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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 45 - Nausea and Vomiting of Pregnancy

Updated: Apr 18

"When we come close to the end of our life, what’s really important makes itself known. It isn’t whether or not we have two Mercedes or whether or not we spent more time at the office. For most people, it’s about relationships. It’s about answering two questions: 'Am I loved?' and 'Did I love well?' So much of what happens around the end of life boils down to those two questions. If those questions are important then, why aren’t they important to us now? Why should we wait until the time of our death to discover the answers or even ask ourselves those questions?" - Frank Ostaseski

2018 Pinot Noir from Hedgeline Vineyards

"Mary Lee, MPH, Pre-Health Advisor at UC Davis, soon to be medical student"

"Jeta Kumaravel, MPH, Health Education Coordinator for First 5 Yolo, soon to be medical student"


PB#189 - Published January 2018


Five Pearls

  1. The decision to treat should be informed by the woman’s perception of the severity of symptoms, her desire for treatment, and the potential effect of treatment on her fetus

  2. Use of prenatal vitamins 1 mo before fertilization may reduce incidence and treating nausea and vomiting of pregnancy (NVP) can prevent progression from NVP to hyperemesis gravidarum (HG)

  3. After dietary and nonpharmacologic options (e.g. ginger) have been tried, first-line pharmacotherapy entails trying vitamin B6 alone or vitamin B6 plus doxylamine

  4. Antithyroid drugs are not recommended for abnormal maternal thyroid tests attributable to gestational transient thyrotoxicosis or HG

  5. Hospitalization for evaluation and treatment of dehydration and electrolyte imbalance is indicated when a woman can’t tolerate liquids without vomiting and hasn’t responded to outpatient management


Background

- up to 80% of women experience nausea in pregnancy

- roughly 50% will experience vomiting

- less than 3% will develop HG

- severity is wide-ranging, and assessment can be aided by inventories like the pregnancy-unique quantification of emesis and nausea (PUQE)

- can significantly impact quality of life, and it can be very expensive to the health care system as well as to the patient (e.g. time taken off from work)

- HG is the most common reason for hospital admission in early pregnancy

- severe N/V usually remits after 11 weeks or so (corresponding w/ plateau of bHCG levels)


Risk factors for N/V in pregnancy

- increased placental mass (molar pregnancy, multiple gestations, etc.)

- history of motion sickness or migraines

- personal history of NV in pregnancy

- family history of HG

- genotypically female fetus


Differential diagnoses

- wide range of things can cause nausea and vomiting (see Box 1)

- rule of thumb: if the N/V starts after 9 wga, it's probably not just pregnancy

- some factors that might also suggest a different etiology: abdominal pain, fever, headache, neuro findings/deficits like double vision, enlarged thyroid, or elevated thyroid hormones.


Note: In the event that you find elevated thyroid hormones, approach judiciously. If you find a goiter on exam or if the patient was diagnosed with primary thyroid disease prior to pregnancy, treatment with antithyroid medication may be warranted. Otherwise, elevated thyroid hormones may be due to gestational transient thyrotoxicosis (bHCG stimulates the thyroid!), which is managed with supportive therapy and no antithyroid drugs


Diagnosing the dreaded but rare case of HG

- these patients generally present w/ persistent vomiting

- other etiologies ruled out

- you generally also see ketonuria and weight loss (at least 5% of pre-pregnancy weight)


So how does this happen?

- well...we don't know

- it might be associated with high estradiol and/or bHCG


Effects of severe N/V on the fetus

- in most severe cases, esp HG, the biggest concern is for small fetus/newborn

- increased perinatal or neonatal mortality have not been demonstrated in large, prospective cohorts

- no long-term health complications have been reported


Effects of severe N/V on the mom

- generally not much to be concerned about as long as she is adequately hydrated and her electrolytes repleted, but there are case reports of associated Wernicke encephalopathy (Vitamin B1 deficiency), splenic avulsion, esophageal rupture, pneumothorax, and acute tubular necrosis with more severe cases of N/V in pregnancy

- Wernicke encephalopathy associated with HG, in particular, has been associated with maternal death or permanent neurologic disability

- and let's not forget that being persistently nauseated for up to 10 weeks is misery and thus can provoke anxiety/depression


Can it be prevented?

- starting prenatal vitamins 1 month before pregnancy might help

- anecdotally, adding vitamin B6 (pyridoxine) 50 mg daily for a month or greater may reduce the risk as well


Non-pharmacologic tx options

- try ginger and vitamin B6 before moving to pharmacologic agents

- smaller meals may also help, as well as avoiding spicy or fatty foods

- several studies have found benefit from acupressure, acupuncture, and electrical nerve stimulation of the Neiguan point (located three finger breadths below the wrist on the inside of the wrist in between the two tendons )

- if these therapies aren't cutting it, you have several drugs to choose from


Pharmacologic tx options

- several mechanisms to consider:

  • anti-histaminic

  • anti-seritonergic

  • anti-dopaminergic






Anti-histaminic drugs (H1 blockers)

- no single approach has proven to be better than others, though doxylamine + B6 is a favorite place to start

- promethazine (also weak D2 blocker, Cat C)

- doxylamine (Cat B)

- diphenhydramine (Cat B)

- all will make her sleepy


Anti-seritonergic drugs (5HT-3 blockers)

- ondansetron (Cat B)

- granisetron (Cat B)

- when combined with antipsychotics and many other medications may prolong QT (remember Torsades?!)

- can be very constipating


Anti-dopaminergic drugs (D2 blockers)

- metoclopramide (Cat B) works by blocking D2 and 5HT-3 centrally, but it also increases tone in the lower esophageal sphincter and agonizes muscarinic receptors and 5HT-4 receptors in the gut)

- prochlorperazine (Cat C)

- promethazine (Cat C)

- chlorpromazine (Cat C)

- metoclopramide carries lowest risk of dyskinesia

- be cautious when using D2 blockers together given increased risk for extrapyramidal side effects (though prochlorperazine has a higher affinity than promethazine) or, rarely, neuroleptic malignant syndrome

- anecdotally, of all drugs, I have seen the best results with metoclopramide for managing nausea in early pregnancy, which makes sense given bHCG's proposed activity in the chemoreceptor trigger zone


Other agents

  • steroids - reserved for extreme cases due to fetal risk

  • benzos - useful outside of pregnancy

  • gabapentin - generally not helpful


ACOG's treatment algorithm. Keep in mind that not all of these drugs are approved by the FDA for use in pregnant women


How can lab work and other diagnostic studies help?

- labs are helpful in making diagnosis and assessing severity

- in HG, you may find:

  • blood: abnormal LFTs

  • blood: hyperbilirubinemia

  • blood: elevated amylase or lipase (5x greater than normal)

  • blood: hypochloremic metabolic alkalosis

  • urine: elevated specific gravity

  • urine: ketonuria

- severely elevated LFTs may indicate primary hepatitis

- 5-10x greater than normal elevation of amylase may indicate acute pancreatitis - if no response to treatment, consider testing for H. pylori infection, which can cause gastric ulcers

- if other clinical signs of hyperthyroidism, check TSH and thyroid hormone levels (if hyperthyroidism is related to HG alone, you can expect it to resolve by 20 wga)


When is parenteral hydration/nutrition recommended?

- start with IV hydration; add dextrose and thiamine if indicated

- for the worst cases (unresponsive to outpatient therapy and continuing to lose weight), total parenteral nutrition (TPN) may be indicated

- TPN carries risk for thrombosis and sepsis, so be judicious


When is hospitalization recommended?

- completely unable to tolerate PO and electrolyte abnormalities or severe malnourishment are suspected especially if mental status changes or hemodynamic instability are observed

- hospitalize to provide IV hydration, nutritional support, and electrolyte normalization, then OK to discharge home w/ close outpatient follow-up once tolerating PO

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