June 2005


We just discovered that Dr Whitington has just had another article published:

Whitington, P.F & Padmini, M, 2005, “Neonatal Hemochromatosis: Is It an Alloimmune Disease?”, Journal of Pediatric Gastroenterology and Nutrition, Vol 40 pp 544- 549, May 2005

Unfortunately there’s no abstract available on the internet.  So I’d recommend accessing the article through your doctor.  To date it’s the most useful paper I’ve read, so here’s my attempt to summarise what it says (along with a few explanatory comments of my own).

What is neonatal hemochromatosis (NH)?

  • NH is a severe neonatal liver disease associated with iron deposition and resulting damage in other organs and tissues.
  • NH has similar characteristics to hereditary hemochromatosis
  • NH is considered a rare disease

What causes NH?

  • Causes are still unknown.
  • Some have suggested it’s a syndrome where a number of factors (infection, genetic-metabolic disease, and toxic insult) all lead to the same outcome or characteristics.
  • Is it genetic? The article argues that the evidence suggests not.  The reoccurrence rate of the disease once it has appeared in one child is around 80%.  This is much higher than recurrence rates associated with recessive autosomal inheritance (the common genetic inheritance process).  In addition the disease hasn’t been observed to reoccur in family trees.
  • Is it caused by infection? There is no known infectious disease that can recurrently generate the characteristics of NH.

So… the evidence led the authors to hypothesise that NH could be an alloimmune disease.  That is, a disease where the mother’s immune system generates antibodies against fetus antigens resulting in damage to the fetus.

How does an alloimmune disease cause fetal problems?
The mother generates antibodies against fetal antigens (an antigen is simply a molecule that stimulates the immune system to produce antibodies and could be any type of protein).  There are a number of mechanisms by which damage is done to the fetus when the mother’s antibodies attack the fetal antigens.

There are four classes of antibodies.  Only the immunoglobulin G (IgG) class are transported across the placenta to the fetus.  These antibodies (the IgG) provide the fetus with protection against antigens to which the fetus has not yet been exposed.  So IgG is the way that the mother helps give the fetus’ immune system a kick start.  In the case of pregnancy, alloimmune disease represents a failure of the mother’s IgG (antibodies) to recognise and respond to fetal proteins (the antigens).

Other known alloimmune diseases are hydrops fetalis and alloimmune thrombocytopenia.

How does the intravenous immunoglobulin treatment help?
The paper describes a treatment protocol for administering intravenous immunoglobulin to mothers.  The treatment protocol is a dose of 1g/kg each week (if you weigh 70kg, you’ll receive a 70g dose).   This dose is based on treatment for Rh incompatibility.

The treatment starts at week 18, since this is when active transport of IgG across the placenta starts.

It is thought that the IgG treatment potentially works via one of three mechanisms:

  1. blunting the maternal immune response;
  2. flooding the placental transport pathway with “good” antibodies.
  3. nonspecific antibody binding limiting the number of “bad” antibodies binding to the fetal antigens

How successful has the IgG treatment protocol been?
The treatment has been used to treat 18 women through 22 pregnancies, whose most recent pregnancy had resulted in NH. Normally the disease recurs at a rate of 80% and in the vast majority of cases NH is fatal without liver transplant.

To date all 22 babies have survived!  However, 6 babies showed evidence of liver disease, and there was other evidence that the majority of the babies (17) were affected with NH.

When analysed the treatment protocol is positively correlated with improved infant survival (p=0.0009!)  The paper therefore concludes that the treatment modifies NH so that it is no longer lethal and that the results provide evidence supporting their alloimmune disease hypothesis.

Where is the research heading in the future?
The authors hypothesise that a fetal liver protein associated with iron control is the antigen that is targeted by the mother’s antibodies.

Blood samples and analysis from women in the treatment program have identified some evidence to support this hypothesis.  However the exact nature and role of the protein is yet to be determined.  Identitying and understanding this protein is the next step.

It is hoped that if the protein can be identified blood tests can be developed to diagnose NH in mothers and also help streamline preventative treatments.

What a relief, exitement, relief, anticipation, relief… Today was probably the last ultrasound scan. From what we understand of NH it onsets reasonably late in the pregnancy, but Ellen was born at 36 weeks, and Basil is already 34 weeks. Considering the multiple problems that Ellen had you would expect that if Basil had similar problems they would be evident in the ultrasound… wouldn’t you? It’s hard to get anything out of the doctors on this front, we just concentrate on the positives; everything looks fine, both from a NH point of view or eclampsia.

Currently Basil is about 2.7kg (already 0.5kg) heavier than Ellen. The only thing I’m not quite sure of is how good he looks. I’m pretty sure this isn’t his best angle, but here’s his latest look. Do you think he’s voguing?

The pictures from the ultrasound look a lot better earlier in the pregnancy. It’s harder to get decent views once they grow a bit and start to take up the space.

We saw our doctor afterwards and he confirmed that all looked good. The plan is still to have a cesaerian on 25 July unless things look like they’re going to happen naturally of their own accord at about the same time. Unfortunately I think those 4 weeks are going to go pretty slowly.

This evening I heard an interview with Shirley Hazzard, the Australian author.  Shirley, now in her 70’s, talked briefly about the loss of her husband.  She had a really interesting take on her life now, that she often felt was living and enjoying life for her husband as well.

I’ve never thought of Ellen in the same way, I guess that’s because in reality I never knew her… only the thought of her.  And she wasn’t the lifelong friend and companion that a husband was to a widow.  But, the idea that I’m now enjoying life for Ellen immediately struck a cord.  Mary said that she’s sometimes had this thought.  It’s certainly a reassuring one.  I think I’ll keep it handy.

If you go surfing the net to look for information on other family’s experiences with NH then it’s a frustratingly fruitless search.  The most useful site we found is dedicated to Katelyn Michelle Madsen.

If you’ve read our account of Ellen, you’ll be struck, as we were, by the similarities.  The early contractions – trip to the hospital – no amniotic fluid – emergency cesaerian.  There were also many differences, which highlight the many unknowns that surround NH.

I’ve often wondered whether if we’d been living in a major city and not in Mount Isa would Ellen have survived.  Perhaps her life would have been extended for a few weeks but based on all the information I’ve read the outcome would most likely have been the same.

There are a couple of other sites that families have set up:

Aiden’s Story.  Aiden survived NH thanks to a liver transplant.  One of the few recognised treatments available.  His story shows the huge emotional rollercoaster ride that you board in this situation.

Pray for Andrew.  Andrew also survived NH (I think the stories of survival are easier to tell. I wonder if I would be writing this for if I didn’t believe that the next chapter in our own story will include a miracle).  Faith in God was obviously an immense source of strenth for Andrew’s family.  I know it meant a great deal to Mary that we had people praying for Ellen, Mary and our family.    

Finally there’s a memorial page on the neonatalhemochromatosis.org web site that contains others’ stories.

We attended the last of the antenatal classes this evening. The highlight included a video which really clearly set out all the potential reasons why you may want to reconsider having a baby! Sleepless nights, lack of time, crying babies… and I’m hooked.

I said to Mary over the weekend that sometime in the last week I’ve let my guard down. It’s a subconscious thing, but up until now I don’t think I’ve wanted to let myself believe that this is all happening. But now… I’m excited! When I think about it the pregnancy experience has been a bit strange. I’m normally the sort of person with a lot of questions and wanting to read all about it. But looking back I’ve pretty much avoided reading about the product of pregnancy, and when I have read up on the topic, it’s been about the neonatal haemochromatosis issues.

It is really like a blind being drawn back – sometimes there are steps in journey that I didn’t even know were there.

The problem is I’m now even more nervous about things. Mary nearly feinted at one stage today while she was at home. It’s potentially normal, but it’s hard not to worry… being alive.