Birth weight. In recent long-term followups of babies weighing less than 1,000 g at birth, researchers found that 24% to 25% of subjects had major neurologic abnormalities, 37% to 42% exhibited subnormal scores (less than 70) on the Bayley Mental Developmental Index, and 29% demonstrated subnormal scores (again, less than 70) on the Psychomotor Developmental Index.12,13
Fetal growth. Studies also appear to show a cause-and-effect relationship between chronic placental insufficiency leading to intrauterine growth restriction and cerebral palsy. In such cases, the already-affected fetus may exhibit intrapartum signs that prompt intervention, based on the assumption that the underlying cause of the fetal distress is still reversible.5 This decision to intervene in the presence of presumable signs of fetal distress may later be erroneously considered evidence of an acute intrapartum event.
Increased rates in multiple births. Multiple pregnancy offers a useful example of how preterm birth, low birth weight, and aberrant fetal growth act in concert to increase cerebral palsy rates.14
Laplaza et al15 compiled data from 11 cerebral palsy series and found a 7.4% average prevalence of twins among cerebral palsy cases. Studies from England and the United States have shown a similar prevalence of cerebral palsy in twins compared with singletons: 7.4 versus 1 in 1,000 survivors to 1 year9 and 6.7 versus 1.1 in 1,000 survivors to 3 years.16
The prevalence of cerebral palsy in triplets exceeds that of twins and of singletons: 28 versus 7.3 versus 1.6 per 1,000 survivors to 1 year17 and 44.8 versus 12.6 versus 2.3 per 1,000 survivors to age 3.18 Japanese data confirm this trend in quadruplets, noting incidence rates of 11.1%, 3.1%, and 0.9% for quadruplets, triplets, and twins, respectively.19 Taken together, the cerebral palsy prevalence among multiples exhibits an exponential relationship with plurality.20
Multiple and singleton pregnancies have similar risks for cerebral palsy until term. However, while the risk for singletons decreases with advanced gestational age and increased birth weight, the risk for multifetal pregnancies increases. The excess risk for cerebral palsy in twins beyond 37 weeks may be attributed to the likelihood that “term” occurs earlier in twins. In addition, multiple pregnancy offers unique “opportunities” for cerebral palsy, such as monochorionicity, twin-twin transfusion syndrome, single fetal demise, and anomalies.14,20
In the United States, an estimated 8% increase in the prevalence of cerebral palsy is due solely to the rise in multiple births.
Technology’s unexpected role
It might be expected that modernized medical assessment and treatment would decrease the frequency of cerebral palsy. Two examples suggest the opposite.
Electronic fetal monitoring. Prompt cesarean section in cases of nonreassuring fetal heart-rate pattern does not decrease the rate of intrapartum brain damage. Nor has the implementation of electronic fetal monitoring during labor changed the incidence of cerebral palsy21—mainly because such monitoring has an extremely high false-positive rate.5 In fact, except for the unequivocal normal pattern and the unmistakable pattern associated with potentially damaging acidemia (i.e., absent variability in the presence of persistent late or variable decelerations or bradycardia), the entire range of fetal heart-rate patterns is subject to wide interpretation among clinicians as to appropriateness of intervention.5
Assisted reproductive technology. A significant proportion of multiple births result from assisted reproductive technology; these are rightly termed iatrogenic multiple pregnancies.22 The estimated rates of cerebral palsy are significantly lower after spontaneous conception (2.7 per 1,000 neonates) than after the transfer of 3 embryos (16.86 per 1,000) or 2 embryos (8.77 per 1,000), or after the transfer of 3 embryos with a reduction of triplets to twins (10.31 per 1,000).23 Kiely and colleagues24 estimated that, in the United States, there is an 8% increase in the prevalence of cerebral palsy due solely to the rise in multiple births. This increase in multiple births is largely the result of infertility treatment.
Goals of research
At present, we are unable to identify the point at which brain damage becomes irreversible during pregnancy. Signs of fetal compromise, as in the case of suspected intrauterine growth restriction, are not sufficient to indicate earlier delivery, because it is unclear whether such a policy reduces the incidence of cerebral palsy without amplifying the risks of prematurely born infants.
One of the major difficulties in correlating events during pregnancy, labor, and early neonatal life with future outcome is that brain damage is usually diagnosed remotely from the event. We also lack qualitative and quantitative means of assessing the fetal brain at a cellular level.
Overcoming these obstacles would require the ability to obtain dysfunction signals at a subcellular level using noninvasive means. Use of various magnetic resonance imaging methods for brain assessment of neonates at risk for cerebral palsy is under investigation. The potential of such neuroimaging to differentiate reversible and irreversible antepartum brain damage appears promising.