Editing Pregnancy

Research on outcomes of '''pregnancy''' for women with ME is limited. There is some evidence of symptom improvement or remission in various inflammatory and autoimmune diseases during pregnancy. This may be due to hormonal or immune changes.<ref>{{Cite journal | date = 2013-08-01 | title = Do pregnancy-related changes in the microbiome stimulate innate immunity?|url=https://www.sciencedirect.com/science/article/pii/S1471491413001093|journal=Trends in Molecular Medicine|language=en|volume=19|issue=8 | pages = 454–459|doi=10.1016/j.molmed.2013.06.002|issn=1471-4914}}</ref>

== Biological changes during pregnancy ==

===Development of the placenta===

The placenta is a vascular organ that develops during pregnancy, attaching to the wall of the uterus. The umbilical cord connects the placenta to the developing fetus, allowing for blood to pass from the mother. The placenta allows for nutrient supply, thermoregulation, waste elimination, and gas exchange for the developing fetus, as well as production of hormones that support pregnancy for the mother. Towards the end of the pregnancy, the placenta provides antibodies to the fetus for protection against infectious pathogens after birth.<ref name=":4">{{Cite web|url=https://www.pregnancybirthbaby.org.au/what-is-the-placenta | title = What is the placenta? | last = | first = | date = July 2017 | website = Pregnancy, Birth & Baby|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref>  

The fetus and the placenta may be detected as foreign threat by the mother's immune system. To prevent this from happening, the placenta secretes molecules containing Neurokinin-B. This is the same mechanism that parasitic nematodes use to evade detection by the host immune system. Additionally, there is a presence of lymphocytic suppressor cells in the fetus, which can inhibit maternal [[Cytotoxic T cell|cytotoxic T cells]].<ref name=":4" /><ref>{{Cite journal | last = Sakamoto | first = Rie | last2 = Osada | first2 = Hisao | last3 = Iitsuka | first3 = Yoshinori | last4 = Masuda | first4 = Kentarou | last5 = Kaku | first5 = Kenshi | last6 = Seki | first6 = Katsuyoshi | last7 = Sekiya | first7 = Souei | date = May 2003 | title = Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy|url=https://www.ncbi.nlm.nih.gov/pubmed/12699441|journal=Clinical Endocrinology|volume=58|issue=5 | pages = 597–600|issn=0300-0664|pmid=12699441}}</ref>  [[File:Pregnant non pregnant histamine ascorbic acid.jpg|right|350x350px]]

===Immune system===

As a prerequisite for a successful pregnancy, the [[immune system]] undergoes changes so that the mother's body will not reject the fetus.<ref name=":2">{{Cite journal | last = Reinhard | first=G. | last2 = Noll | first2 = A. | last3 = Schlebusch | first3 = H. | last4 = Mallmann | first4 = P. | last5 = Ruecker | first5 = A.V. | date = 1998-04-28 | title = Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes|url=https://www.ncbi.nlm.nih.gov/pubmed/9588218|journal=Biochemical and Biophysical Research Communications|volume=245|issue=3 | pages = 933–938|doi=10.1006/bbrc.1998.8549|issn=0006-291X|pmid=9588218}}</ref> To do so, there is a general shift of the immune system from the a pro-inflammatory state (Th1) to an anti-inflammatory state (Th2) during pregnancy. Helper T cells (Th) of the immune system are divided into two main categories, Th1 and Th2, that have opposite functional activity. An immune response can be categorized as a Th1 response (pro-inflammatory, usually in response to pathogens or injury) or a Th2 response (anti-inflammatory, can be used to down-regulate the Th1 state). While both Th1 and Th2 responses are at play, the immune system tends to be dominated by one or the other depending on the Th1/Th2 balance.<ref>{{Cite journal | last = Kidd | first=Parris | date = Aug 2003 | title = Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease|url=https://www.ncbi.nlm.nih.gov/pubmed/12946237|journal=Alternative Medicine Review: A Journal of Clinical Therapeutic|volume=8|issue=3|pages=223–246|issn=1089-5159|pmid=12946237}}</ref>

One study has shown that T cells from pregnant women produce less Th1 cytokines and more Th2 cytokines, indicating a general shift toward the Th2 anti-inflammatory state. Additionally, levels of regulatory T cells [[Treg|(Tregs)]], progesterone, and estrogen increase during pregnancy, which have anti-inflammatory properties.<ref>{{Cite journal | last = Munoz-Suano | first = Alba | last2 = Hamilton | first2 = Alexander B. | last3 = Betz | first3 = Alexander G. | date=May 2011 | title = Gimme shelter: the immune system during pregnancy|url=http://www.ncbi.nlm.nih.gov/pubmed/21488887|journal=Immunological Reviews|volume=241|issue=1|pages=20–38|doi=10.1111/j.1600-065X.2011.01002.x|issn=1600-065X|pmid=21488887}}</ref>

In contrast, the T cells in women with recurrent spontaneous abortions produce normal, non-pregnancy levels of Th1 and Th2 cytokines, indicating a Th1 pro-inflammatory state in unsuccessful pregnancies.<ref name=":2" /> In this way, many spontaneous abortions are similar to organ transplant rejections; a Th2 state is required for successful pregnancies and organ transplants, and failed organ transplants usually occur in people who remain in a Th1 dominant state.<ref name=":2" />  

==Pregnancy and ME/CFS ==

=== Fertility ===

Women with [[chronic fatigue syndrome]] report higher rates of [[polycystic ovarian syndrome]] (PCOS) and anovulatory cycles, higher rates of [[dysmenorrhea]] and higher rates of [[endometriosis]].<ref name=":0">{{Cite journal | last = Allen | first = Peggy Rosati | date = Jul 2008 | title = Chronic fatigue syndrome: implications for women and their health care providers during the childbearing years|url=https://www.ncbi.nlm.nih.gov/pubmed/18586181|journal=Journal of Midwifery & Women's Health|volume=53|issue=4|pages=289–301; quiz 399|doi=10.1016/j.jmwh.2007.12.001|issn=1542-2011|pmid=18586181}}</ref>

=== Symptoms during pregnancy ===

There has been very little research on pregnancy and ME/CFS. One retrospective survey found that 41% of respondents reported no change in symptoms during pregnancy, 30% improved and 39% got worse.<ref name=":1">{{Cite journal | last = Schacterle | first = Richard S. | last2 = Komaroff | first2 = Anthony L. | date = 2004-02-23 | title = A Comparison of Pregnancies That Occur Before and After the Onset of Chronic Fatigue Syndrome|url=http://archinte.jamanetwork.com/article.aspx?articleid=216675|journal=Archives of Internal Medicine|language=en|volume=164|issue=4 | pages = 401|doi=10.1001/archinte.164.4.401|issn=0003-9926}}</ref> 

In clinical practice, Dr. [[Nancy Klimas]], Dr. [[Lucinda Bateman]], and Dr. [[Charles Lapp]] report higher rates of improvement or remission during pregnancy. Klimas reports that in the 20 women she has followed through pregnancy, improvement in symptoms during pregnancy was "almost universal" and in some cases resulted in total temporary remission. Dr. Lapp reported that 25 out of 27 patients in his practice felt better during pregnancy. Dr. Klimas suggests that improvement may be due to increased blood volume during pregnancy or hormonal changes.<ref name=":0" />

=== Postpartum ===

In one survey, after delivery, 30% had no change in symptoms, 20% improved, and 20% got worse. Dr. Klimas reports that her patients typically do well postpartum until about 3 to 6 months after, at which time there is often a severe relapse.<ref name=":0" /> Another study indicates that postpartum relapse or worsening of symptoms is likely due to the extra effort of taking care of a baby, as well as the shift away from pregnancy-related hormones and the TH2 state.<ref name=":3" /> 

Postpartum depression is two to three times more common in mothers with ME/CFS compared to healthy mothers.<ref name=":3" /> 

=== Complications ===

When comparing these women's pregnancies after illness onset to pregnancies before illness onset (but not to healthy controls), the rate of complications were similar. In pregnancies occurring after illness onset, there was a higher rate of miscarriages (30% vs. 8%) and development delays or learning disabilities (21% vs. 8%).<ref name=":1" /> However, this may be explained by maternal age (pregnancies before illness onset occurred when women were younger than pregnancies occurring after illness onset).<ref name=":1" />

== Significant studies ==

===Schacterle and Komaroff (2004) ===
Schacterle and Komaroff (2004) conducted a retrospective study on women with ME/CFS who had undergone pregnancy before and/or after onset of illness. Many women with ME/CFS have to make the difficult decision of whether to have a child, and concern due to illness has resulted in lower rates of pregnancy. Of interest, "women who had children before the onset of CFS and decided to continue to have children had more pregnancies after the onset. Among the 19 patients (22%) who reported pregnancies both before and after the onset of CFS, 30 pregnancies occurred before and 46 occurred after the onset."

The study showed that during pregnancy, symptoms were unchanged or improved in 71% of women with ME/CFS. After pregnancy, symptoms were unchanged or improved in 50% of patients. Many women report concern over adverse outcomes for their children, yet there is little evidence that this occurs. Importantly, most maternal and offspring outcomes from pregnancies that occurred after illness onset were not systematically worse than pregnancies occurring prior to illness onset. These data are overall encouraging for women with ME/CFS considering pregnancy. <ref name=":1" />

== Pregnancy in other conditions ==

In general, [[Th1]] dominant immune disorders tend to improve during pregnancy while [[Th2]] dominant immune disorders tend to worsen.<ref>{{Cite journal | last = ØSTENSEN | first = MONICA | date = 1999-06-01 | title = Sex Hormones and Pregnancy in Rheumatoid Arthritis and Systemic Lupus Erythematosus|url=http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1999.tb07630.x/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=|journal=Annals of the New York Academy of Sciences|language=en|volume=876|issue=1|doi=10.1111/j.1749-6632.1999.tb07630.x/abstract|issn=1749-6632}}</ref> For example, in a study of women with [[rheumatoid arthritis]] 75% of patients experienced remission of their RA during pregnancy and 62% experienced a worsening of symptoms after delivery.<ref>{{Cite journal | last = Østensen | first = Monika | last2 = Aune | first2 = Berit | last3 = Husby | first3 = Gunnar | date = Jan 1983 | title = Effect of Pregnancy and Hormonal Changes on the Activity of Rheumatoid Arthritis|url=http://www.tandfonline.com/doi/abs/10.3109/03009748309102886|journal=Scandinavian Journal of Rheumatology|language=en|volume=12|issue=2 | pages = 69–72|doi=10.3109/03009748309102886|issn=0300-9742}}</ref> 92% of pregnant women with RA relapse within the first three months after delivery.<ref>{{Cite journal | date = 2010-01-01 | title = The impact of pregnancy on rheumatoid arthritis outcome: The role of maternofetal HLA class II disparity|url=https://www.sciencedirect.com/science/article/pii/S1297319X09001997|journal=Joint Bone Spine|language=en|volume=77|issue=1|pages=36–40|doi=10.1016/j.jbspin.2009.11.009|issn=1297-319X}}</ref> The course of [[Crohn's disease]] and [[ulcerative colitis]] improves during and after pregnancy.<ref>{{Cite journal | date = 2013-08-01 | title = Do pregnancy-related changes in the microbiome stimulate innate immunity?|url=https://www.sciencedirect.com/science/article/pii/S1471491413001093|journal=Trends in Molecular Medicine|language=en|volume=19|issue=8 | pages = 454–459|doi=10.1016/j.molmed.2013.06.002|issn=1471-4914}}</ref> In relapsing-remitting [[multiple sclerosis]], rates of relapse decrease during the first two trimesters and increase significantly postpartum.<ref>{{Cite journal | last = Confavreux | first = Christian | last2 = Hutchinson | first2 = Michael | last3 = Hours | first3 = Martine Marie | last4 = Cortinovis-Tourniaire | first4 = Patricia | last5 = Moreau | first5 = Thibault | date = 1998-07-30 | title = Rate of Pregnancy-Related Relapse in Multiple Sclerosis|url=http://www.nejm.org/doi/full/10.1056/nejm199807303390501|journal=New England Journal of Medicine|language=EN|volume=339|issue=5|pages=285–291|doi=10.1056/nejm199807303390501|issn=0028-4793}}</ref>

By contrast, pregnancy increases rates of [[lupus]] flares.<ref>{{Cite journal | last = Ruiz-Irastorza | first=G. | last2 = Lima | first2 = F. | last3 = Alves | first3 = J. | last4 = Khamashta | first4 = M.A. | last5 = Simpson | first5 = J. | last6 = Hughes | first6 = G. R.V. | last7 = Buchanan | first7 = N.M.M. |  date = 1996-02-01 | title = INCREASED RATE OF LUPUS FLARE DURING PREGNANCY AND THE PUERPERIUM: A PROSPECTIVE STUDY OF 78 PREGNANCIES|url=https://academic.oup.com/rheumatology/article/35/2/133/1782393|journal=Rheumatology|language=en|volume=35|issue=2|pages=133–138|doi=10.1093/rheumatology/35.2.133|issn=1462-0324}}</ref> In a retrospective study of [[fibromyalgia]] patients based on personal interviews, nearly all patients surveyed experienced a worsening of symptoms during pregnancy, especially during the third trimester. Fibromyalgia did not appear to have an adverse effect on the outcome of pregnancy or the health of the baby.<ref>{{Cite journal | last = Østensen | first = Monika | last2 = Rugelsjoen | first2 = Anne | last3 = Wigers | first3 = Sigrid Horven | date = Jan 1997 | title = The Effect of Reproductive Events and Alterations of Sex Hormone Levels on the Symptoms of Fibromyalgia|url=http://www.tandfonline.com/doi/abs/10.3109/03009749709065698|journal=Scandinavian Journal of Rheumatology|language=en|volume=26|issue=5|pages=355–360|doi=10.3109/03009749709065698|issn=0300-9742}}</ref>

== Related potential therapy ==

===Human Placental Extract===

HPE is used as a type of Complementary and Alternative Medicine therapy in various conditions involving chronic inflammation for its anti-inflammatory properties. In one interventional trial, injections of subcutaneous human placental extract (HPE) were found to improve symptoms in ME/CFS patients. Of note, the study did not find a difference between HPE injections and placebo. <ref>{{Cite journal | last = Park | first = Sat Byul | last2 = Kim | first2 = Kyu-Nam | last3 = Sung | first3 = Eunju | last4 = Lee | first4 = Suk Young | last5 = Shin | first5 = Ho Cheol | date = 2016 | title=Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study|url=https://www.jstage.jst.go.jp/article/bpb/advpub/0/advpub_b15-00623/_article|journal=Biological & Pharmaceutical Bulletin|language=en|volume=39|issue=5 | pages = 674–679|doi=10.1248/bpb.b15-00623|issn=0918-6158}}</ref>
== See also ==

*[[Menstrual cycle]]
==Learn more==
*[http://emerge.org.au/about-mecfs/diagnosis/managing-symptoms-daily-basis/pregnancy-motherhood-mecfs/#.Vkp1cLSYe6x Pregnancy, Motherhood, Parenthood and ME/CFS]<ref>{{Cite news | url=http://emerge.org.au/about-mecfs/diagnosis/managing-symptoms-daily-basis/pregnancy-motherhood-mecfs/#.Vkp1cLSYe6x | title = Pregnancy, Motherhood, Parenthood and ME/CFS - Emerge Australia|work=Emerge Australia|access-date=2018-08-11|language=en-US}}</ref>
*2010, [http://www.njcfsa.org/wp-content/uploads/2010/09/Pregnancy-in-Women-with-ME-CFS.pdf Pregnancy in Women with Chronic Fatigue Syndrome (ME/CFS)]<ref name=":3">{{Cite news | url=http://www.njcfsa.org/wp-content/uploads/2010/09/Pregnancy-in-Women-with-ME-CFS.pdf | title = Pregnancy in Women with Chronic Fatigue Syndrome (ME/CFS) | last = Underhill | first = Rosemary | date = |work=NJCFSA|access-date=|archive-url=|archive-date=|url-status=|publisher=New Jersey Chronic Fatigue Syndrome Association|format=PDF}}</ref> 
*2016, [https://batemanhornecenter.org/pregnancy-and-mecfs/ Pregnancy and ME/CFS]<ref>{{Cite news | url=https://batemanhornecenter.org/pregnancy-and-mecfs/ | title = Pregnancy and ME/CFS | last = Reynolds | first = Leigh | date = 2016-07-06|work=Bateman Horne Center|access-date=2018-08-11|archive-url=|archive-date=|url-status=|publisher=Bateman Horne Center|language=en-US}}</ref>
*[https://www.healthrising.org/blog/2014/03/02/pregnancy-chronic-fatigue-syndrome-four-mothers-talk-offer/ Pregnancy and Chronic Fatigue Syndrome-- Four Mothers Who've Been Through It Talk]

== References ==
{{Reflist}}

[[Category:Triggers and risk factors]]
[[Category:Reproductive system‎]]