Neonatal Hypoglycemia (and all of the other neonatal emergencies that Ethan is making me cover to fulfill the ACGME requirement) Philippa Augustin, MD Objective  Review definition, pathophysiology, risk factors, evaluation and treatment of neonatal hypoglycemia  Attempt to cover maybe 1 or 2 others… Neonatal Emergencies  Neonatal hypoglycemia  RDS  Neonatal seizures  Apparent Life Threatening Events  Neonatal sepsis  Surgical Emergencies  NEC  Congenital Heart Disease Neonatal Hypoglycemia  Common problem, with 10% of neonates being unable to maintain glucose >30 if feeding is delayed for 3-6hrs after birth  Greater risk if SGA or LGA Definition  No clear consensus about what levels are dangerous • Current definition is <40 for 1st 24hrs, then <50 after that • Severe is <25 • Neonates are able to tolerate much lower plasma glucose levels than adults Gluconeogenesis  Glutamate, aspartate and alanine • Neonatal brain is also able to use lactate and ketone bodies Pathogenesis    Umbilical venous glucose concentration is 60-80% of maternal levels During 1st 2hrs after birth, falls to nadir of 40, then stabilizes at 4-6hrs to 45-80 • Stabilized by glycogenolysis, stimulated by epinephrine and glucagon – Hepatic glycogen depleted after 8-12hrs • Also supported by gluconeogenesis – Requires substrate (lactate, amino acids, glycerol) If either is inadequate, hypoglycemia results Decreased glucose production   Inadequate stores • Glycogen stored in liver mostly during the 3rd trimester – Which infants will be at risk because of this? • IUGR also have reduced stores – Chronic intrauterine hypoxia leads to inefficient glucose metabolism Metabolic disorders • Glycogen storage diseases, galactosemia, fructose intolerance, maple syrup urine disease, propionic acidemia, methylmalonic acidemia)  Endocrine disorders • Deficiency of any of the hormones that regulate glucose homeostasis (cortisol, GH, epi, glucagon)  Other • Maternal beta blockers – Interrupts epinephrine stimulating glycogenolysis • Hypothermia • Liver failure Increased Utilization  Hyperinsulinemia • Infants of diabetic mothers – Usually transient, neonate has increased production of insulin secondary to chronic intrauterine hyperglycemia (premature maturation of pancreatic islet cells) – IDMs also have depressed counterregulatory response (glucagon and catecholamines) – Suspect in LGA/macrosomia • Beckwith-Wiedemann syndrome – hyperinsulinism • • • • Erythroblastosis Perinatal asphyxia Intrapartum glucose infusion Exogenous insulin – Given for hyperglycemia, infants must be carefully monitored after administration Increased utilization without hyperinsulinism  Utilization may increase with poor perfusion and poor oxygenation • Lower energy produced with anaerobic glycolysis (5%)  Sepsis  Polycythemia  Neurohypoglycemia • Mechanism unknown • Increased RBC mass  increased glucose metabolism • Nml plasma glucose, but def of GLUT1 results in lack of transport across BBB – Seizures at 2-3 mos, developmental delay, acquired microcephaly Manifestations  Jitteriness, tremors  Hypotonia  Altered LOC (irritable, lethargic, stupor)  Apnea, bradycardia, cyanosis  Tachypnea  Poor feeding/sucking  Hypothermia  Seizures Infants at higher risk  Preterm  LGA/SGA  IDM  NICU (sepsis, asphyxia)  Mother tx’d with Bblockers or oral hypoglycemic agents Monitoring  Start within 1-2 hrs after birth (sooner for any symptoms) • Preprandial glucose levels • Maintain above 50 (40 may be adequate, but BAEPs are abnormal <45, although this abnormality reverses with euglycemia) Treatment  Oral breast milk or formula if asymptomatic and not severe hypoglycemia (<25, which will result in permanent neuron death)  IV glucose of 6mg/kg/min if symptomatic, unable to be fed, or persistently hypoglycemic  Glucocorticoid if persistent hypoglycemia after 2-3 days of glucose at >12 mg/kg (and consult pedi endo) Oral feeds  ASAP after birth • Negligible benefit on early hypoglycemia, may prevent subsequent hypoglycemia • If screening is <40 in asx term infant, repeat with blood sample for lab • Repeat 20-30 min after feeding, feed q2-3hrs • If preterm with glucose <40, most likely will need parenteral supplementation Parenteral Glucose Indications  Neonate with severe hypoglycemia (20-25)  Persistent hypoglycemia after feeding (<40)  Neonataes unable to tolerate po  Unclear if asymptomatic hypoglycemia in premature infants leads to neurologic damage Prognosis  Symptomatic hypoglycemia leads to changes in brain MRI • 33 of 35 neonates had detectable white matter changes – 15 mild, 8 mod, 3 with severe impairment – earlier onset of MRI findings means worse outcome • transient MRI changes with glucose <46 • injuries usually result in neuro developmental delay an decreased intellectual fxn RDS (aka hyaline membrane disease)  Common cause of respiratory distress, especially in premature infants  caused by surfactant deficiency • surfactant expressed by lung tissue during 3rd trimester • lipid/protein complex that lowers lung surface tension preventing alveolar collapse RDS  Without surfactant, alveoli collapse, causing decreased lung volum and decreased lung compliance • collapsed alveoli lead to V/Q mismatch that leads to hypoxemia  low surfactant levels also lead to resp epithelial injury that causes inflammation and pulmonary edema Inflammation  In animal studies, depletion of neutrophils prevents pulmonary edema in absence of surfactant  atelectasis --> inflammatory cascade --> increased cytokine expression --> increased neutrophil accumulation • increased protein rich fluid causes inactivation of any remaining surfactant Pulmonary edema  Caused by inflammation, but also caused by decreased fluid absorption • epithelial sodium channel (ENaC) expression occurs during 3rd trimester Presentation  Presents at birth, and if untreated, worsens over next 48hrs  nearly always premies  Symptoms • • • • • tachypnea, nasal flaring, grunting, retractions, cyanosis decreased breath sounds decreased peripheral pulses increased peripheral edema decreased UOP in first 24-48hrs Disease progression  If surfactant is not administered, dz will progress over 24-72 hrs and then improve neonate produces surfactant  Diagnosis: neonate with increased WOB, increased O2 need, and typical x-ray (ground glass)  DDx: TTN, penumonia, congenital heart disease Neonatal seizures  Symptomatic vs. neonatal epileptic syndrome • majority are symptomatic seizures (acute reactive neonatal seizures) Neonatal epileptic syndromes  Benign neonatal convulsions  benign neonatal familial convulsions  early myoclonic encephalopathy  early infantile epileptic encephalopathy Acute reactive neonatal seizures  Many causes • • • • • • • neonatal hypoxic-ischemia encephalopathy ICH CNS infection cerebral infarct metabolic chromosomal “cryptogenic” Acute reactive neonatal seizures  Many causes • • • • • • • neonatal hypoxic-ischemia encephalopathy ICH CNS infection cerebral infarct metabolic chromosomal “cryptogenic” Acute reactive neonatal seizures  Many causes • • • • • • • neonatal hypoxic-ischemia encephalopathy ICH CNS infection cerebral infarct metabolic chromosomal “cryptogenic” Acute reactive neonatal seizures  Many causes • • • • • • • neonatal hypoxic-ischemia encephalopathy ICH CNS infection cerebral infarct metabolic chromosomal “cryptogenic” Benign neonatal convulsions  Idiopathic  2-7% neonatal seizures  90% in DOL 4-6  term/late preterm, no FHx, nml pregnancy and delivery, nml neuro exam between seizures  unifocal clonic, occ cuase apnea, lasts 1-3 min and recur for 24-48hrs  Diagnosis of exclusion • • • • • Apgar >7 at 1 min typical age (4-6 days) nml neuro exam before and interictally nml labs/imaging no FHx  AEDs, may stop 24-48hrs after Benign neonatal familial convulsions  14.4/100K live births  autosomal dominant with 85% penetration • “channelopathy” of voltage gated K+ channel  focal or multifocal clonic/tonic seizures  FHx neonatal seizures  nml neuro exam  Onset - days-1wk of life  Seizures are usually brief and resolve in 2- 3 monts  Tx: AEDs • good prognosis, but do have slight increase in risk of future epilepsy Early myoclonic encephalopathy  EME • onset - early neonatal • occ familial • usually have inborn errors of metabolism  Clinical features • abnml neuro exam - altered LOC at time of onset • initially with segmental erratic myoclonic seizures in 1st few hrs • partial motor or focal clonic seizures develop after that • repetitive tonic spasms at 3-4 months  Tx: AEDs, but seizures refractory to meds  Prognosis: poor • do not develop neurologically • 50% die in 1st yr • survivors - persistent vegetative state EIEE  AKA Ohtara’s syndrome  Onset - infancy (within 1st 3 months)  frequent tonic spasms and suppression- burst pattern on EEG  secondary to structural anomalies  tonic spasm seizures  neuro exam abnml even before onset of seizures  Tx: AEDs  prognosis: poor; 50% die in infancy, survivors have severe MR, quadriplegia ALTE  Apparent Life Threatening Events • some combo of apnea, color change, change in muscle tone, choking/gagging • Recovery occurs after stimulation/rescusitation (being patted or picked up doesn’t count) ALTE  Unclear if connected to SIDS • • • • • • 5% of SIDS had prior ATLE ALTE not always fatal ALTE dx depends on parental observation 80% SIDS 12am-6am, 80% ALTE 8am-8pm SIDS interventions have not decreased ATLE different risk factors  Cause identified in >50% • 30% GERD • 15-20% neurologic – seizures, ventricular hemorrhage, hydrocephalus • Accidental/intentional poisoning  GERD • no direct association to ATLE • more likely if gross emesis at time of ALTE, occur when infant awake and supine, infant had obstructive apnea • may use low risk interventions, but also r/o other causes  Abuse • Munchausen’s by proxy vs abusive head injuries Initial eval  History and PE (eval for respiratory obstruction)  Lbs, CXR, brain imaging, EEG, echo, PSG, CXR  Consider consulting infant apnea specialist  Admit for inpt obs if hx suggests physiologic compromise Recurrence risk factors  Idiopathic ALTE • high incidence of false apnea alarms on home monitors  immaturity, hx of multiple ALTE prior to admit, viral URI, Recs  Caregivers should be given CPR training  train caregivers in creating safe sleeping environment  home monitoring (case by case) Prognosis  In premies - good, as lungs mature  death occurs in <1% • if have recurrent ATLE requiring CPR, risk of SIDS is 10-30% Neonatal Sepsis  Objectives • • • • Review terminology Risk factors Presentations of neonatal sepsis Most common organisms and treatments Terminology  Rule out sepsis  Neonate with fever (neonate is 0-28 days)  Neonatal fever  Neonatal sepsis  Serious bacterial infection  Occult bacteremia Neonate with fever  Infant of 0-28 days with rectal temp of 100.4F or higher should automatically be admitted • Immature immune system – Cellular immunity – neonatal PMN deficient in chemotaxis and killing capacity – Impaired macrophage chemotaxis, with lower absolute numbers in lung, liver and spleen – Immature T-cells – Low numbers of natural killer cells in peripheral blood – Humoral immunity – Immunoglobulin transfer from mother occurs in late gestation, putting premies at risk – Low IgM levels at birth – Deficiency of terminal complement cascade necessary for G- pathogens • Perinatal pathogen exposure (low barrier function) • High rate if infections in infants <3 months – >4% 0-28 days with bacteremia or meningitis – 10% with UTI – Higher risk of bacteremia with higher fever • May appear well and have infxn Frequency  2/1000 live births in US • 7-13% neonates are evaluated, only 3-8% have cx proven sepsis • Aggressive evaluation is indicated as mortality for untreated sepsis is 50%  Neonatal meningitis 2-4/1000 live births How to judge if admission is needed…  Rochester criteria  Philadelphia criteria  Boston criteria Risk factors  Prematurity or low birth weight  Maternal GBS  Sepsis in previous sibling  PROM  Maternal chorio  Need for resuscitation  Male  Multiple gestation Signs/Sx  Fever/hypothermia  Poor tone  Irritability  Shrill/weak cry  Skin - pallor, poor perfusion, mottling, petechiae, jaundice, cyanosis Signs/Sx  Nonspecific, and are associated with many other disorders • • • • • • Poor feeding Vomiting/diarrhea Hypo or hyperglycemia tachypnea and/or retractions Tachy/bradycardia Hypotension Signs/Sx (cont)  Low SpO2  Sunken or bulging fontanelle Differential Diagnosis  Metabolic acidosis  Bowel obstruction  Coarctation of aorta  Congenital diaphragmatic hernia  Congenital lung malformations  Congenital pneumonia  CHF DDx (cont)  Hemolytic disease of the newborn  Hemorrhagic disease of the newborn  Hypoglycemia  Hypoplastic left heart syndrome  Meconium aspiration syndrome  Bacterial meningitis  Necrotizing enterocolitis DDx (cont) Osteomyelitis  Pericarditis  Pulmonary atresia  Pulmonary HTN  Pulmonary hypoplasia  RDS  Single ventricle  UTI  Labs  Check everything! • • • • • • Blood, urine and CSF cultures CBC with diff CSF studies CRP level (which you will get back in 2 wks) Serum IgM may indicate an intrauterine infxn HSV PCR if CNS abnormalities, skin vesicles, or not responding to abx Imaging  CXR • May look like RDS in sepsis  CT or MRI late in course of meningitis  Head ultrasound may be useful in meningitis What are we treating?  Early pathogens (1st week) • • • • • • GBS E coli Gram neg rods (esp in urine) Listeria HSV Enterovirus Later bugs…  Late onset sepsis (1-2 wks) • • • • GBS or grp A strep Enterococcus in urine HSV Enterovirus, RSV, influenza Treatment  Begin abx as soon as labs done • IV aminoglycoside and expanded-spectrum penicillin – Usually tx for 7-10 days even if cx neg after 48-72 hrs • Oxacillin if nosocomial infection is suspected • Meningitis requires tx for 2wks after sterilization of CSF Prognosis  Term infants usually have no long term sequelae if treated early • Residual neuro problems occur in 15-30% with septic meningitis  Preterm infants have higher rates of cognitive defects, CP, and other neuro disabilities Surgical Emergencies  Pyloric stenosis  Congenital diaphragmatic hernia  Tracheoesophageal fistula  Abdominal wall defects • Gastroschisis • Omphalocele • Necrotizing enterocolitis Necrotizing enterocolitis  Intestinal wall inflammation or injury caused by bacterial invasion or previously injured or ischemic bowel wall  Incidence: 5-10% infants <1500 gm  Mortality: 10-30% Risk Factors  PREMATURITY (yes, again…)  Others… • • • • • • • Ischemia Bacterial infxn Enteral feeding Congenital heart disease Hyperosmolar formula Hx umbilical arterial catheter Hx exchange transfusion Early Signs  Temp instability  Poor feeding  Bilious vomiting  Lethargy  Mucoid or bloody stool  Apnea  bradycardia Late signs  Hemodynamic instability  Anemia  Thrombocytopenia  DIC  Prerenal azotemia  Metabolic acidosis Imaging  Abdominal x-ray • Bowel obstruction, edematous bowel, ileus, intramural air, pneumoperitoneum Medical Management  Initial, for 7-10 days; 75% successful • • • • • • No enteral feeds for 10-14 days NGT to intermittent suction Hydration, ‘lyte management Respiratory support Abx Blood and platelets if needed Surgical management  10-50% mortality  Indications • Absolute – Bowel perforation – Intestinal gangrene • Relative – Metabolic acidosis – Resp failure – Oliguria – Thrombocytopenia – Leukocytosis – Air in portal vein – Bowel wall edema – Persistent dilated bowel loops