OBJECTIVES (note these will be achieved within the collaboration; ALSPAC will contribute to some but not all and for each objective more than one study will always contribute)

1a. To determine how metabolomic profiles change with age from birth through to old age.

1b. To explore the extent to which markers of reproductive health (age at menarche, age at first birth, parity, age at menopause, transition through menopausal transition) alter general age related trajectories

1c. To explore the associations of adiposity and change in adiposity with change in metabolomic profiles with increasing age.

1d. To explore the associaitons of reproductive hormones and change in reproductive hormones with change in metabolomic profiles with increasing age.

2a. To determine the extent to which blood-based metabolic profiles (assessed at different ages), in addition to clinical characteristics, improve stratification of women into different levels of risk for infertility

2b. To determine the extent to which blood-based metabolic profiles improve risk prediction of live birth obtained from IVFpredict.

2c.To determine the extent to which blood-based metabolic profiles (assessed at different pre-pregnancy and gestational ages), in addition to clinical characteristics, improve stratification of women who become pregnant into different levels of risk for hypertensive disorder of pregnancy, gestational diabetes, preterm birth, large for gestational age and small for gestational age.

2d. To develop the best prediction tools for single and combined adverse pregnancy/perinatal outcomes

3a. To determine the role of blood-based metabolic profiles (assessed at different ages) in the causal pathway between greater adiposity and subsequent reproductive and perinatal outcomes

3b. To determine the role of maternal gestational and fetal (assessed in cord-blood) blood-based metabolomics in the causal pathway between maternal gestational adiposity and weight gain and subsequent offspring (and the next generation - grandchildren) adiposity and cardiometabolic health

4a. To determine the extent to which metabolic profiles change as women go throug the menopausal transition and determine whether any change is independent of age related change

4b. To determine the extent to which reproductive hormone changes as women go through the perimenopausal transition are related to menopausal transition changes in metabolic profiles

4c. To determine the extent to which any menopausal transition changes in metabolic profiles result in future cardiometabolic diseases.