Lecture nine
Neonatal seizures :Are not uncommon in the neonatal period subtle seizures which manifest as rhythmic eye deviation or blinking lip smacking tongue thrusting , fluctuation of vital signs or apnea are the most common form followed by generalized tonic , multifocal clonic , focal clonic and myoclonic seizures .
Seizures may be difficult to differentiate from benign jitteriness or from tremulousness in infants of diabetes mother , in infants with narcotic withdrawal .in contrast to seizures , jitteriness and tremors are sensory dependent elicited by stimuli and interrupted by holding the extremity . seizure activity becomes manifested as coarse , fast and slow clonic activity , whereas jitteriness is characterized by fine rapid movement . seizures may be associated with abnormal eye movement .
Etiology :
Asphyxia .
Brain anomalies .
Intracranial hemorrhage
Systemic metabolic disorders ( hypoglycemia , hyponatremia ,hypernatremia , hypocalcemia ,hyperammonemia ) and inborn error of amino acid and organic acid metabolism .
Meningitis and encephalitis .
Pyridoxine deficiency .
Diagnosis : the following evaluation should be made in effort to pin point the cause of the seizure activity :
Neurological examination .
EEG .
Ultrasound and CT scanning
Screening for metabolic disorders involving ( glucose , calcium , or sodium ) for inborn error of metabolism ( amino acid s or organic acid .
Lumbar puncture and evaluation of the SCF for sepsis .
Treatment :
The treatment of neonatal seizures may be specific such as treatment of meningitis or the correction of hypoglycemia , hypocalcemia , hypomagnesemia , hyponatremia or vitamin B6 deficiency or dependency . in the absence of identifiable cause , therapy shloud involve anticonvulsant agent such as ( 20-40 mg/kg of phenobarbital ) (10-20 mg/kg of phenytion ) or ( 0.1-0.3 mg/kg of diazepam ) followed by one of the two longer acting drugs . the long term outcome for neonatal seizure usually is related to the underlying cause and to the primary pathology such as hypoxic- ischemic encephalopathy , meningitis , drug withdrawal , stroke or hemorrhage .
Neonatal hypoglycemia :
Neonatal hypoglycemia is defined as a plasma glucose concentration less than 35 mg/dl during the first 24 hrs and lees than 45 mg/dl thereafter . hypoglycemia is very common in infants of diabetes mother as well as in infants who are born after various perinatal complication , including prematurity , IUGR , and asphyxia .
Pathogenesis . the pathogenesis varies depending on the clinical setting and the associated conditions affecting the infants .
Maternal diabetes , the hypoglycemia in infants of diabetes is the result of a hyperinsulinemia state that persist after the umbilical cord is cut and the maternal supply of glucose is interrupted .
Prematurity . preterm infants become hypoglycemia owing to diminished glycogen store and to immaturity of gluconeogenic enzymes .
Growth retardation . growth retarded infants frequently are depleted of hepatic glycogen and quickly become hypoglycemic .
Perinatal asphyxia . forces the fetus to use anaerobic metabolism , which quickly depletes stored glycogen and result in hypoglycemia.
Cold stress . increased oxygen consumption as well as glucose consumption . it also may increase free acids and result in hypoglycemia .
Sepsis. May cause hypoglycemia , although hyperglycemia also is observed which presumably is caused by insulin insensitivity .
Beckwith-Wiedmann syndrome . is characterized by hypoglycemia , visceromegaly , macroglossia and omphalocele . hyperinsulinemia secondary to pancreatic islet cell hyperplasia is responsible for hypoglycemia .
Nesidioblastosis and pancreatic islet cell adenoma are associated with hyperinsulinemia and hypoglycemia .
Metabolic disorder such as galactosemia and panhypopituitarism .
Clinical features :
Infants with hypoglycemia are not always symptomatic . however the following symptoms may occur ( hypotonia or jitteriness , apnea or tachypnea, cyanosis ,hypothermia , poor feeding and seizures .Therapy :
Primary therapy is intravenous glucose . the glucose infusion may be required for several days until the basal insulin secretion rate decreases , glycogen stores are replenished or gluconeogenesis improves . bolus infusion of hypertonic glucose should be avoided because they may result in a rebound hypoglycemia .intravenous glucose should be administered as a constant infusion begun at a rate of 6-8mg/kg/min .this may be increased to a rate of up to 20mg/kg/min ( a central venous access should be used for infusion given at a rate above 15 mg/kg/min .A small ( 0.5-1.0 g/kg ) bolus may be used for extreme hypoglycemia or if severe symptoms related to hypoglycemia . this shloud always be followed by a constant infusion .
Hypoglycemia that is secondary to hyperinsulinemia and resistant to intravenous glucose should be treated with corticosteroid or diazoxide . if drug treatment fails partial pancreatectomy should be performed . these more aggressive forms of therapy rarely are necessary except for hypoglycemia that associated with Beckwith-Wiedmann syndrome , nesidioblastosis , or islet cell adenoma .
Infant of diabetic mother
Women with diabetes in pregnancy are at increased risk for adverse pregnancy outcome . adequate glycemic control before and during pregnancy is crucial to improving outcome .The effect of diabetes on the fetus depend in part on severity of the diabetes state , age of onset of diabetes , duration of treatment with insulin and presence of vascular disease .poorly control maternal diabetes leads to maternal and fetal hyperglycemia that stimulates the fetal pancreas , resulting in hyperplasia of the islets of Langehans .fetal hyperinsulinemia results in increased fat and protein synthesis and fetal macrosomia except brain and ossification centers .
Hypoglycemia develops in about 25-50% of of infants of diabetic mother and 15-25% of infants of mothers with gestational diabetes . infants should initiate feeding within 1 hour after birth and a screen glucose test should be performed within 30 mint. Of the first fed. In asymptomatic infants treatment indicated if plasma glucose less than 30mg/dl . in symptomatic infants the treatment indicated if plasma glucose less than 40% . treatment of hypoglycemia as mention above .
Neonatal problems of diabetic mother :
Birth asphyxia and birth trauma due to macrosomia .
Hypoglycemia , hypocalcemia , hypomagnecia .
Polycythemia and indirect jaundice .
Congenital anomalies is increased 3-folds like congenital heart disease .
Neurological disorders like neural tube defect and holoprosencephaly .
Renal disorders likes renal agenesis ,double ureter , renal vein thrombosis .
Respiratory likes RDS due low surfactant synthesis and TTN .
Preterm labor is common and the result of fetal distress or a planed early delivery .
Prognosis :
The neonatal mortality rate is > 5 times that of infants of non diabetic mother .the subsequent incidence of diabetes mellitus in infants of diabetic mother is a higher than that in general population .The key to optimal outcome is consistent euglycemia in the mother .
Neonatal hypocalcemia :
Hypocalcemia is a common in sick and premature newborn . total serum calcium levels less than 6 mg/dl and ionized calcium levels of lees than 3 to 3.5 mg/dl are considered hypocalcemia .Early onset neonatal hypocalcemia occurs in the first 3 days of life and is often asymptomatic and can result from transient hypoparathyroidism or congenital absence of the parathyroid gland and DiGeorge syndrome .
Hypomagnesemia ( < 1.5 mg/dl ) may be seen with hypocacemia that may need to treat both conditions .
Late onset neonatal hypocalcemia or neonatal tetany often is the result of high phosphate containing milk or the inability to excrete the usual phosphorus in commercial infant formula . vitamin D deficiency and malabsorption also can be associated with late onset hypocalcemia .
The clinical manifestations of hypocalcemia include ( apnea , muscle twitching seizures , laryngospasm .
Chevostek sign and Trousseau sign can be see more with late onset hypocalcemia .
Neonatal hypocalcemia may be prevented by administration of IV or oral supplement at a rate of 25 to 75 mg /kg /day .
Early asymptomatic hypocalcemai of preterm infants and infants of diabetic mother often resolved spontaneously .
Symptomatic hypocalcemia should be treated with 2- 4 ml /kg of 10% calcium gluconate given intravenously and slowely over 10 to 15 minutes followed by a continous infusion of 75 mg/kg/day of elemental calcium .
If hypomagnesemia is associated with hypocalcemia , 50% magnesium sulfate 0.1 ml/kg should be given by IM and repeated every 8 to 12 hrs .
The treatment of late hypocalcemia include immediate management as in early hypocalcemia plus the initiation of feeding with low phosphate formula .
Infection
Infection continues to be a major cause of neonatal mortality and morbidity despite advance in therapy . although perinatally acquired bacterial infections are the most common infections that are acquired in utero remain important source of long term disability .General consideration :
Predisposing factors . the newborn is particularly susceptible to infection owing to immaturity of immune system mechanism including
Neutrophil chemotaxis .
Neurtophil phagocytosis .
Bacterial activity .
Humeral components.
Timing and route of infection . the causative organism and abnormalities associated with neonatal infection vary with time and route of infection .
Organisim responsible for transplacental infections before birth are ( CMV , HIV , Rubella virus , toxoplasma gondi , echovirus and listeria monocytogenes ) .and can cause abnormalities associated with infection acquired in the first trimester ( congenital malformation , IUGR , microcephaly , hydrocephalus and still birth ) and also can cause abnormalities with infection acquired later in pregnancy ( microcephaly , hydropes fetalis , DIC , anemia , IVH , hepatosplenomegaly , jaundice , skin and eye lesions beside still birth ) .
Perinatal infection include infections acquired through the fetal membrane ascending infections acquired after rupture of membrane and infection acquired via the birth canal . common causative organisims are ( Group B Beta-hemolytic streptococcus , E-coli . Klebsiella species , streptococcus pneumoniae Herpes simplex virus, Chlamydia trochomatis , neisseria gonorrhoeae , neisseria meningitidis ) .and can cause the following abnormalities ( respiratory distress , temperature instability , septic shock , neuropenia , thrombocytopenia , meningitis ) .
Postnatal infections most often are required as a result of nosocomial or community exposure . hospitalized newborns who are premature or require instrumentation are particularly susceptible . common causative organisms are ( staphylococcus aureus , staphylococcus epidermidis , pseudomonas aeruginosa , candida albicans , E –coli , klebsiella,clostridia, enterococcus)and associated abnormalities are ( respiratory distress , feeding intolerance , apnea, anemia shock , DIC , hypoglycemia and temperature instability )
Bacterial infection and neonatal sepsis . bacterial infection most frequently are acquired via the birth canal or nosocomialy . the infection almost always is bacteremic and associated with systemic symptoms – a condition referred to as neonatal infection .
Incidence . neonatal sepsis is common in premature infants . about 1-4% of these infants have at least one episode of sepsis during their hospitalization . sepsis in term infants are rare , occurring in less than 1% .
Risk factors for early neonatal sepsis include :
Premature labor .
Low birth weight .
Prolonged rupture of the fetal membrane .
Chorioamnionitis .
Maternal fever .
Etiology . . the most common causative organisims include :
Gram-positive cocci especially group B Beta –hemolytic streptococci , but also staphylococcus aureus and staphylococcus epidermidis .
Gram- negative rods especially E-coli and klebsiella pneumoniae .
Gram-positive rods like listeria monocytogenes .
features :
Signs and symptoms of bacterial infections include :
Unexplained respiratory distress .
Unexplained feeding intolerance .
Temperature instability .
Hypoglycemia and hyperglycemia .
Apnea , lethargy or irritability .
Laboratory findings include :
Abnormal white blood cell count ,including neutropenia or un elevated ratio of immature to total neutrophil suggest sepsis .
Prolonged of PT and PTT .
Tracheal aspirate , gastric aspirate for neutrophil count , gram stain and culture .
Blood culture .
A lumber puncture .
Urine for general exam and culture .
Chest radiograph ,
Arterial blood gas analysis .
Therapy :
1-Empiric antibiotics therapy should begin after the diagnostic work up and consist of a broad –spectrum penicillin ( usually ampicillin ) and un aminoglycoside ( usually gentamicin ) . once culture data available . therapy should be tailored to the specific organism .2-The initial choice of antibiotics for nosocomial infection depend on nursery . community and individual patient exposure information.
3-The duration of therapy usually is 7-10 days except for invasive infections ( e.g. meningitis , osteomyelitis ) which require longer course of antibiotics therapy
4-Other complication can be treated accordingly for example treatment of shock with fluid and vasopressor .
Monitoring serum drug level .
Persistent signs of infections despite antibacterial treatment suggest candidal or viral sepsis .