PREGNANCY: In utero exposure to maternal inflammation affects baby’s brain

Exposure of the baby to maternal inflammation, in utero during pregnancy, at the very moment of brain development, can then considerably affect its cerebral and cognitive aging, 50 years later . This is the remarkable conclusion of this extreme longitudinal study, conducted by a team from Mass General Brigham (MGB, Boston), published in the journal Molecular Psychiatry. If prenatal immune activity thus affects the development of the brain of the “offspring” in the very long term, this factor is not the only one, the researchers specify, and is combined with a whole series of environmental factors

PREGNANCY: In utero exposure to maternal inflammation affects baby’s brain

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Molecular Psychiatry

Exposure of the baby to maternal inflammation, in utero during pregnancy, at the very moment of brain development, can then considerably affect its cerebral and cognitive aging, 50 years later . This is the remarkable conclusion of this extreme longitudinal study, conducted by a team from Mass General Brigham (MGB, Boston), published in the journal Molecular Psychiatry. If prenatal immune activity thus affects the development of the brain of the “offspring” in the very long term, this factor is not the only one, the researchers specify, and is combined with a whole series of environmental factors.

It is estimated that more than 150 million people could be living with the disease.AlzheimerIn 2050, each risk factor must be better understood and better taken into account.

The research, which followed its participants from before they were even born until they were 50, suggests a new clue about the origins of Alzheimer’s disease: stress-related immune activity during the late second or early third trimester of pregnancy could have very long-term effects on the child’s circuits, functions and memory decline, and thus increase the risk of Alzheimer’s later in life.

Research has reached different conclusions depending on the sex of the child , and neuroscientists caution that sex differences in immune function begin as early as fetal development. While it is widely recognized that the brain circuits underlying memory differ by biological sex, sex-related factors in aging and Alzheimer’s disease are poorly understood

Brain aging is also linked to brain development

The study analyzes data from 18,000 participants followed before birth and for more than 50 years and highlights the impact of maternal immune activity during a critical period on the baby’s brain development. The analysis focuses on 204 individuals born during the follow-up, exposed or not to an unfavorable in utero immune environment,

that is, at high levels of immune markers, such as the cytokines IL-6 and TNF-a,

who were followed up until their fifties, 50 years later. The team used functional brain imaging to examine the impact of this early exposure on brain regions of memory circuits that are rich in these cytokine receptors and sex hormone receptors and that show sex differences in development and function as early as fetal development.

• high levels of IL-6 and TNF-a in mothers during pregnancy are linked to differences in brain activity;
• These differences are unfavourable differently depending on the sex, particularly in memory circuits later in life: this negative effect is more significant in women, after menopause;
• These postmenopausal women, formerly exposed to maternal inflammation in utero, express these same pro-inflammatory markers in their fifties;
• the impact of these immune markers also occurs in childhood, and is manifested by a reduction in cognitive performance in children at the age of 7;
• This high prenatal maternal immune activity also appears to contribute to the development of increased stress and immune sensitivity in offspring, which are further predisposing factors to memory disorders, such as Alzheimer’s disease, later in life;
• the effect of in utero exposure to maternal inflammation is sex-dependent;
• Maternal inflammation thus impacts the circuits and functioning of long-term memory in offspring during childhood and in middle age,
• with different patterns for men and women.

One of the lead authors, Dr. Jill M. Goldstein, professor of psychiatry and medicine at Harvard Medical School, concludes: “Brain aging is also linked to brain development, and understanding sex differences in brain development is essential to understanding sex differences in the aging brain. That’s why understanding the fetal origins of Alzheimer’s disease , which, like many chronic diseases, develops throughout life and is influenced by early development, is essential.”

The research continues and continues to follow participants as they age , tracking amyloid levels and other measures of Alzheimer’s markers. Better understanding how maternal immune activity influences fetal brain development and aging may allow us to intervene earlier and reduce the incidence of Alzheimer’s disease somewhat. For future generations.

Source: Molecular Psychiatry Nov 20, 2024 DOI: 10.1038/s41380–024–02798-