To evaluate C to T substitution at nucleotide 677 of N(5), N(10)-methylenetetrahydrofolate reductase gene in women with prior preeclamptic or normotensive pregnancies.
Methylenetetrahydrofolate reductase genotypes were determined in 113 Finnish women with preeclamptic first pregnancies and 103 controls with one or more normotensive pregnancies, using polymerase chain reaction and restriction enzyme analysis. Preeclampsia was defined as severe in 100 women who fulfilled one or more of the subsequent criteria: systolic blood pressure (BP) at least 160 mmHg, diastolic BP at least 110 mmHg, or proteinuria at least 2 g per 24-hour urine collection.
There were no significant differences in prevalences of the methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) between groups (57%, 40%, and 3% in the preeclamptic group and 54%, 39%, and 7%, respectively, in controls). The frequency of the T677 allele was 0.23 in the preeclamptic group and 0.26 in the control group (difference 0.03; 95% confidence interval -0.08, 0.14; P =.51). Our sample had 60% power to detect a difference of the allele frequencies similar to that (0.12) reported previously. The result was similar when analysis was restricted to patients with severe preeclampsia (T677 allele frequency 0.22).
A carrier status for the T677 allele of the methylenetetrahydrofolate reductase gene does not predispose to preeclampsia, at least in the Finnish population.
Congenital heart block without intracardiac anatomic malformations is a potentially lethal disease affecting children and newborns. The mother often has an autoimmune disorder with autoantibodies against SS-A/Ro and/or SS-B/La antigens. However, only a minority of the children of these mothers develop complete heart block. It is believed that the maternal antibodies are pathogenic, but other immunological mechanisms such as cell-mediated injury cannot be excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and thus some children may be more susceptible to heart block than others, depending on their HLA genetics. The purpose of this study was to evaluate whether there are HLA differences between children with heart block and their healthy siblings. Six affected children in four families and their siblings were studied. MHC class I were typed serologically and class II and some non-HLA alleles were typed by DNA techniques. DQB1*03/04 were seen more often in the affected children than in the siblings. Some other differences were also seen in the other antigens of the MHC area.
Since there are few data on the use of various birth control methods in systemic lupus erythematosus (SLE), we performed a cross-sectional study of the actual contraceptive practices in a group of 85 Finnish female SLE patients of reproductive age. We also recorded side-effects experienced during the use of oral contraceptives (OCs) and intrauterine devices (IUDs). The use of contraception was lower in SLE patients than in healthy women of the same age (59 vs 77%, P
Preterm birth is a major cause of neonatal morbidity and mortality, occurring in 5-13% of deliveries in developed countries. Genetic thrombophilia can theoretically contribute to the induction of preterm delivery, but the role of thrombophilia as risk factor is unclear.
To assess factor V Leiden, FII G20210A and other selected inherited and acquired variables as risk factors for preterm birth.
We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Clinical data were obtained from medical records and standardized questionnaires. We studied 324 cases with preterm delivery at or after 22 and before 37 completed weeks of gestation, and 752 controls.
FV Leiden was associated with a 2.4-fold risk (95% confidence interval [CI] 1.3-4.6) of preterm birth in all pregnancies, and a 2.6-fold risk (95% CI 1.4-5.1) in singleton pregnancies. FV Leiden was especially associated with late preterm birth at or after 32 weeks of pregnancy, with an odds ratio (OR) of 2.9 (95% CI 1.5-5.6) in all pregnancies and an OR of 3.1 (95% CI 1.6-6.2) in singleton pregnancies. FII G20210A was not associated with preterm birth. Twin pregnancy (OR 12.0, 95% CI 6.0-24.1) and a history of venous thrombosis (OR 3.8, 95% CI 1.4-9.8) were associated with increased risk. High educational level and modest overweight (body mass index 25-29.9 kg m(-2) ) had protective effects.
Maternal carriage of FV Leiden was associated with increased risk of late but not early preterm birth. FII G20120A was not associated with preterm birth.
To assess the number of live births in a population-based, retrospective cohort of women and men with childhood-onset type 1 diabetes, and matched controls.
The reproductive histories of people in a Finnish cohort of 2,307 women and 2,819 men with type 1 diabetes and two matched controls (for each case) were obtained from National Population Register data. All persons with diabetes were diagnosed with the disease in 1965-1979 at the age of 17 or under. A proportional hazards model was used to model the association between the rate of live births as a function of the age of an individual and the observed covariates (sex and age at onset of diabetes).
Both women and men with diabetes had a smaller number of live births than the controls; the HR of having a first child for diabetic women compared with controls was 0.66 (95% CI 0.62, 0.71) and for men was 0.77 (95% CI 0.72, 0.83). In women, a birth cohort effect was detected; in more recent birth cohorts, the difference between diabetic women and controls as regards having children was significantly smaller than in earlier cohorts. Later age at onset of diabetes was associated with a higher rate of having a first child among men (p = 0.04) and having a second live birth among women (p = 0.002).
Type 1 diabetes affects the number of live births in both women and men. The age at onset of diabetes is associated with the pattern of reproduction in both diabetic women and men.
Fetal outcome in systemic lupus erythematosus (SLE) was retrospectively analysed in 242 pregnancies in 112 unselected patients, and the outcome was compared with that of 417 pregnancies in 192 control women matched for age, parity and socio-economic status. Relative risk for fetal loss after the diagnosis of SLE was 2.5 (95% confidence interval (CI), 1.4-4.5), for prematurity 5.8 (3.2-10.5) and for intra-uterine growth retardation (IUGR) 8.6 (3.0-24.3). Fetal outcome of pregnancy in patients with pre-existing stable lupus nephritis was no worse than in other SLE pregnancies. Relations of three lupus anticoagulant (LA) assays and tree anticardiolipin (aCL) enzyme-linked immunosorbent assays to fetal outcome were studied. Patients positive by any LA assay had a previous fetal loss more often than patients negative by all LA assays (odds ratio 3.4; 95% CI, 1.3-9.0; P = 0.01). Of the 41 patients whose antiphospholipid antibody (aPL) tests were all negative, five (12%) had a history of fetal loss (16% in controls). As a group, aCL was more sensitive for fetal loss than LA (64% vs 50%), but LA was more specific (77% vs 52%). Combinations of one aCL assay with one LA assay had a 41-73% sensitivity and a 64-73% specificity for a history of fetal loss. aPL did not correlate to prematurity or fetal growth retardation. In conclusion, fetal loss in SLE is 2.5 times more prevalent than in the normal population. The presence of LA indicates a high risk for fetal loss, and the absence of aPL is an indication of a favorable pregnancy outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
To study the occurrence and significance of pregnancy-associated hypertension and pre-eclampsia in systemic lupus erythematosus (SLE), we studied retrospectively 34 pregnancies in 27 SLE patients in 1981-87. Eleven pregnancies (32%) were hypertensive (group A). The remaining 18 patients during their 23 pregnancies had a normal blood pressure (group B). Previous nephritis was slightly more common in the hypertensive group (54.5% vs. 26.1%, NS). Preeclampsia was present in seven of the pregnancies (21%) and of whom four were superimposed. Flare-ups of the disease were more common in the non-hypertensive group (30.4%) than in group A (9.1%) (NS). Duration of pregnancy was the same in the two groups. Intra-uterine growth retardation was present in 27.3% of the pregnancies in group A and in 13.0% of group B (NS). Fetal loss occurred only in 2 patients of the non-hypertensive group; one patient had exacerbation of SLE and the other (with two stillbirths) high anticardiolipin antibodies. Our data suggest that pregnancy-associated hypertension and pre-eclampsia do not cause increased fetal loss in pregnancies affected by SLE. There seem to be other factors that are more important, such as antiphospholipid antibodies and flare-ups of the disease.
To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child.
This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sj?gren's syndrome (SS) with healthy children.
High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34).
Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.
This study aims to assess the association between parity and mortality in adults with childhood-onset type 1 diabetes (T1D) and their matched controls.
Individual data (308 617 person-years) on mortality and the reproductive histories of a Finnish cohort of 2307 women and 2819 men with T1D, each with two matched controls, were obtained from the National Population Register. All persons with diabetes had been diagnosed with T1D in 1965-1979 at the age of 17 or under.
All-cause mortality in people without offspring was significantly higher than that in people with children among both people with diabetes and non-diabetic control persons in both sexes (all p-values