Category Archives: Neonatology

Hypoglycaemia

Endocrinology, General paediatrics, Metabolic, Neonatology

Glucose levels are maintained after a meal by release from glycogen stores in liver (glycogenolysis), driven by Glucagon. When glycogen stores are low, then glucose can be produced from fat stores by fatty acid oxidation (via ketones) and from protein by gluconeogenesis. The switching over is moderated by cortisol, and growth hormone (reduces insulin resistance) also important.  Insulin is the only hormone that lowers blood sugar levels.

Cortisol increases gluconeogenesis, adrenaline increases lipolysis. Hypoglycaemia makes you grumpy, sweaty, pale. You can feel sick with it, and it can give you palpitations.  It can cause a wide range of acute, transient neurological symptoms including tremor, confusion, ataxia, weakness, visual disturbance.  If severe, it causes seizures, which causes release of glucose from muscles. Some cases of sudden unexpected death are thought to be due to inborn errors of metabolism causing hypoglycaemia.

Recurrent severe episodes in infancy can lead to permanent neurodisability.

There is debate about what level of blood sugar is abnormal, or whether it is only symptomatic low blood sugar that is important.  What the level in the blood is, is not the same as levels in the brain, of course.  Less than 2.6mmol/l is uncontroversial (note that near patient tests are not very accurate at low levels, which they are not really designed for, so lab confirmation is always required).  Generally <3.3 used in practice, but clinical signs important.

Usual cause is acute viral illness with reduced oral intake and vomiting.  But this can also be a trigger that reveals an underlying metabolic disorder…

  • Neonate? If big liver, remember Galactosaemia and Fructosaemia (reducing sugars in urine). Else Beckwith Wiedemann Syndrome.
  • High glucose requirement (see below)? =Hyperinsulinism
  • High ammonia? If encephalopathic, metabolic. Else Hyperammonaemia hyperinsulinaemia –  second most common congenital cause of hyperinsulinism. Gain of function mutations in the mitochondrial enzyme glutamate dehydrogenase (GDH). Can treat with diazoxide.
  • Signs of adrenal insufficiency? Abdominal/back pain, low Na, high K/Ca! Hyperpigmentation.
  • Signs of hypopituitarism? Growth failure, midline defects, micropenis.
  • Encephalopathy (esp vomiting)? Consider organic aciduria
  • Odour? Consider Maple syrup urine disease etc
  • Ketones should be present. If not then Fatty acid oxidation disorder eg MCAD.
  • Hepatomegaly? Glycogen storage disorders, also galactosaemia, acute liver failure eg Reyes syndrome (this may also be the mechanism in respiratory chain disorders).
  • With sepsis and shock consider galactosaemia – usually big liver too
  • Overdose? Propranolol, alcohol, salicylates in particular.
  • Consanguinity?
  • Time of last meal? Endocrine problems can cause symptoms at any time, as can hyperinsulinism. Glycogen storage/synthase problems cause early hypoglycaemia (ie within 3-8 hours).

Investigations

Get 1 ml lactate & 6 ml lithium heparin, bloodspots on neonatal screening card during hypo, and first urine (freeze).

Glucose requirement (mg/kg/minute) can be calculated from the following formula:

  • from IV fluids = Infusion rate (ml/hr) x % of glucose infusion x 0.1677/weight.
  • from oral feed: glucose content of standard infant formula is 7.2g/ 100ml, and of LBW formula is 8.6g/ 100ml.

Normal is 4-6 mg/kg/min, over 8 is suspicious of hyperinsulinism.

  • Insulin and C-peptide. Insulin should be undetectable, C-peptide 0.3-1.12 if hypoglycaemic with appropriate insulin response. Else hyperinsulinism (exogenous, or congenital)
  • Blood Glucose – below 2.6 considered true hypoglycaemia.  Note that BM sticks are not really designed for low sugars, and are not reliable.
  • Lactate – should be normal, otherwise high (with ketones) suggests glycogen storage disorder (with notable exception of Glycogen synthase defect)
  • TFTs – hypopituitarism
  • Cortisol – hypoadrenalism (cortisol should be high as part of stress response – else consider hypoadrenalism (Addison’s). Infants under 6 months should go over 800, older should be over 500. If low cortisol but GH >15 unlikely to be pituitary problem.
  • LFTs – beware primary liver problem
  • U&Es, Calcium – Low sodium, high potassium/Ca seen in hypoadrenalism
  • Ammonia – for organic acidaemias etc, or primary liver problem
  • Amino acids – for Maple Syrup Urine Disease etc
  • Carnitine, hydroxybutyrate – for Fatty Acid Oxidation (FAO) disorders
  • Acylcarnitines (blood spot) – for FAO disorders
  • Free Fatty acids – for FAO disorders, esp FFA/3OH-butyrate ratio (ketones are made from FFA so should be higher or not much lower, else block)
  • Blood gas – ?Acidosis
  • Urine for reducing sugars (Galactosaemia etc),
  • Urine/blood for organic acids

Prognosis

Mostly ketotic hypoglycaemia, due to starvation/vomiting. Adequate history?  Beware encephalopathy, raised ammonia, hepatomegaly.

75 LGA newborns with hypoglycaemia followed up to age 4 – no late effects. [Archives of Disease in Childhood 2005;90]

Listeria

Congenital, General paediatrics, Infectious disease, Neonatology

An intracellular gram positive rod – not many of those, apart from in probiotic drinks!  Resistant to cold and salt, so particularly a problem in ready to eat foods eg deli meats, hot dogs (unless steaming hot), cheese esp soft (incl blue veined, but excl mozzarella), raw and cooked poultry, ice cream, raw vegetables, raw and smoked fish (unless in shelf stable form). Melons and hummus have been sources in US.  In adults, tends to affect those with underlying health problems.

Infection in pregnancy often undiagnosed. May cause preterm labour or intrauterine death. Infection at birth may be severe, with classic fine papular rash, widespread microabscesses and granulomas, and bacteria visible on gram stain of the meconium. Or infection may be late in onset eg 1-2 weeks, with meningitis (note low counts cf other causes), else endocarditis, osteomyelitis etc.

Preterm meconium staining of the amniotic fluid (MSAF) is a “classic” feature – was observed in 4.3% of infants below 33/40. No maternal or infant listeriosis was identified in any of the 1000 cases. MSAF was associated with prolonged rupture of the membranes and severe (grade 3/4) intraventricular haemorrhage (OR 2), not sepsis or mortality. (Simpsons, Arch Dis Child Fet 2004)

Surveillance study of bacterial meningitis in infants aged <90 days in the UK 2010-11 showed that then usual three bacteria (GBS, E. Coli and Listeria) remained dominant, their frequency varied significantly by month of life. In the first 30 days of life. L. monocytogenes was the third most common bacteria, responsible for 6% of cases. The median age of meningitis due to L. monocytogenes was 13 days (IQR 3–18 days) with the oldest infant being 29 days; Listeria meningitis was therefore not seen beyond the 1st month of life. Of the 11 cases of Listeria meningitis, a good number (although a minority) were preterm and most first became unwell when at home. 2 cases had serious complications but no deaths.

Public Health England have published 24 years data on listeria septicaemia and meningitis. 97% of all cases presented in the first 30 days of life. Bacteraemia is more common but tends to be early onset (<7 days of age) whereas most meningitis were late onset.

It is also prudent to consider the possibility of Listeria infection in older infants (and therefore add amoxicillin) if:

  • Gram-positive rods are seen in the cerebrospinal fluid,
  • if the infant is immunocompromised
  • or if the clinical response to empirical therapy is suboptimal

Treat with high dose amoxicillin/ampicillin. Gentamicin is synergistic but does not penetrate intracellular compartment (or CSF) – can be stopped after a week assuming good clinical improvement. For allergic, TMP-SMX (Septrin) is best alternative! Cephalosporins are useless! Treat for 2 weeks if no meningitis, at least 3 weeks if meningitis, longer if abscesses or heart involvement.

[Okike, Arch Dis Child 2015;100:426-431]

Stillbirth

Neonatology

Stillbirth (after 24/40), not due to congenital anomalies, is associated with fetal growth restriction, smoking but also obesity.  Could it be because obesity reduces accuracy of scans?  Advanced maternal age has been a risk factor in some metanalyses.

Food protein–induced enterocolitis syndrome (FPIES)

Allergy, Gastro, General paediatrics, Immunology, Neonatology, Nutrition

Non–IgE-mediated severe gastrointestinal food hypersensitivity, typically presents in early infancy with repeated vomiting, dehydration, lethargy, metabolic acidosis (even mimicking sepsis).  Watery diarrhoea (sometimes with blood and/or mucus) can develop in some cases. The severity is really what makes it worthy of a distinct name, debatable if it is actually distinct from other non-IgE mediated food allergy.

Probably underdiagnosed.

A few unusual features cf type 1 allergy.

The most common offending foods are cow’s milk and soy in young infants; in older infants, there are a range of food triggers including some foods usually not considered allergenic eg rice, oat, chicken, sweet potato!  Egg surprisingly a very unusual cause!  Cases in breastfed infants have been reported.

Acute symptoms occur 1 to 5 hours after ingesting the offending food.  Lasts up to 24 hours. Not always consistent, which might suggest co-factors important.

Most kids only have an issue with one or two foods.

Chronic FPIES less well characterised – Japan, Korea more? Usually young babies fed formula. Chronic vomiting, diarrhoea, faltering growth, hypoalbuminaemia. Chronic usually turns into acute on challenge!

Diagnosis is based, predictably for a non-IgE condition, on clinical history and food challenges. Leucocytosis and methaemoglobinaemia are associated but low specificity/sensitivity.  Oral food challenge where FPIES suspected would be done with IV access, and divided portions of 0.15-0.3g/kg over 1 hour.

Rechallenge

No consensus on when to rechallenge. Hospital challenge, obviously. 12 months to 18 month seems reasonable. IV access recommended. Ondansetron given at start of reaction may shorten duration. 2017 International Consensus Guideline suggest using 0.3g of food protein per kilogram of body weight (max 3 g of protein or 10 g of total food or 100 ml of liquid), in 3 equal doses over 30 minutes followed by 4-6 hours of observation. But since likely to be delayed (unless IgE pos), not v logical. Lower starting dose (0.06g protein/kg body weight) +/or longer interval between doses recommended for those with history of severe reaction.

In study by Barni,  25% of the total dose (0.3 g protein/kg body weight) was given initially, followed by a full dose 4 hours later. This seemed to work well – mean latency of 136 minutes (range 60-230 minutes). Another study found this worked well for 80% of patients.

In a retrospective study of 153 children in Philadelphia with egg FPIES, 36.6% had positive skin prick testing. More than 60% of patients who tried to introduce baked egg after a period of avoidance were able to tolerate it. Only a minority (23%) were able to eat baked egg before tolerating regular unbaked egg. Positive SPT did not affect prognosis but obviously was associated with a higher likelihood of immediate reactions.

FPIES is usually outgrown by school age. Management is simply avoidance of the offending food, natural history appears to vary for different foods which makes it difficult to judge reintroduction.

Parent support at https://www.fpiesuk.org.

[Calvani update] [Guibas 2014 review]

Annals of Allergy, Asthma & Immunology, Volume 107, Issue 2, August 2011, Pages 95–101

Congenital varicella

Congenital, Infectious disease, Neonatology,

If a pregnant woman is infected during the first trimester (risk extends to 20th week), a fetus has a 1% chance of developing widespread scarring, hypoplastic limbs, cataracts and brain lesions (congenital varicella). Affected infants have a poor neurodevelopmental outlook.

Risk of neonatal VZV (severe, disseminated disease in newborn) if chickenpox is contracted by the mother 4 days before birth, to 2 days after  (risk 20%).  Before that, good chance that maternal immune response will protect baby, after that the dose of infection transmitted to the baby via the umbilical cord is likely to be small (although will still be exposed to droplets).

See Maternal for advice on varicella exposure in pregnancy and in neonates.

 

 

Hirschsprung’s disease

Gastro, General paediatrics, Neonatology, Surgical

Congenital absence of ganglion cells in distal bowel, beginning at the internal sphincter and extending proximally.  Fails to relax, hence functional obstruction.  Mostly present as neonates, with delayed meconium and abdo distension, else mostly under 2yr with intractable constipation, failure to thrive, repeated vomiting. Rarely soiling! 1/3 of these later presenting patients present with enterocolitis, with fever, shock, bloody stools.  Probably due to abnormal colonic mucosa, a problem that seems to persist even after surgery.

Some series describe patients without symptoms in neonatal/infancy period!

1 in 5000 births. 4:1 males:females.  FH 30%. Assoc with downs, cong deafness.

Empty rectum on AXR (ie gas pattern disappears)! [insert axr] May be forceful expulsion at PR (which may also spoil diagnostic value of barium or manometry studies). Barium enema can be useful but high false neg in first 3/12, and need to avoid PR examination and enemas for preceding 48hr else distal narrowing lost.

Treatment – resection of affected segment.  Postop do well, risk of anal hypertonicity (enterocoitis), stricture.