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Why older mothers likely face birth complications

Pregnant women over 35 years old are more likely to have complications at birth due to delayed and longer labor stages, suggests new research.

It is well known that older mothers are more likely to experience complicated births, and new research identifies physiological changes in the body that could explain why.

Using mouse models, researchers from King's College London discovered that maternal age influences the structure of the uterus.

Specifically, they examined (1) how the uterine muscle contracts, (2) the way it responds to oxytocin  — an important drug to speed up labor — and (3) the number of mitochondria (a cell's 'battery') available in a cell to provide energy for uterine muscle contraction. They also found altered hormonal signals that underpin the delay of labor onset.

The work is published in The Journal of Physiology.

The average age for women to have their first child is increasing, with more women giving birth to their first child over 35 years of age.

This parallels an increase in pregnancy complications such as inducing women pass their due date, failure to progress in labour, and bleeding after delivery.

Older women are also more at risk of requiring a caesarean section or instrumented delivery (e.g., with forceps), suggesting there may be issues with the way their uterus can contract during labour.

The research team developed and used a pregnant mouse model of maternal aging. Pregnant mice at different ages were used to mimic the human situation. The average mouse has a peak fertile period between 3 - 5 months, so mice at 8 months were used to represent an older mother. They analysed the functions and physiological changes in the cervix and uterine muscles from these pregnant mice.

In older mice, muscle contraction properties in the uterus were impaired, less sensitive to oxytocin and had reduced numbers of mitochondria indicating the uterus muscles are less able to contract. Signalling of the pregnancy-related hormone progesterone was also altered and triggering a delay in labour.

Dr. Rachel M. Tribe, Reader in Women's Health at King's College London and lead investigator of the study explained: "Our research highlights that there are key physiological and cellular changes associated with a mother's age that result in labour dysfunction. Timing of delivery and progress of labour is directly related to maternal age and this can cause complications during birth."

Dr Rima Patel, Research Associate at the Division of Women's Health, King's College London and fellow researcher added: "Our study uses a mouse model so further research involving measuring hormones and analysing uterus tissue in older pregnant women is now needed. Studies like this in maternal aging are essential to inform future clinical management strategies for older mothers to ensure more hassle-free and successful births."

Advanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth, and post-term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young), 5 (intermediate) months vs. 8 months (older) of age using infra-red video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3 month old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin-43 mRNA expression were reduced in myometrium from 8 month vs. 3 month old mice (P < 0.05, P < 0.01 respectively) in tandem with more frequent, but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, but there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8 month old mice provide a useful model of reproductive ageing. This study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women.

Rima Patel, James D. Moffatt, Evangelia Mourmoura, Luc Demaison, Paul T. Seed, Lucilla Postson,
Rachel M. Tribe

Accepted manuscript online: 12 January 2017Full publication history
DOI: 10.1113/JP273350
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Fiona and Paul Lister with baby Izaak, whose birth (2008) came as a near miracle to the proud parents.
Image Credit: Northern Star - Australia



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