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Am J Perinatol 2019; 36(05): 460-471
DOI: 10.1055/s-0038-1669398
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuropathology of Early Sudden Infant Death Syndrome—Hypoplasia of the Pontine Kolliker-Fuse Nucleus: A Possible Marker of Unexpected Collapse during Skin-to-Skin Care

Anna M. Lavezzi
1   Department of Biomedical, Surgical and Dental Sciences, “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, University of Milan, Milan, Italy
,
Stefano Ferrero
1   Department of Biomedical, Surgical and Dental Sciences, “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, University of Milan, Milan, Italy
2   Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
,
Beatrice Paradiso
1   Department of Biomedical, Surgical and Dental Sciences, “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, University of Milan, Milan, Italy
3   Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
,
Liliya Chamitava
4   Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
,
Francesco Piscioli
5   Institute of Pathology, Hospital of Rovereto, Trento, Italy
,
Teresa Pusiol
5   Institute of Pathology, Hospital of Rovereto, Trento, Italy
› Author Affiliations Funding None.

Ethical Approval Permission from the Ethics Committee was not required for this study as our research center (“Lino Rossi” Research Center of the Milan University) is the national referral center for sudden unexplained fetal and infant death, in accordance with the aforementioned Italian Law no. 31. Study approval was anyway granted by the Institutional Review Board of Milan University.
Further Information

Publication History

22 February 2018

21 July 2018

Publication Date:
31 August 2018 (online)

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Abstract

Objective To find a possible pathogenetic mechanism of the early sudden infant death occurring in newborns during the skin-to-skin care (SSC), through the examination of neuronal centers regulating the vital activities.

Study Design This is an in-depth examination of the brain stem in 22 healthy term newborns, suddenly died in the first hour of life without the identification of a cause at autopsy (early sudden infant death syndrome [eSIDS]), 12 of them concomitantly with SSC, and 10 with age-matched controls died of known pathology.

Results Developmental alterations of neuronal structures of the brain stem were highlighted in 19 of the 22 eSIDS, but not in control. The hypoplasia of the pontine Kölliker-Fuse nucleus (KFN), an important respiratory center, was diagnosed at the histological examination, validated by morphometric quantifications, in 11 of the 12 eSIDS while they were placed on the mother's chest and in 2 of the 10 SSC unrelated neonatal deaths.

Conclusion The delayed development of the KFN could represent a specific finding of eSIDS occurring during SSC. Therefore, it is necessary to point out that the SSC represents a further risk factor that must be added to others already known for sudden infant death syndrome. Then this practice needs appropriate monitoring strategies of the infant's conditions.

Keywords

skin-to-skin care - sudden unexpected postnatal collapse - sudden infant death syndrome - early sudden infant death syndrome - risk factors - neuropathology - brain stem - Kölliker-Fuse nucleus

Note

Parents of all the infants included in the study provided written informed consent to autopsy and related research.


 

  • References

  • 1 Whitelaw A, Heisterkamp G, Sleath K, Acolet D, Richards M. Skin to skin contact for very low birthweight infants and their mothers. Arch Dis Child 1988; 63 (11) 1377-1381
    CrossrefPubMedGoogle Scholar
  • 2 Mori R, Khanna R, Pledge D, Nakayama T. Meta-analysis of physiological effects of skin-to-skin contact for newborns and mothers. Pediatr Int 2010; 52 (02) 161-170
    CrossrefPubMedGoogle Scholar
  • 3 Ludington-Hoe SM, Anderson GC, Simpson S. , et al. Skin-to-skin contact beginning in the delivery room for Colombian mothers and their preterm infants. J Hum Lact 1993; 9 (04) 241-242
    CrossrefPubMedGoogle Scholar
  • 4 Legault M, Goulet C. Comparison of kangaroo and traditional methods of removing preterm infants from incubators. J Obstet Gynecol Neonatal Nurs 1995; 24 (06) 501-506
    CrossrefPubMedGoogle Scholar
  • 5 Wahlberg V, Affonso D, Persson B. A retrospective comparative study using the Kangaroo method as a complement to the standard incubator care. Eur J Public Health 1992; 2: 34-37
    CrossrefPubMedGoogle Scholar
  • 6 Anderson GC, Moore E, Hepworth J, Bergman N. Early skin-to-skin contact for mothers and their healthy newborn infants. Cochrane Database Syst Rev 2003; 2 (02) CD003519
    PubMedGoogle Scholar
  • 7 Feldman R, Weller A, Sirota L, Eidelman AI. Skin-to-skin contact (Kangaroo care) promotes self-regulation in premature infants: sleep-wake cyclicity, arousal modulation, and sustained exploration. Dev Psychol 2002; 38 (02) 194-207
    CrossrefPubMedGoogle Scholar
  • 8 Feldman R, Eidelman AI. Skin-to-skin contact (Kangaroo care) accelerates autonomic and neurobehavioural maturation in preterm infants. Dev Med Child Neurol 2003; 45 (04) 274-281
    PubMedGoogle Scholar
  • 9 Herlenius E, Kuhn P. Sudden unexpected postnatal collapse of newborn infants: a review of cases, definitions, risks, and preventive measures. Transl Stroke Res 2013; 4 (02) 236-247
    CrossrefPubMedGoogle Scholar
  • 10 Ferrarello D, Carmichael T. Sudden unexpected postnatal collapse of the newborn. Nurs Womens Health 2016; 20 (03) 268-275
    CrossrefPubMedGoogle Scholar
  • 11 Chen L, Hsu TY, Ou-Yang MC. , et al. Sudden unexpected postnatal collapse of a neonate during skin-to-skin contact. J Clin Case Rep 2016; 6: 12
    PubMedGoogle Scholar
  • 12 Nakamura T, Sano Y. Two cases of infants who needed cardiopulmonary resuscitation during early skin-to-skin contact with mother. J Obstet Gynaecol Res 2008; 34 (4 Pt 2): 603-604
    CrossrefPubMedGoogle Scholar
  • 13 Feldman-Winter L, Goldsmith JP. ; COMMITTEE ON FETUS AND NEWBORN; TASK FORCE ON SUDDEN INFANT DEATH SYNDROME. Safe sleep and skin-to-skin care in the neonatal period for healthy term newborns. Pediatrics 2016; 138 (03) e20161889
    CrossrefPubMedGoogle Scholar
  • 14 Constitution of the Italian Republic Law no. 31. Regulations for diagnostic post-mortem investigation in victims of sudden infant death syndrome (SIDS) and unexpected fetal death. Official Gazette of the Italian Republic, General Series 2006 34. 4 . Available at: http://users.unimi.it/centrolinorossi/files/gazz_ufficiale.pdf . Accessed May 29, 2015
    PubMed
  • 15 Becher JC, Bhushan SS, Lyon AJ. Unexpected collapse in apparently healthy newborns. A prospective national study of a missing cohort of neonatal deaths and near-death events. Arch Dis Child Fetal Neonatal Ed 2012; 97 (01) F30-F34
    CrossrefPubMedGoogle Scholar
  • 16 Nelson EA, Taylor BJ. . ICCPS Study Group. International child care practices study: infant sleep position and parental smoking. Early Hum Dev 2001; 64 (01) 7-20
    CrossrefPubMedGoogle Scholar
  • 17 Fleming P, Blair PS. Sudden infant death syndrome and parental smoking. Early Hum Dev 2007; 83 (11) 721-725
    CrossrefPubMedGoogle Scholar
  • 18 Mitchell EA, Milerad J. Smoking and the sudden infant death syndrome. Rev Environ Health 2006; 21 (02) 81-103
    PubMedGoogle Scholar
  • 19 Connor Gorber S, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M. The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res 2009; 11 (01) 12-24
    CrossrefPubMedGoogle Scholar
  • 20 Lavezzi AM, Ferrero S, Roncati L, Piscioli F, Matturri L, Pusiol T. Nicotinic receptor abnormalities in the cerebellar cortex of sudden unexplained fetal and infant death victims-Possible correlation with maternal smoking. ASN Neuro 2017; 9 (04) 1759091417720582
    PubMedGoogle Scholar
  • 21 Lavezzi AM, Cappiello A, Pusiol T, Corna MF, Termopoli V, Matturri L. Pesticide exposure during pregnancy, like nicotine, affects the brainstem α7 nicotinic acetylcholine receptor expression, increasing the risk of sudden unexplained perinatal death. J Neurol Sci 2015; 348 (1-2): 94-100
    CrossrefPubMedGoogle Scholar
  • 22 Lavezzi AM, Ferrero S, Roncati L, Matturri L, Pusiol T. Impaired orexin receptor expression in the Kölliker-Fuse nucleus in sudden infant death syndrome: possible involvement of this nucleus in arousal pathophysiology. Neurol Res 2016; 38 (08) 706-716
    CrossrefPubMedGoogle Scholar
  • 23 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33 (01) 159-174
    CrossrefPubMedGoogle Scholar
  • 24 Lavezzi AM, Ottaviani G, Rossi L, Matturri L. Cytoarchitectural organization of the parabrachial/Kölliker-Fuse complex in man. Brain Dev 2004; 26 (05) 316-320
    CrossrefPubMedGoogle Scholar
  • 25 Dutschmann M, Mörschel M, Kron M, Herbert H. Development of adaptive behaviour of the respiratory network: implications for the pontine Kolliker-Fuse nucleus. Respir Physiol Neurobiol 2004; 143 (2-3): 155-165
    CrossrefPubMedGoogle Scholar
  • 26 Ludington S, Ferreira C, Wang JIJ. . Preliminary cardiorespiratory, thermal, and behavioral outcomes for 10 days of skin-to-skin contact for incubator care premature infants. In Proceedings of the International Clinical Update and Research Symposium of the National Association of Neonatal Nurses, Seattle, WA, April 13–16, 1995 . Petaluma, CA: NANN 93
    PubMed
  • 27 Suzuki S. Effect of early skin-to-skin contact on breast-feeding. J Obstet Gynaecol 2013; 33 (07) 695-696
    CrossrefPubMedGoogle Scholar
  • 28 Bohnhorst B, Heyne T, Peter CS, Poets CF. Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation. J Pediatr 2001; 138 (02) 193-197
    CrossrefPubMedGoogle Scholar
  • 29 American Academy of Pediatrics Task Force on Infant Positioning and SIDS. Positioning and sudden infant death syndrome (SIDS): update. Pediatrics 1996; 98 (6 Pt 1): 1216-1218
    PubMedGoogle Scholar
  • 30 Kepler J, Gibson E, Dembofsky C, Greenspan J. Changes in SIDS rate and infant sleep practices since the initiation of the “Back to Sleep” campaign. Pediatr Res 1997; 41: 200A
    PubMedGoogle Scholar
  • 31 Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate 1994; 65 (3-4): 194-197
    CrossrefPubMedGoogle Scholar
  • 32 Wright S, Mathieson K, Brearley L. , et al. Ending Newborn Deaths: Ensuring Every Baby Survives. London, United Kingdom:: Save the Children; 2014: 60
    Google Scholar
  • 33 Gnigler M, Ralser E, Karall D, Reiter G, Kiechl-Kohlendorfer U. Early sudden unexpected death in infancy (ESUDI)--three case reports and review of the literature. Acta Paediatr 2013; 102 (05) e235-e238
    CrossrefPubMedGoogle Scholar
  • 34 Niblock MM, Luce CJ, Belliveau RA. , et al. Comparative anatomical assessment of the piglet as a model for the developing human medullary serotonergic system. Brain Res Brain Res Rev 2005; 50 (01) 169-183
    CrossrefPubMedGoogle Scholar
  • 35 Alheid GF, Milsom WK, McCrimmon DR. Pontine influences on breathing: an overview. Respir Physiol Neurobiol 2004; 143 (2-3): 105-114
    CrossrefPubMedGoogle Scholar
  • 36 Kron M, Mörschel M, Reuter J, Zhang W, Dutschmann M. Developmental changes in brain-derived neurotrophic factor-mediated modulations of synaptic activities in the pontine Kölliker-Fuse nucleus of the rat. J Physiol 2007; 583 (Pt 1): 315-327
    CrossrefPubMedGoogle Scholar
  • 37 Ezure K, Tanaka I. Distribution and medullary projection of respiratory neurons in the dorsolateral pons of the rat. Neuroscience 2006; 141 (02) 1011-1023
    CrossrefPubMedGoogle Scholar
  • 38 Segers LS, Shannon R, Lindsey BG. Interactions between rostral pontine and ventral medullary respiratory neurons. J Neurophysiol 1985; 54 (02) 318-334
    CrossrefPubMedGoogle Scholar
  • 39 Dutschmann M, Herbert H. The Kölliker-Fuse nucleus gates the postinspiratory phase of the respiratory cycle to control inspiratory off-switch and upper airway resistance in rat. Eur J Neurosci 2006; 24 (04) 1071-1084
    CrossrefPubMedGoogle Scholar
  • 40 Dutschmann M, Dick TE. Pontine mechanisms of respiratory control. Compr Physiol 2012; 2 (04) 2443-2469
    PubMedGoogle Scholar
  • 41 Mörschel M, Dutschmann M. Pontine respiratory activity involved in inspiratory/expiratory phase transition. Philos Trans R Soc Lond B Biol Sci 2009; 364 (1529): 2517-2526
    CrossrefPubMedGoogle Scholar
  • 42 Dutschmann M, Herbert H. The Kölliker-Fuse nucleus mediates the trigeminally induced apnoea in the rat. Neuroreport 1996; 7 (08) 1432-1436
    CrossrefPubMedGoogle Scholar
  • 43 Dutschmann M, Herbert H. Fos expression in the rat parabrachial and Kölliker-Fuse nuclei after electrical stimulation of the trigeminal ethmoidal nerve and water stimulation of the nasal mucosa. Exp Brain Res 1997; 117 (01) 97-110
    CrossrefPubMedGoogle Scholar
  • 44 Miyaoka Y, Takahashi Y, Sato S, Shimada K. Autonomic nervous reflexes in respiration elicited by mechanical stimulation of the velopharyngeal region in rabbits. J Auton Nerv Syst 1989; 26 (02) 177-180
    CrossrefPubMedGoogle Scholar
  • 45 Bongianni F, Mutolo D, Carfì M, Fontana GA, Pantaleo T. Respiratory neuronal activity during apnea and poststimulatory effects of laryngeal origin in the cat. J Appl Physiol (1985) 2000; 89 (03) 917-925
    CrossrefPubMedGoogle Scholar
  • 46 Dutschmann M, Paton JF. Influence of nasotrigeminal afferents on medullary respiratory neurones and upper airway patency in the rat. Pflugers Arch 2002; 444 (1-2): 227-235
    CrossrefPubMedGoogle Scholar
  • 47 Paton JF. Rhythmic bursting of pre- and post-inspiratory neurones during central apnoea in mature mice. J Physiol 1997; 502 (Pt 3): 623-639
    CrossrefPubMedGoogle Scholar
  • 48 Radulovacki M, Pavlovic S, Saponjic J, Carley DW. Intertrigeminal region attenuates reflex apnea and stabilizes respiratory pattern in rats. Brain Res 2003; 975 (1-2): 66-72
    CrossrefPubMedGoogle Scholar
  • 49 Dhingra RR, Dutschmann M, Galán RF, Dick TE. Kölliker-Fuse nuclei regulate respiratory rhythm variability via a gain-control mechanism. Am J Physiol Regul Integr Comp Physiol 2017; 312 (02) R172-R188
    CrossrefPubMedGoogle Scholar
  • 50 Bautista TG, Dutschmann M. Inhibition of the pontine Kölliker-Fuse nucleus abolishes eupneic inspiratory hypoglossal motor discharge in rat. Neuroscience 2014; 267: 22-29
    CrossrefPubMedGoogle Scholar
  • 51 Harris MB, Milsom WK. Apneusis follows disruption of NMDA-type glutamate receptors in vagotomized ground squirrels. Respir Physiol Neurobiol 2003; 134 (03) 191-207
    CrossrefPubMedGoogle Scholar
  • 52 Lavezzi AM, Corna MF, Matturri L. Disruption of the brain-derived neurotrophic factor (BDNF) immunoreactivity in the human Kölliker-Fuse nucleus in victims of unexplained fetal and infant death. Front Hum Neurosci 2014; 8: 648
    PubMedGoogle Scholar
  • 53 Levitt ES, Abdala AP, Paton JF, Bissonnette JM, Williams JT. μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive. J Physiol 2015; 593 (19) 4453-4469
    CrossrefPubMedGoogle Scholar
  • 54 Lavezzi AM, Casale V, Oneda R, Weese-Mayer DE, Matturri L. Sudden infant death syndrome and sudden intrauterine unexplained death: correlation between hypoplasia of raphé nuclei and serotonin transporter gene promoter polymorphism. Pediatr Res 2009; 66 (01) 22-27
    CrossrefPubMedGoogle Scholar
  • 55 Matturri L, Ottaviani G, Alfonsi G, Crippa M, Rossi L, Lavezzi AM. Study of the brainstem, particularly the arcuate nucleus, in sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD). Am J Forensic Med Pathol 2004; 25 (01) 44-48
    CrossrefPubMedGoogle Scholar
  • 56 Lavezzi AM, Weese-Mayer DE, Yu MY. , et al. Developmental alterations of the respiratory human retrotrapezoid nucleus in sudden unexplained fetal and infant death. Auton Neurosci 2012; 170 (1-2): 12-19
    CrossrefPubMedGoogle Scholar
  • 57 Lavezzi AM, Matturri L. Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death. Front Hum Neurosci 2012; 6: 322
    PubMedGoogle Scholar
  • 58 Lavezzi AM, Mecchia D, Matturri L. Neuropathology of the area postrema in sudden intrauterine and infant death syndromes related to tobacco smoke exposure. Auton Neurosci 2012; 166 (1-2): 29-34
    CrossrefPubMedGoogle Scholar
  • 59 Lavezzi AM, Corna MF, Matturri L. Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking. Neural Dev 2010; 5: 17-25
    CrossrefPubMedGoogle Scholar
  • 60 Paterson DS, Trachtenberg FL, Thompson EG. , et al. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA 2006; 296 (17) 2124-2132
    CrossrefPubMedGoogle Scholar
  • 61 Ozawa Y, Okado N. Alteration of serotonergic receptors in the brain stems of human patients with respiratory disorders. Neuropediatrics 2002; 33 (03) 142-149
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Mikhail Y, Ahmed YY. Outline of the arcuate nucleus in the human medulla oblongata. Acta Anat (Basel) 1975; 92 (02) 285-291
    CrossrefPubMedGoogle Scholar
  • 63 Matturri L, Biondo B, Mercurio P, Rossi L. Severe hypoplasia of medullary arcuate nucleus: quantitative analysis in sudden infant death syndrome. Acta Neuropathol 2000; 99 (04) 371-375
    CrossrefPubMedGoogle Scholar
  • 64 Filiano JJ, Kinney HC. Arcuate nucleus hypoplasia in the sudden infant death syndrome. J Neuropathol Exp Neurol 1992; 51 (04) 394-403
    CrossrefPubMedGoogle Scholar
  • 65 Kinney HC. Brainstem mechanisms underlying the sudden infant death syndrome: evidence from human pathologic studies. Dev Psychobiol 2009; 51 (03) 223-233
    CrossrefPubMedGoogle Scholar
  • 66 Roncati L, Termopoli V, Pusiol T. Negative role of the environmental endocrine disruptors in the human neurodevelopment. Front Neurol 2016; 7: 143
    PubMedGoogle Scholar
  • 67 Roncati L, Piscioli F, Pusiol T. The endocrine disruptors among the environmental risk factors for stillbirth. Sci Total Environ 2016; 563-564: 1086-1087
    CrossrefPubMedGoogle Scholar