Risk Factors for Sudden Infant Death Syndrome Among Northern Plains Indians FREE

The infant mortality rate among American Indians is consistently above the national average, primarily due to a higher death rate during the postneonatal period (28-364 days). Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality, and until 1997, was also the leading cause of infant mortality among American Indians.^1- 3 SIDS is defined as the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including the performance of a complete autopsy, an examination of the death scene, and a review of the infant's clinical history.⁴ In 1999, the SIDS rate was 1.5 per 1000 live births for American Indian infants and 0.7 per 1000 live births for all races combined.⁵

The Aberdeen Area Indian Health Service (AAIHS), which serves Indian communities in North Dakota, South Dakota, Nebraska, and Iowa, has the highest rate of infant mortality among the Indian Health Service (IHS) areas.^6- 7 SIDS is the leading cause of infant deaths in the Aberdeen Area, accounting for more than one fourth of the infant deaths and more than half of the postneonatal deaths. Although there was a 42% decline in the SIDS rates for all IHS regions, from 2.77 per 1000 live births in 1992-1994⁶ to 1.61 per 1000 in 1996-1998,⁷ the rate in the Aberdeen Area has remained relatively constant: 3.66, 3.55, and 3.46 per 1000 live births for 1992-1994, 1994-1996, and 1996-1998, respectively.^6- 8

One of the objectives of the Aberdeen Area Infant Mortality Study (AAIMS), which was conducted in collaboration with the Aberdeen Area Tribal Chairman's Health Board, was to determine prenatal and postnatal risk and protective factors for SIDS among Northern Plains American Indian infants.

From December 1, 1992, through November 30, 1996, a case-control study was conducted in the AAIHS. Nine tribes and 1 urban American Indian community, constituting two thirds of the service area population, participated. The methodology has been previously described⁹ and is summarized below.

Tribal resolutions of support for the study were obtained. After investigators obtained input from tribal spiritual leaders, the AAIHS and the National IHS institutional review boards approved the study protocol. Informed consent was obtained from a parent or legal guardian to conduct the parental interviews and review the medical records.

Eligible cases were American Indian infants residing on or near reservations or participating communities who died before 1 year of age, excluding infants who died during their delivery hospitalization. Case infants were classified as American Indian if either of their parents was an enrolled tribal member or if they were eligible for care at an IHS facility. Reports from public health nurses (PHNs), medical record department staff, emergency staff, members of the Perinatal Infant Mortality Review (PIMR) Committee, death certificates on American Indian infants, and obituaries in local newspapers were reviewed to identify cases.⁹

Two living control infants were matched to each case infant by postnatal age and community or reservation of residence. For age matching, AAIMS investigators used a list of eligible American Indian live-born infants by birth date and selected those born just before and just after each case. There were 3 refusals among the controls, and they were replaced with the next eligible infant with the closest birth date to the case.

All data were collected retrospectively. Two American Indian nurse interviewers conducted parental interviews using an eighth-grade level, culturally competent questionnaire that solicited information about demographic and socioeconomic factors; maternal medical and obstetric history; neonatal history; and a wide range of potential risk factors including fetal and infant exposures.

Mothers were asked about use of cigarettes, alcohol, and illicit drugs during the 3 months prior to pregnancy, during each trimester, and during the postpartum period. Similarly, mothers were asked about binge drinking (≥5 drinks in 1 sitting). The alcohol use questions had been used in the clinical setting prior to the study and were subsequently formally validated in this population.¹⁰

Standardized autopsy protocols were used. The majority of autopsies were performed by 3 pathologists whose jurisdiction included the study area and who participated in the study as members of the steering committee and the PIMR. Standard death scene investigation protocols were developed and tribal and county coroners were trained to use them. Medical records for cases and controls were abstracted and reviewed.

The PIMR committee determined the cause of death for all infants after reviewing all available information. The committee confirmed a diagnosis of SIDS only if an autopsy was performed and sufficient information from the autopsy and scene supported the diagnosis. In the absence of an autopsy, or if the cause of death was uncertain, the committee assigned a diagnosis of "undetermined."

To assess risk factors for SIDS, we examined characteristics of case and control infants using the χ² test for categorical variables and the 2-tailed t tests for continuous variables and performed a matched conditional logistic regression using the proportional hazards regression procedure in the Statistical Analysis System.¹¹ We performed multivariate analyses using likelihood methods to build models that included significant factors obtained from univariate analyses, while taking into account biological plausibility. We therefore modeled starting with the 4 most significant independent variables and removing or adding the other variables to a current model based on −2 log likelihood. We modeled maternal drinking (any drinking during the 3 months before pregnancy or first trimester in model 1) and binge drinking (first trimester binge drinking in model 2) separately. We included maternal smoking in the final models given its significance in other studies. Potential confounders such as maternal age, education, marital status, and birth weight were assessed. Interactions between bed sharing or sleep position and prenatal maternal smoking or alcohol use, postnatal alcohol use or smoking, and layers of clothing were examined and considered significant at P = .10. Odds ratios (ORs) were considered significant if their 95% confidence intervals (CIs) excluded 1.0 or if the P values were <.05.

Seventy-two deceased American Indian infants younger than 1 year were enrolled. Autopsy reports were obtained in 56 cases (5 infants whose deaths were classified as "unexplained" were not autopsied and were assigned a diagnosis of undetermined; 9 infants whose deaths were "explained" did not have autopsies ordered; and 2 infants whose deaths were classifed as "infectious" had autopsies but reports could not be located). Thirty-seven cases were SIDS, 27 cases had explained causes (infections, injuries, congenital anomalies), and 8 cases were undetermined. Among the 37 SIDS cases, 1 parent refused to be interviewed and 3 parents had moved and could not be located. For the 33 cases with parental interviews, the death scene protocol was completed by the coroner or from police reports in 24 cases, and in 9 cases, summaries of scene investigations were reviewed by the PIMR and determined to be compatible with a diagnosis of SIDS.

Data for 66 control infants matched to the 33 case infants were analyzed. Five cases and their matching controls were from an urban Indian community and the rest were from rural Indian reservations. The median age difference between case and control infants was 2 days (range, 0-30 days). The median interval from the date of death of the index case to the parental interview was 30 days (range, 8-250 days) for case infants and 33 days (range, 2-330 days) for control infants.

The mean age at death of the SIDS infants was 109 days, 51.5% were male, and 64.7% died during the autumn and winter months. We found no significant differences between case and control infants in the mean values of selected maternal and infant sociodemographic and health care utilization factors, except in mean monthly household income (Table 1).

Sociodemographic and Health-Related Factors. Parents of SIDS infants were significantly more likely than control parents to have 12 years of education or less and less likely to have a telephone in the home (Table 2). Infants born to mothers who reported fewer than 7 prenatal visits were at a significantly increased risk for SIDS as were those whose mothers reported that inadequate transportation was a barrier. Infants whose mothers reported being visited by a PHN either before or after birth had a significantly lower risk for SIDS.

Adverse Maternal Behaviors. A higher percentage of case mothers reported smoking cigarettes during the 3 months prior to pregnancy and during the 3 trimesters than control mothers, but these differences were not statistically significant (Table 2). Smoking rates were high among both cases and controls with the highest rates during the 3 months preceding pregnancy, decreasing during each of the subsequent trimesters, and increasing after delivery to almost prepregnancy levels. Among those who reported smoking during pregnancy, the average number of cigarettes smoked per day did not vary significantly by case or control status (5.8 vs 6.2 cigarettes per day).

A higher percentage of case mothers reported using alcohol during the 3 months prior to pregnancy and during each trimester than controls (Table 2). The difference in the percentage using alcohol was statistically significant during the first trimester only. Alcohol use for both groups was highest 3 months prior to pregnancy and lowest during the second and third trimester and increased after delivery.

Binge drinking was more common among case than control mothers, but the difference was significant only for the first trimester (Table 2). First trimester binge drinking was associated with a 6-fold increased risk for SIDS. Rates of binge drinking decreased during pregnancy, but remained higher among case mothers than control mothers.

Among drinkers, case mothers consumed an average of 4.5 drinks per day vs 4.1 for control mothers on the days that they drank (P<.08); case mothers had an average of 1.9 drinking days per month vs 1.1 for control mothers (P<.03); and case mothers had an average of 4.8 binge drinking days per trimester vs 2.6 for control mothers (P<.08).

To explore whether the association between SIDS and maternal binge drinking reflects differences in maternal nutritional status, we examined maternal pregravid body mass index and trimester-specific hematocrit and hemoglobin levels. Maternal pregravid body mass index of less than 25 (69% of case and 55% of control mothers) was associated with a small nonsignificant increased risk for SIDS (OR, 1.8; 95% CI, 0.6-4.7). Using standard trimester-specific cut-offs, we compared low vs high levels of hematocrit (<33%, <32%, and <33% for trimesters 1, 2, and 3, respectively) and hemoglobin (<11.0 g/dL, 10.5 g/dL, and 11.0 g/dL for trimesters 1, 2, and 3, respectively). The OR for the association between low hematocrit values and SIDS progressively decreased from the first through the third trimester but none were statistically significant (OR, 4.45 [95% CI, 0.24-81.7]; OR, 1.41 [95% CI, 0.26-7.6]; OR, 0.85 [95% CI, 0.18-4.0]). We found similar associations between low hemoglobin levels and SIDS.

About 10% of mothers reported using illicit drugs during pregnancy, but differences between case and control mothers were not statistically significant. Marijuana was the most frequently used drug.

Infant Sleep Care Factors. More than half of the infants usually shared a bed with their parent at night in the 2 weeks preceding the case infant's death (Table 2), with similar percentages for case and control infants. No significant interactions (P = .10) were observed between usual bed sharing and maternal cigarette smoking or alcohol consumption.

The percentage of infants usually put to sleep on their stomachs in the 2 weeks prior to death did not differ between case and control infants (15.2% vs 13.6%). The percentages on their sides and backs were also similar as were the percentages usually found on their stomachs during the night. No significant interactions (P = .10) were observed between usual sleep position and cigarette smoking or alcohol consumption during pregnancy or the postpartum period.

Infants who had 2 or more layers of clothing or covers were at an increased risk for SIDS, although the increase was only statistically significant for infants with 2 or more layers of clothing (Table 2). No significant interactions (P = .10) were observed between layers of clothing or covers and usual sleep position or bed sharing.

Those who had fewer than 3 well-baby visits were at almost 14 times greater risk for SIDS. Two thirds of case mothers and half of control mothers reported that they ever breast-fed their infant, but the difference was not statistically significant.

We evaluated the following variables in a conditional logistic regression model: maternal education (≤12 years vs >12 years), paternal education (≤12 years vs >12 years), telephone in the home (present vs absent), number of prenatal visits (<7 vs ≥7), maternal smoking during pregnancy (mothers who reported smoking during pregnancy vs those who did not), layers of clothing (0-1 vs ≥2), periconceptional maternal alcohol use (mothers who reported using alcohol during the 3 months before or the first trimester of pregnancy vs those that did not), binge drinking (mothers who reported binge drinking during the first trimester vs those who did not), prenatal or postnatal PHN visit (any vs none) and well-baby visits (<3 vs ≥3).

Periconceptional alcohol drinking (model 1) was associated with an increased risk for SIDS (adjusted OR [aOR], 6.2; 95% CI, 1.6-23.3) (Table 3) as was first trimester drinking, but the model fit was slightly better for periconceptional drinking. First trimester maternal binge drinking (model 2) was associated with SIDS (aOR, 8.2; 95% CI, 1.9-35.3). Neither binge drinking nor use of alcohol during the second or third trimester was associated.

Infants who usually had 2 or more layers of clothing had a greater risk of dying of SIDS than those who had fewer layers (aOR, 6.2; 95% CI, 1.4-26.5). When we excluded 4 of 33 matched triplets for which case mothers were interviewed in the winter and control mothers in the summer, the OR fell from 6.2 to 5.2 but remained significant. Infants whose homes were visited by a PHN had a significantly lower risk for SIDS than those who were never visited (aOR, 0.2; 95% CI, 0.1-0.8). Maternal smoking was associated with an increased risk for SIDS, but the OR did not reach statistical significance. We found no significant interactions among the risk factors included in the final model.

This study of SIDS among American Indians identified 3 factors that are amenable to public health action and further research: (1) visits by PHNs, (2) periconceptional maternal alcohol drinking and first trimester binge drinking, and (3) infant layers of clothing.

Infants in homes that had any visit by a PHN before or after birth were one-fifth less likely to die of SIDS than those in homes that were never visited. Public health nursing is an integral component of the IHS programs and is entirely community based. One possible explanation for the absence of a visit is inaccessibility. However, nurse visits were not correlated with reports of transport barriers to care, the number of well-baby visits, or the number and timing of prenatal visits (data not shown). Further study is needed to confirm the protective effect of PHN visits and to identify the effective components of outreach activities.

A recent evaluation of home visiting programs concluded that variability in results from one program to another indicates that the benefits of the programs cannot be generalized.¹² Two randomized controlled trials of home visitation during the mother's pregnancy and her child's first 2 years of life showed that such visits were associated with positive pregnancy and childhood outcomes.^13- 15 In another study, the implementation of a universal postpartum nurse-visiting program resulted in a significant reduction in acute care visits during the infant's first 2 weeks of life.¹⁶

To our knowledge, this is the first study to report an association between SIDS and periconceptional maternal alcohol consumption and binge drinking during the first trimester. Few published studies have reported a relationship between maternal alcohol use and SIDS, and none of them found an independent correlation between maternal prenatal alcohol use and the risk of SIDS.^17- 19 However, one study did find a significant association between postnatal maternal alcohol use and SIDS. One study examined maternal binge drinking during the month before the infant's death but did not find it to be associated with SIDS.¹⁹

The proportion of pregnant control mothers reporting alcohol use during the third trimester in the AAIMS (6.6%) is similar to the proportion of mothers in the AAIHS (6.3%) who reported drinking during pregnancy on birth certificates in 1994-1996.⁸ The proportion is 4.5% for all IHS areas and 1.5% for all races in the United States.

In our study population, the pattern of drinking is predominantly binge drinking, and the OR for maternal binge drinking and SIDS was highest during the first trimester. Craniofacial anomalies, low birth weight, decreased head circumference, and congenital anomalies have been correlated with alcohol exposure in the first trimester in other studies.^20- 22 However, in this study, none of the infants who died had microcephaly, craniofacial anomalies, or major brain malformations. We also found no evidence to suggest that the association between alcohol and SIDS is mediated by poor prenatal maternal nutritional status.

In addition, by definition, assignment of the SIDS diagnosis meant that there was no evidence of abuse or neglect associated with excessive postnatal alcohol consumption. More research is needed to confirm these findings and elucidate the pathways leading to increased risk.

Excess thermal insulation for a given room temperature has been associated with increased SIDS risk,^23- 24 and the risk is further increased by viral illness²⁵ and prone sleep position.²⁴ We found that usually wearing 2 or more layers of clothing at night, not including the diaper, increased an infant's risk for SIDS more than 6-fold. Neither the number of covers nor the type (thin or thick blanket, sheet, quilt, or comforter) was significantly associated with SIDS risk.

Bed sharing in combination with maternal smoking during pregnancy has been shown to be associated with an increased risk for SIDS.^19,26- 28 This increased risk is also associated with other risk factors, ie, recent maternal alcohol consumption, the infant being covered by a duvet, and parental tiredness.²⁸ Bed sharing is routine among Northern Plains Indians. While we did not observe significant interactions between bed sharing and cigarette smoking or alcohol consumption, this study may lack the power to adequately assess the relationship of bed sharing to other risk factors.

The primary limitation of the study is the small sample size. The study had a 40% power to detect a 2-fold difference in smoking between case and control mothers and a 42% power to detect a 2-fold difference in gestational age between case and control infants. However, despite the small sample size, positive associations of potentially modifiable contributors to SIDS were found, although CIs were wide.

Another limitation is that the standard death scene form was not completed on all unattended deaths in spite of the availability of formal coroner training programs. Tribal police investigated half of the deaths because there was no enabling tribal legislation for coroners. The PIMR reviewed coroner, police, and emergency medical technician reports. When written reports of the scene investigation were not provided, the personnel who investigated the deaths were interviewed for information on possible homicide, overlying, or other diagnoses.

Recall bias regarding events during pregnancy or around the time of infant death is another potential limitation. However, it is unlikely that differential maternal recall bias between cases and controls occurred because of the high self-reported rates of smoking and alcohol use and the similar interval between death and interview of the cases and controls. Other case-control SIDS studies that examined recall bias did not find an appreciable impact on the important associations.^29- 30

Our results provide new evidence that factors in the periconceptional period contribute to SIDS risk in addition to those identified in the prenatal and postnatal periods. They suggest that public health outreach and programs to reduce alcohol consumption among women of childbearing age could have an impact on SIDS rates in this population.