Assisted ventilation immediately after birth with self-inflating bag versus T-piece resuscitator in preterm infants.

OBJECTIVE: To compare proportions of target range tidal volumes achieved with the self-inflating bag vs. the T-piece in resuscitation of preterm newborns at delivery. STUDY DESIGN: This randomized controlled trial was conducted at a tertiary Children's Hospital. 20 preterm infants≤32 weeks' gestational age with no congenital anomalies who needed positive pressure ventilation after birth were enrolled. Positive pressure ventilation was provided with the self-inflating bag or T-piece resuscitator. The primary outcome was proportion of inflations within a target range of 4-8 ml/kg. Chi-square and logistical regression analyses were performed. RESULTS: In the self-inflating bag (SIB) group 29% of inflations (117/419) and in the T-Piece (TP) group 51% of inflations (300/590) delivered expiratory tidal volume (TVe) of 4-8 ml/kg (p < 65.001). In the SIB group 60% of all inflations (254/419), and in the TP group 35% of all inflations (204/590) delivered TVe < 4 ml/kg (p < 0.001). In the SIB group 11% of all inflations (48/419), and in the TP group, 15% of all inflations (86/590) delivered TVe > 8 ml/kg (p = 0.18). The OR of having expiratory tidal volume of 4-8 ml/kg using the T-piece was 1.8 (CI 1.1-3.1), p = 0.02. CONCLUSION: Manual inflations provided by the TP deliver expiratory tidal volumes in the range of 4-8 ml/kg more consistently than SIB.

Cerebral Venous Thrombosis in COVID-19: A New York Metropolitan Cohort Study.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is associated with hypercoagulability. We sought to evaluate the demographic and clinical characteristics of cerebral venous thrombosis among patients hospitalized for coronavirus disease 2019 (COVID-19) at 6 tertiary care centers in the New York City metropolitan area. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study of 13,500 consecutive patients with COVID-19 who were hospitalized between March 1 and May 30, 2020. RESULTS: Of 13,500 patients with COVID-19, twelve had imaging-proved cerebral venous thrombosis with an incidence of 8.8 per 10,000 during 3 months, which is considerably higher than the reported incidence of cerebral venous thrombosis in the general population of 5 per million annually. There was a male preponderance (8 men, 4 women) and an average age of 49 years (95% CI, 36-62 years; range, 17-95 years). Only 1 patient (8%) had a history of thromboembolic disease. Neurologic symptoms secondary to cerebral venous thrombosis occurred within 24 hours of the onset of the respiratory and constitutional symptoms in 58% of cases, and 75% had venous infarction, hemorrhage, or both on brain imaging. Management consisted of anticoagulation, endovascular thrombectomy, and surgical hematoma evacuation. The mortality rate was 25%. CONCLUSIONS: Early evidence suggests a higher-than-expected frequency of cerebral venous thrombosis among patients hospitalized for COVID-19. Cerebral venous thrombosis should be included in the differential diagnosis of neurologic syndromes associated with SARS-CoV-2 infection.

Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

BACKGROUND: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). METHODS: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. RESULTS: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. CONCLUSION: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

Early Pulse Oximetry Data Improves Prediction of Death and Adverse Outcomes in a Two-Center Cohort of Very Low Birth Weight Infants.

BACKGROUND: We previously showed, in a single-center study, that early heart rate (HR) characteristics predicted later adverse outcomes in very low birth weight (VLBW) infants. We sought to improve predictive models by adding oxygenation data and testing in a second neonatal intensive care unit (NICU). METHODS: HR and oxygen saturation (SpO2) from the first 12 hours and first 7 days after birth were analyzed for 778 VLBW infants at two NICUs. Using multivariate logistic regression, clinical predictive scores were developed for death, severe intraventricular hemorrhage (sIVH), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (tROP), late-onset septicemia (LOS), and necrotizing enterocolitis (NEC). Ten HR-SpO2 measures were analyzed, with first 12 hours data used for predicting death or sIVH and first 7 days for the other outcomes. HR-SpO2 models were combined with clinical models to develop a pulse oximetry predictive score (POPS). Net reclassification improvement (NRI) compared performance of POPS with the clinical predictive score. RESULTS: Models using clinical or pulse oximetry variables alone performed well for each outcome. POPS performed better than clinical variables for predicting death, sIVH, and BPD (NRI > 0.5, p < 0.01), but not tROP, LOS, or NEC. CONCLUSION: Analysis of early HR-SpO2 characteristics adds to clinical risk factors to predict later adverse outcomes in VLBW infants.

Non-invasive inhaled nitric oxide in the treatment of hypoxemic respiratory failure in term and preterm infants.

OBJECTIVES: Inhaled nitric oxide (iNO) is effective in conjunction with tracheal intubation (TI) and mechanical ventilation (MV) for treating arterial pulmonary hypertension and hypoxemic respiratory failure (HRF) in near-term and term newborns. Non-invasive respiratory support with nasal continuous positive airway pressure (CPAP) is increasingly used to avoid morbidity associated with TI and MV, yet the effectiveness of iNO delivery via nasal CPAP remains unknown. To evaluate the effectiveness of iNO delivered via the bubble nasal CPAP system in term and preterm newborns with HRF. STUDY DESIGN: Electronic medical records from all infants admitted to the neonatal intensive care unit (NICU) during 2005 to 2014 (n=10, 895) were screened for treatment with iNO therapy for HRF. Detailed data on population characteristics and cardiorespiratory, iNO and respiratory support indices were abstracted for all infants, who were administered iNO non-invasively using bubble nasal CPAP. Change in relevant indices at baseline (before initiating non-invasive iNO) and at 3, 6, 12 and 24 h after non-invasive iNO therapy were analyzed using repeated measures analysis of variance. RESULTS: Of 795 infants treated with iNO (7.3% of total NICU admissions) over a 10-year period, 107 infants (13.4% of iNO treated) with birth weight 2448±1112 g and gestational age 35.3±5.8 weeks received iNO non-invasively. 25 infants received iNO exclusively non-invasively, whereas in remaining 82 infants non-invasive route followed invasive delivery via TI and MV. Indications for using non-invasive iNO included idiopathic pulmonary hypertension (39%), congenital heart disease (37%), bronchopulmonary dysplasia (10%), meconium aspiration syndrome (9%) and congenital diaphragmatic hernia (5%). Over the 24 h following initiation of non-invasive iNO, fractional oxygen requirements decreased (0.38 to 0.32; P<0.0005) and SpO2 increased (90.7 to 91.6%; P<0.01) with no significant changes in heart rate, respiratory rate, blood pressure, pH and PaCO2. On average non-invasive iNO was initiated on day of life 9 with a maximal dose was 20 p.p.m. The average duration of iNO therapy and the duration over which it was weaned off were 134 and 51 h, respectively. Analysis of environmental gases during non-invasive iNO therapy revealed median ambient nitrogen dioxide and nitric oxide levels of 0.30 and 0.01 p.p.m., respectively. CONCLUSIONS: Initiation of iNO in infants on bubble nasal CPAP or continuation of iNO in infants transitioning from MV to bubble nasal CPAP is associated with improved oxygenation during HRF in term and preterm infants. Non-invasive iNO may have a synergistic effect with airway recruitment strategies such as nasal CPAP.

Novel heart rate parameters for the assessment of autonomic nervous system function in premature infants.

Autonomic nervous system (ANS) balance is a key factor in homeostatic control of cardiac activity, breathing and certain reflex reactions such as coughing, sneezing and swallowing and thus plays a crucial role for survival. ANS impairment has been related to many neonatal pathologies, including sudden infant death syndrome (SIDS). Moreover, some conditions have been identified as risk factors for SIDS, such as prone sleep position. There is an urgent need for timely and non-invasive assessment of ANS function in at-risk infants. Systematic measurement of heart rate variability (HRV) offers an optimal approach to access indirectly both sympathetic and parasympathetic influences on ANS functioning. In this paper, data from premature infants collected in a sleep physiology laboratory in the NICU are presented: traditional and novel approaches to HRV analyses are applied and compared in order to evaluate their relative merits in the assessment of ANS activity and the influence of sleep position. Indices from time domain and nonlinear approaches contributed as markers of physiological development in premature infants. Moreover, significant differences were observed as a function of sleep position.

A possible alternative to the error prone modified Hodge test to correctly identify the carbapenemase producing Gram-negative bacteria.

CONTEXT: The modified Hodge test (MHT) is widely used as a screening test for the detection of carbapenemases in Gram-negative bacteria. This test has several pitfalls in terms of validity and interpretation. Also the test has a very low sensitivity in detecting the New Delhi metallo-ß-lactamase (NDM). Considering the degree of dissemination of the NDM and the growing pandemic of carbapenem resistance, a more accurate alternative test is needed at the earliest. AIMS: The study intends to compare the performance of the MHT with the commercially available Neo-Sensitabs - Carbapenemases/Metallo-ß-Lactamase (MBL) Confirmative Identification pack to find out whether the latter could be an efficient alternative to the former. SETTINGS AND DESIGN: A total of 105 isolates of Klebsiella pneumoniae resistant to imipenem and meropenem, collected prospectively over a period of 2 years were included in the study. SUBJECTS AND METHODS: The study isolates were tested with the MHT, the Neo-Sensitabs - Carbapenemases/MBL Confirmative Identification pack and polymerase chain reaction (PCR) for detecting the blaNDM-1 gene. RESULTS: Among the 105 isolates, the MHT identified 100 isolates as carbapenemase producers. In the five isolates negative for the MHT, four were found to produce MBLs by the Neo-Sensitabs. The Neo-Sensitabs did not have any false negatives when compared against the PCR. CONCLUSIONS: The MHT can give false negative results, which lead to failure in detecting the carbapenemase producers. Also considering the other pitfalls of the MHT, the Neo-Sensitabs--Carbapenemases/MBL Confirmative Identification pack could be a more efficient alternative for detection of carbapenemase production in Gram-negative bacteria.

Traumatic and spontaneous carotid and vertebral artery dissection in a level 1 trauma center.

This study aimed to compare traumatic and spontaneous carotid artery dissection (CAD) and vertebral artery dissection (VAD) with respect to age, pre-morbid risk factors, and site of dissection. Chart review was performed for 49 patients with CAD and VAD admitted to Westchester Medical Center, a level 1 trauma center, from 1999 to 2007. Presentation was categorized into traumatic (n=28, 57%) or spontaneous dissection (n=21, 43%). Pre-morbid risk factors were analyzed. Location of dissection was identified and categorized into four possible segments. Patients with spontaneous dissection were likely to be over the age of 50 years (p<0.05), and had significantly higher proportions of coronary artery disease (33% compared to 7%, p<0.05), hypertension (57% compared to 18%; p<0.01), and hypercholesterolemia (29% compared to 0%; p<0.01). Of the 49 patients, 42 had imaging studies available for segmental analysis. In both traumatic CAD and VAD, dissection at Segment III (corresponds with the first and second cervical vertebrae), was the most common site (37.5% and 50%, respectively, p<0.05). In contrast, Segment I (origin of the vessel to the fifth cervical vertebrae) was the most common site for spontaneous CAD and VAD (55% and 77%, respectively, p<0.05). This cross-sectional study suggests that etiology plays an important role in the location of dissection. Traumatic CAD and VAD occur most commonly in Segment III. Spontaneous CAD and VAD occur most commonly in Segment I and are associated with increasing age and premorbid cerebrovascular risk factors.

Interactions among peripheral perfusion, cardiac activity, oxygen saturation, thermal profile and body position in growing low birth weight infants.

AIMS: To investigate the correlation between the 'perfusion index' (PI) and other commonly used estimates of cutaneous blood flow [heart rate (HR), surface temperatures (ST) and central-to-peripheral thermal gradients (C-P grad)] and to use this new non-invasive tool to compare differences between prone and supine sleep position in low birth weight (LBW) infants. METHODS: Six-hour continuous recordings of pulse oximetry, cardiac activity and absolute ST from three sites (flank, forearm and leg), along with minute-to-minute assessment of behavioural states were performed in 31 LBW infants. Infants were randomly assigned to the prone or supine position for the first 3 h and then reversed for the second 3 h. PI data were correlated with HR and C-P grad, and compared across sleep positions during quiet sleep (QS) and active sleep (AS). RESULTS: Perfusion index correlated significantly with HR (r(2) = 0.40) and flank-to-forearm thermal gradient (r(2) = 0.28). In the prone position during QS, infants exhibited higher PI (3.7 +/- 0.9 vs. 3.1 +/- 0.7), HR (158.4 +/- 8.9 vs. 154.1 +/- 8.8 bpm), SpO(2) (95.8 +/- 2.6 vs. 95.2 +/- 2.6%), flank (36.7 +/- 0.4 vs. 36.5 +/- 0.4 degrees C), forearm (36.1 +/- 0.6 vs. 35.5 +/- 0.4 degrees C) and leg (35.4 +/- 0.7 vs. 34.7 +/- 0.7 degrees C) temperatures and narrower flank-to-forearm (0.6 +/- 0.4 vs. 0.9 +/- 0.3 degrees C) and flank-to-leg (1.3 +/- 0.6 vs. 1.8 +/- 0.7 degrees C) gradients, compared to those of the supine position. Similar differences were observed during AS. CONCLUSION: Perfusion index is a good non-invasive estimate of tissue perfusion. Prone sleeping position is associated with a higher PI, possibly reflecting thermoregulatory adjustments in cardiovascular control. The effects of these position-related changes may have important implications for the increased risk for sudden infant death syndrome in prone position.

Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections.

The search for newer more cost effective treatments for infectious diseases remains a challenge. Cytomegalovirus (CMV) infection, which is especially common in the immunosupressed, is an important challenge for treating physicians. Gangciclovir's cost is a major hurdle in developing countries. Leflunomide is cheaper and is easily given orally. It works by a novel mechanism inhibiting virion assembly. It also has immunosuppressive properties. It and has been shown to be effective in both gangciclovir sensitive as well as resistant cases of CMV infection. Given these considerations we believe that leflunomide is an exiting new drug for CMV infection. However, hepatotoxicity and teratogenicity are known side effects. The exact dose and duration of treatment for CMV infection, for secondary prophylaxis, and in situations of gangciclovir resistance need further study.

Sleeping position and electrocortical activity in low birthweight infants.

OBJECTIVE: To evaluate the effects of prone and supine sleeping positions on electrocortical activity during active (AS) and quiet (QS) sleep in low birthweight infants. DESIGN: Randomised/crossover study. SETTING: Infant Physiology Laboratory at Children's Hospital of New York. PATIENTS: Sixty three healthy, growing, low birthweight (birth weight 795-1600 g) infants, 26-37 weeks gestational age. INTERVENTIONS: Six hour continuous two channel electrocortical recordings, together with minute by minute behavioural state assignment, were performed. The infants were randomly assigned to prone or supine position during the first three hours, and positions were reversed during the second three hours. OUTCOME MEASURES AND RESULTS: Fast Fourier transforms of electroencephalograms (EEGs) were performed each minute and the total EEG power (TP), spectral edge frequency (SEF), absolute (AP) and relative (RP) powers in five frequency bands (0.01-1.0 Hz, 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz) were computed. Mean values for TP, SEF, AP, and RP in the five frequency bands in the prone and supine positions during AS and QS were then compared. In the prone sleeping position, during AS, infants showed significantly lower TP, decreased AP in frequency bands 0.01-1.0 Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz, increased RP in 1-4 Hz, and a decrease in SEF. Similar trends were observed during QS, although they did not reach statistical significance. CONCLUSIONS: The prone sleeping position promotes a shift in EEG activity towards slower frequencies. These changes in electrocortical activity may be related to mechanisms associated with decreased arousal in the prone position and, in turn, increased risk of sudden infant death syndrome.

Motion resistant pulse oximetry in neonates.

BACKGROUND: Pulse oximetry is widely used in neonates. However, its reliability is often affected by motion artefact. Clinicians confronted with questionable oxygen saturation (SpO(2)) values often estimate the reliability by correlating heart rate (HR) obtained with the oximeter with that obtained by electrocardiogram. OBJECTIVE: To compare the effects of motion on SpO(2) and HR measurements made with Masimo signal extraction technology and those made with a Nellcor N-200. DESIGN: Continuous pulse oximetry and HR monitoring were performed in 15 healthy, term infants (mean (SD) birth weight 3408 (458) g) undergoing circumcision, using Masimo and Nellcor pulse oximeters and a standard HR monitor (Hewlett-Packard). Simultaneous minute by minute behavioural activity codes were also assigned. Baseline data were collected for 10 minutes when the infant was quietly asleep and then continued during and after circumcision for a total duration of one hour. The oximeter HR and SpO(2) values were compared and related to HR values obtained by ECG during all three periods. The effect of behavioural activity on SpO(2) and HR was also evaluated. RESULTS: When compared with results obtained with the Nellcor, the mean SpO(2) and HR were higher and the incidence of artefact lower with the Masimo during all three periods. Masimo HR more accurately predicted HR obtained with a standard monitor, with lower residual error. SpO(2) and HR values obtained with the Nellcor were lower and more variable during all behavioural states, especially crying, when excessive motion artefact was most likely. CONCLUSIONS: The data suggest that Masimo signal extraction technology may offer improvement in pulse oximetry performance, particularly in clinical situations in which extreme motion artefacts are likely.

Frequency of perinatal transfer by day of the week and holidays.

OBJECTIVE: To describe the pattern of obstetric transfers to a rural tertiary center relative to weekends and holidays. METHODS: A 2-year retrospective cohort study. RESULTS: A total of 903 patients were received in transfer over the study period. Tuesday was the most frequent day (17.4%) for transfer and Sunday was the least frequent day (9.2%). Friday was the most frequent day for transfer of patients who did not deliver (18.6%) and Sunday the least frequent day for transfer (7.6%). Subset analysis by delivery status found no statistical difference in the frequency of transfer by delivery status and day of the week (p = 0.28). Tuesday had the highest mean at 1.51 +/- 1.13 and Sunday had the lowest mean at 0.8 +/- 0.89. No difference in transfer volume by day of the week was observed by ANOVA (p = 0.25). The number of transfers occurring around the 7 days surrounding the six major holidays averaged 7.67 +/- 3.63, which did not differ significantly from the weekly average of 8.59 +/- 2.74 (p = 0.29). CONCLUSION: There is no apparent bias to transfer of patients based on the day of the week or holidays. Individual assessment by regional centers may assist in planning for staffing of transport services and resources.

Effects of quality of energy intake on growth and metabolic response of enterally fed low-birth-weight infants.

Carbohydrate and fat may vary in their ability to support protein accretion and growth. If so, variations in the source of nonprotein energy might be used to therapeutic advantage in enterally fed low-birth-weight infants. To test the hypothesis that high-carbohydrate diets are more effective than isocaloric high-fat diets in promoting growth and protein accretion, low-birth-weight infants weighing 750-1600 g at birth were randomized in a double blind study to receive one of five formulas differing only in the quantity and quality of nonprotein energy. Groups 1, 2, and control received 130 kcal x kg(-1) x d(-1) with 35, 65, and 50% of the nonprotein energy as carbohydrate. Groups 3 and 4 received energy intake of 155 kcal x kg(-1) x d(-1) with 35 and 65% of the nonprotein energy as carbohydrate. Protein intake of all groups was 4 g x kg(-1) x d(-1). Growth and metabolic responses were followed weekly, and macronutrient balances including 6-h indirect calorimetry were performed biweekly. Greater rates of weight gain and nitrogen retention were observed at high-carbohydrate intake compared with high-fat intake at both gross energy intakes. Greater rates of energy storage and an increase in skinfold thickness were observed in group 4 (high-energy high-carbohydrate diet) despite higher rates of energy expenditure. These data support the hypothesis that at isocaloric intakes, carbohydrate is more effective than fat in enhancing growth and protein accretion in enterally fed low-birth-weight infants. However, a diet with high-energy and high-carbohydrate content also results in increased fat deposition.

Effects of quality of energy on substrate oxidation in enterally fed, low-birth-weight infants.

BACKGROUND: Carbohydrate and fat may differ in their ability to support energy-requiring physiologic processes, such as protein synthesis and growth. If so, varying the constituents of infant formula might be therapeutically advantageous. OBJECTIVE: We tested the hypothesis that low-birth-weight infants fed a diet containing 65% of nonprotein energy as carbohydrate oxidize relatively more carbohydrate and relatively less protein than do infants fed an isoenergetic, isonitrogenous diet containing 35% of nonprotein energy as carbohydrate. DESIGN: Sixty-two low-birth-weight infants weighing from 750 to 1600 g at birth were assigned randomly and blindly to receive 1 of 5 formulas that differed only in the quantity and quality of nonprotein energy. Formula containing 544 kJ x kg(-1) x d(-1) with either 50%, 35%, or 65% of nonprotein energy as carbohydrate was administered to control subjects, group 1, and group 2, respectively. Groups 3 and 4 received gross energy intakes of 648 kJ x kg(-1) x d(-1) with 35% and 65% of nonprotein energy as carbohydrate. Protein intake was targeted at 4 g x kg(-1) x d(-1). Substrate oxidation was estimated from biweekly, 6-h measurements of gas exchange and 24-h urinary nitrogen excretion. RESULTS: Carbohydrate oxidation was positively (r = 0.71, P < 0.0001) and fat oxidation was negatively (r = -0.46, P < 0.001) correlated with carbohydrate intake. Protein oxidation was negatively correlated with carbohydrate oxidation (r = -0.42, P < 0.001). Fat oxidation was not correlated with protein oxidation. Protein oxidation was less in infants receiving 65% of nonprotein energy as carbohydrate than in groups receiving 35% nonprotein energy as carbohydrate. CONCLUSION: These data support the hypothesis that energy supplied as carbohydrate is more effective than energy supplied as fat in sparing protein oxidation in enterally fed low-birth-weight infants.

Maturational changes in heart rate and heart rate variability in low birth weight infants.

To provide insight into the maturation of neural mechanisms responsible for variability in heart rate during quiet and active sleep, 6-hour continuous electrocardiographic recordings and simultaneous minute-by-minute behavioral activity state assignments were performed in 61 healthy, growing low birth weight infants. The infants weighed 795-1600 g at birth and ranged between 31-38 weeks in postconceptional age. During this age interval there was a decrease in heart rate during quiet sleep and an increase in both time domain and frequency domain measures of the variability in cardiac interbeat intervals. In quiet sleep, global variability, measured as SD of R-R intervals, increased in relation to age, as did higher frequency variability, measured as the square root of the mean of squared successive differences in R-R intervals. Developmental changes in the 0.5-2.0 Hz spectral power band of RR-interval variability, another measure of high frequency variability, paralleled the changes seen in the time domain measure. Evaluation of patterns of changes in the magnitude and direction of successive interbeat intervals provided evidence that the incidence of sustained accelerations or decelerations increased whereas the incidence of no change in consecutive RR-intervals decreased as infants matured. Among the various measures of heart rate variability, the incidence of sustained change and no change in successive interbeat intervals were most closely related to postconceptional age in both sleep states. The overall decrease in heart rate, increase in heart rate variability, and increase in the pattern of changes in interbeat interval with postconceptional age are consistent with the maturation of the autonomic cardio-regulatory activity from 31-38 weeks age.