Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration.

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions. Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses. Design: We will develop deeper understanding of 'burdensomeness' and 'complexity' through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential 'preventable moments', defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout.

A conceptual framework for characterising lifecourse determinants of multiple long-term condition multimorbidity.

Objective: Social, biological and environmental factors in early-life, defined as the period from preconception until age 18, play a role in shaping the risk of multiple long-term condition multimorbidity. However, there is a need to conceptualise these early-life factors, how they relate to each other, and provide conceptual framing for future research on aetiology and modelling prevention scenarios of multimorbidity. We develop a conceptual framework to characterise the population-level domains of early-life determinants of future multimorbidity. Method: This work was conducted as part of the Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B) study. The conceptualisation of multimorbidity lifecourse determinant domains was shaped by a review of existing research evidence and policy, and co-produced with public involvement via two workshops. Results: Early-life risk factors incorporate personal, social, economic, behavioural and environmental factors, and the key domains discussed in research evidence, policy, and with public contributors included adverse childhood experiences, socioeconomics, the social and physical environment, and education. Policy recommendations more often focused on individual-level factors as opposed to the wider determinants of health discussed within the research evidence. Some domains highlighted through our co-production process with public contributors, such as religion and spirituality, health screening and check-ups, and diet, were not adequately considered within the research evidence or policy. Conclusions: This co-produced conceptualisation can inform research directions using primary and secondary data to investigate the early-life characteristics of population groups at risk of future multimorbidity, as well as policy directions to target public health prevention scenarios of early-onset multimorbidity.

Exploring the associations between number of children, multi-partner fertility and risk of obesity at midlife: Findings from the 1970 British Cohort Study (BCS70).

BACKGROUND: Early parenthood, high parity, and partnership separation are associated with obesity. However, the emergence of non-marital partnerships, serial partnering and childbearing across unions, means that it is important to consider their association to obesity. This paper examined the associations between number of biological children and multi-partner fertility (MPF)-defined as having biological children with more than one partner, with obesity at midlife. METHOD: The sample consisted of 2940 fathers and 3369 mothers in the 1970 British Cohort Study. The outcome was obesity (BMI 30 or over) at age 46. Fertility and partnership histories ascertained the number of live biological children and MPF status by age 42. The associations were tested using logistic regression adjusting for confounders at birth, age 10 and age 16. Adult factors recorded at age 42 including age at first birth, smoking status, alcohol dependency, educational attainment and housing tenure were considered as mediators. RESULTS: For fathers, obesity odds did not differ according to number of children or MPF. In unadjusted models, mothers with one child (OR 1.24 95%CI 1.01-1.51), mothers who had two children with two partners (OR 1.45 95%CI 1.05-1.99), and mothers who had three or more children with two or more partners (OR 1.51 95%CI 1.18-1.93) had higher odds of obesity. In adjusted models, there remained an association between mothers with one child and odds of obesity (OR 1.30 95%CI 1.05-1.60). All other associations were attenuated when confounders were included. CONCLUSIONS: Mothers who had children with multiple partners had higher odds of obesity. However this association was completely attenuated when parental and child confounders were accounted for; suggesting that this association may be explained by confounding. Mothers who had one child only may be at increased odds of obesity, however this could be due to multiple factors including age at first birth.

Sleep hours and quality before and after baby: Inequalities by gender and partnership.

While prior studies have examined sleep across the lifecourse, few studies have investigated sleep around the birth of a child, one of the most important events to cause sleep deprivation. This study investigates changes in sleep hours and quality, paying attention to differences by gender and partnership status. Using the UK Household Longitudinal Study, we follow approximately 1,000 participants as they transition into parenthood in a three-year window. We use OLS and logistic regression to analyze changes in sleep hours and sleep quality. Results suggest that women's sleep is reduced by an average of 0.7 hours (42 min) on becoming a mother. Whilst before parenthood women sleep more than men, after childbirth women and men sleep similar amounts. Cohabiting men experience a greater reduction in sleep by around 0.5 hours (30 min) than married men, to the level similar to women, suggesting that new cohabiting fathers may experience more sleep disturbances.

Uncertain steps into adulthood: Does economic precariousness hinder entry into the first co-residential partnership in the UK?

This study uses prospective data spanning 27 years (1991-2018) to explore the relationship between economic precariousness and transitions to first co-residential partnership among Britons aged 18-34 across three dimensions: age, historical time, and sex. Economic precariousness is measured using eight objective and subjective indicators, including income, employment, housing, and financial perceptions. Our results show that economic precariousness has a strong negative relationship with entering the first co-residential partnership among those aged 20-30, but the pattern is less clear among the youngest and oldest. Objective measures are easier to interpret than subjective measures. Historical analyses suggest that not being employed decreases the probability of union formation more in recessionary periods than in non-recessionary ones. Among working women, low labour income started to be a predictor of union formation in the most recent periods. Labour income is the only indicator presenting trends in line with our hypotheses across all dimensions.

The mediating pathways between parental separation in childhood and offspring hypertension at midlife.

Social life course determinants of adult hypertension are relatively unknown. This paper examines how parental separation before age 10 relates to hypertension at age 46. Adjusting for parental confounders and considering the role of adult mediators, we aim to quantify unexplored mediating pathways in childhood using prospectively collected data. Data from the 1970 British Birth Cohort Study are utilised. Hypertension is measured by health care professionals at age 46. Potential mediating pathways in childhood include body mass index (BMI), systolic and diastolic blood pressure, illness, disability, family socioeconomic status (SES) and cognitive and developmental indicators at age 10. Additionally, we explore to what extent childhood mediators operate through adult mediators, including health behaviours, family SES, BMI and mental wellbeing. We also test for effect modification of the relationship between parental separation and hypertension by gender. Nested logistic regression models test the significance of potential mediating variables. Formal mediation analysis utilising Karlson Holm and Breen (KHB) method quantify the direct and indirect effect of parental separation on offspring hypertension at midlife. There was an association between parental separation and hypertension in mid-life in women but not men. For women, family SES and cognitive and behavioural development indicators at age 10 partly mediate the relationship between parental separation and hypertension at age 46. When adult mediators including, health behaviours, family SES, BMI and mental wellbeing are included, the associations between the childhood predictors and adult hypertension are attenuated, suggesting that these childhood mediators in turn may work through adult mediators to affect the risk of hypertension in midlife. We found family SES in childhood, cognitive and behaviour development indicators at age 10, including disruptive behaviour, coordination and locus of control in childhood, to be important mediators of the relationship between parental separation and midlife hypertension suggesting that intervening in childhood may modify adult hypertension risk.

Understanding the early life mediators behind the intergenerational transmission of partnership dissolution.

Whilst research has demonstrated an intergenerational transmission of partnership dissolution, there is limited evidence as to the early life course pathways through which these associations operate, and whether these differ by gender. Many studies have not considered prospective data from early childhood, thus potentially neglecting the importance of the early childhood period in explaining this intergenerational transmission. Given that serial partnering has become increasingly commonplace it is important research considers those who experience multiple partnership dissolution. This paper examines, using data from the 1970 British Birth Cohort Study, the early life mediators underpinning the association between parental separation and the number of offspring partnership dissolutions. Among both men and women there is a significant unadjusted relationship between parental separation and the experience of multiple partnership dissolutions in adulthood. These associations were reduced once parental confounders and childhood mediators are included. Formal mediation analyses demonstrated that early life mediators accounted for more of the association in men than women. Mediators included childhood living standards, and for men child cognition and child behaviour, and for women maternal mental wellbeing. Parental separation and many early life mediators were related to the likelihood of multiple partnership dissolutions through age at first partnership.

Maternal smoking behaviour across the first two pregnancies and small for gestational age birth: Analysis of the SLOPE (Studying Lifecourse Obesity PrEdictors) population-based cohort in the South of England.

Maternal smoking is established to cause adverse birth outcomes, but evidence considering maternal smoking change across successive pregnancies is sparse. We examined the association between self-reported maternal smoking during and between the first two pregnancies with the odds of small for gestational age (SGA) birth (<10th percentile) in the second infant. Records for the first two pregnancies for 16791 women within the SLOPE (Studying Lifecourse Obesity PrEdictors) study were analysed. This is a population-based cohort of prospectively collected anonymised antenatal and birth healthcare data (2003-2018) in Hampshire, UK. Logistic regression was used to relate maternal smoking change to the odds of SGA birth in the second infant. In the full sample, compared to never smokers, mothers smoking at the start of the first pregnancy had higher odds of SGA birth in the second pregnancy even where they stopped smoking before the first antenatal appointment for the second pregnancy (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.10, 2.03]). If a mother was not a smoker at the first antenatal appointment for either her first or her second pregnancy, but smoked later in her first pregnancy or between pregnancies, there was no evidence of increased risk of SGA birth in the second pregnancy compared to never smokers. A mother who smoked ten or more cigarettes a day at the start of both of her first two pregnancies had the highest odds of SGA birth (3.54 [2.55, 4.92]). Women who were not smoking at the start of the first pregnancy but who subsequently resumed/began smoking and smoked at the start of their second pregnancy, also had higher odds (2.11 [1.51, 2.95]) than never smokers. Smoking in the first pregnancy was associated with SGA birth in the second pregnancy, even if the mother quit by the confirmation of her second pregnancy.

The Changing Association Between Homeownership and the Transition to Parenthood.

The literature suggests a positive link between homeownership and the transition to parenthood. However, in recent decades, couples' preference for becoming homeowners before having their first child has been undermined by rising housing unaffordability and housing uncertainty. An archetypal example is Britain, where homeownership rates among young adults have fallen substantially as a result of low wages, unemployment, reductions in the availability of mortgage credit, and rising house prices. This situation has produced a housing crisis. Using longitudinal data from the British Household Panel Survey (1991-2008) and the United Kingdom Household Longitudinal Study (2009-2016), we apply multilevel, discrete-time event-history techniques to a sample of women aged 18-42. We investigate whether and how the link between homeownership and entering parenthood has changed in Britain in recent decades. Our findings reveal that in comparison with the 1990s, the likelihood of becoming a parent has declined among homeowners, whereas childbearing rates among private renters have remained stable. Thus, owner-occupiers and private renters have become more similar in terms of their likelihood of entering parenthood. Overall, our findings question the classical micro-level assumption of a positive link between homeownership and transition to parenthood, at least among Britain's "Generation Rent." These findings are subsequently interpreted in terms of increased housing uncertainty.

Trends in the prevalence and incidence of orphanhood in children and adolescents <20 years in rural KwaZulu-Natal South Africa, 2000-2014.

BACKGROUND: In South Africa, large increases in early adult mortality during the 1990s and early 2000s have reversed since public HIV treatment rollout in 2004. In a rural population in KwaZulu-Natal, we investigate trends in parental mortality and orphanhood from 2000-2014. METHODS: Using longitudinal demographic surveillance data for a population of approximately 90,000, we calculated annual incidence and prevalence of maternal, paternal and double orphanhood in children and adolescents (<20 years) and, overall and cause-specific mortality of parents by age. RESULTS: The proportion of children and adolescents (<20 years) for whom one or both parents had died rose from 26% in 2000 to peak at 36% in 2010, followed by a decline to 32% in 2014. The burden of orphanhood remains high especially in the oldest age group: in 2014, 53% of adolescents 15-19 years had experienced the death of one or both parents. In all age groups and years, paternal orphan prevalence was three-five times higher than maternal orphan prevalence. Maternal and paternal orphan incidence peaked in 2005 at 17 and 27 per 1,000 person years respectively (<20 years) before declining by half through 2014. The leading cause of parental death throughout the period, HIV/AIDS and TB cause-specific mortality rates declined substantially in mothers and fathers from 2007 and 2009 respectively. CONCLUSIONS: The survival of parents with children and adolescents <20 years has improved in tandem with earlier initiation and higher coverage of HIV treatment. However, comparatively high levels of parental deaths persist in this rural population in KwaZulu-Natal, particularly among fathers. Community-level surveillance to estimate levels of orphanhood remains important for monitoring and evaluation of targeted state welfare support for orphans and their guardians.

Understanding the decline in under-18 conception rates throughout England's local authorities between 1998 and 2017.

We consider England's two-decade teenage conception decline in the context of societal changes: rising educational aspirations; growing second- and third-generation teenage ethnic minority populations; increased deprivation associated with economic recession and post-2008 Government austerity; and changing housing availability. Using England's Local Authority Districts (LAD) 1998-2017, we explore the role of area characteristics in explaining spatial differences in under-18 conception rates and how changing characteristics may explain temporal changes. Urban/rural distinctions in teenage conceptions are largely minimised after considering LAD characteristics. Area characteristics continue to partly explain teenage conception rates but are better at explaining area differences than variation over time.

Change in modifiable maternal characteristics and behaviours between consecutive pregnancies and offspring adiposity: A systematic review.

Causal evidence links modifiable maternal exposures during the periconceptional period with offspring obesity. The interconception period may be an important time to intervene. We systematically identified studies examining change in modifiable maternal exposures between pregnancies and offspring adiposity. We searched for longitudinal studies published between 1990 and 2019, which included measurements taken on at least two occasions in the period from 1 year prior to the conception of the first birth to the time of the second birth, and which included a measure of adiposity in second, or higher order, siblings. Age, ethnicity and genetics were not considered modifiable; all other factors including length of the interpregnancy interval were. Eleven studies satisfied the inclusion criteria. Higher interpregnancy weight gain or loss, maternal smoking inception, mothers smoking in their first pregnancy and quitting, increasing the number of cigarettes smoked and longer interpregnancy intervals were positively associated with adiposity in second or higher order children. Vaginal birth after caesarean delivery was protective. Further research is needed to ascertain whether the risk of adiposity is fixed based on first pregnancy exposures or if interpregnancy change alters the risk for a subsequent child. This can inform the type and effectiveness of interventions for mothers prior to a subsequent pregnancy.

Socioeconomic risk factors for labour induction in the United Kingdom.

BACKGROUND: Labour induction is a childbirth intervention experienced by a growing number of women globally each year. While the maternal and socioeconomic indicators of labour induction are well documented in countries like the United States, considerably less research has been done into which women have a higher likelihood of labour induction in the United Kingdom. This paper explores the relationship between labour induction and maternal demographic, socioeconomic, and health indicators by parity in the United Kingdom. METHOD: Logistic regression analyses were conducted using the first sweep of the Millennium Cohort Study, including a wide range of socioeconomic factors such as maternal educational attainment, marital status, and electoral ward deprivation, in addition to maternal and infant health indicators. RESULTS: In fully adjusted models, nulliparous and multiparous women with fewer educational qualifications and those living in disadvantaged places had a greater likelihood of labour induction than women with higher qualifications and women in advantaged electoral wards. CONCLUSIONS: This paper highlights which UK women are at higher risk of labour induction and how this risk varies by socioeconomic status, demonstrating that less advantaged women are more likely to experience labour induction. This evidence could help health care professionals identify which patients may be at higher risk of childbirth intervention.

Associations between birth order with mental wellbeing and psychological distress in midlife: Findings from the 1970 British Cohort Study (BCS70).

BACKGROUND: Previous research indicated that birth order was associated with physical health outcomes in adulthood. However, evidence on its association with mental health was lacking. The aim of this study was to investigate if birth order was associated with mental wellbeing and psychological distress at mid-life, stratified by gender, and taking into account confounding factors in childhood and adulthood. METHOD: The sample consisted of 9,354 participants of the 1970 British Cohort Study (BCS70). The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), the Malaise Index and attending a doctor's consultation in the past year for a mental health issue at age forty-two were used to assess mental wellbeing and psychological distress in midlife. Birth order was ascertained via a parental questionnaire and referred to the numerical birth position of the participants. The associations between birth order, mental wellbeing and psychological distress were tested using linear and logistic regression adjusting for birth characteristics: smoking during pregnancy, maternal age, mother's marital status, father's employment, region of birth, parental years of education and parental social class, and factors at age 42: years of education, employment status and partnership status. Potential mediating variables including breastfeeding and birthweight at birth and parental separation and conduct disorder measured at age ten were also taken into account. RESULTS: We find no evidence to support an association between birth order and midlife psychological distress or attending a doctor's consultation in both men and women. In unadjusted analysis, there was an association between birth order four and above and a reduced WEMWBS score of -0.79 (95% CI -1.57, -0.02) in men only. This association was attenuated after adjusting for birth characteristics and mediators at birth (0.86, 95% -1.78, 0.07) but was maintained once conduct disorder at age 10 was accounted for (-1.19, 95% CI -2.28, -0.09). However, this association was attenuated once again after adjusting for employment status, years in education and partnership status in adulthood (-1.04, 95% CI -2.11, 0.03). CONCLUSIONS: In this study, birth order was not associated with psychological distress or having a mental health issue at midlife. Accounting for employment status, years of education and partnership status in adulthood attenuated the relationship between birth order and mental wellbeing.

Ethnic Differences in Returning Home: Explanations From a Life Course Perspective.

Ethnic differences in leaving and returning home may reflect varying cultural norms regarding intergenerational coresidence, but also differences in transitions in linked domains, for example, employment and partnership transitions. This study uses Dutch population register data to compare returning home among second-generation Turks, Moroccans, Surinamese, and Antilleans with native Dutch who had left the parental home between age 16 and 28 in the period 1999 to 2011 (N = 194,020). All second-generation groups were found to be more likely to return home than native Dutch. A large part of these differences was related to the timing and occurrence of other key events in the life course, such as age at leaving home and partnership dissolution. Although the impact of partnership dissolution on returning home was found to be strong among all origin groups, it was less pronounced among second-generation youth, particularly Turks and Moroccans, than native Dutch youth. Possible explanations and implications are discussed.

Living alone and psychological well-being in mid-life: does partnership history matter?

BACKGROUND: Previous studies have found that the duration since a union dissolution and the number of union dissolutions are associated with psychological well-being. However, these two aspects of partnership history have rarely been considered jointly in models of mental health. This study aims to investigate how the time since the most recent union dissolution and the number of union dissolutions are related to two indicators of psychological well-being-life satisfaction and the General Health Questionnaire-among middle-aged solo-living British men and women. METHODS: Data from the United Kingdom Household Longitudinal Study from 2009 to 2010 are analysed for 1201 50-64 year olds who were living alone and have ever been in a co-resident union (472 men and 729 women). Logistic regression analysis is used to investigate how life satisfaction and General Health Questionnaire 12 (GHQ-12) caseness are associated with partnership characteristics. RESULTS: GHQ-12 caseness is significantly and positively associated with the number of union dissolutions and negatively with the duration since the most recent union dissolution. This is the case among both genders, in models in which these partnership characteristics are entered separately and jointly, and in models controlling for parenthood status, socioeconomic status and physical health. CONCLUSIONS: The results suggest that there is a short-term deterioration in mental health after a partnership break-up and that experiencing multiple union dissolutions is detrimental for psychological well-being. The association between partnership characteristics and the two measures of psychological well-being differs, which is in line with previous research showing that negative affect and life satisfaction are two separate constructs.

Gender, turning points, and boomerangs: returning home in young adulthood in Great Britain.

The idea of a generation of young adults "boomeranging" back to the parental home has gained widespread currency in the British popular press. However, there is little empirical research identifying either increasing rates of returning home or the factors associated with this trend. This article addresses this gap in the literature using data from a long-running household panel survey to examine the occurrence and determinants of returning to the parental home. We take advantage of the longitudinal design of the British Household Panel Survey (1991-2008) and situate returning home in the context of other life-course transitions. We demonstrate how turning points in an individual's life course-such as leaving full-time education, unemployment, or partnership dissolution-are key determinants of returning home. An increasingly unpredictable labor market means that employment cannot be taken for granted following university graduation, and returning home upon completion of higher education is becoming normative. We also find that gender moderates the relationship among partnership dissolution, parenthood, and returning to the parental home, reflecting the differential welfare support in Great Britain for single parents compared with nonresident fathers and childless young adults.