A recent publication in the
Frontiers in Neurology, expands on the growing body of neurological examination of extreme pain and trauma in infancy, and soon after birth, and its triggering implication on SIDS. In "A 'Wear and Tear' Hypothesis to Explain Sudden Infant Death Syndrome" Eran Elhaik presents the following material on infant genital cutting in the United States and its relation to the atypically high SIDS rate in the U.S.
Abstract (excerpt)
We also predict that neonatal male circumcision will account for the SIDS gender bias and that groups that practice high male circumcision rates, such as USA whites, will have higher SIDS rates compared to groups with lower circumcision rates. SIDS rates will also be higher in USA states where Medicaid covers circumcision and lower among people that do not practice neonatal circumcision and/or cannot afford to pay for circumcision. We last predict that winter-born premature infants who are circumcised will be at higher risk of SIDS compared to infants who experienced fewer nociceptive exposures.
Background (excerpt)
Circumcision is one of the most common elective surgical procedures in the world and is performed primarily on males (56). Female circumcision is practiced in nearly 30 African countries, some Southeast Asian and Middle Eastern countries, and in immigrant communities in Europe and North America (57). Despite its relevancy, female neonatal circumcision will not be discussed here since in most western countries it is illegal and thereby under-reported and we lack SIDS data for the remaining countries. In North America, ~1.2 million male infants are circumcised every year (58) often within the first 2 days of life (59). Although not requiring general anesthesia, circumcision is an intensively painful procedure requiring adequate analgesia (60). Circumcision is associated with intraoperative and postoperative risks, including bleeding, shock, sepsis, circulatory shock, and hemorrhage (61–63) that can result in death (63, 64).
Infant deaths following religious neonatal circumcision have been known for at least two millennia (65). Talmud (the central text of Rabbinic Judaism) sages ruled in the first centuries A.D. that mothers with two children who have died following the surgery should receive an exemption from circumcising their infants. During the nineteenth century, developments in medical knowledge on one hand and the rise of Jewish “Enlightenment” on the other hand, brought many Jews to reject the authority of the Talmud and with that the practice of circumcision. A new wave of accusations toward Jewish circumcisers (mohels) and rabbis of infant deaths following circumcision soon appeared and prompted community leaders to appeal to the governing authorities to forbid this practice – efforts that were countered by rabbis’ threats to ban the admission of uncircumcised Jewish children from Jewish schools. The fierce arguments about the necessity of the procedure last to this day and led many Jews to opt their infants out of the procedure, including Theodor Herzl, one of the fathers of modern political Zionism (66). In the UK, Gairdner (67) estimated an annual rate of 16 per 100,000 circumcision-associated deaths for boys under 1-year old in a study that influenced the British government to exclude circumcision coverage from the National Health Service. Remarkably, the SIDS rates in the UK (0.38 per 1000) are much lower than in the USA (0.55 per 1000) (10) where most male infants are circumcised (58). Moreover, most of the deaths in the USA occur in non-Hispanic blacks (83% higher death rate compared with non-Hispanic whites). SIDS rates were 44% lower for Hispanics compared with non-Hispanic whites (68). Interestingly the circumcision rates among Hispanics are about half that of the two other groups (69).
Circumcision contributes to the rise in allostatic load and increased risk for SIDS through multiple conduits. Circumcision produces crush and incisional injuries during amputation, resulting in damage to normal prepuce tissue, the associated nerves, and blood vessels. Wound healing manifested by hyperaemia and swelling at day 7 postoperative is observed in 70% of infants with minimally retractile prepuces seen in infants circumcised before 1 year of age with subsequent bacterial carriage of skin commensals (70). Circumcised males have increased pain responses to childhood immunization 4–6 months post-surgery (71, 72) consistent with central sensitization (73). The abnormal development of sensory pathways in the developing nervous system elicited by the pain during critical postnatal periods is manifested in later life following nociceptive reexposure by abnormal sensory thresholds and pain responses that are not restricted to the original site of postnatal trauma (74–76). Neonatal nociceptive exposure induces long-term hypoalgesia or hyperalgesia depending on the nature and timing of the trauma (54, 77) and is consistent with surgery and pain adversely impacting neurodevelopment independent of anesthetic (76).
Post-circumcision, tactile hypersensitivity increases due to post-surgical and -traumatic mechanisms that contribute toward allostasis and the risk of SIDS. This is evident by the increase in toll-like receptor 4 (78) associated with post-circumcision wound healing, which is also observed in post-surgical tactile hypersensitivity in males and dependent on testosterone (79). Following peripheral nerve injury, the purinergic receptors in the spinal cord microglial cells release BDNF (79) and mitogen-activated protein kinase p38 (80) that contribute to neuropathic pain and tactile hypersensitivity. Due to their testosterone dependency, they are seen only in males (79). The testosterone surge occurring during the first 2- to 4-month period may increase susceptibility to the initial stages of infection and is consistent with the peak in SIDS mortality (81).
Male neonates subjected to circumcision can experience severe cardiorespiratory pain responses, including cyanosis, apnea, increased heart rate (82), and increased pitch (fundamental frequency) of cry (as high as 800–2000 Hz) associated with decreased heart rate variability, i.e., decreased vagotonia (83–85), a likely risk factor for SIDS. Other circumcision sequelae of sufficient severity to require emergency room evaluation or hospital admission and contribute toward allostasis include infection, urinary retention, inflammatory redness and swelling ascribed to healing (86, 87), and amputation/necrosis of the glans (88). Behavioral abnormalities, such as eating disturbance and disturbed sleep, are also the consequence of pain exposure (89).
Postoperative circumcision pain of ample severity to require analgesia is expected for about 10 days for healing with incomplete wound healing past day 14 seen in up to 6% of infants depends on the device used to amputate the foreskin (88), which is also associated with various adverse events (56, 90). The overall complication rate for circumcision ranges from 0.2 to 10% with many USA physicians performing the procedure without formal training, being unaware of contraindications, and incapable of handling post-op complications (56, 91, 92). Lower complication rates for early and late adverse events have been attributed to underreporting with late adverse events mistakenly not attributed to circumcision (92, 93). Consequently, the low number ascribed to circumcision as the cause of death (63) may be underreported and erroneously attributed to other causes, such as sepsis (94) or SIDS.
One mechanism by which circumcision may elicit SIDS concerns the inhibition of nerves involved in nociception processing that produces prolonged apnea while impairing cortical arousal. Neonatal surgery that traumatizes peripheral nerves with associated tactile hypersensitivity followed by a subsequent surgery later in development can increase spinal cord microglia signaling and elicit persistent hyperalgesia (80). It can also produce post-surgical hyperalgesia that subsequently alters postnatal development of the rostral rostroventral medulla (RVM), which controls the excitability of spinal neurons by spinally projecting neurons from the nucleus paragigantocellularis lateralis (PGCL) and the nucleus raphe magnus. Alterations in the RVM result in a descending inhibition of spinal reflex excitability on nociception (95). Inhibition of RVM neurons was shown to limit the duration of the laryngeal chemoreflex and produce prolonged apnea that contributes toward SIDS, particularly when combined with stimuli that inhibit respiration (96). In SIDS, norepinephrine, which depresses respiration, is increased in the PGCL and serotonin 5-HT1A receptor that mediates nociceptive stimuli in the brainstem (97) and decreased in the raphe nuclei and the arcuate nuclei (98). The reduction in 5-HT1A receptors observed in the brainstem of SIDS infants prompts the hypothesis that SIDS is caused by a brainstem abnormality that impairs the ability to generate protective responses to life-threatening challenges (99, 100). This hypothesis, however, does not explain why SIDS peaks at 2–4 months, rather than in an earlier GA (101). Orexin is another important regulator of both pain and sleep dysfunction. Orexin knockout mice presented greater degree of hyperalgesia induced by peripheral inflammation and less stress-induced analgesia than wild-type mice (102). In the rostral ventrolateral medulla and PGCL, orexin receptors are expressed in sympathoexcitatory bulbospinal neurons (103). A significantly decreased orexin immunoreactivity in the hypothalamus and pontine nuclei was observed in SIDS infants (104).
Another mechanism that can explain the SIDS toll following circumcision is the loss of ~1–2 ounces (oz) of blood out of a total of ~11 oz that a 3,000 gram male newborn has (105), the equivalent of ~1–2 blood donations in an adult. Excessive bleeding is highly common in circumcision with reports range from 0.1 to 35% (91, 106) in neonates. However, even moderate bleeding puts the infant as risk, and, being an inherent part of the procedure, it is not reported as a complication. Blood loss of 2–2.5 oz, ~15% of the total blood volume at birth, is sufficient to cause hypovolemia and death. Since a large fraction of newborns (26%), particularly premature infants, weigh much less than 3,000 grams (107), a smaller amount of blood loss may trigger hypovolemic shock. Therefore, when bleeding an infant of low birth weight or GA, the effect may be pathological resulting in a reduced blood pressure that has been associated with obstructive sleep apnea (OSA), a condition where the walls of the throat relax and narrow during sleep, interrupting normal breathing (108). It is, therefore, not surprising that most of the deaths following circumcision in high-income countries were due to bleeding (63). While it is accepted that failure of neural mechanisms causing arousal from sleep may play a role in at least some SIDS cases [e.g., Ref. (109)], it is unclear what causes the initial failure of the respiratory control (110). Comparing the breathing characteristics of 40 infants who eventually died of SIDS with 607 healthy controls, Kato and colleagues reported that SIDS infants have a greater proportion of obstructive and mixed apneic episodes than the control group (111). Although the frequency of these episodes decreased with age, the decrease was smaller in the SIDS infants than in the controls, in support of either immature or impaired respiratory control. Looking at the data by gender, however, shows that only boys exhibit a difference in apnea frequency in support of an impaired respiratory control (111), perhaps due to circumcision.
To date, circumcision in the USA, despite being the most common pediatric surgery, has not been subjected to the same systematic scientific scrutiny looking at immediate and delayed adverse effects, including pain [e.g., Ref. (112)], nor has circumcision status been included as part of a thorough SIDS investigation/registry or analyses [e.g., Ref. (2)] in spite of the male predominance of both neonatal circumcision and SIDS. However, based on assessment of risk of harms versus benefit, despite the latter including decreased risk of urinary tract infection (113), the Royal Australasian College of Physicians, the British Medical Association, the Canadian Paediatric Society (87), and several west European medical societies have recommended against routine neonatal circumcision (114), arguing that the benefits of circumcision to children are minimal, non-existent, or outweighed by the risks, and that circumcision is thereby unwarranted. The AAP’s recommendation in favor of this routine (115) has been widely criticized [e.g., Ref. (116)].
The Significance of the Allostatic Load Model for SIDS
Sudden infant death syndrome occurs when an infant dies suddenly, unexpectedly, and without a cause identified through a forensic autopsy or death-scene investigation. We speculate that SIDS is caused by prolonged and repetitive iatrogenic stressful, painful, or traumatic experiences during critical development stages that constitute allostatic overload (156). Over the past years, allostatic load models were proposed to explain several leading medical conditions, including mental health disorders (157, 158), preterm birth (159), and chronic stress (160).
While the infant’s first environment is typically romanticized as peaceful, painless, hygienic, safe, and harmless, in practicality it may be anything but that. Already in the uterus, the fetus may be exposed to maternal substance use (e.g., smoking and drug use) associated with SIDS (19, 161). During a prolonged hospitalization in the Neonatal Intensive Care Unit that follows a preterm birth, infants may be exposed to extended and repeated pain, which thier unstable and immature physiological systems are unable to offset and will potentially render them more vulnerable to the effects of repeated invasive procedures (38). Neonatal circumcision typically involves maternal separation, pain, bleeding, and shock and, like any operation, puts the infant at risks of hemorrhage and sepsis even when anesthetic is used (67). The long-term consequences of circumcision include, among else, greater pain response to routine immunizations within the few months past birth (72). During winter time, the infant is at risk of infection and illnesses that grows with the number of household members, particularly older children (126), which explains why an elevated immune response is one of the hallmarks of SIDS (123, 128). Other common stressors may include birth trauma, birth injury, traumatic injury, life-threatening event, inadequate nutrition, heel lances, prolonged institutionalization, skin breaks, and air pollution – all contribute to the build-up of toxic allostatic load.
Our model represents a major departure from previous models, such as the “three interrelated causal spheres of influence model” that requires two out of three factors to act simultaneously (subclinical tissue damage, deficiency in postnatal development of reflexes and responses, and environmental factors) (162), or the more popular “triple-risk model,” which advocates that the combined effect of three factors (vulnerable infant, critical development period, and environmental stressors) causes SIDS (163). Our model posits that any infant may succumb to SIDS when the combined and cumulative effect of the environmental stressors has exceeded their tolerance level shaped by their unique genetic and environmental factors (Figure (Figure11).
Testing the Hypothesis (excerpt)
Neonatal Circumcision is a Risk Factor for SIDS
Double-blinded case–control human studies aiming to test our hypothesis are unfeasible due to ethical consideration and the difficulties in matching cases and controls (19). Fortunately, the prepuce has been well conserved throughout mammalian evolution (164), which attests to its functional importance, and allows carrying out animal studies. Our hypothesis can be tested by circumcising the prepuce of mammalian animal models and measuring whether an excess of SIDS is observed among cases when compared with untreated controls. Curiously, none of the studies purporting the “benefits” of neonatal circumcision has ever been demonstrated using animal models, which are the only viable means to carry out double-blinded case–control studies assessing the short- and long-term health impacts of circumcision. In humans, we can expect higher SIDS rates in Anglophone countries that adopted male neonatal circumcision in the nineteenth century, compared to Iberio-American that traditionally have opposed circumcision (66). We can also expect a higher incidence of SIDS in USA states where Medicaid, the most common health insurance, covers circumcision, compares to states where this procedure is not covered by Medicaid after accounting for culture and socioeconomic status. The data for such study can be obtained from the CDC’s SIDS registry (165). Finally, we can compare the circumcision status of SIDS victims versus healthy controls, obtained through autopsies and questionnaires, respectively. New genetic tools, such as Case-control matcher (http://www.elhaik-lab.group.shef.ac.uk/ElhaikLab/index.php), based on biogeographic ancestry tools [e.g., Ref. (166)], can be instrumental in optimizing case–control matches by identifying individuals that have similar population structure and genetic background and minimizing the bias studies due to population stratification.
Male Neonatal Circumcision Accounts for a Large Fraction of the Gender Bias in SIDS
We speculate that the male bias in SIDS observed in western countries may be due to both natural protections that render females more resilient to nociceptive stimuli and legal-cultural ones that protect females from circumcision in these countries. The weights of these two factors are unknown, yet we expect the gender deviations from even proportions in SIDS to be correlated with circumcision rates. Consequently, large male bias is expected in societies that practice neonatal circumcision whereas smaller bias is expected in societies that circumcise both males and females or avoid it altogether.
Circumcised Premature Infants Are at High Risk
We predict that circumcised premature infants would be at higher risk for SIDS compared with intact preterm infants. This can be tested by an analysis of hospital records after properly matching cases with controls (19).
Additional complications that should be considered when testing these predictions in humans include misclassification of SIDS to other categories, inconsistent reports of SIDS over time in certain countries due to changes in definitions, inconsistent reports of circumcision (167), and the absence of legislation requiring an autopsy or thorough death-scene investigation.
Source
Elhaik, E. (2016).
A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome.
Frontiers in Neurology, 7, 180.
References Cited
1.
Mitchell EA, Krous HF. Sudden unexpected death in infancy: a historical perspective. J Paediatr Child Health (2015) 51:108–12.10.1111/jpc.12818 [PubMed] [Cross Ref]
2.
Camperlengo L, Shapiro-Mendoza CK, Gibbs F. Improving sudden unexplained infant death investigation practices: an evaluation of the Centers for Disease Control and Prevention’s SUID Investigation Training Academies. Am J Forensic Med Pathol (2014) 35:278–82.10.1097/PAF.0000000000000123 [PubMed] [Cross Ref]
3.
Garstang J, Ellis C, Sidebotham P. An evidence-based guide to the investigation of sudden unexpected death in infancy. Forensic Sci Med Pathol (2015) 11:345–57.10.1007/s12024-015-9680-x [PubMed][Cross Ref]
5.
Opdal SH, Rognum TO. The sudden infant death syndrome gene: does it exist? Pediatrics (2004) 114:e506–12.10.1542/peds.2004-0683 [PubMed] [Cross Ref]
6.
Horne RS, Hauck FR, Moon RY. Sudden infant death syndrome and advice for safe sleeping. Br Med J(2015) 350:h1989.10.1136/bmj.h1989 [PubMed] [Cross Ref]
7.
Hauck FR, Tanabe KO. International trends in sudden infant death syndrome: stabilization of rates requires further action. Pediatrics (2008) 122:660–6.10.1542/peds.2007-0135 [PubMed] [Cross Ref]
8.
Hakeem GF, Oddy L, Holcroft CA, Abenhaim HA. Incidence and determinants of sudden infant death syndrome: a population-based study on 37 million births. World J Pediatr (2015) 11:41–7.10.1007/s12519-014-0530-9 [PubMed] [Cross Ref]
9.
Waters KA. SIDS symposium–a perspective for future research. Paediatr Respir Rev (2014) 15:285–6.10.1016/j.prrv.2014.09.005 [PubMed] [Cross Ref]
10.
Hauck FR, Tanabe KO. International trends in sudden infant death syndrome and other sudden unexpected deaths in infancy: need for better diagnostic standardization. Curr Pediatr Rev (2010) 6:95–101.10.2174/157339610791317241 [Cross Ref]
11.
Hunt CE, Darnall RA, McEntire BL, Hyma BA. Assigning cause for sudden unexpected infant death. Forensic Sci Med Pathol (2015) 11:283–8.10.1007/s12024-014-9650-8 [PMC free article] [PubMed][Cross Ref]
12.
Sauber-Schatz EK, Sappenfield WM, Shapiro-Mendoza CK. Comprehensive review of sleep-related sudden unexpected infant deaths and their investigations: Florida 2008. Matern Child Health J (2015) 19:381–90.10.1007/s10995-014-1520-1 [PubMed] [Cross Ref]
13.
Hauck FR, Tanabe KO, McMurry T, Moon RY. Evaluation of bedtime basics for babies: a national crib distribution program to reduce the risk of sleep-related sudden infant deaths. J Community Health (2015) 40:457–63.10.1007/s10900-014-9957-0 [PMC free article] [PubMed] [Cross Ref]
14.
Byard R, Beal S. Has changing diagnostic preference been responsible for the recent fall in incidence of sudden infant death syndrome in South Australia? J Paediatr Child Health (1995) 31:197–9.10.1111/j.1440-1754.1995.tb00785.x [PubMed] [Cross Ref]
15.
Malloy MH, MacDorman M. Changes in the classification of sudden unexpected infant deaths: United States, 1992–2001. Pediatrics (2005) 115:1247–53.10.1542/peds.2004-2188 [PubMed] [Cross Ref]
16.
Läer K, Dörk T, Vennemann M, Rothämel T, Klintschar M. Polymorphisms in genes of respiratory control and sudden infant death syndrome. Int J Legal Med (2015) 129:977–84.10.1007/s00414-015-1232-0 [PubMed] [Cross Ref]
17.
Poetsch M, Todt R, Vennemann M, Bajanowski T. That’s not it, either-neither polymorphisms in PHOX2B nor in MIF are involved in sudden infant death syndrome (SIDS). Int J Legal Med (2015) 129:985–9.10.1007/s00414-015-1213-3 [PubMed] [Cross Ref]
18.
Jensen LL, Banner J, Byard RW. Does β-APP staining of the brain in infant bed-sharing deaths differentiate these cases from sudden infant death syndrome? J Forensic Leg Med (2014) 27:46–9.10.1016/j.jflm.2014.07.006 [PubMed] [Cross Ref]
20.
Phillips DP, Brewer KM, Wadensweiler P. Alcohol as a risk factor for sudden infant death syndrome (SIDS). Addiction (2011) 106:516–25.10.1111/j.1360-0443.2010.03199.x [PubMed] [Cross Ref]
21.
Trachtenberg FL, Haas EA, Kinney HC, Stanley C, Krous HF. Risk Factor Changes for Sudden Infant Death Syndrome After Initiation of Back-to-Sleep Campaign. Pediatrics (2012) 129:630–8.10.1542/peds.2011-1419 [PMC free article] [PubMed] [Cross Ref]
22.
Goldstein RD, Trachtenberg FL, Sens MA, Harty BJ, Kinney HC. Overall postneonatal mortality and rates of SIDS. Pediatrics (2016) 137:1–10.10.1542/peds.2015-2298 [PubMed] [Cross Ref]
24.
Sterling P. Allostasis: a model of predictive regulation. Physiol Behav (2012) 106:5–15.10.1016/j.physbeh.2011.06.004 [PubMed] [Cross Ref]
25.
Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol (2009) 19:207–12.10.1016/j.conb.2009.05.009 [PMC free article] [PubMed][Cross Ref]
26.
McEwen BS, Gianaros PJ. Stress-and allostasis-induced brain plasticity. Annu Rev Med (2011) 62:431–45.10.1146/annurev-med-052209-100430 [PMC free article] [PubMed] [Cross Ref]
27.
McEwen BS, Gray JD, Nasca C. 60 years of neuroendocrinology: redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. J Endocrinol (2015) 226:T67–83.10.1530/JOE-15-0121 [PMC free article] [PubMed] [Cross Ref]
28.
McEwen BS. Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology (2000) 22:108–24.10.1016/S0893-133X(99)00129-3 [PubMed] [Cross Ref]
29.
McEwen BS, Seeman T. Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci (1999) 896:30–47.10.1111/j.1749-6632.1999.tb08103.x [PubMed] [Cross Ref]
30.
Katz DA, Sprang G, Cooke C. Allostatic load and child maltreatment in infancy. Clin Case Stud (2011) 10:159–72.10.1177/1534650111399121 [Cross Ref]
32.
Tye K, Pollard I, Karlsson L, Scheibner V, Tye G. Caffeine exposure in utero increases the incidence of apnea in adult rats. Reprod Toxicol (1993) 7:449–52.10.1016/0890-6238(93)90089-P [PubMed][Cross Ref]
33.
Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci (2008) 28:9055–65.10.1523/JNEUROSCI.1424-08.2008 [PMC free article][PubMed] [Cross Ref]
34.
Page GG, Hayat MJ, Kozachik SL. Sex differences in pain responses at maturity following neonatal repeated minor pain exposure in rats. Biol Res Nurs (2011) 15:96–104.10.1177/1099800411419493 [PubMed] [Cross Ref]
35.
Kudielka BM, Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol(2005) 69:113–32.10.1016/j.biopsycho.2004.11.009 [PubMed] [Cross Ref]
36.
Paterson DS, Trachtenberg FL, Thompson EG, Belliveau RA, Beggs AH, Darnall R, et al. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA (2006) 296:2124–32.10.1001/jama.296.17.2124 [PubMed] [Cross Ref]
37.
Malloy M. Prematurity and sudden infant death syndrome: United States 2005–2007. J Perinatol (2013) 33:470–5.10.1038/jp.2012.158 [PubMed] [Cross Ref]
38.
Grunau RE, Holsti L, Peters JW. Long-term consequences of pain in human neonates. Semin Fetal Neonatal Med (2006) 11:268–75.10.1016/j.siny.2006.02.007 [PubMed] [Cross Ref]
39.
Grunau RE, Whitfield MF, Petrie-Thomas J, Synnes AR, Cepeda IL, Keidar A, et al. Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants. Pain (2009) 143:138–46.10.1016/j.pain.2009.02.014 [PMC free article] [PubMed][Cross Ref]
40.
Slater R, Fabrizi L, Worley A, Meek J, Boyd S, Fitzgerald M. Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants. Neuroimage (2010) 52:583–9.10.1016/j.neuroimage.2010.04.253 [PubMed] [Cross Ref]
41.
Anand K, Scalzo FM. Can adverse neonatal experiences alter brain development and subsequent behavior? Neonatology (2000) 77:69–82.10.1159/000014197 [PubMed] [Cross Ref]
42.
Marcus DA. A review of perinatal acute pain: treating perinatal pain to reduce adult chronic pain. J Headache Pain (2006) 7:3–8.10.1007/s10194-006-0267-5 [PMC free article] [PubMed] [Cross Ref]
43.
Cohen G, Katz-Salamon M, Malcolm G. A key circulatory defence against asphyxia in infancy – the heart of the matter! J Physiol (2012) 590:6157–65.10.1113/jphysiol.2012.239145 [PMC free article][PubMed] [Cross Ref]
44.
Fyfe KL, Yiallourou SR, Wong FY, Odoi A, Walker AM, Horne RS. Gestational age at birth affects maturation of baroreflex control. J Pediatr (2015) 166:559–65.10.1016/j.jpeds.2014.11.026 [PubMed][Cross Ref]
45.
Fyfe KL, Yiallourou SR, Wong FY, Odoi A, Walker AM, Horne RS. The effect of gestational age at birth on post-term maturation of heart rate variability. Sleep (2015) 38:1635–44.10.5665/sleep.5064 [PMC free article] [PubMed] [Cross Ref]
46.
Fyfe KL, Odoi A, Yiallourou SR, Wong FY, Walker AM, Horne RS. Preterm infants exhibit greater variability in cerebrovascular control than term infants. Sleep (2015) 38:1411–21.10.5665/sleep.4980 [PMC free article] [PubMed] [Cross Ref]
47.
Hays SR, Deshpande JK. Newly postulated neurodevelopmental risks of pediatric anesthesia: theories that could rock our world. J Urol (2013) 189:1222–8.10.1016/j.juro.2012.11.090 [PubMed] [Cross Ref]
48.
Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity – clinical implications of animal models. N Engl J Med (2015) 372:796–7.10.1056/NEJMp1414786 [PubMed] [Cross Ref]
49.
Psaty BM, Platt R, Altman RB. Neurotoxicity of generic anesthesia agents in infants and children: an orphan research question in search of a sponsor. JAMA (2015) 313:1515–6.10.1001/jama.2015.1149 [PubMed] [Cross Ref]
50.
Nasr VG, Davis JM. Anesthetic use in newborn infants: the urgent need for rigorous evaluation. Pediatr Res (2015) 78:2–6.10.1038/pr.2015.58 [PMC free article] [PubMed] [Cross Ref]
51.
Warner DO, Flick RP. Anaesthetics, infants, and neurodevelopment: case closed? The Lancet (2015) 387:239–50.10.1016/S0140-6736(15)00669-8 [Cross Ref]
52.
Morriss FH, Jr, Saha S, Bell EF, Colaizy TT, Stoll BJ, Hintz SR, et al. Surgery and neurodevelopmental outcome of very low birth weight infants. JAMA pediatrics (2014) 168:746–54.10.1001/jamapediatrics.2014.307 [PMC free article] [PubMed] [Cross Ref]
53.
Walker SM. Biological and neurodevelopmental implications of neonatal pain. Clin Perinatol (2013) 40:471–91.10.1016/j.clp.2013.05.002 [PubMed] [Cross Ref]
54.
Li J, Kritzer E, Craig PE, Baccei ML. Aberrant synaptic integration in adult lamina I projection neurons following neonatal tissue damage. J Neurosci (2015) 35:2438–51.10.1523/JNEUROSCI.3585-14.2015 [PMC free article] [PubMed] [Cross Ref]
55.
American Academy of Pediatrics and Canadian Paediatric Society. Prevention and management of pain in the neonate: an update. Pediatrics (2006) 118:2231–41.10.1542/peds.2006-2277 [PubMed] [Cross Ref]
56.
DeMaria J, Abdulla A, Pemberton J, Raees A, Braga LH. Are physicians performing neonatal circumcisions well-trained? Can Urol Assoc J (2013) 7:260–4.10.5489/cuaj.200 [PMC free article][PubMed] [Cross Ref]
58.
Weiss AJ, Elixhauser A. Trends in Operating Room Procedures in U.S. Hospitals, 2001–2011. Healthcare Cost and Utilization Project (HCUP) (2014). Available from: http://www.hcup-us.ahrq.gov/[PubMed]
60.
Ward RM, Stiers J, Buchi K. Neonatal medications. Pediatr Clin North Am (2015) 62:525–44.10.1016/j.pcl.2014.11.012 [PubMed] [Cross Ref]
61.
Weiss HA, Larke N, Halperin D, Schenker I. Complications of circumcision in male neonates, infants and children: a systematic review. BMC Urol (2010) 10:2.10.1186/1471-2490-10-2 [PMC free article][PubMed] [Cross Ref]
62.
Boyle GJ. Circumcision of infants and children: short-term trauma and long-term psychosexual harm. Adv Sex Med (2015) 5:22–38.10.4236/asm.2015.52004 [Cross Ref]
63.
Edler G, Axelsson I, Barker GM, Lie S, Naumburg E. Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure. Acta Paediatr (2016) 105:842–50.10.1111/apa.13402 [PubMed] [Cross Ref]
65.
Leas BF, Umscheid CA. Neonatal herpes simplex virus type 1 infection and Jewish ritual circumcision with oral suction: a systematic review. J Pediatric Infect Dis Soc (2014) 4:126–31.10.1093/jpids/piu075 [PMC free article] [PubMed] [Cross Ref]
66. Gollaher D. Circumcision: A History of the World’s Most Controversial Surgery. New York: Basic Books; (2001).
67.
Gairdner D. The fate of the foreskin, a study of circumcision. Br Med J (1949) 2:1433–7.10.1136/bmj.2.4642.1433 [PMC free article] [PubMed] [Cross Ref]
68.
Mathews T, MacDorman MF. Infant mortality statistics from the 2009 period linked birth/infant death data set. Natl Vital Stat Rep (2013) 61:1–28. [PubMed]
69.
Xu F, Markowitz LE, Sternberg MR, Aral SO. Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999–2004. Sex Transm Dis (2007) 34:479–84.10.1097/01.olq.0000253335.41841.04 [PubMed] [Cross Ref]
70.
Tarhan H, Akarken I, Koca O, Ozgü I, Zorlu F. Effect of preputial type on bacterial colonization and wound healing in boys undergoing circumcision. Korean J Urol (2012) 53:431–4.10.4111/kju.2012.53.6.431 [PMC free article] [PubMed] [Cross Ref]
71.
Taddio A, Goldbach M, Ipp M, Stevens B, Koren G. Effect of neonatal circumcision on pain responses during vaccination in boys. The Lancet (1995) 345:291–2.10.1016/S0140-6736(95)90278-3 [PubMed][Cross Ref]
72.
Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. The Lancet (1997) 349:599–603.10.1016/S0140-6736(96)10316-0 [PubMed] [Cross Ref]
73.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain (2011) 152:S2–15.10.1016/j.pain.2010.09.030 [PMC free article] [PubMed] [Cross Ref]
74.
Beggs S. Long-term consequences of neonatal injury. Can J Psychiatry (2015) 60:176–80.10.1177/070674371506000404 [PMC free article] [PubMed] [Cross Ref]
75.
Noel M, Palermo TM, Chambers CT, Taddio A, Hermann C. Remembering the pain of childhood: applying a developmental perspective to the study of pain memories. Pain (2015) 156:31–4.10.1016/j.pain.0000000000000001 [PubMed] [Cross Ref]
76.
Ririe DG. How long does incisional pain last: early life vulnerability could make it last a lifetime. Anesthesiology (2015) 122:1189–91.10.1097/ALN.0000000000000660 [PMC free article] [PubMed][Cross Ref]
77.
Schwaller F, Fitzgerald M. The consequences of pain in early life: injury-induced plasticity in developing pain pathways. Eur J Neurosci (2014) 39:344–52.10.1111/ejn.12414 [PMC free article][PubMed] [Cross Ref]
78.
Chen L, Guo S, Ranzer MJ, DiPietro LA. Toll-like receptor 4 plays an essential role in early skin wound healing. J Invest Dermatol (2013) 133:258–67.10.1038/jid.2012.267 [PMC free article] [PubMed][Cross Ref]
79.
Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci (2015) 18:1081–3.10.1038/nn.4053 [PMC free article] [PubMed] [Cross Ref]
80.
Schwaller F, Beggs S, Walker SM. Targeting p38 mitogen-activated protein kinase to reduce the impact of neonatal microglial priming on incision-induced hyperalgesia in the adult rat. Anesthesiology (2015) 122:1377–90.10.1097/ALN.0000000000000659 [PMC free article] [PubMed] [Cross Ref]
81.
Moscovis SM, Hall ST, Burns CJ, Scott RJ, Blackwell CC. The male excess in sudden infant deaths. Innate Immun (2014) 20:24–9.10.1177/1753425913481071 [PubMed] [Cross Ref]
82.
O’Conner-Von S, Turner HN. American Society for Pain Management Nursing (ASPMN) position statement: male infant circumcision pain management. Pain Manag Nurs (2013) 14:379–82.10.1016/j.pmn.2011.08.007 [PubMed] [Cross Ref]
83.
Porter FL, Miller RH, Marshall RE. Neonatal pain cries: effect of circumcision on acoustic features and perceived urgency. Child Dev (1986) 57:790–802.10.2307/1130355 [PubMed] [Cross Ref]
84.
Porter FL, Porges SW, Marshall RE. Newborn pain cries and vagal tone: parallel changes in response to circumcision. Child Dev (1988) 59:495–505.10.2307/1130327 [PubMed] [Cross Ref]
85.
Stewart AM, Lewis GF, Heilman KJ, Davila MI, Coleman DD, Aylward SA, et al. The covariation of acoustic features of infant cries and autonomic state. Physiol Behav (2013) 120:203–10.10.1016/j.physbeh.2013.07.003 [PMC free article] [PubMed] [Cross Ref]
86.
Gold G, Young S, O’Brien M, Babl FE. Complications following circumcision: presentations to the emergency department. J Paediatr Child Health (2015) 51:1158–63.10.1111/jpc.12960 [PubMed][Cross Ref]
87.
Sorokan ST, Finlay JC, Jefferies AL, Canadian Paediatric Society, Fetus and Newborn Committee, Infectious Diseases and Immunization Committee . Newborn male circumcision. Paediatr Child Health(2015) 20:311–5. [PMC free article] [PubMed]
88.
Mavhu W, Larke N, Hatzold K, Ncube G, Weiss HA, Mangenah C, et al. A randomized noninferiority trial of AccuCirc device versus Mogen clamp for early infant male circumcision in Zimbabwe. J Acquir Immune Defic Syndr (2015) 69:e156–63.10.1097/QAI.0000000000000694 [PMC free article] [PubMed][Cross Ref]
89.
Mitchell A, Boss BJ. Adverse effects of pain on the nervous systems of newborns and young children: a review of the literature. J Neurosci Nurs (2002) 34:228–36.10.1097/01376517-200210000-00002 [PubMed] [Cross Ref]
90.
Simpson E, Carstensen J, Murphy P. Neonatal circumcision: new recommendations & implications for practice. Mo Med (2014) 111:222–30. [PubMed]
91.
Sinkey RG, Eschenbacher MA, Walsh PM, Doerger RG, Lambers DS, Sibai BM, et al. The GoMo study: a randomized clinical trial assessing neonatal pain with Gomco vs Mogen clamp circumcision. Am J Obstet Gynecol (2015) 212:664.e1–8.10.1016/j.ajog.2015.03.029 [PubMed] [Cross Ref]
92.
Frisch M, Earp BD. Circumcision of male infants and children as a public health measure in developed countries: a critical assessment of recent evidence. Glob Public Health (2016) 19:1–16.10.1080/17441692.2016.1184292 [PubMed] [Cross Ref]
93.
Ben Chaim J, Livne PM, Binyamini J, Hardak B, Ben-Meir D, Mor Y. Complications of circumcision in Israel: a one year multicenter survey. Isr Med Assoc J (2005) 7:368–70. [PubMed]
94.
Gellis SS. Circumcision. Am J Dis Child (1978) 132:1168–9. [PubMed]
95.
Walker SM, Fitzgerald M, Hathway GJ. Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla. Anesthesiology (2015) 122:1391–400.10.1097/ALN.0000000000000658 [PMC free article] [PubMed] [Cross Ref]
96.
Van der Velde L, Curran AK, Filiano JJ, Darnall RA, Bartlett D, Jr, Leiter JC. Prolongation of the laryngeal chemoreflex after inhibition of the rostral ventral medulla in piglets: a role in SIDS? J Appl Physiol (2003) 94:1883–95.10.1152/japplphysiol.01103.2002 [PubMed] [Cross Ref]
97.
Massey CA, Kim G, Corcoran AE, Haynes RL, Paterson DS, Cummings KJ, et al. Development of brainstem 5-HT1a receptor-binding sites in serotonin-deficient mice. J Neurochem (2013) 126:749–57.10.1111/jnc.12311 [PMC free article] [PubMed] [Cross Ref]
98.
Machaalani R, Waters KA. Neurochemical abnormalities in the brainstem of the Sudden Infant Death Syndrome (SIDS). Paediatr Respir Rev (2014) 15:293–300.10.1016/j.prrv.2014.09.008 [PubMed][Cross Ref]
99.
Kinney HC, Richerson GB, Dymecki SM, Darnall RA, Nattie EE. The brainstem and serotonin in the sudden infant death syndrome. Annu Rev Pathol (2009) 4:517.10.1146/annurev.pathol.4.110807.092322 [PMC free article] [PubMed] [Cross Ref]
101.
Decima PF, Fyfe KL, Odoi A, Wong FY, Horne RS. The longitudinal effects of persistent periodic breathing on cerebral oxygenation in preterm infants. Sleep Med (2015) 16:729–35.10.1016/j.sleep.2015.02.537 [PubMed] [Cross Ref]
102.
Watanabe S, Kuwaki T, Yanagisawa M, Fukuda Y, Shimoyama M. Persistent pain and stress activate pain-inhibitory orexin pathways. Neuroreport (2005) 16:5–8.10.1097/00001756-200501190-00002 [PubMed] [Cross Ref]
103.
Shahid IZ, Rahman AA, Pilowsky PM. Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory, increases barosensitivity and attenuates the somato-sympathetic reflex. Br J Pharmacol (2012) 165:2292–303.10.1111/j.1476-5381.2011.01694.x [PMC free article] [PubMed][Cross Ref]
104.
Hunt NJ, Waters KA, Rodriguez ML, Machaalani R. Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome. Acta Neuropathol (2015) 130:185–98.10.1007/s00401-015-1437-9 [PubMed] [Cross Ref]
105.
Sisson TRC, Whalen LE, Telek A. The blood volume of infants. J Pediatr (1959) 55:430–46.10.1016/S0022-3476(59)80084-6 [PubMed] [Cross Ref]
106.
Kaplan GW. Complications of circumcision. Urol Clin North Am (1983) 10:543–9. [PubMed]
107.
Martin JA, Hamilton BE, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2013. Natl Vital Stat Rep (2015) 64:1–65. [PubMed]
108.
Walter LM, Yiallourou SR, Vlahandonis A, Sands SA, Johnson CA, Nixon GM, et al. Impaired blood pressure control in children with obstructive sleep apnea. Sleep Med (2013) 14:858–66.10.1016/j.sleep.2013.01.015 [PubMed] [Cross Ref]
109.
Kahn A, Groswasser J, Franco P, Scaillet S, Sawaguchi T, Kelmanson I, et al. Sudden infant deaths: stress, arousal and SIDS. Early Hum Dev (2003) 75(Suppl):147–66.10.1016/j.earlhumdev.2003.08.018 [PubMed] [Cross Ref]
110.
Thach BT. The role of respiratory control disorders in SIDS. Respir Physiol Neurobiol (2005) 149:343–53.10.1016/j.resp.2005.06.011 [PubMed] [Cross Ref]
111.
Kato I, Groswasser J, Franco P, Scaillet S, Kelmanson I, Togari H, et al. Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome. Am J Respir Crit Care Med (2001) 164:1464–9.10.1164/ajrccm.164.8.2009001 [PubMed] [Cross Ref]
112.
Bisogni S, Dini C, Olivini N, Ciofi D, Giusti F, Caprilli S, et al. Perception of venipuncture pain in children suffering from chronic diseases. BMC Res Notes (2014) 7:735.10.1186/1756-0500-7-735 [PMC free article] [PubMed] [Cross Ref]
113.
Na AF, Tanny SP, Hutson JM. Circumcision: is it worth it for 21st-century Australian boys? J Paediatr Child Health (2015) 51:580–3.10.1111/jpc.12825 [PubMed] [Cross Ref]
114.
Darby R. Risks, benefits, complications and harms: neglected factors in the current debate on non-therapeutic circumcision. Kennedy Inst Ethics J (2015) 25:1–34.10.1353/ken.2015.0004 [PubMed][Cross Ref]
115.
American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics (2012) 130:585–6.10.1542/peds.2012-1989 [PubMed] [Cross Ref]
116.
Frisch M, Aigrain Y, Barauskas V, Bjarnason R, Boddy SA, Czauderna P, et al. Cultural bias in the AAP’s 2012 technical report and policy statement on male circumcision. Pediatrics (2013) 131:796–800.10.1542/peds.2012-2896 [PubMed] [Cross Ref]
117.
Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA (2002) 288:857–61.10.1001/jama.288.7.857 [PubMed] [Cross Ref]
118.
Hartley C, Goksan S, Poorun R, Brotherhood K, Mellado GS, Moultrie F, et al. The relationship between nociceptive brain activity, spinal reflex withdrawal and behaviour in newborn infants. Sci Rep(2015) 5:1–13.10.1038/srep12519 [PMC free article] [PubMed] [Cross Ref]
119.
Goksan S, Hartley C, Emery F, Cockrill N, Poorun R, Moultrie F, et al. fMRI reveals neural activity overlap between adult and infant pain. Elife (2015) 4:e06356.10.7554/eLife.06356 [PMC free article][PubMed] [Cross Ref]
120.
Fabrizi L, Slater R, Worley A, Meek J, Boyd S, Olhede S, et al. A shift in sensory processing that enables the developing human brain to discriminate touch from pain. Curr Biol (2011) 21:1552–8.10.1016/j.cub.2011.08.010 [PMC free article] [PubMed] [Cross Ref]
121.
Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, et al. Procedural pain and brain development in premature newborns. Ann Neurol (2012) 71:385–96.10.1002/ana.22267 [PMC free article][PubMed] [Cross Ref]
122.
Blackwell C, Moscovis S, Hall S, Burns C, Scott RJ. Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection. Front Immunol (2015) 6:44.10.3389/fimmu.2015.00044 [PMC free article] [PubMed] [Cross Ref]
123.
Ferrante L, Opdal SH. Sudden infant death syndrome and the genetics of inflammation. Front Immunol (2015) 6:63.10.3389/fimmu.2015.00063 [PMC free article] [PubMed] [Cross Ref]
124.
Arnestad M, Andersen M, Vege A, Rognum TO. Changes in the epidemiological pattern of sudden infant death syndrome in southeast Norway, 1984–1998: implications for future prevention and research. Arch Dis Child (2001) 85:108–15.10.1136/adc.85.2.108 [PMC free article] [PubMed] [Cross Ref]
125.
Mage DT, Donner EM. Is excess male infant mortality from sudden infant death syndrome and other respiratory diseases X-linked? Acta Paediatr (2013) 103:188–93.10.1111/apa.12482 [PubMed] [Cross Ref]
126. Guntheroth WG. Crib Death: The Sudden Infant Death Syndrome. 3rd ed Armonk, New York: Futura Publishing Co; (1995).
127.
Waaijenborg S, Hahné SJ, Mollema L, Smits GP, Berbers GA, van der Klis FR, et al. Waning of maternal antibodies against measles, mumps, rubella, and varicella in communities with contrasting vaccination coverage. J Infect Dis (2013) 208:10–6.10.1093/infdis/jit143 [PMC free article] [PubMed][Cross Ref]
128.
Ferrante L, Rognum TO, Vege Å, Nygård S, Opdal SH. Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome. Pediatr Res (2016) 80:77–84.10.1038/pr.2016.45 [PubMed] [Cross Ref]
129.
Horne RS, Nixon GM. The role of physiological studies and apnoea monitoring in infants. Paediatr Respir Rev (2014) 15:312–8.10.1016/j.prrv.2014.09.007 [PubMed] [Cross Ref]
130.
Prabhakar NR, Peng YJ, Kumar GK, Nanduri J. Peripheral chemoreception and arterial pressure responses to intermittent hypoxia. Compr Physiol (2015) 5:561–77.10.1002/cphy.c140039 [PMC free article] [PubMed] [Cross Ref]
131.
Indic P, Paydarfar D, Barbieri R. Point process modeling of interbreath interval: a new approach for the assessment of instability of breathing in neonates. IEEE Trans Biomed Eng (2013) 60:2858–66.10.1109/TBME.2013.2264162 [PMC free article] [PubMed] [Cross Ref]
132.
Chung SA, Yuan H, Chung F. A systemic review of obstructive sleep apnea and its implications for anesthesiologists. Anesth Analg (2008) 107:1543–63.10.1213/ane.0b013e318187c83a [PubMed][Cross Ref]
133.
Chouchou F, Khoury S, Chauny JM, Denis R, Lavigne GJ. Postoperative sleep disruptions: a potential catalyst of acute pain? Sleep Med Rev (2014) 18:273–82.10.1016/j.smrv.2013.07.002 [PubMed][Cross Ref]
134.
Hakim F, Gozal D, Kheirandish-Gozal L. Sympathetic and catecholaminergic alterations in sleep apnea with particular emphasis on children. Front Neurol (2012) 3:7.10.3389/fneur.2012.00007 [PMC free article] [PubMed] [Cross Ref]
135.
Kang KT, Chiu SN, Weng WC, Lee PL, Hsu WC. Analysis of 24-hour ambulatory blood pressure monitoring in children with obstructive sleep apnea: a hospital-based study. Medicine, Balt (2015) 94:e1568.10.1097/MD.0000000000001568 [PMC free article] [PubMed] [Cross Ref]
136.
McSharry DG, Saboisky JP, Deyoung P, Jordan AS, Trinder J, Smales E, et al. Physiological mechanisms of upper airway hypotonia during REM sleep. Sleep (2014) 37:561–9.10.5665/sleep.3498 [PMC free article] [PubMed] [Cross Ref]
137.
Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, et al. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats. Sleep(2014) 37:1249–56.10.5665/sleep.3848 [PMC free article] [PubMed] [Cross Ref]
138.
Kato I, Franco P, Groswasser J, Scaillet S, Kelmanson I, Togari H, et al. Incomplete arousal processes in infants who were victims of sudden death. Am J Respir Crit Care Med (2003) 168:1298–303.10.1164/rccm.200301-134OC [PubMed] [Cross Ref]
139.
Longin E, Dimitriadis C, Shazi S, Gerstner T, Lenz T, König S. Autonomic nervous system function in infants and adolescents: impact of autonomic tests on heart rate variability. Pediatr Cardiol (2009) 30:311–24.10.1007/s00246-008-9327-8 [PubMed] [Cross Ref]
140.
Schechtman VL, Raetz SL, Harper RK, Garfinkel A, Wilson AJ, Southall DP, et al. Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome. Pediatr Res (1992) 31:606–12.10.1203/00006450-199206000-00014 [PubMed][Cross Ref]
141.
Schechtman VL, Henslee JA, Harper RM. Developmental patterns of heart rate and variability in infants with persistent apnea of infancy. Early Hum Dev (1998) 50:251–62.10.1016/S0378-3732(97)00047-7 [PubMed] [Cross Ref]
142.
Eyre EL, Duncan MJ, Birch SL, Fisher JP. The influence of age and weight status on cardiac autonomic control in healthy children: a review. Auton Neurosci (2014) 186:8–21.10.1016/j.autneu.2014.09.019 [PubMed] [Cross Ref]
143.
Fernández-Agüera MC, Gao L, González-Rodríguez P, Pintado CO, Arias-Mayenco I, García-Flores P, et al. Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling. Cell Metab (2015) 22:825–37.10.1016/j.cmet.2015.09.004 [PubMed] [Cross Ref]
144.
Sunday ME. Oxygen, gastrin-releasing peptide, and pediatric lung disease: life in the balance. Front Pediatr (2014) 2:72.10.3389/fped.2014.00072 [PMC free article] [PubMed] [Cross Ref]
145.
Cutz E. Hyperplasia of pulmonary neuroendocrine cells in infancy and childhood. Semin Diagn Pathol (2015) 32:420–37.10.1053/j.semdp.2015.08.001 [PubMed] [Cross Ref]
146.
Elliot J, Vullermin P, Carroll N, James A, Robinson P. Increased airway smooth muscle in sudden infant death syndrome. Am J Respir Crit Care Med (1999) 160:313–6.10.1164/ajrccm.160.1.9802024 [PubMed] [Cross Ref]
147.
Krous HF, Haas E, Hampton CF, Chadwick AE, Stanley C, Langston C. Pulmonary arterial medial smooth muscle thickness in sudden infant death syndrome: an analysis of subsets of 73 cases. Forensic Sci Med Pathol (2009) 5:261–8.10.1007/s12024-009-9116-6 [PMC free article] [PubMed] [Cross Ref]
148.
Wilders R. Cardiac ion channelopathies and the sudden infant death syndrome. ISRN Cardiol (2012) 2012:1–28.10.5402/2012/846171 [PMC free article] [PubMed] [Cross Ref]
149.
Tester DJ, Ackerman MJ. Sudden infant death syndrome: how significant are the cardiac channelopathies? Cardiovasc Res (2005) 67:388–96.10.1016/j.cardiores.2005.02.013 [PubMed][Cross Ref]
150.
Neary MT, Breckenridge RA. Hypoxia at the heart of sudden infant death syndrome? Pediatr Res(2013) 74:375–9.10.1038/pr.2013.122 [PMC free article] [PubMed] [Cross Ref]
151.
Perticone F, Ceravolo R, Maio R, Cosco C, Mattioli PL. Heart rate variability and sudden infant death syndrome. Pacing Clin Electrophysiol (1990) 13:2096–9.10.1111/j.1540-8159.1990.tb06949.x [PubMed][Cross Ref]
152.
Evans A, Bagnall RD, Duflou J, Semsarian C. Postmortem review and genetic analysis in sudden infant death syndrome: an 11-year review. Hum Pathol (2013) 44:1730–6.10.1016/j.humpath.2013.01.024 [PubMed] [Cross Ref]
153.
Santori M, Blanco-Verea A, Gil R, Cortis J, Becker K, Schneider PM, et al. Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood. Arch Dis Child (2015) 100:952–6.10.1136/archdischild-2015-308200 [PubMed] [Cross Ref]
154.
Van Norstrand DW, Ackerman MJ. Sudden infant death syndrome: do ion channels play a role? Heart Rhythm (2009) 6:272–8.10.1016/j.hrthm.2008.07.028 [PMC free article] [PubMed] [Cross Ref]
155.
Methner DN, Scherer SE, Welch K, Walkiewicz M, Eng CM, Belmont JW, et al. Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young. Genome Res (2016) 26:1170–7.10.1101/gr.195800.115 [PMC free article] [PubMed][Cross Ref]
156.
McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci (1998) 840:33–44.10.1111/j.1749-6632.1998.tb09546.x [PubMed] [Cross Ref]
157.
Berger M, Juster RP, Sarnyai Z. Mental health consequences of stress and trauma: allostatic load markers for practice and policy with a focus on Indigenous health. Australas Psychiatry (2015) 23:644–9.10.1177/1039856215608281 [PubMed] [Cross Ref]
158.
Elhaik E, Zandi P. Dysregulation of the NF-κB pathway as a potential inducer of bipolar disorder. J Psychiatr Res (2015) 70:18–27.10.1016/j.jpsychires.2015.08.009 [PubMed] [Cross Ref]
159.
Christiaens I, Hegadoren K, Olson DM. Adverse childhood experiences are associated with spontaneous preterm birth: a case-control study. BMC Med (2015) 13:124.10.1186/s12916-015-0353-0 [PMC free article] [PubMed] [Cross Ref]
160.
Juster RP, McEwen BS, Lupien SJ. Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev (2010) 35:2–16.10.1016/j.neubiorev.2009.10.002 [PubMed][Cross Ref]
161.
Carpenter R, McGarvey C, Mitchell EA, Tappin DM, Vennemann MM, Smuk M, et al. Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case–control studies. BMJ Open (2013) 3:e002299.10.1136/bmjopen-2012-002299 [PMC free article] [PubMed][Cross Ref]
162. Emery J. A way of looking at the causes of crib death. In: Tildon J, Roeder L, Steinschneider A, editors. , editors. Proceedings of the International Research Conference on the Sudden Infant Death Syndrome New York: Academic Press (1983). p. 123–32.
163.
Filiano J, Kinney H. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate (1994) 65:194–7.10.1159/000244052 [PubMed] [Cross Ref]
164.
Cold CJ, Taylor JR. The prepuce. Br J Urol (1999) 83:34–44.10.1046/j.1464-410x.1999.0830s1034.x [Cross Ref]
165.
Shapiro-Mendoza CK, Camperlengo LT, Kim SY, Covington T. The sudden unexpected infant death case registry: a method to improve surveillance. Pediatrics (2012) 129:e486–93.10.1542/peds.2011-0854 [PubMed] [Cross Ref]
166.
Elhaik E, Tatarinova T, Chebotarev D, Piras IS, Maria Calò C, De Montis A, et al. Geographic population structure analysis of worldwide human populations infers their biogeographical origins. Nat Commun (2014) 5.10.1038/ncomms4513 [PMC free article] [PubMed] [Cross Ref]
167.
Risser JM, Risser WL, Eissa MA, Cromwell PF, Barratt MS, Bortot A. Self-assessment of circumcision status by adolescents. Am J Epidemiol (2004) 159:1095–7.10.1093/aje/kwh149 [PubMed][Cross Ref]
168.
Mulongo P, Hollins Martin C, McAndrew S. The psychological impact of Female Genital Mutilation/Cutting (FGM/C) on girls/women’s mental health: a narrative literature review. J Reprod Infant Psychol (2014) 32:1–17.10.1080/02646838.2014.949641 [Cross Ref]
169.
Saraçoglu M, Öztürk H. Female circumcision. Androl Gynecol Curr Res (2014) 2:1–3.10.4172/2327-4360.1000120 [Cross Ref]
170.
Warnock F, Sandrin D. Comprehensive description of newborn distress behavior in response to acute pain (newborn male circumcision). Pain (2004) 107:242–55.10.1016/j.pain.2003.11.006 [PubMed][Cross Ref]
