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Biomedical subjects

B Källén

Publications and source records attributed to B Källén.

At least 19 recordsLinked to original sources
PubMed2004

Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study.

AIM: Antiepileptic drugs (AEDs) are known teratogens. Some specificity between different AEDs has been noted in the literature. The aim was to compare the teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy. METHODS: Infants exposed to AEDs (n = 1398) in early pregnancy were identified from the Swedish Medical Birth Registry. The number of infants with congenital malformations and exposed to AED was compared with the expected number estimated from all infants born (n = 582656). RESULTS: 90% (1256) of the AED exposed children were exposed to AEDs in monotherapy, 56% were exposed to CBZ and 21% to VPA. The odds ratio (OR) for having a malformation in the AED exposed group was 1.86 [95% confidence interval (95% CI) 1.42-2.44]. Exposure to VPA in monotherapy compared with CBZ in monotherapy gave OR = 2.51 (95% CI 1.43-4.68) for a neonatal diagnosis of malformations. However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups. CONCLUSION: There was a small increase in the risk of having a major malformation after exposure to AEDs in monotherapy. Exposure to VPA seems to carry a higher risk than exposure to CBZ.

Abnormalities, Multiple↗
PubMed2003

Hospitalization in Sweden of children born to immigrants.

AIM: To study whether excess hospitalization occurs among certain groups of children born in Sweden to immigrant parents. METHODS: The study was based on linkage of the Swedish Medical Birth Register 1987-1997 and the Swedish Hospital Discharge Register 1987-1998. RESULTS: Among children whose parents were of Swedish nationality excess hospitalization was found for children of young mothers, parity 3 or more, and if the mother smoked in early pregnancy. These factors were controlled for in the further analysis. Ten years after birth, a large percentage of children born to parents with foreign nationality could not be followed owing to death or emigration (19.9% vs 1.77% of children with Swedish parents). An excess hospitalization of immigrant children up to the age of about 5 y was seen but after that, if anything, these children were hospitalized less. For the whole group of children born to parents of non-Swedish nationality there was no difference in hospitalization rate after stratification for risk factors and age. When analysis was performed for specific nationalities significantly reduced rates were found for several western European countries while significantly increased rates were seen for the Middle East, north Africa and especially sub-Saharan Africa (odds ratio 1.57, 95% confidence interval 1.49-1.64). CONCLUSION: A moderately increased rate of child hospitalization was only observed for some selected immigrant groups.

Age Factors↗
PubMed2002

Childhood malignancy and maternal diabetes or other auto-immune disease during pregnancy.

Among 4380 children born in 1987-1997 of women with a diagnosis of diabetes and alive at the age of one, 10 were registered in the Swedish Cancer Registry before the end of 1998. The odds ratio for having a childhood cancer after maternal diabetes, stratified for year of birth, maternal age, parity, multiple birth, and 500 g birth weight class was 2.25 (95%CI 1.22-4.15). Among 5842 children born during the period 1973-1997 whose mothers had other auto-immune diseases (SLE, rheumatoid arthritis, Crohn, ulcerous colitis, multiple sclerosis or thyroiditis), the number of observed childhood cancers (9) was close to that expected (8.5). Maternal diabetes but not other auto-immune diseases may be a risk factor for childhood cancer.

Autoimmune Diseases↗
PubMed2002

Neonatal outcome in pregnancies from ovarian stimulation.

OBJECTIVE: To study the neonatal outcome in pregnancies after ovarian stimulation, not including in vitro fertilization. The outcomes studied were multiple birth, preterm birth, and low birth weight among singletons, congenital malformations, and infant death. METHODS: We identified 4029 women who delivered between 1995-1999 after ovarian stimulation alone and compared them with 438,582 women who neither had ovarian stimulation nor in vitro fertilization. We controlled for the confounding effect of year of birth, maternal age, parity, and length of subfertility before the pregnancy. RESULTS: The twinning rate was 5.9% in the study group and 1.2% in the control group. The triplet rate was 0.5% in the study group and 0.02% in the control group. A nearly doubling of the rate of monozygotic twinning was indicated in the study group compared with the control group. There was an excess of singleton preterm births and low birth weight infants in the study group, but this was mainly explainable by confounding of maternal age, parity, and subfertility. The rates of congenital malformations and perinatal deaths were increased, also mainly explainable by maternal characteristics. No increase in specific types of congenital malformations was seen. CONCLUSION: As the deviations in neonatal outcome after ovarian stimulation alone were reduced or disappeared when the confounding of maternal age, parity, and subfertility was taken into consideration, there is probably little direct effect of the stimulation procedure as such.

Adult↗
PubMed2002

Geographic variations in possible risk factors for severe cardiac malformations.

UNLABELLED: The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01). CONCLUSION: The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.

Adolescent↗
PubMed2002

Coeliac disease is associated with intrauterine growth and neonatal infections.

UNLABELLED: To investigate whether factors in the fetal or neonatal period influence the risk of later development of coeliac disease we conducted a population-based register study. The Swedish Medical Birth Register was linked with the Hospital Discharge Register and identified 3392 singleton infants born in the period 1987-97 who developed coeliac disease. Perinatal data for these children were compared with all children born in these years. Exposure variables: Maternal age, parity and smoking habits in early pregnancy, preeclampsia, pregnancy duration and birthweight, birthweight by gestational week, Apgar score, neonatal icterus, neonatal infections, maternal-fetal blood group incompatibility, exchange transfusion, phototherapy. Odds ratios and test-based confidence intervals were calculated. Analyses were made with stratification for year of birth and other risk factors. The risk of developing coeliac disease decreased with maternal age and was lower in first-born than in second-born children. Maternal smoking in early pregnancy was a weak risk factor, as was low birthweight. The most evident risk factors were being exposed to neonatal infections (OR = 1.52, confidence limits 1.19: 1.95) and being small for gestational age (OR = 1.45, confidence limits 1.20; 1.75). These risk factors were independent of each other. CONCLUSIONS: We have demonstrated that the intrauterine environment, mainly as mirrored by a low birthweight for gestational age and, independently, neonatal infection diagnosis, is associated with the risk of developing coeliac disease, supporting the idea of a multifactorial aetiology of the disease.

Bacterial Infections↗
PubMed2002

Use of antihistamine drugs in early pregnancy and delivery outcome.

OBJECTIVE: To study the impact of antihistamine use in early pregnancy on delivery outcome. METHODS: Using prospectively collected information on drug use in early pregnancy, delivery outcome was studied among 17 266 women with 17 776 deliveries and 18 197 infants. The analysis was performed according to the main reason for antihistamine use: nausea and vomiting in pregnancy and allergy. RESULTS: In the nausea and vomiting in pregnancy group, we found a significant increase in twin births and a significant reduction in preterm births, low birth weight and being small-for-gestational age among singletons. The perinatal death rate was reduced and the rate of congenital malformations was normal. A reduction was seen in the occurrence of congenital cardiovascular defects after the use of antihistamines. The odds ratio for specified cardiac defects, with the exception of ventricular and atrium septal defects, after the use of antihistamines for nausea and vomiting in pregnancy (0.54) was significantly lower than that for non-cardiovascular congenital malformations (0.95). No statistically significant effects on delivery outcome were seen after the use of antihistamine drugs for allergy. However, there was a non-significant tendency for a reduced risk for cardiovascular defects (odds ratio 0.71). CONCLUSIONS: The beneficial effects on delivery outcome observed are most probably related to the underlying nausea and vomiting in pregnancy. There is no clear teratogenic effect of the antihistamines studied.

Adult↗
PubMed2002

Hospital care utilization of infants born after IVF.

BACKGROUND: Infants born after IVF are often twins, and singleton IVF babies have an increased risk for preterm birth. Both conditions are likely to increase morbidity. We examined the frequency and duration of hospitalization required by babies born after IVF, and compared this information with all infants born in Sweden during the same time period. METHODS: We used a nationwide registration of IVF pregnancies from 1984 to 1997 and a nationwide register of all in-patient care up to the end of 1998. We identified 9056 live born infants after IVF treatment and compared them with 1 417 166 non-IVF live born infants. RESULTS: The highest odds ratio (OR approximately 3) was seen for neonatal hospitalization, but an increased OR (1.2-1.3) was noted for children up to 6 years of age. The OR for being hospitalized after IVF was 1.8, but when the analysis was restricted to term infants it was 1.3 and this excess was then explainable by maternal subfertility. Statistically significant increased ORs were seen for hospitalization for cerebral palsy (1.7), epilepsy (1.5), congenital malformation (1.8) or tumour (1.6), but also for asthma (1.4) or any infection (1.4). When information from the Swedish Cancer Registry was used, no excess risk for childhood cancer was found. The average number of days spent in hospital by IVF and non-IVF children was 9.5 and 3.6 respectively. CONCLUSIONS: The increased hospitalization of IVF children is, to a large extent, due to the increased incidence of multiple births. Therefore, the increased costs associated with this may be reduced by the use of single embryo transfers, with the savings in health care costs being offset against the increased number of embryo transfer cycles required to maintain the pregnancy rate.

Birth Rate↗
PubMed2001

VATER non-random association of congenital malformations: study based on data from four malformation registers.

This study was undertaken to find a strict, unbiased epidemiological delineation of the VATER non-random association of congenital malformations and, based on registry information, to identify a group of probable VATER association infants suitable for etiological analyses. Information on 5,260 infants with multiple malformations was collected from four large registers of congenital malformations. Data were analyzed using a statistical method in which various putative confounders were controlled for. Our results indicate the existence of a distinct group of malformations corresponding to the VATER association: esophageal atresia, anal atresia, upper preaxial limb reduction defects, and costo-vertebral malformations. A subdivision into an upper and a lower group of VATER association was indicated, with heart malformations associated with the upper group and kidney malformations associated with the lower group. Restricting the inclusion criteria for VATER association to the above mentioned core malformations, few infants seem to belong to the VATER association, thus limiting the possibilities of carrying out etiological analyses. A relatively large number of infants may belong to a family of related conditions among which VATER association is a subgroup. In the search for risk factors, a strict definition of the VATER association is needed in order to not dilute the study material with irrelevant cases. The present study provides such strict inclusion criteria.

Abnormalities, Multiple↗
PubMed2001

Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes.

BACKGROUND: Diabetes type 1 is associated with an increased risk for infant congenital malformations. It is debated whether this is true also at gestational diabetes. AIMS: To study occurrence of congenital malformations in infants whose mothers had preexisting or gestational diabetes. STUDY DESIGN: A register study covering over 1.2 million Swedish births in 1987-1997 based on the Swedish health registries. SUBJECTS: We identified from the Medical Birth Registry 3864 infants born of women with preexisting diabetes and 8688 infants born of women with gestational diabetes. OUTCOMES MEASURES: Congenital malformations identified in the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry. The rates of congenital malformations among these infants was compared with the population rates. RESULTS: At preexisting diabetes, the total malformation rate was 9.5% while the rate at gestational diabetes was similar to the population rate, 5.7%. At preexisting diabetes, certain conditions were more common than expected: orofacial clefts, cardiovascular defects, oesophageal/intestinal atresia, hypospadias, limb reduction defects, spine malformations, and polydactyly. For some of these conditions, an excess was found also for infants whose mothers had gestational diabetes. Infants with multiple malformations were in excess at preexisting diabetes but not at gestational diabetes but the specific type of malformations involved were similar in the two diabetes groups. CONCLUSIONS: It is suggested that in the group of gestational diabetes exists a subgroup with an increased risk for a diabetes embryopathy, perhaps due to preexisting but undetected diabetes type 2.

Cleft Lip↗
PubMed2001

Maternal risk factors for cause-specific stillbirth and neonatal death.

BACKGROUND: To study specific effects of four maternal risk factors: age, parity, educational level, smoking, for specific causes of stillbirth and neonatal death according to a previously described hierarchic classification. METHODS: The study is based on 9,785 stillbirths or neonatal deaths among infants born in Sweden, 1983-1995 (n=1,412,754) and identified with various Swedish health registers. Statistical analysis is performed using Mantel-Haenszel analysis. RESULTS: Some risk factors, known from the literature, were confirmed and could be quantified. In addition, high parity was shown to increase the risk for death associated with multiple births (OR=2.49, 95% CI 2.07-3.01) and low educational level seems to be protective for such death (OR=0.75, 95% CI 0.60-0.93). If the infant is SGA, the risk for death is higher at high than at low parity (1.70, 95% CI 1.19-2.43, and 1.0, 95% CI 1.06-1.15, respectively). Maternal smoking seems to aggravate the placental abruption because the death risk in the presence of abruption increases when the mother smoked (OR = 1.74, 95% CI 45-2.08). CONCLUSIONS: The study shows that the groups of the classification system used (NICE) differ in their association with known risk factors for stillbirth and neonatal deaths and an analysis based on specific causes of death can therefore unravel risk factors hidden when total mortality is used. The computerized method of classification and the cause-of-death classification developed by us is clearly useful for such analyses which requires large materials.

Adult↗
PubMed2001

Delivery outcome in women who used drugs for migraine during pregnancy with special reference to sumatriptan.

OBJECTIVE: To evaluate delivery outcome in women who used drugs for migraine during pregnancy with special reference to sumatriptan. BACKGROUND: The safety of the use of drugs for migraine during pregnancy is not established. DESIGN AND METHODS: Using the Swedish Medical Birth Registry which contains information on drug use reported by women at the first antenatal visit, 912 infants (born in 905 deliveries) whose mothers had used drugs for migraine were identified, the majority of whom (n = 658) had used sumatriptan. RESULTS: These women differed from the general population of women who had delivered by being older and more often of first parity, but they had similar smoking habits. Slightly more often, the infants were preterm, and they had a birth weight less than 2500 g; neither of these effects were statistically significant. There seemed to be no difference between infants exposed to sumatriptan and those exposed to other drugs used for migraine. No increase in the rate of congenital malformations was seen. CONCLUSIONS: The data indicate that use of sumatriptan in early pregnancy does not result in a large increase in teratogenic risk, but do not rule out the possibility of a moderate increase in risk for a specific birth defect.

Adult↗
PubMed2001

Cause-specific stillbirth and neonatal death in Sweden: a catchment area-based analysis.

UNLABELLED: A register-based study of the impact of obstetric and neonatal care on stillbirth and neonatal death rate was performed on all births in Sweden in 1983-1995. Each birth was assigned to a primary delivery hospital where the mother with a term singleton pregnancy was most likely to have been delivered (not possible for 25% of the deliveries), and the catchment areas of each hospital were classified according to the level of care of that hospital. Only small differences in total mortality existed between the different levels of care of the primary hospital: areas served by primary hospitals with obstetric service and resources for neonatal intensive care including continuous positive airway pressure but without facilities for ventilator treatment for prolonged periods showed a 7% excess risk of stillbirth or neonatal death. CONCLUSION: In areas with the lowest level of care of the primary delivery hospitals (with no or only basic neonatal care) the total mortality was not increased, indicating that the referral system works well. When the analysis was repeated for specific causes of death, more marked differences were noted, especially for death due to obstetric complications where the death risk increased with decreasing level of care of the primary delivery hospital. Even though no marked differences in total mortality were seen, a further reduction can be obtained by increasing referral for some specific conditions.

Cause of Death↗
PubMed2001

Regional differences in stillbirth and neonatal death rate in Sweden with a cause-of-death specific analysis.

UNLABELLED: Regional differences in stillbirth and neonatal death rates in Sweden were studied and a cause-of-death analysis was done in the 4 counties (among 24) with an increased mortality. The study is based on a computerized evaluation of infant cause of death, using a slightly modified Wigglesworth classification and a hierarchical classification (NICE: Neonatal and Intrauterine death Classification according to Etiology). Differences between the identified counties with respect to specific causes of death were demonstrated. CONCLUSION: There are differences between Swedish counties with respect to the risk for stillbirth or neonatal death. The NICE cause-of-death classification can be used for the routine surveillance of stillbirths and neonatal deaths in a population and can help in pinpointing weak elements in antenatal, delivery and neonatal care.

Cause of Death↗
PubMed2001

Congenital malformations in infants born after IVF: a population-based study.

The presence of congenital malformations in infants born after IVF was studied from a register consisting of practically all infants born in Sweden after IVF, 1982--1997 (n = 9111). A further 64 infants were studied using only medical records. It is a nation-wide study and has a population-based control group (n = 1,690,577) and relevant potential confounders have been taken into account. There was an excess of congenital malformations registered in the Medical Birth Registry (n = 516, odds ratio = 1.47) but this excess disappeared when confounders were taken into consideration: year of birth, maternal age, parity, and period of unwanted childlessness (odds ratio = 0.89). For some specific conditions, an approximately 3-fold excess risk was seen: neural tube defects, alimentary atresia, omphalocele, and hypospadias (after intracytoplasmatic sperm injection). No excess risk for hypospadias was seen after standard IVF. Various explanations for these findings are discussed. It is postulated that the excess risk for alimentary atresia, like the excess risk for monozygotic twinning after IVF, is a direct consequence of the IVF procedure. The excess risk for hypospadias after ICSI may be related to paternal subfertility with a genetic background. The absolute risk for a congenital malformation in association with IVF is small.

Congenital Abnormalities↗
PubMed2001

Use of multivitamins and folic acid in early pregnancy and multiple births in Sweden.

Folic acid is recommended to reduce the risk of neural tube defects and other congenital malformations. Data from the Swedish Medical Birth Registry were used to study frequency of twinning in women who in early pregnancy reported the use of folic acid. Women (n = 2,569) who in early pregnancy reported the use of folic acid had an increased rate of twin deliveries after consideration of maternal age and of length of involuntary childlessness, both variables being significant confounders. The effect of folic acid was seen also in women who did not report involuntary childlessness. A similar but not statistically significant trend was seen after use of multivitamins without simultaneous use of folic acid tablets (n = 1,979). The increased risk seems to be limited to dizygotic twinning (relative risk = 2.13, 95% CI 1.64-2.74). If this association is causal, wide-spread supplementation with folic acid may represent a hazard larger than the postulated beneficial effect on neural tube defects, at least in low-risk areas.

Adult↗
PubMed2000

OEIS complex--a population study.

Using a novel method for the analysis of infants with multiple malformations, we investigated the cluster of associated malformations called the OEIS (omphalocele, bladder exstrophy, imperforate anus, spine defect) complex among 5,260 infants with multiple malformations identified in four large registers of congenital malformations, corresponding to 5.84 million births. The existence of the OEIS complex was clearly demonstrated and malformations entering it could be defined. Other than the four classical malformations, omphalocele, bladder exstrophy, imperforate anus, and spine malformation, a strong association with spina bifida and intersex was stressed. Spine malformations occurred not only in the lumbosacral level but also more cranially, and an association also with upper spina bifida could be demonstrated. No specific association with any other malformation, including cardiac defects, was apparent. The OEIS complex is an unusually clearly defined entity among the various nonrandom associations which have been described.

Abnormalities, Multiple↗