Juliann Di Fiore

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.

Because neonatal apnea is frequently associated with airway obstruction, we compared relative changes in activity between various upper airway muscles and the diaphragm during hypercapnic stimulation. The technique of hyperoxic CO2 rebreathing was employed in 17 healthy, sleeping preterm infants studied at a postnatal age of 32 +/- 12 days. Surface diaphragm (DIA) electromyograms (EMGs) were recorded in all infants, and noninvasive measurements of posterior cricoarytenoid (PCA), genioglossus (GG), and alae nasi (AN) EMGs were analyzed in 11, 9, and 8 infants, respectively. During the control period, consistent phasic EMGs were recorded from the DIA in all infants and from the PCA in 8 infants, but from the GG and AN each in only one infant. During CO2 rebreathing, minute ventilation and end-tidal CO2 increased linearly as CO2 rose from 31 +/- 5 to 51 +/- 5 Torr. DIA and PCA EMGs also had proportional and comparable increases throughout rebreathing. In contrast, both GG and AN responses differed from the DIA and PCA (P less than 0.001) and exhibited minimal or absent responses at low levels of hypercapnia. Consistent GG and AN EMGs appeared at comparable levels of end-tidal CO2 (47 +/- 5 and 45 +/- 5 Torr, respectively) and subsequently increased linearly in most infants. We conclude that during CO2 rebreathing the initially delayed and subsequently linear responses of the GG and AN EMGs indicate a high CO2 threshold for these muscles.

Because neonates are vulnerable to spontaneous nasal obstruction, this study was designed to evaluate the ventilatory consequences of obstructing a single nasal passage in preterm infants. We employed a nasal pneumotachograph that separately quantified airflow between the two nasal passages and permitted unilateral nasal mask occlusions. Changes in minute ventilation (VI) and total (RT) and inspiratory pulmonary resistance (RI) were measured in response to 30-s unilateral occlusions during quiet and active sleep in 11 subjects. Unilateral nasal obstruction caused VI to fall significantly in both sleep states, because of a fall in both tidal volume and respiratory rate, without alteration in transcutaneous blood gases. RT and RI increased by 27 and 24 cmH2O.1-1.s, respectively, during unilateral nasal occlusion; this increase was greater than would be expected solely from elimination of one nasal passage. In 7 of the 11 infants a single dominant side could be identified as contributing 56-67% to tidal volume. The effect of occlusion on VI, RT, or RI did not differ whether the dominant or nondominant side was occluded. We conclude that unilateral nasal mask occlusion increases RT and RI and decreases VI in preterm infants. The larger than expected increase in resistance suggests that unilateral nasal loading predisposes to narrowing of the extrathoracic airway, and this may explain the comparable ventilatory responses to occluding the dominant and nondominant nasal passage.

To characterize the changes in respiratory mechanics and ventilatory timing that accompany apnea in premature infants, we evaluated 36 apneas in 13 premature infants (birth weight, 1,200 +/- 350 g, postconceptional age at study 34 +/- 3 wk). Apnea was defined as a ventilatory pause > or = 10s accompanied by a decrease in heart rate of 20 beats/min. Nasal airflow was recorded with a pneumotachometer, and esophageal, pharyngeal, and nasal mask pressures were continuously measured. Inspiratory time (TI), expiratory time (TE), tidal volume (VT), and VT/TI were determined over five breaths before and after apnea. In addition, total pulmonary resistance (RT) and supraglottic resistance (Rs) were measured over the same epochs in inspiration and expiration. Before apnea, TE and RT increased (P < 0.05 and < 0.01, respectively); however, Rs did not change. Immediately after apnea, prolongation of TI occurred and both RT and Rs were increased (P < 0.01), consistent with continued upper airway instability. However, within two breaths after resolution of the apnea, RT and Rs returned to normal, reflecting rapid recovery of upper airway and total pulmonary resistance. The ventilatory changes that precede and follow apnea closely resemble those occurring during periodic breathing.

The effects of continuous positive airway pressure (CPAP) on supraglottic and total pulmonary resistance were determined in 10 healthy premature infants (postconceptional age 34 +/- 2 wk, weight at study 1,628 +/- 250 g). Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a 5-Fr Millar or fluid-filled catheter. Nasal CPAP between 0 and 5 cmH2O correlated well with oropharyngeal pressure (r = 0.94). Total supraglottic resistance, total pulmonary resistance, and supraglottic resistance in inspiration and expiration were measured on increasing CPAP. Total supraglottic resistance decreased from 46 +/- 29 to 17 +/- 16 cmH2O.l-1.s (P less than 0.005) between 0 and 5 cmH2O CPAP, and a delay in return of resistance to control values was seen as CPAP was reciprocally decreased to 0. CPAP produced a decrease in supraglottic resistance in both inspiration and expiration, from 41 +/- 26 to 14 +/- 9 and from 33 +/- 17 to 10 +/- 6 cmH2O.l-1.s, respectively (P less than 0.01). Total pulmonary resistance also decreased from 161 +/- 40 to 95 +/- 24 cmH2O.l-1.s (P less than 0.01) between 0 and 5 cmH2O CPAP. The decrease in total supraglottic resistance in these infants accounted for 60% of the change in total pulmonary resistance, which occurred on CPAP of 5 cmH2O. We speculate that CPAP may decrease supraglottic resistance directly through mechanical splinting of the airway. This effect of CPAP may be the primary mechanism by which this form of therapy reduces apnea with an obstructive component in premature infants.

To determine the effect of varying approaches to the measurement of the respiratory disturbance index (RDI) on identification of sleep disordered breathing (SDB) in children. Cross-sectional study of SDB in a well-characterized birth cohort (stratified for term and preterm birth) participating in longitudinal studies of cognition and behavior. Community-based; overnight studies conducted in participant's homes. 433 children, ages 8-11 years, un-referred for clinical assessment of SDB. N/A. Participants underwent unattended overnight in-home recording of respiratory inductance plethysmography, pulse oximetry, body position, and heart rate. The relationships among RDIs derived from various definitions of apnea and hypopneas and thresholds for frequency of events were assessed. Median RDI varied by more than 20-fold for definitions using the more liberal criteria for event definition (all respiratory events; i.e., central or obstructive events and hypopneas with no requirement for ...

Purpose: Preterm infants have an increased prevalence of sleep disordered breathing (SDB) at school age (4.7%) and in young adulthood (13%) (Rosen 2003, Paavonen 2007). We aimed to describe the prevalence of pediatric SDB symptoms in a novel population of VLBW premature infants. In addition, we aimed to identify neonatal risk factors for SDB symptoms, including early exposure to hypoxia and hyperoxia, because animal studies have shown that early intermittent hypoxia affects breathing control later in life. Methods: Our cohort of inborn patients with GA <28wks was prospectively recruited from June 2005 to April 2009. Patients were placed on high resolution pulse oximetry monitors from birth up to eight weeks postnatal age. To evaluate hypoxia and hyperoxia, we calculated the percent time over the first four weeks of life that SaO2<80% and SaO2>98%. Patients were seen in follow-up at postnatal age of 18-22 months and parents completed two domains of the OSA-18 questionnaire f...

Retinopathy of prematurity [ROP] continues to be a significant clinical problem in preterm infants. There is a need for animal models to better understand the roles of hypoxia/hyperoxia in the pathogenesis and management of ROP. To test the hypothesis that multiple daily cycles of intermittent hypoxia, followed by brief hyperoxia, would provide a clinically relevant protocol for generation of ROP in a rat pup. Rat pups were exposed for the first 14 days to one of three protocols: room air [RA], sustained cycles of hyperoxia/hypoxia [SHH] as previously employed to produce ROP in rat pups, and intermittent hypoxia/hyperoxia [IHH] in order to more closely simulate clinical conditions in preterm infants. Retinae were obtained at 18 days and imaged for both avascularization and neovascularization. As expected, the SHH group demonstrated significantly increased avascularity [40.9 ± 7.9% of retina] which was minimal in both RA and IHH groups. All SHH exposed pups exhibited neovascularizati...

Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with...

Neonatal chronic intermittent hypoxia (CIH) enhances the ventilatory sensitivity to acute hypoxia (acute hypoxic ventilatory response, HVR), whereas sustained hypoxia (SH) can have the opposite effect. Therefore, we investigated whether neonatal rats pre-treated with SH prior to CIH exhibit a modified HVR. Rat pups were exposed to CIH (5% O2/5min, 8h/day) between 6 and 15 days of postnatal age (P6-15) after pre-treatment with either normoxia or SH (11% O2; P1-5). Using whole-body plethysmography, the acute (5min, 10% O2) HVR at P16 (1 day post-CIH) was unchanged following CIH (67.9±6.7% above baseline) and also SH (58.8±10.5%) compared to age-matched normoxic rats (54.7±6.3%). In contrast, the HVR was attenuated (16.5±6.0%) in CIH exposed rats pre-treated with SH. These data suggest that while neonatal SH and CIH alone have little effect on the magnitude of the acute HVR, their combined effects impose a synergistic disturbance to postnatal development of the HVR. These data could provide important insight into the consequences of not maintaining adequate levels of oxygen saturation during the early neonatal period, especially in vulnerable preterm infants susceptible to frequent bouts of hypoxemic events (CIH) that are commonly associated with apnea of prematurity.

To test the hypothesis that the effect of red blood cell (RBC) transfusion on intermittent hypoxemia (IH) in extremely low birth weight (ELBW) infants is dependent on postnatal age. Oxygen saturation of 130 ELBW infants, who required transfusion, was monitored continuously for the first 8 weeks of life. We compared the characteristics of IH (SpO2⩽80% for ⩾4 s and ⩽3 min), 24 h before and both 24 h and 24 to 48 h after each RBC transfusion at three distinct time periods: Epoch 1, 1 to 7 days; Epoch 2, 8 to 28 days; and Epoch 3, >28 days. In Epoch 1, the frequency and severity of IH events were not significantly different before and after transfusion. In both Epochs 2 and 3 there was a decrease in IH frequency and severity 24 h after RBC transfusion that persisted for 48 h. In addition, there was a decrease in the overall time spent with SpO2 ⩽80% which persisted for 24 h after transfusion in Epochs 1 and 3, and for 48 h in Epoch 3. The benefit of RBC transfusion on IH is age dependent as improvement in the frequency and severity of IH after transfusion only occurs beyond the first week of life. These observations will aid clinician's decision making by clarifying the benefit of RBC transfusions on patterns of oxygenation in preterm infants.

Preterm infants with neonatal lung injury are prone to wheezing and are often treated with β2-adrenergic receptor (β-AR) agonists although the benefits of β-AR agonists may be lost with chronic use. To investigate if repeated β-AR agonist exposure downregulates β-ARs in the immature lung resulting in a decreased response to bronchodilator rescue and whether hyperoxic exposure aggravates this response. Newborn mice were raised for 21 days in 60 or 21% oxygen and received daily aerosols of formoterol or saline. Respiratory system resistance (Rrs) and compliance (Crs) were measured in response to methacholine challenge and rescue bronchodilation with levalbuterol. Western blot analysis quantified the relative amount of lung β-ARs. Hyperoxia increased the airway reactivity to methacholine. Animals raised in hyperoxia that received daily formoterol were most sensitive to methacholine and exhibited a blunted response to levalbuterol bronchodilation. Hyperoxia-exposed animals receiving daily formoterol versus saline showed a significant decrease in the relative amount of lung β-ARs. In this hyperoxia-exposed neonatal mouse model, repeated β-AR agonist treatments increased the airway reactivity and attenuated the response to a rescue bronchodilator. The blunted bronchodilator response could be explained by a reduced quantity of lung β-ARs. Our findings may account for the time-dependent decrease in the therapeutic benefit of β-AR agonists in preterm infants with neonatal lung injury, which may have clinical consequences for patients already prone to airway hyperreactivity.

The effects of recurrent hypoxia on cardiorespiratory reflexes were characterized in anesthetized piglets at 2-10 d (n=15), 2-3 weeks (n=11) and 8-10 weeks (n=8). Responses of phrenic and hypoglossal electroneurograms (ENG(phr) and ENG (hyp)) to hypoxia (8% 0(2), bal N(2), 5 min), hypercapnia (7% CO(2) bal O(2), 5 min) and intravenous capsaicin were tested before and after recurrent exposure to 11 episodes of hypoxia (8% O(2) bal N(2), 5 min). In piglets 2-10 d, ENG(phr) response to hypoxia declined in proportion to the number of hypoxic exposures; however, ENG (hyp) response to hypoxia was unchanged. In piglets at 2-10 d, intracisternal injection of bicuculline (GABA(A) receptor antagonist) reversed effects of recurrent hypoxia on ENG(phr) hypoxic response, eliminated apnea during hypoxia, as well as the delay in appearance of ENG(phr) after hypoxia. The ENG(phr) response to 7% CO(2) inhalation also decreased after recurrent hypoxia; however, the ENG(phr) response to C-fiber stimulation by capsaicin was unaltered. Piglets at 2-3 and 8-10 weeks were resistant to the depressive effects of recurrent hypoxia on respiratory reflex responses. We conclude that the response of the anesthetized newborn piglet to recurrent hypoxia is dominated by increasing inhibition of phrenic neuroelectrical output during successive hypoxic exposures. Central GABAergic inhibition may contribute significantly to the cumulative effects of repeated hypoxia in the newborn piglet experimental model.

Episodes of apnea, desaturation, and bradycardia are common in preterm infants. Such infants who have persistent cardiorespiratory events detected by clinical bedside monitoring often are referred for overnight apnea monitoring studies. To characterize apnea, bradycardia, and desaturation events in infants referred for an overnight apnea monitoring study and compare them with corresponding events in control infants of similar age and weight with no bedside monitor alarms. Twelve-hour bedside apnea monitoring studies were performed on 68 preterm infants before hospital discharge. This population included 35 infants who were referred by their attending physicians because of persistent bedside monitor alarms (referral group) and 33 infants who had no documented cardiorespiratory events for at least 2 days before the study (control group). Each study monitored respiration via respiratory inductance plethysmography, oxygen saturation (Sao2), and heart rate. Events were defined as meeting 1 of the following criteria: apnea > or =20 seconds, bradycardia < or =80 beats per minute, or Sao2 < or =80%. The incidence of apnea > or =20 seconds was low, with no significant difference between infant groups. Referral infants exhibited a higher occurrence of desaturation episodes (20 +/- 6 vs 6 +/- 3 episodes/12-hour study) and a higher occurrence of bradycardia episodes (4.3 +/- 0.8 vs 1.1 +/- 0.3 episodes/12-hour study) than controls. These episodes of desaturation and bradycardia were always preceded by a respiratory pause, which was shorter in the referral infants (10.0 +/- 0.4 seconds vs 12.0 +/- 1.0 seconds). Baseline Sao2 was lower in referrals than controls (95 +/- 1% vs 98 +/- 1%), and the incidence of periodic breathing was significantly higher. Infants referred for apnea monitoring studies because of persistent bedside monitor alarms have very infrequent prolonged apnea but a higher frequency of desaturation and bradycardia in response to short respiratory pauses than infants without persistent bedside monitor alarms. Referral infants also exhibit a lower baseline Sao2. These abnormalities in oxygenation and cardiorespiratory control may be markers for subtle residual lung disease or functional central nervous system abnormalities.

To examine the temporal relationship between apnea and gastroesophageal reflux (GER) and to assess the effect of GER on apnea duration. A total of 119 preterm infants underwent 12-hour cardiorespiratory monitoring studies using respiratory inductance plethysmography, heart rate, oxygen saturation (SaO2), and esophageal pH. The studies were scored for GER (pH <4 for > or =5 seconds) and apnea > or =15 seconds or > or =10 seconds that occurred within 30 seconds of GER. Apnea > or =10 seconds was used to assess whether GER would prolong apnea duration. There were 6255 episodes of GER. Only 1% of GER episodes were associated with apnea > or =15 seconds, and there was no difference in apnea rate before, during, or after GER. There was also no difference in rate of apnea > or =10 seconds before versus during GER; however, there was a decrease in apnea rate immediately after GER. The presence of GER during apnea did not prolong apnea duration, and GER had no effect on the lowest SaO2 or heart rate during apnea. There is no evidence of a temporal relationship between acid-based GER and apnea in preterm infants. In addition, GER does not prolong apnea duration and does not exacerbate the resultant decrease in heart rate and SaO2.

ABSTRACT Eighteen very-low-birth-weight (VLBW) infants who met study criteria were observed during routinely scheduled feedings, twice in one day, once with a nasogastric (NG) tube and once without, in random order. Breathing and sucking measurements were compared with and without NG tube placement. During the prefeed period, minute ventilation and tidal volume were significantly lower with an NG tube than without the tube. During the continuous sucking (CS) period after commencement of oral feeding, minute ventilation, tidal volume, pulse rate, and oxygen saturation were also lower with the tube. During both CS and subsequent intermittent sucking periods, infants sucked less forcefully and took less formula with the tube. Based on these findings, if VLBW infants have an NG tube in place, clinicians are urged to monitor for breathing compromise, oxygen desaturation, and bradycardia during oral feeding.

Gastroesophageal reflux (GER) and apnea are both common occurrences in premature infants but their relationship is controversial. We present the evidence for and against an association between GER and apnea and discuss the merits and limitations of the various methodologies employed in characterizing such a relationship. Overall, GER and apnea do not appear temporally related in preterm infants, despite strong physiologic evidence that stimulation of laryngeal afferents elicits central apnea and laryngeal adduction. In a subpopulation of infants with neurodevelopmental compromise, there may be an increased incidence of both apnea and GER, although the direct association between GER and apnea in this population is unclear. Therefore, we believe there is no evidence to support widespread use of anti-reflux medications in the treatment of apnea in preterm infants. Further studies are needed to clarify the existence of a small subpopulation of infants who may have GER-induced apnea, to identify potential triggering mechanisms, and to document benefit from newer pharmacological approaches.

The purpose of this study was to analyze a targeted screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDdef) and clinical outcomes of G6PD-deficient vs G6PD normal newborns. Retrospective chart review for 1578 male newborns was performed. The study group was those screened for G6PDdef. Comparisons between G6PD-deficient and normal infants were made with χ (2)-test and unpaired t-test. A total of 1095 male newborns were screened, 11.1% had G6PDdef. 97.8% of screen results were reported by 48 h. Total bilirubin (TB) levels in deficient infants were significantly higher than in normal infants throughout birth hospitalization and they were more likely to receive phototherapy. Nineteen screened newborns were rehospitalized for hyperbilirubinemia, 47% had G6PDdef. In-hospital newborn screening for G6PDdef with rapid turnaround time is possible. G6PDdef is a risk factor for hyperbilirubinemia in American newborns. US centers with large at-risk populations can identify newborns at risk for severe hyperbilirubinemia with similar screening.

This study was designed to determine whether increased respiratory drive induced by inhalation of carbon dioxide would alter the reflex and voluntary components of feeding. For 10 preterm infants (mean +/- SD: postconceptional age at study, 34 +/- 2 weeks; weight, 2.1 +/- 0.2 kg), four trials of nutritive feeding were offered: two while the infants were inhaling a gas mixture containing 40% oxygen and two while the infants were breathing 40% oxygen and 7% carbon dioxide. Nasal airflow was monitored with a pneumotachygraph. Pressure-sensitive catheters in the esophagus and in the feeding nipple were used to detect swallowing and sucking. Sucking frequency and pattern, rate of swallowing, end-tidal carbon dioxide, and minute ventilation were recorded for 30-second epochs during feeding. When the inhaled gas mixture was switched from 40% oxygen to 40% oxygen and 7% carbon dioxide, sucking frequency decreased from 53 +/- 10 to 48 +/- 12 and from 54 +/- 12 to 40 +/- 19 sucks/min, respectively (p < 0.005). Frequency of swallowing also fell during the two feeding epochs on 7% carbon dioxide, from 45 +/- 15 to 40 +/- 15 and from 43 +/- 14 to 31 +/- 16 swallows/min (p < 0.003). Thus acute hypercapnea was accompanied by a decrease in rate of both sucking and swallowing during nutritive feeding. Increased ventilatory drive may directly inhibit nutritive feeding behavior in premature infants.

We tested the hypothesis that healthy preterm infants have attenuated ventilatory responses to hypercapnia, associated with a decreased rib cage contribution to ventilation, in the supine versus prone position. We elicited hypercapnic ventilatory responses from 19 healthy preterm infants (postconceptional age 35 +/- 1 weeks) who were being prepared for hospital discharge. The O2 saturation was continuously monitored. Before and during CO2 rebreathing, ventilation was measured with a nasal mask pneumotachygraph and was derived from chest wall motion as determined by respiratory inductance plethysmograph. This measuring method allowed us to compare both ventilation and the percentage rib cage contribution to ventilation between supine and prone positions. Statistical analysis employed analysis of variance with repeated measures. The supine position was associated with a higher respiratory rate (p < 0.02) and lower O2 saturation (p < 0.007) than the prone position. The increase in ventilation in response to hypercapnia was lower in the supine than in the prone position. This was statistically significant for the respiratory inductance plethysmograph (p < 0.008) but not the pneumotachygraph (p = 0.077), and was associated with a smaller rib cage contribution to ventilation in the supine than in the prone position (p < 0.0001). Respiratory control may be vulnerable when healthy preterm infants are placed supine. Widespread avoidance of the prone position may not be appropriate for such patients.

To characterize postnatal maturation of the biphasic ventilatory response to hypoxia in order to determine whether it persists beyond the first weeks of life in preterm infants, and the contributions of respiratory frequency and tidal volume to this response. Stable preterm infants were studied at two postnatal ages, 2 to 3 weeks (n = 12) and 4 to 8 weeks (n = 12), before hospital discharge at 35 weeks (range, 33 to 38 weeks) of postconceptional age. Infants were exposed to 5 minutes of 15% (or 13%) inspired oxygen; ventilation, oxygen saturation, end-tidal partial pressure of carbon dioxide, and heart rate were simultaneously recorded. Minute ventilation exhibited a characteristic biphasic response to hypoxia at both postnatal ages, regardless of the development of periodic breathing. At both ages there was a transient increase in tidal volume, which peaked at 1 minute, accompanied by a sustained decrease in respiratory frequency as a result of significant prolongation of expiratory time. The characteristic biphasic ventilatory response to hypoxia persists into the second month of postnatal life in preterm infants. We speculate that this finding is consistent with the prolonged vulnerability of such infants to neonatal apnea.

To characterize hypoxemic episodes in very low birth weight infants with mechanically ventilated lungs and to describe their natural history and the effect of body position. Tidal volume, respiratory rate, oxygen saturation, heart rate, and body movement were continuously recorded in 10 very low birth weight infants who exhibited episodes of hypoxemia during mechanical ventilation (birth weight, 810 +/- 133 gm; postconceptional age at study, 30 +/- 1.6 weeks). Frequency of hypoxemic episodes was compared in both prone and supine positions. Seventy-eight percent of hypoxemic episodes began in association with body movement as well as heart rate acceleration. Thereafter the spontaneous and delivered minute ventilation both decreased during the first 15 seconds of hypoxemia. The former decrease was due to a significant decrease in frequency of spontaneous respiration, whereas the latter was associated with a significant decrease in delivered tidal volume. Minute ventilation returned to normal before recovery of oxygenation. A change in body position from supine to prone significantly decreased the frequency of hypoxemic episodes. Hypoxemic episodes in infants who are on ventilatory support are characterized by (1) movement and cardioacceleration at initiation; (2) a decrease in both spontaneous and delivered minute ventilation, and (3) a lower incidence in the prone position. We speculate that spontaneous movement during sleep can trigger cardiopulmonary reflex responses that initiate and propagate these episodes.

Correlate the ventilatory response of preterm infants to hypoxic exposure with incidence of neonatal apnea. Study design Seventeen stable convalescing premature infants underwent bedside cardiorespiratory monitoring of respiration using respiratory inductance plethysmography, heart rate, and oxygen saturation (SaO(2)) for a 12-hour period. These studies were scored for number of apneas > or =15 and > or =20 seconds. Infants then underwent a 3-minute hypoxic exposure. Minute ventilation (V(E)) was calculated for 30-second epochs from the time inspired oxygen reached 15%. Linear regression analysis was used to correlate the change in V(E) normalized for decrease in SaO(2) (DeltaV(E)/DeltaSaO(2)) during the first and third minutes of hypoxic exposure with the number of apneic episodes during the 12-hour study. The majority of infants exhibited an anticipated biphasic ventilatory response to hypoxia. There was a significant positive correlation between DeltaV(E)/DeltaSaO(2) during the first and third minutes of hypoxic exposure and number of apneic episodes > or =15 and > or =20 seconds during the preceding 12 hours. Preterm infants with a greater number of apneic episodes exhibit an increased ventilatory response to hypoxic exposure, suggesting that apnea of prematurity may be associated with enhanced peripheral chemoreceptor activity.

Cup-feeding is recommended for breastfed preterm infants to avoid artificial nipples. However, the oral mechanisms used in cup-feeding, or its safety and efficacy, have not been described. The authors measured sipping, breathing, SaO2, and volume of intake during 15 cup-feeding sessions for 8 infants (mean gestational age at birth was 30.6 weeks). Mean duration of sipping bursts and pauses was 3.6 seconds and 28.1 seconds, respectively. Mean breathing rate during bursts and pauses was similar (46.2 +/- 24.3 vs 45.7 +/- 17.7, respectively), with SaO2 > or = 90% during all bursts. Mean duration of cup-feedings was 15.2 +/- 3.9 minutes (range, 11.0-23.3), whereas mean volume of intake was only 4.6 +/- 2.2 mL (range, 1.5-8). For the 15 sessions, 38.5% of milk taken from the cup was recovered on the bib. Although infants remain physiologically stable, cup-feeding has questionable efficacy and efficiency. Differentiating between actual intake versus spillage of milk merits attention.