Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.
[Effect of advanced age on fertility and pregnancy in women]
at UpToDate
UpToDate, Inc. is a company in the Wolters Kluwer Health division of Wolters Kluwer whose main product is UpToDate, a software system that is a point of care, point-of-care medical resource.
The UpToDate system is an Evidence-based medicine, evide ...
. Author: Ruth C Fretts. Section Editor: Louise Wilkins-Haug. Deputy Editor: Vanessa A Barss. This topic last updated: 3 December 2012. The variability in definitions is in part explained by the effects of increasing age occurring as a
continuum
Continuum may refer to:
* Continuum (measurement), theories or models that explain gradual transitions from one condition to another without abrupt changes
Mathematics
* Continuum (set theory), the real line or the corresponding cardinal number ...
rather than as a threshold effect.
In Western, Northern, and Southern Europe, first-time mothers are on average 27 to 32 years old, up from 23 to 25 years at the start of the 1970s. 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. Asia, Japan and the United States are all seeing average age at first birth on the rise, and increasingly the process is spreading to countries in the
developing world
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
such as
China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
,
Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
and
Iran
Iran, officially the Islamic Republic of Iran, and also called Persia, is a country located in Western Asia. It is bordered by Iraq and Turkey to the west, by Azerbaijan and Armenia to the northwest, by the Caspian Sea and Turkmeni ...
. In the U.S., the average age of first childbirth was 26.9 in 2018.
Advanced maternal age is associated with adverse reproductive effects such as increased risk of
infertility
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
,
and that the children have
chromosomal abnormalities
A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
.
The corresponding
paternal age effect
The paternal age effect is the statistical relationship between the father's age at conception and biological effects on the child. Such effects can relate to birthweight, congenital disorders, life expectancy and psychological outcomes. A 2017 ...
is less pronounced.
History
Having children later 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 are associated with the arrival of 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
Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
being concentrated either among very young or increasingly older mothers. This is sometimes known as the "
rectangularisation" of
fertility patterns.
Examples
In the USA, the average age at which women bore her first child advanced from 21.4 years old in 1970 to 26.9 in 2018.
The German
Federal Institute for Population Research claimed 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.
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
![Age and female fertility](https://upload.wikimedia.org/wikipedia/commons/5/57/Age_and_female_fertility.png)
A woman's fertility peaks lasts during the twenties and first half of thirties, after which it starts to decline, with advanced maternal age causing an increased risk of
female infertility
Female infertility refers to infertility in women. It affects an estimated 48 million women, with the highest prevalence of infertility affecting women in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Cen ...
.
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
** 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
** 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
** 64% will have a conception ending in a live birth within four years.
Risk of birth defects
![Down risk by maternal age](https://upload.wikimedia.org/wikipedia/commons/7/72/Down_risk_by_maternal_age.png)
A woman's risk of having a baby with
chromosomal abnormalities
A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
increases with her age.
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
is the most common chromosomal
birth defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
, and a woman's risk of having a baby with Down syndrome is:
* At age 20, 1 in 2000
* At age 24, 1 in 1300
* At age 25, 1 in 1200
* At age 29, 1 in 950
* At age 30, 1 in 900
* At age 34, 1 in 450
* At age 35, 1 in 350
* At age 39, 1 in 150
* At age 40, 1 in 100
* At age 44, 1 in 40
* At age 45, 1 in 30
* At age 49, 1 in 10
Other effects
Advanced maternal age is associated with adverse outcomes in the
perinatal period
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...
, which may be caused by detrimental effects on
decidua
The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilised egg to support. The decidua is under the influ ...
l and
placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
l development.
The risk of the mother dying before the child becomes an adult increases by more advanced maternal age, such as can be demonstrated by the following data from France in 2007:
The above table is not to be confused with
maternal mortality
Maternal death or maternal mortality is defined in slightly different ways by several different health organizations. The World Health Organization (WHO) defines maternal death as the death of a pregnant mother due to complications related to pre ...
.
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.
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. Finally, although older maternal age doesn’t necessarily imply older paternal age, researchers have suggested links between older
paternal age
The paternal age effect is the statistical relationship between the father's age at conception and biological effects on the child. Such effects can relate to birthweight, congenital disorders, life expectancy and psychological outcomes. A 2017 ...
and improved child outcomes, including increased IQ and educational attainment and increased telomeric length, which is associated with greater longevity. However, it is more or less uncertain whether these entities are ''effects'' of advanced maternal age, are ''contributors'' to advanced maternal age, or common effects of a certain state such as personality type.
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 technology developments cases of
post-menopausal
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
pregnancies have occurred, and there are several known cases of
older women
"Older Women" is a song written by Jamie O'Hara, and recorded by American country music artist Ronnie McDowell
Ronald Dean McDowell Sr. (born March 25, 1950) is an American country music artist, songwriter, and actor. He is best known for his 1 ...
carrying a pregnancy to term, usually with
in vitro fertilization
In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
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
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
.
This decline is tied to a decline in the number of
ovarian follicle
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with th ...
s. Although about 1 million
oocyte
An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
s are present at birth in the human
ovary
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
, only about 500 (about 0.05%) of these
ovulate
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
, and the rest do not (
ovarian follicle atresia
Follicular atresia refers to the process in which a follicle fails to develop, thus preventing it from ovulating and releasing an egg. It is a normal, naturally occurring progression that occurs as mammalian ovaries age. Approximately 1% of mamma ...
). The decline in
ovarian reserve Ovarian reserve is a term that is used to determine the capacity of the ovary to provide egg cells that are capable of fertilization resulting in a healthy and successful pregnancy. With advanced maternal age the number of egg cell that can be succe ...
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
Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
decline with age, there is also a parallel increase in pregnancy failure and
meiotic
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately res ...
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 cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, an ...
s. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
al repair, and it is especially active during
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
. Meiosis is the general process by which
germ cell
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during embry ...
s are formed in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, 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
The origin and function of meiosis are currently not well understood scientifically, and would provide fundamental insight into the evolution of sexual reproduction in eukaryotes. There is no current consensus among biologists on the questions of h ...
). Human primary oocytes are present at an intermediate stage of meiosis, that is prophase I (see
Oogenesis
Oogenesis, ovogenesis, or oögenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage.
O ...
). Titus et al.
also showed that expression of four key
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
genes that are necessary for homologous recombinational repair (''
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'', ''
MRE11
Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''.
Function
This ge ...
'', ''
Rad51
DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to th ...
'' 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
Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
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.
See also
*
Age and female fertility
Female fertility is affected by age and is a major fertility factor for women. A woman's fertility peaks between the late teens and late-20s, after which it starts to decline slowly. While many sources suggest a more dramatic drop at around 35, ...
*
Childlessness
Childlessness is the state of not having children. Childlessness may have personal, social or political significance.
Childlessness, which may be by choice or circumstance, is distinguished from voluntary childlessness, which is voluntarily havin ...
*
Fertility factor (demography)
Fertility factors are determinants of the number of children that an individual is likely to have. Fertility factors are mostly positive or negative correlations without certain causations.
Factors generally associated with increased fertility i ...
*
List of countries by age at first marriage
This is a list of countries by age at first marriage. This list is current from contemporary surveys and does not treat the topic in history. Currency of information varies by country.
Because the age distribution of people at first marriage is ...
*
Pregnancy over age 50
Pregnancy over the age of 50 has, over recent years, become possible for more women, and more easily achieved for many, due to recent advances in assisted reproductive technology, in particular egg donation. Typically, a woman's fecundity ends wi ...
*
Teenage pregnancy
Teenage pregnancy, also known as adolescent pregnancy, is pregnancy in a female adolescent or young adult under the age of 20. This includes those who are legally considered adults in their country. The WHO defines adolescence as the period bet ...
References
Citations
General sources
*
*
*
*
Further reading
* Charlemagne, 9 February 2006
"The Fertility Bust" ''
The Economist
''The Economist'' is a British weekly newspaper printed in demitab format and published digitally. It focuses on current affairs, international business, politics, technology, and culture. Based in London, the newspaper is owned by The Econo ...
''
*
*
*
*
*
* {{cite thesis , last1=Sobotka , first1=Tomás , title=Postponement of childbearing and low fertility in Europe , date=2004 , hdl=11370/7fe0743c-9766-4ae9-befe-3edae1006c6e
External links
Postponement of childbearing and low fertility in EuropePower Point presentation by Tomas Sobotka
InterNational Council on Infertility Information Dissemination
Fertility
Midwifery
Motherhood