Epidemiology of emergency ambulance service calls related to COVID-19 in Scotland: a national record linkage study.

BACKGROUND: COVID-19 has overwhelmed health services across the world; its global death toll has exceeded 5.3 million and continues to grow. There have been almost 15 million cases of COVID-19 in the UK. The need for rapid accurate identification, appropriate clinical care and decision making, remains a priority for UK ambulance service. To support identification and conveyance decisions of patients presenting with COVID-19 symptoms the Scottish Ambulance Service introduced the revised Medical Priority Dispatch System Protocol 36, enhanced physician led decision support and prehospital clinical guidelines. This study aimed to characterise the impact of these changes on the pathways and outcomes of people attended by the SAS) with potential COVID-19. METHODS: A retrospective record linkage cohort study using National Data collected from NHS Scotland over a 5 month period (April-August 2020). RESULTS: The SAS responded to 214,082 emergency calls during the study time period. The positive predictive value of the Protocol 36 to identify potentially COVID-19 positive patients was low (17%). Approximately 60% of those identified by Protocol 36 as potentially COVID-19 positive were conveyed. The relationship between conveyance and mortality differed between Protocol 36 Covid-19 positive calls and those that were not. In those identified by Protocol 36 as Covid-19 negative, 30 day mortality was higher in those not conveyed (not conveyed 9.2%; conveyed 6.6%) but in the Protocol 36 Covid-19 positive calls, mortality was higher in those conveyed (not conveyed 4.3% conveyed 8.8%). Thirty-day mortality rates of those with COVID-19 diagnosed through virology was between 28.8 and 30.2%. CONCLUSION: The low positive predictive value (17%) of Protocol 36 in identifying potential COVID-19 in patients emphasises the importance of ambulance clinicians approaching each call as involving COVID-19, reinforcing the importance of adhering to existing policy and continued use of PPE at all calls. The non-conveyance rate of people that were categorised as COVID-19 negative was higher than in the preceding year in the same service. The reasons for the higher rates of non-conveyance and the relationship between non conveyance rates and death at 3 and 30 days post index call are unknown and would benefit from further study.

What causes the burden of stroke in Scotland? A comparative risk assessment approach linking the Scottish Health Survey to administrative health data.

BACKGROUND: The availability of robust evidence to inform effective public health decision making is becoming increasingly important, particularly in a time of competing health demands and limited resources. Comparative Risk Assessments (CRA) are useful in this regard as they quantify the contribution of modifiable exposures to the disease burden in a population. The aim of this study is to assess the contribution of a range of modifiable exposures to the burden of disease due to stroke, an important public health problem in Scotland. METHODS: We used individual-level response data from eight waves (1995-2012) of the Scottish Health Survey linked to acute hospital discharge records from the Scottish Morbidity Record 01 (SMR01) and cause of death records from the death register. Stroke was defined using the International Classification of Disease (ICD) 9 codes 430-431, 433-4 and 436; and the ICD10 codes I60-61 and I63-64 and stroke incidence was defined as a composite of an individual's first hospitalisation or death from stroke. A literature review identified exposures causally linked to stroke. Exposures were mapped to the layers of the Dahlgren & Whitehead model of the determinants of health and Population Attributable Fractions were calculated for each exposure deemed a significant causal risk of stroke from a Cox Proportional Hazards Regression model. Population Attributable Fractions were not summed as they may add to more than 100% due to the possibility of a person being exposed to more than one exposure simultaneously. RESULTS: Overall, the results suggest that socioeconomic factors explain the largest proportion of incident stroke hospitalisations and deaths, after adjustment for confounding. After DAG adjustment, low education explained 38.8% (95% Confidence Interval 26.0% to 49.4%, area deprivation (as measured by the Scottish Index of Multiple Deprivation) 34.9% (95% CI 26.4 to 42.4%), occupational social class differences 30.3% (95% CI 19.4% to 39.8%), high systolic blood pressure 29.6% (95% CI 20.6% to 37.6%), smoking 25.6% (95% CI 17.9% to 32.6%) and area deprivation (as measured by the Carstairs area deprivation Index) 23.5% (95% CI 14.4% to 31.7%), of incident strokes in Scotland after adjustment. CONCLUSION: This study provides evidence for prioritising interventions that tackle socioeconomic inequalities as a means of achieving the greatest reduction in avoidable strokes in Scotland. Future work to disentangle the proportion of the effect of deprivation transmitted through intermediate mediators on the pathway between socioeconomic inequalities and stroke may offer additional opportunities to reduce the incidence of stroke in Scotland.

Trends and inequalities in the burden of mortality in Scotland 2000-2015.

BACKGROUND: Cause-specific mortality trends are routinely reported for Scotland. However, ill-defined deaths are not routinely redistributed to more precise and internationally comparable categories nor is the mortality reported in terms of years of life lost to facilitate the calculation of the burden of disease. This study describes trends in Years of Life Lost (YLL) for specific causes of death in Scotland from 2000 to 2015. METHODS: We obtained records of all deaths in Scotland by age, sex, area and underlying cause of death between 2000 and 2015. We redistributed Ill-Defined Deaths (IDDs) to more exact and meaningful causes using internationally accepted methods. Years of Life Lost (YLL) using remaining life expectancy by sex and single year of age from the 2013 Scottish life table were calculated for each death. These data were then used to calculate the crude and age-standardised trends in YLL by age, sex, cause, health board area, and area deprivation decile. RESULTS: Between 2000 and 2015, the annual percentage of deaths that were ill-defined varied between 10% and 12%. The proportion of deaths that were IDDs increased over time and were more common: in women; amongst those aged 1-4 years, 25-34 years and >80 years; in more deprived areas; and in the island health boards. The total YLL fell from around 17,800 years per 100,000 population in 2000 to around 13,500 years by 2015. The largest individual contributors to YLL were Ischaemic Heart Disease (IHD), respiratory cancers, Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease and Alzheimer's/dementia. The proportion of total YLL due to IHD and stroke declined over time, but increased for Alzheimer's/dementia and drug use disorders. There were marked absolute inequalities in YLL by area deprivation, with a mean Slope Index of Inequality (SII) for all causes of 15,344 YLL between 2001 and 2015, with IHD and COPD the greatest contributors. The Relative Index of Inequality (RII) for YLL was highest for self-harm and lower respiratory infections. CONCLUSION: The total YLL per 100,000 population in Scotland has declined over time. The YLL in Scotland is predominantly due to a wide range of chronic diseases, substance misuse, self-harm and increasingly Alzheimer's disease and dementia. Inequalities in YLL, in both relative and absolute terms, are stark.

Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care.

RATIONALE: Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level. OBJECTIVES: To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use. METHODS: Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses. MEASUREMENTS AND MAIN RESULTS: Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity. CONCLUSIONS: This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society.

A population-based study of venous thrombosis in pregnancy in Scotland 1980-2005.

OBJECTIVES: Data on time trends in the incidence of pregnancy-related venous thromboembolism (VTE) are sparse. This report charts the incidence of pregnancy-related VTE over the period 1980-2005 in Scotland, and discusses the results in relation to potential risk factors. STUDY DESIGN: 1475301 maternity discharges from Scottish hospitals recorded on the Scottish Morbidity Record 2 (SMR2) were included. Incidences of pregnancy-related VTE, antenatal deep venous thromboembolism (DVT), postnatal DVT and pulmonary embolism (PTE) were derived relative to the number of deliveries, and risk factors were analysed using Poisson regression. RESULTS: Over the period, VTE incidence rose from 13.7 to 18.3 per 10000 deliveries, antenatal DVTs from 8.8 to 12.2 per 10000 deliveries and PTE from 1.5 to 3.0 per 10000 deliveries. Postnatal DVTs, on the other hand, declined from 4.2 to 2.7 per 10000 deliveries. Risk factors were: age over 35 years; three or more previous pregnancies; previous VTE; obstetric haemorrhage; and preeclampsia. Antenatal DVT risk was highest in the most deprived areas, where events started increasing before those in less deprived areas. Postnatal DVT risk was increased following caesarean delivery, especially when unplanned, although after 1996, events following emergency caesarean decreased. CONCLUSION: During the 26-year period, pregnancy-related VTEs increased, with the greatest rise for antenatal DVTs. Postnatal DVTs, on the other hand, declined over the period, particularly following emergency section. Thromboprophylaxis use following emergency delivery may have led to the postpartum reduction. To continue to prevent events, risk assessment and intervention are required, particularly antenatally.

Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren.

BACKGROUND: Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. METHODS AND FINDINGS: We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37-39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12-1.20; 33-36 wk adjusted OR 1.53, 95% CI 1.43-1.63; 28-32 wk adjusted OR 2.66, 95% CI 2.38-2.97; 24-27 wk adjusted OR 6.92, 95% CI 5.58-8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37-39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. CONCLUSIONS: Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery.

Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth.

OBJECTIVE: To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome. METHODS: A nested, case-control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte. RESULTS: Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90-0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91-0.99). Associations were minimally affected by adjustment for maternal characteristics. CONCLUSION: Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.

Previous preeclampsia, preterm delivery, and delivery of a small for gestational age infant and the risk of unexplained stillbirth in the second pregnancy: a retrospective cohort study, Scotland, 1992-2001.

Women with a previous stillbirth are known to be at increased risk of stillbirth in subsequent pregnancies. However, few studies have addressed the association between other complications of pregnancy and the future risk of stillbirth. Using linkage of national pregnancy and perinatal death registries, the authors performed a retrospective cohort study of 133,163 women having a second birth in Scotland between 1992 and 2001 whose first infant was liveborn. The risk of unexplained stillbirth was increased among women with a previous preterm birth (adjusted hazard ratio (HR) = 2.04, 95% confidence interval (CI): 1.34, 3.11), previous delivery of a small for gestational age (SGA) infant (HR = 2.14, 95% CI: 1.59, 2.87), and previous preeclampsia (HR = 1.68, 95% CI: 1.07, 2.62). The associations were similar after adjustment for maternal age, height, marital and smoking status, and interpregnancy interval. There was a statistically significant positive interaction between previous delivery of a SGA infant and previous preeclampsia (p = 0.01): Women with this combination in their first pregnancy had an approximately fivefold risk of unexplained stillbirth in the second pregnancy (HR = 4.95, 95% CI: 2.63, 9.32). Associations were stronger with SGA unexplained stillbirths. The authors conclude that complicated first births of liveborn infants are associated with an increased risk of unexplained stillbirth in the next pregnancy.

Maternal obesity in early pregnancy and risk of spontaneous and elective preterm deliveries: a retrospective cohort study.

OBJECTIVES: We sought to determine the association between maternal body mass index and risk of preterm delivery. METHODS: We assessed 187,290 women in Scotland and estimated adjusted odds ratios for spontaneous and elective preterm deliveries among overweight, obese, and morbidly obese women relative to normal-weight women. RESULTS: Among nulliparous women, the risk of requiring an elective preterm delivery increased with increasing BMI, whereas the risk of spontaneous preterm labor decreased. Morbidly obese nulliparous women were at increased risk of all-cause preterm deliveries, neonatal death, and delivery of an infant weighing less than 1000 g who survived to 1 year of age (a proxy for severe long-term disability). By contrast, obesity and elective preterm delivery were only weakly associated among multiparous women. CONCLUSIONS: Obese nulliparous women are at increased risk of elective preterm deliveries. This in turn leads to an increased risk of perinatal mortality and is likely to lead to increased risks of long-term disability among surviving offspring.

Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity.

BACKGROUND: Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. METHODS: The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24-36 weeks was assessed using a test of the proportional hazards assumption. RESULTS: The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24-28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65 (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. CONCLUSIONS: Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.

Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome.

OBJECTIVE: To describe the association between pregnancy associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP) and adverse perinatal outcome. METHODS: We conducted a multicenter prospective cohort study of 8,483 women attending for prenatal care in southern Scotland between 1998 and 2000. The risk of delivering a small for gestational age infant, delivering preterm, and stillbirth were related to maternal serum levels of PAPP-A and AFP. RESULTS: Women with a low PAPP-A were not more likely to have elevated levels of AFP. Compared with women with a normal PAPP-A and a normal AFP, the odds ratio for delivering a small for gestational age infant for women with a high AFP was 0.9 (95% confidence interval [CI] 0.5-1.6), for women with a low PAPP-A was 2.8 (95% CI 2.0-4.0), and for women with both a high AFP and a low PAPP-A was 8.5 (95% CI 3.6-20.0). The odds ratio for delivering preterm for women with a high AFP was 1.8 (95% CI 1.3-2.7), for women with a low PAPP-A was 1.9 (95% CI 1.3-2.7), and for women with both a low PAPP-A and a high AFP was 9.9 (95% CI 4.4-22.0). These interactions were statistically significant for both outcomes (P = .03 and .04, respectively). There was a nonsignificant trend toward a similar interaction in relation to stillbirth risk. Of the women with the combination of a low PAPP-A and high AFP, 32.1% (95% CI 15.9-52.4) delivered a low birth weight infant. CONCLUSION: Low maternal serum levels of PAPP-A between 10 and 14 weeks and high levels of AFP between 15 and 21 weeks gestation are synergistically associated with adverse perinatal outcome. LEVEL OF EVIDENCE: II-2.

First cesarean birth and subsequent fertility.

OBJECTIVE: To determine whether cesarean delivery is independently associated with later subfertility. DESIGN: Retrospective cohort study. SETTING: Maternity records kept for Scotland, 1980-1999. PATIENT(S): The study included 109,991 women who had first births between 1980 and 1984, excluding multiple or preterm births and perinatal deaths. INTERVENTION(S): Exposures studied were spontaneous vaginal birth, operative vaginal birth, planned cesarean delivery for breach presentation, planned cesarean delivery for other indications, and emergency cesarean delivery. MAIN OUTCOME MEASURE(S): The relative risk of not having a second pregnancy over the following 15 years, the interpregnancy interval, and the number of spontaneous early pregnancy losses between the first and second birth. RESULT(S): Women who delivered by planned cesarean section for breech presentation had an increased risk of not having a second birth compared with women whose first birth was a spontaneous vertex delivery (relative risk [RR]: 1.21, 95% confidence interval [CI]: 1.14 to 1.29). However, after adjustment for maternal and obstetric characteristics, there was no longer a strong association (adjusted RR: 1.07, 95% CI: 1.00 to 1.15). Operative vaginal delivery (forceps and vacuum extraction) and all types of cesarean delivery were associated with longer interpregnancy intervals. There was no relationship between mode of delivery and the number of spontaneous early pregnancy losses between the first and second birth. CONCLUSION(S): It is unlikely that delivering by cesarean section in a first pregnancy decreases a woman's likelihood of having a second viable pregnancy.

Sudden infant death syndrome and complications in other pregnancies.

BACKGROUND: The likelihood of recurrence of sudden infant death syndrome (SIDS) is an issue of biological, clinical, and legal interest. Obstetric complications are associated with an increased risk of SIDS and are likely to recur in subsequent pregnancies. We postulated that women whose infants died from SIDS would be more likely to have had obstetric complications in their other pregnancies. METHODS: We linked national UK databases of maternity-hospital discharges, perinatal deaths, and death certifications. We studied 258 096 women who had consecutive births in Scotland between 1985 and 2001. FINDINGS: Women who had an infant who died from SIDS were at increased risk in their next pregnancy of delivering an infant small for gestational age (odds ratio 2.27, 95% CI 1.54-3.34, p<0.0001) and of preterm birth (2.53, 1.82-3.53, p<0.0001). The risk of SIDS was higher for the children of women whose previous infant had been small for gestational age (1.87, 1.19-2.94, p=0.007) or preterm (1.93, 1.24-3.00, p=0.004). Multivariate analysis showed that all associations were explained by common maternal risk factors for SIDS and obstetric complications and by the likelihood of recurrence of fetal growth restriction and preterm birth. INTERPRETATION: Women whose infants die from SIDS are more likely to have complications in their other pregnancies. Recurrence of pregnancy complications predisposing to SIDS could partly explain why some women have recurrent SIDS.

Predicting cesarean section and uterine rupture among women attempting vaginal birth after prior cesarean section.

BACKGROUND: There is currently no validated method for antepartum prediction of the risk of failed vaginal birth after cesarean section and no information on the relationship between the risk of emergency cesarean delivery and the risk of uterine rupture. METHODS AND FINDINGS: We linked a national maternity hospital discharge database and a national registry of perinatal deaths. We studied 23,286 women with one prior cesarean delivery who attempted vaginal birth at or after 40-wk gestation. The population was randomly split into model development and validation groups. The factors associated with emergency cesarean section were maternal age (adjusted odds ratio [OR] = 1.22 per 5-y increase, 95% confidence interval [CI]: 1.16 to 1.28), maternal height (adjusted OR = 0.75 per 5-cm increase, 95% CI: 0.73 to 0.78), male fetus (adjusted OR = 1.18, 95% CI: 1.08 to 1.29), no previous vaginal birth (adjusted OR = 5.08, 95% CI: 4.52 to 5.72), prostaglandin induction of labor (adjusted OR = 1.42, 95% CI: 1.26 to 1.60), and birth at 41-wk (adjusted OR = 1.30, 95% CI: 1.18 to 1.42) or 42-wk (adjusted OR = 1.38, 95% CI: 1.17 to 1.62) gestation compared with 40-wk. In the validation group, 36% of the women had a low predicted risk of caesarean section (< 20%) and 16.5% of women had a high predicted risk (> 40%); 10.9% and 47.7% of these women, respectively, actually had deliveries by caesarean section. The predicted risk of caesarean section was also associated with the risk of all uterine rupture (OR for a 5% increase in predicted risk = 1.22, 95% CI: 1.14 to 1.31) and uterine rupture associated with perinatal death (OR for a 5% increase in predicted risk = 1.32, 95% CI: 1.02 to 1.73). The observed incidence of uterine rupture was 2.0 per 1,000 among women at low risk of cesarean section and 9.1 per 1,000 among those at high risk (relative risk = 4.5, 95% CI: 2.6 to 8.1). We present the model in a simple-to-use format. CONCLUSIONS: We present, to our knowledge, the first validated model for antepartum prediction of the risk of failed vaginal birth after prior cesarean section. Women at increased risk of emergency caesarean section are also at increased risk of uterine rupture, including catastrophic rupture leading to perinatal death.

Mode of delivery and the risk of delivery-related perinatal death among twins at term: a retrospective cohort study of 8073 births.

OBJECTIVE: To determine the risk of perinatal death among twins born at term in relation to mode of delivery. DESIGN: Retrospective cohort study. SETTING: Scotland 1985-2001. POPULATION: All twin births at or after 36 weeks of gestation, excluding antepartum stillbirths and perinatal deaths due to congenital abnormality (n= 8073). METHODS: The outcome of first and second twins was compared using McNemar's test and the outcome of twin pairs in relation to mode of delivery was compared using exact logistic regression. MAIN OUTCOME MEASURES: Intrapartum stillbirth or neonatal death of either twin. RESULTS: Overall, there were six deaths of first twins and 30 deaths of second twins (OR for second twin 5.00, 95% CI 2.00-14.70). The odds ratio for death of the second twin due to intrapartum anoxia was 21 (95% CI 3.4-868.5). The associations were similar for twins delivered following induction of labour and for sex discordant twins. However, there was no association between birth order and the risk of death among 1472 deliveries by planned caesarean section. There was death of either twin among 2 of 1472 (0.14%) deliveries by planned caesarean section and 34 of 6601 (0.52%) deliveries by other means (P= 0.05, odds ratio for planned caesarean section 0.26 [95% CI 0.03-1.03]). The association was similar when adjusted for potential confounders. Assuming causality, we estimate that 264 caesarean deliveries (95% CI 158-808) would be required to prevent each death. CONCLUSION: Planned caesarean section may reduce the risk of perinatal death of twins at term by approximately 75% compared with attempting vaginal birth. This is principally due to reducing the risk of death of the second twin due to intrapartum anoxia.

Risk of breast cancer after miscarriage or induced abortion: a Scottish record linkage case-control study.

STUDY OBJECTIVE: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. DESIGN: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. SETTING: Scotland. PARTICIPANTS: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. MAIN RESULTS: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02 (0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. CONCLUSION: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer.

First-trimester placentation and the risk of antepartum stillbirth.

CONTEXT: Preterm birth and low birth weight are determined, at least in part, during the first trimester of pregnancy. However, it is unknown whether the risk of stillbirth is also determined during the first trimester. OBJECTIVE: To determine whether the risk of antepartum stillbirth varies in relation to circulating markers of placental function measured during the first trimester of pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, prospective cohort study (conducted in Scotland from 1998 through 2000) of 7934 women who had singleton births at or after 24 weeks' gestation, who had blood taken during the first 10 weeks after conception, and who were entered into national registries of births and perinatal deaths. MAIN OUTCOME MEASURES: Antepartum stillbirths and stillbirths due to specific causes. RESULTS: There were 8 stillbirths among the 400 women with levels of pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile compared with 17 among the remaining 7534 women (incidence rate per 10,000 women per week of gestation: 13.4 vs 1.4, respectively; hazard ratio [HR], 9.2 [95% confidence interval [CI], 4.0-21.4]; P<.001). When analyzed by cause of stillbirth, low level of PAPP-A was strongly associated with stillbirth due to placental dysfunction, defined as abruption or unexplained stillbirth associated with growth restriction (incidence rate: 11.7 vs 0.3, respectively; HR, 46.0 [95% CI, 11.9-178.0]; P<.001), but was not associated with other causes of stillbirth (incidence rate: 1.7 vs 1.1, respectively; HR, 1.4 [95% CI, 0.2-10.6]; P = .75). There was no relationship between having a low level of PAPP-A and maternal age, ethnicity, parity, height, body mass index, race, or marital status. Adjustment for maternal factors did not attenuate the strength of associations observed. There was no association between maternal circulating levels of the free beta subunit of human chorionic gonadotropin and stillbirth risk. CONCLUSION: The risk of stillbirth in late pregnancy may be determined by placental function in the first 10 weeks after conception.

Second-trimester maternal serum levels of alpha-fetoprotein and the subsequent risk of sudden infant death syndrome.

BACKGROUND: Unexplained stillbirth and the sudden infant death syndrome (SIDS) share some features. A raised maternal serum level of alpha-fetoprotein during the second trimester of pregnancy is a marker of placental dysfunction and a strong predictor of the risk of unexplained stillbirth. It is unknown whether alpha-fetoprotein levels also predict the risk of SIDS. METHODS: We linked a prenatal-screening database for women in western Scotland with databases of maternity, perinatal death, and birth and death certifications to assess the association between second-trimester levels of maternal serum alpha-fetoprotein and the subsequent risk of SIDS. RESULTS: Among 214,532 women with singleton births, there were 114 cases of SIDS (incidence, 2.7 per 10,000 births among women with alpha-fetoprotein levels in the lowest quintile and 7.5 per 10,000 births among those with levels in the highest quintile). When the lowest quintile was used as a referent, the unadjusted odds ratios for SIDS for the second through fifth quintiles were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.8 (95 percent confidence interval, 0.9 to 3.7), 2.5 (95 percent confidence interval, 1.3 to 4.8), and 2.8 (95 percent confidence interval, 1.4 to 5.4), respectively (P for trend = 0.001). The risk of SIDS varied inversely with the birth-weight percentile and the gestational age at delivery; after adjustment for these factors, the odds ratios for SIDS were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.7 (95 percent confidence interval, 0.8 to 3.5), 2.2 (95 percent confidence interval, 1.1 to 4.4), and 2.2 (95 percent confidence interval, 1.1 to 4.3), respectively (P for trend = 0.01). CONCLUSIONS: There is a direct association between second-trimester maternal serum alpha-fetoprotein levels and the risk of SIDS, which may be mediated in part through impaired fetal growth and preterm birth.

Factors predisposing to perinatal death related to uterine rupture during attempted vaginal birth after caesarean section: retrospective cohort study.

OBJECTIVE: To determine the factors associated with an increased risk of perinatal death related to uterine rupture during attempted vaginal birth after caesarean section. DESIGN: Population based retrospective cohort study. SETTING: Data from the linked Scottish Morbidity Record and Stillbirth and Infant Death Survey of births in Scotland, 1985-98. PARTICIPANTS: All women with one previous caesarean delivery who gave birth to a singleton infant at term by a means other than planned repeat caesarean section (n = 35 854). MAIN OUTCOME MEASURES: All intrapartum uterine rupture and uterine rupture resulting in perinatal death (that is, death of the fetus or neonate). RESULTS: The overall proportion of vaginal births was 74.2% and of uterine rupture was 0.35%. The risk of intrapartum uterine rupture was higher among women who had not previously given birth vaginally (adjusted odds ratio 2.5, 95% confidence interval 1.6 to 3.9, P < 0.001) and those whose labour was induced with prostaglandin (2.9, 2.0 to 4.3, P < 0.001). Both factors were also associated with an increased risk of perinatal death due to uterine rupture. Delivery in a hospital with < 3000 births a year did not increase the overall risk of uterine rupture (1.1, 0.8 to 1.5, P = 0.67). However, the risk of perinatal death due to uterine rupture was significantly higher in hospitals with < 3000 births a year (one per 1300 births) than in hospitals with >or= 3000 births a year (one per 4700; 3.4, 1.0 to 14.3, P = 0.04). CONCLUSION: Women who have not previously given birth vaginally and those whose labour is induced with prostaglandin are at increased risk of uterine rupture when attempting vaginal birth after caesarean section. The risk of consequent death of the infant is higher in units with lower annual numbers of births.

Caesarean section and risk of unexplained stillbirth in subsequent pregnancy.

BACKGROUND: Caesarean section is associated with an increased risk of disorders of placentation in subsequent pregnancies, but effects on the rate of antepartum stillbirth are unknown. We aimed to establish whether previous caesarean delivery is associated with an increased risk of antepartum stillbirth. METHODS: We linked pregnancy discharge data from the Scottish Morbidity Record (1980-98) and the Scottish Stillbirth and Infant Death Enquiry (1985-98). We estimated the relative risk of antepartum stillbirth in second pregnancies using time-to-event analyses. FINDINGS: For 120633 singleton second births, there were 68 antepartum stillbirths in 17754 women previously delivered by caesarean section (2.39 per 10000 women per week) and 244 in 102879 women previously delivered vaginally (1.44; p<0.001). Risk of unexplained stillbirth associated with previous caesarean delivery differed significantly with gestational age (p=0.04); the excess risk was apparent from 34 weeks (hazard ratio 2.23 [95% CI 1.48-3.36]). Risk was not attenuated by adjustment for maternal characteristics or outcome of the first pregnancy (2.74 [1.74-4.30]). The absolute risk of unexplained stillbirth at or after 39 weeks' gestation was 1.1 per 1000 women who had had a previous caesarean section and 0.5 per 1000 in those who had not. The difference was due mostly to an excess of unexplained stillbirths among women previously delivered by caesarean section. INTERPRETATION: Delivery by caesarean section in the first pregnancy could increase the risk of unexplained stillbirth in the second. In women with one previous caesarean delivery, the risk of unexplained antepartum stillbirth at or after 39 weeks' gestation is about double the risk of stillbirth or neonatal death from intrapartum uterine rupture.