We have presented the case that nausea and vomiting of pregnancy (NVP) has an organic cause by applying information from our own work and the work of 143 other researchers working in the field of early pregnancy presented in 25 separate sections.
A temporal relationship between maternal serum human chorionic gonadotrophin (hCG) and NVP during weeks 7-14 from the first day of the last period (L.M.P.) for a group of pregnant women became a starting point. Other investigators found raised maternal serum hCG in women who had hyperemesis gravidarum, twin pregnancies or hydatidiform moles all three of these conditions are known to be associated with an increase incidence of severe NVP or hypermemsis gravidarum (HG). One outstanding fact is that very high serum hCG in women with choriocarcinoma is not associated with nausea and vomiting. However it is now known that the hCG in this condition is 100% ‘nicked’ in the β sub-unit of the hCG molecule, so becoming biologically inactive. Therefore maternal hCG in normal pregnancy can be related to NVP between weeks 6-14 from LMP. NVP is episodic in nature for the majority of women who have two or more episodes of nausea daily. This type of episodic pattern is also seen in the maternal serum concentration of hCG. However it has not been demonstrated that hCG is a substantially emetic hormone, it may be possible that some other factor either stimulating maternal hCG or which is stimulated by maternal hCG may be the cause of NVP.
Using Med-Line and associated medical papers we found there are at least 14 hormones, cytokines or eicosanoids including Prostaglandin E2, which stimulate the synthesis and release of hCG in syncytiotrophoblast cells in the early trophoblast of the developing placenta. Only Prostaglandin E2 (PGE2) and Prostaglandin F2 alpha (PGF2) of these substances are known to be emetic which was shown when the prostaglandins were given to procure legal terminations of pregnancy.
PGE2 has been demonstrated to be synthesised in the syncytiotrophoblast cells of the human trophoblast at 7-11 weeks from LMP. These cells are in direct contact with maternal blood at the materno-fetal interface. The production of PGE2 in these cells is stimulated by several hormones and cytokines, notably Interleukin-1 and hCG itself. In order for the synthesis of PGE2 in early pregnancy to be properly controlled, the activity of the enzyme Prostaglandin dehydrogenase (PGDH) is present in early trophoblast cells. PGDH controls the first stage in the oxidisation of PGE2 into its inactive metabolite 15 Ketoprostaglandin E2. The syncytiotrophoblast is devoid of PGDH which therefore contains high levels of PGE2. These syncytiotrophoblast cells of the chorionic villi are in direct contact with maternal blood. PGDH is under progesterone control. As progesterone levels fall during weeks 5-9 from LMP, so will PGDH activity in decidual and chorionic villi cells levels fall, while PGE2 in trophoblast and maternal serum levels will rise. Weeks 6-10 from LMP are the weeks of pregnancy when NVP symptoms increase most sharply. A rise in PGE2 has also be associated with the increased NVP when anti-progesterones are given to obtain a legal therapeutic abortion in modern times. Search of medline and associated scientific literature has shown that Prostaglandin E2 is synthesised and released in early pregnancy into the maternal circulation from syncytiotrophoblast and decidual cells as well as in the extra cellular matrix of the decidua. Endovascular trophoblast alter the configuration of the decidual spiral arteries to become low resistance sinusoid sacs which maintain the utero- placental blood flow at very low pressures. We have shown that maternal serum PGE2 was higher when women had NVP than when they had no NVP on the same day. This remained true whether the sample taken at the time she had higher NVP was before or after mid-day. However it would be inadvisable to reduce maternal PGE2 due to its functions of immune suppression and glycogenolytic effects in early pregnancy.
Did you know?
Early access to treatments is likely to be more effective and may prevent symptoms developing into HG
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