Structural and functional brain imaging data have shown that higher levels of prenatal cortisol are associated with amygdala hyper-reactivity and increased amygdala volumes in girls only; an elevated concentration of prenatal cortisol has also been positively associated with affective problems in girls only, an effect that has in part been induced by right amygdala volume and increased amygdala connectivity.
Thus, there is an association between prenatal stress and HPA axis function, postnatal HPA axis regulation and offspring anxiety and depression behaviors in both rats and humans, linked to sex.
Consequently, the low antisocial behavioral problems observed in girls compared with boys during childhood and the increase in anxiety-depressive symptoms, particularly depressive symptoms observed in girls after puberty, could be due to the same cause.
2.6. Prenatal exposures
2.6.1. Exposure to alcohol
Twenty percent of French women continue to occasionally drink alcohol during pregnancy. Fetal alcohol spectrum disorder (FASD) refers to all the effects (such as physical, cognitive and behavioral) that may be observed in a person whose mother drank alcohol during pregnancy.
It includes a set of conditions representing a “continuum”, from the most characteristic, most severe and easiest-to-diagnose form – fetal alcohol syndrome (FAS) – to so-called “incomplete” forms, which are much less well known and will reveal themselves later on through occasionally severe learning and/or behavioral disorders, the causes of which are far from always being identified.
In France, the collective expertise of Inserm “Alcool, effets sur la santé” (Alcohol, effects on health), published in 2001, estimated that 700 to 3,000 children, out of 750,000 annual births, would be affected by this syndrome, with a higher incidence on the island of Reunion, in Nord-Pas-de-Calais, Normandy and Brittany.
The effects on the central nervous system that have functional implications are now well known and include, among others, cognitive, motor, memory, executive function and communication impairments.
Longitudinal studies of alcohol in young adults have also shown that prenatal alcohol exposure is related to adult drinking problems. Exposure to one or more drinks per day during the first trimester of pregnancy has been significantly linked with increased levels of alcohol use at age 22, while controlling other predictors of alcohol use (Goldschmidt and Richardson 2019). These results indicate that individuals exposed to a single drink per day during gestation are at risk of increased alcohol use and alcohol problems at age 22.
2.6.2. Exposure to tobacco
Thirty percent of women smoke before their pregnancy, and 17% still smoke in the third trimester. France ranks seventh out of 50 countries most affected by active smoking during pregnancy. It must be said that some doctors advise smoking more than stress (see previous chapter). This active smoking behavior is more frequent in Brittany than in other regions.
The risk factors for smoking during pregnancy are: young age, poor education, low socioeconomic level, primiparity, geographical origin in metropolitan France, lack of occupation, a smoking spouse, a lack of spouse or associated depression. Multiparity is a risk factor for withdrawal failure during pregnancy.
Prenatal exposure to tobacco has short-, medium- and long-term effects, such as: placental abruption, fetal growth disorders, low birth weight; then poor visuomotor integration, poor verbal skills, poor school performance (not found in the United States, or when confounding factors are controlled) and attention-deficit hyperactivity disorder.
A recent Icelandic study (Kristjansson 2018) examined the relationships between exposure and academic achievement at ages 4, 7 and 10 using data collected at birth, during the neonatal period and at each grade level in the study’s birth cohort. Exposure influenced achievement scores, was negatively associated with math achievement at baseline and continued to negatively affect math achievement over time after controlling for gender, income, cohabitation and baseline math and science scores.
Thus, children whose mothers smoke in the first trimester of pregnancy are, on average, at greater risk of poor school performance over time than children whose mothers do not smoke in their first trimester.
In the EDEN study (Melchior and Hersi 2015), maternal smoking during pregnancy predicted only hyperactivity/attention-deficit through epigenetic mechanisms. By controlling confounding factors, only exposure throughout pregnancy was significantly associated. This correlation was not observed for paternal smoking during pregnancy. This is inconsistent with genetic transmission. Continued maternal use during pregnancy could also be a marker of social and environmental difficulties and poor parenting, with use also associated with more insecure mother–infant attachment (Melchior and Hersi 2015).
Smoking during pregnancy causes a transgenerational effect. Thus, an increased risk of asthma is observed in the grandchildren of maternal smokers.
Finally, children whose mothers continued to smoke during pregnancy are more likely to become smokers, 15 years later. In a way, the mother makes the fetus addicted to tobacco when he/she is building their nicotine receptors.
In conclusion, regardless of the various influences and consequences, it is clear that smoking cessation during pregnancy must be an issue for tobacco prevention workers in the general population, coupled with actions on parental behavior and screening and support for smoking cessation before or at the beginning of pregnancy.
2.6.3. Pollutants and endocrine disruptors
Pregnant women are exposed to a large number of chemicals through their diet, so the fetal period is more sensitive to the effects of these products. The influence of these products is increasingly being cited in phenomena such as the “obesity epidemic“, that is currently affecting children, or the precociousness of puberty.
Various works have shown associations between prenatal exposure to environmental contaminants that cross the placental barrier (particularly endocrine disruptors) and postnatal growth (Traoré et al. 2018). Heavy metals also have an impact, particularly on intellectual development.
In most cases, chemicals are studied individually and potential interactions or additive effects of substances are not taken into account. However, some recent epidemiological studies have identified relationships between exposure to mixtures of substances and their effects on health: the EDEN and ELFE studies have identified the main mixtures to which mothers are exposed, based on the 441 substances analyzed in the second French Total Diet Study3 (Traoré et al. 2018).
Exposure systems and substance composition were identified from co-exposures: individuals were grouped together to define clusters with similar co-exposure patterns. Six clusters associated with eight mixtures were identified. For example, in ELFE, cluster 2, comprising 10% of the population, was characterized by mixtures “Pest-1”, which contained mainly pesticides, and “TE-F-PAH”, which contained trace elements, furans and polycyclic aromatic hydrocarbons. Similar results were observed in the EDEN study.
This work enabled prioritization of mixtures for which it was crucial to investigate possible toxicological effects and to recommend epidemiological studies regarding health effects (Traoré et al. 2018).
2.6.4. Exposure to acrylamide
Acrylamide is a known neurotoxin to humans and animals and has been classified as “probably carcinogenic”
