ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 7.7 | DOI: 10.1530/ey.18.7.7

ESPEYB18 7. Puberty Clinical Guidance (7 abstracts)

7.7. Prenatal exposure to maternal stressful life events and earlier age at menarche: the Raine study

Bräuner EV , Koch T , Juul A , Doherty DA , Hart R & Hickey M

Hum Reprod. 2021 Jun 18;36(7):1959–1969. 10.1093/humrep/deab039

In brief: This large prospective population-based pregnancy cohort study identifies an association between maternal stressful life events during gestation and earlier age at menarche in the daughters.

Comment: Earlier age at menarche is a known risk factor for adverse physical and psychological outcomes (1–2). Therefore, understanding its potential early drivers is important for public health. Literature suggests that childhood stress impacts reproductive function in females and leads to earlier puberty timing (3–5). However, data regarding prenatal stress and pubertal onset is much more scarce.

The authors studied an Australian cohort of 753 mother-daughter pairs. Women were recruited between their 16th and 20th gestational week from 1989 to 1991. 77% of women prospectively reported at least one stressful life event during the pregnancy (63% during early gestation; 54% during late gestation). Median age at menarche in girls exposed to prenatal stressful life events was significantly earlier than non-exposed girls. This association between stressful life events and earlier age at menarche followed a non-linear U-shaped response, meaning that one stressful event was associated with a 3.4 month earlier age at menarche, whilst exposure to 2 or more stressful events were associated with a 1.7 month earlier menarche. The association was not explained by childhood BMI. This data suggests a direct effect of prenatal stress on age at menarche, potentially due to an earlier activation of the hypothalamic-pituitary-adrenal axis. The hypothesis is supported by previous studies that identified an association between maternal stress and altered HPA axis in the offspring (6-7). The non-linear U-shaped response suggests that the first exposure to prenatal stress exerts a greater effect on fetal reproductive development than following exposures, possibly via dramatic initial changes in the HPA axis.

Further studies are needed to understand the underlying mechanisms of this association between prenatal stress and pubertal precocity in girls. However, these results support growing evidence for prenatal determinants of reproductive life with direct implications for women’s physical and psychological health across the life-span.

Reference: 1. Day FR, Elks CE, Murray A, Ong KK, Perry JR.(2015) Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Sci. Rep. 5:11208.2. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. (2003) The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr. Rev. 24:668–693.3. Laurent HK, Leve LD, Neiderhiser JM, Natsuaki MN, Shaw DS, Harold GT, Reiss D.(2013) Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences. Dev. Psychol. 49:876–886.4. Yehuda R, Engel SM, Brand SR, Seckl J, Marcus SM, Berkowitz GS. (2005) Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. J. Clin. Endocrinol. Metab. 90:4115–4118.5. Entringer S. (2013) Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk. Curr Opin Clin Nutr Metab Care 16:320–327.6. Ong KK, Emmett P, Northstone K, Golding J, Rogers I, Ness AR, Wells JC, Dunger DB. (2009) Infancy weight gain predicts childhood body fat and age at menarche in girls. J Clin. Endocrinol. Metab. 94:1527–1532.7. Bratke H, Bruserud IS, Brannsether B, Aßmus J, Bjerknes R, Roelants M, JÚlı´usson PB. (2017) Timing of menarche in Norwegian girls: associations with body mass index, waist circumference and skinfold thickness. BMC Pediatr. 17:138.

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