Influence of maternal preconception and early-pregnancy health on pregnancy and offspring outcomes. From risk selection to interventions in multi-ethnic populations

A suboptimal start of life has long-term health consequences. Children born preterm or with a small or large size at birth have increased risks of common diseases across the full lifecourse, including obesity, cardio-metabolic diseases, asthma and mental health disorders. Recent observational studies, of which many financially supported by the first “ZonMw Zwangerschap en Geboorte” call, suggest that specifically early-pregnancy, and even the preconception period, are important potential windows of opportunity for new prevention strategies focused on a better start of life and lower risks of common chronic diseases throughout the lifecourse in future generations. Findings from observational studies have shown that maternal overweight, high-fat high-sugar diet, smoking, alcohol consumption and stress, are among the most common and modifiable maternal lifestyle factors before and during pregnancy, leading to a suboptimal in-utero environment predisposing offspring to increased risks of short and long-term adverse health outcomes. Knowledge from these observational studies needs to be urgently translated into improved health care practices for populations. The main hypothesis for our project is that preventive strategies from preconception onwards focused on the main adverse maternal lifestyle factors including high BMI, high-fat high-sugar diet, smoking, alcohol consumption and stress, induce better placental and embryonic development and lead to improved pregnancy outcomes and offspring growth, adiposity and behavioral development. We will use an integrated translational approach with a population intervention study embedded within the Generation R Next Study from preconception onwards. First, we will construct a risk score of maternal preconception characteristics for identification of women at risk of adverse pregnancy and offspring outcomes based on previous findings from the Generation R Study. We will focus on maternal socio-demographic and lifestyle factors as risk factors and birth outcomes as outcomes. Second, we will set-up and perform a population lifestyle intervention study from preconception onwards (n=2000 women) to assess the influence of optimizing maternal lifestyle from preconception onwards on maternal and fetal pregnancy outcomes and offspring long-term health outcomes. We will use a 2x2 factorial trial design with cluster randomization by (planned) midwife practice. Participants at risk for adverse outcomes based on the developed risk score will be randomly assigned by (planned) midwife practice to one of 4 trial arms: Control group: regular Dutch antenatal advice; Intervention group 1: regular Dutch antenatal advice + dietary advice; Intervention group 2: regular Dutch antenatal advice + mind-body therapy; Intervention group 3: regular Dutch antenatal advice + dietary advice + mind-body therapy. All women will receive regular Dutch antenatal advice, with emphasis on no smoking and no alcohol consumption in pregnancy. The first intervention is additional advice on healthy dietary intake, focused on stimulating a low-glycemic index diet, optimizing polyunsaturated fatty acids intake and no alcohol consumption. The second intervention is mind-body therapy for stress reduction and reduction of risk behaviors including smoking, alcohol consumption and unhealthy diet. The intervention will be delivered in the preconception period as a group educational session and be reinforced at 8-13 weeks gestation by a research nurse. The primary outcome is a composite outcome of preterm birth (birth<37 weeks of gestation) or SGA (gestational-age-adjusted birth weight<10th percentile) or low Apgar score 5 minutes after birth (APGAR score<7) or LGA (gestational-age-adjusted birth weight>90th percentile) based on the definition of ZonMw Big4-disorders. Secondary outcomes are maternal adherence to lifestyle advice, pregnancy complications, postpartum psychological distress and weight retention, and offspring growth, adiposity and behavior at age 1 year. Independent and interactive effects of the interventions will be assessed. Secondary subgroup analyses focused on ethnic background and socio-economic status will be performed. The intervention study will be designed in detail based on findings from previous studies, including the Generation R Studies, an expert meeting with leading experts on maternal health during pregnancy and a client panel, including the parents-child group of the Generation R Study and the client panel of the ZonMw Regional Consortium Pregnancy & Childbirth Southwest of the Netherlands. This multidisciplinary project is embedded in this regional consortium and the Rotterdam Academic Center for Pregnancy & Childhood, in which the Municipality, health care professionals for mothers and children and the university work closely together. Results from this project will contribute to the development and implementation of new preventive strategies focused on future parents and their children.