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.

Allergic Rhinitis

Allergy, General paediatrics, Immunology, Respiratory,

Under-recognized, particularly when chronic blockage (without itch/sneezing) rather than sneeze/discharge. Late phase reactions involving Eosinphil induction by T cells tends to produce chronic swelling and non-specific irritability eg cold air. Nose problems impact with everything connected eg eyes, sinuses, middle ear, lungs. Differential is wide eg CF/PCD, deviated septum, polyps.

ARIA= allergic rhinitis in asthma report (WHO).

Ethics of genetic testing in childhood

Ethics, General paediatrics, Genetics

Difficult to determine the psychosocial harms and benefits of testing in childhood.  A systematic review (Genetics in Medicine, 2015,   doi:10.1038/gim.2015.181) found that serious adverse psychological outcomes were uncommon, and most studies reported no significant increase in mean anxiety, depression, and distress scores.  However, some children experienced intrafamilial distress, discrimination, and guilt/regret. Some children were more concerned about their own health or their family members’ health.  It wasn’t very easy to anticipate adverse impact.

Objections-

  • No direct or medical benefit? Duty to protect the future autonomy of the child, i.e. preserving the right for the child to make her/his own decision to be tested or not.
  • Possible psychosocial harm from knowing diagnosis? Existing guidelines are often based on assumptions rather than empirical evidence of such harm, viz possible lessened self esteem, distortion of the family’s perception of the child, altered upbringing, discrimination and increased anxiety both of parent and child.

On the other hand, it has been argued that parents have the right to make decisions on behalf of their children because they have primary responsibility for their child and they know their child best.

Similarly, not testing may mean that the child loses the opportunity to grow up with and adapt to genetic knowledge during his/her formative years. Plus, parental anxiety, difficulty of living with uncertainty.

The authors of the systematic review highlighted the lack of data regarding genetic testing for conditions that may not be treatable/modifiable, and the dearth of longitudinal studies. So they conclude that caution remains essential for the ethical integration of genetic testing in children.

British society for human genetics, 2013 report into testing children. http://www.ethox.org.uk/Documents%20and%20images/GTOC_2010_BSHG.pdf

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 an unusual cause in some countries!  Cases in breastfed infants have been reported, even severe hypotension requiring intensive care.

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.

In Europe, rare to get multiple food FPIES but in UK/US/Australia about 25% (English speaking!?).

Diagnosis

Diagnosis is based, predictably for a non-IgE condition, on clinical history and food challenges. Leucocytosis and methaemoglobinaemia are associated but low specificity/sensitivity.  

2017 Consensus out of date but diagnostic criteria still used – 

  • Major – vomiting at 1-4 hours in absence of type 1 skin/resp symptoms.
  • Minor – at least 3 minor criteria eg second episode of repetitive vomiting after same food; extreme lethargy; hypotension; need for hospital care or IV fluids; etc

Probably mild, mod and severe! Proposed BIO-FPIES criteria includes abdominal pain, nausea, increase in neutrophil count (but 3 points for second episode of repetitive vomiting after same food).

Phenotype switching

Egg and nut FPIES often go on to develop IgE sensitisation (about 20%), less for others. Of those, about 30% of milk FPIES will switch to type 1 phenotype, 15% for egg, less for other foods. But overall, unlikely to make much of a difference to care (and doesn’t help predict resolution).

Management

No role for antihistamine/adrenaline!

BSACI has FPIES plan.

Family support at www.fpiesuk.org.

For introducing weaning foods, when known FPIES to one food, start with low risk foods, supervise common triggers eg rice/egg.

Challenge

Challenge is necessary to decide whether things are getting better or not. Consensus is that 12-18 months after last reaction is a good balance between chances of things being better, and risk of causing severe reaction.  

50% milk/soya resolve by age 3-4, more like 4-5 years for other foods. 

Traditional protocol is 0.3g/kg protein, divided into 3 doses over 30 mins.  But unrealistic for low protein foods eg fruit. And doesn’t really make sense to split dose when you don’t expect a reaction for hours (but risk of switch to type 1 allergy for egg/nuts).

2 day protocol (25% portion then whole portion next day) had less severe reactions. 

25-30% of age appropriate portion triggers reaction in most children. [Baked???] Over 50% react after at least 2 hours. 

Beaudoin 2024 has home challenge protocol but brave… 

[Marta Vazquez-Ortiz systematic review]

[BSACI FPIES grand round – Marta Vazquez-Ortiz (Imperial/St Mary’s, BIO-FPIES research network)] [2025 Shaker shared decision making] [2024 Anvari]

Obesity management

Common, General paediatrics, Nutrition, OPD

Public health surveillance use 85th centile as definition for overweight, and 95th centile for obesity (UK says “at risk of obesity”…). Clinical definitions (SACN/RCPCH 2012, NICE) however are different: (UK 1990, use special BMI chart)

  • Obesity = BMI >98th centile for age (2 standard deviations, one tail)
  • Overweight = >91st centile (1.3 SD)

Growth charts then label:

  • Severe obesity = 99.6th centile (2.67 SD)
  • Morbid obesity = 3.33 SD.  High probability of co-morbidity, unlikely to improve by age 16.
  • (some guidelines use Extreme = 4 SD)

Cut off for overweight/obesity high in babies, starts at 18/20 age 2, nadir of 17/19 at age 5, rising to 20/24 at 10 then usual 25/30 at age 18. Girls same as boys, slightly fatter after 10 yrs. [International data, BMJ 320:1242.] Charts are available at the RCPCH.

Centile charts show centile spaces that are equivalent to 2/3 of a standard deviation.  When you get to high centiles, you need something better than “above the 99.8th centile” so you use Z score, which is the number of standard deviations above the mean

Calculators available to calculate BMI and Z-scores eg Phsim.man.ac.uk/SDSCalculator

So secondary referral for:

  • extreme, or
  • ?secondary obesity, eg
    • under 2 yrs with severe (>99.6th centile) obesity
    • short for age
  • co-morbidity eg strong FH type 2 DM, sleep apnoea, idiopathic intracranial hypertension, orthopaedic probs
  • psychological comorbidity,
  • safeguarding.

2nd care history –

  • menstrual hx,
  • sleep eg Chervin questionnaire (adds anything?)

Examination

  • acanthosis nigricans (neck, flexures) – highly associated with insulin resistance
  • buffalo hump.  Striae and obesity as only signs of Cushings v rare. Striae in Cushings more intense red!?
  • Mid-Parental Height – endocrinopathy unlikely if normal growth
  • Waist circumference
  • Goitre – hypothyroidism
  • BP
  • Peak flow
  • Syndrome eg BWS
  • Acne, Hirsutism – polycystic ovary syndrome
  • Telangiectasia

Investigations

Little evidence for investigations, not routine.

  • Fasting glucose, insulin, lipids
  • FBC, U&Es, LFTs
  • TFTs
  • HBA1c
  • SHBG (marker of insulin resistance)

For more severe cases, consider:

  • OGTT – 2hr glucose >11.1=diabetes, 7.8-11.1 = impaired glucose tolerance.  Esp if S Asian, other signs/risks of insulin resistance.
  • ECG
  • Sleep study
  • Molecular genetics (EDTA) eg Prader Willi, Bardet-Biedl syndrome, Cohen syndrome, MOMO syndrome. Scottish Strategic network for genomics medicines has panel including leptin genes, indicated for BMI >3.5 SDS; Age of onset below 5 years (without significant developmental delay or dysmorphic features – those should go to Clinical Genetics as other testing may be more appropriate)
  • Urinary cortisol/creatinine
  • Low dose dexamethasone test (more sensitive than above but needs overnight admission) – cortisol should suppress below 100, else suggests Cushings
  • CT head (if suspicion of raised intracranial hypertension

Homa-IR >4.5 for insulin resistance [Score = (Fasting insulin)*(Fasting glucose) / 405, measuring in mg/dl].  Transient increase in insulin resistance seen in puberty, independent of BMI.

Total choles:HDL 3.6 95th, 4.3 99th but no great paed data.

ALT>70 twice should proceed to USS to look for fatty liver, >100 urgent (for differential more than anything, although non alcoholic fatty liver disease can be progressive).

Communication

Delicate! Moral issue too – for example:

  • uncertain benefits on physical health
  • negative psychosocial consequences including uncertainty, fear, stigmatization
  • aggravating inequalities
  • disregarding the social and cultural value of eating
  • infringement upon personal freedom regarding lifestyle choices and raising children

Addressing these issues may avoid resistance [Erasmus medical centre, Obes Rev. 2011 Sep;12(9):669-79. doi: 10.1111/j.1467-789X.2011.00880.x. Epub 2011 May 4]

PHE “All our health” has child (and adult) obesity thread– use opportunistic moments to open up conversations around weight. “Let’s talk about weight” = short conversations guide.

  • Initiate a conversation. Anticipate defensiveness
  • Discuss “healthier weight” concept
  • Positive, non-judgmental language
  • Terms such as ‘obese’ are not generally well accepted by parents/carers

Opportunistic is good, but probably sensible to check that this is a good time, or at least create an invitation to start this conversation. And then, do more questioning and listening than advising.

What works?

The above section may already have brought up issues of low self-esteem and poor motivation. Building a therapeutic relationship, using motivational interviewing skills, is key then, especially where parents/children may have sensed discrimination and bias in the past.

General advice should include: (SIGN)

  • Healthier eating, and decreased calorie intake
  • At least 60 mins of moderately vigorous activity per day, pref habitual eg brisk walking! Given that evidence that moderate/high levels of cardiorespiratory fitness appear to attenuate or even eliminate the risks, just as important to emphasize fitness as weight loss? 
  • Max 2 hours screen time per day!

But as indicated above, probably more important to ask about the blocks, than to say “eat less, move more”.

OSCA 2012 Viner, arch dis child educ (paeds network)

See Prevention and Treatment.

Urticaria

General paediatrics, Immunology

Or “hives” – itchy plaques or papules (weals), with surrounding flare, typical of histamine reaction in skin. Urticaria can also be accompanied by angioedema – although angioedema on its own may point to hereditary angioedema (else drugs eg NSAID, ACE inhibitors, oestrogens, statins), and absence of angioedema may suggest urticarial vasculitis, Schnitzler syndrome, cryopyrin associated periodic syndromes.

Not always allergy, although it is the classic rash of type 1 (histamine and IgE mediated) allergy.  Can be inducible or spontaneous.  Can be transient, intermittent or chronic (6 weeks minimum).

Burden on quality of life and health services can be substantial.

Inducible

Various kinds of physical stimuli can trigger urticaria, including:

  • Dermatographism – within 10 minutes of pressure
  • cf Delayed pressure type – tight clothing, sitting
  • Heat (including exercise and emotion)
  • Cold – can be secondary to autoimmune conditions or infection. Anaphylaxis risk from swimming!?
  • Sunshine (solar)
  • Water (aquagenic) – cold, hot, even rain…
  • Vibratory angioedema
  • Cholinergic urticaria
  • Contact urticaria

Can be mixed! Some tests have been suggested eg ice cube test (ice cube in a sealed plastic bag over the forearm for up to 10 min – wait for skin to rewarm), flannel test for aquagenic (wet towel for a few minutes on area of skin most affected).

Can be hormonal in girls, therefore cyclical (catamenial).

Differential

These things are considered to have different mechanisms:

  • Hereditary angioedema
  • Delayed food allergy eg alpha gal, or exercise induced
  • Atopic dermatitis
  • Chronic or recurrent infection (consider occult eg dental)
  • Erythema marginatum (as in rheumatic fever, but also a prodrome to HAE!)
  • Erythema multiforme
  • Drug reactions
  • Polymorphous light eruption
  • Thyroid disorders
  • Cutaneous mastocytosis
  • Systemic lupus erythematosus
  • Cryopyrin (autoinflammatory) disorders, typically with fever, arthralgia, eye inflammation eg Muckle Wells
  • Schnitzler syndrome – with monoclonal gammopathy
  • Gleich syndrome – with eosinophilia
  • Urticarial vasculitis (often spectacular, lasts more than 24 hours, bruising develops)
  • Autoimmune urticaria (caused by autoantibodies vs FC epsilon RI alpha, but antibodies do not correlate well with symptoms)
  • Mastocytosis and urticaria pigmentosa
  • Oestrogen, progesterone and pregnancy related dermatoses

And if everything else excluded, that leaves Chronic idiopathic urticaria.

Urticaria Activity Score available – wheals and itch over course of day, score 0-3. Moderate wheals are 20-50. Do for 7 sequential days and add up to give UAS7 score.

Diagnosis

Basophil histamine release assay and autologous serum skin tests suggested, 25% of all chronic urticaria patients are positive for one and/or other, but  50% are negative for both – so struggling for a diagnostic standard.

Essential:

  • FBC, CRP, ESR – CRP raised and eosinophils low in type IIb (mast cell-directed autoantibodies)
  • Total IgE – reduced in type IIb
  • Anti TPO antibody – high in type IIb (high ratio to total IgE)

After that, as indicated, eg:

  • ASOT
  • Immunoglobulin electrophoresis done in adults to look for paraprotein
  • H pylori – some have suggested eradication helps but BSACI come down against routine screening
  • TFTs, Functional autoantibodies eg Thyroid, ANA
  • Pseudoallergen (additives, flavourings, colourings) free diet for 3 weeks? BSACI not v keen
  • Tryptase – systemic mastocytosis? Not in BSACI guideline!
  • TTG – some case reports of association with coeliac disease
  • C3/4 – if suspected urticarial vasculitis, and if reduced, measurement of anti-C1q antibodies [BSACI urticaria guideline]. C4 low in HAE.
  • Cryoglobulins for cold induced
  • Biopsy – but for mastocytosis, bone marrow aspirate most sensitive!
  • Specific tests: ice cube, flannel, dermatographism, hot bath, exercise. 

Incidence of underlying cause varies regionally. And some of these things may simply be aggravating underlying spontaneous urticaria, rather than a cause as such!

Assess for co-morbidity – mental health, autoimmune disease, allergy.

Treatment

Identify triggers – drugs (esp NSAIDs), foods (high histamine, pseudoallergens?), stress, infection.

For acute, non-sedating antihistamines (H1 blockers), else steroids. Evidence for H2 blockers eg ranitidine very weak.

For chronic, continuous non-sedating AH effective in <50% of patients. No evidence that one antihistamine is better than any other. Guidelines recommend up to 4x updosing (studies support for cetirizine, fexofenadine, otherwise desloratadine, levocetirizine, rupatadine!). 

No evidence that using different H1 blockers at the same time has any advantage (moderate consensus only, however…)

Weak evidence for steroids! Suggests maximum 10 days. Similarly montelukast.

Omalizumab is second line for both spontaneous and inducible – monthly SC injections 300mg (not dependent on IgE, as is asthma dosing) every 4 weeks (safety data now from age 1). Increase dose or shorten interval if necessary (up to 600mg every 2 weeks). After that, ciclosporin.

Other treatments with limited evidence include doxepin, ranitidine, methotrexate, dapsone etc. 

Tranexamic acid for angioedema?

No evidence for thyroxine treatment if autoantibodies, if euthyroid.

Plasmapheresis and IVIG have been used…

Tolerance to triggers can be induced (rapidly in some cases, eg within days), but not usually v pleasant, and temporary only…

Note the high rate of anxiety, depression, somatising disorders (50%).

[EAACI/GA2LEN 2021]

Alpha 1 Antitrypsin deficiency

Gastro, General paediatrics, Genetics, Respiratory,

Similar incidence to CF in white populations. Protease inhibitor (PI), counteracts neutrophil elastase. Alleles include PiZ (defective), PiM (normal), PiNull (non functioning). Protein phenotype then described as Z, M, MZ, or None

  • Double Null – very high risk of COPD but no liver disease!
  • ZZ have high risk of COPD and liver disease.
  • SZ also seen, risk of COPD.

The risk of emphysema is increased in males, in asthma and especially in smokers.

PiMZ genotype does not appear to predispose to chronic liver disease (in case control study). On the other hand, patients with decompensated liver disease (of any cause) were significantly more likely to have PiMZ, and particularly in HCV or NAFLD PiMZ was associated with more severe liver disease and need for liver transplantation. Suggests that if you have some other cause for liver disease, PiMZ will do less well.

J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S30-5. [pmid:16819398]

About 10% of children with Z phenotype have prolonged (obstructive) jaundice as babies, most have abnormal LFTs at some point in first year of life. Only 2% progress to liver failure requiring transplantation, however. Risk of hepatocellular carcinoma higher, not surprisingly.

Augmentation therapy with IV AAT approved by FDA, expensive. May slow decline in lung function but not great evidence yet. No intended to treat liver disease.

Screening is really only useful in aggressive smoking and alcohol advice. Non-alcoholic fatty liver disease seems to worsen other causes of liver disease so avoidance of obesity seems important too.

Necrotizing panniculitis associated with AAT deficiency, seems to respond rapidly to AAT treatment.

 

Ulcerative Colitis

Gastro, General paediatrics

About a third of IBD in kids, incidence stable unlike Crohn’s.

Associated with autoimmune disease especially sclerosing cholangitis.
80% kids have pancolitis (cf 20% adults), otherwise proctitis alone or
other local disease.

Acute Severe Colitis

“About saving lives, not saving colons”.

15% severe at presentation, 28% have at some point in childhood.

The first attack of colitis tends to be more severe and disease more
extensive in children than in adults. Many respond to conventional
medical therapy but 8-30% at 1 year will have undergone colectomy for
failed medical treatment (depending on disease severity).

Acute severe colitis is characterised by greater than 6 bloody stools
per day, abdominal tenderness, fever, anaemia, leucocytosis, and
hypoalbuminaemia. This is a typical presentation of ulcerative colitis
or may occur as an exacerbation, but the differential includes:

  • Infectious colitis eg Shigella, E. coli O157
  • Crohn’s colitis
  • pseudomembranous colitis
  • ischaemic colitis

Equivalent to PUCAI >65. Moderate colitis 35-60.  Day 3 PUCAI already predictive of future colectomy, second line therapy.

Clostridioides prev Clostridium difficile- less in kids than adults.  Intermittent shedding so multiple samples required.

CMV colitis – not always immunosuppressed.  But no evidence for treatment or prophylaxis…

1-1.5mg/kg max 60mg IVMP.  If toxic or colonic dilatation then NBM, antibiotics, surgical opinion.

Day 3 under 35 PUCAI can consider oral steroids (120% IV dose).  Over 45 refer tertiary centre, screen for second line therapy, start involving surgeons/stoma therapist, sigmoidoscopy (safer than full colonscopy), check HBV/HCV/TB for starting ANti TNF Rx.

Day 5 over 65 start second line (infliximab).  “Sponge, sieve, shark”.  Dose, timing?  Sponge soaks up Abs.  Shark is immune system removing Ab.  Sieve – leaking Ab?  Not much evidence yet!

No response at day 11 consider colectomy.

Alternative second Rx are ciclosporin, tacrolimus.

Toxic megacolon – pain, distension.  Signs less if already on steroids.  Amp, gent, metro.  40mm under 10, 56mm otherwise.

Thrombosis – recognized risk of stroke.  Consider 3+/12 treatment prophylaxis eg OCP, FH

No evidence for bowel rest!

Number of stools can be over estimated if very close episodes. Some may conceal or underestimate number/blood.

Investigations

  • FBC, coag
  • Group and save – consider Cross match esp if possibly for surgery
  • CRP, ESR
  • U&Es, LFTs, Ca – hypokalaemia can precipitate toxic megacolon
  • Blood culture, stool cultures, stool microscopy, C diff toxin
  • CMV serology if immunocompromised
  • AXR – toxic megacolon = 5.5cm+ dilatation

These also used for monitoring, in addition to PUCAI score, a clinical score:

  • abdominal pain (can be ignored or not),
  • rectal bleeding (some stools, most stools, more blood than stool),
  • stool consistency and frequency,
  • nocturnal stooling,
  • activity level (limitation or not).

Under 10 normal, 10-30 mild, 30-60 moderate.  Best averaged over 2 days unless rapidly changing clinically.

Endoscopy is not considered first line investigation given risk of
performation. Limited sigmoidoscopy may give useful information
however.

Management

  • Fluids and nutrition
  • Blood transfusion, esp if Hb<8 or <10 and symptomatic
  • Consider antibiotics (IV Cef and met) if high risk of infection or pre-surgery
  • Stop aminosalicylates until improving
  • Steroids – Hydrocortisone 10mg/kg in 4 divided doses, max 400mg/d else Methylprednisolone 1mg/kg, max 60mg. Do not delay pending microbiology!
  • TED stockings, LMWH
  • Surgical review

Joint medical/surgical care is appropriate. If surgery is likely to be
needed, a stoma nurse would be useful. PUCAI >45 on day 3 suggests
failure to respond (30-70%, depending on severity). Cyclosporin and
Infliximab are second line.

Maintenance

Azathioprine and 6MP are useful for maintenance, less useful acutely
given delayed onset of action. TPMT deficiency predicts myelotoxicity
(use lower doses). 6MP has less side effects (nausea, vomiting,
headache, fatigue). prob best for younger kids.

Sulphasal liquid, various granule products for older kids.

Mesalazine enemas good but low acceptability.

[Richard Hansen 2016]

Riley Day Familial dysautonomia

Cardiology, General paediatrics, Genetics, Neurology

Seen virtually exclusively in Ashkenazi Jews. Subtype of hereditary
sensory and autonomic neuropathy (cf HSMN).

From birth, absence of tears, poor tone and suck, blotchy skin rashes.
Insensitivity to pain can lead to accidental self mutilation. Speech,
motor development and growth all impaired, but intelligence normal.

Autonomic crises occur, triggered by physical or emotional stress –
sweating, high blood pressure, blotchy rash, vomiting.

Sexual history

Clinical, General paediatrics,

Explain why (cf nosiness), offer confidentiality

Fear of disappointment/disapproval, parent/authority figure, stigma, genital examination.

Closed questions – curiosity not judgement:

  • Who was it with?  How old is she/he (clarify!).  Regular partner or casual (cf one off, one night stand, other judgemental terms).
  • Did you use a condom?  Did you use contraception (not the same thing)?
  • Did you want to?
  • Did you enjoy it? (!)
  • Do you tend to have sex when you’ve been drinking alcohol