Purpose and Goal: CNEP #2006

  • Learn about the symptoms of maternal HELLP syndrome.
  • Understand the effects of HELLP syndrome on the neonate.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for successful completion:

  • Successfully complete the post-test
  • Complete the evaluation form

Date

  • May 2015 – May 2017

Learning Objectives

  • Describe the characteristics of maternal HELLP syndrome.
  • Describe the clinical manifestations of infants exposed to HELLP syndrome.
  • Identify at least two approaches for the treatment of HELLP syndrome.

Introduction

  • HELLP syndrome is a complicated maternal condition
  • Approximately 48,000 women develop HELLP syndrome each year
  • It is the second leading cause of maternal death after embolism
  • The effects of HELLP syndrome on the fetus and neonate can be significant
  • Recognizing the risks for the fetus and neonate can improve neonatal outcomes

HELLP Syndrome

  • The onset and severity of HELLP syndrome varies
  • Most often diagnosed between 27 - 37 weeks gestation
  • Can develop within the first 48 hours post-partum
    • 70% occurs prior to delivery
    • 30% occurs after delivery
  • HELLP syndrome was first recognized in 1982
  • It is thought to be a severe form of preeclampsia
  • HELLP syndrome is characterized by 3 main factors
    • Hemolysis with an abnormal peripheral smear
    • Elevated liver enzymes with an AST > 70 units/L
    • Thrombocytopenia with platelet count < 100K
  • It occurs in 0.1 – 0.8% of all pregnancies
  • It occurs in 10 - 20% of women with:
    • Pregnancy induced hypertension (PIH)
    • Preeclampsia
  • It can also occur in women without hypertension
  • HELLP syndrome can be classified into 3 categories:
    • Class 1 – severe – platelet count < 50K
    • Class 2 – moderate – platelet count 50-100K
    • Class 3 – mild – platelet count 100-150K
  • If left untreated, HELLP syndrome can lead to:
    • Liver rupture
    • Cerebral hemorrhage
    • Death

Risk Factors for HELLP Syndrome

  • The cause of HELLP syndrome is unknown
  • Risk factors include:
    • Type I diabetes
    • Chronic hypertension
    • Multiple gestation
    • Prior preeclampsia
    • Prior eclampsia
    • Prior HELLP syndrome
    • Prior poor pregnancy outcome
    • Pre-pregnancy obesity
    • Extremes of age
    • Assisted reproduction

Clinical Signs of HELLP Syndrome

  • HELLP syndrome has a variable presentation
  • Clinical signs may include:
    • Headache
    • Nausea
    • Vomiting
    • Indigestion
    • Malaise
    • Epigastric tenderness
    • Substernal tenderness
    • Right upper quadrant pain
    • Shoulder pain
    • Bleeding
    • Swelling
    • Visual disturbances
    • Elevated blood pressure
    • Proteinuria
  • These clinical signs are often associated with PIH
    • They may also be signs of preeclampsia
    • They may also be signs of HELLP syndrome

Pathophysiology of HELLP Syndrome

  • The pathophysiology of HELLP syndrome is unclear
  • The main cause is thought to be:
    • Aberrant placental development
    • Aberrant placental function
  • During the 16th-22nd weeks of pregnancy:
    • Defective remodeling of placental circulation → inadequate placental perfusion
  • Inadequate placental perfusion → placental hypoxia
    • Placental hypoxia → cell injury
    • The degree of cell injury may → severity of HELLP syndrome
  • Placental hypoxia and cell injury cause systemic inflammation
  • Systemic inflammation can lead to:
    • Hypertension
    • Proteinuria
    • Platelet activation
    • Platelet aggregation
  • Once inflammation occurs → the clotting cascade is activated
    • Hemolysis occurs
    • Platelets are rapidly consumed

Additional Theories of Pathophysiology

  • Multiple additional theories exist:
    • Preeclampsia precedes HELLP syndrome
    • HELLP syndrome is a variant of preeclampsia
    • Maternal immune rejection of fetal cells
    • Fetal inborn errors of metabolism
    • Fetal long chain fatty acid enzyme deficiency
  • The true pathophysiology of HELLP syndrome is unknown
  • As a result, HELLP syndrome is considered a complex disorder

Fetal Long Chain Enzyme Deficiency

  • Fetal long-chain 3-hydroxyacl CoA dehydrogenase deficiency
    • It is also known as LCHAD
    • It is an inborn error of metabolism
    • It is an abnormality in fatty acid metabolism
  • This fetal metabolic abnormality can cause:
    • Acute Fatty Liver of pregnancy
    • Maternal HELLP syndrome
  • LCHAD occurs in < 2% of infants
  • Infants with LCHAD present with:
    • Hypotonia
    • Persistent hypoglycemia
    • Hypoketotic encephalopathy
    • Hepatosplenomegaly
    • Elevated liver enzymes
    • Signs of liver failure
    • Severe cardiomyopathy
  • Infants diagnosed with LCHAD require special formula
    • They require a diet low in long-chain fatty acids
    • They require medium chain triglyceride (MCT) supplements
  • The prognosis for infants with LCHAD is guarded

Impact on the Fetus and Neonate

  • Perinatal complications are higher in the fetus than the mother
  • Perinatal survival rates:
    • < 23 0/7 weeks - 0%
    • 23 0/7 - 23 6/7 weeks - 18%
    • 24 0/7 - 24 6/7 weeks - 58%
    • 25 0/7 - 25 6/7 weeks - 70%
    • 26 0/7 - 26 6/7 weeks - 90%
  • The effect on the infant is directly related to gestational age
  • Infants delivered < 32 weeks are at highest risk
    • Mortality rate is 32%
  • Infants delivered > 32 weeks have less risk
    • Mortality rate is 8%
  • The leading causes of mortality are:
    • Prematurity
    • Intrauterine growth restriction (IUGR)
    • Asphyxia
    • Placental insufficiency
    • Abruption
  • The overall rate of fetal mortality is 5.1%
  • The overall rate of fetal and neonatal mortality is 7.7 - 60%

Neonatal Clinical Manifestations

  • Infants exposed to HELLP syndrome are at risk for:
    • Prematurity
    • Placental insufficiency → IUGR
    • Asphyxia
    • Abruption
    • Thrombocytopenia
    • Intraventricular hemorrhage
  • Prematurity
    • Premature infants are at risk for:
      • Respiratory distress syndrome
      • Electrolyte imbalances
      • Metabolic complications
      • Sepsis
      • Necrotizing enterocolitis
      • Patent ductus arteriosus
      • Apnea and bradycardia
      • Anemia
      • Intraventricular hemorrhage
  • Placental insufficiency → IUGR
    • IUGR infants are at risk for:
      • Perinatal asphyxia
      • Cold stress
      • Hypoglycemia
      • Polycythemia
      • Cholestasis from TPN support
  • Asphyxia
    • Asphyxiated infants are at risk for:
      • Hypoxic-ischemic encephalopathy
      • Respiratory failure
      • Metabolic acidosis
      • Hypoglycemia
      • Seizure activity
  • Abruption
    • Abruption places infants at risk for:
      • Anemia
      • Hypovolemia
      • Thrombocytopenia
      • Platelet dysfunction
  • Thrombocytopenia
    • Neonatal thrombocytopenia occurs in 15 - 38% of infants
    • Infants with platelet counts < 150K are at risk for:
      • Hemorrhage
      • Intraventricular hemorrhage
  • Intraventricular hemorrhage (IVH)
    • IVH places infants at risk for:
      • Cerebral palsy
      • Poor neurodevelopmental outcomes

Treatment Approaches for HELLP Syndrome

  • The only known cure is prompt delivery of the fetus
  • The goals of treatment are:
    • Close observation or delivery
    • Control of hypertension
    • Prevention of seizures
  • The most common treatment strategies include:
    • Antenatal steroids
    • Magnesium sulfate
    • Blood pressure control
    • Delivery within 72 hours of diagnosis
  • The American College of Obstetricians and Gynecologists (ACOG) recommends:
    • Referral to a facility with advanced NICU care
    • Continuous maternal and fetal monitoring
    • Antihypertensive medications for:
      • Systolic blood pressure > 160
      • Diastolic blood pressure >105
    • Early delivery for:
      • Infants < 23 or > 34 weeks
      • Infants in fetal distress
    • Signs of maternal distress:
      • Eclampsia
      • Abruption
      • Disseminated intravascular coagulation
      • Renal failure
      • Respiratory distress
      • Suspected liver hematoma
    • If no signs of maternal distress are present:
      • For infants 23 - 34 weeks
        • Steroids should be given to the mother
        • Delivery should occur 24 - 48 hours later

Evidence Based Practice

  • Glucocorticoid steroid therapy
    • Initially thought to benefit the fetus
      • Promotes lung maturity
      • Decreases respiratory distress syndrome
    • Current evidence shows possible benefits for the mother
      • Stabilizes the disease process
      • Effective in prenatal and post-partum periods
  • Magnesium sulfate therapy
    • Magnesium has multiple benefits
      • Causes central/peripheral microvascular dilation
      • Reduces systemic vascular resistance
      • Protects blood-brain barrier by reducing edema
      • Provides neuroprotective/anti-seizure action
  • Blood pressure control
    • Blood pressure (BP) control is critical for improving outcomes
      • The risk for stroke is directly related to systolic BP
      • BP control may have side effects for the fetus
        • Lowering BP may decrease placental perfusion

Neuroprotective Effects of Magnesium

  • Cerebral palsy (CP) is a common cause of severe motor disability
  • In utero exposure to magnesium → decreased incidence of CP
  • The mechanism of action is not fully understood
    • Possible neuroprotective actions include:
      • Antioxidant effects
      • Reduction of pro-inflammatory cytokines
      • Increased cerebral blood flow
      • Prevention of labile blood pressure
  • ACOG supports the use of short term magnesium
    • The recommended time frame is 24 hours
    • The recommended dosing:
      • 4 gram bolus loading dose
      • 1 gram/hour continuous drip
    • Retreatment is not generally recommended

Maternal Outcomes

  • The outcome for mothers with HELLP syndrome is good
  • Symptoms generally improve within 48 hours of delivery
  • The most common side effects are:
    • Blood or platelet transfusions 55%
    • Disseminated Intravascular Coagulation 21%
    • Abruption 16%
    • Acute renal failure 8%
    • Pulmonary edema 6%
    • Liver hematoma 1%
    • Retinal detachment 1%
    • Death 1%

Neonatal Outcomes

  • The outcome for infants is associated with gestational age
  • The most common issues are:
    • Prematurity associated morbidities
    • IUGR associated morbidities
  • IUGR is the primary concern
    • Occurs in 15 – 50% of infants
    • Places infants at risk for:
      • Hypothermia
      • Hypoglycemia
      • Sepsis
      • Necrotizing enterocolitis
      • Intraventricular hemorrhage
      • Hypothyroxemia
    • Places children at risk for:
      • Poor growth
      • Poor neurodevelopmental outcomes
      • SIDS (slight increased risk)
    • Places adults at risk for:
      • Hypertension
      • Type II Diabetes
      • Coronary Artery Disease
  • Thrombocytopenia is common
    • Low platelet counts are transient
    • Places infants at risk of hemorrhage
    • Commonly found at 72 hours
    • Usually resolves within 10 days
  • Neutropenia can occur in 50% of infants
    • Low WBC counts are transient
    • Places infants at risk of sepsis
    • Resolves within days to weeks

Summary

  • HELLP syndrome develops in < 1% of all pregnancies
  • It develops in 10 – 20% of mothers with preeclampsia
  • The cause of maternal HELLP syndrome is unknown
  • Early recognition and treatment improves neonatal outcomes

References

  1. Barnhart, L. 2015. HELLP Syndrome and the Effects on the Neonate. Neonatal Network, 34 (5), p. 269-273.
  2. Sibai, B.M. 2015. HELLP Syndrome. Up-To-Date.
  3. Lyell, D.J. 2004. Hypertensive Disorders of Pregnancy: Relevance for the Neonatologist. NeoReviews, 5 (6), p. e240-e246.
  4. Moallem, M. & Koenig, J.M. 2009. Preeclampsia and Neonatal Neutropenia. NeoReviews, 10 (9), p. e454-e459.
  5. Norwitz, E.R. & Funai, E.F. 2015. Expectant Management of Preeclampsia with Severe Features. Up-To-Date.
  6. Simhan, H.N. & Himes, K.P. 2015. Neuroprotective Effects of in utero Exposure to Magnesium Sulfate. Up-To-Date.
  7. Bellig, L.L. 2004. Maternal Acute Fatty Liver of Pregnancy and the Associated Risk for LCHAD Deficiency in Infants. Neonatal Network, 4 (1), p. 26-32.

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