Interventions during pregnancy and childbirth for preventing cerebral palsy: an overview of Cochrane reviews

What is the issue?

Cerebral palsy is a term that includes a group of conditions affecting people's ability to move, and is the most common physical disability in childhood. Cerebral palsy is usually due to events before, during, or after childbirth that lead to injury in babies' developing brains. There is no single cause of cerebral palsy. For many children, the cause of cerebral palsy is unclear, however, there are many known risk factors. The biggest risk factor is birth before 37 weeks of pregnancy (preterm birth). Other risk factors for mothers include some medical conditions (including thyroid problems), abnormalities of the placenta, pre-eclampsia (high blood pressure and protein in the urine), and some bacterial and viral infections. For babies, risk factors include congenital and genetic abnormalities, having a low birthweight or growth restricted as a fetus, being a twin or triplet, some infections, and prolonged loss of oxygen during birth.

Why is this important?

As there are different risk factors and causes for cerebral palsy, it is likely that various different interventions (treatments) may be needed to prevent cerebral palsy by reducing risk factors. This overview summarises the evidence about preventing cerebral palsy from Cochrane reviews of interventions during pregnancy and childbirth.

What evidence did we find?

We searched for evidence on 7 August 2016. We identified 15 Cochrane reviews that assessed interventions during pregnancy or childbirth that reported on cerebral palsy, with information from 27 randomised controlled trials involving 32,490 children. The reviews were all high quality, but the quality of the evidence about cerebral palsy ranged from very low to high.

The interventions assessed were for treating mild to moderate hypertension (two reviews), treating pre-eclampsia (two reviews), diagnosing or preventing fetal compromise (when the unborn baby may not be well) during labour (one review), preventing preterm birth (four reviews), maturing or protecting babies' lungs or brains before preterm birth (five reviews), and managing fetal compromise of preterm babies (one review).

We found high-quality evidence that one intervention was effective for cerebral palsy prevention: preterm children born to mothers who received magnesium sulphate before birth were less likely to develop cerebral palsy than children whose mothers received a placebo (five trials, 6145 children).

We found moderate-quality evidence that two interventions were probably ineffective, and could cause harm: (i) children born to mothers who had received antibiotics for preterm labour when their waters had not broken were more likely to develop cerebral palsy than children whose mothers did not receive antibiotics (one trial, 3173 children); and (ii) preterm children who were born immediately when there was suspected fetal compromise were more likely to develop cerebral palsy than those for whom birth was postponed (one trial, 507 children).

We found moderate-quality evidence that there was no clear difference in the chance of children to develop cerebral palsy whether their mothers received one or more courses of corticosteroids before preterm birth (four trials, 3800 children).

There was low-quality evidence as to whether the other interventions prevented, increased, or had no impact on cerebral palsy, although we did find that children born to mothers who received corticosteroids to help mature their lungs before preterm birth were potentially less likely to develop cerebral palsy than those born to mothers who received a placebo (five trials, 904 children).

What does this mean?

We identified one intervention that was effective in preventing cerebral palsy (magnesium sulphate before preterm birth), two that appeared to cause harm (preventive antibiotics for women in preterm labour when their waters have not broken, and immediate birth for preterm babies with suspected compromise), and one that did not appear to make a clear difference (more than one course of corticosteroids before preterm birth). For the other interventions assessed, there was not enough evidence to reach any conclusions. Further good quality randomised controlled trials, assessing interventions that might impact cerebral palsy risk factors, with long-term follow-up to measure cerebral palsy, are needed. We identified over 60 other Cochrane reviews that may provide more information in the future.

Authors' conclusions: 

This overview summarises evidence from Cochrane reviews on the effects of antenatal and intrapartum interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians and consumers to aid decision-making and evidence translation. We recommend that readers consult the included Cochrane reviews to formally assess other benefits or harms of included interventions, including impacts on risk factors for cerebral palsy (such as the reduction in intraventricular haemorrhage for preterm babies following exposure to antenatal corticosteroids).

Magnesium sulphate for women at risk of preterm birth for fetal neuroprotection can prevent cerebral palsy. Prophylactic antibiotics for women in preterm labour with intact membranes, and immediate rather than deferred birth of preterm babies with suspected fetal compromise, may increase the risk of cerebral palsy. Repeat doses compared with a single course of antenatal corticosteroids for women at risk of preterm birth do not clearly impact the risk of cerebral palsy.

Cerebral palsy is rarely diagnosed at birth, has diverse risk factors and causes, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane reviews assessing antenatal and intrapartum interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of interventions addressing risk factors for cerebral palsy, and consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design, and aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data, to focus research efforts on prevention.

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Background: 

Cerebral palsy is an umbrella term encompassing disorders of movement and posture, attributed to non-progressive disturbances occurring in the developing fetal or infant brain. As there are diverse risk factors and causes, no one strategy will prevent all cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for their contribution to prevention.

Objectives: 

To summarise the evidence from Cochrane reviews regarding the effects of antenatal and intrapartum interventions for preventing cerebral palsy.

Methods: 

We searched the Cochrane Database of Systematic Reviews on 7 August 2016, for reviews of antenatal or intrapartum interventions reporting on cerebral palsy. Two authors assessed reviews for inclusion, extracted data, assessed review quality, using AMSTAR and ROBIS, and quality of the evidence, using the GRADE approach. We organised reviews by topic, and summarised findings in text and tables. We categorised interventions as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm or of lack of effectiveness); probably ineffective (moderate-quality evidence of harm or of lack of effectiveness); and no conclusions possible (low- to very low-quality evidence).

Main results: 

We included 15 Cochrane reviews. A further 62 reviews pre-specified the outcome cerebral palsy in their methods, but none of the included randomised controlled trials (RCTs) reported this outcome. The included reviews were high quality and at low risk of bias. They included 279 RCTs; data for cerebral palsy were available from 27 (10%) RCTs, involving 32,490 children. They considered interventions for: treating mild to moderate hypertension (two) and pre-eclampsia (two); diagnosing and preventing fetal compromise in labour (one); preventing preterm birth (four); preterm fetal maturation or neuroprotection (five); and managing preterm fetal compromise (one). Quality of evidence ranged from very low to high.

Effective interventions: high-quality evidence of effectiveness

There was a reduction in cerebral palsy in children born to women at risk of preterm birth who received magnesium sulphate for neuroprotection of the fetus compared with placebo (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.54 to 0.87; five RCTs; 6145 children).

Probably ineffective interventions: moderate-quality evidence of harm

There was an increase in cerebral palsy in children born to mothers in preterm labour with intact membranes who received any prophylactic antibiotics versus no antibiotics (RR 1.82, 95% CI 0.99 to 3.34; one RCT; 3173 children). There was an increase in cerebral palsy in children, who as preterm babies with suspected fetal compromise, were born immediately compared with those for whom birth was deferred (RR 5.88, 95% CI 1.33 to 26.02; one RCT; 507 children).

Probably ineffective interventions: moderate-quality evidence of lack of effectiveness

There was no clear difference in the presence of cerebral palsy in children born to women at risk of preterm birth who received repeat doses of corticosteroids compared with a single course (RR 1.03, 95% CI 0.71 to 1.50; four RCTs; 3800 children).

No conclusions possible: low- to very low-quality evidence

Low-quality evidence found there was a possible reduction in cerebral palsy for children born to women at risk of preterm birth who received antenatal corticosteroids for accelerating fetal lung maturation compared with placebo (RR 0.60, 95% CI 0.34 to 1.03; five RCTs; 904 children). There was no clear difference in the presence of cerebral palsy with interventionist care for severe pre-eclampsia versus expectant care (RR 6.01, 95% CI 0.75 to 48.14; one RCT; 262 children); magnesium sulphate for pre-eclampsia versus placebo (RR 0.34, 95% CI 0.09 to 1.26; one RCT; 2895 children); continuous cardiotocography for fetal assessment during labour versus intermittent auscultation (average RR 1.75, 95% CI 0.84 to 3.63; two RCTs; 13,252 children); prenatal progesterone for prevention of preterm birth versus placebo (RR 0.14, 95% CI 0.01 to 3.48; one RCT; 274 children); and betamimetics for inhibiting preterm labour versus placebo (RR 0.19, 95% CI 0.02 to 1.63; one RCT; 246 children).

Very low-quality found no clear difference for the presence of cerebral palsy with any antihypertensive drug (oral beta-blockers) for treatment of mild to moderate hypertension versus placebo (RR 0.33, 95% CI 0.01 to 8.01; one RCT; 110 children); magnesium sulphate for prevention of preterm birth versus other tocolytic agents (RR 0.13, 95% CI 0.01 to 2.51; one RCT; 106 children); and vitamin K and phenobarbital prior to preterm birth for prevention of neonatal periventricular haemorrhage versus placebo (RR 0.77, 95% CI 0.33 to 1.76; one RCT; 299 children).

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