Understanding and Preventing the Impact of Endocrine Disruptors on the Hypothalamus-pituitary Axis in Sensitive Populations. Hypiend- Perinatal Study.

Study rationale

1. Extent and evaluation of current knowledge directly linked to the scientific question(s) to be answered by the clinical study.

Human epidemiological data suggest that EDC exposure during the perinatal period can negatively affect infant growth trajectory and neurodevelopment and possibly play an important role in the rapid epidemiological growth of obesity and diabetes. As an example, one study carried out in 460 mother-infant pairs from Korea showed that Mental and/or Psychomotor Developmental Indices of the Bayley Scales of Infant Development were inversely correlated in 6-month-old males with the maternal urinary levels of the phthalate metabolites MEHHP, MEOHP and MBP at the third trimester of pregnancy. Very recently, it was reported that mothers with overweight displayed increased levels of the highly persistent environmental chemicals polychlorinated biphenyls in breast milk 2-weeks postpartum and that there was a negative association between some of these compounds and the head circumference-for-age, weight-for-age, and weight-for-length z-scores of the infant at the age of 6 months.

However, there are discrepancies among findings, which can be attributed to differences in the temporal window of EDC exposure assessment (i.e., early versus late gestation or lactation), in the infants' age at which the measurements were carried out or to a misclassification of EDC exposure due to a single-point analyses of their exposure. In fact, one of the limitations of many epidemiological studies is the use of single spot urine samples at one time-point to estimate the exposure to EDCs. The limitation relies on the short biological half-lives of many of these chemicals and their quick excretion in urine, properties that cause a demand for multiple time point for a precise estimation of exposure assessment. Although different epidemiological studies have found an association between higher exposure to EDCs and neuroendocrine and neurodevelopmental alterations in toddlers and children, as far as we know, no clinical interventions have been carried out to elucidate whether reducing the exposure to EDCs can contribute to counteract/ameliorate these harmful effects.

So far, very few human intervention studies focused on reducing the exposure to EDCs during the perinatal period have been conducted, some carrying out educational approaches and others focused on dietary or other changes. Relevantly, most of them had small sample sizes (<100 people) and analysed a maximum of two different types of EDCs and quite a few were carried out without control groups. Moreover, the level of adherence in this type of interventions is low in general, reflecting the need to implement adequately behavioural change techniques to foster long-term lifestyle habit improvements. 2. Outcomes (efficacy, safety) Of completed and number of ongoing clinical studies utilizing the same intervention in the same indication (including review of public registers)