Sudden Infant Death Syndrome in Emergency Medicine Clinical Presentation

The classic presentation of sudden infant death syndrome (SIDS) begins with an infant who is put to bed, typically after breastfeeding or bottle-feeding. Checks of the baby at varying intervals are unremarkable, but the baby is found dead, usually in the position in which he or she had been placed at bedtime or naptime. Although most of infants are apparently healthy, many parents of infants who died of SIDS state that their babies "were not themselves" in the hours before death. Diarrhea, vomiting, and listlessness have been reported in the 2 weeks prior to death.

Observations most commonly reported with apparent life-threatening events (ALTEs) are cyanosis (50-60%), breathing difficulties (50%), and abnormal limb movements (35%). Antecedent events may provide an indication regarding etiology, particularly the relationship of the ALTE to feeding or descriptions suggestive of seizure.

After calming the parents, it is important to determine the exact sequence before and during the event by taking a detailed history.

• Did the infant have a foreign body, trauma, or ingestion?
• Does the infant have a history of apnea?
• What activity did the infant exhibit prior to the event? Apnea following paroxysmal cough, in an infant with upper respiratory infection, suggests pertussis. Arching with apnea after feeding—with or without milk or formula in the oronasal passages—suggests GER.
• What was the time and amount of the last meal? (Parents may misinterpret postprandial regurgitation as a life-threatening event.)
• Was the baby asleep or awake? GER may occur in an awake infant following feeding.
• What was the child's position?
• What was observed first? Chest wall movement and effort in respiration, in the absence of airflow, indicates obstructive apnea, whereas the absence of chest wall movement, respiratory effort, and airflow is consistent with central apnea.
• What was the period of apnea in seconds? Most healthy babies momentarily stop breathing when they are asleep.
• Did the infant change color? If the patient turned blue, ask "how blue," inquire as to lighting in the room, and ascertain the location of the cyanosis. A number of healthy babies appear to turn blue around the mouth when crying. Acrocyanosis or color changes during defecation may be misinterpreted as life-threatening events.
• What was the baby's tone (eg, limp, stiff, shaking)? Stiffening or clonic movement followed by apnea suggests postictal apnea.
• What was the duration of the event?
• What was done and how (eg, CPR)? Carefully question parents or other witnesses about their efforts to revive the baby. No need for resuscitative effort is consistent with a benign cause, whereas the need for respiratory resuscitation or CPR directs attention to serious pathology.
• Children are poorly served if abuse is not considered in the differential diagnosis of infants with ALTEs.
• Autopsy cannot distinguish death due to sudden infant death syndrome (SIDS) from death by suffocation. Certain elements of the history, however, may raise suspicion as to abuse, although none is pathognomonic.

History surrounding death

• Consistent with SIDS - Apparently healthy infant, fed, put to bed, found lifeless, silent death, Emergency Medical Services (EMS) resuscitation unsuccessful
• Suspicious for child abuse - History atypical for SIDS, discrepant history, unclear history, prolonged interval between bedtime and death
• Age at death - Consistent with SIDS (peak in infants aged 2-4 mo, 90% younger than 7 mo), suspicious for child abuse (6 mo or older at the time of death)

History of pregnancy, delivery, and infancy

• Consistent with SIDS - Prenatal care was minimal to maximal. Frequently, a history of cigarette use during pregnancy as well as a premature delivery or low birth weight is reported. Subtle defects in feeding, crying, and neurological status (eg, hypotonia, lethargy, irritability) may have been present. Other factors include diminished postneonatal height and weight gain, twins, triplets, thrush, pneumonia, spitting, GER, tachypnea, tachycardia, and cyanosis. In one study, infants who died suddenly were 3 times as likely to have previously been admitted to a hospital compared to control infants matched for age (16% vs 5.4%). Signs of antecedent difficulty usually are not present.
• Suspicious factors for child abuse - Unwanted pregnancy, little or no prenatal care, late arrival for delivery, birth outside of hospital, no well-baby care or few visits, no immunizations, use of alcohol and/or other drugs during and after pregnancy, infant described as hard to care for or discipline, deviant feeding practices, previous unexplained medical disorders (eg, seizures), and previous episodes of apnea in the presence of the same person

Previous infant deaths in family

• Consistent with SIDS - First, unexplained, and unexpected infant death
• Suspicious for child abuse - The threshold expressed by Reese is more than 1 previous unexplained or unexpected infant death, whereas the Committee on Child Abuse and Neglect finds suspicious the previous unexpected or unexplained death(s) of 1 or more siblings while under the care of the same unrelated person. According to some reports, the siblings of an infant who died of SIDS are themselves at higher risk for SIDS, although a history of any other infant deaths in the family raises the possibility of inborn errors of metabolism and child abuse.

Previous involvement of law enforcement or child protective services

• Consistent with SIDS - None
• Suspicious for child abuse - Two or more times, 1 or more family member(s) arrested for violent behavior

Clinical assessment following an apparent life-threatening event (ALTE)

Following an ALTE, many patients present to the ED in no acute distress. In 50% of these infants, physical examination is entirely normal. Pyrexia is documented in 25% of patients presenting to the ED; infection is noted in 25%.

The literature has varying recommendations concerning the extensiveness of the ED workup of an apparently healthy infant who presents following an ALTE.

Agreement does exist regarding elicitation of a detailed history and performance of a thorough physical examination.

Findings from the history and physical examination should enable the physician to determine if the child had an ALTE and whether the apneic episode was central, obstructive, or mixed.

Examine the patient after all clothing has been removed.

Direct the physical examination at identifying congenital anomalies of the heart or CNS and to recognizing dysmorphic features indicative of a congenital syndrome.

Findings of poor muscle tone or irregular respirations indicate a true ALTE.

Truncal bruising

Most accidental bruising occurs over bony prominences. Contusions in "soft" sites (eg, cheeks, trunk) suggest abuse. An examination of babies with accidental bruises revealed no infant with a contusion measuring more than 10 mm in any diameter; some infants did have more than 1 contusion.

Development of a contusion is determined by a number of factors, including the amount of blunt force applied to the skin, tissue density, vascularity of the tissue, fragility of blood vessels, and the amount of blood escaping into surrounding tissues.

Bruises on one person, of identical age and cause, may not appear as the same color and may not change at the same rate. Red, blue, purple, or black may occur at any time between 1 hour after the causal trauma and resolution of the contusion. The presence of red coloration therefore has no bearing on the age of the bruise. A bruise with any yellow must be older than 18 hours. Other than describing bruises that are yellow, brown, or green as older, further specification of age is difficult.

• Pinch or human bite marks
• Wounds in different stages of healing
• Scalds or burns, including those caused by cigarettes
• Fractures, particularly if of different ages
• Pupillary changes

Retinal hemorrhages, while strongly associated with inflicted head injury (shaken-impact syndrome), are not specific for that diagnosis. Retinal hemorrhages may be seen in accidental trauma, subarachnoid hemorrhage, sepsis, coagulopathy, severe hypertension, galactosemia (rarely), following resuscitation, in conjunction with papilledema, and in up to 40% of vaginally delivered newborns, with resolution taking up to 1 month after birth.

Southall et al noted frank bleeding from the nose and/or mouth in 11 of 38 suspected child abuse cases, but in none of the control group of 46 children with recurrent ALTE attributable to natural medical cause.^[14]

Contribution of the clinical examination to death investigation

In the case of a deceased infant, the National Association of Medical Examiners makes it very clear that "medical examiners and coroners have the sole legal authority to investigate deaths that are sudden, unexpected, unexplained, and potentially due to external causes such as injury," and that "examination or manipulation of the deceased body by child maltreatment experts without proper statutory authority or family permission may constitute a tort or be a violation of criminal law."

If an infant arrives in cardiopulmonary arrest, relevant findings from a clinical examination conducted during the course of a resuscitation-attempt should be carefully documented in the chart and will complement the autopsy and other components of the death investigation.

The examination should address many of the same elements indicated for assessment of an ALTE, modified as appropriate to the unresponsive patient.

Other findings

In addition to the abnormalities previously presented, the following physical findings suggest death from SIDS versus findings that increase suspicion of infanticide:

• Consistent with SIDS: Serosanguineous watery, frothy, or mucoid discharge from mouth and/or nose is present. The infant's face and dependent portions of the body may have reddish-blue mottling from postmortem lividity. Pressure points of the body may have marks. The infant appears well cared for and there is no significant skin trauma
• Suspicious for child abuse: Malnutrition, neglect, cutaneous injuries, traumatic lesions, or abnormalities of the head or body (eg, conjunctiva, fundi, scalp, intraoral, ears, neck, trunk, anogenital, extremities, including fractures) is noted. Suspicions are increased with distribution of hypostasis indicative that a child was in a different position than that stated or in the presence of pressure ischemia over the nose and mouth.

Absence of physical stigmata does not necessarily mean the death was natural. So-called gentle battering occurs when a physical act leaves no mark, such as when a hand or pillow is placed over the face or when the infant is placed face down on a pillow or soft mattress, occasionally without any criminal intent (eg, to stifle a cry). Physical examination of SIDS infants may reveal evidence of terminal motor activity such as clenched fists.

Do not misinterpret postmortem changes or physical findings often seen in deaths from SIDS, (eg, confusing postmortem lividity or anal dilatation with trauma secondary to abuse).

Over 70 different theories of sudden infant death syndrome (SIDS) have been proposed, and the literature is frequently contradictory as to the relative risk (or absence thereof) posed by disparate conditions.

Several authors classify risk factors into groups such as maternal (eg, drug use during pregnancy, unmarried, anemia during pregnancy, weight gain < 20 lb during pregnancy, urinary tract infection during pregnancy), biological (eg, deficiency in asphyxial arousal), or epidemiological (eg, prone sleeping position, socioeconomic status).

Infants at increased risk of SIDS include term infants who have had an apparent life-threatening event (ALTE), premature infants of low birth weight, infants of substance-abusing mothers, and infants with apnea of infancy.

One to 3% of infants in the general population experience an ALTE. Of all infants who die of SIDS, 5-7% have an ALTE history.^[15]

A large study that reviewed all types of ALTEs found a 1% risk of subsequent SIDS. These data should be interpreted within the context that most studies of ALTEs and SIDS have excluded infants with a history of prematurity, chronic lung disease, or congenital heart disease.

The mortality rate is 4% for infants suffering an apneic episode secondary to infection with RSV.

Strong data associate "serious" ALTEs (infants experiencing an ALTE during sleep and/or those who required vigorous stimulation or CPR) and SIDS. Such infants have an 8-10% risk of SIDS. Infants with a history of more than 1 serious ALTE have a 28% risk of SIDS despite use of home monitoring.

Among the causes of ALTEs are infection (5-40%, depending on the season), laryngeal chemoreceptor stimulation secondary to GER (20%), and seizures and other neurologic disorders (15-20%). Cardiac dysrhythmias and abuse (including Munchausen syndrome by proxy) also should be included in the differential. Cyanotic congenital heart disease generally presents in the first few weeks of life, with difficulty feeding, poor weight gain, and diaphoresis.

Despite extensive workup, no definitive cause can be found for more than 50% of ALTEs.

Anecdotal, pathologic, physiologic, and epidemiologic data suggest that apnea of infancy is a risk factor for SIDS, although there is no conclusive evidence. Patients with apnea of infancy have a mortality rate in the range of 2-6%. The rate climbs to 10% for infants who manifest apnea during sleep on 1-2 occasions; the risk of death triples if there are more than 2 incidents.

Only 2-4% of infants who die from SIDS have a record of apnea of prematurity.

Regurgitation of gastric contents with acidic pH can cause reflexive apnea with resultant hypoxia. While autoresuscitation might be possible in the absence of regurgitation, it is not possible when regurgitation has occurred.^[16]

Berkowitz reports a higher incidence of SIDS in infants with residual bronchopulmonary dysplasia (11% of premature infants in 1 study)^[17] ; however, Gausche maintains that infants with bronchopulmonary dysplasia are not at increased risk for SIDS.^[18]

A study from New Zealand suggests that infants who are not breastfed are at increased risk for SIDS. Other studies, conducted in countries with a low incidence of SIDS, have failed to demonstrate a similar correlation.

The incidence of SIDS is higher in multiple births, with twins or triplets having a rate 2.5 times that of singleton babies. Gausche cites an incidence for triplets of 8.3 cases per 1000 infants.^[18]

Gausche further states that siblings of an infant who dies from SIDS are not at increased for SIDS.^[18] Reece supports this view and reports that, when comparing families matched for maternal age and birth rank, there is no statistically significant difference in SIDS rates or in total infant mortality in families with a history of SIDS and those families without a history of SIDS.^[19]

Other authors, however, indicate that siblings of infants who have succumbed to SIDS are at higher risk as addressed below.

Many of the epidemiologic risk factors for sudden infant death syndrome (SIDS) and other causes of infant mortality are identical.

Some studies have found that siblings of an infant who dies from SIDS have about a 5-fold increased risk of death from SIDS and a 6-fold increase in risk of death from other causes, although it should be noted that the research design of these studies has been criticized. The theory advanced is that genetic factors and the environmental milieu that may have contributed to the death of the first infant would effect siblings.^[20]

To identify which risk factors are specific for SIDS, rather than characteristic of postneonatal deaths in general, data were reviewed on 11,734 infants, of which 649 deaths had been attributed to SIDS and 1221 postneonatal deaths were from other causes.

Factors such as black race, very low birth weight (< 1500 g) and low birth weight (< 2500 g), gestational age at birth less than 37 weeks, 5-minute Apgar score less than 7, male sex, more than 2 previous pregnancies, maternal age younger than 20 years, maternal education level less than 12 years, multiple births, and maternal smoking during pregnancy were examined.

Perinatal and sociodemographic risk factors were not independently associated with SIDS.

Of the risk factors examined, only maternal smoking during pregnancy was independently associated with SIDS.

Gilbert-Barness and Barness maintain that unequivocal evidence shows that a substantial number of deaths from SIDS are preventable by avoiding the prone sleeping position, particularly on any type of soft bedding.^[21] Lazoff and Kauffman, however, point out that prone sleeping is common in Hong Kong and Sweden, both of which have a very low incidence of SIDS.^[22]

Subsequent to strong warnings against the nonsupine sleeping position, dramatic changes were noted in several Scandinavian countries. Oyen et al reported that the combined effect of nonsupine sleeping and other prenatal and maternal risk factors (ie, preterm birth, intrauterine growth retardation, any signs of illness during the first week of life, maternal smoking during pregnancy, maternal age < 25 y, maternal education < 10 y, second or higher birth order, single motherhood) carried very high SIDS risks.^[8] The combination of prone sleeping and birth weight less than 2500 grams was far greater than the sum of the risk from each risk alone. In infants aged 13-24 weeks, the combined effect of nonsupine sleeping and lower birth weight carried the highest risk for SIDS.

Ackerman and Gilbert-Barness reported a related issue concerning 15 fatalities in which infants aged 3 months or younger were placed face down in a level, suspended rocking cradle.^[23] In 14 of the cases, a locking pin to prevent cradle movement was not used. The typical position in which the infants were found was lying in the dependent end of the cradle, with their head pressed against the cradle mesh (with or without obstruction of the nose and mouth); thus, the cradle was either set in motion or infants shifted to one end of the cradle during normal sleep movements.

Wedging the head in the corner of a tilted cradle or positioning the head against gravity, increases the difficulty in moving or turning the head. The rocking cradles involved in these deaths have been removed from the market in the US. These cradles, nevertheless, frequently are passed on from one baby to the next or are bought secondhand. Accordingly, they constitute a potentially lethal sleeping environment unless the locking mechanism is used. Co-sleeping (parent with infant) and sleeping on a soft surface or polystyrene-filled cushion also have been implicated as risk factors for SIDS.

Cigarette smoking during pregnancy is highly significant as a risk factor in the pathogenesis of SIDS, and studies continue to lend weight to the mounting evidence of a causal mechanism between SIDS and maternal smoking. As previously indicated, only maternal smoking during pregnancy was independently associated with SIDS and, in fact, was significantly more prevalent in the SIDS cohort than in infants dying of other causes. In the 1980s, the smoking rate among SIDS mothers was reported to be 70%, whereas it decreased to 42% in the 1990s.^[24]

The incidence of SIDS is 7 times higher among infants whose mothers smoked more than 1 pack per day during pregnancy. Early neuropathologic changes in autonomic pathways are noted with prenatal exposure to maternal smoking.^[12] Research implicates prenatal exposure to nicotine in the alteration of the infant's arousal mechanism, a possible explanation for the increased risk for SIDS associated with prone sleeping position. Decreased volume and compliance of the lung, and decreased heart rate variability in response to stress, are also reported.^[12]

Data indicate that if women refrained from smoking (a completely modifiable risk factor) during pregnancy, up to 30% of SIDS deaths might be prevented. A risk factor independent of prenatal exposure to tobacco is the chronic exposure to cigarette smoke that infants experience when parents smoke. Infants so exposed demonstrate a modest increase in SIDS.

Abuse of drugs other than nicotine is less strongly associated with SIDS. Prenatal exposure to cocaine may cause cocaine-induced maturational delay. Term newborns exposed to cocaine prenatally have respiratory instability similar to that seen in preterm infants not exposed to cocaine. Risks posed by heroin, or particularly the synthetic narcotic, methadone, are higher than that conferred by cocaine.

A study of 2964 infants revealed 44% who tested positive for drugs: 30.5% for cocaine, 20.2% for opiates, and 11.4% for cannabinoids. Over a third (34.4%) of infants whose mothers denied a history of illegal drug use screened positive for drugs. While high perinatal morbidity was seen in infants who were drug positive (with significantly lower birth weight, head circumference, and length), there was no associated increase in overall mortality during the first 2 years of life.

Of particular note, SIDS incidence was not significantly higher among infants who were drug positive, in contrast to other reports. Low birth weight and prematurity, both known consequences of drug use during pregnancy, are important determinants of infant mortality and morbidity. Most infants with low birth weight (≤ 2500 g) tested positive for drugs (often in combination), with 20.5% testing positive for cocaine and 18.7% testing positive for morphine versus 13.6% of infants who tested negative. A significantly higher mortality rate was observed among babies with low birth weight who were exposed to both cocaine and opioids. Forty percent of 43 infants who died when younger than 2 days and whose autopsy failed to identify an obvious anatomic cause of death had toxicologic evidence of cocaine exposure.

A second review of 600 infant deaths found evidence of cocaine exposure in 2.7% of infants younger than 8 months who died suddenly and unexpectedly.

Research reported in 2007 by Kahlert, Rudin, Kind and the Swiss HIV Cohort Study and the Swiss Mother & Child HIV Cohort Study found a greatly increased risk for SIDS of infants born to HIV-infected mothers who used opioids during pregnancy.^[25] The SIDS rate of 14.9 per 1000 live births did not appear to be mediated by the known SIDS risk factors of prematurity or low birth weight, nor by perinatal HIV infection or antiretroviral drug exposure. Kahlert et al note that QT-interval prolongation has been observed in methadone maintenance patients, raising the possibility that a similar phenomenon may have been operative in these SIDS deaths.^[25]

No evidence suggests that maternal alcohol use during pregnancy increases the risk for SIDS.Ford et al first reported an association between caffeine intake in pregnancy and SIDS.^[26] They found heavy caffeine consumption throughout pregnancy in 14% of control mothers and in 28% of mothers whose infants died from SIDS.

Caffeine is a stimulant that can cross the placental barrier, thereby exposing the fetus, an effect potentiated in the last trimester when caffeine elimination from the mother is reduced about 3-fold. Some studies have found an association between caffeine intake and low birth weight and spontaneous abortion. Withdrawal from caffeine at birth can induce apnea in newborns. Even though caffeine has a respiratory stimulant effect, maternal caffeine use during pregnancy has been associated with central apnea in infants.

This raises the possibility that the fetal respiratory center may be altered in the presence of high caffeine concentrations, only to be left with an inadequate respiratory drive when exposed to stressors in the absence of caffeine.

The pathophysiologic mechanism may lie in adenosine receptor sites in the brainstem. Long-term caffeine exposure causes an increase in the number of adenosine receptors, with caffeine serving as a competitive antagonist. Adenosine, which can induce respiratory depression in newborn animals, is produced during episodes of severe hypoxia. Prior in utero exposure to caffeine may increase the vulnerability of an infant who is exposed to episodes of hypoxia after birth. After adjusting for confounding variables (eg, maternal smoking), the relative risk of SIDS for infants born to mothers with heavy caffeine use (consuming >400 mg/d, as in 4 cups of coffee or 10 cups of tea or glasses of cola) was 1.30 for the first trimester, 1.46 for the third trimester, and 1.65 for heavy caffeine use throughout pregnancy.

Increased apoptosis in the brainstem of SIDS infants has been found to be affected by postconceptional age, male gender, prone sleep position, and exposure to cigarette smoke.^[27] The increased cell death in the dorsal column nuclei could result in dampening or loss in relay of touch and proprioception, creating difficulty when an infant in the prone position attempts to turn into the supine position.

In one study reported by Esani et al, the mothers of SIDS infants were more likely to be young (11% were 18 or younger) compared to mothers of infants who experienced an ALTE (5% of whom were 18 or younger).^[15]

Three studies have found a link between SIDS and maternal psychiatric disorders.^[28] Two of the studies reported a link with postnatal depression, and one found an association between a history of depression in the year before birth, and a trend (not reaching statistical significance) for an association between SIDS and depression after birth.

At the time of death, 30-50% of otherwise healthy infants have an acute infection such as gastroenteritis, otitis media and, particularly, upper respiratory tract infection. Infantile botulism may be the cause of 5-10% of sudden infant deaths. Of particular note, RSV is associated with life-threatening apneic episodes, particularly in premature infants and those with a history of apnea. During RSV season, the virus is reportedly causative of up to 40% of ALTEs.

An apparent association exists for infection and SIDS in older males. Approximately 65% of SIDS deaths occur in autumn and winter; infection may play a role in these deaths. Lazoff and Kauffman state that SIDS is not associated with changes in core body temperature, although that view is not universal.^[22] Incidence of SIDS increases with colder outdoor temperature and warmer indoor (room) temperature.

Estimates indicate that 73.7% of all SIDS deaths could be prevented if all infants slept in the supine position.

Elimination of maternal smoking during pregnancy could reduce the number of SIDS deaths by 46.7%.

Prevention of low birth weight could avoid 16.2% of SIDS deaths. As reported by Esani et al, 9% of infants with an ALTE were small for gestational age, versus 19% who died of SIDS.^[15]

One in 5 infants dying of SIDS is premature.^[15]

Low birth weight infants, whether the result of premature birth or other causes, have a maturational delay in the ability to turn their head to the face down position. While the face down position is not desired, turning out of the face down position is a skill that is perfected only after development of the ability to turn face down.^[29]

Two in three infants are in nonparental child care for varying periods of time: 50% are cared for by relatives, 10% by an in-home baby sitter, and 40% in organized child care. The reduction in SIDS deaths already noted has not been reflected in the incidence of SIDS occurring in child care. It is thought this may be a function of infants still being placed prone by a nonparental caregiver. This carries great potential for risk, because when an infant is placed in a prone sleep position to which he or she is not accustomed, the risk of SIDS increases by as much as 18 times.^[9]

Lazoff and Kauffman indicate that 10-25% of apparent SIDS cases are actually homicides.^[22] They also state that human agency is causal in up to 33% of infant deaths in families with multiple cases of apparent SIDS.^[30]

Samuels and Southall report that child abuse was the cause of ALTEs in 33% of patients who received cardiopulmonary resuscitation.^[31]

Failure to diagnose factitious or induced illness leaves the child and any siblings at risk for death, results in continued suffering (perhaps for the lifetime of the victim), and creates the potential that he or she will become an abuser as an adult.

In their landmark study, Southall et al used covert video recordings to study 39 infants with a median age of 9 months (range, 2-44 months), most of whom were referred for evaluation of an ALTE.^[14] Of the 39 suspected cases, 33 involved abuse. Intentional suffocation was documented in 30 cases, with poisonings (disinfectant or anticonvulsant), deliberate fracture, and other emotional and physical abuse identified in the remainder. The first ALTE occurred at a median age of 3.6 months (corrected for expected date of delivery). Of 41 siblings of the suspect patients, 12 deaths had occurred, with 11 of the deaths attributed to SIDS. When parents were confronted with video surveillance evidence, 4 of them admitted the deliberate suffocation of 8 of the children. In comparison, there were 52 siblings of the 46 controls, of whom 2 died, with SIDS listed as the cause of 1 death. The high number of deaths in siblings evidences the long-term risk posed to children in severely dysfunctional families.

The circumstances surrounding the mistreatment of a child may range from a sudden isolated loss of control by a parent, to long-standing premeditated acts intended to harm the child. Multiple personal, familial, and environmental pressures may accumulate to push parents or other caregivers beyond the thresholds of restraint. While no parent had a psychotic mental illness, Munchausen syndrome by proxy was present in some.