Neonatal Seizure: Sepsis or Toxic Syndrome?

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

EM_1113_p40a.jpg

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

EM_1113_p40a.jpg

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

EM_1113_p40a.jpg

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.