Birth after 35 - the older mother

Dr Basil Lee

Midwives magazine: December 2008 /January 2009


The science and signs of the biological clock.

William Ledger, Professor of Obstetrics and Gynaecology and Head of the Academic Unit of Reproductive and Developmental Medicine, University of Sheffield (Co-author).

Many women put off planning their first pregnancy until their late thirties or early forties, and by that age fertility treatment has little to offer if they cannot conceive naturally.
Although the chances of IVF working for younger women are increasing year on year, there has been little progress for the older patient (see Figures).

The ideal age for a woman to have children is between 20 and 35; I speak biology, not sociology. But in the past 20 years the average age for women in the UK becoming pregnant has shifted from 25 to 34, a huge rate of change in demographic terms. Recently, late conceptions increased from 10.7 to 11.3 per 1000 (6% in one year). One may guess at the causes of this, but importantly people do not understand its implications.

There is no appreciation of the health risks of pregnancy in older women, including increased risks of breast cancer, premature birth and fetal abnormality. Similarly, the health risks to offspring of having an older father (heart disease, some cancers, schizophrenia) are not understood.

Although adult men make about 30 million sperm daily, women never make a single new egg once they are born. They have seven million primordial follicles at five to seven months of their fetal lives, but only two million survive to birth, and there is further attrition throughout life.  Its not only the quantity but the quality of the eggs that also declines with increasing age; chromosomal abnormalities develop resulting in miscarriage, Down's syndrome and so on.


How can we measure ovarian reserve?

I am interested in the use of a blood test taken on the second day of the menstrual cycle. Inhibins are secreted in the ovaries in the early phase of follicle development. Inhibin B is a product of the granulosa cells, and identifying low levels of this throughout the menstrual cycle up to ovulation  indicates poor quantity and quality of eggs for IVF. Good inhibin B levels promise eggs in sufficient quantity and more embryos.  Measurement of follicle stimulating hormone (FSH) alone would not have shown the difference. An early fall in inhibin levels indicates the onset of the menopause earlier than a rise in FSH. Anti-Mullerian hormone (AMH), another granulosa cell product, is an even better indicator than inhibin B, and is now a useful predictor of IVF outcome.

It may be useful to combine these markers to derive an ovarian reserve index (ORI),  derived mathematically from unstimulated day 2 or 3 inhibin B, AMH and FSH. This optional test is offered to women of  between 30 and 45 who are planning to defer having children. They must have regular periods (27 - 35 day cycle), must not be using the oral contraceptive pill or other hormonal medications and must have had at least three periods following childbirth. Polycystic ovary syndrome (PCOS), endometriosis, and other medical disorders, medications  and so on, contraindicate the test.

The ORI reflects the remaining number of follicles in the ovaries, establishes an individual’s ORI in relation to her age group, and with repetition establishes a trend. It is not a complete ‘fertility test’, since it takes no account of male, uterine, and tubal factors. We warn older women of the risks of deferring pregnancy even if they have normal ORIs.

As more women defer childbirth the problems of the  biological clock become more acute. Nowadays 40 years is the new 20; but women are living to  85, while their fertility is still failing at 40 as it was hundreds of years ago when women died at 45.


Consequences of being an older mother in pregnancy
Dr Katrina Erskine, Consultant Obstetrician and Physician, Homerton University Hospital (Co-author).
 
Compared to women aged under 35 years, the older woman is more likely to be in a stable relationship,  be more mature, and to have better financial resources. I shall be discussing a number of problems to which they are more prone because of their age. These include in no particular order stress incontinence, abnormal weight gain, obesity, antepartum haemorrhage, premature rupture of the membranes, malpresentation, fetopelvic disproportion, instrumental delivery, sphincter rupture, caesarean section, late stillbirth and reduced energy. And grandparents are more likely to die earlier in a child's life. For the older woman I can be seen as the 'bad news' doctor!

More women are delaying childbirth to their late 30s; they tend to be of higher socioeconomic status in developed countries. Being less fertile, they are more likely to need fertility assistance. They are 1.5 to  two times more likely to have multiple births, have an increased risk of stillbirth, are more likely to have a chronic disease, and are more likely to have pregnancy complications in both developed and developing countries.

There are serious issues around fertility treatment. After adjusting for age and parity, women receiving fertility treatment face a number of increased risks. The odds ratio (OR – the ratio of the odds of an event occurring in one group to the odds of it occurring in another group) for pre-eclampsia is 1.9 , and significantly higher when ovum donation has been used. The OR for placenta praevia is 3.9,  and placental abruption 1.8, caesarian section (CS) 2.1, and preterm delivery  1.7. In total, 10% of women having fertility treatment by ovum donation will have postpartum haemorrhages requiring hysterectomy, a statistic rarely mentioned by the professionals.

Pregnancy with dichorionic twins carries a four-fold increase in perinatal mortality and significantly increased risks of  pre-eclampsia, preterm delivery, CS and cerebral palsy.

Essential hypertension is more common among older mothers, and here too there are increased risks of pre-eclampsia, utero-placental dysfunction and abruption with possible stillbirth. If more than one anti-hypertensive is required and there is significant proteinuria by 20 weeks the risks are even greater. Also, some anti-hypertensive drugs have teratogenic effects.

The increased risks which diabetics run include miscarriage, fetal abnormality, macrosomia  and babies small for gestational age (SGA), and stillbirth. They more frequently require CS, and their condition is liable to be affected by pregnancy.

When in labour the older mother may expect longer first and second stages, and an increased requirement for oxytocin in both stages. Older women are more likely to need delivery by CS: OR 5.42 for elective CS , 2.67 for emergency CS. They have an increased risk of postpartum haemorrhage , and admission of their babies for neonatal care is more likely. 

Advanced maternal age has an independent risk of stillbirth,  approximately doubling, possibly due to the increased incidence of pregnancy-induced hypertension or gestational diabetes.There is an increase in stillbirth at 37 to 41 weeks, usually unexplained; increased surveillance should be carefully considered in older women after 37 weeks.

As professionals we should be informing younger childless women of the risks of leaving childbearing until later.  Older women are often unaware of the increased risks they face. We need to discuss their pregnancy intentions, their reducing fertility, the pregnancy complications and the risks of assisted conception, including multiple birth.

The older mother: a blessing, a fear or a fuss? 

Ms Lowri Turner, Journalist

I am a woman who left pregnancy late – my babies were born from age 35 to 42. I have polycystic ovaries, had problems conceiving but eventually conceived naturally. Older women who read and otherwise attend to the media are now panicking, having learned of all the problems of pregnancy in their age group and that they have left it too late. Research has concentrated on the diminishing reserve of our ovaries and has omitted studying positive aspects. However, I cannot believe that young women who are binge drinking and smoking are in the best condition to have their babies either. Back then my lifestyle was much the same, and my parents would have been horrified, even embarrassed, to think that I was wasting an education and a career by getting pregnant at that age. If a gynaecologist had asked me then to consider my fertility I would have felt insulted - none of his/her business. We don't want to be defined by our fertility or gender. Men  can and do ignore the biological realities; we're not allowed to do that but we want to. The government may ordain maternity leave, but do we want it? We would prefer to get back  to work, and arrange child care - not ideal for our babies to be sure.    
 
We older women feel our age and are adopting healthier lifestyles, but the messages are scaring and punishing. And there's nothing to read about the problems which older fathers face – it has come as news to me that their babies may miscarry or, if born, have a greater risk of developing schizophrenia.

One of the pressures on older women to conceive is divorce and remarriage; we regard fertility treatment as a magic wand, and it has come as a shock to me to learn of its dangers. Even at our age the medical profession patronises us; we're not given credit for mature decision-making, but it is we who are taking folic acid and have up to a point informed ourselves of the risks we run. We still need information, but do not deserve to be scolded or stigmatised. The problem of equating our needs with the capabilities of our bodies remains.


The older mother from the perspective of the anti-ageing culture
David Alpert, Founder of the International Institute for anti-ageing, London

Anti- ageing medicine is not to be confused with aesthetic medicine – it looks at ways to improve the health span - extending the healthy years and reducing the risk and incidence of age-related disease as chronological age advances. The biological age is that at which the body is functioning, and is preferably less than the chronological age. A 74 year-old non-smoker with a low alcohol consumption who is active and eats five daily servings of fruit and vegetables has the same risk of dying as a 60 year old who has none of these advantages. This is anti-ageing behaviour.

Professor Ledger and Dr Erskine have described the degree to which the average age of conception has increased in recent years, the liability of  the older group to develop the diseases of ageing  –  diabetes,  hypertension, obesity –  and the difficulties they face with conception, assisted or otherwise.

Between the years of 1997 and 2006 the incidence of chlamydia increased  by 166% and of gonorrhoea by 46%; consider the contribution of sexually transmitted diseases to infertility. The pollution of the environment by heavy metals, plastics, pesticides and industrial chemicals has a like effect.

Factors contributing to male infertility, aside from the well known tight underwear, include bathing in hot water, smoking marijuana, the use of  laptop computers and cell phones, and cigarette smoking. Coffee on the other hand has been shown to improve male fertility.

Smoking before pregnancy or during breastfeeding reduces the fertility of both male and female offspring, while higher intake of beef by their mothers has a similar effect on the males.
The high intake of carbohydrates increases ovulatory infertility; where fats are concerned the greatest single factor having a negative effect on fertility is trans fat (found in most margarines, many fast foods and commercially baked products, they may be even more unhealthy than saturated fats, boosting LDL cholesterol and triglycerides). The converse is true of unsaturated fats.

The higher the proportion of plant rather than animal protein in the diet the better for fertility; the benefits of moderate exercise, full fat dairy products, and zinc are well documented. Unfortunately, the past 50 years have seen the loss of substantial amounts of beneficial elements in vegetables, fruit and meat.
Any hormonal treatment is best balanced to achieve homoeostasis, using bioidentical products in physiological dosage.

Finally, the negative effects of stress, overt or subclinical, on fertility are not to be ignored.

Vitamin A has an important role in healthy cell differentiation, DNA repair and apoptosis (a form of programmed cell death in multicellular organisms), yet women are being advised to avoid it in pregnancy –when giving subfertile women nutritional advice, we must separate the wheat from the chaff.

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