Time-space clustering of date at birth in childhood-onset diabetes.

OBJECTIVE: To investigate whether there was a temporal and geographical clustering of time of birth for infants with childhood-onset diabetes. RESEARCH DESIGN AND METHODS: The nationwide Swedish Childhood Diabetes Registry, which ascertains 99% of children with recent-onset diabetes (0-14 years), was linked with the Swedish Medical Birth Registry. Clustering of 3,725 patients as to place and time of birth was studied compared with the general population. For each municipality (and in the three large cities of Sweden for each parish), the observed number of patients was compared with the expected number calculated from the average total rate and the number of births in that municipality. Clustering in time of birth within municipality was analyzed using a modification of a set technique by Chen (14). RESULTS: There was no consistent variability in diabetes risk by calendar birth month, but for specific years, the risk varied during the year. When geographic localization for place of birth was studied on a municipality level, four municipalities showed a statistically significant case excess while one would have been expected by chance. When we looked for clusters in both time and space for date of birth, clearly more clusters than expected were identified (P < 0.01). Of the total of 198 primary clusters, 42 included three or more patients being born in the same municipality within an unlikely short period always < 2 years. CONCLUSIONS: This is the first study indicating a clustering according to place and time of birth for later risk to develop type I diabetes. Such a phenomenon would agree with the hypothesis that infections in early life, including fetal infections, can increase the risk for diabetes.

Diabetes insipidus and use of desmopressin (Minirin) during pregnancy.

With the use of two central health registries in Sweden, the Hospital Discharge Registry and the Medical Birth Registry, we identified 100 infants born of women who had been hospitalized for diabetes insipidus. By checking the medical records of these women, 29 infants were identified whose mothers had diabetes insipidus prior to the pregnancy and had been treated through the pregnancy with desmopressin. These infants had a normal birth weight and gestational length; there was only one congenital malformation identified (a ventricular septum defect with a patent ductus arteriosus and simian lines). This child died at the age of 14 years in a hypophyseal disease. This is the largest material published on desmopressin during pregnancy. The results suggest that maternal diabetes insipidus and treatment with desmopressin during the whole pregnancy does not constitute a major risk for the infant.

A computer-based method for cause of death classification in stillbirths and neonatal deaths.

BACKGROUND: In large-scale epidemiological studies of stillbirths and neonatal deaths a method is needed to replace detailed medical record audits in order to determine the cause of death. METHODS: A computer-based method is presented for determination of the cause of death in stillbirths and in neonatal deaths. It utilizes information in the Swedish medical registries. The study comprises 6044 dead infants born in Sweden from 1983-1990. For each infant the program determines 31 basic characteristics which are important in deciding the cause of death. Based on these characteristics a modified Wigglesworth's classification is used to find the cause of death. The validity of the method was checked by comparing the computer generated information with information obtained by scrutinizing medical records for a 10% representative sample (603 infants). RESULTS: Specificity and sensitivity for each basic characteristic varied, but for the modified Wigglesworth cause of death classification the concordance was 88%. The weakest data refer to intrauterine deaths, where pertinent information was often missing in the medical registries. CONCLUSION: The method can be used for large-scale epidemiological studies.

NICE, a new cause of death classification for stillbirths and neonatal deaths. Neonatal and Intrauterine Death Classification according to Etiology.

BACKGROUND: Stillbirths and neonatal deaths are often the result of a complicated chain of events. For epidemiological purposes a classification into single cause of death groups is essential. For large-scale studies, a method is needed which enables such grouping based on available register data. METHODS: A cause of death classification system called NICE is presented. It is hierarchical and is aetiologically orientated. A computerized method is adapted which makes use of data in four central Swedish registries. A validation of the computer method has been made from the medical records on a 10% sample of all stillbirths and neonatally dead infants in Sweden from 1983 to 1990. RESULTS: The specificity of the computer method is high, sensitivity is less satisfactory for some subgroups. A time trend analysis illustrates the usefulness of the classification system and shows a decline with time for two groups: placental abruption and obstetric complications. CONCLUSIONS: The NICE classification system fulfils the criteria of an aetiologically orientated classification system which can be used in a computerized environment.

A modified method for the epidemiological analysis of registry data on infants with multiple malformations.

BACKGROUND: Infants with multiple malformations are important in birth defect epidemiology and malformation monitoring because human teratogens have often caused complex malformations. Various methods for the analysis of multimalformed infants have been tried. METHOD: By using data from four large registries of congenital malformations, 5256 infants were identified with two or more among 73 selected malformations. Pairwise associations between malformations were detected by multiple logistic regression analyses, and putative confounders (programme, maternal age, autopsy, etc.) were controlled for. For each significant pairwise association, further analyses were performed in order to find associations with a possible third malformation. RESULTS: The importance of controlling for several confounders was demonstrated. Several well-known associations were found, which supports the technique used. The interpretation of three-way associations was discussed. Results from the present study were compared with those obtained using some other methods. CONCLUSIONS: Different confounders can cause biased associations. The method presented in the paper takes this into consideration and is therefore more likely than previously used techniques to give unbiased information on the clustering of different malformations among multimalformed infants.

Drinking water chlorination and delivery outcome-a registry-based study in Sweden.

By using the Swedish Medical Birth Registry and official data on drinking water chlorination, three cohorts were identified and compared: women who lived in areas where drinking water was disinfected with chlorine dioxide, women who lived in areas that used sodium hypochlorite disinfection, and women who lived in areas where there was no chlorination of the drinking water. There was a statistically significant increase in short gestational duration and low birth weight and especially in short body length and very small head circumference in areas using sodium hypochlorite, but no significant effects on these variables were found in areas using chlorine dioxide. No effects on congenital malformations, childhood cancer, infant mortality, low Apgar score, neonatal jaundice, or neonatal hypothyroidism were associated with either of the two drinking water chlorination methods. Because the exposure information in this study was based on the chlorination method and not the amount of byproducts in the water, the general lack of significant effects could be due to a low concentration of such byproducts.

Nonsteroidal anti-inflammatory drugs in early pregnancy.

A study was performed of congenital malformations in infants whose mothers used nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy. Data were obtained from an ongoing prospective recording of drug use during the first trimester. During the period July 1, 1995 through December 31, 1998, 2557 infants were born to women who reported the use of NSAIDs in early pregnancy. The OR (after consideration of maternal age, parity, and smoking habits) for any congenital malformation was 1.04 (95%CI 0.84-1.29), but the OR for cardiac defects reported to the Medical Birth Registry was 1.86 (1.32-2.62) based on 36 instances, and for orofacial clefts 2.61 (1.01-6.78) based on only six instances. By using other information sources, another four infants with cardiac defects were identified. There was no drug specificity for cardiac defects but among six mothers of infants with orofacial clefts, five had used naproxen.

The epidemiology of preaxial limb malformations.

The epidemiology of preaxial limb malformations was studied in an effort to find similarities and differences between different types that could help to define suitable groups of malformations for etiologic studies. Material from three large congenital malformation registers was used, with a total of 1646 infants with such malformations among over 5 million births. We compared different types of preaxial malformations with respect to bilaterality, maternal age and parity, racial differences, sex distribution, twinning, and associated malformations. From many epidemiologic aspects, different types of preaxial malformations showed similarities, but there were some distinct differences between upper and lower limb anomalies. We conclude that in searches for etiologic factors, it may be useful to group all preaxial malformations together but to differentiate between upper and lower limb defects.

Use of omeprazole during pregnancy--no hazard demonstrated in 955 infants exposed during pregnancy.

OBJECTIVES: To evaluate the magnitude of possible fetal risks involved in maternal use of omeprazole during pregnancy. STUDY DESIGN: Infants whose mothers used omeprazole during pregnancy were identified from the Swedish Medical Birth Registry. A total of 955 exposed infants born in 1995-1999 were identified: 863 of which were exposed in early pregnancy and 131 later in pregnancy and 39 who had been exposed both in early and late pregnancy. Delivery outcome was studied: presence of congenital malformations, perinatal survival, low birth weight, low Apgar score and hospitalization up to the end of 1997. RESULTS: No clear-cut indication of ill effects were seen. Five infants were stillborn and the rate of congenital heart defects was slightly increased, but both effects may be random. CONCLUSIONS: The present dataset and previously published data give no reason for concern after exposure for omeprazole during pregnancy.

Hormone therapy during pregnancy and isolated hypospadias: an international case-control study.

Mothers of boys with hypospadias and control mothers were interviewed in eight malformation monitoring programs around the world. Hormone therapy was used quite frequently in five but rarely in three of the programs. The odds ratio for hypospadias after hormone therapy during pregnancy was 2.8 (95% confidence limits 1.2, 6.9) but there was no correlation between the timing of hormone therapy and the location of the urethral orifice, nor between the severity of the malformation and hormone therapy. Programs with the highest hormone exposure rate showed the lowest odds ratio for pregnancy bleeding, the most common reason for hormone therapy. These latter findings cast doubts on the causal association between hormone therapy and isolated hypospadias. Alternative explanations are recall or interviewer bias or unidentified confounders.

Lack of precision in neonatal death classifications based on the underlying causes of death stated on death certificates.

Large-scale analyses of causes of neonatal deaths are usually based on death-certificate information. A new computer-based method has been introduced to define the cause of stillbirths and neonatal deaths in large amounts of material and to classify them according to two different models [Wigglesworth and Neonatal and Intrauterine death Classification according to (a)Etiology (NICE)]. The method is based on a combination of detailed information from health care registries and the death-certificate information. The present study aimed to compare these two classification models with a previously published method based solely on death certificate information [International Collaborative Effort (ICE)]. The study population comprised 2378 neonatal deaths in Sweden between 1987 and 1992. Cross-tabulation was made between the ICE classification and the other two classification models. In addition, case examples are presented in detail, exemplifying how classification errors arose. The ICE classification gives a rather low precision, notably for two important causes of death: asphyxia and immaturity. Among 328 infants dying from asphyxia according to computerized Wigglesworth classification, ICE classified 59% as asphyxia and 22% were labelled immaturity. When ICE classified the deaths as due to asphyxia, this was verified in only 50%. Among 792 infants dying from immaturity according to computerized Wigglesworth classification, 64% were classified as such by ICE. The findings cast doubts on the results of studies based exclusively on death-certificate information. Whenever possible in the analysis of neonatal deaths, death-certificate information should be supplemented with more detailed data. The computer-based method introduced here makes such analyses possible for large databases.