Good news for those women who suffer with NVP or the more severe Hyperemesis Gravidarum (HG), a drug that has been used worldwide for the past forty years has now been launched in the UK. It is a combination of antihistamine and vitamin B6 (do NOT attempt to make your own combination of this as it can be dangerous in the wrong dosage). What is NVP/HG? his is a debilitating condition that over 70% of pregnant women suffer with to some extent, at worse it can hospitalize you, it is under-diagnosed as many women do not know this is a real condition and do not see their GP about it. Do they know what causes HG, they may have found a genetic link to this condition.
"The UK Medicines and Healthcare products Regulatory Agency (MHRA) approved the marketing authorisation application for the drug in July this year. Office of National Statistics and the Royal College of Obstetricians and Gynaecologists report indicated NVP affects nearly 751,923 women in the UK each year" according to an article in Pharmaceutical Technology.
NVP and HG are forms of nausea and vomiting in pregnancy (NVP), the most severe form being Hypermesis Gravidarum (HG), these forms of sickness do not respond to any other forms of remedies available and the term morning sickness does not adequately describe these symptoms.
NVP is a common condition that over 70% of pregnant women will suffer from to some extent, 45% will have the vomiting with nausea, and only 25% will have nausea alone. HG however is much more difficult to asses as it does go under-diagnosed to a greater extent but it is thought to affect 1%-1.5% according to the charity Pregnancy Sickness Support. HG clinically presents as severe intractable vomiting which leads to nutritional deficiencies, dehydration, electrolyte disruption, weight loss and ketonuria.
Now turning to the possible etiology of HG, the results of twin studies published in Nature Communications by Marlena S. Fejzo et al proposed they had identified associating genetic signals in HG which are the placenta and appetite genes GDF15 and IGFBP7. Whilst the studies do not establish a causal link they do present a possible etiological pathway of this chronic condition. The GDF15 encodes a TGF-β superfamily member to increase a trophoblast protein that helps the placentation and maintenance of the pregnancy in the first two trimesters. It is also a physiological regulator in the hypothalamus and area postrema which is the vomiting centre of the brainstem.
Similarly the role of Insulin-like growth factor binding protein 7 (IGFBP7) in placentation, cachexia, and feeding behavior to GDF15 is the proposed involvement in this condition, this protein is also upregulated and expressed highly after implantation and decidualization (which is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy), in the uterus. Inhibition of IGFBP7 caused repressed uterine decidualization in another study model, it was also suggested that it may play a role in neuronal coordination between metabolic status and feeding behavior. Further studies using larger replication sample sizes should be the future research focus.
UK-based specialty pharmaceutical firm Alliance Pharma are behind the launch of the drug Xonvea, this is the first drug available to help with this condition that is to be used when all other traditional management approaches have failed. The drug has been in use as a first line pharmacotherapy with over 33 million pregnancies in the US and Canada. The active ingredients in this drug are a combination of doxylamine and pyridoxine, an antihistamine and vitamin B6, which are metabolised in the liver and excreted through the kidney. Per tablet they are 10 mg of each doxylamine and pyridoxine and dosage varies building dosage in the more severe cases.
The pathology of antihistamines is that they block the the vestibular system or the H1 receptors and also the chemoreceptor trigger zone or the H2 receptors. There have been over 20 controlled trials using various antihistamines and data shows that those women who were exposed within the first trimester have had a slightly lower risk for both major and minor malformations in comparison to those not exposed during pregnancy. Xonvea may cause somnolence due to the anticholinergic properties of doxylamine, (The word "somnolence" is derived from the Latin "somnus" meaning "sleep", so makes you drowsy). Certain contraindications for their usage are stated within the drug, so those who have any of these conditions, the drug may not be suitable for;
Hypersensitivity to doxylamine or any component of the formulation; narrow angle glaucoma; asthmatic attack; prostatic hypertrophy; stenosing peptic ulcer, pyloroduodenal obstruction; bladder-neck obstruction; concurrent use with monoamine oxidase-inhibitors.
Very high doses of 100 mg and above may result in unusual cases of a neonatal dependency which could cause seizures these are rare cases and the dosage from this drug (whilst higher than the recommended daily allowance for a pregnant woman), still comes under the low risk assessment.There have been studies on the safety of high doses of 50 mg vitamin B6 in the first trimester looking at risk of maternal adverse events, major malformations, miscarriages or low birth weight which showed no adverse effects. If you are prescribed this drug then speak to your consultant about any concerns you may have (they will also look into your diet to make sure you are not getting too much B6). Also getting as much support as you can will help you through this, added are a few support groups you may find helpful.
HER Foundation ; http://www.helpher.org
https://twitter.com/HGmoms
https://www.facebook.com/HERFoundation/
Pregnancy Sickness Support; https://www.pregnancysicknesssupport.org.uk/get-help/
The Ayden Rae Foundation; https://www.aydenraefoundation.org/internationalhgsupport
References.
emc (2018) Xonvea 10 mg/10 mg gastro-resistant tablets [Internet]. Data Pharm, Alliance Pharmaceuticals. Availablr from: <https://www.medicines.org.uk/emc/product/9344/smpc> [08/09/18].
Pharmaceutical Technology (2018) Alliance Pharma launches morning sickness drug Xonvea in UK[Internet]. Verdict Media. Available from: <https://www.pharmaceutical-technology.com/news/alliance-pharma-xonvea-launch/> [03/09/18].
Fejzo M.S. et al (2018) Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.Nature Communications,9 (1178)
King, T.L. & Aikins Murphy, P. (2009) Evidence-based approaches to managing nausea and vomiting in early pregnancy.J Midwifery Womens Health.Nov-Dec 54(6)430-44
Gospe, Jr. S,M. [2017] Pyridoxine-Dependent Epilepsy. Gene Reviews [Internet] Available from: <https://www.ncbi.nlm.nih.gov/books/NBK1486/> [06/09/18]
Shrim A et al [2006] Pregnancy outcome following use of large doses of vitamin B6 in the first trimester. [Internet]. Pub Med, NCBI. Available from: <DOI: 10.1080/01443610600955826> [09/09/18]
Graph.
Figure of genome-wide association scans for nausea and vomiting of pregnancy. The Manhattan plot shows distribution of association test statistics vs. genomic position for SCAN1 (binary phenotype). Source Figure Fejzo MS, et al.'s paper. No changes made.
