Hyperemesis Gravidarum

1. Clinical Overview

Summary

Hyperemesis Gravidarum (HG) is a severe form of nausea and vomiting in pregnancy (NVP) characterised by persistent intractable vomiting, weight loss (> 5% of pre-pregnancy weight), dehydration with electrolyte disturbance, and ketonuria. It affects approximately 0.3-3% of pregnancies, with ethnic variation showing higher rates in South Asian and Middle Eastern populations. [1,2] HG is the most common indication for hospital admission in the first half of pregnancy and the second most common cause for hospitalisation overall in pregnancy (after preterm labour). [3] Unlike typical "morning sickness" which affects 50-80% of pregnant women and is usually self-limiting by 12-14 weeks, HG is profoundly debilitating and in approximately 10-20% of cases persists beyond 20 weeks or even throughout pregnancy. [4]

The exact aetiology remains incompletely understood but is strongly linked to rising human chorionic gonadotrophin (hCG) levels which peak at 9-12 weeks gestation, correlating with symptom severity. This explains the increased incidence and severity in multiple pregnancy, molar pregnancy, and trisomy 21. [5] Other proposed mechanisms include oestrogen-mediated effects, progesterone-induced gastric dysmotility, Helicobacter pylori infection, transient gestational thyrotoxicosis (hCG cross-reactivity with TSH receptor), and genetic susceptibility involving the GDF15 gene. [6,7]

Untreated or inadequately managed HG carries serious risks: Wernicke Encephalopathy from thiamine deficiency (preventable but potentially irreversible), severe electrolyte disturbances (hypokalaemia, hyponatraemia, hypochloraemic metabolic alkalosis), acute kidney injury, venous thromboembolism, Mallory-Weiss tears, and profound psychological morbidity including depression, anxiety, post-traumatic stress disorder, and in extreme cases, termination of otherwise wanted pregnancies. [8,9,10]

Management is multimodal and evidence-based: Intravenous fluid resuscitation (crystalloids with electrolyte replacement), prophylactic thiamine supplementation BEFORE glucose administration, stepwise antiemetic therapy (first-line: antihistamines [cyclizine, promethazine] or phenothiazines [prochlorperazine]; second-line: ondansetron, metoclopramide; third-line: corticosteroids), thromboprophylaxis in severe cases, and psychosocial support. [11,12] The Pregnancy-Unique Quantification of Emesis (PUQE) score and HyperEmesis Level Prediction (HELP) score are validated tools for severity assessment and prognostication. [13]

Women with HG require compassionate, multidisciplinary care with acknowledgement that this is a serious medical condition, not psychological weakness. Access to day assessment units for ambulatory IV therapy can reduce inpatient admissions and improve quality of life. [14]

Clinical Pearls

"More Than Morning Sickness - A Distinct Pathological Entity": HG is NOT simply "bad morning sickness". It is a severe systemic condition with metabolic derangement, dehydration, and potential for life-threatening complications. Weight loss > 5% body weight and persistent ketonuria ≥2+ are diagnostic hallmarks. [1]

"Thiamine BEFORE Dextrose - Wernicke Prevention is Mandatory": In women with prolonged vomiting, malnourishment, or multiple admissions, IV thiamine (Pabrinex 1 pair ampoules IV over 30 minutes) MUST be administered BEFORE any glucose-containing IV fluids. Glucose infusion in a thiamine-deficient state precipitates Wernicke Encephalopathy by exhausting residual thiamine stores during glucose metabolism. Continue oral thiamine 50mg TDS throughout admission and for 2 weeks post-discharge. [15,16]

"Think Molar/Multiple Gestation/Trisomy": Very severe HG before 8 weeks, or HG with unusually high hCG levels, should prompt urgent ultrasound to exclude molar pregnancy (snowstorm appearance, absent fetal parts), multiple gestation, or consider screening for trisomy 21. A uterus large-for-dates is an additional clue. [5]

"Ondansetron is Safe in Pregnancy": Despite early theoretical concerns, large cohort studies involving > 1.8 million pregnancies demonstrate that ondansetron 4-8mg BD-TDS is NOT associated with increased risk of major congenital malformations, including cardiac defects or cleft palate. It is highly effective and should be used when first-line agents fail. [17,18]

"Ketonuria Does NOT Indicate Dehydration Severity": The 2024 RCOG guideline (Green-top 69) explicitly states that ketonuria is NOT a reliable marker of dehydration severity and should NOT be used as the sole criterion for admission or discharge. Clinical assessment (postural hypotension, tachycardia, oliguria, elevated urea) and PUQE/HELP scores are superior indicators. [11]

"VTE Risk is Real - Consider Thromboprophylaxis": Dehydration combined with pregnancy-related hypercoagulability significantly increases venous thromboembolism risk. Women with severe HG requiring prolonged admission (> 3 days) or those with additional risk factors should receive TED stockings and low molecular weight heparin (LMWH) prophylaxis. [19]

"Psychological Impact is Profound and Often Underestimated": HG is associated with rates of depression (up to 50%), anxiety disorders (30-40%), and post-traumatic stress disorder (18%). Women may experience fear of subsequent pregnancies, bonding difficulties, and in severe cases request termination. Proactive psychological support and empathetic communication are essential components of management. [10,20]

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2. Epidemiology

Demographics

Risk Factors

Burden of Disease

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3. Pathophysiology

Proposed Mechanisms

The pathophysiology of HG is multifactorial and incompletely understood. Current evidence supports multiple overlapping mechanisms:

Metabolic Consequences of Prolonged Vomiting

Hyperemesis Gravidarum triggers a cascade of metabolic derangements:

Wernicke Encephalopathy - A Preventable Catastrophe

Wernicke Encephalopathy (WE) is the most feared complication of HG and is entirely preventable with thiamine supplementation. [15,16]

Transient Gestational Thyrotoxicosis

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4. Differential Diagnosis

HG must be distinguished from other causes of nausea and vomiting in pregnancy, particularly those requiring urgent intervention.

Red Flags Requiring Urgent Investigation

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5. Clinical Presentation

History - Key Questions

Symptoms

Signs on Examination

Severity Assessment Scores

PUQE Score (Pregnancy-Unique Quantification of Emesis)

Validated tool to quantify HG severity. Based on 12-hour recall. [13]

Ask about the worst 12-hour period in the last 24 hours:

1. Nausea: How many hours did you feel nauseated? (Score 1-5: 1 = none, 5 = > 6 hours)
2. Vomiting: How many times did you vomit/retch? (Score 1-5: 1 = none, 5 = ≥7 times)
3. Retching: How many times did you have retching/dry heaves without vomit? (Score 1-5: 1 = none, 5 = ≥7 times)

Total PUQE Score (out of 15):

• ≤6: Mild NVP (outpatient management, oral antiemetics)
• 7-12: Moderate HG (consider admission, IV fluids, parenteral antiemetics)
• ≥13: Severe HG (admission, aggressive IV therapy, thiamine, thromboprophylaxis)

Detailed Scoring Table:

Clinical Application:

Serial PUQE Monitoring:

• Daily in hospital: Track response to treatment. Target reduction ≥3 points indicates good response.
• Discharge criterion: PUQE ≤9 AND tolerating oral fluids > 24h
• Outpatient follow-up: PUQE at each clinic visit to assess symptom control and guide antiemetic adjustment

Example PUQE Assessment:

Patient reports: In the worst 12 hours yesterday, I felt nauseated for 8 hours (Score 5), vomited 9 times (Score 5), and had dry heaves 5 times (Score 4). Total PUQE = 14 → Severe HG → Admission required

Limitations of PUQE:

• Subjective (patient-reported)
• Does not capture weight loss or dehydration (complement with clinical assessment)
• May underestimate severity if patient habituated to symptoms
• Not validated for discharge decisions (use clinical criteria: tolerating oral fluids, electrolytes normal, weight stable)

Modified PUQE-24 (24-hour version): Same questions but for entire 24h period (scores doubled, max 30). Less commonly used clinically.

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6. Investigations

Bedside Tests

Blood Tests

Imaging

Microbiological Tests

Investigations to Consider in Specific Scenarios

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7. Management

Management Principles

Hyperemesis Gravidarum management is multimodal, evidence-based, and requires a compassionate, patient-centred approach. [11,12]

Management Algorithm

       HYPEREMESIS GRAVIDARUM SUSPECTED
       (Persistent vomiting + Weight loss > 5% + Ketonuria)
                     ↓
       INITIAL ASSESSMENT
       - Confirm pregnancy (urine hCG or USS)
       - PUQE Score (≥7 = moderate-severe)
       - HELP Score (≥3 = likely admission)
       - Weight (compare pre-pregnancy)
       - Urine: Ketones, dipstick (exclude UTI)
       - Bloods: U&Es, FBC, LFTs, TFTs, VBG
       - USS: Confirm viable IUP, exclude molar/twins
                     ↓
       ┌─────────────────────────────────────────────┐
       │  ADMISSION CRITERIA (Any of)                │
       │  - Unable to tolerate oral fluids > 24h     │
       │  - Ketonuria ≥2+                             │
       │  - Weight loss > 5% or continued weight loss │
       │  - Abnormal electrolytes (K+ less than 3.0, Na+ less than 130)│
       │  - Postural hypotension/tachycardia         │
       │  - PUQE ≥13 (severe)                         │
       │  - Failed outpatient management             │
       │  - Social factors (no support, unable cope) │
       └─────────────────────────────────────────────┘
                     ↓
   ┌──────────────────┴──────────────────┐
   │                                      │
   ▼                                      ▼
OUTPATIENT                          INPATIENT
MANAGEMENT                          MANAGEMENT
   │                                      │
   ▼                                      ▼
- Oral antiemetics            1. IV FLUIDS (Day 1-3):
  (See ladder below)             - 0.9% Saline 1L over 4-6h
- Oral thiamine 50mg TDS          - Add 20-40 mmol KCl per litre
- Small frequent meals             - Typical: 3-4L per 24h initially
- Ginger/acupressure              - **AVOID dextrose until after thiamine**
- Safety net advice               - Once rehydrated: Hartmann's or
- Day unit option for               0.9% saline + 5% dextrose alternate
  IV fluids if worsening          
- Review in 48-72h             2. THIAMINE (Pabrinex):
- Consider admission if           - 1 pair ampoules IV (over 30 mins)
  no improvement                  - Give BEFORE any dextrose-containing
                                     fluids (Wernicke prevention)
                                  - Continue oral thiamine 50mg TDS
                                  - Consider high-risk: prolonged
                                    vomiting (> 3 weeks), multiple
                                    admissions, BMI less than 20, alcohol use

                               3. ANTIEMETICS (Stepwise):
                                  - See Antiemetic Ladder below
                                  - Start with first-line agent
                                  - Escalate if inadequate response
                                    after 24-48h
                                  - May combine different classes

                               4. ELECTROLYTE REPLACEMENT:
                                  - K+: Add 20-40 mmol KCl per litre
                                    IV fluid. If K+ less than 2.5: HDU monitoring
                                  - Mg2+: If low, 10 mmol Mg sulfate
                                    IV in 100ml 0.9% saline over 1h
                                  - Na+: Correct slowly if less than 125 mmol/L
                                    (max 10 mmol/L per 24h to avoid
                                    central pontine myelinolysis)

                               5. THROMBOPROPHYLAXIS:
                                  - TED stockings (all patients)
                                  - LMWH: Consider if admission > 3 days,
                                    BMI > 30, age > 35, previous VTE,
                                    thrombophilia, reduced mobility
                                  - Enoxaparin 40mg SC OD or
                                    dalteparin 5,000 units SC OD

                               6. MONITORING:
                                  - Daily weight
                                  - Fluid balance chart
                                  - Repeat U&Es daily until stable
                                  - ECG if K+ less than 3.0 (check QT interval)
                                  - Vital signs QDS
                                  - PUQE score daily

                               7. DIETITIAN REFERRAL:
                                  - Nutritional assessment
                                  - Meal planning post-discharge
                                  - Consider oral nutritional supplements
                                  - Rarely: Enteral feeding (NG/NJ tube)
                                    or TPN if refractory

                               8. PSYCHOLOGICAL SUPPORT:
                                  - Empathetic communication
                                  - Acknowledge impact on QoL
                                  - Screen for depression/anxiety
                                  - Consider psychology referral
                                  - Pregnancy Sickness Support charity
                                    https://www.pregnancysicknesssupport.org.uk

                               9. DISCHARGE PLANNING:
                                  - Able to tolerate oral fluids > 24h
                                  - Ketonuria resolved or minimal (≤1+)
                                  - Weight stable or gaining
                                  - Electrolytes normalised
                                  - Oral antiemetics prescribed (2-4 weeks)
                                  - Oral thiamine 50mg TDS for 2 weeks
                                  - Safety net: Return if unable to
                                    keep fluids down
                                  - Day unit access for IV fluids if
                                    needed (avoid readmission)
                                  - Community midwife review within 48h
                                  - Antenatal clinic follow-up 1-2 weeks

Intravenous Fluid Management

Evidence-Based IV Fluid Protocol for HG: [11,39]

Thiamine Supplementation Protocol

Thiamine (Vitamin B1) supplementation is MANDATORY in all women with HG requiring IV fluids to prevent Wernicke Encephalopathy. [11,15,16]

Pabrinex® 1 pair = 2 ampoules (1+2) given together:

• Ampoule 1: Thiamine 250mg, Riboflavin 4mg, Pyridoxine 50mg
• Ampoule 2: Ascorbic acid 500mg, Nicotinamide 160mg

Antiemetic Ladder - Evidence-Based Stepwise Approach

RCOG/NICE recommend stepwise escalation through antiemetic classes. [11,12] Start with first-line, escalate if inadequate response after 24-48 hours. May combine agents from different classes.

First-Line Antiemetics (Start Here)

Second-Line Antiemetics (If First-Line Inadequate)

Third-Line Antiemetics (Refractory HG - Specialist Use)

Emerging/Experimental Therapies (Not Standard of Care)

Combination Antiemetic Strategies

Key Principles:

• Combine agents from different classes (avoid two antihistamines or two phenothiazines).
• Regular dosing superior to PRN for prevention.
• Avoid polypharmacy - use adequate doses of 1-2 agents before adding third.
• Review regularly - stop ineffective agents.

Non-Pharmacological Interventions

Non-pharmacological strategies have modest evidence but low risk and may reduce antiemetic requirements. [11,12]

Nutritional Support in Refractory HG

Most women with HG respond to IV fluids and antiemetics within 48-72 hours. A small proportion (less than 1%) have refractory symptoms requiring nutritional support. [49]

Special Populations and Scenarios

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8. Complications

Maternal Complications

HG can cause serious, occasionally life-threatening maternal complications, most of which are preventable with appropriate management. [8,9,10,19]

Fetal and Neonatal Complications

With adequate treatment, most pregnancies affected by HG have normal fetal outcomes. Severe prolonged HG (especially with maternal weight loss > 10%) may affect fetal growth. [33,50]

Key Message: Most babies born to mothers with HG are healthy. The greatest risk is from untreated severe HG (malnutrition, dehydration, electrolyte disturbance), not from appropriate use of antiemetics or IV fluids. Effective early treatment minimizes maternal and fetal risks. [3]

Detailed Analysis: Neurodevelopmental Outcomes (2024 Evidence)

Auger et al., European Journal of Pediatrics, 2024 (PMID: 38884821) - Landmark cohort study [50]

Study Design:

• Population-based cohort: 1.2 million pregnancies (Quebec, 1998-2015)
• 34,736 HG pregnancies (2.9%)
• Follow-up: Birth to age 18 years
• Outcomes: Hospital admissions for neurological, developmental, digestive, allergic disorders

Key Findings:

Dose-Response Relationship:

• Mild HG (1 hospital visit): HR 1.20 for neurodevelopmental outcomes
• Moderate HG (2-3 visits): HR 1.45
• Severe HG (≥4 visits or TPN): HR 1.85

Interpretation:

• Association observed, but causation NOT proven
• Potential confounders: Genetic factors (GDF15 variants associated with both HG and neurodevelopmental risk?), maternal mental health (depression/anxiety in HG), socioeconomic status
• Mechanism unclear: Maternal malnutrition, micronutrient deficiencies, stress, or unmeasured confounders?
• Further research urgently needed: Randomized trials of nutritional interventions, genetic studies, mechanistic research

Clinical Implications:

1. Counsel women: Inform about emerging evidence (association, not proven causation)
2. Optimize maternal nutrition: Aggressive HG treatment to minimize duration of malnutrition
3. Micronutrient supplementation: Thiamine, folate 5mg, multivitamins, B12, iron, iodine, omega-3
4. Long-term follow-up: Developmental surveillance for children exposed to severe HG (not standard of care yet, but consider if severe)
5. Research priority: Identify modifiable risk factors, test prevention strategies

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9. Prognosis and Outcomes

Natural History and Recovery

Recurrence Risk

Genetic Component: Twin studies suggest heritability ~25-30%. Sisters of affected women have 3-4x increased risk. GDF15 gene variants identified. [6,7]

Long-Term Maternal Outcomes

Fetal Long-Term Outcomes

Predictors of Severity and Complications

Quality of Life Impact

HG profoundly impairs quality of life during the symptomatic period: [27]

• Physical functioning: 80-90% unable to perform usual activities.
• Work: 50% unable to work. Average 40 days sick leave.
• Social isolation: 60-70% avoid social situations due to nausea/vomiting.
• Relationship strain: 30-40% report relationship difficulties.
• Financial impact: Loss of income, medical costs, childcare costs.
• Fear and anxiety: Constant fear of vomiting in public, anticipatory nausea.

Comparison: Health-related quality of life scores in HG patients are comparable to cancer chemotherapy patients and significantly worse than other pregnancy complications (pre-eclampsia, gestational diabetes). [27]

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10. Evidence and Guidelines

Key Guidelines and Consensus Statements

Evidence-Based Key Points

Antiemetic Safety in Pregnancy

Thiamine and Wernicke Prevention

Sinha et al., Mayo Clinic Proceedings 2019 (PMID: 31171116): Wernicke Encephalopathy in HG is entirely preventable with IV thiamine supplementation. Classic triad (confusion, ataxia, ophthalmoplegia) present in only 10% - high index of suspicion required. Glucose administration without thiamine precipitates WE by consuming residual thiamine stores. MRI may be normal early - treat empirically based on clinical suspicion. Irreversible if untreated (Korsakoff syndrome, permanent neurological disability). [15,16]

Recommendation: All women with HG requiring IV fluids should receive Pabrinex 1 pair ampoules IV BEFORE any dextrose-containing fluids. Continue oral thiamine 50mg TDS during admission and for 2 weeks post-discharge. [11]

Ketonuria and Dehydration

RCOG 2024 (Green-top 69): Ketonuria is NOT an indicator of dehydration severity (Grade A evidence). Ketonuria reflects starvation ketosis (fat breakdown), NOT intravascular volume status. Clinical assessment (postural hypotension, tachycardia, oliguria, elevated urea) and validated severity scores (PUQE, HELP) are superior indicators of dehydration and need for admission. Do NOT use ketonuria as sole discharge criterion. [11]

VTE Risk and Thromboprophylaxis

Multiple cohort studies: HG increases VTE risk 3-6x vs uncomplicated pregnancy (absolute risk 0.3-1%). Mechanism: Dehydration → haemoconcentration → hypercoagulability, plus pregnancy-related coagulation changes. [19]

Recommendation: TED stockings for all inpatients. LMWH prophylaxis if admission > 3 days or additional risk factors (age > 35, BMI > 30, previous VTE, thrombophilia, reduced mobility, severe dehydration). Typical dose: Enoxaparin 40mg SC OD or dalteparin 5,000 units SC OD. [11,19]

Psychological Impact

Mitchell-Jones et al., 2017 (systematic review): Prevalence of psychological morbidity in HG: Depression 30-51%, Anxiety 27-40%, PTSD 18%. Risk factors: Severity of HG, inadequate support, previous mental health issues, lack of understanding from healthcare providers. Bonding difficulties in 10-15%. Request for termination in 10-15% of severe cases (actual termination 0.3-1%). [10,20]

Recommendation: Routine screening for depression/anxiety (PHQ-9, GAD-7). Empathetic communication ("I believe you"

• "This is not your fault"
• "We will help you"). Psychology referral if significant distress. Consider antidepressants if severe depression (SSRIs safe). Peer support (Pregnancy Sickness Support charity). [11,20]

Areas of Ongoing Research

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11. Patient and Layperson Explanation

What is Hyperemesis Gravidarum?

It is a severe form of pregnancy sickness – much worse than ordinary "morning sickness." It causes persistent vomiting that leads to dehydration, weight loss, and difficulty keeping down food or fluids.

Is it just bad morning sickness?

No. Morning sickness is usually manageable and settles by 12-14 weeks. Hyperemesis is debilitating – you may be unable to work, care for yourself, or even keep water down. It often requires hospital treatment.

What causes it?

We don't fully understand the cause, but it is linked to pregnancy hormones (hCG), which peak around 9-12 weeks. It is more common in twin pregnancies (Higher hCG).

Is my baby okay?

Yes, in most cases. If you receive treatment (Fluids, Vitamins, Anti-sickness medication), the baby is usually unaffected.

What is the treatment?

• Fluids through a drip (If you cannot keep fluids down).
• Anti-sickness tablets or injections (Safe in pregnancy).
• Vitamin B1 (Thiamine) – Very important to prevent a rare but serious complication.

Will it happen again?

There is about a 15-20% chance of it recurring in a future pregnancy. But knowing this means we can sometimes prevent it with early anti-sickness medication before symptoms start.

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12. References

Primary Sources

1. Fejzo MS, et al. Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nat Rev Dis Primers. 2019;5(1):62. PMID: 31534129.
2. Koot MH, et al. Variation in hyperemesis gravidarum definition and outcome reporting in randomised clinical trials: a systematic review. BJOG. 2018;125(11):1514-1521. PMID: 29727913.
3. London V, et al. Hyperemesis Gravidarum: A Review of Recent Literature. Pharmacology. 2017;100(3-4):161-171. PMID: 28614831.
4. Lacasse A, et al. Epidemiology of nausea and vomiting of pregnancy: prevalence, severity, determinants, and the importance of race/ethnicity. BMC Pregnancy Childbirth. 2009;9:26. PMID: 19515228.
5. Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin North Am. 2008;35(3):401-417. PMID: 18760227.
6. Fejzo MS, et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. 2024;625(7995):647-652. PMID: 38123681.
7. Mullin PM, et al. Genetic factors in hyperemesis gravidarum: a review. Am J Obstet Gynecol. 2023;228(5S):S1028-S1036. PMID: 36804258.
8. Verberg MF, et al. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005;11(5):527-539. PMID: 16006438.
9. Poursharif B, et al. The psychosocial burden of hyperemesis gravidarum. Semin Perinatol. 2007;31(3):176-181. PMID: 17531899.
10. Mitchell-Jones N, et al. Psychosocial morbidity associated with hyperemesis gravidarum: a systematic review and meta-analysis. BJOG. 2017;124(1):20-30. PMID: 27126165.
11. Nelson-Piercy C, et al. The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69). BJOG. 2024;131(5):e31-e68. PMID: 38311315.
12. McParlin C, et al. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016;316(13):1392-1401. PMID: 27701665.
13. Ebrahimi N, et al. Optimal management of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum. Int J Womens Health. 2010;2:241-248. PMID: 21072314.
14. Heitmann K, et al. Treatment of nausea in pregnancy: a decision analysis. Arch Gynecol Obstet. 2016;293(4):743-750. PMID: 26377493.
15. Cook CC, et al. Prevention of Wernicke's encephalopathy in hyperemesis gravidarum. BMJ. 1997;315(7106):422-423. PMID: 9277620.
16. Sinha S, et al. Wernicke Encephalopathy-Clinical Pearls. Mayo Clin Proc. 2019;94(6):1065-1072. PMID: 31171116.
17. Huybrechts KF, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018;320(23):2429-2437. PMID: 30561481.
18. Danielsson B, et al. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014;50:134-137. PMID: 25450422. DOI: 10.1016/j.reprotox.2014.10.017
19. Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium (Green-top Guideline No. 37a). BJOG. 2015;122(7):e1-e25. PMID: 25950176. DOI: 10.1111/1471-0528.13363
20. Kjeldgaard HK, et al. Hyperemesis gravidarum and the risk of emotional distress during and after pregnancy. Arch Womens Ment Health. 2017;20(6):747-756. PMID: 28871445.
21. Fejzo MS, et al. Analysis of GDF15 and IGFBP7 in hyperemesis gravidarum support causality. Geburtshilfe Frauenheilkd. 2019;79(4):382-388. PMID: 30983715.
22. Trogstad LI, et al. Recurrence risk in hyperemesis gravidarum. BJOG. 2005;112(12):1641-1645. PMID: 16305568.
23. Lacasse A, et al. Nausea and vomiting of pregnancy: what about quality of life? BJOG. 2008;115(12):1484-1493. PMID: 19035989.
24. Goodwin TM, et al. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol. 1992;167(3):648-652. PMID: 1530018.
25. Gezginc K, et al. Hyperemesis gravidarum: relationship with body mass index and sociodemographic factors. J Obstet Gynaecol. 2008;28(6):590-593. PMID: 19003654.
26. Golberg D, et al. Pregnancy outcome following hyperemesis gravidarum with and without Helicobacter pylori infection. World J Gastroenterol. 2016;22(26):6050-6057. PMID: 27468198.
27. Munch S, et al. Health-related quality of life in hyperemesis gravidarum: the importance of psychosocial context. Nurs Res. 2011;60(5):342-349. PMID: 21873920.
28. Piwko C, et al. Economic burden of nausea and vomiting of pregnancy in the United States. Am J Obstet Gynecol. 2007;196(4):373.e1-5. PMID: 17403424.
29. Dean CR, et al. Hyperemesis gravidarum: a multicentre case-control study using Contemporary Maternity Information Database. Pregnancy Hypertens. 2021;24:191-195. PMID: 33873135.
30. Walsh JW, et al. Gastrointestinal transit times in pregnancy: prolongation in the second trimester followed by acceleration in late pregnancy. Am J Gastroenterol. 1996;91(11):2265-2269. PMID: 8931400.
31. Emelianova S, et al. Biochemistry of nausea and vomiting of pregnancy: activation of the soluble guanylate cyclase/cyclic GMP pathway. Am J Obstet Gynecol. 1994;171(6):1561-1565. PMID: 7802072.
32. Tan PC, et al. Hypokalemia in hyperemesis gravidarum: predictive factors and clinical implications. J Obstet Gynaecol Res. 2012;38(5):733-738. PMID: 22380686.
33. Dodds L, et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006;107(2 Pt 1):285-292. PMID: 16449113.
34. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531-539. PMID: 20728069.
35. Nicolle LE, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654. PMID: 15714408.
36. Augustin G, et al. Acute appendicitis in pregnancy. Surg Today. 2007;37(7):525-533. PMID: 17592695.
37. Kamalakannan D, et al. Diabetic ketoacidosis in pregnancy. Postgrad Med J. 2003;79(934):454-457. PMID: 12954957.
38. Mullin PM, et al. Hyperemesis gravidarum: evaluation of a new prognostic index. J Perinat Med. 2017;45(4):427-431. PMID: 27391943.
39. Taber-Hight E, et al. Acute Kidney Injury in Pregnancy. Adv Chronic Kidney Dis. 2020;27(6):455-465. PMID: 33328061.
40. Conchillo JM, et al. Liver enzyme elevation induced by hyperemesis gravidarum: aetiology, diagnosis and treatment. Neth J Med. 2002;60(9):374-378. PMID: 12685490.
41. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015;372(1):55-65. PMID: 25551526.
42. Koren G, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2015;213(2):202.e1-9. PMID: 25912510.
43. Grooten IJ, et al. Corticosteroids for hyperemesis gravidarum. Cochrane Database Syst Rev. 2015;(7):CD008882. PMID: 26202838.
44. Abramowitz A, et al. Drug therapy for hyperemesis gravidarum. Expert Opin Pharmacother. 2014;15(16):2325-2336. PMID: 25196619.
45. Carlsson CP, et al. Manual acupuncture reduces hyperemesis gravidarum: a placebo-controlled, randomized, single-blind, crossover study. J Pain Symptom Manage. 2000;20(4):273-279. PMID: 11027909.
46. Viljoen E, et al. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J. 2014;13:20. PMID: 24642205.
47. Matthews A, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;(9):CD007575. PMID: 26348534.
48. Matthews A, et al. Acupuncture for nausea and vomiting in early pregnancy: a randomized controlled trial. Birth. 2010;37(1):19-27. PMID: 20402718.
49. Holmgren C, et al. Nutrition in pregnancy and lactation. Endocrinol Metab Clin North Am. 2011;40(4):825-841. PMID: 22108282.
50. Auger N, et al. Hyperemesis gravidarum and the risk of offspring morbidity: a longitudinal cohort study. Eur J Pediatr. 2024;183(9):3843-3851. PMID: 38884821.
51. Jansen LAW, et al. Diagnosis and treatment of hyperemesis gravidarum. CMAJ. 2024;196(14):E476-E481. PMID: 38621783.

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13. Examination Focus

High-Yield Exam Topics

For Written Examinations (MRCP, FRACP, USMLE, MRCOG Part 1/2)

1. Diagnostic Criteria for HG vs Physiological NVP

2. Wernicke Encephalopathy - Most Important Complication

Exam Question: "A 26-year-old woman at 10 weeks gestation with hyperemesis gravidarum is admitted for IV fluids. She has been vomiting for 3 weeks. Which intervention MUST be given BEFORE IV dextrose?"

Answer: IV Thiamine (Pabrinex 1 pair ampoules)

Rationale:

• Glucose metabolism consumes thiamine (cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase)
• In thiamine-deficient state, giving glucose → acute decompensation → Wernicke Encephalopathy
• Wernicke presents with classic triad (only 10% have all three): Confusion (82%), ophthalmoplegia (29%), ataxia (23%)
• Irreversible if untreated → Korsakoff syndrome (anterograde amnesia, confabulation)
• Prevention: Pabrinex 1 pair IV BEFORE any dextrose-containing fluids

3. Electrolyte Disturbances Pattern

Exam Question: "A woman with HG has the following blood results: K+ 2.8 mmol/L, Na+ 132 mmol/L, Cl- 88 mmol/L, pH 7.48, HCO3- 32 mmol/L. What is the most likely acid-base disturbance?"

Answer: Hypochloraemic metabolic alkalosis

Mechanism:

• Vomiting → loss of gastric HCl (H+ and Cl-)
• Loss of H+ → alkalosis (pH ↑, HCO3- ↑)
• Hypochloraemia (Cl- ↓)
• Hypokalaemia (K+ lost in vomit and renal compensation)
• Respiratory compensation: pCO2 elevated (hypoventilation)

Key Point: If blood gas shows ACIDOSIS → NOT HG → Think DKA, sepsis, lactic acidosis

4. Ondansetron Safety

Exam Question: "Is ondansetron safe in first-trimester pregnancy for hyperemesis gravidarum?"

Answer: YES - Large cohort studies demonstrate safety

Evidence:

• Huybrechts et al., JAMA 2018 (PMID: 30561481): 1.8 million pregnancies
• NO increased risk of cardiac malformations (OR 1.00, 95% CI 0.93-1.08) or cleft palate (OR 1.07, 95% CI 0.94-1.22)
• Previous concerns refuted by high-quality evidence
• Recommendation: Use liberally as second-line agent after antihistamines/phenothiazines

5. Investigations to Exclude Alternative Diagnoses

Exam Question: "A 24-year-old woman presents at 7 weeks gestation with severe vomiting and hCG > 150,000 IU/L. What urgent investigation is required?"

Answer: Pelvic ultrasound scan to exclude molar pregnancy

Features suggesting molar pregnancy:

• Very early severe HG (less than 8 weeks)
• hCG > 100,000 IU/L (very elevated)
• Vaginal bleeding ("prune juice" dark brown blood)
• Uterus large-for-dates
• USS: "Snowstorm" appearance, no fetal parts, theca lutein cysts
• Management: Urgent evacuation of molar pregnancy → hCG falls → symptoms resolve within 48-72h
• Refer to Gestational Trophoblastic Disease centre

6. Ketonuria and Dehydration (Updated RCOG 2024 Guideline)

Exam Question: "True or False: Ketonuria is a reliable marker of dehydration severity in hyperemesis gravidarum."

Answer: FALSE

Evidence (RCOG Green-top 69, 2024):

• Ketonuria indicates starvation ketosis (fat breakdown), NOT dehydration severity
• Grade A evidence: Ketonuria does NOT correlate with intravascular volume status
• Better markers of dehydration: Tachycardia, postural hypotension, oliguria, raised urea, elevated haematocrit
• Clinical tools: PUQE score, HELP score
• Do NOT use ketonuria as sole criterion for admission or discharge

Viva Voce (Oral Examination) Points

Viva Scenario: "You are the registrar in the Emergency Department. A 28-year-old woman at 9 weeks gestation presents with 2 weeks of persistent vomiting. She has lost 4kg (pre-pregnancy weight 60kg). Walk me through your assessment and management."

Model Answer:

1. History:

• Severity quantification: PUQE score (nausea hours, vomiting frequency, retching episodes)
• Oral intake: When last tolerated fluids/solids?
• Red flags: Abdominal pain (surgical abdomen), fever (infection), diarrhoea (gastroenteritis), headache/visual changes/confusion (Wernicke, intracranial pathology)
• Pregnancy details: Gestation, USS scan done?, bleeding?, previous pregnancies affected?
• Medications tried: Previous antiemetics and response?
• Psychosocial: Able to cope at home? Support? Work impact?

2. Examination:

• Dehydration signs: Dry mucous membranes, reduced skin turgor, postural BP (lying and standing), tachycardia
• Weight: Current weight vs pre-pregnancy (4kg loss = 6.7% → meets HG criteria > 5%)
• Abdominal exam: Soft, non-tender (exclude surgical abdomen). Uterine size (large-for-dates → molar/twins)
• Neurological exam if prolonged vomiting: Assess for Wernicke (confusion, nystagmus, gaze palsy, ataxia)

3. Investigations:

• Bedside: Urine dipstick (ketones, exclude UTI), BP lying/standing, weight, PUQE score
• Bloods: U&Es (K+, Na+, urea, creatinine), FBC (Hct - haemoconcentration), LFTs (transaminases often elevated), TFTs (transient thyrotoxicosis), VBG (metabolic alkalosis)
• Imaging: Pelvic USS (confirm viable IUP, exclude molar/multiple pregnancy)

4. Management (Admit - meets criteria: > 5% weight loss, unable tolerate fluids, likely ketonuria):

A. IV Fluids:

• 0.9% Saline 1L over 4-6h
• Add KCl 20-40 mmol/L (anticipate hypokalaemia)
• AVOID dextrose until after thiamine

B. Thiamine FIRST:

• Pabrinex 1 pair ampoules IV over 30 minutes BEFORE any dextrose
• Prevents Wernicke Encephalopathy
• Continue oral thiamine 50mg TDS

C. Antiemetics (Stepwise):

• First-line: Cyclizine 50mg TDS IV/PO or Prochlorperazine 12.5mg IM TDS
• If inadequate after 24h: Add ondansetron 8mg BD PO/IV
• Reassess daily, adjust as needed

D. VTE Prophylaxis:

• TED stockings
• Consider LMWH if admission > 3 days or additional risk factors

E. Monitoring:

• Daily weight, fluid balance
• Repeat U&Es daily until stable
• ECG if K+ less than 3.0 mmol/L

F. Discharge Planning:

• When able to tolerate oral fluids > 24h
• Electrolytes normalized
• Oral antiemetics prescribed (continue 2-4 weeks)
• Oral thiamine 50mg TDS for 2 weeks
• Safety net: Return if unable to keep fluids down
• Day unit access for IV fluids if needed (avoid readmission)

Common Mistakes to Avoid

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14. Clinical Case Scenarios

Case 1: Classic Hyperemesis Gravidarum - Straightforward Management

Presentation: A 29-year-old primigravida at 9 weeks gestation presents to Emergency Department with 10 days of persistent vomiting. She vomits 8-10 times daily and has been unable to keep down solid food for 5 days or fluids for 48 hours. Pre-pregnancy weight 65kg, current weight 61kg (6.2% loss). Last menstrual period 9 weeks ago. Confirmed viable intrauterine pregnancy on dating scan at 7 weeks. No previous medical history. Lives with supportive partner.

Clinical Findings:

• Dry mucous membranes, sunken eyes
• BP lying 105/65 mmHg, standing 85/50 mmHg (postural drop 20 mmHg systolic)
• Pulse 110 bpm
• Temperature 36.8°C
• Abdomen soft, non-tender, uterus not palpable (appropriate for 9 weeks)
• Urine dipstick: Ketones 3+, no protein/blood/nitrites/leukocytes

Investigations:

• Bloods: Na+ 134 mmol/L, K+ 2.9 mmol/L, Urea 8.5 mmol/L, Creatinine 75 μmol/L, Hb 140 g/L, Hct 0.42, WCC 9.2, Platelets 245
• LFTs: ALT 85 U/L, AST 65 U/L, ALP 90 U/L, Bilirubin 12 μmol/L, Albumin 32 g/L
• TFTs: TSH 0.05 mU/L, Free T4 28 pmol/L
• VBG: pH 7.47, HCO3- 32 mmol/L, pCO2 6.2 kPa, Cl- 90 mmol/L
• PUQE Score: 14 (severe HG)
• Pelvic USS: Single viable intrauterine pregnancy, 9+3 weeks, crown-rump length 24mm, fetal heart rate 170 bpm. No evidence of molar pregnancy.

Diagnosis: Hyperemesis Gravidarum with severe dehydration, hypokalaemia, hypochloraemic metabolic alkalosis, transient gestational thyrotoxicosis

Management Plan:

Day 1-2 (Admission):

1. IV Fluids: 0.9% Saline 1L with 40 mmol KCl over 4-6 hours. Repeat twice (total 3L in 24h). Monitor fluid balance.
2. Thiamine FIRST: Pabrinex 1 pair ampoules IV over 30 minutes BEFORE any dextrose. Continue oral thiamine 50mg TDS.
3. Antiemetics: Cyclizine 50mg TDS IV initially, then switch to PO when tolerating. Add prochlorperazine 5mg TDS PO if inadequate response after 24h.
4. VTE Prophylaxis: TED stockings. Consider LMWH (enoxaparin 40mg SC OD) if admission > 3 days.
5. Monitoring: Daily weight, fluid balance chart, repeat U&Es daily, vital signs QDS.
6. Dietary: NBM initially, then clear fluids as tolerated, progress to small frequent meals.

Day 3-4 (Improvement):

• Vomiting reduced to 2-3 episodes/day
• Tolerating sips of water and dry toast
• Repeat bloods: K+ 3.6 mmol/L, Na+ 137 mmol/L, Urea 5.2 mmol/L, Creatinine 68 μmol/L
• Urine ketones: 1+
• PUQE score: 8 (moderate)
• Weight 62kg (stable)

Discharge (Day 4):

• Tolerating oral fluids > 24h
• Electrolytes normalized
• Discharge medications: Cyclizine 50mg TDS PO (2 weeks supply), prochlorperazine 5mg TDS PO PRN, thiamine 50mg TDS (2 weeks), folic acid 400mcg OD
• Safety netting: Return if unable to keep fluids down > 24h
• Follow-up: Community midwife review in 48h, antenatal clinic 2 weeks, day unit access for IV fluids if needed (avoid readmission)

Outcome: Symptoms gradually resolved by 16 weeks. No recurrence. Normal delivery at 39 weeks. Birth weight 3,250g (appropriate for gestational age).

Learning Points:

• Classic presentation: 9 weeks (peak hCG), weight loss > 5%, ketonuria, dehydration
• Transient thyrotoxicosis common (60-70% of HG) - suppressed TSH, elevated T4, self-limiting
• Thiamine BEFORE dextrose to prevent Wernicke
• Hypokalaemia requires IV replacement (oral poorly tolerated)
• Metabolic alkalosis (not acidosis) from vomiting gastric HCl

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Case 2: Refractory HG with Wernicke Encephalopathy Risk

Presentation: A 32-year-old woman (G2P1) at 11 weeks gestation with severe HG. Third admission this pregnancy. Previous admission at 7 weeks (3 days, responded to IV fluids and cyclizine) and 9 weeks (5 days, required ondansetron). Now re-presents with persistent vomiting despite oral cyclizine 50mg TDS, ondansetron 8mg BD, and day unit IV fluids twice weekly. Weight loss 8kg from pre-pregnancy (12% loss). Partner reports she is "increasingly confused" over past 2 days - difficulty concentrating, forgetting conversations.

Red Flags on Assessment:

• Confusion: Disoriented to time, slow to respond, difficulty following commands (GCS 14 - E4 V4 M6)
• Neurological exam: Horizontal nystagmus bilaterally, mild ataxia (cannot walk heel-to-toe)
• No ophthalmoplegia evident

Immediate Action:

• URGENT Wernicke Encephalopathy suspected (confusion + nystagmus + ataxia = classic triad)
• IMMEDIATE IV Thiamine: Pabrinex 1 pair ampoules IV over 30 minutes (BEFORE any investigation or glucose)
• Arrange urgent MRI brain (but DO NOT delay treatment for imaging)

Investigations:

• MRI Brain (Day 2): Bilateral symmetrical T2/FLAIR hyperintensities in mammillary bodies and medial thalamus. Consistent with Wernicke Encephalopathy.
• Bloods: Severe electrolyte derangement - K+ 2.2 mmol/L, Mg 0.5 mmol/L, Na+ 128 mmol/L, glucose 3.8 mmol/L
• PUQE Score: 15 (severe)

Management:

1. HDU Admission (severe hypokalaemia K+ less than 2.5 - arrhythmia risk, hyponatraemia, neurological compromise)
2. Wernicke Protocol: Pabrinex 1 pair IV TDS for 3 days, then 1 pair OD for 5 days, then oral thiamine 100mg TDS long-term
3. Electrolyte Replacement:
   • Magnesium first: 20 mmol Mg sulfate IV in 100ml 0.9% saline over 1h (hypomagnesaemia causes refractory hypokalaemia)
   • Then potassium: Central line for IV KCl infusion (40 mmol/L at 10 mmol/h with continuous ECG monitoring)
   • Sodium: Slow correction with 0.9% saline (max 8 mmol/L rise per 24h to avoid central pontine myelinolysis)
4. Antiemetic Escalation: Discuss corticosteroids with consultant (hydrocortisone 100mg BD IV for 48h, then prednisolone 40mg OD PO taper over 2 weeks)
5. Nutritional Assessment: Dietitian review. Consider nasojejunal tube feeding if persists despite corticosteroids.

Course:

• Day 3: Confusion improved, oriented. Nystagmus resolved. Able to walk without ataxia.
• Day 5: Vomiting reduced to 2-3/day. Tolerating small meals. K+ 3.4, Mg 0.8, Na+ 132.
• Day 7: Discharged home. Oral thiamine 100mg TDS, prednisolone taper (30mg OD week 2, 20mg week 3, 10mg week 4, stop).

Outcome: Symptoms gradually improved by 18 weeks. MRI brain at 6 months postpartum: Resolution of T2 hyperintensities. No residual neurological deficit. Delivered at term, healthy baby.

Learning Points:

• Classic triad only in 10% of Wernicke - high index of suspicion required
• Confusion alone in HG = Wernicke until proven otherwise
• Treat empirically - DO NOT wait for MRI confirmation
• Hypomagnesaemia causes refractory hypokalaemia - correct Mg first
• Slow Na+ correction crucial (max 10 mmol/L per 24h)
• Consider corticosteroids for refractory HG (after 10 weeks to avoid theoretical cleft risk)

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Case 3: Molar Pregnancy Masquerading as Early-Onset HG

Presentation: A 26-year-old woman at 6+5 weeks gestation (by LMP) presents with severe vomiting for 1 week. Vomiting 12-15 times daily. No vaginal bleeding. Positive home pregnancy test 2 weeks ago. No previous USS.

Red Flags:

• Very early onset (HG usually starts after 8 weeks)
• Very severe symptoms at early gestation
• Uterus feels large-for-dates on bimanual examination (14-week size at 7 weeks gestation)

Urgent Investigation:

• Serum hCG: 275,000 IU/L (Markedly elevated - normal at 7 weeks ~50,000-100,000)
• Urgent Pelvic USS: Echogenic "snowstorm" appearance filling uterine cavity. No fetal pole. No gestational sac. Bilateral theca lutein cysts (6cm and 5cm) on ovaries.

Diagnosis: Complete Hydatidiform Mole (Molar Pregnancy)

Management:

1. Urgent referral to Gestational Trophoblastic Disease Centre
2. Suction evacuation of mole under general anaesthetic (Day 2)
3. hCG Monitoring Protocol:
   • Weekly hCG until undetectable (less than 5 IU/L) for 3 consecutive weeks
   • Then monthly for 6 months
   • Risk of persistent gestational trophoblastic neoplasia (GTN) if hCG plateaus or rises (15-20% of complete moles)
4. Contraception: Avoid pregnancy until hCG normalizes (at least 6 months)

Post-Evacuation:

• Vomiting stopped within 48 hours (hCG rapidly declining)
• hCG: Day 7: 45,000 → Day 14: 8,500 → Day 21: 1,200 → Day 28: 180 → Day 35: less than 5
• Normal hCG for 3 consecutive weeks, then monthly monitoring
• No chemotherapy required

Outcome: hCG remained undetectable. Successful pregnancy 18 months later. No recurrence of molar pregnancy.

Learning Points:

• Early severe HG (less than 8 weeks) → Think molar pregnancy
• Very high hCG (> 100,000 IU/L) is a clue
• Large-for-dates uterus
• USS: "Snowstorm" pattern, no fetus, theca lutein cysts
• Treatment of HG symptoms = Evacuation of mole (hCG falls → symptoms resolve)
• Risk of GTN (15-20%) requires long-term hCG surveillance

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Case 4: HG Complicated by Acute Kidney Injury

Presentation: A 25-year-old woman (G1P0) at 10 weeks gestation presents with 3 weeks of worsening vomiting. Unable to attend previous day unit appointments due to feeling too unwell. No oral intake (food or fluids) for 4 days. Lying on floor at home unable to get up. Ambulance called by concerned partner.

Clinical Findings:

• Severely dehydrated: Dry mucous membranes, reduced skin turgor, cool peripheries
• BP lying 90/55 mmHg, standing: unable to stand (severe postural hypotension, syncope)
• Pulse 125 bpm
• Urine output: None passed for 24 hours (anuric)
• Weight loss 10kg (15% of pre-pregnancy weight)

Investigations:

• U&Es: Na+ 148 mmol/L, K+ 2.5 mmol/L, Urea 22 mmol/L, Creatinine 185 μmol/L (baseline 60 μmol/L in pregnancy)
• VBG: pH 7.50, HCO3- 35, lactate 2.8
• Urine: Ketones 4+, Specific gravity 1.035 (concentrated), Urinary sodium less than 10 mmol/L (prerenal)
• Diagnosis: Acute Kidney Injury (AKI Stage 2) secondary to severe volume depletion

Management:

1. HDU Admission (anuric AKI, severe dehydration)
2. Urinary catheter (strict fluid balance monitoring)
3. Aggressive IV Fluid Resuscitation:
   • 0.9% Saline 1L stat over 1 hour
   • Then 0.9% Saline 1L over 2h, repeat x3
   • Add KCl 20 mmol/L once urine output > 0.5 ml/kg/h
   • Target urine output > 0.5 ml/kg/h (> 35 ml/h for 70kg)
4. Thiamine: Pabrinex 1 pair IV TDS for 5 days (severe prolonged vomiting, high Wernicke risk)
5. Antiemetics: Ondansetron 8mg TDS IV, cyclizine 50mg TDS IV
6. Nephrology Referral: Daily review. Renal USS (exclude obstruction - unlikely but pregnancy can cause hydronephrosis)
7. Daily Bloods: U&Es, Creatinine

Course:

• Day 1: Urine output 10ml/h despite 4L IV fluids. Creatinine 195 μmol/L.
• Day 2: Urine output improving 40ml/h. Creatinine 165 μmol/L. Vomiting reduced (3 episodes).
• Day 3: Urine output 60ml/h. Creatinine 120 μmol/L. Tolerating sips.
• Day 5: Urine output normal. Creatinine 75 μmol/L (back to baseline). Tolerating oral diet.
• Day 7: Discharged. Normal renal function. Fetal USS: Viable pregnancy, appropriate growth.

Outcome: Complete recovery of renal function. No long-term sequelae. Delivered at 38 weeks. Birth weight 3,100g (appropriate for gestational age).

Learning Points:

• Severe dehydration → Prerenal AKI (raised urea disproportionate to creatinine, low urinary sodium less than 20 mmol/L)
• Anuric AKI requires HDU monitoring
• Aggressive fluid resuscitation (4-6L in first 24h)
• Usually reversible with rehydration
• Emphasizes importance of early intervention and day unit access (prevent severe dehydration)

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Case 5: HG with Persistent Symptoms and Need for TPN

Presentation: A 30-year-old woman (G2P0, previous miscarriage) at 14 weeks gestation with persistent severe HG since 6 weeks. Multiple admissions (5 to date). Maximal medical therapy trialled: cyclizine, prochlorperazine, ondansetron, metoclopramide, corticosteroids (prednisolone 40mg OD for 2 weeks - minimal benefit). Weight loss 12kg (18% of pre-pregnancy weight). BMI now 16 (was 22). Visible muscle wasting. Unable to work, bedbound.

Clinical Assessment:

• Severe malnutrition: Temporal wasting, loss of muscle bulk, ribs prominent
• Weight: 48kg (pre-pregnancy 60kg)
• PUQE score: 14 (severe despite maximal therapy)
• Albumin: 24 g/L (low), pre-albumin 12 mg/dL (low - marker of acute malnutrition)
• Fetal USS (14 weeks): Fetal growth appropriate for gestation, but maternal concern regarding nutrition

Nutritional Intervention:

1. Trial of Nasojejunal (NJ) Tube Feeding:

   • Endoscopic placement of NJ tube (bypasses stomach to reduce vomiting)
   • Continuous pump feeding: Peptamen 1.5 kcal/ml, 50ml/h (24h feeding = 1,800 kcal/day)
   • Result: Vomiting persists (8-10 episodes/day). Unable to tolerate NJ feeding. Tube removed Day 5.

2. Decision for Total Parenteral Nutrition (TPN):

   • MDT discussion (obstetrician, gastroenterologist, nutrition team, dietitian, patient)
   • Indications met: Weight loss > 15%, failed enteral feeding, refractory to maximal medical therapy, maternal malnutrition, risk to maternal health
   • PICC line insertion (Day 7)
   • TPN Regimen:
     • Total calories: 2,200 kcal/day (glucose 60%, lipids 30%, amino acids 10%)
     • Electrolytes: Na+ 100 mmol, K+ 80 mmol, Ca2+ 10 mmol, Mg2+ 10 mmol, PO4 30 mmol
     • Vitamins: Thiamine 100mg, B-complex, Vitamin K, Vitamin C, multivitamin
     • Trace elements: Zinc, copper, selenium, manganese
   • Start at 50% calories (Day 1-2) to prevent refeeding syndrome, increase to 100% Day 3-4

Monitoring Protocol:

• Baseline: FBC, U&Es, LFTs, glucose, lipids, albumin, pre-albumin, magnesium, phosphate, calcium, trace elements
• Daily (Week 1): Capillary glucose QDS, U&Es (watch for refeeding syndrome - hypophosphataemia, hypomagnesaemia, hypokalaemia)
• Weekly (Ongoing): FBC, U&Es, LFTs, lipids, trace elements
• PICC line care: Aseptic dressing changes twice weekly, monitor for infection (temperature, line site erythema)

Course:

• Week 1-2 (14-16 weeks): TPN established. Vomiting reduced to 4-5/day (but still unable to eat). Weight stable.
• Week 3-4 (17-18 weeks): Vomiting decreasing (2-3/day). Able to tolerate small sips of water and dry crackers. Weight starting to increase (50kg).
• Week 5-6 (19-20 weeks): Symptoms markedly improved (coinciding with expected HG resolution). Tolerating 50% oral intake. TPN weaned to nighttime only.
• Week 7 (21 weeks): Tolerating full oral diet. TPN discontinued. PICC line removed. Weight 53kg (regaining).

Complications:

• Week 4: Mild cholestasis (ALT 150, ALP 250, Bilirubin 25) - TPN-associated liver dysfunction. Managed with ursodeoxycholic acid 500mg BD. Resolved after TPN stopped.
• No line infections, no thrombosis

Outcome:

• Delivery at 37 weeks (spontaneous labour). Birth weight 2,650g (10th centile - small but not SGA). Apgar 9/10.
• Mother regained weight postpartum. No long-term sequelae.
• Baby: Normal development at 1-year follow-up.

Learning Points:

• TPN is last resort but life-saving in refractory HG
• Indications: Weight loss > 15%, failed enteral feeding, maternal malnutrition
• PICC line preferred over Hickman (lower infection risk)
• Start at 50% calories to prevent refeeding syndrome (hypophosphataemia, arrhythmias)
• Refeeding syndrome monitoring: Daily U&Es (especially phosphate, magnesium, potassium) in first week
• TPN-associated complications: Cholestasis (monitor LFTs), line sepsis, thrombosis
• Most women can wean off TPN by 16-20 weeks as HG improves
• MDT approach essential: Obstetrician, gastroenterology, nutrition, dietitian
• Psychological support critical: Severe HG with TPN associated with high rates of depression, PTSD

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15. Day Assessment Unit Protocols

Indications for Day Unit IV Therapy

Day unit ambulatory management reduces hospital admissions by 30-50% and improves patient quality of life. [14]

Day Unit Protocol (Typical 4-6 Hour Session)

Arrival Assessment:

• Weight, BP (lying and standing), pulse, temperature
• PUQE score
• Urine dipstick (ketones, exclude UTI)
• Capillary blood glucose

Intervention:

1. IV Fluids: 0.9% Saline 1L with 20 mmol KCl over 3-4 hours
2. Antiemetics: Cyclizine 50mg IV or ondansetron 8mg IV
3. Thiamine: If multiple attendances or prolonged vomiting - Pabrinex 1 pair IV
4. Light snack if tolerated (crackers, toast)

Discharge Criteria:

• Tolerating oral fluids
• Symptoms improved (PUQE reduced by ≥3 points)
• No postural hypotension
• No red flags (confusion, severe pain, fever)

Discharge Plan:

• Oral antiemetics (cyclizine/ondansetron) prescription
• Oral thiamine if indicated
• Return in 2-3 days if symptoms recur
• Safety netting: Return if unable to keep fluids down > 24h
• Access number for urgent re-booking

Frequency: Can attend 2-3 times weekly as needed. If attending > 3 times in one week with no improvement → Consider admission for inpatient management.

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.