Pregnancy: Better Never Than Late?

18. July 2017
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More and more frequently women aged 35 plus are getting pregnant. Experiencing baby bliss in later life is nonetheless a risk factor. Nothing much is altered here by molecular biology, nor by recommendations based on cohort studies.

Singer Gianna Nannini gave birth to her daughter at the age of 54. Even though this is an extreme example, the overall age of mothers at childbirth is indeed increasing. More and more often mothers over the age of 40 are experiencing the bliss of motherhood. Scientists contentiously discuss the successes and risks of later pregnancies.

When molecular threads tear up

Human geneticists have for a long time known that increasing maternal age brings with it a sharp rise in the frequency of hereditary diseases. At 40 years of age, embryonic chromosomal defects are present in more than one third of all pregnancies. These primarily include aneuploidy, ie the faulty distribution of chromosomes In egg formation, and therefore the wrong number of chromosomes in oocytes.

Scientists explain this phenomenon predominantly as being due to cohesines. These protein complexes stabilise the chromatin in cells and thus the structure of chromosomes. The genetic material is folded into loops in the cell nucleus. Cohesines initially enclose the DNA strand at an arbitrary position. The DNA is then pressed through the ring until molecular barriers stop it. The purpose and aim of this mechanism is to directly bring removed sections of the genome into direct contact, in order to regulate gene activity:

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Mechanism of loop formation through cohesine © IMP – Research Institute for Molecular Pathology

 

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Risk of trisomy 21 depending on maternal age. © James Heilman, MD / Wikipedia, CC BY-SA 3.0

Already several years ago, scientists from the University Clinic Carl Gustav Carus Dresden (Germany) found indicators in a mouse model that cohesines are formed during embryonic oocyte development and are not later renewed. They explain the age-dependent occurrence of aneuploidy in terms of slow destruction of cohesine molecules.

Severe complications accumulate

Sarka Lisonkova, scientist at the University of British Columbia, Vancouver, has now found evidence of further complications. As part of a retrospective population-based cohort study, she analysed data from 828,269 pregnant women. Known risk factors, such as obesity or artificial insemination, were corrected for in advance.

“Morbidity rose exponentially in association with women over 39 years of age”, Lisonkova writes. From age 40 onwards, the risk was 1.2 times and at age 50 plus was even 5.4 times higher. Mothers between 40 and 44 years of age therefore had a threefold higher risk of shock and an eightfold higher risk of amniotic fluid embolism. The comparison group was one aged from 25 and 29 years of age.

Partial all-clear in the case of birth weight

In view of the numerous dangers, an article published by Alice Goisis and colleagues is surprising. Goisis conducts research at the London School of Economics and Political Science. The basis of her retrospective cohort study was a Finnish population register taking in 124,098 children from 1987 to 2000. In order to rule out statistical distortions, the authors compared identical women of different ages. The idea was to exclude risk factors aside from chronological age. As Goisis writes, there are disruptive influences between families, but not between several pregnancies in the same woman.

Where women had several children, a higher age did not increase the risk of having a premature birth early or of bringing a child with a small weight to the world. When Goisis however compared women from different families, she saw the well-known effect. From 40 years of age the risk of having a baby of low birth weight was, at 4.4 percent, twice as high as among women from 25 to 29 years of age (2.2 percent). Coauthor Mikko Myrskylä, Director of the Max Planck Institute for Demographic Research (MPIDR) in Rostock (Germany), explains the observations by way of “individual living circumstances and behaviours”.

Myrskylä and colleagues were however not able to find out the actual reasons on the basis of their data base. Potential reasons include individual age-independent fertility problems, unhealthy behaviour and stress. Whether contrary tendencies such as more experience or less stress on the part of the mother perhaps function protectively was not able to be extrapolated with the data. Socio-economic trends, such as higher household income with increasing age, were however statistically corrected.

False hope stoked

As is known, the significance of association studies is limited. With respect to the practical value of her publication Myrskylä states in a report: “A doctor who knows only the age of a pregnant woman can still use it to assess the birth risks.” Nevertheless, Alice Goisis’ summary is quite surprising: “With respect to the individual mother, however, her age is not the real reason for possibly increased birth risks”. In the case of lay persons, such statements can have disastrous results. Despite individual differences, the experience of advanced age motherhood is associated with numerous medical risks.

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