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<!-- Definition and symptoms -->
<!-- Definition and symptoms -->
'''Hyperemesis gravidarum''' ('''HG''') is a [[complication of pregnancy|pregnancy complication]] that is characterized by severe [[nausea]], [[vomiting]], [[weight loss]], and possibly [[dehydration]].<ref name=Drug2013>{{cite journal|title=Management of hyperemesis gravidarum.|journal=Drug Ther Bull|date=November 2013|volume=51|issue=11|pages=129-9|doi=10.1136/dtb.2013.11.0215|pmid=24227770}}</ref> Signs and symptoms may also include vomiting several times a day and [[Lightheadedness|feeling faint]].<!-- <ref name=Women2010/> --> Hypremesis gravidarum is considered more severe than [[morning sickness]].<!-- <ref name=Women2010/> --> Often symptoms get better after the 20th week of pregnancy but may last the entire pregnancy duration.<ref name=Women2010>{{cite web|title=Pregnancy|url=http://www.womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html|website=Office on Women's Health|accessdate=5 December 2015|date=September 27, 2010}}</ref>
'''Hyperemesis gravidarum''' ('''HG''') is a [[complication of pregnancy|pregnancy complication]] that is characterized by severe [[nausea]], [[vomiting]], [[weight loss]], and possibly [[dehydration]].<ref name=Drug2013>{{cite journal|title=Management of hyperemesis gravidarum.|journal=Drug Ther Bull|date=November 2013|volume=51|issue=11|pages=129-9|doi=10.1136/dtb.2013.11.0215|pmid=24227770}}</ref> Signs and symptoms may also include vomiting several times a day and [[Lightheadedness|feeling faint]].<!-- <ref name=Women2010/> --> Hypremesis gravidarum is considered more severe than [[morning sickness]].<!-- <ref name=Women2010/> --> Often symptoms get better after the 20th week of pregnancy but may last the entire pregnancy duration.<ref name=Women2010>{{cite web|title=Pregnancy|url=http://www.womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html|website=Office on Women's Health|accessdate=5 December 2015|date=September 27, 2010|deadurl=no|archiveurl=https://web.archive.org/web/20151210060201/http://womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html|archivedate=10 December 2015|df=}}</ref>


<!-- Cause and diagnosis -->
<!-- Cause and diagnosis -->
The exact causes of hyperemesis gravidarum are unknown.<ref name=BMC2010/> Risk factors include the first pregnancy, [[multiple pregnancy]], obesity, prior or family history of HG, [[trophoblastic disorder]], and a history of [[eating disorder]]s.<ref name=BMC2010/><ref name=Fer2013>{{cite book|last1=Ferri|first1=Fred F.|title=Ferri's clinical advisor 2013 5 books in 1|date=2012|publisher=Elsevier Mosby|isbn=9780323083737|page=538|edition=1st|url=https://books.google.ca/books?id=OR3VERnvzzEC&pg=PA538}}</ref> Diagnosis is usually made based on the observed signs and symptoms.<!-- <ref name=BMC2010/> --> HG has been technically defined as more than three episodes of vomiting per day such that weight loss of 5% or three [[kilogram]]s has occurred and [[Ketone bodies|ketones]] are present in the urine.<ref name=BMC2010>{{cite journal|last1=Jueckstock|first1=JK|last2=Kaestner|first2=R|last3=Mylonas|first3=I|title=Managing hyperemesis gravidarum: a multimodal challenge.|journal=BMC medicine|date=15 July 2010|volume=8|pages=46|pmid=20633258|doi=10.1186/1741-7015-8-46|pmc=2913953}}</ref> Other potential causes of the symptoms should be excluded including [[urinary tract infection]] and [[thyrotoxicosis|high thyroid levels]].<ref name=Sheehan07/>
The exact causes of hyperemesis gravidarum are unknown.<ref name=BMC2010/> Risk factors include the first pregnancy, [[multiple pregnancy]], obesity, prior or family history of HG, [[trophoblastic disorder]], and a history of [[eating disorder]]s.<ref name=BMC2010/><ref name=Fer2013>{{cite book|last1=Ferri|first1=Fred F.|title=Ferri's clinical advisor 2013 5 books in 1|date=2012|publisher=Elsevier Mosby|isbn=9780323083737|page=538|edition=1st|url=https://books.google.ca/books?id=OR3VERnvzzEC&pg=PA538|deadurl=no|archiveurl=https://web.archive.org/web/20151208051113/https://books.google.ca/books?id=OR3VERnvzzEC&pg=PA538|archivedate=2015-12-08|df=}}</ref> Diagnosis is usually made based on the observed signs and symptoms.<!-- <ref name=BMC2010/> --> HG has been technically defined as more than three episodes of vomiting per day such that weight loss of 5% or three [[kilogram]]s has occurred and [[Ketone bodies|ketones]] are present in the urine.<ref name=BMC2010>{{cite journal|last1=Jueckstock|first1=JK|last2=Kaestner|first2=R|last3=Mylonas|first3=I|title=Managing hyperemesis gravidarum: a multimodal challenge.|journal=BMC medicine|date=15 July 2010|volume=8|pages=46|pmid=20633258|doi=10.1186/1741-7015-8-46|pmc=2913953}}</ref> Other potential causes of the symptoms should be excluded including [[urinary tract infection]] and [[thyrotoxicosis|high thyroid levels]].<ref name=Sheehan07/>


<!-- Prevention and treatment -->
<!-- Prevention and treatment -->
Treatment includes drinking fluids and a bland diet.<ref name=Women2010/> Recommendations may include [[electrolyte-replacement drinks]], [[thiamine]], and a higher protein diet.<ref name=BMC2010/><ref name=Gab2012>{{cite book|last1=Gabbe|first1=Steven G.|title=Obstetrics : normal and problem pregnancies|date=2012|publisher=Elsevier/Saunders|isbn=9781437719352|page=117|edition=6th|url=https://books.google.ca/books?id=-3ufSTqeb6cC&pg=PA117}}</ref> Some women require [[intravenous fluids]].<ref name=Women2010/> With respect to medications [[pyridoxine]] or [[metoclopramide]] are preferred.<ref name=Sheehan07/> [[Prochlorperazine]], [[dimenhydrinate]], or [[ondansetron]] may be used if these are not effective.<ref name=BMC2010/><ref name=Sheehan07/> Hospitalization may be required.<!-- <ref name=BMC2010/> --> [[Psychotherapy]] may improve outcomes.<!-- <ref name=BMC2010/> --> Evidence for [[acupressure]] is poor.<ref name=BMC2010/>
Treatment includes drinking fluids and a bland diet.<ref name=Women2010/> Recommendations may include [[electrolyte-replacement drinks]], [[thiamine]], and a higher protein diet.<ref name=BMC2010/><ref name=Gab2012>{{cite book|last1=Gabbe|first1=Steven G.|title=Obstetrics : normal and problem pregnancies|date=2012|publisher=Elsevier/Saunders|isbn=9781437719352|page=117|edition=6th|url=https://books.google.ca/books?id=-3ufSTqeb6cC&pg=PA117|deadurl=no|archiveurl=https://web.archive.org/web/20151208074242/https://books.google.ca/books?id=-3ufSTqeb6cC&pg=PA117|archivedate=2015-12-08|df=}}</ref> Some women require [[intravenous fluids]].<ref name=Women2010/> With respect to medications [[pyridoxine]] or [[metoclopramide]] are preferred.<ref name=Sheehan07/> [[Prochlorperazine]], [[dimenhydrinate]], or [[ondansetron]] may be used if these are not effective.<ref name=BMC2010/><ref name=Sheehan07/> Hospitalization may be required.<!-- <ref name=BMC2010/> --> [[Psychotherapy]] may improve outcomes.<!-- <ref name=BMC2010/> --> Evidence for [[acupressure]] is poor.<ref name=BMC2010/>


<!-- History, epidemiology and prognosis -->
<!-- History, epidemiology and prognosis -->
While vomiting in pregnancy has been described as early as 2,000 BC, the first clear medical description of hyperemesis gravidarum was in 1852 by [[Antoine Dubois]].<ref>{{cite book|last1=Davis|first1=Christopher J.|title=Nausea and Vomiting : Mechanisms and Treatment|date=1986|publisher=Springer |isbn=9783642704796|page=152|url=https://books.google.ca/books?id=ufoqBAAAQBAJ&pg=PA152}}</ref> Hyperemesis gravidarum is estimated to affect 0.3–2.0% of pregnant women.<ref name=Goodwin2008>{{cite journal|last=Goodwin|first=TM|title=Hyperemesis gravidarum|journal=Obstetrics and gynecology clinics of North America|date=September 2008|volume=35|issue=3|pages=401–17, viii|pmid=18760227|doi=10.1016/j.ogc.2008.04.002}}</ref> While previously known as a common cause of death in pregnancy, with proper treatment this is now very rare.<ref>{{cite book|last1=Kumar|first1=Geeta|title=Early Pregnancy Issues for the MRCOG and Beyond|date=2011|publisher=Cambridge University Press|isbn=9781107717992|page=Chapter 6|url=https://books.google.ca/books?id=lfSUAwAAQBAJ&pg=PT61}}</ref><ref>{{cite book|last1=DeLegge|first1=Mark H.|title=Handbook of home nutrition support|date=2007|publisher=Jones and Bartlett|location=Sudbury, Mass.|isbn=9780763747695|page=320|url=https://books.google.ca/books?id=KtSF221KP-0C&pg=PA320}}</ref> Those affected have a low risk of [[miscarriage]] but a higher risk of [[premature birth]].<ref name=Fer2013 /> Some pregnant women choose to [[abortion|end their pregnancy]] due to HG's symptoms.<ref name=Gab2012/>
While vomiting in pregnancy has been described as early as 2,000 BC, the first clear medical description of hyperemesis gravidarum was in 1852 by [[Antoine Dubois]].<ref>{{cite book|last1=Davis|first1=Christopher J.|title=Nausea and Vomiting : Mechanisms and Treatment|date=1986|publisher=Springer|isbn=9783642704796|page=152|url=https://books.google.ca/books?id=ufoqBAAAQBAJ&pg=PA152|deadurl=no|archiveurl=https://web.archive.org/web/20151208045341/https://books.google.ca/books?id=ufoqBAAAQBAJ&pg=PA152|archivedate=2015-12-08|df=}}</ref> Hyperemesis gravidarum is estimated to affect 0.3–2.0% of pregnant women.<ref name=Goodwin2008>{{cite journal|last=Goodwin|first=TM|title=Hyperemesis gravidarum|journal=Obstetrics and gynecology clinics of North America|date=September 2008|volume=35|issue=3|pages=401–17, viii|pmid=18760227|doi=10.1016/j.ogc.2008.04.002}}</ref> While previously known as a common cause of death in pregnancy, with proper treatment this is now very rare.<ref>{{cite book|last1=Kumar|first1=Geeta|title=Early Pregnancy Issues for the MRCOG and Beyond|date=2011|publisher=Cambridge University Press|isbn=9781107717992|page=Chapter 6|url=https://books.google.ca/books?id=lfSUAwAAQBAJ&pg=PT61|deadurl=no|archiveurl=https://web.archive.org/web/20151208043543/https://books.google.ca/books?id=lfSUAwAAQBAJ&pg=PT61|archivedate=2015-12-08|df=}}</ref><ref>{{cite book|last1=DeLegge|first1=Mark H.|title=Handbook of home nutrition support|date=2007|publisher=Jones and Bartlett|location=Sudbury, Mass.|isbn=9780763747695|page=320|url=https://books.google.ca/books?id=KtSF221KP-0C&pg=PA320|deadurl=no|archiveurl=https://web.archive.org/web/20151208055738/https://books.google.ca/books?id=KtSF221KP-0C&pg=PA320|archivedate=2015-12-08|df=}}</ref> Those affected have a low risk of [[miscarriage]] but a higher risk of [[premature birth]].<ref name=Fer2013 /> Some pregnant women choose to [[abortion|end their pregnancy]] due to HG's symptoms.<ref name=Gab2012/>


==Signs and symptoms==
==Signs and symptoms==
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Symptoms can be aggravated by [[hunger]], [[fatigue (medical)|fatigue]], [[prenatal vitamins]] (especially those containing [[iron]]), and [[diet (nutrition)|diet]].<ref name="Guide to Women's Health">{{cite book|author1=Carlson, Karen J., MD |author2=Eisenstat, Stephanie J., MD |author3=Ziporyn, Terra |title=The New Harvard Guide to Women's Health|year=2004|publisher=Harvard University Press |isbn=0-674-01343-3 |pages=392–3}}</ref> Many people with HG are extremely sensitive to [[odor]]s in their environment; certain smells may exacerbate symptoms. This is known as [[olfaction|hyperolfaction]]. [[Drooling|Ptyalism]], or hypersalivation, is another symptom experienced by some women suffering from HG.
Symptoms can be aggravated by [[hunger]], [[fatigue (medical)|fatigue]], [[prenatal vitamins]] (especially those containing [[iron]]), and [[diet (nutrition)|diet]].<ref name="Guide to Women's Health">{{cite book|author1=Carlson, Karen J., MD |author2=Eisenstat, Stephanie J., MD |author3=Ziporyn, Terra |title=The New Harvard Guide to Women's Health|year=2004|publisher=Harvard University Press |isbn=0-674-01343-3 |pages=392–3}}</ref> Many people with HG are extremely sensitive to [[odor]]s in their environment; certain smells may exacerbate symptoms. This is known as [[olfaction|hyperolfaction]]. [[Drooling|Ptyalism]], or hypersalivation, is another symptom experienced by some women suffering from HG.


Hyperemesis gravidarum tends to occur in the first trimester of pregnancy<ref name="Ahmed2013">{{Cite journal|author=Ahmed KT, Almashhrawi AA, Rahman RN, Hammoud GM, Ibdah JA|title=Liver diseases in pregnancy: diseases unique to pregnancy|journal=World J Gastroenterol |volume=19 |issue=43 |pages=7639–46 |date=November 2013|pmid= 24282353|pmc=3837262| doi=10.3748/wjg.v19.i43.7639|last2=Almashhrawi|last3=Rahman|last4=Hammoud|last5=Ibdah}}</ref> and lasts significantly longer than morning sickness. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their [[second trimester]], some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth.<ref name=":0">{{cite web|title=Do I Have Morning Sickness or HG?|url=http://www.helpher.org/mothers/hyperemesis-or-morning-sickness/index.php|publisher=H.E.R. Foundation|accessdate=6 December 2012}}</ref>
Hyperemesis gravidarum tends to occur in the first trimester of pregnancy<ref name="Ahmed2013">{{Cite journal|author=Ahmed KT, Almashhrawi AA, Rahman RN, Hammoud GM, Ibdah JA|title=Liver diseases in pregnancy: diseases unique to pregnancy|journal=World J Gastroenterol |volume=19 |issue=43 |pages=7639–46 |date=November 2013|pmid= 24282353|pmc=3837262| doi=10.3748/wjg.v19.i43.7639|last2=Almashhrawi|last3=Rahman|last4=Hammoud|last5=Ibdah}}</ref> and lasts significantly longer than morning sickness. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their [[second trimester]], some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth.<ref name=":0">{{cite web|title=Do I Have Morning Sickness or HG?|url=http://www.helpher.org/mothers/hyperemesis-or-morning-sickness/index.php|publisher=H.E.R. Foundation|accessdate=6 December 2012|deadurl=no|archiveurl=https://web.archive.org/web/20121130110105/http://www.helpher.org/mothers/hyperemesis-or-morning-sickness/index.php|archivedate=30 November 2012|df=}}</ref>


A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.{{citation needed|date=December 2015}}
A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.{{citation needed|date=December 2015}}
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* Elevated liver enzymes
* Elevated liver enzymes
* Decreased [[lower esophageal sphincter]] pressure
* Decreased [[lower esophageal sphincter]] pressure
* Increased levels of sex steroids in hepatic portal system<ref>{{Cite journal|url=http://humupd.oxfordjournals.org/content/11/5/527.long|last1=Verberg|first1=MF|last2=Gillott|first2=DJ|last3=Al-Fardan|first3=N|last4=Grudzinskas|first4=JG|title=Hyperemesis gravidarum, a literature review|journal=Human Reproduction Update|date=September–October 2005|volume=11|issue=5|pages=527–539|pmid=16006438|doi=10.1093/humupd/dmi021}}</ref>
* Increased levels of sex steroids in hepatic portal system<ref>{{Cite journal|url=http://humupd.oxfordjournals.org/content/11/5/527.long|last1=Verberg|first1=MF|last2=Gillott|first2=DJ|last3=Al-Fardan|first3=N|last4=Grudzinskas|first4=JG|title=Hyperemesis gravidarum, a literature review|journal=Human Reproduction Update|date=September–October 2005|volume=11|issue=5|pages=527–539|pmid=16006438|doi=10.1093/humupd/dmi021|deadurl=no|archiveurl=https://web.archive.org/web/20161215210712/http://humupd.oxfordjournals.org/content/11/5/527.long|archivedate=2016-12-15|df=}}</ref>
|-
|-
| Gastrointestinal tract || ''Helicobacter pylori''|| Increased steroid levels in circulation<ref>{{cite journal|last1=Bagis|first1=T|last2=Gumurdulu|first2= Y|last3= Kayaselcuk|first3=F|last4=Yilmaz|first4= ES|last5= Killicadag|first5= E|last6= Tarim|first6= E|title=Endoscopy in hyperemesis gravidarum and ''Helicobacter pylori'' infection|journal=International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics|date=November 2002|volume=79|issue=2|pages=105–9|pmid=12427393|doi=10.1016/s0020-7292(02)00230-8}}</ref>
| Gastrointestinal tract || ''Helicobacter pylori''|| Increased steroid levels in circulation<ref>{{cite journal|last1=Bagis|first1=T|last2=Gumurdulu|first2= Y|last3= Kayaselcuk|first3=F|last4=Yilmaz|first4= ES|last5= Killicadag|first5= E|last6= Tarim|first6= E|title=Endoscopy in hyperemesis gravidarum and ''Helicobacter pylori'' infection|journal=International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics|date=November 2002|volume=79|issue=2|pages=105–9|pmid=12427393|doi=10.1016/s0020-7292(02)00230-8}}</ref>
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==Diagnosis==
==Diagnosis==
Hyperemesis gravidarum is considered a [[diagnosis of exclusion]].<ref name="Emergency"/> HG can be associated with serious problems in the mother or baby, such as [[Wernicke's encephalopathy]], [[coagulopathy]], [[peripheral neuropathy]].<ref name=Sheehan07>{{cite journal |url=http://www.racgp.org.au/afpbackissues/2007/200709/200709sheenan.pdf |last1=Sheehan |first1=P |title=Hyperemesis gravidarum—assessment and management |journal= Australian Family Physician|volume=36|issue=9|pages=698–701 |date=September 2007|pmid=17885701 |format=PDF}}</ref>
Hyperemesis gravidarum is considered a [[diagnosis of exclusion]].<ref name="Emergency"/> HG can be associated with serious problems in the mother or baby, such as [[Wernicke's encephalopathy]], [[coagulopathy]], [[peripheral neuropathy]].<ref name=Sheehan07>{{cite journal |url=http://www.racgp.org.au/afpbackissues/2007/200709/200709sheenan.pdf |last1=Sheehan |first1=P |title=Hyperemesis gravidarum—assessment and management |journal=Australian Family Physician |volume=36 |issue=9 |pages=698–701 |date=September 2007 |pmid=17885701 |format=PDF |deadurl=no |archiveurl=https://web.archive.org/web/20140606225903/http://www.racgp.org.au/afpbackissues/2007/200709/200709sheenan.pdf |archivedate=2014-06-06 |df= }}</ref>


Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.<ref>{{cite web |url=http://my.clevelandclinic.org/healthy_living/pregnancy/hic_hyperemesis_gravidarum_severe_nausea_and_vomiting_during_pregnancy.aspx |title=Hyperemesis Gravidarum (Severe Nausea and Vomiting During Pregnancy) |year=2012 |work= |publisher=Cleveland Clinic |accessdate=23 January 2013}}</ref><ref name="Medline">{{cite web |url=http://www.nlm.nih.gov/medlineplus/ency/article/001499.htm |title=Hyperemesis gravidarum |author=Medline Plus |year=2012 |work= |publisher=National Institutes of Health |accessdate=30 January 2013}}</ref> The onset of the nausea and vomiting in hyperemesis gravidarum is typically before the twenty-second week of pregnancy.<ref name="Emergency"/>
Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.<ref>{{cite web |url=http://my.clevelandclinic.org/healthy_living/pregnancy/hic_hyperemesis_gravidarum_severe_nausea_and_vomiting_during_pregnancy.aspx |title=Hyperemesis Gravidarum (Severe Nausea and Vomiting During Pregnancy) |year=2012 |work= |publisher=Cleveland Clinic |accessdate=23 January 2013 |deadurl=no |archiveurl=https://web.archive.org/web/20121215124015/http://my.clevelandclinic.org/healthy_living/pregnancy/hic_hyperemesis_gravidarum_severe_nausea_and_vomiting_during_pregnancy.aspx |archivedate=15 December 2012 |df= }}</ref><ref name="Medline">{{cite web |url=http://www.nlm.nih.gov/medlineplus/ency/article/001499.htm |title=Hyperemesis gravidarum |author=Medline Plus |year=2012 |work= |publisher=National Institutes of Health |accessdate=30 January 2013 |deadurl=no |archiveurl=https://web.archive.org/web/20130127162906/http://www.nlm.nih.gov/medlineplus/ency/article/001499.htm |archivedate=27 January 2013 |df= }}</ref> The onset of the nausea and vomiting in hyperemesis gravidarum is typically before the twenty-second week of pregnancy.<ref name="Emergency"/>


===Differential diagnosis===
===Differential diagnosis===
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===Investigations===
===Investigations===
Common investigations include [[blood urea nitrogen]] (BUN) and electrolytes, [[liver function tests]], [[urinalysis]],<ref name="Medline"/> and [[thyroid function tests]]. Hematological investigations include [[hematocrit]] levels, which are usually raised in HG.<ref name="Medline" /> An [[ultrasound scan]] may be needed to know gestational status and to exclude molar or partial molar pregnancy.<ref name=manual7>{{cite book |editor-first=Arthur T. |editor-last=Evans|title=Manual of obstetrics|year=2007|publisher=Wolters Kluwer / Lippincott Williams & Wilkins|isbn=9780781796965|pages=265–8|edition=7th |url=https://books.google.com/books?id=NWKW3KZv9roC&pg=PA265}}</ref>
Common investigations include [[blood urea nitrogen]] (BUN) and electrolytes, [[liver function tests]], [[urinalysis]],<ref name="Medline"/> and [[thyroid function tests]]. Hematological investigations include [[hematocrit]] levels, which are usually raised in HG.<ref name="Medline" /> An [[ultrasound scan]] may be needed to know gestational status and to exclude molar or partial molar pregnancy.<ref name=manual7>{{cite book|editor-first=Arthur T.|editor-last=Evans|title=Manual of obstetrics|year=2007|publisher=Wolters Kluwer / Lippincott Williams & Wilkins|isbn=9780781796965|pages=265–8|edition=7th|url=https://books.google.com/books?id=NWKW3KZv9roC&pg=PA265|deadurl=no|archiveurl=https://web.archive.org/web/20170911002137/https://books.google.com/books?id=NWKW3KZv9roC&pg=PA265|archivedate=2017-09-11|df=}}</ref>


==Management==
==Management==
Dry bland food and oral rehydration are first-line treatments.<ref>{{cite web |url=http://womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html |title=Pregnancy Complications |author=Office on Women's Health |year=2010 |work= |publisher=U.S. Department of Health and Human Services |accessdate=27 October 2013}}</ref> Due to the potential for severe dehydration and other complications, HG is treated as an emergency. If conservative dietary measures fail, more extensive treatment such as the use of [[antiemetic]] medications and intravenous [[rehydration]] may be required. If oral nutrition is insufficient, intravenous nutritional support may be needed.<ref name="Ahmed2013"/> For women who require hospital admission, [[Compression stockings|thromboembolic stockings]] or [[Low molecular weight heparin|low-molecular-weight heparin]] may be used as [[thromboprophylaxis|measures to prevent the formation of a blood clot]].<ref name=handbook />
Dry bland food and oral rehydration are first-line treatments.<ref>{{cite web |url=http://womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html |title=Pregnancy Complications |author=Office on Women's Health |year=2010 |work= |publisher=U.S. Department of Health and Human Services |accessdate=27 October 2013 |deadurl=no |archiveurl=https://web.archive.org/web/20131029192747/http://womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html |archivedate=29 October 2013 |df= }}</ref> Due to the potential for severe dehydration and other complications, HG is treated as an emergency. If conservative dietary measures fail, more extensive treatment such as the use of [[antiemetic]] medications and intravenous [[rehydration]] may be required. If oral nutrition is insufficient, intravenous nutritional support may be needed.<ref name="Ahmed2013"/> For women who require hospital admission, [[Compression stockings|thromboembolic stockings]] or [[Low molecular weight heparin|low-molecular-weight heparin]] may be used as [[thromboprophylaxis|measures to prevent the formation of a blood clot]].<ref name=handbook />


===Intravenous fluids===
===Intravenous fluids===
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===Infant===
===Infant===
The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.<ref name=handbook>{{cite book |editor-first=Thomas H. |editor-last=Bourne, |editor2-first=George |editor2-last=Condous|title=Handbook of early pregnancy care|year=2006|publisher=Informa Healthcare |isbn=9781842143230|pages=149–154}}</ref> Infants of women with severe hyperemesis who gain less than 7&nbsp;kg (15.4&nbsp;lb) during pregnancy tend to be of lower [[birth weight]], [[small for gestational age]], and born before 37 weeks gestation.<ref name="Ahmed2013"/> In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7&nbsp;kg appear similar to infants from uncomplicated pregnancies.<ref>{{cite journal |author=Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. |title=Outcomes of pregnancies complicated by hyperemesis gravidarum |journal=Obstet Gynecol. |volume=107 |issue=2 Pt 1 |pages=285–92 |year=2006| pmid=16449113 |doi=10.1097/01.AOG.0000195060.22832.cd|last2=Fell |last3=Joseph |last4=Allen |last5=Butler }}</ref> There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG.<ref name="Emergency"/> Children born to mothers with undertreated Hyperemesis have a fourfold increase in neurobehavioral diagnoses.<ref>{{cite journal |vauthors=Fejzo MS, Magtira A, Schoenberg FP, Macgibbon K, Mullin PM |title=Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum |journal=Eur J Obstet Gynecol Reprod Biol |volume=189 |issue= |pages=79–84 |date=June 2015 |pmid=25898368 |doi=10.1016/j.ejogrb.2015.03.028 |url=http://www.helpher.org/HER-Research/downloads/Neurodevelopmental%20delay%20HG%20EJOG%202015%20pdf.pdf}}</ref>
The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.<ref name=handbook>{{cite book |editor-first=Thomas H. |editor-last=Bourne, |editor2-first=George |editor2-last=Condous|title=Handbook of early pregnancy care|year=2006|publisher=Informa Healthcare |isbn=9781842143230|pages=149–154}}</ref> Infants of women with severe hyperemesis who gain less than 7&nbsp;kg (15.4&nbsp;lb) during pregnancy tend to be of lower [[birth weight]], [[small for gestational age]], and born before 37 weeks gestation.<ref name="Ahmed2013"/> In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7&nbsp;kg appear similar to infants from uncomplicated pregnancies.<ref>{{cite journal |author=Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. |title=Outcomes of pregnancies complicated by hyperemesis gravidarum |journal=Obstet Gynecol. |volume=107 |issue=2 Pt 1 |pages=285–92 |year=2006| pmid=16449113 |doi=10.1097/01.AOG.0000195060.22832.cd|last2=Fell |last3=Joseph |last4=Allen |last5=Butler }}</ref> There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG.<ref name="Emergency"/> Children born to mothers with undertreated Hyperemesis have a fourfold increase in neurobehavioral diagnoses.<ref>{{cite journal |vauthors=Fejzo MS, Magtira A, Schoenberg FP, Macgibbon K, Mullin PM |title=Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum |journal=Eur J Obstet Gynecol Reprod Biol |volume=189 |issue= |pages=79–84 |date=June 2015 |pmid=25898368 |doi=10.1016/j.ejogrb.2015.03.028 |url=http://www.helpher.org/HER-Research/downloads/Neurodevelopmental%20delay%20HG%20EJOG%202015%20pdf.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20160304102531/http://www.helpher.org/HER-Research/downloads/Neurodevelopmental%20delay%20HG%20EJOG%202015%20pdf.pdf |archivedate=2016-03-04 |df= }}</ref>


==Epidemiology==
==Epidemiology==
Line 168: Line 168:


==Notable cases==
==Notable cases==
Author [[Charlotte Brontë]] is often thought to have suffered from hyperemesis gravidarum. She died in 1855 while four months pregnant, having been afflicted by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even water.<ref>{{cite news|last=McSweeny|first=Linda|title=What is acute morning sickness?|url=http://www.theage.com.au/lifestyle/diet-and-fitness/what-is-acute-morning-sickness-20100602-wzuy.html|accessdate=2012-12-04|newspaper=The Age|date=2010-06-03}}</ref>
Author [[Charlotte Brontë]] is often thought to have suffered from hyperemesis gravidarum. She died in 1855 while four months pregnant, having been afflicted by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even water.<ref>{{cite news|last=McSweeny|first=Linda|title=What is acute morning sickness?|url=http://www.theage.com.au/lifestyle/diet-and-fitness/what-is-acute-morning-sickness-20100602-wzuy.html|accessdate=2012-12-04|newspaper=The Age|date=2010-06-03|deadurl=no|archiveurl=https://web.archive.org/web/20121206055217/http://www.theage.com.au/lifestyle/diet-and-fitness/what-is-acute-morning-sickness-20100602-wzuy.html|archivedate=2012-12-06|df=}}</ref>


[[Catherine, Duchess of Cambridge]], was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a similar condition during the subsequent two.<ref>{{cite web| url=http://www.cbc.ca/news/world/prince-william-kate-expecting-2nd-child-1.2758929 |title=Prince William, Kate expecting 2nd child |date=8 September 2014 |accessdate=8 September 2014}}</ref><ref>{{Cite web|url=https://twitter.com/KensingtonRoyal/status/904633975381127168|title=Read the press release in full ↓pic.twitter.com/vDTgGD2aGF|last=Kensington Palace|first=|date=2017-09-04|website=@KensingtonRoyal|archive-url=|archive-date=|dead-url=|access-date=2017-09-04}}</ref>
[[Catherine, Duchess of Cambridge]], was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a similar condition during the subsequent two.<ref>{{cite web |url=http://www.cbc.ca/news/world/prince-william-kate-expecting-2nd-child-1.2758929 |title=Prince William, Kate expecting 2nd child |date=8 September 2014 |accessdate=8 September 2014 |deadurl=no |archiveurl=https://web.archive.org/web/20140908133456/http://www.cbc.ca/news/world/prince-william-kate-expecting-2nd-child-1.2758929 |archivedate=8 September 2014 |df= }}</ref><ref>{{Cite web|url=https://twitter.com/KensingtonRoyal/status/904633975381127168|title=Read the press release in full ↓pic.twitter.com/vDTgGD2aGF|last=Kensington Palace|first=|date=2017-09-04|website=@KensingtonRoyal|archive-url=https://web.archive.org/web/20170904205914/https://twitter.com/KensingtonRoyal/status/904633975381127168|archive-date=2017-09-04|dead-url=no|access-date=2017-09-04|df=}}</ref>


[[The Saturdays]] singer [[Frankie Bridge]] had hyperemesis gravidarum during her second pregnancy.<ref>{{cite web|url=http://www.mirror.co.uk/3am/celebrity-news/frankie-bridge-gives-birth-baby-6256305?ICID=FB_mirror_main|title=Frankie Bridge gives birth to baby boy|date=15 August 2015}}</ref>
[[The Saturdays]] singer [[Frankie Bridge]] had hyperemesis gravidarum during her second pregnancy.<ref>{{cite web|url=http://www.mirror.co.uk/3am/celebrity-news/frankie-bridge-gives-birth-baby-6256305?ICID=FB_mirror_main|title=Frankie Bridge gives birth to baby boy|date=15 August 2015|deadurl=no|archiveurl=https://web.archive.org/web/20150817150514/http://www.mirror.co.uk/3am/celebrity-news/frankie-bridge-gives-birth-baby-6256305?ICID=FB_mirror_main|archivedate=17 August 2015|df=}}</ref>


==References==
==References==

Revision as of 00:21, 11 September 2017

Hyperemesis gravidarum
SpecialtyGynecology
SymptomsNausea and vomiting such that weight loss and dehydration occur[1]
DurationOften gets better but may last entire pregnancy[2]
CausesUnknown[3]
Risk factorsFirst pregnancy, multiple pregnancy, obesity, prior or family history of hyperemesis gravidarum, trophoblastic disorder, history of an eating disorder[3][4]
Diagnostic methodBased on symptoms[3]
Differential diagnosisUrinary tract infection, high thyroid levels[5]
TreatmentDrinking fluids, bland diet, intravenous fluids[2]
MedicationPyridoxine, metoclopramide[5]
Frequency~1% of pregnant women[6]

Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration.[1] Signs and symptoms may also include vomiting several times a day and feeling faint. Hypremesis gravidarum is considered more severe than morning sickness. Often symptoms get better after the 20th week of pregnancy but may last the entire pregnancy duration.[2]

The exact causes of hyperemesis gravidarum are unknown.[3] Risk factors include the first pregnancy, multiple pregnancy, obesity, prior or family history of HG, trophoblastic disorder, and a history of eating disorders.[3][4] Diagnosis is usually made based on the observed signs and symptoms. HG has been technically defined as more than three episodes of vomiting per day such that weight loss of 5% or three kilograms has occurred and ketones are present in the urine.[3] Other potential causes of the symptoms should be excluded including urinary tract infection and high thyroid levels.[5]

Treatment includes drinking fluids and a bland diet.[2] Recommendations may include electrolyte-replacement drinks, thiamine, and a higher protein diet.[3][7] Some women require intravenous fluids.[2] With respect to medications pyridoxine or metoclopramide are preferred.[5] Prochlorperazine, dimenhydrinate, or ondansetron may be used if these are not effective.[3][5] Hospitalization may be required. Psychotherapy may improve outcomes. Evidence for acupressure is poor.[3]

While vomiting in pregnancy has been described as early as 2,000 BC, the first clear medical description of hyperemesis gravidarum was in 1852 by Antoine Dubois.[8] Hyperemesis gravidarum is estimated to affect 0.3–2.0% of pregnant women.[6] While previously known as a common cause of death in pregnancy, with proper treatment this is now very rare.[9][10] Those affected have a low risk of miscarriage but a higher risk of premature birth.[4] Some pregnant women choose to end their pregnancy due to HG's symptoms.[7]

Signs and symptoms

When vomiting is severe it may result in the following:[11]

Symptoms can be aggravated by hunger, fatigue, prenatal vitamins (especially those containing iron), and diet.[14] Many people with HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. This is known as hyperolfaction. Ptyalism, or hypersalivation, is another symptom experienced by some women suffering from HG.

Hyperemesis gravidarum tends to occur in the first trimester of pregnancy[12] and lasts significantly longer than morning sickness. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth.[15]

A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.[citation needed]

Causes

There are numerous theories regarding the cause of HG, but the cause remains controversial. It is thought that HG is due to a combination of factors which may vary between women and include genetics.[11] Women with family members who had Hyperemesis are more likely to develop the disease.[16]

One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (hCG).[17][18] This theory would also explain why hyperemesis gravidarum is most frequently encountered in the first trimester (often around 8–12 weeks of gestation), as hCG levels are highest at that time and decline afterward. Another postulated cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to nausea/vomiting).[11]

Pathophysiology

Morning sickness

Although the pathophysiology of HG is poorly understood, the most commonly accepted theory suggests that levels of hCG are associated with it.[5] Leptin may also play a role.[19]

Possible pathophysiological processes involved are summarized in the following table:[20]

Source Cause Pathophysiology
hCG
Placenta
  • Decreased gut mobility
  • Elevated liver enzymes
  • Decreased lower esophageal sphincter pressure
  • Increased levels of sex steroids in hepatic portal system[21]
Gastrointestinal tract Helicobacter pylori Increased steroid levels in circulation[22]

Diagnosis

Hyperemesis gravidarum is considered a diagnosis of exclusion.[11] HG can be associated with serious problems in the mother or baby, such as Wernicke's encephalopathy, coagulopathy, peripheral neuropathy.[5]

Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat.[23][24] The onset of the nausea and vomiting in hyperemesis gravidarum is typically before the twenty-second week of pregnancy.[11]

Differential diagnosis

Diagnoses to be ruled out include the following:[20]

Type Differential diagnoses
Infections
(usually accompanied by fever or associated neurological symptoms)
Gastrointestinal disorders
(usually accompanied by abdominal pain)
Metabolic
Drugs
  • Antibiotics
  • Iron supplements
Gestational trophoblastic diseases (rule out with urine β-hCG)

Investigations

Common investigations include blood urea nitrogen (BUN) and electrolytes, liver function tests, urinalysis,[24] and thyroid function tests. Hematological investigations include hematocrit levels, which are usually raised in HG.[24] An ultrasound scan may be needed to know gestational status and to exclude molar or partial molar pregnancy.[25]

Management

Dry bland food and oral rehydration are first-line treatments.[26] Due to the potential for severe dehydration and other complications, HG is treated as an emergency. If conservative dietary measures fail, more extensive treatment such as the use of antiemetic medications and intravenous rehydration may be required. If oral nutrition is insufficient, intravenous nutritional support may be needed.[12] For women who require hospital admission, thromboembolic stockings or low-molecular-weight heparin may be used as measures to prevent the formation of a blood clot.[20]

Intravenous fluids

Intravenous (IV) hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. Likewise, supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy.[27] A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, electrolyte levels should be monitored and supplemented; of particular concern are sodium and potassium.

After IV rehydration is completed, patients in general progress to frequent small liquid or bland meals. After rehydration, treatment focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making continuing care necessary. Home care is available in the form of a PICC line for hydration and nutrition (called total parenteral nutrition).[28] Home treatment is often less expensive than long-term or repeated hospitalizations.

Medications

A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), and phenothiazines (such as promethazine).[29] With respect to effectiveness, it is unknown if one is superior to another for improving nausea or vomiting.[29] Limited evidence from published clinical trials suggests the use of medications to treat hyperemesis gravidarum.[30]

While pyridoxine/doxylamine, a combination of vitamin B6 and doxylamine, is effective in nausea and vomiting of pregnancy,[31] some have questioned its effectiveness in HG.[32] Ondansetron may be beneficial, however, there are some concerns regarding an association with cleft palate,[33] and there is little high-quality data.[29] Metoclopramide is also used and relatively well tolerated.[34] Evidence for the use of corticosteroids is weak; there is some evidence that corticosteroid use in pregnant women may slightly increase the risk of oral facial clefts in the infant and may suppress fetal adrenal activity.[11][35] However, hydrocortisone and prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.[11]

Nutritional support

Women not responding to IV rehydration and medication may require nutritional support. Patients might receive parenteral nutrition (intravenous feeding via a PICC line) or enteral nutrition (via a nasogastric tube or a nasojejunal tube). There is only limited evidence from trials to support the use of vitamin B6 to improve outcome.[30] Hyperalimentation may be necessary in certain cases to help maintain volume requirements and allow weight gain.[25] A physician might also prescribe Vitamin B1 (to prevent Wernicke's encephalopathy) and folic acid supplementation.[20]

Alternative medicine

Acupuncture (both with P6 and traditional method) has been found to be ineffective.[30] The use of ginger products may be helpful, but evidence of effectiveness is limited and inconsistent, though three recent studies support ginger over placebo.[30]

Complications

Pregnant woman

If HG is inadequately treated, anemia,[11] hyponatremia,[11] Wernicke's encephalopathy,[11] kidney failure, central pontine myelinolysis, coagulopathy, atrophy, Mallory-Weiss tears,[11] hypoglycemia, jaundice, malnutrition, pneumomediastinum, rhabdomyolysis, deconditioning, deep vein thrombosis, pulmonary embolism, splenic avulsion, or vasospasms of cerebral arteries are possible consequences. Depression and PTSD [36] are common secondary complications of HG and emotional support can be beneficial.[11]

Infant

The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.[20] Infants of women with severe hyperemesis who gain less than 7 kg (15.4 lb) during pregnancy tend to be of lower birth weight, small for gestational age, and born before 37 weeks gestation.[12] In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kg appear similar to infants from uncomplicated pregnancies.[37] There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG.[11] Children born to mothers with undertreated Hyperemesis have a fourfold increase in neurobehavioral diagnoses.[38]

Epidemiology

Vomiting is a common condition affecting about 50% of pregnant women, with another 25% having nausea.[39] However, the incidence of HG is only 0.3–1.5%.[5] After preterm labor, hyperemesis gravidarum is the second most common reason for hospital admission during the first half of pregnancy.[11] Factors such as infection with Helicobacter pylori, a rise in thyroid hormone production, low age, low body mass index prior to pregnancy, multiple pregnancies, molar pregnancies, and a past history of hyperemesis gravidarum have been associated with the development of HG.[11]

History

Thalidomide was prescribed for treatment of HG in Europe until it was recognized that thalidomide is teratogenic and is a cause of phocomelia in neonates.[40]

Etymology

Hyperemesis gravidarum is from the Greek hyper-, meaning excessive, and emesis, meaning vomiting, and the Latin gravidarum, the feminine genitive plural form of an adjective, here used as a noun, meaning "pregnant [woman]". Therefore, hyperemesis gravidarum means "excessive vomiting of pregnant women".

Notable cases

Author Charlotte Brontë is often thought to have suffered from hyperemesis gravidarum. She died in 1855 while four months pregnant, having been afflicted by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even water.[41]

Catherine, Duchess of Cambridge, was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a similar condition during the subsequent two.[42][43]

The Saturdays singer Frankie Bridge had hyperemesis gravidarum during her second pregnancy.[44]

References

  1. ^ a b "Management of hyperemesis gravidarum". Drug Ther Bull. 51 (11): 129–9. November 2013. doi:10.1136/dtb.2013.11.0215. PMID 24227770.
  2. ^ a b c d e "Pregnancy". Office on Women's Health. September 27, 2010. Archived from the original on 10 December 2015. Retrieved 5 December 2015. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  3. ^ a b c d e f g h i Jueckstock, JK; Kaestner, R; Mylonas, I (15 July 2010). "Managing hyperemesis gravidarum: a multimodal challenge". BMC medicine. 8: 46. doi:10.1186/1741-7015-8-46. PMC 2913953. PMID 20633258.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ a b c Ferri, Fred F. (2012). Ferri's clinical advisor 2013 5 books in 1 (1st ed.). Elsevier Mosby. p. 538. ISBN 9780323083737. Archived from the original on 2015-12-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ a b c d e f g h i j Sheehan, P (September 2007). "Hyperemesis gravidarum—assessment and management" (PDF). Australian Family Physician. 36 (9): 698–701. PMID 17885701. Archived from the original (PDF) on 2014-06-06. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  6. ^ a b Goodwin, TM (September 2008). "Hyperemesis gravidarum". Obstetrics and gynecology clinics of North America. 35 (3): 401–17, viii. doi:10.1016/j.ogc.2008.04.002. PMID 18760227.
  7. ^ a b Gabbe, Steven G. (2012). Obstetrics : normal and problem pregnancies (6th ed.). Elsevier/Saunders. p. 117. ISBN 9781437719352. Archived from the original on 2015-12-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ Davis, Christopher J. (1986). Nausea and Vomiting : Mechanisms and Treatment. Springer. p. 152. ISBN 9783642704796. Archived from the original on 2015-12-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ Kumar, Geeta (2011). Early Pregnancy Issues for the MRCOG and Beyond. Cambridge University Press. p. Chapter 6. ISBN 9781107717992. Archived from the original on 2015-12-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  10. ^ DeLegge, Mark H. (2007). Handbook of home nutrition support. Sudbury, Mass.: Jones and Bartlett. p. 320. ISBN 9780763747695. Archived from the original on 2015-12-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  11. ^ a b c d e f g h i j k l m n o p Summers A (2012). "Emergency management of hyperemesis gravidarum". Emergency Nurse. 20 (4): 24–8. doi:10.7748/en2012.07.20.4.24.c9206. PMID 22876404.
  12. ^ a b c d Ahmed KT, Almashhrawi AA, Rahman RN, Hammoud GM, Ibdah JA; Almashhrawi; Rahman; Hammoud; Ibdah (November 2013). "Liver diseases in pregnancy: diseases unique to pregnancy". World J Gastroenterol. 19 (43): 7639–46. doi:10.3748/wjg.v19.i43.7639. PMC 3837262. PMID 24282353.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  13. ^ Matthews DC, Syed AA (2011). "The role of TSH receptor antibodies in the management of Graves' disease". European Journal of Internal Medicine. 22 (3): 213–6. doi:10.1016/j.ejim.2011.02.006. PMID 21570635.
  14. ^ Carlson, Karen J., MD; Eisenstat, Stephanie J., MD; Ziporyn, Terra (2004). The New Harvard Guide to Women's Health. Harvard University Press. pp. 392–3. ISBN 0-674-01343-3.{{cite book}}: CS1 maint: multiple names: authors list (link)
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  16. ^ Zhang Y, Cantor RM, MacGibbon K, Romero R, Goodwin TM, Mullin PM, Fejzo MS (2011). "Familial aggregation of hyperemesis gravidarum". American Journal of Obstetrics and Gynecology. 204 (3): 230.e1–7. doi:10.1016/j.ajog.2010.09.018. PMC 3030697. PMID 20974461.
  17. ^ Cole, LA (August 2010). "Biological functions of hCG and hCG-related molecules". Reproductive biology and endocrinology. 8 (102): 102. doi:10.1186/1477-7827-8-102. PMC 2936313. PMID 20735820.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ Hershman JM (June 2004). "Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid". Best Pract. Res. Clin. Endocrinol. Metab. 18 (2): 249–65. doi:10.1016/j.beem.2004.03.010. PMID 15157839.
  19. ^ Aka N, Atalay S, Sayharman S, Kiliç D, Köse G, Küçüközkan T; Atalay; Sayharman; Kiliç; Köse; Küçüközkan (2006). "Leptin and leptin receptor levels in pregnant women with hyperemesis gravidarum". The Australian & New Zealand journal of obstetrics & gynaecology. 46 (4): 274–7. doi:10.1111/j.1479-828X.2006.00590.x. PMID 16866785.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ a b c d e Bourne,, Thomas H.; Condous, George, eds. (2006). Handbook of early pregnancy care. Informa Healthcare. pp. 149–154. ISBN 9781842143230.{{cite book}}: CS1 maint: extra punctuation (link)
  21. ^ Verberg, MF; Gillott, DJ; Al-Fardan, N; Grudzinskas, JG (September–October 2005). "Hyperemesis gravidarum, a literature review". Human Reproduction Update. 11 (5): 527–539. doi:10.1093/humupd/dmi021. PMID 16006438. Archived from the original on 2016-12-15. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  22. ^ Bagis, T; Gumurdulu, Y; Kayaselcuk, F; Yilmaz, ES; Killicadag, E; Tarim, E (November 2002). "Endoscopy in hyperemesis gravidarum and Helicobacter pylori infection". International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 79 (2): 105–9. doi:10.1016/s0020-7292(02)00230-8. PMID 12427393.
  23. ^ "Hyperemesis Gravidarum (Severe Nausea and Vomiting During Pregnancy)". Cleveland Clinic. 2012. Archived from the original on 15 December 2012. Retrieved 23 January 2013. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  24. ^ a b c Medline Plus (2012). "Hyperemesis gravidarum". National Institutes of Health. Archived from the original on 27 January 2013. Retrieved 30 January 2013. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  25. ^ a b Evans, Arthur T., ed. (2007). Manual of obstetrics (7th ed.). Wolters Kluwer / Lippincott Williams & Wilkins. pp. 265–8. ISBN 9780781796965. Archived from the original on 2017-09-11. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  26. ^ Office on Women's Health (2010). "Pregnancy Complications". U.S. Department of Health and Human Services. Archived from the original on 29 October 2013. Retrieved 27 October 2013. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  27. ^ British National Formulary (March 2003). "4.6 Drugs used in nausea and vertigo – Vomiting of pregnancy". BNF (45 ed.).
  28. ^ Tuot, D; Gibson, S; Caughey, AB; Frassetto, LA (March 2010). "Intradialytic hyperalimentation as adjuvant support in pregnant hemodialysis patients: case report and review of the literature". International urology and nephrology. 42 (1): 233–7. doi:10.1007/s11255-009-9671-5. PMC 2844957. PMID 19911296.
  29. ^ a b c Jarvis, S; Nelson-Piercy, C (June 2011). "Management of nausea and vomiting in pregnancy". BMJ (Clinical research ed.). 342: d3606. doi:10.1136/bmj.d3606. PMID 21685438.
  30. ^ a b c d Matthews, Anne; Haas, David M.; O'Mathúna, Dónal P.; Dowswell, Therese (2015-09-08). "Interventions for nausea and vomiting in early pregnancy". The Cochrane Database of Systematic Reviews (9): CD007575. doi:10.1002/14651858.CD007575.pub4. ISSN 1469-493X. PMID 26348534.
  31. ^ Tan, PC; Omar, SZ (April 2011). "Contemporary approaches to hyperemesis during pregnancy". Current Opinion in Obstetrics and Gynecology. 23 (2): 87–93. doi:10.1097/GCO.0b013e328342d208. PMID 21297474.
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External links

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