Analyzing sibship correlations in birth weight using large sibships from Norway

Data from the Medical Birth Registry of Norway were used to estimate sibship correlations in large sibships (each with ≥5 infants among singleton live births surviving the first year of life), while adjusting for covariates such as infant gender, gestational age, maternal age, parity, and time since last pregnancy. This sample of 12,356 full sibs in 2,462 sibships born in Norway between 1968 and 1989 was selected to maximize the information on parity, and a robust approach to estimating both regression coefficients and the sibship correlation using generalized estimating equations (GEE) was employed. In concordance with previous studies, these data showed a high overall correlation in birth weight among full sibs (0.48 ± 0.01), but this sibship correlation was influenced by parity. In particular, the correlation between the firstborn infant and a subsequent infant was slightly lower than between two subsequent sibs (0.44 ± 0.01 vs. 0.50 ± 0.01, respectively). The effect of time between pregnancies was statistically significant, but its predicted impact was modest over the period in which most of these large families were completed. While these data cannot discriminate whether factors influencing birth weight are maternal or fetal in nature, this analysis does illustrate how robust statistical models can be used to estimate sibship correlations while adjusting for covariates in family studies. Genet. Epidemiol. 14:423–433,1997. © 1997 Wiley-Liss, Inc.     

Post-neonatal mortality in Norway 1969-95: a cause-specific analysis

BACKGROUND: We recently reported increased social inequality for post-neonatal death. The aim of the present study was to investigate the association between socioeconomic status and cause-specific post-neonatal death. METHODS: All 1,483,857 live births recorded in the Medical Birth Registry of Norway from 1969-95 with information on parents' education were included. During the post-neonatal period (from 28 to 364 days of life) 4,464 infants died. Differences between education groups were estimated as risk differences, relative risks, population attributable fractions, and relative index of inequality. RESULTS: The major causes of death were congenital conditions, sudden infant death syndrome (SIDS), and infections. Post-neonatal mortality declined from 3.2/1,000 in the 1970s to 1.9/1,000 in the 1990s, mainly due to reduced mortality from congenital conditions. The absolute risk for SIDS increased by 0.51/1,000 in the same period among infants whose mothers had low education, while it decreased by 0.56/1,000 for those whose mothers had high education. The relative risk for SIDS among infants whose mothers had low education increased from 1.02 in the 1970s to 2.39 in the 1980s and 5.63 in the 1990s. Among infants whose fathers were not recorded in the Birth Registry, the absolute risk of SIDS increased by 0.79/1,000 from the 1970s to the 1990s. CONCLUSIONS: Increased social inequality for post-neonatal death was primarily due to increases in the absolute and relative risks of SIDS among infants whose mothers have low education. Social inequality widened during the study period for SIDS and deaths caused by infections.     

Event-related potentials in alcoholics and their first-degree relatives

Preliminary results are presented for auditory ERPs recorded from members of alcoholic families during performance of a counting task and a choice reaction task. Alcoholic families included three adult male siblings (alcoholic proband, a second affected sib, and an unaffected sib) and parents. Control families included two adult male sibs and parents. In all experimental conditions, the N100 component was decreased in amplitude for all sibs (affected and unaffected) of the alcoholic families. The latency of the P300 component was increased for both affected and unaffected sibs compared to controls in the counting task, indicating a familial difference irrespective of drinking status. In the choice reaction task, longer P300 latencies were observed among the probands and their affected sibs as compared to their unaffected sibs, suggesting that in this more demanding task, increased latency was associated with a significant drinking history. ERP findings for children of the alcoholic probands are also discussed. The effects of differences in task complexity, drinking variables, and criteria for family selection are considered.     

Maternal occupation and congenital heart defects: a case-control study

Summary This paper reports a Swedish analysis of the possible effect of maternal occupation on the occurrence of congenital heart defects. The analysis included 3324 infants (1108 cases and 2216 controls) born during the period 1982–1986. Information on maternal occupation was retrieved using two sources: the 1985 census and the Medical Birth Registry. A comparison between these two sources using the information on mothers of 756 infants born in 1986 showed a good concordance although 11% of the women were reported with a different employment status. No association appeared between the type of maternal occupation and the occurrence of infant congenital heart defects although some odds ratios were slightly above 1.     

Saving Newborn Babies – The Benefits of Interventions in Neonatal Care in Norway over More Than 40 Years

The aim of this study was to examine the effect that the introduction of new medical interventions at birth has had on mortality among newborn babies in Norway during the period 1967–2011. During this period, there has been a significant decline in mortality, in particular for low birth weight infants. We identified four interventions that together explained about 50% of the decline in early neonatal and infant mortality: ventilators, antenatal steroids, surfactant and insure. The analyses were performed on a large set of data, encompassing more than 1.6 million deliveries (Medical Birth Registry of Norway). The richness of the data allowed us to perform several robustness tests. Our study indicates that the introduction of new medical interventions has been a very important channel through which the decline in mortality among newborn babies occurred during the second half of the last century. Copyright © 2016 John Wiley & Sons, Ltd.     

Accuracy of proband reported family history: The NHLBI Family Heart Study (FHS)

Proband‐reported family histories are widely used in research and counseling, yet little is known about the validity of family history reporting. The Family Heart Study (FHS), a population‐based study of familial cardiovascular disease, gathered family history information from 3,020 middle‐aged probands in four U.S. communities. Probands reported on the history of coronary heart disease (CHD), diabetes, hypertension, and asthma among a total of 10,316 living relatives (9,186 siblings, 1,130 parents) and 2,685 spouses. Questionnaires were returned by 6,672 siblings, 901 parents, and 2,347 spouses, yielding response rates of 73, 79, and 87%, respectively. Utilizing the relatives' self‐report as the standard, sensitivity of the proband report on their spouse, parent, and sibling was 87, 85, and 81% for CHD, 83, 87, and 72% for diabetes, 77, 76, and 56% for hypertension, and 66, 53, and 39% for asthma, respectively. Most specificity values were above 90%. Analyses using generalized estimating equations (GEE) were performed to evaluate differences in proband accuracy based on the proband's age, gender, disease state, center, and ethnicity. In multivariate models, age, gender, and disease status were significantly associated with the accuracy of proband's report of sibling disease history, but had little effect on the accuracy of their report on spouses or parents. In general, older probands were significantly less accurate reporters of disease than younger probands. These results demonstrate that CHD family history can be captured effectively based on proband reports, but suggest that additional family contacts may be helpful when working with older probands or with chronic diseases that have few recognized medical events or procedures. Genet. Epidemiol. 17:141–150, 1999.© 1999 Wiley‐Liss, Inc.     

Families with birth defects: is birth weight of nonmalformed siblings affected?

Infants with congenital malformations have on average lower birth weight than do infants without malformations. Preterm delivery and low birth weight are known to recur in sibships. The aim of the study was to compare the birth weight of siblings to malformed infants with the birth weight of infants in families without malformed infants. Data were from the Medical Birth Registry in Norway from 1967 to 1998. Births were linked to their mothers through the unique personal identification number, providing sibship files with the mother as the observation unit. The study was based on 551,478 mothers with at least two singleton infants and 209,423 mothers with at least three singletons. The authors grouped the families according to whether and in which birth order an infant had a registered congenital malformation and compared birth weight and gestational age between infants of the same birth order in families with malformations and without. Overall, in families where one or two infants had a congenital malformation, the crude and adjusted mean birth weight of nonmalformed siblings did not differ from that of infants in unaffected families, whereas it was significantly reduced for the malformed infant itself. We conclude that reduced birth weight associated with congenital anomalies is specific to the affected pregnancy.     

Respiratory distress syndrome in preterm infants and risk of epilepsy in a Danish cohort

Infant respiratory distress syndrome (IRDS) may be complicated by intracerebral hemorrhage, a known trigger of epilepsy. However, few data exist on long term epilepsy risk following IRDS. We therefore examined the association between IRDS in preterm infants and childhood epilepsy. We conducted a population-based cohort study using individual-level data linkage among nationwide registries. All infants born at 32–36 weeks of gestation in 1978–2009 were identified in the Medical Birth Registry. We identified children with IRDS and those with epilepsy using the Danish National Patient Registry. We computed the cumulative incidence of epilepsy with follow-up from birth until epilepsy, emigration, death, age 15, or December 31, 2014. We used Cox’s regression analysis to compute hazard ratios comparing children with and without IRDS, adjusting for sex, birth year, gestational age, multiplicity, major malformations, and maternal age. We identified 95,026 infants, of whom 6426 (6.8%) had IRDS. The cumulative incidence of epilepsy was 3.4% by age 15 in children with IRDS and 2.1% in children without IRDS. The adjusted hazard ratio of epilepsy among children with IRDS compared to those without was 1.4 (95% CI 1.2–1.6). When we restricted the IRDS cohort to children with no simultaneous morbidities that had clinical symptoms overlapping with IRDS, the overall adjusted HR was 1.1 (95% CI 0.9–1.4). In children born preterm at 32–36 weeks’ gestation, IRDS was associated with increased risk of childhood epilepsy.     

Cryptorchidism: a registry based study in Sweden on some factors of possible aetiological importance.

STUDY OBJECTIVE: To examine the epidemiological characteristics of boys with cryptorchidism. DESIGN: Cohort survey using the Swedish personal identification code and Medical Birth Registry to link cryptorchid boys with their pregnancy and delivery data. They were compared with the total population of male births during the same period. SUBJECTS: 2861 cryptorchid boys born in Sweden between 1973 and 1982 were identified. Of these 437 could not be linked with their Medical Birth Registry information for various reasons, or were excluded because they were under 1 year of age at the end of 1982, leaving 2424 cases for study. The reference population comprised all boys born in Sweden during the same period (n = 458,601). MEASUREMENTS AND MAIN RESULTS: For each study variable, the observed number of cases among boys with cryptorchidism was compared with the expected number calculated from the whole population. A significant increase in intensity ratio for cryptorchidism was found with the first birth, caesarean section, toxaemia of pregnancy, and certain congenital abnormalities (hypospadias and subluxation of the hip). It was also more common in small for dates infants. There was a seasonal variation in cryptorchidism, with increased incidence in January-March. CONCLUSIONS: Cryptorchidism may be caused by hormonal influences during pregnancy, which could be affected by utero-placental factors involving placental dysfunction or by daylight hours, through pineal activity.     

Fetal growth, maternal prenatal smoking, and risk of invasive meningococcal disease: a nationwide case-control study

BACKGROUND: The prenatal period may be important for susceptibility to infections. We evaluated whether low birthweight, prematurity, and prenatal maternal smoking were associated with increased risk of invasive meningococcal disease. METHODS: We linked the Danish nationwide National Registry of Patients, the Birth Registry, and social registries to obtain data on fetal growth and social factors on 1921 cases of meningococcal disease hospitalized between 1 January, 1980 and 31 December, 1999 (median age 31 months, interquartiles 13-65 months) and 37 451 population controls. The impact of maternal smoking was examined in a subsample of 462 cases and 9240 controls born after 1990, when data on smoking became available in the Birth Registry. RESULTS: The adjusted odds ratios (OR) of meningococcal disease associated with low birthweight (<2500 g) varied between 1.6 (95% CI: 1.1, 2.3) in infants <12 months to 1.5 (95% CI: 1.0, 2.3) in children >60 months of age at hospitalization for meningococcal disease. Premature children had an increased risk of meningococcal disease during the first year of life only (adjusted OR = 1.3, 95% CI: 1.1, 1.9). The effect of low birthweight was very similar among mature and premature children. The adjusted OR for maternal smoking was 1.8 (95% CI: 1.4, 2.2). CONCLUSIONS: Low birthweight is associated with an increased risk of meningococcal disease throughout childhood, while an effect of prematurity persists only for 12 months. Maternal prenatal smoking was associated with the risk of meningococcal disease.     

Families with a perinatal death: is there an association between the loss and the birthweight of surviving siblings?

Our objective was to study birthweight among surviving siblings in families with and without a perinatal loss, and to evaluate whether different causes of death were associated with the results. Data were for 1967-98 from the Norwegian Medical Birth Registry. Births were organised with the mother as the observation unit through the personal identification number, providing sibship files. We analysed 550 930 sibships with at least two singletons, 208 586 sibships with at least three singletons and 45 675 sibships with at least four singleton births. We compared mean birthweight and gestational age between infants in sibships with and without a perinatal loss, total losses and the different causes of death. Surviving siblings in families with a perinatal loss had significantly lower mean birthweights than their counterparts in unaffected families, after adjusting for gestational age, interpregnancy interval, time period and marital status. An exception was found when cause of death was a birth defect, when growth retardation among surviving siblings was not found on average. We conclude that families who have lost an infant because of a birth defect do not appear to have an increased risk of adverse birth outcome associated with growth restriction.     

A quality study of a medical birth registry

A quality control study was made of the Swedish Medical Birth Registry. This registry used one mode of data collection during 1973-1981 and another from 1982 onwards. The number of errors in the register was checked by comparing register information with a sample of the original medical records, and the variability in the use of diagnoses between hospitals was studied. Different types of errors were identified and quantified and the efficiency of the two methods of data collection evaluated.     

Estimating effects of proband characteristics on familial risk: II. The association between age at onset and familial risk in the Maryland schizophrenia sample.

In this report we apply methods outlined in the companion paper [Liang, Genet Epidemiol 8:329-338, 1991] to study the association between proband age at onset and familial risk among first-degree relatives of 374 schizophrenic probands. The analyses take into consideration the potential problems of censoring and correlation of age at onset within families. All analyses were done by gender of the proband; age at onset was dichotomized. The results of the analyses of the male probands suggest that there is an increased risk of schizophrenia among the relatives of male probands who have an onset prior to age 17 when compared to relatives of male probands who have an onset later than 16. We did not find an association between age at onset and familial risk among the female probands, but this may be due to the smaller number of female probands and the lower power associated with the analyses.     

School attainment of children who had a single umbilical artery at birth

Lilja M. School attainment of children who had a single umbilical artery at birth. Paediatric and Perinatal Epidemiology 2010; 24: 166–170. To the best of our knowledge, this is the first registry study of school achievements among children born with a single umbilical artery (SUA). A total of 1600 infants born with SUA during 1983–86 were studied. We linked the Swedish Medical Birth Registry with the Swedish School Registry, which contains the school grades of all children in Sweden when leaving compulsory school. Risks were estimated as odds ratios (OR) using the Mantel‐Haenzel procedure, after adjustment for four potential confounders: year of birth, maternal age, parity and maternal education. There was a 60% excess of children born with SUA who did not complete compulsory school after removal of infants born preterm, small‐for‐gestational age and low Apgar score (OR = 1.60 [95% confidence interval 1.28, 2.00]). When sports and the three core school subjects (mathematics, English and Swedish) were studied, there was an increased risk for ‘not passed’ in all subjects except sport and a slight decrease in the probability of achieving ‘passed with distinction or excellence’. In the three core subjects there was an association with gender, boys with SUA being more likely to have ‘not passed’ than girls. In conclusion the children born with SUA are more likely than children born with three vessels to show impaired school achievements.     

Is the Prevalence of Specific Types of Congenital Heart Defects Different for Non-Hispanic White,Non-Hispanic Black and Hispanic Infants?

Background Our purpose was to determine the prevalence of specific types of CHD among non-Hispanic (NH)-Black, NH-White, and Hispanic infants. Methods We conducted a retrospective cohort study with 9,352 singleton infants diagnosed with conotruncal, right or left obstructive or septal CHDs from the Florida Birth Defects Registry, born 1998–2003 to resident NH-White, NH-Black, and Hispanic women aged 15–49. Defect-specific prevalence rates, prevalence ratios and P-values were calculated for each type of CHD and by number of defects for each racial/ethnic group. Results Compared to NH-Whites, NH-Blacks had higher rates of pulmonary valve atresia/stenosis but lower frequency of aortic valve atresia/stenosis and ventricular septal defect. Hispanics had lower rates of aortic valve atresia/stenosis and atrioventricular septal defects than NH-Whites. Conclusions Although few racial/ethnic differences in prevalence are present among infants with major CHD, observed differences are clinically meaningful. However, the underlying etiologies for the observed differences remain unknown.     

Birthweight and perinatal mortality: paradoxes,social class,and sibling dependencies

BACKGROUND: Birthweight distributions among second-born infants depend on the birthweights of older siblings, with implications for weight-specific perinatal mortality. We wanted to study whether these relations were explained by socioeconomic levels, and to study time trends in a situation with decreasing perinatal mortality rates. METHODS: Births in the Norwegian Medical Birth Registry from 1967 to 1998 were linked to their mothers through their national identification numbers. The study population was 546 688 mothers with at least two singletons weighing >/==" BORDER="0">500 g at birth. Weight-specific perinatal mortality for second-born siblings in families with first-born siblings in either the highest or the lowest birthweight quartile was analysed. Maternal education and cohabitation status were used as measures of socioeconomic level. RESULTS: For all 500-g categories below 3500 g, mortality rates were significantly higher among second-born infants with an older sibling in the highest rather than the lowest weight quartile. This pattern was the same across three educational levels. The exclusion of preterm births did not change the effect pattern. A comparison of perinatal mortality among second siblings in terms of relative birthweight (z-scores) showed a reversal of the relative risks, although these were only significantly different from unity for the smallest infants. Conclusion The crossover in weight-specific perinatal mortality for second siblings by weight of first sibling is largely independent of socioeconomic level, and is not weakened by the decreasing perinatal mortality rates in the population over time. Family data should be taken into consideration when evaluating the risk of adverse pregnancy outcome relating to weight.     

Birth weight related to social indicators in Norway

The relationship between parental social position and birthweight is being studied. A total population of 102,638 singleborn, first-born infants was included in the study. Census informationfrom 1980 was linked to the Medical Birth Registry for the years1978-1982. Children of parents with a high education (more than15 years) had the highest birth weight. The association wasdistinct and linear between low birth weight and education.The same tendency appeared for paternal socio-economic status,but differences were comparatively small. When examining incomethe pattern was different. The highest maternal income grouphad the highest proportion of low birth weight offspring. Whenexamining parental education jointly, it was found that themothers' education had the greatest impact on birth weight.By adjusting for female smoking, using survey data, the associationbetween maternal education and birth weight was weakened. However,assuming that birth weight is decreased by 200 g from smoking,the effect was still significant.     

Mixed abuse of alcohol and drugs in teenagers in Sweden vs a group from the general population

We compared the subsequent life and development of 182 teenagers (the controls) from the general population and 345 teenagers of the same ages (the probands) who were taken care of by the Social Service Department, all of them from Greater Stockholm. All of the probands but none of the controls abused alcohol and drugs, and the probands had more psychosocial problems than the controls. The probands had grown up in families with more abuse of alcohol and drugs, broken homes, an alcohol-abusing father and mother and had taken up their parents' concomitant drug and alcohol abuse by parental influences. There were differences in social adjustment and health status between the probands compared with the controls. Social assistance was required to a much greater extent by the probands and they were registered in the Temperance Register and the Criminal Offenders Register and were in contact with the child welfare authorities more often than the controls. The proband children were also registered for sick-leave more often than the boys and girls from the general population and accounted for a larger number of visits to the wards and outpatient clinics for somatic symptoms and to psychiatric clinics and wards. The two groups of boys and girls of the probands were like “twin” groups in that they were almost equally often involved in crimes with drugs and their social maladjustment and health status resembled each other.     

Fatness and obesity of the parents of obese individuals

As shown in 1419 pairings of obese probands with their parents drawn from a larger series of greater than 9000 proband-parent pairings, the fathers and mothers of obese probands are of increased fatness level (+0.27 Z scores) and more often obese than expected (odds ratio 1.50 overall). However, the tendency towards increased fatness and a greater prevalence of obesity among the parents of obese probands bears a curvilinear relationship to the age of the proband, being least when the probands are young, peaking when the sons and daughters are teen-agers, and declining thereafter. Parents of lean probands in turn tend to be lean themselves (averaging -0.25 Z scores) and least often obese when their progeny are teen-aged. As shown in a two-generational context, familial obesity is best demonstrated in adolescents and their parents, either reflecting years spent in common or a specific etiology for adolescent-onset obesity.     

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.