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R T Lie

Publications and source records attributed to R T Lie.

At least 19 recordsLinked to original sources
PubMed2025

Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.

OBJECTIVES: Nonsyndromic orofacial clefts (OFCs) involve complex genetic and environmental factors, with over 60 risk loci accounting for only a minority of estimated heritability and residing in non-coding regions with unclear functional relevance. We hypothesize that some genetic variants alter orofacial cleft risk by modifying DNA methylation (DNAm) at regulatory sequences essential for craniofacial development, acting as methylation quantitative trait loci (meQTLs). METHODS: We analyzed 10 well-established OFC-associated SNPs against genome-wide DNAm profiles in 409 cases and 456 controls, identifying 23 potential meQTLs. We validated findings using 358 cleft-discordant sibling pairs analyzed with quantitative MethyLight assays. Cross-referencing with the mQTL Database assessed temporal patterns across human development. Functional annotation used GeneHancer and craniofacial enhancer databases. RESULTS: Nine meQTLs were successfully replicated, including the highly significant rs987525 (8q24) - cg16561172 (MYC) association (P = 9.610E-6). This association mapped to a mesendoderm-active enhancer upstream of MYC, providing mechanistic explanation for the longstanding 8q24 cleft locus. Additional validated associations involved MAFB-PLCG1, NOG-PPM1E, FOXE1-FRZB, and SPRY2-LGR4 interactions. Independent differential methylation analysis revealed significant differences between discordant siblings at three CpG sites. Cross-referencing confirmed concordance with population-level methylation effects, with childhood representing the critical developmental window for most associations. CONCLUSIONS: This systematic meQTL characterization in OFCs demonstrates that genetic variants influence disease risk through epigenetic mechanisms. The 8q24-MYC regulatory pathway evidence provides crucial mechanistic insight into a major OFC risk locus. These findings bridge genetic associations with functional consequences, address missing heritability challenges, and suggest potential biomarkers and therapeutic targets for OFC prevention and treatment.

Journal Article↗
PubMed1997

Birth defects and parental consanguinity in Norway.

The study compares frequencies of birth defects between immigrant groups and the rest of the Norwegian population in Norway and estimates the influence of consanguinity and socioeconomic factors on these frequencies. The authors studied all 1.56 million births in Norway from 1967 to 1993. Of these, 7,494 children had two Pakistani parents, 84,688 had one Norwegian and one immigrant parent, and 25,891 had two immigrant parents from countries other than Pakistan. The risk of birth defects relative to the Norwegian group was 0.98 (95% confidence interval 0.92-1.03) in the group with one foreign and one Norwegian parent, 1.39 (95% confidence interval 1.22-1.60) in the group with two Pakistani parents, and 1.04 (95% confidence interval 0.95-1.14) in the group with two parents from other foreign countries; 0.1% of the Norwegian and 30.1% of the Pakistani children had parents who were first cousins. There was no difference in risk between children of nonconsanguineous Pakistani parents and the other groups. The relative risk of birth defects among children whose parents were first cousins was about 2 in all groups. Among the Pakistani, 28% of all birth defects could be attributed to consanguinity. Low paternal educational level was associated with a slightly increased risk in the Norwegian group, while independent effects of parental educational levels were not found in any other groups.

Confidence Intervals↗
PubMed1997

[Congenital hip dislocation. Ultrasonic screening of newborn infants].

Despite the introduction of clinical screening and early treatment of congenital dislocation of the hip (CDH), the prevalence of subluxated/luxated hips in later infancy is still reported to be as high as 1-3 per 1,000 infants. Using ultrasound, it is possible to evaluate both hip morphology and hip stability. Hip morphology is best evaluated using Graf's coronal section through the deepest part of the acetabulum. Classification of the hips into different categories can then be based on measuring the angle of inclination of the acetabulum (alpha-angle) or femoral had coverage. Hip stability can be assessed by a Barlow-equivalent provocation test during the ultrasound examination. In the Norwegian newborn population approximately 85% of the infants have morphologically normal hips (based on the alpha-angle) while 12% have immature and 3% dysplastic hips. About 80-90% of infants with dysplastic acetabula show only minor changes, and many of the hips may normalize without treatment. Several studies indicate that universal ultrasound screening might reduce the occurrence of late diagnosed congenital dislocation of the hip.

Hip Dislocation, Congenital↗
PubMed1997

Environmental epidemiology at the Medical Birth Registry of Norway; strengths and limitations.

A national registry of all pregnancy-outcomes was started in Norway. in 1967 to facilitate epidemiological surveillance. One aim was to detect increases in birth detect prevalences that was caused by new harmful exposures. Over the years several studies of unexpected time-trends and regional differences have been performed, but specific harmful exposures have so far not been detected. In a study of possible effects of the Chernobyl fallout, the registry enabled a detailed investigation of a possible increase in prevalence of birth detects that occurred specifically in the most exposed areas of Norway. The strength of this approach was the population coverage of the registry, while important limitations were incomplete reporting (outcome misclassification) and crude exposure information (exposure misclassification). While still taking advantage of the population coverage of the medical birth registry, a new generation of studies with more complete case ascertainment and individual exposure information are being prepared. One particularly interesting new option is to use molecular genetic tools to identity susceptible mothers or children. Collection and storage of biological specimens on a large scale is challenging, but in the search for gene-environment interactions, population-based studies are particularly attractive.

Congenital Abnormalities↗
PubMed1997

Prediction of fetal growth based on maternal serum concentrations of human chorionic gonadotropin, human placental lactogen and estriol.

BACKGROUND: The purpose was to determine the usefulness of maternal serum concentrations of human chorionic gonadotropin (hCG), human placental lactogen (hPL) and estriol as predictors of fetal growth. METHOD: From a large cohort serum obtained serially at 17, 25, 33 and 37 weeks of gestation were analyzed for randomly selected pregnancies resulting in small for gestational age (SGA, n = 102) and non-SGA (n = 112) infants. RESULTS: There were no significant correlations between birthweight ratio (ratio of birthweight to mean weight for gestational age) and hCG, but between birthweight ratio on one hand and estriol for all stages of pregnancy (r = 0.19-0.38, p < 0.01 - p < 0.001) and hCL except at 33 weeks (r = 0.11-0.40, p ns-p < 0.001) on the other. There were statistically significant, but small median differences and substantial overlaps between the SGA and non-SGA infants for hCG at 17 and 37 weeks, for hPL at 17, 33 and 37 weeks, and for estriol at all the stages of pregnancy. The sensitivity and positive predictive value of low hormone concentrations (below the 10th percentile) in predicting the birth of an SGA infant were in the range of 6-26% and 17-39%, respectively. The corresponding specificity and prediction of a non-SGA infant from normal levels were 91-93% and 85-88%. CONCLUSIONS: HPL and estriol, but not hCG concentrations, are positively related to the size of the fetus, but the relationships are too weak to be of predictive value in an unselected population.

Adult↗
PubMed1997

Cell division in placentas of appropriate and small-for-gestational-age infants. A flow cytometry study.

BACKGROUND: The purpose of this study was to examine if placentas of small- for-gestational-age (SGA) and non-SGA infants differ with respect to proliferative cell activity. METHOD: Cell cycle distribution was studied in placentas from 181 SGA (birthweight < 10th percentile) and 528 non-SGA births by flow cytometry measurements of relative DNA content. RESULTS: The fraction of cells in various cell cycle phases (G1-, S- and G2-phases) did not differ with gestational age from 30 to 43 weeks in either of the groups. The placentas of the SGA infants had a significantly lower mean (+/-1 SEM) growth fraction than placentas of non-SGA infants (S-phase 5.2 +/- 0.2 vs 5.5 +/- 0.1, p = 0.05, and G2-fraction 5.4 +/- 0.2 vs 6.3 +/- 0.1, p < 0.001), but the overlaps of the distributions were large. Thus sensitivity, specificity and predictive values of low fractions did not differ substantially-from a purely random prediction of SGA. CONCLUSIONS: Cell division in the placenta is maintained until and beyond term. Placentas of SGA infants have on average, lower proliferative activity than placentas of non-SGA infants, but the difference is too small to be of predictive value in identifying intrauterine growth retardation.

Adult↗
PubMed1996

[Maternal diabetes--normalized perinatal mortality, but still high fetal growth].

Studies suggest that maternal diabetes can cause both placental insufficiency and exaggerated foetal growth. Pregnant mothers with diabetes have suffered high risk of losing their child. Data from the Medical Birth Registry of Norway show a decrease in the still birth rate from 16th week of gestation from 115.7 per 1,000 in 1967-75 to 12.8 in 1986-92 in the diabetes groups. The relative risks were 7.8 and 1.4 respectively for the two time periods. The early neonatal mortality rate decreased correspondingly. The proportion of Caesarean sections in mothers with diabetes, and the proportion of children with low birth weight or born prematurely also increased in the diabetes group. However, children in the diabetes group were on average still as big at gestational age in the most recent period as in the first period. Our data suggest that the improved metabolic control of maternal diabetes has reduced the occurrence and degree of placental insufficiency, with inherent decreases in mortality and risk of complications, but without reducing the foetal growth-stimulating effect of maternal diabetes.

Birth Weight↗
PubMed1996

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.

BACKGROUND: Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. METHODS AND RESULTS: Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. CONCLUSIONS: These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Aged↗
PubMed1996

Developmental dysplasia of the hip: prevalence based on ultrasound diagnosis.

The prevalence of sonographically normal, immature and dysplastic hips, the association between hip morphology and gender, and known risk factors for developmental dysplasia of the hip (DDH) were determined for 3613 randomly selected, healthy newborns. Hip morphology was determined according to a modified Graf's method, and stability was evaluated using a Barlow equivalent maneuver. A higher proportion of girls than boys had immature hips [16.9 % vs 9.3 %; relative risk (RR) = 2.0, 95 % confidence interval (CI) = 1.6-2.4], minor dysplasia (4.5 % vs 1.0 %; RR = 4.8, 95 % CI = 2.9-8.1), and major dysplasia (1.2 % vs 0.2 %; RR = 5.5, 95 % CI = 1.9-16.2). An increased risk was associated with having a sibling or parent with DDH (RR = 2.2, 95 % CI = 1.0-4.6 and RR = 3.6, 95 % CI = 1.1-12.5 for girls and boys, respectively), but not with DDH in more distant relatives. Breech delivery represented a significant risk factor only for the girls (RR = 2.2, 95 % CI = 1.1-4.4). There was a strong association between hip morphology and sonographic stability (gamma = 0.98).

Female↗
PubMed1996

Survival after peptic ulcer perforation: a time trend analysis.

The survival of 1098 patients with ulcer perforation in Norway during the period 1952-1990 was compared with expected survival. Cox regression models incorporating population mortality rates, were used to analyse effects of sex, age, year of birth, and year at risk on excess mortality. Survival was lower in patients than in the general population through a follow-up period of 38 years. Relative survival was lower in women as compared to men, due to more delayed treatment. Long-term survival was lower after praepyloric perforations than after the other perforation types. Relative survival was higher in patients treated 1952-1970 than in those treated more recently. However, adjustment for year of birth revealed a decline in short-term mortality with calendar time, which is in accordance with improved management during the study period. Relative mortality, particularly long-term mortality, was higher in younger birth cohorts, suggesting a shift towards more serious etiologies.

Cohort Effect↗
PubMed1996

Developmental dysplasia of the hip. A population-based comparison of ultrasound and clinical findings.

Clinical and ultrasound findings were compared in 3613 newborns examined for developmental dysplasia of the hip (DDH) within 48 hours of delivery. Clinical and sonographic hip stability was described as stable, borderline unstable, dislocatable or dislocated, and the morphology on ultrasound as normal, immature or dysplastic. Persistent clinical or sonographic dislocatability or dislocation, major dysplasia or minor dysplasia combined with an unstable femoral head were indications for early treatment. A total of 123 (3.4%) infants were subjected to early treatment, of which 55 (45%) fulfilled the criteria for treatment on both clinical and ultrasound examinations, 52 (42%) were treated on the basis of ultrasound findings alone, and 16 (13%) on the basis of clinical findings alone. Thirty per cent of the infants with clinically dislocated or dislocatable hips were judged to have stable or just borderline unstable hips on the first clinical examination. Of 486 (13.5%) infants with sonographically immature or minor dysplastic but stable hips, 472 (97%) normalized spontaneously, while treatment was initiated in 14 (3%) of them at 1-3 months of age because of lack of sonographic improvement. Only one infant presented with late DDH during an observation period of 3 years. Accepting sonographic dysplasia as a criterion for early splinting may result in a treatment rate which is almost twice the rate based on clinical criteria, but late dislocation may be virtually eliminated.

Cross-Sectional Studies↗
PubMed1996

Spina bifida and cleft lip among newborns of Norwegian women with epilepsy: changes related to the use of anticonvulsants.

OBJECTIVES: This study examined the connection between the use of anticonvulsants for epilepsy during or before pregnancy and the risk of spina bifida and cleft lip in newborns. METHODS: Among mothers registered from 1967 to 1992 by the Medical Birth Registry of Norway, 7588 who had epilepsy were identified and their newborns' prevalence of spina bifida and cleft lip examined. RESULTS: The odds ratio of spina bifida in children of mothers with epilepsy compared with other children increased from 1.5 in 1967 through 1980 (95% confidence interval [CI] = 0.3, 4.5) to 4.4 in 1981 through 1992 (95% CI = 2.0, 8.5). The odds ratio of cleft lip, however, decreased from 3.0 before 1981 (95% CI = 1.6, 5.1) to 1.1 after 1981 (95% CI = 0.4, 2.3). CONCLUSIONS: This shift toward more serious birth defects is consistent with the different teratogenic effects of newer and older anticonvulsants.

Anticonvulsants↗
PubMed1995

Neurohumoral measurements as indicators of long-term prognosis after acute myocardial infarction.

The objective of this study was to evaluate the prognostic accuracy and usefulness of neurohumoral determination as a risk stratification tool after acute myocardial infarction (AMI) by comparing the long-term prognostic value of subacute neurohumoral measurements with other established indicators of adverse outcome. The study included 145 patients with documented AMI. During a median follow-up of 3.7 years, 30 cardiovascular and 6 noncardiovascular deaths occurred. By univariate analysis, plasma atrial natriuretic factor (ANF) and endothelin levels were strongly related to long-term cardiovascular mortality. In multivariate models, both peptides added prognostic information to that obtained from clinical evaluation, but not to that obtained from left ventricular ejection fraction (LVEF). Estimation of the area under the receiver-operating characteristic curve showed comparable prognostic accuracy for LVEF (0.7788), plasma ANF (0.7795), plasma endothelin (0.7493), and Killip classification (0.8203), meaning that for all these prognostic indicators, a randomly selected patient from the group of patients dying will have a test value larger than that of a randomly selected patient from the group of surviving patients 75% to 82% of the time. The clinical usefulness of neurohumoral determination in routine risk stratification after AMI appears to be limited since no additional prognostic information to that provided by objective evaluation of LV systolic function is obtained. However, in patients for whom objective assessment of LV performance is not readily available, measurement of plasma ANF and endothelin may be helpful in identifying asymptomatic patients at risk for cardiac death.

Aged↗
PubMed1995

Incidence of perforated ulcer in western Norway, 1935-1990: cohort- or period-dependent time trends?

Previous reports have shown that peptic ulcer mortality follows birth cohorts. To the authors' knowledge, temporal variation in ulcer incidence has not been studied. Therefore, they present incidence data for a defined area of western Norway where 1,312 patients born between 1845 and 1975 were treated for ulcer perforation between 1935 and 1990. A rise and subsequent fall in incidence was observed in successive birth cohorts for both sexes, with the highest incidence observed for males born between 1900 and 1919 and females born between 1920 and 1929. Age-period-cohort analyses based on Poisson regression techniques were adapted to provide a statistical tool for testing specific cohort and period effects. Age-cohort models without period effects explained the variations in incidence for both sexes and all ulcer locations, suggesting cohort-dependent etiology. A cohort pattern in prevalence of smoking partly explained the cohort pattern in perforation risks for both sexes. No period effects were seen that could be attributed to the increase in the sale of non-steroidal anti-inflammatory drugs, to the introduction of antibiotics around 1950, or to World War II. Susceptibility to ulcer perforation seems to follow birth cohorts, and major etiologic factors should be sought in prenatal life, in childhood, or in life-style patterns that follow birth cohorts.

Adolescent↗
PubMed1995

Reliability of ultrasound in the early diagnosis of developmental dysplasia of the hip.

The purpose of this study was to determine inter- and intra-observer agreement in assessing hip morphology and stability by ultrasound. Three groups of infants, of 206, 74 and 78 newborns respectively, were examined. Morphology was classified into four categories (normal, immature, minor dysplastic and major dysplastic) according to subjective assessment, objective measurement (of the acetabular inclination angle alpha) or a combination of the two. Inter- and intra-observer agreement was determined for reading of recorded ultrasound scans, and for examination (recording plus reading of the scans). Hip stability was subjectively classified as stable, unstable, dislocatable or dislocated, and inter-observer agreement was determined. There was a high degree of agreement for morphological classification based on repeated readings of recorded scans by the same observer (206 infants, kappa = 0.7 and 0.8 for the two observers, respectively) while the degree of agreement between observers was moderate (kappa = 0.5). The agreement between observers for repeated readings and recordings was moderate when based on a subjective classification (kappa = 0.5). Adding the alpha angle did not improve agreement. There was a moderate inter-observer agreement in determining hip stability (70 infants, kappa = 0.4). The authors concluded that a high degree of inter- and intra-observer agreement in classifying hip morphology may be obtained for the reading of recorded ultrasound scans. Inter- and intra-observer agreement in producing the scans is poorer than for reading. To obtain a high degree of inter-observer agreement in assessing hip morphology and stability in the newborn, substantial training, attention to details in the technique, and evaluation of results are necessary.

Hip Dislocation, Congenital↗
PubMed1995

Cost-effectiveness of alternative screening strategies for developmental dysplasia of the hip.

OBJECTIVE: To compare the cost-effectiveness of adding either a general or a selective ultrasound screening program to the routine clinical examination for developmental dysplasia of the hip (DDH) with use of the data from a large, randomized study of 11,925 newborns. METHODS: Our previous study comparing the clinical outcomes of three strategies for screening infants for DDH suggested (but results were not statistically significant) that general ultrasound screening resulted in fewer children requiring hospitalization and surgery for DDH than did a strategy based on ultrasound screening of the 11.8% of infants considered to be at increased risk of DDH or one with no ultrasound screening. General ultrasound screening led to early splinting of 3.4% of the newborns compared with 2.0% for the selectively screened group and 1.8% for the group not receiving ultrasound screening. Using these data, we decided on sequences and intervals of diagnostic and therapeutic actions considered to be sufficient for each regimen. We applied estimates of the costs of screening, treatment of DDH discovered early and late, and follow-up examinations to arrive at total program costs for each strategy. RESULTS: Total program costs were similar for each of the three screening strategies (costs varied by < 5%). However, treatment of late cases accounted for only 22% of total costs in the group undergoing general screening vs 65% in the two latter groups. The cost estimates were sensitive to several variables. Application of the data to a hypothetical ultrasound program in which all girls and only boys at increased risk for DDH underwent an ultrasound examination showed substantially reduced total program costs. CONCLUSIONS: Application of costs from other centers to our data regarding frequency of clinical outcomes may yield different comparative program costs. If the findings of our clinical study can be generalized to other centers, a strategy of screening all girls and boys with risk factors for DDH may be the most cost-effective approach.

Cost-Benefit Analysis↗
PubMed1994

A population-based study of the risk of recurrence of birth defects.

BACKGROUND: Certain birth defects are known to recur in families, but most estimates of the risk of recurrence have come from clinic-based studies. In this study we estimated the risk of recurrent birth defects using a population-based registry. METHODS: The study was based on the records of the first and second infants delivered by 371,933 women from 1967 through 1989. The records are maintained by the Medical Birth Registry of Norway. For the 9192 women whose first infant had a birth defect, we determined the relative risk of similar and dissimilar defects in the second infant. The reference population was women whose first infant had no defect. RESULTS: Among first infants, 2.5 percent had a birth defect. The mothers of affected first infants were 2.4 times as likely as other women to have second infants with any registered defect. This increased risk was due primarily to an increased (7.6 times higher) risk of the same defect in the second infant as in the first (95 percent confidence interval, 6.5 to 8.8) and secondarily to a slightly increased (1.5 times higher) risk of a different defect in the second infant (95 percent confidence interval, 1.3 to 1.7). Among the women who lived in the same municipality during both pregnancies, the relative risk of having a second infant with the same defect was 11.6, as compared with 5.1 among the women who moved to another municipality after the birth of their first infant (P < 0.001). CONCLUSIONS: Among women whose first infant has a birth defect, the risk of the same defect in the second infant is substantially increased and the risk of a different defect in the second infant is slightly increased. Environment plays a strong part in repeated defects.

Confidence Intervals↗