Hyperemesis gravidarum

Hyperemesis Gravidarum is the most common cause of hospitalization in 1st Trimester.

1. Hyperemesis gravidarum

2. Dr. Niranjan Chavan MD, FCPS, DGO, DFP, MICOG, DICOG, FICOG Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H Chairperson, FOGSI Oncology and TT Committee (2012-2014) Treasurer, MOGS (2017- 2018) Chair and Convener, FOGSI Cell- Violence against Doctors (2015-2016) Chief Editor, AFG Times (2015-2017) Editorial Board, European Journal of Gynecologic Oncology Editor of FOGSI FOCUS, MOGS, AFG & IAGE Newsletters Member, Managing Committee, IAGE (2013-2017) Member, Oncology Committee, AOFOG (2013 -2015) Recipient of 6 National & International Awards Author of 15 Research Papers and 19 Scientific Chapters Course Co-Ordinator, of 11 batches, of MUHS recognized Certificate Course of Basic Infertility Management Including Endoscopy (BIMIE) at LTMGH

3. introduction Nausea and Vomiting of Pregnancy diagnosed when onset is in the first trimester of pregnancy and other causes of nausea and vomiting have been excluded . Hyperemesis Gravidarum is defined as protracted Nausea and Vomiting of Pregnancy with the triad of > 5 % pre pregnancy weight loss D ehydration and E lectrolyte imbalance.

4. incidence The incidence of women with severe symptoms vary from 0.3 to 3 % of pregnancies. In a prospective study published in 2016 which included 800 patients, 57 % reported nausea and 27 % reported both nausea and vomiting by 8 weeks of gestation. * Hinkle SN, Mumford SL, Grantz KL, et al. Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss: A Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med 2016; 176:1621 .

5. Risk factors Multiple gestation H ydatidiform mole Non-use of multivitamins before 6 weeks of gestation or during the peri-conceptional period H eartburn and acid reflux Nulligravida Nonpregnant women who experience nausea and vomiting related to oestrogen-based medication

6. Risk factors Motion sickness Migraine Female fetus Family history of Hyperemesis Gravidarum Smoking and Alcohol are protective factors .

7. pathogenesis

8. pathogenesis

9. pathogenesis HORMONAL CHANGES Estrogen Progesterone Beta hCG These hormones relax smooth muscle and thus slow gastrointestinal transit time and may alter gastric emptying.  Relax the lower oesophageal sphincter

10. In a 2014 systematic review and meta-analysis of 26 epidemiological studies published in American Journal of Obstetrics & Gynaecology , a significant association was found between  H. pylori  infection and hyperemesis gravidarum/nausea and vomiting of pregnancy compared with asymptomatic controls (OR 3.21 ) 

11. Natural course Mean onset of symptoms  five to six weeks of gestation Peak  nine weeks Subsides by  16 to 20 weeks of gestation 60 % become asymptomatic six weeks after onset of nausea. Persisted symptoms till third trimester  15 to 20 % Persisted symptoms till delivery  5 %

12. Clinical presentation Nausea and vomiting Weight loss (> 5% of pre pregnant weight or >3 kg) Ketonuria Orthostatic hypotension Physical signs of dehydration Ptyalism (Hyper salivation)

13. DIAGNOSTIC SCORING SYSTEM The Motherisk – PUQE (Pregnancy Unique Quantification of Emesis ) scoring system Rhodes score Modified PUQE Score ( symptoms over the course of the entire first trimester) Assess the symptoms for past 12 hours

14. RHODES INDEX : none: 0, mild: 1-8, moderate: 9-16, severe: 17-24, great: 24-32 .

15. Modified puqe score Mild NVP 3–6 M oderate 7–12 and Severe NVP/HG ≥13

16. investigations Electrolyte Imbalance: hypokalemia hypochloremia hypomagnesaemia If Mg2+ < 0.8 mEq /L  resistance to parathormone  Hypocalcemia Hematocrit: due to hemoconcentration Liver Function Test : ALT & AST (in 50%) : bilirubin (do not rise > 4) Serum  amylase and lipase  ( 10 to 15 %) Thyroid Function: Mild hyperthyroidism due to raise B – hCG : Transient Biochemical Hyperthyroidism is  is defined as a free T4 index higher than the upper range of normal, or a thyroid-stimulating hormone (TSH) level less than 0.4  mU /L.

17. Differential diagnosis Multiple gestation H ydatidiform mole Preeclampsia, HELLP, and acute fatty liver of pregnancy (late onset) Pancreatitis Migraine Hyperparathyroidism in pregnancy C annabinoid hyperemesis syndrome

18. management

19. As per ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy . 2018 Nausea & Vomiting of Pregnancy (NVP) should be treated according to the severity N ausea alone V omiting without dehydration V omiting with dehydration.

20. Management of nausea alone Diet changes : small meals every 2 hrs avoid triggers add ginger to diet Pyridoxine:   10 to 25 mg orally every 6 - 8 hours; the maximum 200  mg/day.  Doxylamine succinate and pyridoxine: each tablet contains doxylamine 10 mg and pyridoxine 10 mg, 2 – 4 tabs/day Acupuncture or acupressure – P6 acupressure wristbands Hypnosis

21. Management of vomiting without dehydration Antihistaminic (H1 antagonists ): Diphenhydramine, Meclizine, Dimenhydrinate Dopamine Antagonist: Metoclopramide, Promethazine, Prochlorperazine Serotonin Antagonist:  Ondansetron, granisetron, and dolasetron  Acid-reducing agents: antacids, H2 blockers, proton pump inhibitors

22. Management of vomiting with dehydration IV Fluid & Electrolyte Correction Vitamins & Mineral Antiemetics Diet therapy

23. IV Rehydration and Electrolyte Correction 2 L intravenous Ringer's lactate infused over 3 – 5 hrs Isotonic saline if serum Na+ levels >120  mEq /L    D extrose 5 % in 0.45 % saline with 20 mEq   KCl  at 150 mL/hour to patients with normal K- levels   U rine output of at least 100 mL/hour S erum K +  3.0 to 3.4  mEq /L. Treatment is usually started with 10 to 20 mEq of K+ given 2 - 4times per day (20 to 80  mEq /day )

24. VITAMINS & mINERALS THIAMINE: 100mg IV for 3 days FOLIC ACID: 0.6mg daily VITAMIN B6: 25mg in 1 litre fluid daily MVI: 10 ml with IV Fluid MAGNESIUM :   2 g (16 mEq ) magnesium sulfate  infused as a 10 percent solution over 10 to 20 minutes , followed by 1 g (8 mEq ) in 100 mL of fluid per hour.

25. CLASS DRUG DOSE SIDE EFFECTS FDA CATEGORY Antihistaminics Diphenhydramine 25 – 50 mg QID B Meclizine 25 mg QID Cleft palate B Dimenhydrinate 25 mg QID, MAX 400mg B Dopamine antagonist Metochlopramide 10mg PO/IV/IM 30 min before each meal Metoclopramide-induced tardive dyskinesia B Promethazine (H1 + Dopamine antagonist 12.5 – 25mg PO/PR/IV every 4 hours Sedation Dystonia Lower seizure threshold C Prochlorperazine 10 mg PO QID 25 mg PR BD QT prolongation Urinary retention Extrapyramidal symptoms C 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist Ondensetron 4mg PO/IV QID Headache Constipation QT prolongation Serotonin syndrome B Granisetron Can be given transdermal Same as ondensetron B

26. Refractory cases The ACOG suggests consideration of testing for  H. pylori  infection in patients who are unresponsive to standard therapy. CORTICOSTEROIDS :  methylprednisolone (16 mg) IV/ 8 hours for 48 to 72 hours Hydrocortisone 100mg IV BD for 2 – 3 days After IV, Prednisolone 40mg for 1 day  20 mg for 3 days  5mg for 7 days Parenteral Nutrition : continued till the women is able to take 1000kcal/day per oral

27. conclusion Nausea and vomiting in pregnancy is the most common indication for hospitalization in 1 st trimester. Severity of NVP should be evaluated using PUQE score and treated accordingly. Diet changes, avoidance of the trigger and Doxylamine + Pyridoxine is the 1 st line of therapy PUQ> 13 with dehydration should be treated with IV rehydration, electrolyte correction and ondansetron. Refractory cases might require corticosteroids and parenteral nutrition .

28. references Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol 2018; 131:e15 . The management of nausea and vomiting of pregnancy and hyperemesis gravidarum, Green Top Guideline No 69, June 2016 Sartori J, Petersen R, Coall DA, Quinlivan J. The impact of maternal nausea and vomiting in pregnancy on expectant fathers: findings from the Australian Fathers' Study. J Psychosom Obstet Gynaecol 2017; :1. Matthews A, Haas DM, O'Mathúna DP, Dowswell T. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2015; :CD007575 . Tan A, Lowe S, Henry A. Nausea and vomiting of pregnancy: Effects on quality of life and day-to-day function. Aust N Z J Obstet Gynaecol 2017. Heitmann K, Nordeng H, Havnen GC, et al. The burden of nausea and vomiting during pregnancy: severe impacts on quality of life, daily life functioning and willingness to become pregnant again - results from a cross-sectional study. BMC Pregnancy Childbirth 2017; 17:75 .