Martin Ward Platt

Epidemiology of SIDS and Explained Sudden Infant Deaths

Objectives. To establish whether epidemiologic characteristics for sudden infant death syndrome (SIDS) have changed since the decrease in death rate after the “Back to Sleep” campaign in 1991, and to compare these characteristics with sudden and unexpected deaths in infancy (SUDI) from explained causes. Design. Three-year, population-based, case-control study. Parental interviews were conducted soon after the death and for 4 controls matched for age and date of interview. All sudden unexpected deaths were included in the study and the cause of death was established by a multidisciplinary panel of the relevant health care professionals taking into account past medical and social history of the mother and infant, the circumstances of death, and a full pediatric postmortem examination. Contributory factors and the final classification of death were made using the Avon clinicopathologic system. Setting. Five regions in England, with a total population of >17 million people, took part in the study. The number of live births within these regions during the particular time each region was involved in the study was 473 000. Study Participants. Three hundred twenty-five SIDS infants (91.3% of those available), 72 explained SUDI infants (86.7% of those available), and 1588 matched control infants (100% of total for cases included). Results. Many of the epidemiologic features that characterize SIDS infants and families have remained the same, despite the recent decrease in SIDS incidence in the United Kingdom. These include the same characteristic age distribution, few deaths in the first few weeks of life or after 6 months, with a peak between 4 and 16 weeks, a higher incidence in males, lower birth weight, shorter gestation, and more neonatal problems at delivery. As in previous studies there was a strong correlation with young maternal age and higher parity and the risk increased for infants of single mothers and for multiple births. A small but significant proportion of index mothers had also experienced a previous stillbirth or infant death. The majority of the SIDS deaths (83%) occurred during the night sleep and there was no particular day of the week on which a significantly higher proportion of deaths occurred. Major epidemiologic features to change since the decrease in SIDS rate include a reduction in the previous high winter peaks of death and a shift of SIDS families to the more deprived social grouping. Just more than one quarter of the SIDS deaths (27%) occurred in the 3 winter months (December through February) in the 3 years of this study. In half of the SIDS families (49%), the lone parent or both parents were unemployed compared with less than a fifth of control families (18%). This difference was not explained by an excess of single mothers in the index group. Many of the significant factors relating to the SIDS infants and families that distinguish them from the normal population did not distinguish between SIDS and explained SUDI. In the univariate analysis many of the epidemiologic characteristics significant among the SIDS group were also identified and in the same direction among the infants dying as SUDI attributable to known causes. The explained deaths were similarly characterized by the same infant, maternal, and social factors, 48% of these families received no waged income. Using logistic regression to make a direct comparison between the two index groups there were only three significant differences between the two groups of deaths: 1) a different age distribution, the age distribution of the explained deaths peaked in the first 2 months and was more uniform thereafter; 2) more congenital anomalies were noted at birth (odds ratio [OR] = 3.14; 95% confidence intervals [CI]: 1.52–6.51) among the explained deaths (20%) compared with the SIDS (8%), which was not surprising given that 10% of these deaths were explained by congenital anomalies; and 3) a higher incidence of maternal smoking during pregnancy among the SIDS mothers, the proportion of smokers within the explained SUDI group was much higher (49%) than the controls (27%), but among SIDS mothers the proportion of smokers was higher still (66%) and this difference was significant (66% vs 49%; OR = 2.03; 95% CI: 1.16–3.54). The largest subgroup of explained SUDI deaths were those attributable to infection (46%). There was a winter peak of deaths from infection, the highest number occurring in December (21%) but this was not significant. A multivariate model of these deaths showed parental unemployment to be the most significant factor (OR = 27.74; 95% CI: 3.19–241.34). Short gestational age (OR = 11.67; 95% CI: 1.84–74.14), neonatal problems (OR = 14.27; 95% CI: 1.89–107.81), and higher prevalence of males (OR = 9.26; 95% CI: 1.63–52.52) were also significant. Half of the deaths from infection occurred in crowded households (>1 adult or child per room excluding hallways, toilets, bathrooms, and kitchens if not used as a dining room) which was also a significant factor (OR = 10.37; 95% CI: 1.08–99.59). Conclusions. The study identifies changes in the epidemiologic characteristics of SIDS that have followed the “Back to Sleep” campaign, and confirms that many underlying factors are similar between infants who die as SIDS and those dying suddenly of explained causes. Many studies investigating SIDS have reported numerous epidemiologic characteristics and risk factors strongly associated with SIDS when compared with live control infants. It has been generally assumed that these factors are specific to SIDS to the extent that the syndrome has been described as an “epidemiologic entity.” Many of the factors associated with SIDS that were significantly different from the control population were not significantly different when compared with the explained deaths. This suggests that SUDI share some of the same underlying factors irrespective of the clinical or pathologic findings, and challenges a rigid concept of SIDS as an epidemiologic entity. The particular finding that the incidence of maternal smoking during pregnancy, although high among mothers of explained SUDI infants, was significantly higher among SIDS mothers, lends weight to the mounting evidence that the association between smoking and SIDS may be part of a causal mechanism.

Pacifier use and sudden infant death syndrome: results from the CESDI/SUDI case control study

OBJECTIVES To investigate the relation between pacifier use and sudden infant death syndrome (SIDS). DESIGN Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING Five regions in England (population > 17 million). SUBJECTS 325 infants who had died from SIDS and 1300 control infants. RESULTS Significantly fewer SIDS infants (40%) than controls (51%) used a pacifier for the last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence interval (CI), 0.46 to 0.83) and the difference increased when controlled for other factors (multivariate OR, 0.41; 95% CI, 0.22 to 0.77). However, the proportion of infants who had ever used a pacifier for day (66% SIDS v 66% controls) or night sleeps (61% SIDS v 61% controls) was identical. The association of a risk for SIDS infants who routinely used a pacifier but did not do so for the last sleep became non-significant when controlled for socioeconomic status (bivariate OR, 1.39 (0.93 to 2.07)). CONCLUSIONS Further epidemiological evidence and physiological studies are needed before pacifier use can be recommended as a measure to reduce the risk of SIDS. Key messages There was no difference between victims of SIDS and control infants in routine use of a pacifier (“dummy” or “soother”) for day or night sleeps The use of a pacifier was associated with a lower prevalence and shorter duration of breast feeding, lower socioeconomic status, and mothers who smoked more heavily There was no association between pacifier use and sleeping position More control infants used a pacifier for the last/reference sleep, giving an apparent “protective” effect against SIDS; the significance of this association increased when controlled for other factors Further epidemiological evidence and physiological studies are needed before we can recommend pacifier use as protective against SIDS

Difficulties in selecting an appropriate neonatal thyroid stimulating hormone (TSH) screening threshold

Background The UK Newborn Screening Programme Centre recommends that a blood spot thyroid stimulating hormone (TSH) cut-off of 10 mU/l is used to detect congenital hypothyroidism (CHT). As the value used varies from 5 to 10 mU/l, we examined the implications of altering this threshold. Methods Our regional blood spot TSH cut-off is 6 mU/l. Positive or suspected cases were defined as a TSH >6 mU/l throughout the study period (1 April 2005 to 1 March 2007). All term infants (>35 weeks) whose first TSH was 6–20 mU/l had a second TSH measured. The biochemical details of infants with a TSH between 6.1 and 10.0 mU/l and then >6 mU/l on second sampling were sent to paediatric endocrinologists to determine approaches to management. Results 148 of 65 446 infants (0.23%) had a first blood spot TSH >6.0 mU/l. 120 were term infants with 67 of these (0.1% of all infants tested) having a TSH between 6.1 and 10.0 mU/l and 53 a TSH >10.0 mU/l. Of the 67 term infants with a TSH between 6.1 and 10.0 mU/l on initial testing, four continued to have a TSH >6 mU/l. One with a TSH >10 mU/l and one infant with a TSH <10 mU/l on the second blood spot have been diagnosed with CHT. The survey of endocrinologists highlighted significant differences in practice. Conclusions A reduced threshold of 6 mU/l will increase the number of false positive term infants by 126%, but abnormalities of thyroid function requiring treatment will be detected. We suspect that the additional expense involved in setting a lower threshold is justified.

The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study

Abstract Objectives: To investigate whether the accelerated immunisation programme in the United Kingdom is associated, after adjustment for potential confounding, with the sudden infant death syndrome. Design: Population based case-control study, February 1993 to March 1996. Parental interviews were conducted for each death and for four controls matched for age, locality, and time of sleep. Immunisation status was taken from records held by the parents. Setting: Five regions in England with a combined population of over 17 million. Subjects: Immunisation details were available for 93% (303/325) of infants whose deaths were attributed to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained sudden deaths; and 95% (1515/1588) of controls. Results: After all potential confounding factors were controlled for, immunisation uptake was strongly associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval 0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43)) after further adjustment for other factors specific to the infants sleeping environment. Similar proportions of SIDS deaths and reference sleeps (corresponding to the time of day during which the index baby had died) among the controls occurred within 48 hours of the last vaccination (5% (7/149) v 5% (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term temporal association with immunisation was found (P=0.78). Of the SIDS infants who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of illness that suggested that medical contact was required, compared with 26% (16/61) of the non-immunised SIDS infants of similar age. The findings for the infants who died suddenly and unexpectedly but of explained causes mirrored those for SIDS infants. Conclusions: Immunisation does not lead to sudden unexpected death in infancy, and the direction of the relation is towards protection rather than risk. What is already known on this topic Some studies have suggested a link between the sudden infant death syndrome and primary immunisation, but most have failed to show a link Potential bias in the studies includes lack of a comparative control group with similar low immunisation uptake and misclassification of cause of death What this study adds This study investigated explained sudden infant deaths as well as the sudden infant death syndrome and took into account potential bias After confounding was controlled for, immunisation uptake was lowest among the infants who died, with no temporal relation or correlation with signs and symptoms of illness

A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal?

OBJECTIVES To compare the clinical characteristics associated with sudden infant death syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI). DESIGN Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING Five regions in England (population, > 17 million; live births, > 470 000). SUBJECTS SIDS: 325 infants; explained SUDI: 72 infants; controls: 1588 infants. RESULTS In the univariate analysis, all the clinical features and health markers at birth, after discharge from hospital, during life, and shortly before death, significant among the infants with SIDS were in the same direction among the infants who died of explained SUDI. In the multivariate analysis, at least one apparent life threatening event had been experienced by more of the infants who died than in controls (SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81; 95% CI, 2.52 to 112.30). Using a retrospective illness scoring system based on “Baby Check”, both index groups showed significant markers of illness in the last 24 hours (SIDS: 22%v 8% controls; OR = 4.17; 95% CI, 1.88 to 9.24; explained SUDI: 49% v 8% controls; OR = 31.20; 95% CI, 6.93 to 140.5). CONCLUSIONS The clinical characteristics of SIDS and explained SUDI are similar. Baby Check might help identify seriously ill babies at risk of sudden death, particularly in high risk infants. Key messages There are clinical features and health markers characterising increased vulnerability of infants who die suddenly and unexpectedly that are evident at birth, during life, and just before death These features, important among the infants with sudden infant death syndrome, are in the same direction among the explained sudden unexpected deaths Clinical features common to both groups of explained and unexplained deaths after controlling for possible confounders included a higher prevalence of an apparent life threatening event and ill health in the 24 hours before death “Baby Check” might help identify seriously ill babies at risk of sudden death, particularly in high risk infants

Congenital anomaly and childhood cancer: A population‐based, record linkage study

The cause of the majority of childhood malignancies is unknown. Association with the presence of congenital anomalies has been noted in some studies. In this study, we describe and quantify the association between congenital anomalies and childhood cancer.

Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia due to a urea cycle disorder

It is difficult to prevent hyperammonaemia in patients with urea cycle disorders that present in the newborn period. This is true, even if treatment is started prospectively because of an affected relative. We propose several additional measures that could be used in conjunction with conventional therapy to improve the metabolic control. Catabolism could be reduced by delivering the babies by elective caesarean section, by starting intravenous glucose immediately after delivery and, possibly, by using β-blockers or octreotide and insulin. The effectiveness of sodium benzoate and sodium phenylbutyrate might be increased by giving phenobarbital to the mother before delivery and subsequently to the baby to induce the enzymes for conjugation. We would expect the proposed measures to reduce the risk of hyperammonaemia and to improve the outcome for these patients. They have not, however, previously been used in this context, so families would need to be counselled carefully and controlled studies should be undertaken.

Mortality of twin and singleton livebirths under 30 weeks’ gestation: a population-based study

Objective: To determine the mortality rates of liveborn twins compared with singletons of less than 30 weeks’ gestation in relation to gestational age, mode of delivery and year of birth in a geographically defined population. Study design: Comparison of early neonatal, late neonatal and infant death rates in 479 twin babies and 1538 singletons, liveborn between 23 and 29 completed weeks of gestation in the north of England over two epochs, 1998–2001 and 2002–5. Results: Twins and singletons had similar mortality rates except at the extreme of gestation (23–25 weeks) where twins had higher infant mortality (OR 2.04, 95% CI 1.37 to 3.02). This higher rate was attributable to early and late neonatal deaths (OR 1.86, 95% CI 1.28 to 2.72, and 2.11, 95% CI 1.13–3.94, respectively). When analysed in two epochs, the excess mortality was confined to babies born in 1998–2001. There was no effect of gender or chorionicity. Conclusions: The excess mortality among twins of less than 30 weeks’ gestation was confined to neonatal deaths in babies of 25 weeks or less, and to the earlier epoch (1998–2001). In the modern era, there appears to be no excess mortality in neonates less than 30 weeks’ gestation when compared with singletons.

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk

AIMS To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS). DESIGN Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference. SETTING Five regions in England (population greater than 17 million, more than 470 000 live births over three years). SUBJECTS 247 SIDS cases and 1110 controls. RESULTS The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (δzw) = −0.38 (SD 1.40)v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1.48–2.07, p < 0.0001) than for those with lower birth weight (OR = 1.09, 95% CI 0.61–1.95, p = 0.76). There was no evidence of increased growth retardation before death. CONCLUSIONS Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment. Key messages The lower weight of SIDS infants compared to the control infants which was apparent at birth was even more notable in the two weeks before death SIDS infants, particularly those of normal birth weight, exhibited poorer weight gain than their controls Although poor growth was evident among SIDS infants there was no evidence of accelerated retardation in the weeks prior to death The difference in growth between SIDS and control infants was apparent within the first five to seven weeks of life

The North of England Survey of Twin and Multiple Pregnancy

The population-based Northern Survey of Twin and Multiple Pregnancy (NorSTAMP, formerly the Multiple Pregnancy Register) has collected data since 1998 on all multiple pregnancies in North of England (UK) from the earliest point of ascertainment in pregnancy. This paper updates recent developments to the NorSTAMP and presents some early mortality data from the first 10 years of data collection (1998-2007). Since 2005, mothers have been asked to give explicit consent for their identifiable data to be held by the survey, in line with changing guidance and legal frameworks for identifiable data. In 2009, regional standards of care for multiple pregnancies were developed, agreed, and disseminated. During 1998-2007, 4,865 twin maternities (pregnancies with at least one live birth or stillbirth) were registered, with an average twinning rate of 14.9 per 1,000 maternities. The overall stillbirth and neonatal mortality rates in twins were 18.0/1,000 births and 23.0/1,000 live births respectively. Stillbirth and neonatal mortality rates were significantly higher in monochorionic than dichorionic twins: 44.4 versus 12.2 per 1,000 births (relative risk [RR] 3.6, 95% Confidence Intervals [CI] 2.6-5.1), and 32.4 versus 21.4 per 1,000 live births (RR 1.5, 95% CI 1.04-2.2) respectively. There was no significant improvement during this period in either stillbirth or neonatal mortality rates in either chorionicity group. This population-based survey is an important source of data on multiple pregnancies, which allows monitoring of trends in multiple birth rates and pregnancy losses, providing essential information to support improvements in clinical care and for epidemiological research.