Obstetrical Complications and Chronic Health Along the Lifecourse: What We Know, What We Don’t, and Where We Go From Here?

The demographic and clinical characteristics of women of reproductive age have undergone dramatic shifts in recent decades. This includes women postponing their first pregnancies, an increase in the prevalence of underlying health conditions, and a rising use of assisted reproductive technologies. These trends have, in part, contributed to the increase in obstetrical complications and severe maternal morbidity and mortality prompting a shift in the management and counseling of women before, during, and after pregnancy. Additionally, accumulating evidence has highlighted the link between obstetrical complications, and an increased burden of chronic conditions in both mothers and offspring.¹ These obstetrical complications include hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, and preterm delivery. While existing studies have laid the groundwork for understanding the underlying aetiologies of obstetrical complications, further research is needed to gain a better understanding of the complex interplay of risk factors in the development of health conditions throughout a woman’s life, particularly how her complete reproductive and clinical history may influence and contribute to these outcomes. This special issue of Paediatric and Perinatal Epidemiology is a collection of studies that examines how preconception and perinatal risk factors influence chronic health conditions throughout the life span of women and children. We highlight the unique contributions of these studies in how they fill important gaps in our current knowledge of how obstetrical complications shape the risks of chronic health across the life course and discuss areas for future work. Every study that is featured in this special issue is accompanied by a commentary by experts in the field.

Preconception exposures

An important facet of this research is the influence of preconception (both in early life and before pregnancy) risk factors on the risk of both obstetrical complications and chronic conditions across the life course. Brown and colleagues² identified patterns of co-occurring chronic conditions among women of reproductive age using validated algorithms and latent class analyses. In a population-based cohort of pregnant women in Ontario, Canada, with universal healthcare coverage, they grouped preconception patterns of multiple chronic conditions. Importantly, they included all recognised pregnancies to improve the generalisability of the findings. Using validated algorithms to define chronic comorbidities and clinical judgment to classify these conditions into distinct subgroups, they identified four classes of subgroups of conditions with mood and anxiety disorders included in all four groups.

Rasmussen and colleagues³ further explored the role of preconception factors through their examination of the effects of maternal and paternal macrosomia on infant birthweight. Leveraging the longitudinal availability of data from mothers and fathers in the Norwegian Birth Registry, the authors explored both the role of maternal and parental history of macrosomia and maternal history of macrosomia in combination with preconception body mass index (BMI). Accounting for several important confounders, the research points to the potential influence of parental birthweight and maternal prepregnancy BMI to an infant’s birthweight.

Harville and colleagues⁴ in a similar manner assessed how trajectories of cardiovascular risk factors in childhood shaped pregnancy and birth outcomes in adulthood. Using the International Childhood Cardiovascular Consortium—The Bogalusa Heart Study and the and the Cardiovascular Risk in Young Finns Study, the authors followed children up until early adulthood and assessed the contribution of traditional cardiovascular risk factors to the risk of obstetrical complications within two distinct cohorts. Leveraging longitudinal repeat measures of clinical, biochemical, and anthropometric measures across the life span, the research was able to define distinct patterns across seven individual cardiovascular risk factors and their association with maternal and infant pregnancy complications. Across the seven risk factors, stable and worsening trajectories were associated with obstetrical complications. These works suggest that examining the role of preconception risk factors to the development of obstetrical complications and chronic conditions across the lifespan is feasible but relies on the availability of longitudinal cohorts with historical data across the lifespan.

Short-term maternal outcomes

While prior studies have consistently pointed to the impact of obstetrical complications on long-term maternal morbidity and mortality,¹ the impact on short-term maternal outcomes primarily in the immediate post-partum period (<1 year following delivery) requires further attention. Magnus and colleagues⁵ examine the influence of the use of assisted reproductive technologies on the risk of stroke in the first year following delivery. This registry-based cohort study included data from four Nordic countries (Denmark, Finland, Norway, and Sweden) with universal healthcare coverage, longitudinal follow-up, and information on important confounders (e.g., parity). The research found no effect of assisted reproductive technologies on the risk of stroke within the first year following a delivery, which was consistent across the entire year of follow-up.

Lee and colleagues⁶ likewise examine the impact of HDP on cardiovascular mortality within the first year following a delivery. Using a nationally representative sample of in-hospital deliveries in the United States and information on cause-specific deaths, the research was able to examine cardiovascular-related mortality by subtypes of HDP. The authors found an association for all subtypes (except for gestational hypertension) with a consistent trend across the year following delivery. While these works provide important insights, they should be extended to identify high-quality sources of data that can be leveraged to improve surveillance of maternal morbidity and mortality in the immediate postpartum period.

Long-term maternal outcomes

Despite the accruing evidence on the impact of obstetrical complications on long-term maternal health, the ability to answer this question has relied on the availability of historical data with sufficient follow-up to expand the current knowledge gaps on the role of obstetrical complications to long-term health outcomes. Mitro and colleagues⁷ leveraged a cohort of women enrolled in the Collaborative Perinatal Project (1959-1966) to examine the risk of all-cause and cause-specific mortality associated with a history of multifetal gestations. Using a historical cohort of women with up to 57 years of follow-up and detailed data on obstetrical history, the study found no association between multifetal gestation and all-cause or cause-specific mortality. Though these findings were limited by the availability of information on pregnancies that occurred during the study period, details regarding a woman’s complete history of multifetal gestations were unavailable.

In contrast, Wyatt and colleagues⁸ leveraged the availability of the Norwegian birth registry linked to vital statistics data to examine the risk of CVD mortality associated with HDP across a woman’s lifetime reproductive history. Using the complete reproductive history of women, the research was able to examine the order and timing of HDP (preterm versus term) across pregnancies and how this impacts CVD risk. They found that CVD mortality was highest among women with two affected pregnancies, and a preterm HDP in the first pregnancy. Interestingly, this research challenges prior studies restricted to first pregnancies. These works highlight the need for longitudinal data with granular information on obstetrical and clinical history to ensure accurate estimation of the cumulative effects of obstetrical complications on long-term health outcomes.

Offspring outcomes

While the developmental origins of the adult disease hypothesis have long posited the influence of the intrauterine environment on the development of health conditions in children, the specific influence of preconception and perinatal risk factors on offspring health is less clear. Nielsen and colleagues⁹ aim to examine how cumulative exposures to inflammation influence attention-deficit/hyperactivity disorders (ADHD) in offspring. Using a population-based cohort of children in New South Wales, Australia with information from birth admissions and hospital admissions during pregnancy, they were able to capture information on preconception and pregnancy-related measures of inflammatory-related conditions. The research found an increased risk of ADHD in offspring across all seven inflammatory conditions, with a dose-dependent response by the number of conditions. While this work aligns with prior research, it highlights the need for further consideration of how composite exposures can be quantified and defined to optimise the identification of women and offspring at risk for future outcomes.

Methods and study design

A common thread that has resonated throughout the works presented in this special issue is the need for high-quality data and rigorous methods to accurately estimate the impact of obstetrical complications on health conditions in mothers and infants. The work by Johnston and colleagues¹⁰ echoes this point through their overview of methodological considerations for researchers examining the risk of cardiovascular disease (CVD) associated with a history of HDP using administrative data sources. They highlight the need for clearly defining the research question using a conceptual framework, robust metrics for the identification of study variables with established validity, and a fundamental knowledge of the underlying population from which the study population originates.

The need for robust and valid data sources is further emphasised by Ananth and colleagues,¹¹ in their work describing the design and process for data linkage for the construction of a longitudinal cohort of mothers-child dyads delivered (either liveborn or stillborn) in New Jersey, United States. They present the availability of detailed information on clinical and obstetrical characteristics that can inform current knowledge gaps regarding the contribution of placental abruption (and other obstetrical complications) to maternal and offspring health outcomes.

Next steps and future directions

Most studies have focused on CVD risks, but little is known about how prepregnancy and obstetrical complications affect the risks of other chronic conditions along the life course, including renal disorders, cancers, and neurological impairments, including dementia, Parkinson’s disease, and schizophrenia. We propose a blueprint that shows the progression of pre-existing risk factors from before pregnancy, complications that occur during pregnancy, the postpartum period, and beyond (Figure 1). While this list is not exhaustive, it summarises the current state of evidence and points to areas for future research.

Figure 1.

Progression of risk factors and medical conditions from pre-pregnancy to obstetrical complications during pregnancy, and postpartum periods on chronic conditions along the life course

Ongoing efforts to conceptualise how obstetrical complications impact the short- and long-term health of mothers and infants to inform prevention strategies and identify women at the highest risk are worthy targets to mitigate the risks of chronic conditions along the life course. Capitalising on the strengths of artificial intelligence and machine learning, prediction models that include pre-pregnancy risk factors, and biomarkers, to identify a sub-group of subjects at impending risk of chronic disease may lend well to design interventions to reduce the burden of CVD, haematologic, and neurologic sequelae (including Alzheimer’s disease, dementia, Parkinson’s disease, etc.). Needless to mention, these population-based efforts will require high-quality data sources and rigorous methods to optimise surveillance and quantification of effects. While gaining new epidemiologic and clinical insights to understand how obstetrical complications shape future risks of chronic conditions is incremental, we hope this special issue will spur broader debates on the topic and encourage investigators to accelerate the learning process. Such efforts will be a welcome addition to recognising how obstetrical complications impact the life course.

Biographies

Sonia Grandi is a Scientist in the Child Evaluative Sciences Program at the Research Institute at the Hospital for Sick Children and an Assistant Professor in the Division of Epidemiology at the Dalla Lana School of Public Health at the University of Toronto. Her research program is funded by the Canadian Institutes of Health Research and is focused on examining the role of adverse pregnancy outcomes in long-term cardiovascular health in mothers and the development of effective screening tools and targeted strategies for the early identification of women at risk of future cardiovascular disease. She is also interested in the application of novel methods in perinatal epidemiology and leveraging administrative health data to help inform clinical practice. She serves as a junior editor of Paediatric and Perinatal Epidemiology.

Cande V. Ananth is a Professor and Chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School, NJ. His research portfolio is funded by the National Institutes of Health and focuses on (i) Ischaemic placental disease, preterm delivery, and long-term risks of coronary heart disease and stroke outcomes in mothers and offspring along the life course; (ii) Impact of air pollution and weather exposures on ischaemic placental disease; and (iii) Applications of innovative analytic approaches, including causal models and mediation methods, to studies in human reproduction. He is the editor-in-chief of Paediatric and Perinatal Epidemiology.