Neonatal Apnea Research Articles

Impact of G-CSF on Outcomes of Pregnancy in Women with Severe Chronic Neutropenia

Abstract 4786Pregnancy in patients with severe chronic neutropenia is associated with high risk of spontaneous abortions. Patients and physicians often ask about benefits and safety of G-CSF administration during pregnancy. We therefore conducted a telephone survey of women of child-bearing potential with the diagnoses of congenital, cyclic, idiopathic or autoimmune neutropenia who are enrolled in the North American branch of the Severe Chronic Neutropenia International Registry (SCNIR).We identified 99 women who had 214 pregnancies before and on G-CSF for this cross sectional study, expanding our previous preliminary investigation, (Boxer et al, ASH abstract 2010). In this population, 31 women had pregnancies before availability of G-CSF, 35 were on long term G-CSF at the time of their pregnancies and 33 were taking G-CSF for some, but not all, of their pregnancies. For those on G-CSF during their pregnancies, the median G-CSF dose was 1.30 mcg/kg/day (mean dose 2.2 ± 0.4 [SEM] mcg/kg/day, dose range 0.1 to 28 mcg/kg/day). Treatment was administered throughout the pregnancy in 74% (49/65) of the pregnancies. Five percent (3/65) were treated only in the 1st trimester, 11% (7/65) were treated only in the last 2 trimesters, 5% (3/65) treated for the last trimester only, and 5% (3/65) treated in 2 of 3 trimesters (2 treated in 1st and 3rd trimesters, 1 treated in the 1st and 2nd trimesters). Sixty-two women with 137 pregnancies while not on G-CSF [congenital neutropenia (CN) N=3, cyclic neutropenia (CyN) N=15, idiopathic neutropenia (IN) N=43, autoimmune neutropenia (AN) N=1] were compared with 47 women having 77 pregnancies while on G-CSF therapy [CN=9, CyN=14, IN=21, AN=3].Pregnancies occurring in neutropenic women without G-CSF therapy had the following complications: premature labors (8), premature rupture of membranes (1), life-threatening infections (2), and minor infections (5). Patients on G-CSF during pregnancy reported no premature labors (0), no life threatening infections (0), minor infections (5), thrombocytopenia (1), placenta previa (1), abruptio placenta (1), and death following incomplete elective termination (1). By diagnostic category complications in the no G-CSF mothers occurred in 16 patients (CN=1, CyN=5, IN=9, AN=1), compared with nine in the G-CSF treated group (CN=1, CyN=4, IN=4). There were 31 spontaneous miscarriages in the women not on G-CSF (CyN=8, and IN=23) compared with 5 in the women (CyN=4, IN=1) on G-CSF.There were 93 live births from 137 pregnancies in the non G-CSF group. Thirteen of these infants had neonatal neutropenia. Other major neonatal complications in the no G-CSF group included significant infections (3) [meningitis 1, septicemias 2], minor infection (1), cerebral palsy associated with prematurity (1), respiratory distress syndrome (1), and collapsed lung (1). In the G-CSF treated group there were 65 live births from 77 pregnancies. Fifteen of these infants were neutropenic. Other complications in the G-CSF treated group included minor infections (2), abruptio placenta associated with neonatal apnea (1), and premature infants with associated complications (2). There were 2 congenital abnormalities: tracheal esophageal fistula (1) and hydronephrosis (1) in 65 live births, a frequency similar to the general population.This study showed that women with chronic neutropenia who were on G-CSF during pregnancy had a higher percentage of live births, 84% (65/77) than those not on G-CSF, 68% (93/137) (p=0.011, two tailed Fisher exact test). G-CSF therapy was associated with a lower number of spontaneous abortions, with a 6% (5/77) spontaneous abortion rate in the G-CSF treated group versus 23% (31/137) in the non G-CSF group (p=0.003, two tailed Fisher exact test). G-CSF therapy was also associated with a lower rate of serious maternal complications. Two common congenital anomalies (2/65) were observed in the offspring of the G-CSF treated mothers and no anomalies were observed in the offspring of the mothers not receiving G-CSF. Overall the newborns from the G-CSF treated mothers appeared to have fewer neonatal complications. Based on this analysis, we recommend that G-CSF therapy should be offered and continued during pregnancy in women with severe chronic neutropenia. The available data indicates that administration throughout pregnancy is well tolerated and protective of maternal health, including reducing the risk of infections and spontaneous abortions. Disclosures:Boxer:Amgen: Equity Ownership. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Heart Rate Characteristics Monitoring and Central Neonatal Apnea

Background: Heart rate characteristics monitoring using the HeRO score detects reduced variability and transient decelerations that occur prior to clinical signs of neonatal sepsis, and reduces VLBW mortality when displayed to clinicians. Neonatal apnea causes HR decelerations. Aim: We tested the hypothesis that central apneas are the cause of high HeRO scores. Methods: We fashioned an algorithm to detect central neonatal apnea that efficiently removes the cardiac component of the chest impedance signal. We identified 0.9 episodes per day lasting more than 30 sec and accompanied by bradycardia and desaturation in 1837 non-ventilated days in 105 VLBW infants in the University of Virginia NICU. Results: Severe central apneas accounted for only 17% of the variance in HeRO scores but were highly significant predictors of high HeRO score even after birth weight, Apgar, and hospital day were taken into account. Individual records (Figure), though, showed inconsistent temporal association of HeRO score (shade) and the number of severe apneas (line), here in an infant who died of lung disease - some but not all, synchronized with HeRO. Figure Conclusion: Frequent and severe central neonatal apneas can correlate with elevated HeRO scores, and may be partly causative. We speculate that abnormal heart rate control in sepsis may have mechanisms in addition to hypoxemia caused by central apnea.

Clinical Effects of Carnitin Supplementation on Hypoglycemia, Apnea and Sepsis in Very Low Birth Weight Neonates

Background Systemic carnitine deficiency may present with apnea, hypotonia, and poor growth. Premature infants often manifest these symptoms and are at risk of developing carnitine deficiency because of immaturity of the biosynthetic pathway, lack of sufficient predelivery transplacental transport, and lack of sufficient exogenous supplementation. Objective This study was undertaken to examine the effect of carnitine supplementation on hypoglycemia, apnea and sepsis in premature infants. Methods In this clinical study 60 preterm infants less than <1500 g birth weight were enrolled. The subjects in the carnitine group received 20 mg/kg/day oral supplemental by nasogastric tube in addition to routine nursing care within 96 hours of birth. Episodes of apnea, hypoglycemia and sepsis were the primary outcome measures recorded. The control group received routine nursing care. Results Episodes of apnea and the hypoglycemia were similar between the two groups. (P=0.55 and 0.69 respectively). Conclusion: In this study treatment with carnitine supplementation had no effect on apnea, hypoglycemia and sepsis in very low birth weight neonates.

Relationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea

Maternal smoking is associated with disturbed cardiorespiratory control in the infant. Despite lacking knowledge of whether the harmful effects of smoking are caused by combustion products in tobacco smoke or by nicotine, it has been argued that nicotine-replacement therapy during pregnancy is safer than smoking. The goal of this study was to investigate if the disturbances in cardiorespiratory control associated with maternal smoking are also seen in infants prenatally exposed to snuff. We hypothesized that prenatal nicotine exposure (via moist snuff) causes disturbances in autonomic control and thereby increases the risk of apnea in the newborn. In a nationwide Swedish cohort study, we studied associations between maternal tobacco use during pregnancy and neonatal apnea. Of 609 551 live-born singleton infants, 7599 were born to snuff-using mothers, 41 391 and 16 928 were born to light (1-9 cigarettes per day) and heavy (≥ 10 cigarettes per day) smokers, respectively. Logistic regression was used to calculate odds ratios, using 95% confidence intervals. Compared with infants of nontobacco users, infants with prenatal exposure to snuff were at an increased risk of apnea even after adjustment for differences in gestational age (odds ratio: 1.96 [95% confidence interval: [1.30-2.96]) Smoking was associated with increased risk of apnea before, but not after, adjusting for gestational age. Snuff use during pregnancy is associated with a higher risk of neonatal apnea than smoking. Maternal use of snuff or nicotine-replacement therapy cannot be regarded as an alternative to smoking during pregnancy.

Relationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea

Relationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea

Outcomes of Pregnancies for Women with Severe Chronic Neutropenia with or without G-CSF Treatment.

AbstractAbstract 1490There are currently no established guidelines for granulocyte colony stimulating factor (G-CSF) therapy during pregnancy for women with severe chronic neutropenia. To establish treatment recommendations, we reviewed records of women with the diagnoses of congenital, cyclic, idiopathic or autoimmune neutropenia and blood neutrophil counts chronically or recurrently <0.5 × 109/L who were enrolled in the North American branch of the Severe Chronic Neutropenia International Registry (SCNIR). We identified 88 women who had 183 pregnancies for this cross sectional study. We compared outcomes for women treated or not treated with G-CSF during their pregnancies.Fifty-five women [congenital neutropenia (CN) N=4, cyclic neutropenia (CyN) N=13, idiopathic neutropenia (IN) N=37, autoimmune neutropenia (AN) N=1] with 123 pregnancies while not on G-CSF therapy were compared with 41 women (CN =7, CyN=16, IN=15, AN=3) having 60 pregnancies while on G-CSF therapy.During pregnancy the patients not treated with G-CSF had the following complications: 6 premature labors, 1 premature rupture of membranes, 2 life-threatening infections, and 2 minor infections. The G-CSF treated group had no premature labors, no life threatening infections, 5 minor infections, and 1 patient developed severe thrombocytopenia. By diagnostic category the complications in the no G-CSF mothers occurred in 11 patients (IN=9, CyN=1, AN=1), compared with six in the G-CSF treated group (IN=3, CyN=2, CN=1). There were 32 spontaneous miscarriages in the women not on G-CSF (CN=1, CyN=8, and IN=23) compared with 3 in the women (CyN=3) on G-CSF.There were 82 live births from 123 pregnancies in the no G-CSF group. Thirteen of these infants had neonatal neutropenia. Other major neonatal complications in this group included 3 significant infections (1 meningitis, 2 septicemias), 1 minor infection (umbilical cord infection), 1 cerebral palsy, 1 respiratory distress syndrome, and 1 collapsed lung. In the G-CSF treated group there were 53 live births from 60 pregnancies. Twelve of these infants were neutropenic. Other complications in the G-CSF treated group included 1 umbilical cord infection (in a patient of mother with congenital neutropenia) and 1 tracheal esophageal fistula, 1 abruptio placenta associated with neonatal apnea, and 1 hydronephrosis (in infants with cyclic neutropenic mothers).The median G-CSF dose was 1.07 mcg/kg/day for all trimesters. Treatment was administered throughout the pregnancy in 62% (37/60) of the pregnancies. Seventeen percent (10/60) were treated only in the first trimester, 13% (8/60) were treated only in the last two trimesters, 3% (2/60) treated for the last trimester only, and 5% (3/60) treated in two of three trimesters (2 treated in 1st and 3rd trimesters, 1 treated in the 1st and 2nd trimesters). The two live births with congenital abnormalities occurred in G-CSF treated patients; one with tracheal esophageal fistula was exposed in the first trimester, one with hydronephrosis was exposed in all three trimesters.In summary, we found that G-CSF treatment was associated with a higher percentage of live births, 67% (82/123) without G-CSF compared with 88% (53/60) with G-CSF therapy (p=0.002, Fisher exact test). G-CSF therapy was associated with a lower number of spontaneous abortions, 26% (32/123) in the no G-CSF group versus 5% (3/60) in the G-CSF treated group (p=0.001). G-CSF therapy was associated with a lower rate of serious maternal complications. Two common congenital anomalies were observed in the offspring of the G-CSF treated mothers and no anomalies were observed in the offspring of the mothers not receiving G-CSF. Overall the newborns from the G-CSF treated mothers appeared to have fewer neonatal complications.Based on this analysis, we recommend that G-CSF therapy should be offered and continued during pregnancy in women with severe chronic neutropenia. The available data indicates that administration throughout pregnancy is well tolerated and protective of maternal health. Disclosures:Boxer:Amgen, Inc.: Equity Ownership. Dale:Amgen: Consultancy, Research Funding.

161 Prenatal Nicotine Exposure Increases the Risk of Neonatal Apnea -A National Birth-Cohort Study

Background: Smoking during pregnancy is associated with disturbed cardio-respiratory control of the infant and is a major risk factor for sudden infant death syndrome (SIDS). Although it is not known whether the harmful effects of smoking are caused by nicotine or other toxic substances in tobacco smoke, nicotine replacement therapy (NRT) during pregnancy is often regarded as being safer than smoking.Aim of study: To investigate if the disturbances in cardio-respiratory control seen in infants exposed to smoke are also noticed in infants exposed to nicotine (in the form of snuff) prenatally.Method: We conducted a population-based cohort study in the Swedish Medical Birth Register, 1999-2006, to study the association between maternal tobacco use and neonatal apnea.Of 569,859 newborns, 7,599 were born to snuff-using mothers, 41,391 and 16,928 born to light smokers (1-9 cig./day) and heavy smokers (≥10 cig./day), respectively. Apnea was defined by using ICD-10 codes P28.2-P28.4. Logistic regression was used for statistical analysis.Results: Compared with infants to non-users, prenatal exposure to snuff doubled the risk of apnea, and this risk was not confounded by maternal or neonatal characteristics (OR 1.97; CI [1.30-2.98]). In contrast, the smoking-related increased risk of apnea was no longer significant after adjustment for gestational age.Conclusion: Prenatal nicotine (snuff) is associated with a higher risk of neonatal apnea than smoking. This implies that it is not safe to recommend nicotine replacement therapy (NRT) for smoking cessation during pregnancy.

Continuous positive airway pressure treatment of neonatal apnea repeatedly analysis of 118 cases

Objective Of continuous positive airway pressure(CPAP) for the treatment of neonatal apnea effects of repeated. Methods Observed before and after CPAP treatment changes in the number of apnea episodes and the changes in blood gas before and after treatment to determine efficacy. Results As a result of the original incidence varied in different effects,with a total effective rate of 80%. After treatment,pH and PaO2 significantly increased,the partial pressure of carbon dioxide had no significant change(P ＞0.05). Conclusion CPAP treatment of neonatal apnea repeatedly significant,it is worth at all levels to promote the use of the hospital. Key words: Apnea; Newborn; Continuous positive airway pressure; Blood gas analysis

Evaluation of healthy full-term and late preterm infants presenting with apnea in the newborn nursery: A comparison of neonatal apnea and infantile acute life threatening event (ALTE)

Objective: To describe common etiologies and diagnostic evaluations performed on term and late preterm neonates with neonatal and to compare these etiologies and evaluations with those infants with infantile acute life threat ening event (ALTE). Methods: Infants 35 weeks, with diagnosis of or ALTE were identified at Bo ston Children's Hospital from June 2000 to June 2009. Medical rec ords were reviewed for diagnostic evaluations and discharge diagnoses. For analysis, neonates who presented with neonatal within the first week of life and prior to discharge f rom the birth hospitalization were classified as the Inpatient Grou p and infants who presented with post discharge were identified as the Outpatient Group. Infants with clear presenting etiologies were excluded from the study. Results: One hundred otherwise healthy subjects with diagnosis of or ALTE in the study period were identified. Approxi- mately one third were classified as the Inpatient Group. Diag nostic evaluations were highly variable, but testing for ba cterial or viral sepsis was most commonly performed. In most cases, an etiology was not determined, and the diagnosis of apnea of imma- turity was assigned. Other defined etiologic diagnoses inc luded viral infection or pertussis, reflux/aspiration, lar yngomalacia, and seizures. Conclusions: Diagnostic evaluation for apnea, in otherwise well-appearing full-term and late preterm infants, remains highly variable. Testing for infection, seizure, laryngomalacia and reflux may determine the majority of treatable etiologie s. Guidelines for diagnostic evaluations and treatment strategies are cl early needed.

Managing “healthy” late preterm infants

Late preterm infants are often managed in nursery rooms despite the risks associated with prematurity. The objective of this study was to determine the risks facing late preterm infants admitted to nursery rooms and to establish a management strategy. A total of 210 late preterm infants and 2648 mature infants were assessed. Infants born at 35 and 36 weeks' gestation weighing >or=2000 grams admitted to a nursery room and not requiring medical intervention at birth were of particular interest. The admission rates to the neonatal intensive care unit were evaluated according to the chart review. Infants born at 35 and 36 weeks' gestation weighing >or=2000 grams had significantly higher admission rates than term infants at birth (Cochran-Mantel-Haenszel test, P < 0.001; common risk ratio, 4.27; 95% confidence interval, 2.41-7.55) and after birth (P < 0.001; common risk ratio, 3.57; 95% confidence interval, 2.40-5.33). More than 80% of admissions from the nursery room to the neonatal intensive care unit after birth were due to apnea or hypoglycemia in neonates born at 35 and 36 weeks' gestation. The admission rates due to apnea increased with decreasing gestational age. The admission rates due to hypoglycemia with no cause other than prematurity accounted for 24.3% of admissions for those born at 35 weeks' gestation and 14.1% of admissions for those born at 36 weeks' gestation; hypoglycemia due to other causes accounted for fewer admissions. The management strategy for late preterm infants should be individualized, based on apnea and hypoglycemia. The respiratory state of late preterm infants should be monitored for at least 2 days, and they should be screened for hypoglycemia on postnatal day 0.

What to do about apnea of prematurity?

apnea of prematurity and resultant intermittent hypoxic episodes are universal in preterm infants. These events range from presumably benign “periodic” breathing to clinically significant events that may require mechanical ventilation. Persistence of these events is a major factor in prolonging

"Growing" meconium cyst in one of a discordant twin: a case report

IntroductionGiant meconium cyst resulting from antenatal bowel perforation is rare and hardly reported in multiple gestations. We found only four documented cases in the electronic literature.Case presentationWe report a giant meconium cyst in an 11-hour-old Nigerian boy of a discordant twin having ultrasonographic and plain radiographic diagnosis and surgical confirmation. Increasing abdominal girth from 35 cm to 41 cm within four hours of admission without ascites, pneumoperitneum and significant bowel distension make us assumed the meconium cyst to be “growing” in size. We reviewed the literature and proposed that where the fibrinous wall of meconium cyst allows for distensibility and the communication between the perforated bowel and meconium cyst persists, the meconium cyst acting as reservoir may continue to “grow” in size without remarkable intestinal distension probably, until the elastic limit is lost.ConclusionMeconium cyst can occur in twin pregnancy, grow to occupy the abdomen almost completely and may cause neonatal apnoea. The outcome is good post surgery.

A randomised controlled trial of two feeding schedules in neonates weighing ≤1750 g

Objectives. To study the incidence of feed intolerance, apnea and hypoglycemia in neonates weighing ≤1750 g given 3 hourly feeds as against 2 hourly feeds.Methods. Ninety-two neonates, weighing ≤1750 g and medically fit to receive feeds, were randomised to receive feeds either at 3 hourly or 2 hourly intervals.Results. The incidence of feed intolerance was not different between 3 hourly and 2 hourly feeding groups [13%vs. 19%, OR 0.69 (95% CI 0.19–2.49)]. The incidence of apnea was 25 and 28%[OR 0.86 (95% CI 0.3–2.48)] and that of hypoglycemia was 21 and 26%[OR 0.75 (95% CI 0.24–2.3)] in 3 hourly and 2 hourly feeding groups, respectively. The incidence of necrotising enterocolitis was also similar (7%) in both the feeding groups. The total nursing time spent on feeding per day was significantly less in 3 hourly group.Conclusions. In comparison to a 2 hourly schedule, a 3 hourly feeding schedule did not decrease the incidence of feed intolerance; it, however, did not increase the incidence of hypoglycemia or apnea. For practical convenience, a 3 hourly feeding schedule may be preferred over 2 hourly schedule in neonates weighing ≤1750 g.

Long-term neurodevelopmental disorders in mice with apneas during prematurity

Epidemological evidence points towards a link between the severity of apneas of prematurity and developmental disorders. However, the causality in this relation has not yet been established. In this study, we made use of a genetic mouse model (Phox2b) that is characterized by an increased apnea time (approximately 6-fold at age P5 compared to wildtype littermates) during normoxia. These breathing problems are, however, confined to 2 to 5 days of postnatal age (≈ severe to moderate prematurity in humans) and mice survive normally without ventilatory support. Furthermore, Phox2b is not expressed in higher brain areas, thus excluding direct effects of the mutation on cognitive development. The described phenotype is particularly useful in light of our interest in the consequences of apneas of prematurity on cognitive functioning. To address this issue, we conducted a behavioural test battery in Phox2b adult mice. We conducted a behavioural study in a genotype (Phox2b heterozygote (HZ) vs wildtype (WT))- and gender-mixed group of adult mice ( N =37). Neuromotor performance (rotarod, grip strength) and cage activity were tested, as well as anxiety and exploration (open field, social exploration and elevated plus maze), and learning and memory (passive avoidance learning and Morris water maze). Phox2b HZ mice showed no differences in weight, nor alterations in neuromotor performance or activity level compared to controls. During the open field and social exploration tests Phox2b HZ exhibited significantly less exploratory behaviour than WT. This behavioural observation was also confirmed in the elevated plus maze. Passive avoidance learning was abolished in a subgroup of Phox2b heterozygotes. Moreover, we found that Phox2b HZ mice were slower to acquire learning in the Morris water maze and displayed small but significant memory deficits in both Morris water maze protocols we applied. In this study, we investigated the long term effects of postnatal apneas by conducting a behavioural study on adult Phox2b mice. We found important deficits in exploratory behaviour, and learning and memory functioning in Phox2b HZ. Since Phox2b is not expressed in higher brain regions which are involved in behavioural tests, these differences are likely to arise from neonatal apneas.

Neonatal Apnea: What's New?

Apnea of prematurity (AOP) remains a major clinical problem in present day neonatology that warrants frequent evaluations and imposes challenges in therapeutic strategies. Although the pathogenesis of AOP is poorly understood, it is probably a manifestation of physiologic immaturity of breathing control rather than a pathologic disorder. Immature breathing responses to hypoxia, hypercapnia and exaggerated inhibitory pulmonary reflexes in preterm infants might also contribute to the occurrence or severity of AOP. Recent data suggest a role for genetic predisposition. Although typically resolve with maturation, the role of bradycardia and desaturation episodes associated with AOP in the development of sleep disorder breathing and neurodevelopmental delay needs further clarification. Pharmacological treatment with methylxanthines and CPAP remain the mainstay for treatment of AOP. However, recent studies have implicated central inhibitory neuromodulators including prostaglandins, GABA and adenosine in its pathogenesis, the fact that might provide future specific targets for treatment. This review will summarize new insights involving these issues as well as others involving the pathogenesis, treatment strategies and consequences of apnea in premature infants.

Control of respiration and management of Apnea in neonates and infants

Control of respiration and management of Apnea in neonates and infants

Influence of Thermal Drive on Central Sleep Apnea in the Preterm Neonate

The incidence of apnea in neonates depends on a number of factors, including sleep state and thermoregulation. To assess the role of thermal drive (body heat loss [BHL]) in the mechanisms underlying short episodes of central apnea during active and quiet sleep in neonates. Twenty-two neonates (postconceptional age: 36.3 +/- 0.9 weeks) were exposed at thermoneutral (incubator temperature: 32.5 degrees C), warm (34.2 degrees C), and cool (30.4 degrees C) conditions during 3 consecutive morning naps. Oxygen consumption (VO2), skin and rectal temperatures, and central apnea were scored during active sleep and quiet sleep. The thermal drive was expressed as BHL calculated using indirect partitional calorimetry. As expected, apnea occurred more frequently in active sleep than in quiet sleep (P < 0.001). The frequency of apnea in active sleep was higher in the warm condition (P < 0.05). In contrast, apnea episodes were less frequent (P < 0.05) and shorter (P < 0.05) for cool exposure, during which VO2 and rectal temperature increased. The frequency (P < 0.001, r2 = 0.31), mean (P < 0.05, r2 = 0.06), and maximum (P < 0.001, r2 = 0.19) durations of apnea were correlated with the BHL: the greater the BHL (body cooling), the less frequent and the shorter the apnea episodes. In contrast, no relationship between apnea and mean skin or rectal temperature was observed. Apneic events were more closely related to BHL than to body temperatures. In cool exposure, the decreases in the duration and frequency of apneic episodes suggest that these events depend on the metabolic drive (which is proportional to energy expenditure).

Neurodevelopmental outcome of infants with apnea of infancy.

The neurodevelopmental outcome of premature infants with persistent apnea of prematurity (AOP) is reported. Sixty premature infants (birthweight [BW], 1469 +/- 533 gm; gestational age [GA , 31 +/- 3 weeks) with AOP were compared to 47 control infants (BW, 1586 +/- 581 gm; GA, 31 +/- 3 weeks) matched for gestational age and degree of neonatal illness. The infants were enrolled in a multidisciplinary follow-up program, and outcome data between 12 and 24 months are reported. Assessments included the Bayley Scores of Infant Development, neurologic examinations, speech and hearing examinations. There were no significant differences in the cognitive outcome between the premature infants with AOP and the premature control group. In 50 of 60 infants the Bayley Mental Developmental Index was in the normal range (112 +/- 18) as was 39 of 47 of the control group (112 +/- 13). Delays in motor development were seen in both premature groups, although a greater percentage of premature infants with persistent apnea had mild motor delays than did control infants. There was a comparable incidence of cerebral palsy (8% vs 11%), speech delays (20% vs 23%), retinopathy (8% vs 13%), and esotropia (7% vs 4%) between the infants with AOP and the premature control infants. The presence of persistent neonatal apnea without additional adverse perinatal events did not appear to be associated with a higher incidence of significant developmental problems.

Chronic intermittent hypoxia abolishes respiratory LTF in rat pups and enhances apnea frequency

We tested the hypothesis that chronic intermittent hypoxia (IH) alters respiratory long‐term facilitation (LTF) induced by acute hypoxic episodes in newborn rats. Rat pups were exposed to normal room air (controls) or chronic IH (IH: O2 levels cycled between 21% and 5% every 10 minutes for 1h; 1h normoxia, 24h/day) during postnatal days 1–10. To assess LTF, we measured minute ventilation (VE ‐ whole body plethysmography) in normoxia and during a recovery period of 2 hours following 10 acute hypoxic episodes. VE gradually increased (+23%) during recovery in controls, but decreased (−15%) in IH rats. In controls, frequency of apneas (≥2 missed breaths, measured before and at the end of recovery) slightly increased following acute hypoxic episodes (from 23±3 to 34±5 apneas/hour), while it dramatically increased in IH rats (from 26±4 to 61±6 apneas/hour). There was no gender‐specific effect. We conclude that in 10‐day old rats: i) LTF is present, ii) chronic IH abolishes LTF and iii) LTF appears to have a protective role against apneas. Neonatal apnea with IH may abolishe endogenous protective mechanisms, and contribute to increase apnea frequency in neonates. (FRSQ, CIHR, Sick kids foundation).

Apnea in the newborn

Apnea, defined as cessation of breathing resulting in pathological changes in heart rate and oxygen saturation, is a common occurrence especially in preterm neonates. It is due to immaturity of the central nervous system (apnea of prematurity) or secondary to other causes such as metabolic disturbances etc. Secondary causes of apnea should be excluded before a diagnosis of apnea of prematurity is made. Methylxanthines and continuous positive airway pressure form the mainstay of treatment. Mechanical ventilation is reserved for apnea resistant to the above therapy. An approach to the management of apnea in neonates is described.