Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

A 2.1 Mb deletion adjacent but distal to a 14q21q23 paracentric inversion in a family with spherocytosis and severe learning difficulties.

A familial q21.1q23.2-inversion on chromosome 14 that co-segregated with spherocytosis and learning difficulties or mild mental retardation was extensively investigated by bacterial artificial chromosome fluorescence in situ hybridization and array-comparative genomic hybridization. As expected, a deletion of the beta-spectrin gene SPTB, a known cause of spherocytosis, was found. More unexpectedly, this deletion was approximately 1.6 Mb distal to the 14q23.2-inversion breakpoint. The deletion spanned approximately 2.1 Mb and contained 15 annotated genes in addition to SPTB, among them PLEKHG3, a guanide nucleotide exchange factor for Rho GTPases. This gene is highly expressed in the brain and our best candidate for causing the mild mental retardation. The case illustrates that inversions can be associated with microdeletions close to but not including one of the inversion breakpoints.

Maternal anthropometric and metabolic factors in the first half of pregnancy and risk of neonatal macrosomia in term pregnancies. A prospective study.

OBJECTIVE: The prevalence of maternal overweight and fetal macrosomia is increasing. Fetal macrosomia is associated with increased risk of maternal and neonatal complications. The objective of the present study was to investigate if maternal metabolic parameters associated with maternal overweight were independent determinants of macrosomia (birth weight > 4500 g or above the 95 percentile of the z-score for standardized birth weight). DESIGN: Prospective population based cohort study of 2050 pregnancies and nested case control study. METHODS: Outcome measures were adjusted risks for macrosomia in relation to early second trimester maternal serum lipids, glucose and insulin (cohort study) and leptin and insulin-like growth factor (73 cases and 146 matched controls). RESULTS: Gestational diabetes was not independently associated with fetal macrosomia. First trimester body mass index (BMI), gestational weight gain and placental weight were associated with macrosomia. High serum insulin and non-high density lipoprotein (HDL)-cholesterol and low serum HDL-cholesterol were associated with increased risk of macrosomia independent of BMI, weight gain, placental weight and gestational diabetes. Slim women with macrosomic infants had higher insulin compared with those with normal weight infants. This relation was not found among obese women. Leptin was not associated with macrosomia after adjusting for maternal BMI. CONCLUSIONS: Blood parameters known to be associated with the metabolic syndrome were risk factors for macrosomia independent of maternal BMI.

Circadian variations in sudden infant death syndrome: associations with maternal smoking, sleeping position and infections. The Nordic Epidemiological SIDS Study.

AIM: To study circadian variation in the sudden infant death syndrome (SIDS) and possible associations with risk factors for SIDS. METHODS: A questionnaire-based case-control study matched for place of birth, age and gender was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. The study comprised 244 SIDS victims and 869 control infants between September 1992 and August 1995. The main outcome was hour found dead. RESULTS: A significant circadian pattern was observed among the 242 SIDS victims with a known hour found dead, with a peak at 08.00-08.59 in the morning (n = 33). Of the SIDS victims, 12% were found dead at 00.00-05.59, 58% at 06.00-11.59, 21% at 12.00-17.59 and 9.0% at 18.00-23.59. When comparing night/morning SIDS and day/evening SIDS (found dead 00.00-11.59 and 12.00-23.59, respectively), the proportion of night/morning SIDS was high among infants of smoking mothers (81% vs 53%, p < 0.001), infants with a reported cold (82% vs 64%, p = 0.007) and infants sleeping side/supine (81% vs 60%, p < 0.001). No associations were observed between hour found dead and other sociodemographic risk factors for SIDS. Risk (odds ratio and 95% confidence interval) of night/morning SIDS and day/evening SIDS was 7.0 (4.5-10.9) and 1.5 (0.8-2.5), respectively, for maternal smoking, 2.2 (1.5-3.1) and 0.6 (0.3-1.3), respectively, if the infant had a reported cold, 3.7 (2.1-6.6) and 3.1 (1.1-8.4), respectively, if the infant was put to sleep in the side position (supine reference), and 11.0 (5.9-20.2) and 21.6 (7.6-60.8), respectively, if the infant was put to sleep in the prone position. CONCLUSION: The observed higher proportion of night/morning cases in SIDS if the mother smoked, if the infant was reported to have a cold and if the infant was sleeping side/supine may contribute to the understanding of some epidemiological characteristics of SIDS.

Changes in the epidemiology of sudden infant death syndrome in Sweden 1973-1996.

BACKGROUND: From the early 1970s to the early 1990s, there was a significant rise in the incidence of sudden infant death syndrome (SIDS) in Scandinavia. Following the risk reducing campaign, the incidence has fallen to about the same level as in 1973. AIMS: To identify the changes that have occurred in the epidemiology of SIDS. METHODS: We compared the Swedish part of the Nordic Epidemiological SIDS Study (NESS), covering the years 1992-1995, with two earlier, descriptive studies during this period. To assess the changing effects of risk factors, we analysed data from the Medical Birth Registry of Sweden, covering the years 1973-1996. RESULTS: There was a predominance of deaths during weekends in the 1970s and 1990s. The seasonal variation was most notable in the 1980s. The proportion of young mothers decreased from 14% to 5%. Cohabitation (living with the biological father) was as frequent in the 1990s as in the 1970s. The prevalence of high parity, admissions to neonatal wards, low birth weight, prematurity, and multiple pregnancies were all increased in the 1990s compared to the 1970s. No significant change in the prevalence of previous apparent life threatening events was found. Deaths occurring in cars diminished from 10% to below 2%. In the data from the Medical Birth Registry of Sweden, there were significantly increased odds ratios after the risk reducing campaign of the risk factors smoking during early pregnancy and preterm birth. We could find no increased effects of maternal age, parity, or being small for gestational age over time. The rate of deaths at weekends remained increased; the median age at death fell from 90 to 60 days. Seasonal variation was less notable in the periods of low incidence.

Infants' length at birth: an independent effect on perinatal mortality.

AIM: To investigate whether variations in birth length (crown-heel-length) were associated with perinatal mortality rate independent of birth weight. MATERIAL: The study population was singleton live- and stillbirths from 16 weeks of gestation compiled in the Medical Birth Registry of Norway from 1967 to 1997, totaling 1,705,652 births. METHOD: The total population was analyzed using z-scores for length at birth, birth weight and gestational age. Variation in perinatal mortality by length at birth was studied within birth weight strata (250 g) by logistic regression. RESULTS: Perinatal mortality varied more by birth length than by birth weight or gestational age, especially for values above the population means. Within birth weight strata, the association between perinatal mortality and length was similar in all 250 g birth weight categories above 1,500 grams: mortality was lowest at birth lengths 0-2 cm below average, with mortality rates increasing exponentially in either direction. CONCLUSION: Within all birth weight strata, and adjusted for gestational age, long infants had the higher risk of perinatal death, suggesting that length at birth may be a valuable predictor when assessing the risk of perinatal mortality.

Recurrence of gestational age in sibships: implications for perinatal mortality.

The authors studied the extent to which preterm birth and perinatal mortality are dependent on the gestational ages of previous births within sibships. The study was based on data collected by the Medical Birth Registry of Norway from 1967 to 1995. Newborns were linked to their mothers through Norway's unique personal identification number, yielding 429,554 pairs of mothers and first and second singleton newborns with gestational ages of 22-46 weeks, based on menstrual dates. Siblings' gestational ages were significantly correlated (r = 0.26). The risk of having a preterm second birth was nearly 10 times higher among mothers whose firstborn child had been delivered before 32 weeks' gestation than among mothers whose first child had been born at 40 weeks. However, perinatal mortality in preterm second births was significantly higher among mothers whose first infant had been born at term, compared with mothers whose firstborn child was delivered at 32-37 weeks. Since perinatal mortality among preterm infants is dependent on the gestational age in the mother's previous birth, a common threshold of 37 weeks' gestation for defining preterm birth as a risk factor for perinatal death may not be appropriate for all births to all mothers.

Caffeine and alcohol as risk factors for sudden infant death syndrome. Nordic Epidemiological SIDS Study.

OBJECTIVE: To assess whether alcohol and caffeine are independent risk factors for sudden infant death syndrome (SIDS). MATERIALS AND METHODS: Analyses based on data from the Nordic epidemiological SIDS study, a case control study in which all parents of SIDS victims in the Nordic countries from 1 September 1992 to 31 August 1995 were invited to participate with parents of four controls, matched for sex and age at death. Odds ratios (ORs) were calculated by conditional logistic regression analysis. RESULTS: The crude ORs for caffeine consumption > 800 mg/24 hours both during and after pregnancy were significantly raised: 3.9 (95% confidence interval (CI), 1.9 to 8.1) and 3.1 (95% CI, 1.5 to 6.3), respectively. However, after adjustment for maternal smoking in 1st trimester, maternal age, education and parity, no significant effect of caffeine during or after pregnancy remained. For maternal or paternal alcohol use, no significant risk increase was found after adjusting for social variables, except for heavy postnatal intake of alcohol by the mother, where the risk was significantly increased. CONCLUSIONS: Caffeine during or after pregnancy was not found to be an independent risk factor for SIDS after adjustment for maternal age, education, parity, and smoking during pregnancy. Heavy postnatal but not prenatal intake of alcohol by the mother increased the risk.

Interactions of infectious symptoms and modifiable risk factors in sudden infant death syndrome. The Nordic Epidemiological SIDS study.

The aim of the study was to investigate the effect of infection on sudden infant death syndrome (SIDS) and to analyse whether modifiable risk factors of SIDS, prone sleeping, covered head and smoking act as effect modifiers. In a consecutive multicentre case-control study of SIDS in Denmark, Norway and Sweden, questionnaires on potential risk factors for SIDS were completed by parents of SIDS victims, and for at least two controls matched for gender, age and place of birth. All SIDS cases were verified by an autopsy. The study comprised 244 SIDS cases and 869 controls, analysed by conditional logistic regression. Significantly more cases than controls presenting symptoms of infectious diseases during the last week and/or last day were treated with antibiotics and had been seen by a physician. The finding is consistent with the hypothesis of an infectious mechanism in SIDS induced by local microorganism growth and toxin or cytokine production, and also adds further support to a possible association between infection and SIDS by loss of protective mechanisms, such as arousal. The risk of SIDS among infants with the combined presence of infectious symptoms and either of the other modifiable risk factors, prone sleeping, head covered or parental smoking, was far greater than the sum of each individual factor. These risk factors thus modify the dangerousness of infection in infancy.

A case-control study of smoking and sudden infant death syndrome in the Scandinavian countries, 1992 to 1995. The Nordic Epidemiological SIDS Study.

AIM: To establish whether smoking is an independent risk factor for sudden infant death syndrome (SIDS), if the effect is mainly due to prenatal or postnatal smoking, and the effect of smoking cessation. METHODS: The analyses were based on data from the Nordic epidemiological SIDS study, a case-control study with 244 cases and 869 controls. Odds ratios were computed by conditional logistic regression analysis. RESULTS: Smoking emerged as an independent risk factor for SIDS, and the effect was mainly mediated through maternal smoking in pregnancy (crude odds ratio 4.0 (95% confidence interval 2.9 to 5.6)). Maternal smoking showed a marked dose-response relation. There was no effect of paternal smoking if the mother did not smoke. Stopping or even reducing smoking was beneficial. SIDS cases exposed to tobacco smoke were breast fed for a shorter time than non-exposed cases, and feeding difficulties were also more common. CONCLUSIONS: Smoking is an independent risk factor for SIDS and is mainly mediated through maternal smoking during pregnancy. Stopping smoking or smoking less may be beneficial in reducing the risk of SIDS.

Sociodemographic risk factors for sudden infant death syndrome: associations with other risk factors. The Nordic Epidemiological SIDS Study.

The aim of this study was to investigate associations between sudden infant death syndrome (SIDS) and social factors in the Nordic countries. A case-control study was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. Parents of 244 SIDS infants and 869 control infants matched on gender, age at death and place of birth filled in questionnaires. The dataset was analysed by conditional logistic regression. In univariate analysis, the following sociodemographic factors were associated with an increased risk of SIDS: low maternal age [odds ratio (OR) 7.8; 2.8-21.5], high birth order (OR 4.4; 2.5-7.5), single motherhood (OR 2.9; 1.7-5.0), low maternal education (OR 4.5; 2.8-7.1), low paternal education (OR 3.0; 1.9-4.7), maternal unemployment (OR 2.4; 1.8-3.4) and paternal unemployment (OR 4.0; 2.7-5.9). In a multivariate analysis where maternal smoking was also included, only paternal unemployment, young maternal age and high birth order remained significantly associated with SIDS. Housing conditions were not associated with SIDS. However, the risk of SIDS was high if the family had lived in their present home for only a few years (OR 2.3; 1.3-4.1). Sociodemographic differences remain a major concern in SIDS in a low-incidence situation and even in an affluent population with adequate health services.

The decline in the incidence of SIDS in Scandinavia and its relation to risk-intervention campaigns. Nordic Epidemiological SIDS Study.

A prospective case-control study of sudden infant death syndrome (SIDS) in Norway, Denmark and Sweden between September 1, 1992 and August 31, 1995 comprised 244 cases and 869 matched controls. After the introduction of risk-intervention campaigns, the SIDS incidence decreased from 2.3/1000 live births in Norway, 1.6 in Denmark and 1.0 in Sweden to 0.6/1000 or fewer in all the Scandinavian countries in 1995. The decrease paralleled a decline in the prone sleeping position and there was an accompanying parallel fall in total postneonatal mortality in all three countries. Thus, the risk-reducing campaigns for SIDS have been successful not only in Norway and Denmark, starting from relatively high incidences, but also in Sweden, starting from a low incidence. During the study period, a gradual increase was observed for the effects of prone sleeping, smoking and bottle-feeding as risk factors for SIDS.

Combined effects of sleeping position and prenatal risk factors in sudden infant death syndrome: the Nordic Epidemiological SIDS Study.

OBJECTIVE: Prone sleeping is a strong risk factor for sudden infant death syndrome (SIDS). We investigated whether the combined effect of prone sleeping position and prenatal risk factors further increased the SIDS risk. METHODS: In the Nordic Epidemiological SIDS Study, parents of SIDS victims in Denmark, Norway, and Sweden completed a questionnaire on potential risk factors for SIDS. Forensic pathologists verified the SIDS diagnosis. Four controls of the same gender, age, and place of birth were selected. This matched case-control study, which included 244 SIDS cases and 869 controls from 1992 to 1995, was analyzed by conditional logistic regression. RESULTS: Odds ratios (ORs) for prone and side sleeping compared with supine sleeping for the last sleep were 13.9 (95% confidence interval 8.2-24) and 3.5 (2.1-5.7). Infants 13 to 24 weeks old had particularly high risk in prone and side sleeping, at 28.5 (7.9-107) and 5.9 (1.6-22). OR for prone sleeping was higher in girls, at 30.4 (11-88), than in boys, 10.3 (5.5-19). We found strong combined effects of sleeping position and prenatal risk factors (more than multiplicative). The OR for prone and side sleeping was increased for infants with birth weight <2500 g, at 83 (25-276) and 36.6 (13-107); for preterm infants, at 48.8 (19-128) and 40.5 (14-115); and for intrauterine growth retarded, at 38.8 (14-108) and 9.6 (4.3-22), compared with supine position in infants without these prenatal factors. The combined effect of nonsupine positions and intrauterine growth retarded was highest among 13- to 24-week-old infants. Effects of combined presence of nonsupine sleeping positions and each of the factors of smoking in pregnancy, young maternal age, higher parity, low level of maternal education, and single motherhood were more than additive. Attributable fractions in the population for prone and side sleeping were 18.5% and 26.0%. CONCLUSIONS: Both prone and side sleeping increased the risk of SIDS. The risk was increased further in low birth weight infants, preterm infants, and infants at the age of 13 to 24 weeks, suggesting that SIDS may be triggered by nonsupine sleeping in infants with prenatal risk factors during a vulnerable period of postnatal development.

Interactions between maternal smoking and other prenatal risk factors for sudden infant death syndrome (SIDS).

In numerous investigations, maternal smoking increases the risk of sudden infant death syndrome (SIDS). In the present study we investigated whether prenatal risk factors for SIDS modify the effect of maternal smoking on SIDS mortality. We analysed data from a population-based cohort study (222 cases, 260,604 infants at risk) within the Westphalian Perinatal Inquiry in Germany between 1990 and 1994. In the stratified analysis, smoking was classified into non-smoking, moderate (1-10 cigarettes/d) and heavy smoking (> 10 cigarettes/d). Multiplicative interactions between smoking and other prenatal risk factors were assessed in a logistic regression model. The relative risk (RR) for maternal smoking was 2.4 (95% confidence interval 1.7-5.4) for moderate and 7.2 (5.3, 9.7) for heavy smokers. Previous established risk factors for SIDS, such as preterm birth, low birthweight, and number of prenatal visits did not increase the risk of SIDS among non-smokers, but became important risk factors among smokers. In preterm infants (< 37 weeks) of heavy smokers, the RR was 19.6 (10.4, 36.8) compared to term infants of non-smokers. Low birthweight infants (< 2500 g) of heavy smokers had a RR of 16.3 (8.4, 31.2) compared to normal weighted infants of non-smokers. Adjustment for occupational status did not change the crude estimates. The RR of < 6 prenatal visits in the heavy smoking subgroup was 14.8 (7.2, 29.6) compared to > 9 prenatal visits in the non-smoking strata. Heavy smoking potentiates other prenatal risk factors for SIDS suggesting an increased susceptibility towards the adverse effects of tobacco smoke in utero. In infants born to non-smoking mothers, prenatal risk factors are absent and postnatal factors may be of major importance.

The epidemic of SIDS in Norway 1967-93: changing effects of risk factors.

Time trends on the association of maternal age, birth order, and marital status with the risk of sudden infant death syndrome (SIDS) and non-SIDS deaths in Norway were analysed: 2356 postperinatal SIDS deaths and 4069 postperinatal non-SIDS deaths were ascertained during 1967-93. The SIDS incidence was 1.25 per 1000 in 1967, reached a peak of 2.69 in 1988, and fell to 1.22 in 1990 after the initiation of an intervention programme to avoid prone sleeping. In the entire period, young maternal age, high birth order, and unmarried motherhood were associated with SIDS. The adverse effects of young maternal age and high birth order increased continuously with time. From 1967-71 to 1990-93, the relative risk for maternal age < 20 years v maternal age 25-29 changed from 2.5 (95% confidence interval 2.0 to 3.2) to 7.0 (95% CI 4.2 to 11.9) (p < 0.0001), and for birth order 4+ nu birth order 1 from 3.2 (95% CI 2.5 to 4.2) to 14.4 (95% CI 8.3 to 24.9) (p < 0.0001). Effects on non-SIDS deaths were far weaker and no secular trends were observed. The strong association of young maternal age, high birth order, and marital status in SIDS, but not in non-SIDS, provides evidence that SIDS is an epidemiological entity. The increasing effects of young maternal age and high birth order, which continued after the sudden drop in the SIDS rate in 1990, suggest that further efforts to prevent SIDS should be aimed particularly at identifying causal mechanisms in high risk groups.

Mothers' birth weight and survival of their offspring: population based study.

OBJECTIVE: To test the hypothesis that a baby's survival is related to the mother's birth weight. DESIGN: Population based dataset for two generations. SETTING: Population registry in Norway. SUBJECTS: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). RESULTS: A mother's birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother's weight and infant survival. There was, however, a strong interaction between mother's birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother's birth weight had been high (> or = 4000 g) than if the mother had been small (2500-2999 g). CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed > or = 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother's birth weight are at increased risk of mortality.

Maternal smoking, birthweight and gestational age in sudden infant death syndrome (SIDS) babies and their surviving siblings.

To evaluate the effect of maternal smoking on intrauterine growth of babies who died of sudden infant death syndrome (SIDS), birthweights of SIDS infants and their surviving siblings were compared with birthweights of infants in sibships were all infants survived the first year of life. We studied 184,349 mothers with at least two births registered in the population-based Swedish Medical Birth Registry during 1983-91. The mother being the unit of analysis, birthweight and gestational age of her infants were the repeated measures used in a repeated measures analysis of variance. Mothers whose first two infants survived at least 1 year, smoked less than mothers of SIDS infants, 25 and 41% (P < 0.01). Overall, SIDS mothers did not smoke more while pregnant with the SIDS infant than while pregnant with the surviving sibling. SIDS siblings weighted, on average, 90 g less than infants in non-affected sibships. SIDS babies were even lighter, 193 g, and had 3.8 days shorter mean gestational age, compared with same birth-order babies in non-affected sibships. After adjustment for gestational age, the birthweight difference changed only slightly for SIDS siblings, while the difference for SIDS infants was reduced from 193 to 110 g. Further adjustment for smoking reduced the birthweight difference for SIDS siblings, from 74 to 50 g, and SIDS infants, from 110 to 82 g. Intrauterine growth retardation of sibships with a SIDS baby is explained only partly by maternal smoking. The even lower birthweight of the SIDS baby, resulting from shorter gestational age, cannot be explained by smoking, suggesting pregnancy factors specific to the SIDS baby and not to its siblings.

Population-based recurrence risk of sudden infant death syndrome compared with other infant and fetal deaths.

To investigate the recurrence of sudden infant death syndrome (SIDS) among siblings, the authors analyzed data for all 352,475 mothers whose first and second single births were reported to the Medical Birth Registry of Norway during 1967-1988. Recurrence of stillbirths from the 16th week of gestation onward and infant deaths other than SIDS were also studied. Relative risk of recurrence for SIDS was 5.8 (95% confidence interval (CI) 2.1-13.2); for asphyxia- and immaturity-related infant deaths, 12.5 (9.2-17.4); for congenital malformations, 7.2 (4.7-11.0); and for other causes of infant death, 8.0 (2.0-22.1). Deaths due to infections did not recur. Similar categories of infant deaths had higher overall relative risk, 9.1, compared with 1.6 for dissimilar categories. Previous early stillbirth (16-27 weeks) had a high recurrence (relative risk (RR) = 21.8, 95% CI 17.5-26.9), while late stillbirth (> or = 28 weeks) had lower recurrence (RR = 4.6, 95% CI 3.7-5.8). Previous SIDS was associated with an increased risk of all other types of loss. In contrast, previous late stillbirth and previous asphyxia- and immaturity-related infant deaths were associated with a reduced risk of subsequent SIDS (RR = 0.31, 95% CI 0.08-0.84, and RR = 0.23, 95% CI 0.01-1.13, respectively). In conclusion, as with other infant and fetal deaths, SIDS deaths showed strong sibship aggregation consistent with a genetic susceptibility in subsets of SIDS that may interact with environmental factors. The authors also suggest common pregnancy-specific risk factors for late stillbirths, asphyxia- and immaturity-related infant deaths, and SIDS.

Fetal growth retardation in sudden infant death syndrome (SIDS) babies and their siblings.

To evaluate the intrauterine growth potential of infants that die from sudden infant death syndrome (SIDS), the authors compared SIDS infants with their surviving siblings. The SIDS sibships themselves were also compared with sibships where all infants survived. Data from the population-based Medical Birth Registry of Norway, with 1.3 million births during 1967-1988, were used. From the birth cohorts, 1,984 SIDS cases were identified. All births were linked into sibships. The mean birth weight and gestational age were calculated across sibships of different sizes for first to fourth birth order. In a further analysis, birth weights were standardized to adjust for gestational age. Mothers of SIDS infants give birth to smaller babies in general. SIDS infants weighed, on average, 85 g less at birth than their siblings and 164 g less compared with babies in nonaffected sibships. When birth weights were standardized for gestational age, most of the weight difference between SIDS infants and siblings was due to a shorter gestational age of SIDS infants, while the difference between surviving siblings of SIDS infants and births from nonaffected sibships remained. All births in sibships with a SIDS infant were intrauterine growth retarded. This may reflect factors that contribute to SIDS risk (such as maternal smoking). The factors that contribute to shorter gestational age and further slowing of growth in the SIDS infants may specifically influence the SIDS infant and not its siblings.

Sleeping position and sudden infant death syndrome in Norway 1967-91.

OBJECTIVE: To investigate, in a population based national study, the association between sleeping position of infants and the occurrence of sudden infant death syndrome (SIDS). DESIGN: A retrospective survey and registry based ecological study. A questionnaire based surveillance of sleeping position was obtained in a random sample (n = 34,799) and surveillance of SIDS was based on all infants born in Norway 1967-91, surviving the perinatal period. Variables studied from the questionnaire were usual sleeping position (placed), breast feeding at 3 months, and maternal smoking in pregnancy, and from the Medical Birth Registry maternal age, birth order, and birth weight. RESULTS: Proportion of infants sleeping prone increased from 1970 (7.4%) to 1989 (49.1%) and dropped in 1990 (26.8%) and 1991 (28.3%). Occurrence of SIDS increased from 1970 (1.1/1000) to 1989 (2.0) before dropping in 1990 and 1991 (1.1). IMPLICATION AND RELEVANCE OF RESULTS: A cause effect relationship between prone sleeping and SIDS as suggested in previous studies is supported by the present; and so far only, national study of infants' sleeping position.