syndrome and a long history of recurrent bouts of colitis was studied by sigmoidoscopy, barium enema x-ray film, and colon biopsy. A nonspecific colitis characterized by shallow mucosal ulcerations and submucosal mononuclear infiltration in the absence of meaningful roentgenolographic changes was seen. A histopathological comparison was made between the oral and colonic lesions. The aphthous colitis appears, therefore, to be a colonic manifestation of Behçet syndrome, differing from typical chronic nonspecific ulcerative colitis in terms of clinical course, severity, and histologic appearance. The simultaneous occurrence of Behçet syndrome and inflammatory disease of the colon was discussed in terms of the differential diagnosis of colitis.

The flow of oral and nasal secretions into the pharynx is a recognized source of pulmonary aspiration during sleep in infants and adults alike. Such aspiration probably accounts for many cases of bacterial pneumonia. In infants, swallowing occurs frequently in sleep, and the rate of swallowing appears to be far greater than that of the sleeping adult. Such swallowing during sleep appears to be the major mechanism whereby oral and nasal secretions are transported to the digestive tract. Certain aspects of those swallows, such as "swallow-breaths" and their coordination with the respiratory cycle, have been documented. A brief period of airway closure is always seen during such nonfeeding swallows. Nonfeeding swallows are usually seen during mixed and obstructive apneic spells in preterm infants. The underlying reflex mechanisms responsible for such swallows during apnea are unclear. During ordinary postfeeding regurgitation, upper airway closure and swallowing occur in close temporal sequence. These events appear to be major mechanisms of airway protection during regurgitation. In certain infants, regurgitation and prolonged apnea often occur simultaneously. The mechanism underlying their association is unclear but may involve laryngeal chemoreceptors.

The effective elastance of the respiratory system (E‣rs) is a measure of its ability to resist a change in tidal volume under conditions of changing elastic loads. E‣rs was measured while subjects breathed air and 2% CO2 and 4% CO2 in air in two groups of premature infants of different gestational ages at 1 day 3–4 days, and 7–10 days of age. E‣rs was shown to decrease with increasing maturation and was independent of changes in control tidal volume. The decrease of E‣rs with increased gestational age could be accounted for by differences in calculated thoracic gas volumes in all but one instance, where E‣rs was lower in one group on the 3rd day of life. The activity of the Hering-Breuer reflex, as measured by the degree of slowing of inspiratory time after occlusion at FRC, has been previously reported to be normal to increased in similar infants. This suggests that differences related to size account for most of the maturational changes of E‣rs in newborns.

We examined the characteristics of spontaneous restoration of airflow after airway obstruction during neck flexion in normal sleeping infants. In 22 of 27 episodes of complete airway obstruction in 5 of 8 infants, there was some resumption of airflow, although the angle of neck flexion was maintained. The airway reopening was usually delayed, after 1 to 3 obstructed inspiratory efforts, and usually without evidence of behavioral arousal. The time course of this delayed response suggested chemoreceptor mediation. In those trials where arousal was observed, airflow resumed immediately. Our observations suggested that activation of the genioglossus and other airway-maintaining muscles leads to airway reopening neck flexion in infants and that tonic genioglossus activity maintains airway patency. These observations represented the first description of restoration of airway patency after airway occlusion in infants.

The effect of maturation and motor activity on recovery from hypoxic apnea by gasping (autoresuscitation) was investigated in Swiss Webster mice and a SW-related strain. Apnea was induced with 97% N2–3% CO2 and air given at its onset. In 69 Swiss Webster-related strain mice that gasped for at least 5s, the survival rates were 100% in 1- to 16-day-old mice, 19% in 17- to 23-day-old mice, and 90% in adults. The rates in 81 Swiss Webster mice were 100, 70, and 95%, respectively. The decrease in survival in 17- to 23-day-old mice was statistically significant for both strains, as was the difference in survival in 17- to 23-day-old mice between the two strains. Gasping was absent or of brief (less than 5s) duration in 15 Swiss Webster mice that failed to recover. Seizure-like activity was observed during hypoxic apnea and gasping but was not seen significantly more often in mice that died. Simultaneous recordings of limb movement (electromyogram) and breathing pattern indicated that movement did not interfere with the occurrence of gasping. We conclude that in adults and very young mice autoresuscitation is a powerful mechanism for recovery from hypoxia, but at an intermediate age, it is frequently unsuccessful.

The progressive respiratory response to occlusion of the airway at FRC was measured in a group of full-term and premature human infants. The sleep state of the full-term infants was shown to affect the response primarily through variations in the phase of thoracic and abdominal movements. The weakest responses were seen in those infants who demonstrated parodoxical respiration prior to occlusion. Most infants developed paradoxical respiratory movements after occlusion, but this did not affect the strength of the load-compensatory response. An increase in response related to both gestationaland postnatal age was observed. This increase could not be accounted for byvariations in the amount of paradoxical and in-phase respiration and thus may represent an increase in the sensitivity of infants to chemical stimuli with maturation.

To investigate the reflex mechanisms of sighs (spontaneous large breaths)(VT greater than 2 X control VT) in infants, recordings of respiratory flow and tidal volume (VT) were made during sleep. The frequency of sighs was greater at 1 than at 5 days of age, while respiratory frequency and controlVT did not change. Most sighs (93%) had a biphasic pattern of inspiratory flow characterized by an inspiratory duration nearly twice that of control breaths, with an abrupt change in flow rate halfway through inspiration. Interruption of ventilation (3–7 s of airway occlusion) appeared to generate astimulus for biphasic sighs, since sighs occurred during the first breath after termination of airway occlusion more frequently after long thanafter brief occlusions. However, a biphasic inspiratory pattern in airway pressure was rarely observed while the airways were occluded, regardless of occlusion duration. This suggests that increase in lung volume during the initialpart of the biphasic inspiration following occlusion is a stimulus for the second part. Thus the underlying reflex mechanism of sighs in human infantsappears to be the same as occurs in the so-called Head's paradoxical response to lung inflation.

We studied breathing pattern and transcutaneous oxygen tension (TcPO2) during episodes of sustained generalized motor activity in 18 hospitalized preterm infants. We used a newly developed quantitative method for assessing minute ventilation in infants during vigorous motor activity. We recorded respiratory air flow, tidal volume, esophageal pressure, TcPO2, and electromyograms of various muscle groups. We observed a distinctive pattern of breathing ("exertional breathing pattern") that was invariably associated with episodes of "squirming" motor activity. This breathing pattern is characterized by reduced minute volume, intermittent Valsalva maneuvers, and obstructed inspiratory effects (obstructive apnea). Episodes of squirming with the accompanying altered breathing pattern were usually followed by a decrease in TcPO2. These episodes occurred spontaneously or could be induced by sensory stimulation. They appear to be a significant cause of obstructive apnea and TcPO2 instability in hospitalized preterm infants, and were responsible for 30% of sudden decreases in TcP[O2 of 10 mmHg or greater.

Breathing variability and apnea characteristic of rapid eye movement (REM) sleep was investigated in a newborn infant with complete interruption of intercostal to phrenic neural pathways due to intrapartem transection of the cervical spinal cord. Breath-to-breath variability in inspiratory duration (TI), breath duration (Ttot), tidal volume (VT), and ventilation (VI) was significantly greater in REM than in quiet sleep and was similar to the variability in these parameters seen in normal infants. In addition, brief periods of diaphragmeatic apnea were observed during REM sleep. The phenomenon of shortened TI during airway occlusion previously attributed to intercostal-to-phrenic reflexes was examined in the quadriplegic infant and in seven healthy term infants. The frequency of this response was increased when airway occlusion was delayed until after onset of inspiration. Shortening of TI by occlusion occurred no less frequently in the quadriplegic than in the control infants. The constant paradoxical inward movement of the rib cage during inspiration observed in the quadriplegic infant suggests that supraspinal innervation of intercostal muscle limits such paradoxical movements in the normal infant. The quadriplegic infant's end-expiratory volume was consistently above his passive functional residual capacity, as inferred from respiratory volume and pressure measurements.

To better document and describe the phenomenon of swallowing during apneic spells, we compared the frequency of swallowing during epidsodes of prolonged apnea with nonapnea control periods in 9 preterm and 1 term infant. Infants with a history of idiopathic prolonged apnea were studied for 2 to 3 h by monitoring, electrocardiogram, nasal air flow, oral CO2, abdominal respiratory movements, chin electromyogram, pharyngeal pressure, and pH. In 7 of the infants, additional observations were performed without the intrapharyngeal recording devices. One or more swallows occurred during 75% of the 100 spells observed. Swallows were far more common during apneic spells than during nonapnea control periods, and were more frequent during mixed and obstructive apnea than during central apnea (p less than .01). Asphyxia, regurgitation, and the intrapharyngeal recording devices did not appear to cause the increased frequency of swallows during apneic spells. Swallowing was temporally related to spontaneous recovery from apnea, with a swallow usually preceding recovery by 5 to 6 s. During apneic spells, we observed that swallows were often associated with a brief obstructed inspiratory effort ("swallow-breath"), a normal component of nonfeeding swallows in infants. These swallow-breaths were interspersed with higher amplitude "ordinary" obstructed breaths during apneic episodes. Thus, 2 distinctly different types of obstructed inspiratory efforts were identified during mixed and obstructive apnea episodes in infants. The sequence of events during apneic spells in the term and preterm infants was similar.

We unknowingly "screened" all NICU infants for elevated levels of serum benzyl alcohol (Bz-OH) over a three-month period. The fortuitous "screening" procedure resulted from the interference by Bz-OH with a routine blood CO2 assay used for all infants; validity was proved by (1) replication of the interference pattern with Bz-OH or benzoic acid; (2) confirmation of elevated benzoic acid levels in serum in two of the four screening positive infants tested but not in control infants, and (3) disappearance of the interference patterns when Bz-OH solutions were discontinued in affected infants. Screened Bz-OH-positive infants were compared to screened negative control infants, matched for weight (less than 1000 g), severity of RDS (on respirators), exposure to Bz-OH, and survival for longer than 48 hours. Intraventricular hemorrhage (IVH), metabolic acidosis appearing prior to IVH, and mortality were increased in Bz-OH-positive infants (P less than .05 in each case); hyperbilirubinemia and thrombocytopenia were not. Gasping respirations were not a major symptom. It is concluded that Bz-OH poisoning was a major cause of morbidity and mortality in NICU infants weighing less than 1000 g at birth during the three-month screening period. A retrospective review of patient records covering a 16-month period showed significant improvement in the survival rate of infants weighing less than 1000 g following the discontinuation of Bz-OH solutions.

We have previously demonstrated that fluctuating cerebral blood flow velocity and arterial blood pressure (ABP) are associated with intraventricular hemorrhage (NEJM 309, 1983). The cause of these ABP fluctuations (ABP Flues) is unknown. In the present study we determined the relation of respiratory muscle activity to fluctuations in ABP. We studied four preterm infants on ventilators for RDS with ABP Flucs. We monitored esophageal (Pes), gastric (Pg), and ABP pressure. Consistent findings were: 1) ABP flucs have the same frequency and direction of change as Pes and Pg changes associated with spontaneous breathing; 2) spontaneous apneic pauses were accompanied by sudden and complete cessation of ABP Flucs; 3) large cough-like swings in Pes and Pg, seen in all infants were associated with the largest ABP Flucs; 4) cutaneous stimulation had no effect on ABP Flucs provided no change in Pes and Pg occurred; 5) respirator pressure swings had only small effects on ABP Flucs in one infant; 6) the effects of change in Pes and Pg on ABP were nearly simultaneous (0.05-.2 s.), thus respiratory pressure changes appeared to be superimposed on cardiac swings in ABP. These findings suggest that the fluctuations in ABP are caused by two mechanisms: 1) direct transmission of pleural and abdominal pressure to the cardiovascular system during spontaneous breathing and/or 2) fluctuations in venous return produced by breathing pressures. (Funding NIH HD 10993)