Advanced maternal age

Average age at first childbirth has been increasing, especially in OECD countries, among which the highest average age is 32.6 years (South Korea) followed by 32.1 years (Ireland and Spain). In a number of European countries (Spain), the mean age of women at first childbirth has crossed the 30-year threshold. This process is not restricted to Europe. Japan and the United States are seeing average age at first birth on the rise, and increasingly the process is spreading to countries in the developing world such as China, Turkey and Iran. In the U.S., the average age of first childbirth was 26.9 in 2018.

Advanced maternal age is associated with adverse maternal and perinatal outcomes. Possible maternal complications due to advanced maternal age include preterm labor, pre-eclampsia, gestational diabetes mellitus, stillbirth, chromosomal abnormalities, spontaneous miscarriage and cesarean delivery. Advanced age can also increase the risk of infertility. Some of the possible fetal outcomes due to advanced maternal age include admission to neonatal intensive care units (NICU), intrauterine growth restrictions, low Apgar score, chromosomal abnormalities and infants smaller for gestational age. The corresponding paternal age effect is less pronounced.

History

Having children well into middle age was not exceptional in the past, when families were larger and women often continued bearing children until the end of their reproductive age. What is so radical about this recent transformation is that it is the age at which women give birth to their first child, which is becoming comparatively high, leaving an ever more constricted window of biological opportunity for second and subsequent children, should they be desired. Unsurprisingly, high first-birth ages and high rates of birth postponement accompany low and lowest-low fertility.

This association has now become especially clear, since the postponement of first births in a number of countries has now continued unabated for more than three decades and has become one of the most prominent characteristics of fertility patterns in developed societies. A variety of authors (in particular, Lesthaeghe) have argued that fertility postponement constitutes the "hallmark" of what has become known as the "second demographic transition".

Others have proposed that the postponement process itself constitutes a separate "third transition". On this latter view, modern developed societies exhibit a kind of dual fertility pattern, with the majority of births being concentrated either among very young or increasingly older mothers. This is sometimes known as the "rectangularisation" of fertility patterns.

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Possible factors that influence childbearing age

There are many factors that may influence childbearing age in women, although they are mostly correlations without certain causations. For instance, older maternal age at first childbirth is associated with higher educational attainment and income.

Two studies show that generous parental leave allowances in Britain encourage young motherhood and that parental-leave allowance reduces postponement in Sweden.

Effects

Decreased fertility

A woman's fertility peaks during her twenties and first half of her thirties, after which it starts to decline. Advanced maternal age causes an increased risk of female infertility. A woman's individual level of fertility can be tested through a variety of methods.

According to Henri Leridon, PhD, an epidemiologist with the French Institute of Health and Medical Research, of women trying to get pregnant, without using fertility drugs or in vitro fertilization:

At age 30, 75% will have a conception ending in a live birth within one year, and 91% will have a conception ending in a live birth within four years.
At age 35, 66% will have a conception ending in a live birth within one year, and 84% will have a conception ending in a live birth within four years.
At age 40, 44% will have a conception ending in a live birth within one year, and 64% will have a conception ending in a live birth within four years.

Menopause typically occurs between 44 and 58 years of age. DNA testing is rarely carried out to confirm claims of maternity at advanced ages, but in one large study, among 12,549 African and Middle Eastern immigrant mothers, confirmed by DNA testing, only two mothers were found to be older than 50, the oldest mother being 52.1 years with natural conception (and the youngest mother 10.7 years old). IVF can be used post-menopause, with the oldest confirmed mother through this method being 73.

Risk of birth defects

A woman's risk of having a baby with chromosomal abnormalities increases with her age. Down syndrome is the most common chromosomal birth defect, and a woman's risk of having a baby with Down syndrome is:

Risk of having a baby with Down syndrome

Other effects

Advanced maternal age is associated with adverse outcomes in the perinatal period, which may be caused by detrimental effects on decidual and placental development.

The risk of the mother dying before the child becomes an adult increases with advanced maternal age, as seen in the following data from France in 2007:

The above table is not to be confused with maternal mortality.

Advanced maternal age continues to be associated with a range of adverse pregnancy outcomes including low birth weight, pre-term birth, stillbirth, unexplained fetal death, and increased rates of Caesarean section. However, over time, improvements in (and improvements in access to) medical services and social resources have decreased the negative association between older maternal age and low birth weight.

According to a meta analysis from 2017 of 63 cohort studies and 12 case control studies, advanced maternal age (≥35 years) increased the risk of stillbirth (OR 1.75, 95%CI 1.62–1.89). It also increased the risk for FGR (fetal growth restriction) (OR 1.23; 95%CI 1.01–1.52). It is suggested that the rise in the risk could be due to conditions related to placental pathology/dysfunction.

On the other hand, advanced maternal age is associated with a more stable family environment, higher socio-economic position, higher income and better living conditions, as well as better parenting practices (including better disciplinary methods). A qualitative study on couples in the United States who used in-vitro fertilization to conceive their first child when the woman was aged 40 or older at the time of delivery found that 72% of the women and 57% of the men believed that they had enhanced emotional preparedness for parenting which benefitted both their children and themselves. In quantitative studies, mother's older age at first birth has been associated with increases in children's psychiatric health, language skills, cognitive ability, and fewer social and emotional difficulties. Further, a study in the United Kingdom showed that older maternal age at first birth was associated with fewer hospital admissions and fewer unintentional injuries for children up to age 5 and a greater likelihood of having had all of their immunizations by 9 months of age – all outcomes used as indicators of child wellbeing in reports from the World Health Organisation.

Risks associated with childbearing over the age of 50 include an increased incidence of gestational diabetes, hypertension, delivery by caesarean section, miscarriage, preeclampsia, and placenta previa. In comparison to mothers between 20 and 29 years of age, mothers over 50 are at almost three times the risk of low birth weight, premature birth, and extremely premature birth; their risk of extremely low birth weight, small size for gestational age, and fetal mortality was almost double.

Changes in interpregnancy interval

Kalberer et al. have shown that despite the older maternal age at birth of the first child, the time span between the birth of the first and the second child, the interpregnancy interval, decreased over the last decades. If purely biological factors were at work, it could be argued that interpregnancy interval should have increased, as fertility declines with age, which would make it harder for the woman to get a second child after postponed birth of the first one. This not being the case shows that sociologic factors (see above) prime over biological factors in determining interpregnancy interval.

With technological developments, cases of post-menopausal pregnancies have occurred, and there are several known cases of older women carrying a pregnancy to term, usually with in vitro fertilization of a donor egg. A 61-year-old Brazilian woman, aided by the implantation of a donor egg, gave birth to twins in October 2012.

Ovarian aging

As women age, they experience a decline in reproductive performance leading to menopause. This decline is tied to a decline in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 of them (about 0.05%) ovulate, and the rest do not (ovarian follicle atresia). The decline in ovarian reserve appears to occur at a constantly increasing rate with age, and leads to nearly complete exhaustion of the reserve by about age 51. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions.

Titus et al. have proposed an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Meiosis is the general process by which germ cells are formed in eukaryotes, and it appears to be an adaptation for efficiently removing damages in germ line DNA by homologous recombinational repair (see Origin and function of meiosis). Human primary oocytes are present at an intermediate stage of meiosis, that is prophase I (see Oogenesis). Titus et al. also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in ability to repair double-strand damages can account for the accumulation of these damages, which then likely contributes to the decline in ovarian reserve.

Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely, suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. Genomic data from about 70,000 women were analyzed to identify protein-coding variation associated with age at natural menopause. Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and including a common coding variant in the BRCA1 gene.

Epidemiology

In the United States, between 1997 and 1999, 539 births were reported among mothers over age 50 (four per 100,000 births), with 194 being over 55. In the US, the average age at which women bore their first child advanced from 21.4 years old in 1970 to 26.9 in 2018.

The German Federal Institute for Population Research stated in 2015 the percentage for women with an age of at least 35 giving birth to a child was 25.9%. This figure rose from 7.6% in 1981. According to statistics from the Human Fertilisation and Embryology Authority, in the UK more than 20 babies are born to women over age 50 per year through in vitro fertilization with the use of donor oocytes (eggs).

List of oldest mothers

Erramatti Mangamma, who gave birth at the age of 74 through in-vitro fertilisation via caesarean section in the city of Hyderabad, India, is believed to currently hold the record for being the oldest living mother. She delivered twin baby girls, making her also the oldest mother to give birth to twins. The previous record for being the oldest living mother was believed to be held by Daljinder Kaur Gill from Amritsar, India, who gave birth to a baby boy at age 72 through in-vitro fertilisation.

Maria del Carmen Bousada de Lara formerly held the record of being the oldest verified mother; she was aged 66 years 358 days when she gave birth to twins, 130 days older than Adriana Iliescu, who gave birth in 2005 to a baby girl. In both cases, the children were conceived through IVF with donor eggs. The oldest verified mother to conceive naturally (listed currently as of 26 January 2017 in the Guinness Records) is Dawn Brooke (Guernsey); she conceived a son at the age of 59 in 1997.

Debate

Pregnancies among older women have been a subject of controversy and debate. Some argue against motherhood late in life on the basis of the health risks involved, or out of concern that an older mother might not be able to give proper care for a child as she ages, while others contend that having a child is a fundamental right and that it is commitment to a child's wellbeing, not the parents' ages, that matters.

A survey of attitudes towards pregnancy over age 50 among Australians found that 54.6% believed it was acceptable for a post-menopausal woman to have her own eggs transferred and that 37.9% believed it was acceptable for a post-menopausal woman to receive donated ova or embryos.

Governments have sometimes taken actions to regulate or restrict later-in-life childbearing. In the 1990s, France approved a bill which prohibited post-menopausal pregnancy, which the French Minister of Health at the time, Philippe Douste-Blazy, said was "... immoral as well as dangerous to the health of mother and child". In Italy, the Association of Medical Practitioners and Dentists prevented its members from providing women aged 50 and over with fertility treatment. Britain's then-Secretary of State for Health, Virginia Bottomley, stated, "Women do not have the right to have a child; the child has a right to a suitable home". However, in 2005, age restrictions on IVF in the United Kingdom were officially withdrawn.

Legal restrictions are only one of the barriers confronting women seeking IVF, as many fertility clinics and hospitals set age limits of their own.

General and cited references

Jabcosson, B.; Ladfords, L.; Milsom, I. (2004). "Advanced maternal age and adverse perinatal outcome". Obstetrics & Gynecology. 104 (4): 727–733. doi:10.1097/01.aog.0000140682.63746.be. PMID 15458893. S2CID 8652247.
Khashan, Ali S.; et al. (2013). "Advanced maternal age and adverse pregnancy outcome: Evidence from a large contemporary cohort". PLOS ONE. 8 (2): 1–9. Bibcode:2013PLoSO...856583K. doi:10.1371/journal.pone.0056583. PMC 3577849. PMID 23437176.
Lorentzon, M.; et al. (2012). "Advancing maternal age is associated with lower bone mineral density in young adult male offspring". Osteoporosis International. 23 (2): 475–482. doi:10.1007/s00198-011-1558-5. PMC 3261413. PMID 21350896.
Nilsen, A.B.; et al. (2012). "Characteristics of women who are pregnant with their first baby at an advanced age". Acta Obstetricia et Gynecologica Scandinavica. 91 (3): 353–362. doi:10.1111/j.1600-0412.2011.01335.x. PMID 22150020. S2CID 38149716.