“Birth asphyxia” (lack of oxygen and blood flow to the baby’s brain) is a label and convenient explanation given to parents by paediatricians when a baby is delivered with low Apgar scores, requires resuscitation, or if neonatal fits occur. The second diagnosis that often follows is hypoxic ischaemic encephalopathy.
However, umbilical arterial blood cord gases, when available, seldom confirm significant ‘asphyxia’, hypoxia ( low oxygen) by not showing a severe metabolic acidosis (too much acid in your blood). Even if confirmed, this does not indicate the timing of the metabolic disturbance, or its cause. But acute severe intrapartum (in labour) hypoxia is commonly presumed, and intrapartum cardiotocographic (CTG) tracings are often retrospectively interpreted as supporting an intrapartum hypoxaemic situation.
The introduction of “no win – no fee” litigation in Australia and the very high legal quantum in cerebral palsy cases (millions of dollars) was a major influence on the rapid escalation of obstetricians medical insurance rates and the practice of defensive obstetrics contributing to a rise in caesarean delivery rates over more recent years. A small group of plaintiff so called “expert” witnesses could be reliably commissioned for a fee to explain that the “birth asphyxia” was acute, recognisable and probably preventable with earlier delivery. This iniquitous situation led to a consensus statement to better define the criteria for elucidating a causal relation between acute intrapartum events and cerebral palsy (MacLennan et al BMJ 1999;319:1054-9).
Modern Prof. Alistair MacLennan is revolutionising the understanding of many cases of cerebral palsy where currently about a third of cerebral palsy cases have one of many rare genetic variants that cause cerebral palsy through various metabolic pathways. A systematic review and meta-analysis of 13 small studies using exome sequencing (examining that part of human’s genes responsible for protein synthesis) found a likely causative genetic variations in more than 30% of patients (Gonzalez Mantilla et al JAMA Pediatr 2023;177:472-8).
Now a study investigating a Chinese cohort of more than 1,500 children with cerebral palsy (using mostly exome sequencing) showed a diagnostic rate of 25% (Wang et al Nat Med 2024 doi 10.1038/s41591-024-02912-z). This study was large enough to allow a sub-analysis of all those who had been clinically labelled as having ‘asphyxia’ at birth. The genetic diagnostic rate of children labelled at birth with perinatal asphyxia was much higher than the rate in children without asphyxia (P=0.0033). This suggests that the genetic anomalies were often responsible for the poor condition of the child at birth and the subsequent cerebral palsy.
It is important to note that as the sophistication of genomic screening improves, the diagnostic rates of causative genetic variations in cerebral palsy is increasing. Whole genome screening appears more productive than exome screening for single nucleotide and copy number variants and mitochondrial mutations. Mosaicism is being detected and, in each cohort described, there are many rare variants of unknown significance (10-30%) which may be pathogenic.
So, what is the message…
If significant neonatal resuscitation is required teh obstetrician:
- collect and record arterial cord gases
- send the placenta to histology as placental pathology such as chorioamnionitis is informative
- obtain parental consent and paediatric collaboration to send an infant blood sample for whole genome sequencing. It may help understand causation and direct treatment.
This article is an adaptation of an article in RANZCOG JASS February 2024 email written by Prof. Alistair MacLennan. It is published on my website with Prof. MacLennan’s permission
