Sandra Bonellie

Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy.

CONTEXT For patients on T(4) replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms. OBJECTIVE The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T(4) replacement. DESIGN We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001. SETTING A population-based study of all patients in Tayside, Scotland, was performed. PATIENTS All patients taking T(4) replacement therapy (n = 17,684) were included. MAIN OUTCOME MEASURES Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (<or=0.03 mU/liter), low TSH (0.04-0.4 mU/liter), normal TSH (0.4-4.0 mU/liter), or raised TSH (>4.0 mU/liter). RESULTS Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73-2.21), 1.80 (1.33-2.44), and 1.83 (1.41-2.37), respectively; and patients with a suppressed TSH: 1.37 (1.17-1.60), 1.6 (1.10-2.33), and 2.02 (1.55-2.62), respectively, when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes [hazards ratio: 1.1 (0.99-1.123), 1.13 (0.88-1.47), and 1.13 (0.92-1.39), respectively]. CONCLUSIONS Patients with a high or suppressed TSH had an increased risk of cardiovascular disease, dysrhythmias, and fractures, but patients with a low but unsuppressed TSH did not. It may be safe for patients treated with T(4) to have a low but not suppressed serum TSH concentration.

Centile charts for birthweight for gestational age for Scottish singleton births

BackgroundCentile charts of birthweight for gestational age are used to identify low birthweight babies. The charts currently used in Scotland are based on data from the 1970s and require updating given changes in birthweight and in the measurement of gestational age since then.MethodsRoutinely collected data of 100,133 singleton births occurring in Scotland from 1998–2003 were used to construct new centile charts using the LMS method.ResultsCentile charts for birthweight for sex and parity groupings were constructed for singleton birth and compared to existing charts used in Scottish hospitals.ConclusionMean birthweight has been shown to have increased over recent decades. The differences shown between the new and currently used centiles confirm the need for more up-to-date centiles for birthweight for gestational age.

Contribution of smoking during pregnancy to inequalities in stillbirth and infant death in Scotland 1994-2003: retrospective population based study using hospital maternity records

Objective To quantify the contribution of smoking during pregnancy to social inequalities in stillbirth and infant death. Design Population based retrospective cohort study. Setting Scottish hospitals between 1994 and 2003. Participants Records of 529 317 singleton live births and 2699 stillbirths delivered at 24-44 weeks’ gestation in Scotland from 1994 to 2003. Main outcome measures Rates of stillbirth and infant, neonatal, and post-neonatal death for each deprivation category (fifths of postcode sector Carstairs-Morris scores); contribution of smoking during pregnancy (“no,” “yes,” or “not known”) in explaining social inequalities in these outcomes. Results The stillbirth rate increased from 3.8 per 1000 in the least deprived group to 5.9 per 1000 in the most deprived group. For infant deaths, the rate increased from 3.2 per 1000 in the least deprived group to 5.4 per 1000 in the most deprived group. Stillbirths were 56% more likely (odds ratio 1.56, 95% confidence interval 1.38 to 1.77) and infant deaths were 72% more likely (1.72, 1.50 to 1.97) in the most deprived compared with the least deprived category. Smoking during pregnancy accounted for 38% of the inequality in stillbirths and 31% of the inequality in infant deaths. Conclusions Both tackling smoking during pregnancy and reducing infants’ exposure to tobacco smoke in the postnatal environment may help to reduce stillbirths and infant deaths overall and to reduce the socioeconomic inequalities in stillbirths and infant deaths perhaps by as much as 30-40%. However, action on smoking on its own is unlikely to be sufficient and other measures to improve the social circumstances, social support, and health of mothers and infants are needed.

Social inequalities in preterm birth in Scotland 1980-2003: findings from an area-based measure of deprivation.

Objective  The preterm birth rate in Scotland has been increasing in recent years. Although preterm birth rates show a social gradient, it is unclear how this gradient has been affected by the overall increase. We examined time trends in singleton live preterm birth rates in relation to area‐based socio‐economic indicators.

Comparison of risk factors for cerebral palsy in twins and singletons

The aim of this study was to investigate the difference in rates of cerebral palsy (CP) between singletons and twins by considering factors that may be predictive of CP. Data were taken from the Scottish Register of Children with a Motor Deficit of Central Origin and the Scottish Morbidity Record series. All children born in Scotland between 1984 and 1990 inclusive comprised the cohort. There were 646 children with CP (370 males, 276 females) of whom 57 were from twin pregnancies. Prevalence of CP was higher in twins than in singletons. Also, for singleton and twin births, the prevalence of CP was higher for infants who had low birthweight for gestational age (GA), were preterm, and who were male. Prevalence of CP by GA followed a different pattern for twins than for singletons, being lower for twins in the middle range of GAs than for singletons. After allowing for GA and birthweight, twins appeared to be at increased risk for CP compared with singletons. The type of CP in singletons and twins also differed with 64.9% of twins having spastic bilateral CP compared with 48.5% for singletons. The aetiology of CP in twins and singletons may differ.

Socio-economic inequalities in cerebral palsy prevalence in the United Kingdom: a register-based study

Evidence is unclear as to whether there is a socio-economic gradient in cerebral palsy (CP) prevalence beyond what would be expected from the socio-economic gradient for low birthweight, a strong risk factor for CP. We conducted a population-based study in five regions of the UK with CP registers, to investigate the relationship between CP prevalence and socio-economic deprivation, and how it varies by region, by birthweight and by severity and type of CP. The total study population was 1 657 569 livebirths, born between 1984 and 1997. Wards of residence were classified into five quintiles according to a census-based deprivation index, from Q1 (least deprived) to Q5 (most deprived). Socio-economic gradients were modelled by Poisson regression, and region-specific estimates combined by meta-analysis. The prevalence of postneonatally acquired CP was 0.14 per 1000 livebirths overall. The mean deprivation gradient, expressed as the relative risk in the most deprived vs. the least deprived quintile, was 1.86 (95% confidence interval [95% CI 1.19, 2.88]). The prevalence of non-acquired CP was 2.22 per 1000 livebirths. For non-acquired CP the gradient was 1.16 [95% CI 1.00, 1.35]. Evidence for a socio-economic gradient was strongest for spastic bilateral cases (1.32 [95% CI 1.09, 1.59]) and cases with severe intellectual impairment (1.59 [95% CI 1.06, 2.39]). There was evidence for differences in gradient between regions. The gradient of risk of CP among normal birthweight births was not statistically significant overall (1.21 [95% CI 0.95, 1.54]), but was significant in two regions. There was non-significant evidence of a reduction in gradients over time. The reduction of the higher rates of postneonatally acquired CP in the more socioeconomically deprived areas is a clear goal for prevention. While we found evidence for a socio-economic gradient for non-acquired CP of antenatal or perinatal origin, the picture was not consistent across regions, and there was some evidence of a decline in inequalities over time. The steeper gradients in some regions for normal birthweight cases and cases with severe intellectual impairment require further investigation.

A comparison of customized and population-based birth-weight standards: The influence of gestational age

OBJECTIVES We examined how customized birth-weight standards compare to population birth-weight references at term (> or =37 weeks), nearly term (34-36 weeks), moderately preterm (32-33 weeks) and for the very preterm births (28-31 weeks), with respect to perinatal mortality. STUDY DESIGN Data from the national Swedish Medical Births Register for the years 1992-2001, consisting of a total of 783,303 singletons born at or after 28 completed gestational weeks. Infants were classified as small for gestational age (SGA, <10th centile) according to a conventional population based birth-weight reference and a customized standard. Risk ratios (RR) for still birth and neonatal death were compared between standards by prematurity of the birth. Diagnostic performance measures of specificity, sensitivity and positive and negative predictive values were also evaluated. RESULTS More than half, 59% (209), of the 355 infants still-born between 28 and 31 weeks gestation were classified as SGA by the customized standard, but only 23% (80), were so classified as SGA by the population reference. However, only 14% (95%CI 13-16) of the 1461 very preterm infants classified as SGA by the customized standard were still-born, compared to 23% (95%CI 19-28) of the 348 infants classified as SGA by the population reference. Therefore, the relative risk of still birth for those classified as SGA by the customized standard is lower, 2.02 (95%CI: 1.65, 2.46), than for the population reference 2.64 (95%CI: 2.11, 3.30). Similar results were observed for the risk of neonatal death. For term weeks, customized standards showed stronger relationships than population references (RR: 4.30 (95%CI 3.82, 4.84) vs. 4.00 (95%CI 3.55, 4.51) for still births). CONCLUSIONS Customized standards categorize a higher absolute number of preterm infants who are still-born as SGA. However, infants classified as SGA by population references are at higher risk of perinatal mortality than infants classified as SGA by customized standards.

Intrauterine growth and survival in cerebral palsy

Background and objectives: Deviations in birth weight from an optimum, thought to be just above average for gestational age, are known to increase both the risk of developing cerebral palsy and the risk of developing cerebral palsy of a more severe form. Influences on survival of such deviations from average birth weight for gestational age are not known. Methods: Using a well-established, well-defined and large UK cohort of children and adults with cerebral palsy, followed from birth for nearly 25 years, we investigate the influence of deviations from average birth weight for gestational age, on survival duration, after allowing for severity of impairments. Results: A total of 3946 cases, born between 1980 and 1996 were included. For those born much lighter than average for gestational age, more than 30% (n = 313) had a severe motor or cognitive impairment, rising to as much as 40% (n = 239) for extremely low weights. For female infants, the proportions severely impaired increased to as much as 35% (n = 49) among those born much heavier than average; no such increase was observed for heavier than average male infants. For those with four severe impairments and a birth weight close to average for gestational age, around 60% (n = 140) survived to age 15 years, compared with less than 40% (n = 9) of those born much heavier than average for gestational age. A 2-year-old child with four severe impairments and born heavy for gestational age has a predicted median life expectancy of 79% (95% CI 70% to 88%) of the average. Conclusions: Infants with a birth weight lighter than average for gestational age have an increased likelihood of developing a more severe form of cerebral palsy. Surprisingly, among the infants who are very severely impaired, those born much lighter than average for gestational age have the longest life expectancy, and those born much heavier than average for gestational age have the shortest life expectancy.