Fifty years ago, an extraordinary group of pathologists, pediatricians, and epidemiologists met to address the limited research and numerous diagnoses applied to unexplained, largely sleep-related pediatric deaths. Their efforts led to the identification of a new category of disease, sudden infant death syndrome (SIDS). Among the observations fueling the creation of the category was the relative sparing of neonates despite what should be increased vulnerability in the early days of life. When Dr Bruce Beckwith, the conference’s leader, asked whether anyone doubted this age-related sparing, not a single objection was raised.1  Yet, humility about what was not yet known led to broader diagnostic criteria of “any infant or young child.” Years later, SIDS was redefined as pertaining to infants <1 year of age.2  Still later, when classification practices scattered because of objections about the concept of SIDS and the varied use of alternative terminologies, the composite of sudden unexplained infant death (SUID) came to stand in.3 

In this issue of Pediatrics, big data concur with the pioneering thinkers and draw the demarcation at 1 week. In “Distinct Populations of Sudden Unexpected Infant Death Based on Age,” Lavista Ferres et al4  used elegant, unbiased computational modeling without predetermined age boundaries to determine distinct age-related subgroups in SUID. Using profiles that included birth order, birth weight, marital status, maternal age, and smoking, they showed that associated features of SUID during the first week of life were statistically divergent from SUID during the remainder of the first year. Their efforts join other recent contributions5,6  arguing that this earliest unexplained neonatal mortality may represent something different from SIDS and its analogs. At first glance, this accumulated research is reminiscent of findings that led to the demise of what was once called “near SIDS,” when differences in risk factors and incidence over time led to the conclusion that apparent life-threatening events, now called brief resolved unexplained events, were unrelated to SIDS.7 

This analysis centers on birth and death statistics in early life and is especially reliant on day 0 data. But accounting for mortality near the time of birth is notorious for its challenges. The definition of live birth is broad, and accounting for intrapartum and neonatal death is tangled.8  The World Health Organization’s definition of a live birth requires breathing or “any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles, whether or not the umbilical cord has been cut or the placenta is attached,”9  which is a permissive category. Half of all stillbirths occur during labor and often involve highly emotional intrapartum complications and unpredictable odds for survival. They involve delivered newborns who cannot be resuscitated and resuscitated newborns who live only briefly. More than 60% of deaths in the first month occur on the first day, largely in the first hour.10  This leads to inconsistencies as to which deceased infants receive birth certificates (and are thus included in mortality statistics) and which do not. In Lavista Ferres et al’s4  research, 47% of the infants in their distinct early mortality population died on day 0. Compared with the human drama in these moments, clean data are a small consideration. Nonetheless, the quality of the data makes conclusions derived from them hazardous.

The past 50 years of research have led to other advances that are hard to reconcile with their conclusions. Research on SIDS and stillbirths suggests a biological continuum between fetal vulnerabilities and SIDS, not a disconnect.11,12  Although the researchers showed that controlling for the effects of prematurity and low birth weight did not affect their analysis, there is a substantial body of research showing that pregnancies before and after an infant who experienced SIDS have higher rates of poor fetal growth and early labor and that risk for SIDS can be calculated from obstetric characteristics.13,14  Elevated α fetoprotein levels during pregnancy are associated with both stillbirth and SIDS.15  Stillbirth and SIDS share certain brain abnormalities16  and variants in cardiac arrhythmia genes.17  Although Lavista Ferres et al’s4  research may point to an area that requires new thinking, misclassification may exaggerate the differences within SUID and mask these commonalities. In fact, their study’s identification of birth order differences in the 2 populations may reflect the association between SIDS and less successful later pregnancies.

In the flawed and contradictory universe of perinatal data, the best way forward is a continued struggle for better definitions, careful analysis, and the integration of varied research findings. This requires serious inquiry and a healthy dialogue, without overstatement. To whatever degree distinctions are unduly influenced by weaknesses in current methods of surveillance, the exchange of different ideas and conclusions sharpens our questions, and that is hard-earned progress on a difficult problem. In “Distinct Populations of Sudden Unexpected Infant Death Based on Age,” Lavista Ferres et al4  have made an important contribution to the conversation.

Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.

FUNDING: No external funding.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-1637.

     
  • SIDS

    sudden infant death syndrome

  •  
  • SUID

    sudden unexplained infant death

1
Bergman
AB
,
Beckwith
JB
,
Ray
CG
.
Sudden Infant Death Syndrome. Proceedings of the Second International Conference on Causes of Sudden Death in Infants
.
Seattle, WA
:
University of Washington Press
;
1970
2
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
(
5
):
677
684
3
Goldstein
RD
,
Blair
PS
,
Sens
MA
, et al
.
Inconsistent classification of unexplained sudden deaths in infants and children hinders surveillance, prevention and research: recommendations from The 3rd International Congress on Sudden Infant and Child Death [published online ahead of print September 9, 2019]
.
Forensic Sci Med Pathol
.
doi:10.1007/s12024-019-00156-9
4
Lavista Ferres
JM
,
Anderson
TM
,
Johnston
R
,
Ramirez
JM
,
Mitchell
EA
.
Distinct populations of sudden unexpected infant death based on age
.
Pediatrics
.
2020
;
145
(
1
):
e20191637
5
Bass
JL
,
Gartley
T
,
Lyczkowski
DA
,
Kleinman
R
.
Trends in the incidence of sudden unexpected infant death in the newborn: 1995-2014
.
J Pediatr
.
2018
;
196
:
104
108
6
Frøen
JF
,
Arnestad
M
,
Vege
A
, et al
.
Comparative epidemiology of sudden infant death syndrome and sudden intrauterine unexplained death
.
Arch Dis Child Fetal Neonatal Ed
.
2002
;
87
(
2
):
F118
F121
7
Esani
N
,
Hodgman
JE
,
Ehsani
N
,
Hoppenbrouwers
T
.
Apparent life-threatening events and sudden infant death syndrome: comparison of risk factors
.
J Pediatr
.
2008
;
152
(
3
):
365
370
8
Joseph
KS
,
Kinniburgh
B
,
Hutcheon
JA
, et al
.
Rationalizing definitions and procedures for optimizing clinical care and public health in fetal death and stillbirth
.
Obstet Gynecol
.
2015
;
125
(
4
):
784
788
9
Barfield
WD
;
Committee on Fetus and Newborn
.
Standard terminology for fetal, infant, and perinatal deaths
.
Pediatrics
.
2016
;
137
(
5
):
e20160551
10
Oza
S
,
Cousens
SN
,
Lawn
JE
.
Estimation of daily risk of neonatal death, including the day of birth, in 186 countries in 2013: a vital-registration and modelling-based study
.
Lancet Glob Health
.
2014
;
2
(
11
):
e635
e644
11
Goldstein
RD
,
Kinney
HC
,
Willinger
M
.
Sudden unexpected death in fetal life through early childhood
.
Pediatrics
.
2016
;
137
(
6
):
e20154661
12
Fifer
WP
,
Myers
MM
.
Sudden fetal and infant deaths: shared characteristics and distinctive features
.
Semin Perinatol
.
2002
;
26
(
1
):
89
96
13
Smith
GC
,
Wood
AM
,
Pell
JP
,
Dobbie
R
.
Sudden infant death syndrome and complications in other pregnancies
.
Lancet
.
2005
;
366
(
9503
):
2107
2111
14
Smith
GC
,
White
IR
.
Predicting the risk for sudden infant death syndrome from obstetric characteristics: a retrospective cohort study of 505,011 live births
.
Pediatrics
.
2006
;
117
(
1
):
60
66
15
Smith
GC
,
Wood
AM
,
Pell
JP
,
White
IR
,
Crossley
JA
,
Dobbie
R
.
Second-trimester maternal serum levels of alpha-fetoprotein and the subsequent risk of sudden infant death syndrome
.
N Engl J Med
.
2004
;
351
(
10
):
978
986
16
Grafe
MR
,
Kinney
HC
.
Neuropathology associated with stillbirth
.
Semin Perinatol
.
2002
;
26
(
1
):
83
88
17
Crotti
L
,
Tester
DJ
,
White
WM
, et al
.
Long QT syndrome-associated mutations in intrauterine fetal death
.
JAMA
.
2013
;
309
(
14
):
1473
1482

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The author has indicated he has no financial relationships relevant to this article to disclose.