Mapping domains of early life determinants of future multimorbidity across three UK longitudinal cohort studies.

Many studies use a reductionist approach to isolate the influence of one factor in childhood on multimorbidity rather than consider the combined effect of wider determinants. We explored how potential multiple early life determinants of multimorbidity can be characterised across three UK cohort studies. We used the National Child Development Study (NCDS), the 1970 British Cohort Study (BCS70), and the Aberdeen Children of the 1950s Study (ACONF) to identified early life variables that fit into 12 conceptualised domains of early life determinants of multimorbidity. Variables were assigned into 12 domains; principal component analysis reduced the dimensionality of the data and structured variables into subgroups. The data audit identified 7 domains in ACONF, 10 domains in NCDS and 12 domains in BCS70. Dominant components included maternal fertility histories within the prenatal, antenatal and birth domain, long-term illnesses within the child health domain, educational ability within the child education and health literacy domain, ethnicity within the demography domain, parental health behaviours within the transgenerational domain, housing within the socioeconomic domain and parental-child interactions within the parental-family domain. We demonstrated that if multiple large scale longitudinal studies are used, there is enough data available for researchers to consider conceptualising early life risk factors of multimorbidity across groups or domains. Such conceptualisation can help challenge the existing understanding of disease aetiology and develop new ideas for prevention of multimorbidity.

Pregnancy rates and outcomes in women with cystic fibrosis in the UK: comparisons with the general population before and after the introduction of disease-modifying treatment, 2003-17.

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment. DESIGN: A population-based longitudinal study, 2003-17. SETTING: United Kingdom. POPULATION: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. METHODS: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age. MAIN OUTCOME MEASURES: Pregnancy and live-birth rates and child gestational age. RESULTS: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age. CONCLUSIONS: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor. TWEETABLE ABSTRACT: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate.

Hospital admissions in infants with Down syndrome: a record-linked population-based cohort study in Wales.

BACKGROUND: Despite recent advances, mortality in children with Down syndrome remains five times higher than in the general population. This study aims to describe the burden, patterns and causes of hospital admissions in infants with Down syndrome, and compare this with infants without Down syndrome in a population-based cohort. METHODS: This study used data from the Wales Electronic Cohort for Children, a cohort of all children born in Wales between 1990 and 2012. The cohort was generated from routine administrative data, linked to create an anonymised data set within the Secure Anonymised Information Linkage databank. This analysis is based on all infants born between January 2003 and January 2012 who were followed to their first birthday, a move out of Wales, death, or until 31 October 2012 (end of follow-up). Infants with Down syndrome were identified using the Congenital Anomaly Register and Information Service in Wales. Multivariable Cox regression was used to compare the time to first hospital admission. Admission codes were used to identify the commonest indications for hospitalisation and to determine the presence of other congenital anomalies. RESULTS: We included 324 060 children, 356 of whom had Down syndrome. Of infants with Down syndrome, 80.3% had at least one hospital inpatient admission during the first year of life, compared with 32.9% of infants without Down syndrome. These first admissions were earlier [median of 6 days interquartile range (IQR) (3, 72) compared with 45 days [IQR 6, 166)] and longer [median of 4 days (IQR 1, 15) compared with 1 day (IQR 0, 3)] than in infants without Down syndrome. The most common causes of admissions were congenital abnormalities, respiratory diseases, conditions originating in the perinatal period and infectious diseases. The presence of other congenital abnormalities increased hospitalisations in all infants, but more so in infants with Down syndrome who spent a median of 21 days in hospital (IQR 11, 47) during their first year of life. CONCLUSION: Infants with Down syndrome are at high risk for early, more frequent and longer hospital admissions. Congenital heart disease and respiratory infections remain a major burden in this population. More research is needed to understand how to better manage these conditions particularly in the first month of life when most admissions occur.

Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

OBJECTIVES: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018. STUDY DESIGN: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets. METHODS: We used routine statistics from the Office for National Statistics for the period 2002-2018 on population and deaths in Wales stratified by age, gender, Welsh Index of Multiple Deprivation (WIMD) 2019 quintile and cause of death, categorised by International Classification of Disease, version 10, code into 15 categories of public health relevance. We aggregated data to 3-year rolling figures to account for low numbers of events in some groups annually. Next, we estimated life expectancy at birth by quintile, gender and period using life table methods. Lastly, we performed a decomposition analysis using the Arriaga method to identify the specific disease categories and ages at which excess deaths occur in more disadvantaged areas to highlight potential areas for action. RESULTS: Life expectancy inequalities between the most and least WIMD quintiles rose for both genders between 2002 and 2018: from 4.69 to 6.02 years for women (an increase of 1.33 years) and from 6.34 to 7.42 years for men (an increase of 1.08 years). Exploratory analysis of these trends suggested that the following were most influential for women: respiratory disease (1.50 years), cancers (1.36 years), circulatory disease (1.35 years) and digestive disease (0.51 years). For men, the gap was driven by circulatory disease (2.01 years), cancers (1.39 years), respiratory disease (1.25 years), digestive disease (0.79 years), drug- and alcohol-related conditions (0.54 years) and external causes (0.54 years). Contributions for women from respiratory disease, cancers, dementia and drug- and alcohol-related conditions appeared to be increasing, while among men, there were rising contributions from respiratory, digestive and circulatory disease. CONCLUSIONS: Life expectancy inequalities in Wales remain wide and have been increasing, particularly among women, with indications of worsening trends since 2010 following the introduction of fiscal austerity. As agencies recover from the pandemic, these findings should be considered alongside any resumption of services in Wales or future health and public policy.

Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study.

OBJECTIVES: Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years. STUDY DESIGN: The study design used in the study is a population-based electronic cohort study. METHODS: We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors. RESULTS: There were 107,479 and 43,648 children included in the analysis, with follow-up to 6-7 years (KS1) and 10-11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09-1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10-1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37-1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04-1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84-2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment. CONCLUSION: The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation.

Evaluation of the effectiveness of the Family Nurse Partnership home visiting programme in first time young mothers in Scotland: a protocol for a natural experiment.

INTRODUCTION: Individual, social and economic circumstances faced by young mothers (19 years or under) can challenge a successful start in life for their children. Intervening early might enhance life chances for both mother and child. The Family Nurse Partnership (FNP) is an intensive nurse-led home visiting programme developed in the US which aims to improve prenatal health behaviours, birth outcomes, child development and health outcomes, and maternal life course. Establishing evidence of effectiveness beyond the original US setting is important to understand where further adaptation is required within a country specific context. OBJECTIVE: This study will form one strand of the Scottish Government's plan to evaluate the effectiveness of FNP as compared to usual care for mothers and their children in Scotland and will focus only on outcomes that can be identified using routine administrative data systems. METHODS: This study is a natural experiment with a case-cohort design using linked anonymised routine health, educational and social care data. Cases will be women enrolled as FNP Clients in ten NHS Health Boards in Scotland and Controls will be women who met FNP eligibility criteria but were pregnant at a time when the programme was not recruiting. Outcomes are mapped to the Scottish FNP logic model. All comparative analyses will be pre-specified, conducted on an intention to treat basis and will use multilevel regression models to compare outcomes between groups. DISCUSSION: The study protocol is based upon the specification of FNP commissioned by the Scottish Government. This study design is novel for the evaluation of the FNP/NFP programmes which are primarily evaluated with an RCT. Outcomes included within the study have been selected on the basis that they are outcomes FNP aims to influence and where there is routine data available to assess the outcome.

The causal web of foetal alcohol spectrum disorders: a review and causal diagram.

Foetal alcohol spectrum disorders (FASDs) are a leading cause of developmental disability. Prenatal alcohol use is the sole necessary cause of FASD, but it is not always sufficient. Multiple factors influence a child's susceptibility to FASD following prenatal alcohol exposure. Much of the FASD risk factor literature has been limited to discussions of association, rather than causation. While knowledge of predictor variables is important for identifying who is most at risk of FASD and for targeting interventions, causal knowledge is important for identifying effective mechanisms for prevention and intervention programmes. We conducted a systematic search and narrative synthesis of the evidence and used this to create a causal diagram (directed acyclic graph; DAG) to describe the causal pathways to FASD. Our results show that the aetiology of FASD is multifaceted and complex. FASD risk is determined by a range of lifestyle, sociodemographic, maternal, social, gestational, and genetic factors. The causal diagram that we present in this review provides a comprehensive summary of causal risk factors for FASD and can be used as a tool to inform data collection and statistical modelling strategies to minimise bias in future studies of FASD.

Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.

INTRODUCTION: Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic. AIMS AND OBJECTIVES: This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation. METHODS: Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked. CONCLUSION: We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.

Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study.

BACKGROUND: The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening. METHODS: We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20yrs. RESULTS: Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results. CONCLUSION: The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended.

Birth outcomes following treatment for precancerous changes to the cervix: a population-based record linkage study.

OBJECTIVE: To examine whether treatments for precancerous changes to the cervix are associated with adverse birth outcomes in subsequent pregnancies. DESIGN: Population-based retrospective cohort study using electronic linkage of data from the Welsh cervical screening programme and a national routine child health database. SETTING: Wales. POPULATION: A total of 174,325 women aged 20-39 years who received cervical screening between April 2001 and March 2004. METHODS: Logistic regression was used to compare the odds of each birth outcome between women who had negative cervical smears and women who received either colposcopy ± punch biopsy only or colposcopy and excisional or ablative treatments, adjusted for confounding factors (e.g. age, social deprivation and smoking). MAIN OUTCOME MEASURES: Preterm birth (before 37, 32 and 28 weeks of gestation), and low birthweight (<2500 g). RESULTS: Compared with women who had negative cervical smears, the odds ratio for preterm birth (<37 weeks) was significantly increased in women who had colposcopy only (adjusted odds ratio 1.54, 95% CI 1.32-1.80) and single excisional treatment (adjusted odds ratio 1.77, 95% CI 1.47-2.13). Similar results were observed for preterm birth at <32 weeks of gestation. There was no increased risk of preterm birth or low birthweight for women who had treatment compared with women who had colposcopy only. CONCLUSION: Women who were referred for colposcopy had an increased risk of preterm births regardless of whether or not they received treatment to the cervix. This increased risk could be the result of common risk factors for abnormal smears and preterm birth.

Interventions at caesarean section for reducing the risk of aspiration pneumonitis.

BACKGROUND: Various interventions are used as prophylaxis for aspiration pneumonitis in obstetric anaesthesia. This review, based on a Cochrane systematic review currently being updated, examines whether interventions given before caesarean section reduce the risk of aspiration pneumonitis. METHODS: Twenty-two studies, involving 2658 women providing data in a usable format for meta-analysis were identified. RESULTS: Compared to no treatment or placebo, there was a significant reduction in the risk of intra-gastric pH <2.5 with antacids (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.09-0.32), H2 antagonists (RR 0.09, 95% CI 0.05-0.18) and proton-pump antagonists (RR 0.26, 95% CI 0.14-0.46). H2 antagonists were associated with a reduced risk of intra-gastric pH <2.5 when compared with proton-pump antagonists (RR 0.39, 95% CI 0.16-0.97), but compared with antacids the findings were unclear. Combined use of antacids plus H2 antagonists was associated with a significant reduction in the risk of intra-gastric pH <2.5 when compared with placebo (RR 0.02, 95% CI 0.00-0.15) or compared with antacids alone (RR 0.12, 95% CI 0.02-0.92). CONCLUSION: The quality of evidence was weak and may not reflect a reduction in the risk of aspiration pneumonitis since none of the studies assessed substantive clinical outcomes or potential adverse effects. Further work is required to validate the suitability of surrogate markers of pH and gastric volume for clinical outcomes in the context of aspiration pneumonitis.

The incidence and aetiology of epistaxis in infants: a population-based study.

OBJECTIVE: To estimate the incidence and describe the aetiology of epistaxis in infants. DESIGN: Population-based study including a retrospective hospital admission database analysis and a postal questionnaire to clinicians. SETTING: Wales, United Kingdom. METHODS: Cases of epistaxis over a 6-year period (1999-2004) were identified from the Patient Episode Dataset for Wales (PEDW) and validated using clinical information to calculate the population-based incidence and ascertain the causes of epistaxis in infants in Wales. RESULTS: 36 confirmed cases were identified over the 6-year period giving an estimated annual incidence of epistaxis of 19.3 (95% CI 14.0 to 26.7) per 100,000 infants. The median age at admission was 12 weeks (interquartile range 4-33) (min 1 week, max 49 weeks). 23 of the infants had a recognised cause for their epistaxis (trauma (five), coagulation disorder (four), congenital anomaly (two), acute rhinitis or coryza (11), abusive smothering event (one)). No cause for the epistaxis was identified for 13 cases. Coagulation disorder was excluded in seven of these 13 infants but in the other six no attempt was made to exclude this disorder. Child abuse was suspected but excluded in four of the 13 cases. CONCLUSION: Hospital admission for epistaxis is a rare event. In the majority of cases in this study a simple explanation was available and proven physical abuse was rare. A bleeding disorder should always be considered and, if additional evidence suggests physical abuse, this must be excluded.

Teenage pregnancy: who suffers?

In this review, we examine the epidemiology of teenage pregnancy (girls aged 15-17 years) in the UK and consider the evidence for its impact on the health and well-being of the mother, the baby, the father and society. There has been some decrease in the teenage pregnancy rate over the last decade in the UK but rates are still considerably higher than those in other European countries. Pregnancy and childbirth during the teenage years are associated with increased risk of poorer health and well-being for both the mother and the baby, possibly reflecting the socio-economic factors that precede early pregnancy and childbirth. There is little evidence concerning the impact of teenage fatherhood on health and future studies should investigate this. The effect on society is a perpetuation of the widening gap in health and social inequalities. Public health interventions should aim to identify teenagers who are vulnerable and support those who are pregnant with evidence based interventions such as teenage antenatal clinics and access to initiatives that provide support for early parenthood.

Perinatal and infant autopsy.

OBJECTIVES: To measure perinatal and infant autopsy rate in Wales over a 10-year period and study factors influencing the decision to perform an autopsy. DESIGN: Retrospective cohort analysis of data from the All Wales Perinatal Survey. METHODS: Autopsy rates were calculated over a 10-year period (1994-2003), and reasons for not performing an autopsy were noted. Two time periods, 1994-1996 and 2001-2003 were compared, to study changing autopsy patterns. RESULTS: Over the 10-year period, there were 4393 perinatal and infant deaths, with data available for 4306 (98%) cases. Consent for autopsy was requested in 89% of cases and granted in 68%. When compared, the 3-year cumulative autopsy rate fell from 67.5% (95% confidence interval (CI) 65% to 69%) in 1994-1996, to 52.7% (CI 49% to 55%) in 2001-2003. The difference in the proportion of autopsies performed between the two time periods was 14.8% (CI 11% to 18%). Parental consent was granted in 76.2% (CI 73% to 78%) of cases in 1994-1996 and 60% (CI 57% to 63%) of cases in 2001-2003. The difference in proportion in consent for autopsy in the two time periods was 16% (CI 12% to 20%). CONCLUSIONS: A decrease in perinatal and infant autopsy rates has been found in Wales over the past 10 years. Parental refusal has been the main cause of this decline.

How much variation in CS rates can be explained by case mix differences?

OBJECTIVE: To quantify the amount of variation in caesarean section (CS) rates between maternity units explained by case mix differences. DESIGN: Cross-sectional study. SETTING: All 216 maternity units in England and Wales. POPULATION: Women giving birth at these maternity units between May and July 2000. METHODS: Logistic regression models were developed to investigate the relationship between case mix characteristics, and odds of (i) CS before labour, (ii) CS in labour. Using these results, overall CS rates standardised for case mix were calculated for each maternity unit. Random-effects meta-analysis was used to examine heterogeneity between maternity units. MAIN OUTCOME MEASURES: CS before labour and CS during labour. RESULTS: Adjustment for case mix differences between maternity units explained 34% of the variance in CS rates. Odds of CS (before and in labour) increased with maternal age. Women from ethnic minority groups had lower odds of CS before labour, and increased odds of CS in labour. Women with a previous vaginal delivery had lower odds of CS, although the magnitude of this for CS before and in labour is markedly different. CONCLUSIONS: Case mix adjustment is important to enable understanding of the factors that influence the CS rate. These include organisational and staffing levels as well as women's preferences for childbirth and clinician's attitudes. An understanding of how these factors influence the CS rate is essential for evaluation of quality and appropriateness of obstetric care provided to women.

An audit of the management of induced abortion in England and Wales.

OBJECTIVES: To assess the quality of care provided to women undergoing induced abortion. METHODS: The design was a single round audit questionnaire aimed at the providers of abortion services throughout England and Wales (NHS hospitals, clinics under NHS, agency agreements and private units. The levels of care were assessed against agreed audit criteria. RESULTS: Responses were received from 240 (74%) of the 324 units providing abortion care in England and Wales. These units undertook 80% of the 176,000 termination procedures. Generally standards of care were appropriate, but there were clear areas for improvement including choice of method, infection screening, and delays in referral. A number of unnecessary investigations were still evident, including cross-matching, while lower doses and alternative drug regimens might reduce costs. Only half of the units audited procedures and complications. CONCLUSIONS: This audit was carried out prior to the publication of the RCOG evidence-based guideline and a further round of audit to assess the impact of the guideline should now be considered.

Interstitial cystitis coexisting with vulvar vestibulitis in a 4-year-old girl.

Interstitial cystitis (IC) is a disorder that is difficult to diagnose and is thought to be uncommon in children. We report the first case of IC coexisting with vulvar vestibulitis in a 4-year-old girl. She presented with urinary symptoms and pelvic and vulvar pain. Cystoscopic and histological investigation confirmed interstitial cystitis and vulvar vestibulitis. Gynecologists are often called upon to deal with symptoms referable to the genital tract. It is important to always include interstitial cystitis in the differential diagnosis of urinary symptoms associated with pelvic pain.