Zika and its effects on babies: microcephaly and ‘congenital Zika syndrome’

This is the first of a three-part series on Zika’s effects during pregnancy. 

 

In this post, I will introduce ‘congenital Zika syndrome’ and describe how Zika is responsible for a lot more than just microcephaly.

 

I also thought I would compare Zika with other infectious causes of birth defects, to put the numbers being affected into context. 

 

I hope you find the post useful and informative!

I previously wrote a brief overview of the Zika virus, in which I mentioned that children of pregnant mothers with Zika are at risk of being born with something called ‘microcephaly‘ – medical speak for a baby with a small head as a result of an under-developed brain.

czs skin folds.png
Microcephaly. Left and middle: examples of the small and unusually-shaped head. Right: redundant skin-folds as a result of an under-developed brain and skull.
How we first found out about the link between Zika and microcephaly

The link between Zika and microcephaly was first suspected after astute doctors noticed that there had been a huge rise in the number of cases of microcephaly during the same time period that the Zika virus was circulating — initially in North-East Brazil (which is the part of Brazil that I’m visiting) and then in the rest of Latin America.

microcephaly case nos brasil
In 2015-2016 (the period of the Zika virus outbreak) the number of cases of microcephaly increased by around 15 times compared with what it was in previous years. In nearly half of these cases of microcephaly, blood tests (PCR) also showed that the mother had Zika virus during pregnancy (blue bar).

Studies soon followed which showed that women who were affected by Zika during pregnancy were more likely to give birth to children with microcephaly than mothers who did not have Zika infection during their pregnancy.

One such study, conducted in Rio de Janeiro, Brazil, followed 125 pregnant women with Zika virus at some point during their pregnancy and compared them with 62 Zika-unaffected pregnancies. 42% of the babies from Zika-affected pregnancies had congenital brain abnormalities, compared with just 5% in the Zika-unaffected pregnancies.

Further evidence emerged and the scientific community reached a consensus that Zika virus causes microcephaly in March 2016.

Microcephaly is just the tip of the iceberg

Despite the initial focus on microcephaly, it wasn’t long before doctors and researchers realised that Zika virus causes much more than just a small brain in the developing fetus. In addition to the microcephaly, the virus appeared to cause a whole list of problems, which became known as ‘congenital Zika syndrome’.

It’s important to emphasise that not all of these features will occur in all children with congenital Zika syndrome; many children will have only a few of these features.

The syndrome is best thought of as a spectrum: at one end, infants with very small brains, some of whom won’t even survive until birth. At the other end, children with just a few ‘intracerebral calcifications’ who will grow up normally, perhaps with only mild learning difficulties and the occasional seizure throughout childhood.

The abnormalities which make up ‘congenital Zika syndrome’ include:

  • Microcephaly
  • ‘Intracerebral calcifications’ – ‘calcified’ spots within the brain (a bit like the lime-scale that builds up inside your kettle)
  • ‘Lissencephaly’ – a loss of the normal undulations on the brain’s surface
  • Enlargement of the ventricles (the fluid-filled cavities within the brain)
  • Hearing loss
  • Problems with vision
  • ‘Arthrogryposis’ – contractions and twisting of joints in arms and legs
  • ‘Muscular atrophy’ – reduced muscle mass
  • Latest evidence even suggest a possible link to congenital heart disease

 

czs scans.png
Brain scans of two infants with microcephaly. In A, the dark, fluid-filled spaces within the brain are too large and there are calcifications (white streaks to the side of the dark fluid-filled spaces). In B, the syndrome is not as severe, with just a few calcifications (white specks).

Microcephaly received all the initial attention, probably because it was the most obvious and easily detectable feature. Babies born with microcephaly have an obviously small head to look at, so it’s not surprising that it was this that first got noticed. Because it’s so simple to measure – you just need a tape-measure – it was also easiest to use this feature for surveillance work (tracking the extent of the outbreak).

However, the other features of congenital Zika syndrome seem to be quite a lot more common than microcephaly. In the study from Rio de Janeiro that I mentioned above, there were only 4 cases of microcephaly among the 49 babies with ‘congenital brain abnormalities’ from Zika-affected pregnancies – microcephaly is really just the tip of the iceberg!

Other causes of birth defects

To put all this into context, it’s worth discussing briefly the other causes of birth defects. Worldwide, around 3-6% of babies are born with birth defects of some sort.

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In as many as 80% of babies born with birth defects, we are never able to identify a particular cause. However, among the babies where a cause is identified, genetic problems are the most common cause and among these, the majority are due to ‘chromosomal’ abnormalities, such as Down’s syndrome. From a study in the BMJ.

As well as genetic mutations, certain things in the environment, known as ‘teratogens’ can also cause birth defects. These ‘teratogens’ include medications, such as thalidomide and the anti-epileptic medication sodium valproate. Cigarette smoke, alcohol and cocaine are also teratogens.

A mother who gets diabetes during her pregnancy is at increased risk of having a child with birth defects, especially if her blood sugars are not well controlled. Malnutrition, particularly a lack of folic acid in the diet, can increase risk of birth defects.

Finally, there are several infectious diseases which are known to be cause birth defects. At medical school, we’re taught to be particularly wary of the ‘ToRCHeS’ diseases in the pregnant mother: Toxoplasmosis, Rubella, Cytomegalovirus (CMV), Herpes and Syphillis.

These diseases are now relatively rare in the more economically developed world, but worldwide they still affect a considerable number of pregnancies. It’s estimated that 12-40/100,000 births are affected by neonatal herpes infection and around 40/100,000 births are affected by CMV in low/middle-income countries.

In Brazil, during 2015-16 there were 2,266 cases of microcephaly which were confirmed to be a result of maternal Zika virus exposure, equivalent to around 43/100,000 births. Rates of Zika-induced microcephaly were therefore very similar to those of birth defects resulting from CMV and herpes infections.

However, what made Zika special was that it was the first infectious disease to ever cause a such a sudden increase in birth defects. The numbers of children born with microcephaly was about 15 times what it had been in previous years! Never before has such a dramatic increase in the number of congenital malformations been seen as the result of an infectious disease.

Zika is also significant for being the only virus in its family (flavivirus) and the only insect-borne virus (arbovirus) known to cause fetal malformations.

~~~~~

Next up, I’ll be writing about what the risk of congenital Zika syndrome is for a mother infected with Zika virus during her pregnancy and why we may be under-estimating the full effects of the Zika virus.

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