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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20110202.23_25.tpArticle in press - uncorrected proof 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 Brought to you by Furman University J.B. Duke Library Download Date 6/26/14 5:52 PM Article in press - uncorrected proof 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 Brought to you by Furman University J.B. Duke Library Download Date 6/26/14 5:52 PM Article in press - uncorrected proof 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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and child health: basic principles. Arch Dis Child. Epub 2010Aug 16 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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