Related Articles

Background

A depressed Apgar score at 5 minutes is a marker for perinatal insults, including neurologic damage. We examined the association between 5-minute Apgar score and the risk of epilepsy hospitalization in childhood.

Methods

Using records linked from population registries, we conducted a cohort study among singleton children born alive in the period 1978–2001 in North Jutland County, Denmark. The first hospital discharge diagnosis of epilepsy during the follow-up time was the main outcome. We followed each child for up to 12 years, calculated absolute risks and risk differences, and used a Poisson regression model to estimate risk ratios for epilepsy hospitalization. We adjusted risk ratio estimates for birth weight, gestational age, mode of delivery, birth presentation, mother's age at delivery, and birth defects.

Results

One percent of the 131,853 eligible newborns had a 5-minute Apgar score <7. These children were more likely to be hospitalized with epilepsy during the follow-up than were children with an Apgar score of 7 or greater. The crude risk difference for epilepsy hospitalization was 2.5 cases per 100 (95% confidence interval [CI] 1.3 to 3.8). The risk difference estimates were greater in the presence of other perinatal risk factors. The adjusted risk ratio was 2.4 (95% CI 1.5 to 3.8). Half of the 12-year risk for epilepsy hospitalization in those with a depressed Apgar score occurred during the first year of life. The risk ratio during the first year of life was 4.9 (95% CI 2.0 to 12.3).

Conclusion

An Apgar score <7 at five minutes predicts an increase in the subsequent risk of epilepsy hospitalization. This association is amplified by other perinatal risk factors.

Aim

The aim of this study was to investigate the association between maternal socioeconomic position and a persistent low Apgar score (a score of < 7 at 1 and 5 min following birth).

Methods

The research is based on a population cohort study of 183 637 males born in Sweden between 1973 and 1976. Data from the Medical Birth Register were linked to Population and Housing Censuses.

Results

There was evidence that mothers working in non-manual (Odds ratio (OR) 0.83 (0.72–0.97)) and self-employed (OR 0.64 (0.44–0.93)) occupations were less likely to have an infant with a low Apgar score, compared to manual workers. There was evidence that the risk of a low Apgar score decreased as the mother's level of education increased, if the infant was born by instrumental (OR 0.86 (0.74–0.99)) or caesarean section (OR 0.80 (0.68–0.93)) delivery, but not by unassisted vaginal delivery (OR 1.01 (0.92–1.10)).

Conclusion

There was a lower risk of poor birth condition in male infants born to more educated and non-manual/self-employed mothers. These differences may contribute to our understanding of socioeconomic differences in infant health and development although the results may not be applicable due to changes over the last 30 years.

OBJECTIVE: To investigate whether prenatal growth affects the risk of development of childhood onset insulin dependent (type I) diabetes mellitus. DESIGN: Population based case-control study. SETTING: Data from a nationwide childhood diabetes case register were linked with data from the nationwide Swedish Medical Birth Registry. SUBJECTS: Data from a total of 4584 diabetic children born after 1973 and diagnosed with diabetes from 1978 to 1992 were studied. For each child with insulin dependent diabetes three control children were randomly selected from among all infants born in the same year and at the same hospital as the proband. MAIN OUTCOME MEASURES: Birth weight, gestation, maternal age and parity, number of previous spontaneous abortions, and sex specific birth weight by gestational week expressed as multiples of the standard deviation (SD). RESULTS: There was a clear trend in the odds ratio for childhood onset diabetes according to SD of birth weight. The odds ratio (95% confidence interval) for small for gestational age after stratification for maternal age, parity, smoking habits, and maternal diabetes was 0.81 (0.65 to 0.99) and for large for gestational age after similar stratification was 1.20 (1.02 to 1.42). CONCLUSIONS: Intrauterine conditions that affect prenatal growth seem also to affect the risk of development of childhood diabetes in the way previously described for postnatal growth: a poor growth decreases and an excess growth increases the risk. The mechanism for this association is unclear.

Objective. To study mode of birth, perinatal health and death in children born to mothers with intellectual disability (ID) in Sweden. Design. Population-based register study. Setting. National registers; the National Patient Register linked to the Medical Birth Register. Sample. Children of first-time mothers with ID (n = 326; classified in the International Classification of Diseases 8–10) were identified and compared with 340 624 children of first-time mothers without ID or any other psychiatric diagnosis between 1999 and 2007. Methods. Population-based data were extracted from the National Patient Register and the Medical Birth Register. Main outcome measures. Mode of birth, preterm birth, small for gestational age, Apgar score, stillbirth and perinatal death. Results. Children born to mothers with ID were more often stillborn (1.2 vs. 0.3%) or died perinatally (1.8 vs. 0.4%) than children born to mothers without ID. They had a higher proportion of cesarean section birth (24.5 vs. 17.7%) and preterm birth (12.2 vs. 6.1%), were small for gestational age (8.4 vs. 3.1%) and had lower Apgar scores (<7 points at five minutes; 3.7 vs 1.5%) compared with children born to mothers without ID. Logistic regression adjusted for maternal characteristics confirmed an increased risk of small for gestational age (odds ratio 2.25), stillbirth (odds ratio 4.53) and perinatal death (odds ratio 4.25) in children born to mothers with ID. Conclusions. Unborn and newborn children of mothers with ID should be considered a risk group, and their mothers may need better individual-based care and support.

Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53 811 children of more than 36 000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968–1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0–19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0–2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9–1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia. © 2000 Cancer Research Campaign

Objective: To examine whether the combination of a low five minute Apgar score and symptoms of neonatal encephalopathy is associated with minor impairments at school age.

Design: Population based cohort study.

Setting: Norway.

Participants: All 727 children of the cohort were born between 1983 and 1987, had normal birth weights, no congenital malformations, and no major neurological abnormalities. The cohort comprised three groups with five minute Apgar scores of 0–3, 4–6, and 7–10, and were followed from birth to 8–13 years of age by combining data from The Medical Birth Registry, questionnaires, hospital discharge summaries, and the National Insurance Scheme.

Main outcome measure: Neurodevelopmental impairments such as learning, behavioural, and minor motor difficulties.

Results: Children with a five minute Apgar score of 3 or less and signs consistent with neonatal encephalopathy had a significantly increased risk of developing minor motor impairments (odds ratio (OR) 12.8, 95% confidence interval (CI) 2.6 to 63.2), epilepsy (OR 7.0, 95% CI 1.3 to 39.2), need of extra resources in kindergarten (OR 7.0, 95% CI 1.3 to 39.2) or at school (OR 3.4, 95% CI 1.8 to 6.3), and had reduced performance in reading (OR 4.6, 95% CI 2.3 to 9.5) and mathematics (OR 3.3, 95% CI 1.5 to 7.3), compared with children with normal Apgar scores and no neonatal symptoms. They also more often had problems related to tractability, aggressivity, passivity, anxiety, academic performance, and fine motor development.

Conclusion: Children with low Apgar scores and subsequent signs of cerebral depression who do not develop cerebral palsy may still have an increased risk of developing a variety of neurodevelopmental impairments and learning difficulties.

Objectives To assess the association of Apgar score 5 minutes after birth with cerebral palsy in both normal weight and low birthweight children, and also the association with the cerebral palsy subdiagnoses of quadriplegia, diplegia, and hemiplegia.

Design Population based cohort study.

Setting The Medical Birth Registry of Norway was used to identify all babies born between 1986 and 1995. These data were linked to the Norwegian Registry of Cerebral Palsy in Children born 1986-95, which was established on the basis of discharge diagnoses at all paediatric departments in Norway.

Population All singletons without malformations born in Norway during 1986-95 and who survived the first year of life (n=543 064).

Main outcome measure Cerebral palsy diagnosed before the age of 5 years.

Results 988 children (1.8 in 1000) were diagnosed with cerebral palsy before the age of 5 years. In total, 11% (39/369) of the children with Apgar score of less than 3 at birth were diagnosed with cerebral palsy, compared with only 0.1% (162/179 515) of the children with Apgar score of 10 (odds ratio (OR) 53, 95% CI 35 to 80 after adjustment for birth weight). In children with a birth weight of 2500 g or more, those with an Apgar score of less than 4 were much more likely to have cerebral palsy than those who had an Apgar score of more than 8 (OR 125, 95% confidence interval 91 to 170). The corresponding OR in children weighing less than 1500 g was 5 (95% CI 2 to 9). Among children with Apgar score of less than 4, 10-17% in all birthweight groups developed cerebral palsy. Low Apgar score was strongly associated with each of the three subgroups of spastic cerebral palsy, although the association was strongest for quadriplegia (adjusted OR 137 for Apgar score <4 v Apgar score >8, 95% CI 77 to 244).

Conclusions Low Apgar score was strongly associated with cerebral palsy. This association was high in children with normal birth weight and modest in children with low birth weight. The strength of the association differed between subgroups of spastic cerebral palsy. Given that Apgar score is a measure of vitality shortly after birth, our findings suggest that the causes of cerebral palsy are closely linked to factors that reduce infant vitality.

Background

Apgar score is used for rapid assessment of newborns. Low five-minute Apgar score has been associated with increased risk of severe neurologic outcome, but data on milder outcomes, particularly in the long term, are limited. We aimed to examine the association of five-minute Apgar score with prevalence of neurologic disability and with cognitive function in early adulthood.

Methods

We conducted a prevalence study among draft-liable men born in Denmark in 1978–1983 and presenting for the mandatory army evaluation in a northern Danish conscription district. We linked records of this evaluation, which includes medical exam and intelligence testing, with the conscripts' records in the Medical Birth Registry, containing perinatal data. We examined prevalence of neurologic disability and of low cognitive function according to five-minute Apgar score.

Results

Less than 1% (136/19,559) of the conscripts had 5-minute Apgar scores <7. Prevalence of neurologic disability was 2.2% (435/19,559) overall; among conscripts with Apgar scores <7, 7–9, and 10 (reference), it was 8.8%, 2.5%, and 2.2% respectively. The corresponding prevalences of low cognitive function (intelligence test score in the bottom quartile) were 34.9%, 27.2%, and 25.0%. The outcomes were more prevalent if Apgar score <7 was accompanied by certain fetal or obstetric adversities. After accounting for perinatal characteristics, 5-mintue Apgar score <7 was associated with prevalence ratios of 4.02 (95% confidence interval: 2.24; 7.24) for neurologic disability and 1.33 (0.94; 1.88) for low cognitive function.

Conclusion

A five-minute Apgar score <7 has a consistent association with prevalence of neurologic disability and with low cognitive function in early adulthood.

The authors evaluated the association between gestational age, birth weight, intrauterine growth and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 individuals were registered with epilepsy in the Danish National Hospital Register as inpatients (1979-2002) and outpatients (1995-2002). Information on gestational age and birth weight was obtained from Danish Medical Birth Registry. Children small at birth were identified through two methods: 1) sex-, birth order-, and gestational-age-specific z-score, and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios (IRR) for epilepsy in the first year of life were more than five-fold in children born at 22-32 weeks compared with children born at 39-41 weeks, and in children with a birth weight <2,000 grams compared with children of 3,000-3,999 grams. The IRRs decreased with age, but remained elevated into early adulthood. Children identified as growth-restricted according to either of the two methods had increased IRRs for epilepsy, even among children with a ‘normal’ birth weight of 3,500-3,999 grams. Low gestational age at birth and low birth weight are associated with an increased risk of epilepsy throughout childhood and persisting into puberty. Intrauterine growth restriction is associated with an increased risk of epilepsy, even among children with a birth weight in a normal range.

Background

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are fluorinated organic compounds present in the general population at low concentrations. Animal studies have shown that they may affect neuromuscular development at high concentrations.

Objectives

We investigated the association between plasma levels of PFOS and PFOA in pregnant women and motor and mental developmental milestones of their children.

Methods

We randomly selected 1,400 pairs of pregnant women and their children from the Danish National Birth Cohort. PFOS and PFOA were measured in maternal blood samples taken in early pregnancy. Apgar score was abstracted from the National Hospital Discharge Register in Denmark. Developmental milestones were reported by mothers using highly structured questionnaires when the children were around 6 months and 18 months of age.

Results

Mothers who had higher levels of PFOA and PFOS gave birth to children who had similar Apgar scores and reached virtually all of the development milestones at the same time as children born to mothers with lower exposure levels. Children who were born to mothers with higher PFOS levels were slightly more likely to start sitting without support at a later age.

Conclusion

We found no convincing associations between developmental milestones in early childhood and levels of PFOA or PFOS as measured in maternal plasma early in pregnancy.

Background

Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes.

Methods

Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided.

Results

Survivors’ children were more likely to be born preterm than the siblings’ children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P<.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight).

Conclusions

Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.

To examine the relationship between birth characteristics and childhood cancer mortality, a retrospective cohort study of Korean children was conducted using data collected by the national birth register between 1995 and 2006, which were then individually linked to death data. A cohort of 6,479,406 children was followed from birth until their death or until December 31, 2006. Poisson regression analyses were used to calculate rate ratios of childhood cancer deaths according to birth characteristics. A total of 1,469 cancer deaths were noted and the childhood cancer mortality rate was found to be 3.43 per 100,000 person-years in Korea during the period of 1995-2006. The birth characteristics examined in this study (i.e. , birth weight, gestational age, multiple births, parental ages, and number of siblings) were generally found to be not significantly associated with childhood cancer mortality, and the associations did not vary meaningfully with gender nor with cancer sites. However, among children aged 5-11 yr, higher birth weight was associated with elevated childhood cancer mortality (rate ratio = 1.28, 95% confidence interval 1.04-1.58). Our results offer no overall associations between childhood cancer mortality and birth characteristics, but suggest that the association may be specific to age group.

Background

Being born small for gestational age (SGA) is associated with decreased insulin sensitivity and increased blood pressure in childhood, but the association with clinical disease in early adulthood is less certain. The Danish Medical Birth Registry has registered all births in Denmark since 1973, but due to variable data quality, data is most often used only from 1981 onwards, and birth registers in other countries may have similar problems for the early years. We wanted to examine whether the data can be used for identification of children born SGA and used in future research.

Methodology/Principal Findings

All persons born between 1974 and 1996 were identified in the Danish Medical Birth Registry (n = 1.704.890). Immigrants and children without data on gestational age and birth weight were excluded, and a total of 1.348.106 children were included in the analysis. The difference between the different variables used in the history of the registry were examined, and the quality of data in the birth registry from 1974-1981 was examined and compared to subsequent years.

Data on birth weight and gestational age in the early years of the registry is inconsistent, and the identification of children born SGA is inaccurate, with 49% false-positives. The biggest source of error is due to the rough and inaccurate intervals used for gestational age. By using –3 standard deviations as a cut-off for the identification of children born SGA, the number of false-positives was reduced to 9%, while the amount of false-negatives were increased.

Conclusion

Choosing –3 standard deviations for identifying children born SGA is a viable, though not optimal solution for identifying children born SGA. Overall the data in the registry is of sufficient quality to be used in further medical research.

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.

British Journal of Cancer (2002) 86, 1078–1080. DOI: 10.1038/sj/bjc/6600192 www.bjcancer.com

© 2002 Cancer Research UK

Background & Aims

Studies on pregnancy characteristics and mode of delivery and risk of later celiac disease in offspring are inconsistent. In recent decades rates of cesarean delivery and preterm birth survival have increased while at the same time the prevalence of celiac disease has doubled.

Methods

In this population-based case-control study we examine the risk of celiac disease in individuals exposed to cesarean delivery and adverse fetal events (i.e. low Apgar score, small for gestational age, low birth weight, preterm birth, and neonatal infections). Prospectively recorded pregnancy data were obtained from the Swedish Medical Birth Register between 1973 and 2008. Study participants consisted of 11,749 offspring with biopsy-verified celiac disease identified through histopathology reports from Sweden’s 28 pathology departments and 53,887 age- and sex-matched controls from the general population.

Results

We found a positive association between elective cesarean delivery and later celiac disease (adjusted odds ratio (AOR) = 1.15; 1.04-1.26; p = 0.005), but no increased risk of celiac disease following emergency (AOR = 1.02; 0.92-1.13; p = 0.749) or any cesarean delivery (AOR = 1.06; 0.99-1.13; p = 0.074). Infants born small for gestational age were at a 21% increased risk of celiac disease (95% CI = 1.09-1.35; p = 0.001), whereas other pregnancy exposures did not increase the risk of future celiac disease.

Conclusions

The positive association with elective, but not emergency, cesarean delivery is consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease.

Objective

To increase our knowledge of the occurrence of substandard care during labour.

Design

A population-based case–control study.

Setting

Stockholm County.

Population

Infants born in the period 2004–2006 in Stockholm County.

Methods

Cases and controls were identified from the Swedish Medical Birth Register, had a gestational age of ≥33 complete weeks, had planned for a vaginal delivery, and had a normal cardiotocographic (CTG) recording on admission. We compared 313 infants with an Apgar score of <7 at 5 minutes of age with 313 randomly selected controls with a full Apgar score, matched for year of birth.

Main outcome measure

Substandard care during labour.

Results

We found that 62% of cases and 36% of controls were subject to some form of substandard care during labour. In half of the cases and in 12% of the controls, CTG was abnormal for ≥45 minutes before birth. Fetal blood sampling was not performed in 79% of both cases and controls, when indicated. Oxytocin was provided without signs of uterine inertia in 20% of both cases and controls. Uterine contractions were hyperstimulated by oxytocin in 29% of cases and in 9% of controls, and the dose of oxytocin was increased despite abnormal CTG in 19% and 6% of cases and controls, respectively. Assuming that substandard care is a risk factor for low Apgar score, we estimate that up to 42% of the cases could be prevented by avoiding substandard care.

Conclusions

There was substandard care during labour of two-thirds of infants with a low Apgar score. The main reasons for substandard care were related to misinterpretation of CTG, not acting on an abnormal CTG in a timely fashion and incautious use of oxytocin.

OBJECTIVE—Low birth weight is consistently associated with an increased risk of type 2 diabetes in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. We therefore investigated the significance of these two factors separately.

RESEARCH DESIGN AND METHODS—We identified a cohort of subjects born preterm or with low birth weight at term at four major delivery units in Sweden from 1925 through 1949. A comparison cohort of subjects was identified from the same source population. Of 6,425 subjects in all, 2,931 were born at <37 weeks of gestation and 2,176 had a birth weight <2,500 g. Disease occurrence among participants was assessed through nationwide hospital registers from 1987 through 2006.

RESULTS—During follow-up, there were 508 cases of diabetes. Low birth weight was strongly negatively associated with risk of diabetes (P for trend <0.0001). Both short gestational duration and poor fetal growth were associated with later diabetes (P for trend <0.0001 and <0.0004, respectively). Very preterm birth (≤32 weeks of gestation at birth) was associated with a hazard ratio (HR) of 1.67 (95% CI 1.33–2.11) compared with term birth. Birth weights below 2 SDs of mean birth weight for gestational age were associated with an HR of 1.76 (1.30–2.38) compared with birth weights between the mean weight and the weight at 1 SD above the mean.

CONCLUSIONS—Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age.

Background

Previous studies on the association between maternal age and risk of childhood leukemia found inconsistent results.

Objectives

We aimed to assess whether there is an association between maternal age and risk of childhood leukemia and whether such an association is modified by maternal year of birth.

Methods

By linking nationwide Swedish registers, we analyzed leukemia incidence among all children between 1 and 5 years of age born between 1960 and 1999. We estimated incidence time trends by child year of birth (overall and stratified by maternal age) and incidence rate ratios (RRs) for maternal age groups stratified by maternal birth cohort. We tested the interaction between maternal age and child year of birth through the likelihood ratio test between nested Poisson regression models.

Results

We observed 1,562 leukemia cases. The overall annual percent change (APC) was 1.00 [95% confidence interval (CI), 0.51 to 1.49]. Stratifying by maternal age classes, APCs decreased from 1.66 (0.68 to 2.65) for mothers ≤ 24 years to 0.23 (−0.93 to 1.40) for mothers ≥ 35 years at delivery. RRs for children born to the oldest with respect to the youngest mothers were 2.42 (1.31 to 4.67), 1.68 (1.00 to 2.72), 1.34 (0.87 to 2.01), and 0.87 (0.46–1.54) for mothers born in 1930–1934, 1940–1944, 1950–1954, and 1960–1964, respectively.

Conclusions

Childhood leukemia risk increased with maternal age for mothers born in the past, whereas maternal age had no effect on this risk for mothers born more recently. This finding may explain the inconsistency of previous studies and suggests that leukemia risk may be related to an environmental factor to which women’s exposure has changed over time.

Analysis of recent cancer registrations from Great Britain suggests that there has been an increase in the incidence of childhood acute lymphoid leukaemia for children born after about 1964. The increase is statistically significant for boys aged 0-4 years, and a lesser increase may also have occurred for girls in this age group. Reasons are given for believing that the increase is not purely an artifact attributable to improved registration procedures. Registration data from the Manchester Children's Tumour Registry, Denmark and Sweden support the suggestion that an increase h as occurred. It is not at present possible to say whether a change in incidence will also be seen at higher ages or will be confined to the youngest children, who may represent an aetiologically distinct sub-group. There is no obvious explanation for the findings reported here.

OBJECTIVE:

Preterm birth is associated with asthma-like symptoms in childhood and possibly in adolescence, but the longer-term risk of asthma is unknown and increasingly relevant as larger numbers of these individuals enter adulthood. Our objective was to evaluate whether those who were born preterm are more likely to be prescribed asthma medications in young adulthood than those who were born term.

PATIENTS AND METHODS:

We conducted a national cohort study of all singleton infants born in Sweden from 1973 through 1979 (n = 622 616), followed to ages 25.5 to 35.0 years to determine whether asthma medications were prescribed in 2005–2007. Asthma medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. To improve the positive predictive value for asthma, the outcome was defined as prescription of (1) both a β-2 agonist inhalant and a glucocorticoid inhalant or (2) a combination inhalant containing a β-2 agonist and other drugs for obstructive airway diseases.

RESULTS:

Young adults who were born extremely preterm (23–27 weeks' gestation) were 2.4 times more likely (adjusted 95% CI: 1.41–4.06) to be prescribed asthma medications than those who were born term. No association was found between later preterm birth (28–32 or 33–36 weeks' gestation) and asthma medications in young adulthood.

CONCLUSIONS:

This is the first study with sufficient statistical power to evaluate the risk of asthma beyond adolescence in individuals who were born extremely preterm. The results suggest that extreme preterm birth (23–27 weeks' gestation), but not later preterm birth, is associated with an increased risk of asthma at least into young adulthood.

Background

During the last decades there has been a steady increase of twin births. A combination of improved medical treatment of preterm and small-for-gestational age children has contributed to a higher number of surviving twins. Prematurity is known to affect reproduction in a negative way. Few studies have focused on the potential effect twinning may have on future reproduction. Thus, the aim of this study was to investigate the effect of being born a twin compared to being born a singleton have on future reproduction.

Methods

In a national population-based register study, all individuals born between 1973–1983 who were alive and living in Sweden at 13 years of age (n = 1 016 908) constituted the sample. Data on each study subject’s own birth as well as the birth of their first offspring, and parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios and corresponding 95% CI was calculated using Cox proportional hazards model.

Results

Twins, both men and women, had a reduced likelihood of reproducing compared to singletons (women: HR = 0.89, 95% CI = 0.86-0.93; men: HR = 0.92, 95% CI = 0.87-0.97). This difference in birth rates can only partly be explained by diverging birth characteristics. Amongst men and women born very preterm, twins had an increased likelihood of reproducing compared to singletons (women: HR = 1.25, 95% CI = 1.02-1.62; men: HR = 1.34, 95% CI = 1.01-1.78).

Conclusions

Twins have lower reproduction rates compared to singletons, which only to a certain degree can be explained by diverging birth characteristics.

Background

The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring.

Methods

We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1 777 765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1 769 0795 children without a paternal history of cancer, 25 926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided.

Results

The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, Pinteraction = .84).

Conclusion

We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.

Objective

To examine prenatal and perinatal risk factors for subsequent development of schizophrenia and affective and reactive psychosis.

Design

Three population based, case-control studies conducted within a Sweden-wide cohort of all children born during 1973-9. This was done by linking individual data from the Swedish birth register, which represents 99% of all births in Sweden, to the Swedish inpatient register.

Subjects

Patients listed in inpatient register as having been first admitted to hospital aged 15-21 years with a main diagnosis of schizophrenia (n=167), affective psychosis (n=198), or reactive psychosis (n=292). For each case, five controls were selected.

Main outcome measures

Risks of schizophrenia and affective and reactive psychosis in relation to pregnancy and perinatal characteristics.

Results

Schizophrenia was positively associated with multiparity (odds ratio 2.0), maternal bleeding during pregnancy (odds ratio 3.5), and birth in late winter (odds ratio 1.4). Affective psychosis was associated with uterine atony (odds ratio 2.2) and late winter birth (odds ratio 1.5). Reactive psychosis was related to multiparity (odds ratio 2.1). An increased risk for schizophrenia was found in boys who were small for their gestational age at birth (odds ratio 3.2), who were number four or more in birth order (odds ratio 3.6), and whose mothers had had bleeding during late pregnancy (odds ratio 4.0).

Conclusions

A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency.

Key messagesThe role of prenatal and perinatal risk factors in the development of schizophrenia and affective and reactive psychosis in early adult life were investigated by linking individual data from the Swedish birth and inpatient registriesAdverse prenatal and perinatal factors were more common in patients with schizophrenia of early onset than in controls and seemed more important in the aetiology of schizophrenia than in that of affective and reactive psychosisMultiparity, bleeding during pregnancy, and small size for gestational age were associated with a threefold to fourfold increased risk for schizophrenia among malesThere was no support for previous claims that head circumference is small in preschizophrenic infantsLate winter birth was associated with increased risk of both schizophrenia and affective psychosis

BACKGROUND—Previous studies have suggested that, in addition to genetic liability and environment in early childhood, intrauterine life also influences the risk for asthma beyond childhood. Low birth weight, prematurity, young maternal age, and maternal smoking have all shown an association with asthma. The effect of perinatal factors on the risk for asthma in relation to familial and social risk factors was studied in a nationwide population-based sample of adolescent twins. In addition to a distribution of birth characteristics among twins which differs from that of singletons, data on twins enable a distinction to be made between genetic and environmental sources of variation.
METHODS—Questionnaires were sent to five consecutive birth cohorts of Finnish 16 year old twins born in 1975-9 and to their parents (3065 families). The outcome measure was life time prevalence of doctor-diagnosed asthma in these adolescents. The association between asthma and potential risk factors was assessed by multiple logistic regression and discordant twin pair analysis.
RESULTS—Risk for asthma increased with increasing ponderal index (p for trend <0.01) and decreasing maternal age (p for trend <0.05). Among the 25% of twins with the highest ponderal index, the odds ratio for asthma was 1.82 (95% confidence interval 1.18 to 2.79) compared with those in the lowest 25%. Neither birth weight, gestational age, nor Apgar score was associated with asthma. When perinatal risk factors were combined with familial and social risk factors, ponderal index, maternal smoking, parental asthma, and sibship size were all significant independent determinants of asthma in these adolescents.
CONCLUSIONS—The risk for asthma in adolescent twins increases with increasing ponderal index when adjusted for familial and social factors.



Background

Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population-based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland) from 1973 to 2006 and explores possible explanations for these different trends.

Methods

Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172), Sweden (n = 188,783) and Geneva (n = 5,755) from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer.

Results

Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries.

Conclusions

This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect.