chasing lifetime risk factors in prenatal and early postnatal life

Preconceptional parental health, pregnancy health, and early infant environment play key roles in the child’s and later adult’s lifetime health.

These factors are explored in ‘BABY1000’, a pilot study meant to test a study design and identify factors acting over three periods to shape the individual’s future health.

The report of the study appeared in the BMJ.

Study: Cohort profile: the BABY1000 pilot prospective longitudinal birth cohort study based in Sydney, Australia. Image Credit: Meteoritka/Shutterstock.com 

Introduction

According to the developmental hypothesis, health and disease risk across an individual’s lifespan and of the following generations, depends on factors active during the first 1,000 days of life, beginning at conception and extending to the child’s second birthday.

These include environmental factors that affect epigenetic modification of the genome.

For instance, obesity appears to follow the same recurrence pattern across generations. Worldwide, obesity is increasing in prevalence. Therefore, many more children are being exposed to excessive nutrient availability in utero, feeding obesity to the next generation.

This points to the need for interventions that begin before conception if this cycle is to be broken. Other factors act adversely on the child’s long-term health, including the mother’s preconceptional weight, physical activity, weight gain during pregnancy, levels of stress, mental health, smoking, gestational diabetes, and the gut microbiome of the mother.

Little is known about how and when these factors act or how they may be mitigated. The current study is one of several aimed at identifying associated health factors and outcomes. Unlike other birth cohort studies, the data collection began before conception, broadening the field of investigation.

The focus of this study is on obesity as an intergenerational phenomenon. The study was conceived as a prospective pilot study to assess the feasibility and acceptability of the project.

Participants in the study were residents of Sydney, Australia, and all entered before or at 12 weeks from conception. All participants were followed up until postpartum, while children were followed up until two years.

What did the study show?

The study is ongoing. The findings available at present include participant demographic and dietary data at baseline, with a detailed description of how the research questions were arrived at and refined.

Some of the research questions eventually determined to be of top priority include whether early weight loss intervention, before or between pregnancies, helps better the outcomes for the offspring of mothers with excessive body mass; the best interventions to alleviate the adverse effects of overweight and obesity for both mothers and infants; how maternal dietary practices affect the cardiovascular and metabolic health of the offspring; the best pre conceptional diet pattern; how to optimize cardiometabolic health in infants with suboptimal birth weights; and mechanisms of long-term benefit in breastfed infants.

Questions that also made the list include those about breastfeeding strategies; infant gut microbiome with breast- vs. formula feeding or combined feeding; socioeconomic influences on maternal and baby health during and after pregnancy; influences on choice of diet in pregnancy; the role of social support groups; and the effect of insulin resistance before conception on glucose intolerance in and after pregnancy, and on the offspring.

A three-step process was used to finalize the research questions. First, potential questions were gathered during semi-structured interviews with scientists and health professionals in the field. This led to 134 questions covering the three life stages of preconception, pregnancy, and early life.

A workshop was then organized with three groups corresponding to the three life stages. Each group analyzed the questions relating to the corresponding life stages, adding their own, if any. The most relevant questions were submitted to the panel for a final selection.

The decisions as to the final 15 questions were made by an online survey to all the original attendees with others interested in this question. These questions were ranked by the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation).

All participants were 18 or older and planned conception within 6-12 months, but the majority (211/225) were within the first 13 weeks of pregnancy. Most attended a clinic at the Royal Prince Alfred Hospital (RPAH), Sydney, and intended to deliver at RPAH. This is among the largest public teaching hospitals in the city.

A few women were from other hospitals but were willing to share their data with the investigators.

Recruitment began in December 2017 and was slated to continue until August 2020. The onset of the pandemic led to earlier than expected shutting down recruitment, limiting the study size to 225 rather than the planned 250.

Moreover, follow-up was also limited by the public health restrictions on research imposed as part of pandemic measures. This inevitably affected study completeness.

Of the 225 participants, 180 remained in the study at the time of birthing, and ~120 had completed a questionnaire at six weeks postpartum. The mean age was 33 years, slightly higher than the national and state means of ~31 years. Half of the women were in their first pregnancy.

Half were born in Australia, and 55% were of European origin, followed by 31% who were Southern, Eastern, or Southeast Asian. No indigenous Australians participated, despite making up 5% of the pregnant population nationwide and state-wide.

About 40% were overweight or obese, compared to the 37% of RPAH birthing mothers or 42% in NSW.

Preconceptional dietary quality was inadequate by Australian norms. Nearly seven of eight women were getting too much energy from saturated fat before and during pregnancy.

Micronutrient intake from food was insufficient, with almost all women not receiving adequate iron from their food. About 80% did not meet dietary requirements for iodine or calcium either, important for the baby’s thyroid and bone metabolism, and about half were not getting enough dietary folate without supplements.

What are the implications?

This highlighted that maternal diet quality and nutrient intakes in the BABY1000 cohort may not be conducive to supporting optimal perinatal or long-term offspring health.”

Other large birth cohort studies are being conducted across Australia, such as The Origins Project, GenV, the Queensland Family Cohort Study, and NEW1000.

Collaborations are likely to occur across studies, in part or full, which could help fill out different study areas in greater detail.