Aspiration of Gastric Contents in Sudden Infant Death Syndrome without Cardiopulmonary Resuscitation

Article Outline

• Abstract
• Methods
  • Data Analysis
• Results
• Discussion
• Acknowledgment
• References
• Copyright

Objectives

(1) To compare demographic profiles among sudden infant death syndrome (SIDS) infants with or without gastric aspiration, for whom cardiopulmonary resuscitation (CPR) had not been attempted; (2) to review the severity and potential significance of aspiration in those SIDS cases; and (3) to assess the risk of supine sleep position with regard to gastric aspiration.

Study design

Retrospective review of records and microscopic slides for all postneonatal SIDS cases (29 to 365 days of age) accessioned by the San Diego County Medical Examiner from 1991 to 2004.

Results

Ten (14%) of 69 cases of SIDS infants who had not undergone CPR before autopsy revealed microscopic evidence of gastric aspiration into the distal lung; this group was not otherwise clinically or pathologically different from cases of SIDS infants without aspiration. Similar proportions of infants were found supine or prone, regardless of gastric aspiration.

Conclusions

Gastric aspiration is not uncommon in infants dying of SIDS, and supine sleep position does not increase its risk. Gastric aspiration may be a terminal event that some infants, representing a subset of SIDS cases, cannot overcome.

Abbreviations: ALTEs, Apparent life-threatening events, CPR, Cardiopulmonary resuscitation, GER, Gastroesophageal reflux, SIDS, Sudden infant death syndrome

Gastric contents are present in the lungs of 30% to 40% of infants whose deaths are attributed to sudden infant death syndrome (SIDS).¹, ², ³ Studies in adults indicate that intrapulmonary migration of gastric contents can occur postmortem as a result of cardiopulmonary resuscitation (CPR) or transport of the body.⁴ Accordingly, the majority of pediatric pathologists have dismissed aspiration of gastric contents (henceforth referred to as “gastric aspiration”) as a cause of death, believing it to be a postmortem artifact. The pathology literature addressing gastric aspiration in SIDS is not only limited, but, most importantly, none of the studies has controlled for the potential role of CPR in forcing gastric contents from the oral cavity and/or pharynx into the distal lung.¹, ², ³ Therefore, the aims of our study are to: (1) compare the demographic characteristics and findings from the death scene and autopsy in SIDS infants with or without gastric aspiration who had no CPR attempted before autopsy; (2) review the degree and significance of aspiration in this subset of SIDS cases; and (3) assess the risk of supine sleep position relative to gastric aspiration.

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Methods 

The Rady Children’s Hospital-Health Center Institutional Review Board approved this study. A search of the records of all postneonatal infants (29-365 days of age) dying suddenly and unexpectedly who were autopsied at the Medical Examiner’s Office in San Diego County, California, between January 1, 1991 and December 31, 2004 and accessioned into the San Diego SIDS Research Project database at Children’s Hospital-San Diego revealed 69 cases of infants who had a diagnosis of SIDS and had not undergone CPR before autopsy.

Case data were selected from the medical history, death scene, investigative and autopsy reports, and from two standardized data protocols for the death scene investigation and autopsy. In 1989, a California statute mandated use of standardized scene investigation and autopsy protocols (developed by a multidisciplinary expert committee) for cases of sudden, unexpected infant death without external evidence of inflicted injuries. Trained, experienced investigators from the Medical Examiners Office are charged with collecting this information within 30 hours of an infant’s death. The data are not complete for every case.

A diagnosis of SIDS was made when criteria from the recent definition proposed in 2004 were fulfilled.⁵ For analytical purposes, the cases were divided into two groups: Group I, SIDS cases with gastric aspiration, and Group II, SIDS cases without gastric aspiration.

Microscopic lung sections stained with hematoxylin and eosin were available in all cases; the mean numbers of sections for Group I cases with aspiration and Group II without aspiration were 4.9 ± 2.2 and 4.3 ± 1.2, respectively; the ranges for the two groups were 1 to 10 and 1 to 6, respectively. Two pathologists (HFK and HM) reviewed the slides. Inter- and intra-observer reproducibility (κ) testing was calculated; inter-observer κ-value was 0.82, intra-observer results ranged from 0.82 to 1.00. Gastric contents were identified by the presence of amorphous and finely granular and/or faintly basophilic eosinophilic material. Isolated clumps of bacterial colonies were not interpreted as gastric aspiration (see discussion). The severity of gastric aspiration (defined as gastric contents identifiable in distal bronchioles [Figure], with or without extension into the intra-alveolar spaces) was assessed semiquantitatively according to the following scale: 0 = absent, 1 = very mild, 2 = mild, 3 = moderate, and 4 = severe.

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• Figure. 

  Aspirated gastric contents distend a distal bronchiole (dashed arrow) and extend into adjacent alveoli (solid arrow) of the lung of this 3-month-old male found prone with his face to the side. Hematoxylin and eosin, ×100.

Data Analysis 

Categorical variables were analyzed using the χ² or Fisher’s exact test, along with odds ratios. Continuous data were analyzed with two-sample t tests and are summarized using means ± standard deviations. Calculations were performed with Epi Info v. 3.3, Statcalc v. 6 (Centers for Disease Control and Prevention, Atlanta, GA), or Statistical Package for the Social Sciences v. 11.5 (SPSS Inc., Chicago, IL). A P value < .05 was considered significant.

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Results 

Group I (SIDS cases with aspiration) includes 10 (14%) of the 69 cases. No demographic findings were significantly different between the two groups (Table I). The majority of infants in both groups were male, born term, delivered vaginally, and fed formula as their last meal. None of the infants who were breast-fed for their last meal had evidence of gastric aspiration. Clinically documented gastroesophageal reflux (GER) was more common in cases with aspiration (20% vs 2%); a history of apnea or apparent life-threatening events (ALTEs) was uncommon in both groups. Approximately one quarter of the infants in both groups was bed-sharing when they died. The interval from time of last feeding to time of discovery was similar between the two groups as was the postmortem interval. Only one of the Group I cases had grade 4 aspiration.

Table I. Demographic, clinical, and perimortem variables in SIDS cases without CPR by presence or absence of gastric aspiration

	Group I with gastric aspiration (N = 10)	Group II without gastric aspiration (N = 59)	P
Age (days)
Mean ± SD	95.8 ± 40.3	83.3 ± 43.9	NS
Range	56-178	30-291
Sex			NS
Male	6(60%)	37(63%)
Female	4(40%)	22(37%)
Gestation	N = 9	N = 47	NS
Preterm	1(11%)	13(28%)
Term	8(89%)	34(72%)
Delivery	N = 9	N = 52	NS
Vaginal	7(78%)	41(79%)
Cesarean	2(22%)	11(21%)
Last meal	N = 6	N = 46	NS
Formula	6(100%)	34(74%)
Breast milk		8(17%)
Other⁎		4(9%)
History of GER	2of10(20%)	1of46(2%)	NS
History of ALTE	0 of 7	1of46(2%)	NS
Bed-sharing	2of10(20%)	16of58(28%)	NS
Fed interval (hours)	N = 9	N = 53	NS
Mean ± SD	6.7 ± 3.2	7.5 ± 2.8
Range	3.5-12.3	0.3-15.7
<4 hours	2(22%)	3(6%)
PMI (hours)			NS
Mean ± SD	20.5 ± 7.9	24.2 ± 5.8
Range	4.3-27.6	3.9-32.9
<12 hours	2(20%)	4(7%)
12-24 hours	3(30%)	17(29%)
>24 hours	5(50%)	38(64%)

NS, Not significant; PMI, postmortem interval.

No significant differences in the death scene and postmortem findings between groups were identified, including the positions the infant was placed for sleep or found, the position of the face when found, gastric contents in the tracheobronchial lumen, and intrathoracic petechiae (Table II). Seventy percent of the Group I cases had very mild to mild gastric aspiration; moderate or severe gastric aspiration was present in less than one third of the cases. There was no association between age and the severity of gastric aspiration.

Table II. Death scene and postmortem findings in SIDS cases without CPR by presence or absence of gastric aspiration

	Group I with gastric aspiration (N = 10)	Group II without gastric aspiration (N = 59)	P
Position body placed	N = 6	N = 37	NS
Supine	1(17%)	11(30%)
Side		5(14%)
Prone	5(83%)	21(57%)
Position body found	N = 9	N = 53	NS
Supine	1(11%)	13(25%)
Side		4(8%)
Prone	8(89%)	36(68%)
Position face found	N = 8	N = 43	NS
Up	1(13%)	6(14%)
Side	5(63%)	18(42%)
Down	2(25%)	19(44%)
Tracheobronchial gastric contents at autopsy	2(20%)	2(3%)	NS
Intrathoracic petechiae	9(90%)	51(86%)	NS
Vomitus when found⁎	3(30%)	3(5%)	.04
Gastric aspiration score†
0		59(100%)
1	4(40%)
2	3(30%)
3	2(20%)
4	1(10%)

NS, Not significant.

Details of the 10 Group I infants with gastric aspiration are given in Table III. Eight of 9 (89%) for which body position was known were discovered prone. Face position when found was known in 8 cases; 7 (88%) were face down or to the side. None had a history of ALTE, 2 (20%) had previously documented GER, and 9 (90%) had intrathoracic petechiae at autopsy. Three infants, one of which was the only infant with grade 4 aspiration, had evidence of vomitus when discovered lifeless. The Figure is from Case F (Table III) and shows a bronchiole distended with gastric contents.

Table III. Clinical and pathologic findings in SIDS cases with gastric aspiration

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Discussion 

Prone sleep position has been long recognized as one of the most important risk factors for SIDS.⁶, ⁷, ⁸, ⁹, ¹⁰ Adoption of the supine sleep position as recommended in the Back to Sleep campaign and other similar public education programs has resulted in a dramatic reduction in the incidence of SIDS.⁹, ¹¹, ¹² However, some segments of the population have not followed the supine sleep recommendation, causing disparities in the decreasing rates of SIDS.¹³, ¹⁴, ¹⁵, ¹⁶ Fear of gastric aspiration leading to death is among the variety of reasons that supine sleep position has not been adopted,¹⁶ although epidemiological and postmortem evidence to support this fear has not been forthcoming from studies in Australia, the United Kingdom, and the United States.¹⁰, ¹⁷, ¹⁸ In fact, a report from the Infant Care Practice Study provides data to indicate the safety of supine sleeping with regard to a number of health outcomes, including GER and vomiting.¹⁹

Although our study does not identify significant differences between the groups with and without gastric aspiration, there are several noteworthy findings: (1) all but one of the nine case infants with gastric aspiration for whom body position was known were found prone; (2) the majority of infants (>85%) in both groups were found with their faces down or to the side; (3) approximately one quarter of each group was bed-sharing at the time of their deaths; and (4) none of the infants who were last breast-fed had evidence of gastric aspiration.

In contrast to previous studies of gastric aspiration in sudden infant death,¹, ², ²⁰ the principal and unique strength of our study is inclusion of only SIDS infants who had not undergone CPR before autopsy. We were, therefore, able to eliminate CPR as a cause of gastric contents in the distal parts of the lung. Consequently, we found gastric aspiration in 14% of our SIDS cases, a proportion somewhat less than that observed by other investigators in cases of sudden infant death.¹, ²⁰, ²¹

Two previous studies have analyzed cases or subsets of infant death cases limited to SIDS.¹, ²⁰ Their analyses are confounded, however, by inclusion of cases of infants who had undergone CPR before autopsy. Bajanowski et al did not identify “deep aspiration,” defined as the presence of gastric contents in bronchioles and alveoli, in any of 131 cases of SIDS infants whether found prone, supine, or on their side.¹ In contrast, Alex et al identified aspirated gastric contents in 37% of 99 SIDS cases. The degree of aspiration was never severe nor considered a cause of death.²⁰ These investigators included the presence of milk in typical form with or without clumps of bacteria, clumps of bacteria having a similar distribution but without other airway contents identifiable as milk, and other food particles as evidence of aspirated gastric contents. We did not accept isolated bacterial clumps as evidence of gastric aspiration in our study, and we agree with others that CPR even after death can account for this finding.¹, ²², ²³ Alex et al also found that the risk of gastric aspiration was significantly increased in association with being found supine or having the autopsy performed on the day after death or later. In contrast, we found no association between sleep position or the duration of the postmortem interval and gastric aspiration in our study.

Other epidemiological and pathological studies that combined SIDS cases with cases of infants who died of other causes into a single group have shown that supine sleep position did not increase the risk of gastric aspiration. After reviewing vital statistics for the United States for the years 1991, 1995, and 1996, Malloy determined that gastric aspiration had not accounted for any increase in postneonatal mortality.¹⁰ This finding is important given that the prevalence of prone positioning for infant sleep decreased from 70% in 1992 to 14% in 2000 (<http://www.nichd.nih.gov/publications/pubs/BTS_Q_A_Healthproviders.cfm>) and supine positioning increased from 13% to 35%.¹⁵ During the same interval, Malloy determined that postneonatal aspiration-related deaths dropped from 1.39 per 100,000 live births in 1991 to 0.93 in 1996.¹⁰ In their review of 196 cases of infant and early childhood death, Byard and Beal identified the cases of three infants with severe gastric aspiration into airways and alveoli, all of whom were discovered prone and one with the face in a pool of vomitus, and concluded that supine positioning did not increase the risk of aspiration.² In this regard, it is worth noting again that 8 of the 9 cases of infants positive for gastric aspiration for whom the data were available were found prone (Table III).

Considerable evidence indicates that young infants are susceptible to numerous conditions that cause episodes of severe hypoxemia resulting in loss of consciousness. The vast majority of these infants autoresuscitate, as a result of hypoxic gasping. In such cases brainstem centers initiate the autoresuscitation reflex mechanisms. This is the last chance for survival after arousal or other protective responses have failed.²⁴ Terminal gasping has been recorded in infants being monitored at the time of their deaths, suggesting that at least a subset of SIDS cases may represent a failure of autoresuscitation.²⁵, ²⁶ In a mouse model using saline infused into the pharynx during hypoxic gasping, reflexive swallowing facilitates successful autoresuscitation.²⁷ In cases where swallowing does not occur, resuscitation fails, presumably because of intrapulmonary aspiration. This is supported by Stevens’ observations of human infants who died rapidly of unknown causes; he witnessed repeated successful autoresuscitations in the absence of regurgitation; however autoresuscitation eventually failed when vomitus appeared in the upper airway.²⁸ Considering these and other observations, Gardner suggested that agonal aspiration may be the coup de grace leading to death in some.⁴ It is therefore reasonable to speculate that when a hypoxic comatose infant regurgitates and fails to swallow, then pulmonary aspiration can prevent autoresuscitation. In such cases, failure to swallow might be enhanced by abnormalities in brainstem centers regulating respiratory functions during hypoxic coma.²⁹, ³⁰, ³¹, ³²

Regardless of the association between gastric aspiration and infant positioning, important questions remain regarding the pathophysiological significance of aspiration. For example, why should gastric aspiration not be considered the immediate cause of death, especially in those cases with considerable aspiration into distal bronchioles and alveoli? There were three (4%) such cases in our study diagnosed as SIDS by the medical examiner. Vomitus was present at the scene where one of these infants was found lifeless. Gastric contents were present in the tracheobronchial lumen of the other two at the time of autopsy, possibly the result of postmortem manipulation of the body.⁴ We agree with others that gastric contents in the distal bronchioles and alveoli must be a consequence of terminal gasping during attempts at autoresuscitation, especially when the possibility of forced entry into these sites by CPR has been excluded.¹, ²⁴ Gastric contents in the distal lung, in the absence of such material in the trachea and larger bronchi, effectively rules out postmortem migration. Furthermore, postmortem manipulation of an infant’s body may result in changes at a much lower pressure than that of gasping and would likely be insufficient to cause migration of gastric contents into the intra-alveolar spaces. For migration of gastric contents to occur, gastric contents would have to be in the pharynx before death. Reflexive apnea as a result of regurgitation could have precipitated hypoxia just before hypoxic gasping.²⁴

The observation that none of the infants whose last feed consisted exclusively of breast milk had evidence of gastric aspiration, although not statistically significant, deserves comment. Rates of gastric emptying are faster in breast-fed versus formula-fed infants.³³, ³⁴ Given that infants with severe GER may be more likely to have significantly delayed gastric emptying,³⁵ it may be that breast-fed infants are less likely to have GER than formula-fed infants. With less GER, it follows that there is less risk of gastric aspiration.³⁶, ³⁷ Large, prospective studies are required to clarify the relationship between breast-feeding and the risk of aspiration.

Our data do not suggest that bed-sharing increases the risk of gastric aspiration, given that roughly one quarter of cases in both groups (Table I) were bed-sharing. Similarly, there were no significant differences between the two groups with respect to either histories of ALTEs or mean interval between the time last fed and the time of their pronounced deaths. Proportional differences in history of GER, though striking, were not statistically significant in our small sample.

Our study is unable to address a potentially lethal role of gastric aspiration in cases in which gastric contents were not observed in the pharynx at postmortem examination. It is tempting to dismiss any role when this material is not seen, but the pharynx is not always carefully inspected during postmortem examination. Experiments with mice have shown that considerable adverse physiological consequences can follow the introduction of even small volumes of irritant solutions into the pharynx.²⁷

In conclusion, our data describe the presence of gastric contents in the distal lung fields in 14% of SIDS cases for which CPR was not attempted. Approximately two thirds of infants with or without pulmonary gastric aspiration were found prone, suggesting that sleep position does not affect the risk of aspiration. Our findings also suggest that gastric aspiration may be a terminal event that some infants, representing a subset of SIDS cases, cannot overcome. Therefore, gastric aspiration may be a potentially more important causal factor in a subset of SIDS cases than previously thought and should be a renewed focus for future research.

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The generous donations of the San Diego Guild for Infant Survival, the Orange County Guild for Infant Survival, and the many parents of SIDS victims to the San Diego SIDS/SUDC Research Project are greatly appreciated, as is the assistance of the Office of the Medical Examiner of San Diego County, California. We are grateful for the statistical support of Ms. Azarnoush Maroufi.

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References 

1. Bajanowski T, Ott A, Jorch G, Brinkmann B. Frequency and type of aspiration in cases of sudden infant death (SID) in correlation with the body position at the time of discovery. J Sudden Infant Death Syndrome Infant Mortality. 1996;1:271–279
   • View In Article
2. Byard RW, Beal SM. Gastric aspiration and sleeping position in infancy and early childhood. J Paediatr Child Health. 2000;36:403–405
   • View In Article
   • MEDLINE
   • CrossRef
3. Isaksen CV, Helweg-Larsen K. The impact of attempted resuscitation in SIDS: postmortem findings. In:  Rognum TO editors. Sudden Infant Death Syndrome (New Trends in the Nineties). Oslo: Scandinavian University Press; 1995;p. 70–73
   • View In Article
4. Gardner AMN. Aspiration of food and vomit. Q J Med. 1958;27:227–242
   • View In Article
   • MEDLINE
5. Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, et al. Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics. 2004;114:234–238
   • View In Article
   • CrossRef
6. Mitchell EA, Scragg R, Stewart AW, Becroft DM, Taylor BJ, Ford RP, et al. Results from the first year of the New Zealand cot death study. N Z Med J. 1991;104:71–76
   • View In Article
   • MEDLINE
7. Taylor JA, Krieger JW, Reay DT, Davis RL, Harruff R, Cheney LK. Prone sleep position and the sudden infant death syndrome in King County, Washington: a case-control study. J Pediatr. 1996;128:626–630
   • View In Article
   • Abstract
   • Full-Text PDF (435 KB)
   • CrossRef
8. Fleming PJ, Gilbert R, Azaz Y, Berry PJ, Rudd PT, Stewart A, et al. Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study. BMJ. 1990;301:85–89
   • View In Article
   • MEDLINE
   • CrossRef
9. Hauck FR. Changing epidemiology. In:  Byard RW,  Krous HF editor. Sudden Infant Death Syndrome: Problems, Progress & Possibilities. London: Arnold; 2001;p. 31–57
   • View In Article
10. Malloy MH. Trends in postneonatal aspiration deaths and reclassification of sudden infant death syndrome: impact of the “Back to Sleep” program. Pediatrics. 2002;109:661–665
    • View In Article
    • CrossRef
11. Dwyer T, Ponsonby AL. The decline of SIDS: a success story for epidemiology. Epidemiology. 1996;7:323–325
    • View In Article
    • MEDLINE
12. Gibson E, Dembofsky CA, Rubin S, Greenspan JS. Infant sleep position practices 2 years into the “back to sleep” campaign. Clin Pediatr (Phila). 2000;39:285–289
    • View In Article
    • MEDLINE
    • CrossRef
13. Brenner RA, Simons-Morton BG, Bhaskar B, Mehta N, Melnick VL, Revenis M, et al. Prevalence and predictors of the prone sleep position among inner-city infants. JAMA. 1998;280:341–346
    • View In Article
    • MEDLINE
    • CrossRef
14. Willinger M, James LS, Catz C. Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol. 1991;11:677–684
    • View In Article
    • MEDLINE
15. Willinger M, Hoffman HJ, Wu KT, Hou JR, Kessler RC, Ward SL, et al. Factors associated with the transition to nonprone sleep positions of infants in the United States: the National Infant Sleep Position Study. JAMA. 1998;280:329–335
    • View In Article
    • MEDLINE
    • CrossRef
16. Willinger M, Ko CW, Hoffman HJ, Kessler RC, Corwin MJ. Factors associated with caregivers’ choice of infant sleep position, 1994-1998: the National Infant Sleep Position Study. JAMA. 2000;283:2135–2142
    • View In Article
    • MEDLINE
    • CrossRef
17. Ponsonby AL, Dwyer T, Couper D. Sleeping position, infant apnea, and cyanosis: a population-based study. Pediatrics. 1997;99:e3
    • View In Article
    • CrossRef
18. Hunt L, Fleming P, Golding J The ALSPAC Study Team. Does the supine sleeping position have any adverse effects on the child? I (Health in the first six months). Pediatrics. 1997;100:E11
    • View In Article
    • CrossRef
19. Hunt CE, Lesko SM, Vezina RM, McCoy R, Corwin MJ, Mandell F, et al. Infant sleep position and associated health outcomes. Arch Pediatr Adolesc Med. 2003;157:469–474
    • View In Article
    • MEDLINE
    • CrossRef
20. Alex N, Thompson JM, Becroft DM, Mitchell EA. Pulmonary aspiration of gastric contents and the sudden infant death syndrome. J Paediatr Child Health. 2005;41:428–431
    • View In Article
    • MEDLINE
    • CrossRef
21. Iwadate K, Doy M, Ito Y. Screening of milk aspiration in 105 infant death cases by immunostaining with anti-human alpha-lactalbumin antibody. Forensic Sci Int. 2001;122:95–100
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (687 KB)
    • CrossRef
22. Althoff H. Sudden infant death syndrome (S.I.D.S) (Veroffentfichungen aus der morphologischen Pathologie). Stuttgart: Fischer; 1980;
    • View In Article
23. Mueller B. Gerichtliche Medizin. Berlin, Heidelberg, New York: Springer; 1976;
    • View In Article
24. Thach BT. Sudden infant death syndrome: can gastroesophageal reflux cause sudden infant death?. Am J Med. 2000;108(suppl 4a):144S–148S
    • View In Article
25. Poets CF, Meny RG, Chobanian MR, Bonofiglo RE. Gasping and other cardiorespiratory patterns during sudden infant deaths. Pediatr Res. 1999;45:350–354
    • View In Article
    • MEDLINE
    • CrossRef
26. Sridhar R, Thach BT, Kelly DH, Henslee JA. Characterization of successful and failed autoresuscitation in human infants, including those dying of SIDS. Pediatr Pulmonol. 2003;36:113–122
    • View In Article
    • MEDLINE
    • CrossRef
27. Khurana A, Thach BT. Effects of upper airway stimulation on swallowing, gasping, and autoresuscitation in hypoxic mice. J Appl Physiol. 1996;80:472–477
    • View In Article
    • MEDLINE
28. Stevens LH. Sudden unexplained death in infancy. Amer J Dis Child. 1965;110:243–244
    • View In Article
29. Kinney HC, Filiano JJ, White WF. Medullary serotonergic network deficiency in the sudden infant death syndrome: review of a 15-year study of a single dataset. J Neuropathol Exp Neurol. 2001;60:228–247
    • View In Article
    • MEDLINE
30. Kinney HC. Abnormalities of the brainstem serotonergic system in the sudden infant death syndrome: a review. Pediatr Dev Pathol. 2005;8:507–524
    • View In Article
    • MEDLINE
    • CrossRef
31. Kinney HC, Myers MM, Belliveau RA, Randall LL, Trachtenberg FL, Fingers ST, et al. Subtle autonomic and respiratory dysfunction in sudden infant death syndrome associated with serotonergic brainstem abnormalities: a case report. J Neuropathol Exp Neurol. 2005;64:689–694
    • View In Article
    • MEDLINE
    • CrossRef
32. Ottaviani G, Matturri L, Mingrone R, Lavezzi AM. Hypoplasia and neuronal immaturity of the hypoglossal nucleus in sudden infant death. J Clin Pathol. 2006;59:497–500
    • View In Article
    • MEDLINE
    • CrossRef
33. Cavell B. Gastric emptying in infants fed human milk or infant formula. Acta Paediatr Scand. 1981;70:639–641
    • View In Article
    • MEDLINE
34. Van Den Driessche M, Peeters K, Marien P, Ghoos Y, Devlieger H, Veereman-Wauters G. Gastric emptying in formula-fed and breast-fed infants measured with the 13c-octanoic acid breath test. J Pediatr Gastroenterol Nutr. 1991;29:46–51
    • View In Article
    • MEDLINE
    • CrossRef
35. Hillemeier AC, Lange R, McCallum RI, Seashore J, Gryboski J. Delayed gastric emptying in infants with gastroesophageal reflux. J Pediatr. 1981;98:190–193
    • View In Article
    • Abstract
    • Full-Text PDF (340 KB)
    • CrossRef
36. Orenstein SR. An overview of reflux-associated disorders in infants: apnea, laryngospasm, and aspiration. Am J Med. 2001;111(suppl 8A):60S–63S
    • View In Article
37. Sandhu BK, Sawczenko A. Gastroesophageal reflux in children. Indian J Pediatr. 1999;66:S52–S55
    • View In Article
    • MEDLINE