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J. Perinat. Med. 41 (2013) 23-25 • Copyright by Walter de Gruyter • Berlin • Boston. DOI 10.1515/JPM.2011.115
Optimization of women's health before conception when
pregnancy has been postponed
Joachim W. Dudenhausen1, Amos Grunebaum1 and
rarely features in the public debate. The data in the literature
Ursula M. Staudinger2
on the medical risks of late motherhood are contradictory. It
is striking that in societies with a high incidence of late
Department of Obstetrics and Gynecology, Weill MedicalCollege of Cornell University, New York, NY, USA
motherhood, the maternal and fetal mortality among that
2 Jacobs Center of Lifelong Learning and Institutional
group is significantly lower than in societies with a low inci-
Development, Jacobs University Bremen, Bremen,
dence of late motherhood w2x. We conclude after a careful
review of the literature that women entering motherhood latein life but with few other risks have good pregnancy out-come, although they are still subject to greater risks com-
pared with younger women.
Objectives: In the industrialized world, the mean age at
Those differences arise, inter alia, from the fact that as the
which mothers give birth to their first child has increased.
age at pregnancy increases so does the rate of medical and
The purpose of this article was to review the available evi-
surgical disease; that is, there is a greater incidence of car-
dence in order to optimize preconception care in women who
diovascular, metabolic, renal, oncological, and autoimmune
have postponed childbearing to the later years of the repro-
diseases. A large population-based study w11x demonstrated
ductive life cycle.
in the case of pregnancy after age 40 years, above all, an
Methods: Review of literature.
increased rate of cesarean delivery (primiparous age
Results: There is a paucity of evidence and rigorous studies
40s47% vs. age 20–29s23%), an increased incidence of
to advise mothers on the potential interventions for optimiz-
intrauterine growth restriction (primiparous age 40s3% vs.
ing pregnancy outcome.
age 20–29s1%), an increased incidence of gestational dia-
Conclusions: Evidence-based guidelines for advising wom-
betes (primiparous age 40s7% vs. age 20–29s2%), and a
en who postponed childbearing are scant, and further
shorter pregnancy term (primiparous age 40s273 days vs.
research in this important area is urgently needed.
age 20–29s278 days). Other studies have drawn attentionto the greater incidence of pre-eclampsia, the greater inci-
Keywords: Delayed motherhood; nutrition; plasticity; pre-
dence of postpartum bleeding, and the increased number of
conception care.
There have been calls for more intense and complete level
of preconception care and counseling w4, 6–8x. On the basis
of preventive concern for the child, previous studies haverecommended the taking of periconceptional folic acid to
Demographic statistics indicate that, over recent decades,
encourage vaccinations before pregnancy, and in the case of
there has been a considerable increase in the mean age at
chronic diseases the adjustment of treatment strategies to
which mothers in the industrialized world give birth to their
reflect the planned pregnancy.
first child. For example, in Bavaria (Germany), since the1980s the share of pregnant women accounted for by the age
Pregnancy at the end of the reproductive cycle represents
group 35–39 has roughly tripled from 4% to 12% w17x. In
a major test to the multiple organ systems of the potential
the United States, between 1990 and 2001 the rate of those
mother. Thus, successful late motherhood depends on the
giving birth in the age groups 35–39, 40–44, and 45–49
availability and the activation of physical resources. Timely
increased by 30%, 47%, and 190%, respectively w5x. This
preventive measures may help avoid the depletion of such
development toward later childbearing also needs to be seen
resources as well as their replenishment.
in conjunction with the tremendous extension of the average
The recommendation given to women, in the context of
life expectancy (i.e., by 45 years) that modern societies have
family planning counseling, of not delaying their pregnancy
experienced during the last 150 years.
is often unrealistic. As a result, the aim of family planning
Much emphasis has been placed on the relations between
counseling seeking to ensure low-risk and successful preg-
the frequency of chromosomal anomalies and advancing
nancies with a positive outcome should be to recommend to
maternal age, as well as the risk of multiple pregnancies in
women preventive measures that contribute to a favorable
women with late motherhood. However, the extensive liter-
pregnancy and birthing process at a later age. Compelling
ature on the risks of late motherhood both for the mother
evidence for such counseling has not been fully established.
and the fetus, and on the subsequent prognosis for the child
In this context, the age of the father and the quality of his
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24 Dudenhausen et al., Preconception care in women with late motherhood
semen are important and were not valued highly. However,
who enter motherhood late in life would produce protective
both practice and research offer support for this approach.
effects in that regard. The authors are unaware of any clinicalstudies on that question. However, molecular cell culturestudies appear to support the hypothesis w25x.
Possible preventive measures
Evidence (or lack thereof) is rare from preventive areas, such
as nutrition recommendations. Other factors, such as micro-nutrients, alcohol consumption, smoking, vitamin D intake,omega fatty acids, estrogen levels, stress, and sports are
Research on environmentally induced biological changes
reviewed and put in context here.
during aging—that is, focusing on the organism's adaptive
An important preventive measure that can be taken before
plasticity w24x—is particularly crucial to this area especially
pregnancy is to observe a healthy and balanced diet consist-
with regard to the pathophysiology and prevention of age-
ing of 20% protein, 35% fat, and 45% carbohydrates, as well
related diseases (e.g., high blood pressure or diabetes).
as to avoid excess weight. Women who are overweight and
Compared to behavioral sciences and neurosciences we.g.,
obese are more likely to experience complications, such as
w26x w27xx, the notion of facilitating positive plasticity seems
cardiovascular disease, diabetes mellitus type 2, and hyper-
underdeveloped in medical research. Human development
tension. Preventive action should include adoption of a diet
and aging are not determined but rather are the result of
reflecting the food pyramid and the avoidance of excess
continuous interactions between biology, context, and the
weight and obesity w16x. Intervention studies involving
aging individual w3x. Thus, it is of utmost importance to
weight reduction before pregnancy suggest a lowering of
explore the conditions under which developmental potential
pregnancy risks for women who were previously obese w1x
can be activated. It is known that this plasticity is greatest
as the incidence of birthing complications, diabetes, and pre-
at the beginning of the lifespan and decreases thereafter.
eclampsia was reduced. It is recommended that women
However, some plasticity is maintained until death unless a
should aim for a body mass index between 20 and 25 w22,
severe pathology intervenes. In this context, the notion of
‘‘the cell as a memory storage of environmental signals'' is
The question of whether deficiencies in micronutrients can
extremely attractive for medical research w13x. More system-
exacerbate the aging process and if supplementation can
atic knowledge is necessary about the historical changes in
delay such a process remains to be established by evidence-
vital parameters in order to learn about the biological differ-
based research.
ence between succeeding cohorts.
The prolonged consumption of high quantities of alcohol
The current state of research also lacks evidence-based
by women (more than 40 g/day over a long period) results
findings that demonstrate links between epigenetic events
in organic changes w9x that contribute to increased risks dur-
and age-related phenotypic phenomena. However, in the
ing pregnancy at any age.
light of the considerable research in this area, it is increas-
Smoking causes considerable long-term harm to women's
ingly recognized that the epigenome is plastic and that this
bodies w21x. This explains the well-respected and widespread
plasticity is at its greatest when the organism is young. None-
recommendation not to smoke at any time.
theless, the extent to which targeted environmental measures
Women of reproductive age who wish to have a child may
can be used as epigenetic events and thus influence the phe-
be advised to take vitamin D supplements (400 IU vitamin
notype in the desired manner remains largely speculative.
D daily), inter alia, with a view of increasing the likelihood
Thus, considerable research is still required both on the phys-
that a subsequent pregnancy will result in a successful spon-
iological changes in the body and on the possibilities to exert
taneous delivery w12x. For a definitive assessment of that
a preventive influence. For example, we propose that phys-
recommendation, detailed observational studies are needed,
iological changes in the Doppler flow patterns in the uterine
focusing on vitamin D levels in non-pregnant women, the
arteries be examined with reference to a woman's age and
progress of their subsequent pregnancy, and fetal outcome.
her preexisting diseases and following preventive action.
The concentration of unsaturated fatty acids in tissues is
Also, it would be highly recommendable to very closely
important for healthy development w14, 15, 18, 19x. At pres-
investigate women who successfully gave birth to a child
ent, there are no intervention studies under way in connection
rather late in life in order to derive further ideas about the
with the issue addressed in our paper. For that reason, no
conditions, and their interactions, that might foster the suc-
recommendations can be given. However, evidence concern-
cess of late childbearing. Subsequently, controlled clinical
ing the resolution of mucosal inflammatory responses
studies testing such hypotheses need to follow.
orchestrated by chemical mediators w20x would suggest that
In all areas, recommendations should take account of the
useful findings might follow.
fact that fertility decreases with age. Whereas in the case of
From the very beginning of life, estrogens are crucial for
20–24-year-old women seeking to have a child, some 90%
the development of many features of the human organism
will become pregnant within a year, in the case of 30–39-
w10x. It is unknown whether estrogen substitution in women
year-olds that figure drops to 50%. Whether that percentage
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Dudenhausen et al., Preconception care in women with late motherhood
is likely to change in the future, in light of the suggestions
advanced in this article, remains entirely open.
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The authors stated that there are no confl icts of interest regarding the
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w14x Hadders-Algra M, Bouwstra H, van Goor SA, Dijck-Brouwer
Received August 16, 2011. Revised August 30, 2011. Accepted
DA, Muskiet FA. Prenatal and early postnatal fatty acid status
August 31, 2011. Previously published online November 3, 2011.
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Cell Physiol Biochem 2015;37:651-665 DOI: 10.1159/000430384 © 2015 S. Karger AG, Basel Published online: September 08, 2015 Spaas et al.: Chondr ogenic Priming Enhances MSC Adhesion ed: August 04, 2015 This is an Open Access article licensed under the terms of the Creative Commons Attribution- NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to
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