The ORACLE Children Study

Prematurity in babies

Every year, about one in eight babies, or 80,000 a year, are born prematurely (before 37 weeks) in the UK. Prematurity is the most common reason for babies to die in the first month after birth. Premature babies who survive are more likely to have short-term problems such as breathing and feeding difficulties and infections. They may also have longer-term problems with functioning, behaviour and learning. Whatever happens, having a premature baby is often a traumatic and upsetting experience for women and their families.

Research, like the ORACLE Trial and Children Study, to try to find the best ways to treat premature labour and reduce short and long term problems is very important.

Results of the original ORACLE Trial: women whose waters broke early

The antibiotic erythromycin seemed to be helpful for babies in the short-term. In the Erythromycin Group, babies were more likely to stay in the womb longer, and were less likely to need help with breathing, to have infections, or to have an abnormal brain scan.

The other antibiotic, co-amoxiclav, also increased the time babies stayed in the womb and reduced their need for oxygen. But the trial discovered an important problem with co-amoxiclav. There was a small increase in the number of babies born with a rare, sometimes very serious bowel condition called necrotising enterocolitis (NEC) to women with broken waters who were in the Co-amoxiclav Group. Because of its large size and design, the ORACLE trial was able to identify this rare risk, even though co-amoxiclav had previously been routinely used in pregnancy without reported problems.

 

Results of the original ORACLE Trial: women who had signs of going into labour early but didn’t have broken waters

The antibiotics used in the trial (erythromycin and co-amoxiclav) did not have any short-term effects (good or bad) for babies born to women with signs of early labour without broken waters.

What was measured in the ORACLE Children study

 

The questionnaire aimed to find out about children’s health, wellbeing and educational attainment. These are areas where there may sometimes be problems in any baby born early.

Functioning: The questionnaire asked about the child’s vision, hearing, speech, walking, dexterity (using their hands), emotions, pain, and aspects of thinking such as learning and remembering. Children were classed by researchers as having a ‘functioning’ difficulty if parents reported that children had any difficulties at all in any of these areas. As a result, ‘functioning’ difficulties can range from the child having minor difficulties (things like wearing glasses, requiring a hearing aid, not always being completely happy, or having some difficulty when trying to solve day to day problems), to more severe problems (such as being unable to walk, see, hear or speak, or having severe difficulties with thinking and remembering).

Health problems and behaviour: The questionnaire asked about chest symptoms, hospital admissions, fits/seizures, and specific medical conditions (including cerebral palsy), as well as behaviour, emotions, hyperactivity, and relationships with others.

Educational attainment: The National Curriculum (Key Stage 1) tests for reading, writing and maths, which are undertaken by children aged 7 in England, were used to assess how well the children were doing at school

Results of the ORACLE Children Study: women whose waters broke early

•    For mothers whose waters broke early, having antibiotics (erythromycin or co-amoxiclav) in the ORACLE trial did not make any difference to their child’s functioning, behaviour, most medical conditions, or Key Stage 1 results.

•    Parents were specifically asked about bowel problems because of the findings of the ORACLE trial (mentioned earlier). The Children Study found that in the Co-amoxiclav Group, there was a small increase in the number of children with bowel problems (2.7%) compared with those who were not given co-amoxiclav at all (1.6%). However, the bowel problems in children reported by these parents were mostly not serious (such as constipation).

There is, therefore, little evidence of long term effects (good or bad) for children of women who had antibiotics when their waters broke early, but there is a need for caution about use of co-amoxiclav in this situation.

 

Results of the ORACLE Children Study: women who had signs of going into labour early without broken waters.

•    For mothers who had signs of early labour without broken waters, having antibiotics (erythromycin or co-amoxiclav) did not make any difference to their child’s behaviour, most medical conditions, or Key Stage 1 results.

•           Functioning problems are common in children whose mothers showed signs of early labour without broken waters. It is normal for about 40% (4 in every 10) children born in this situation to have some kind of functioning problem. Being in the Co-amoxiclav Group did not make any difference to children’s functioning. However, in the Erythromycin Group, there were slightly more children with a ‘functioning’ problem compared with those whose mothers who did not have any erythromycin. These functioning problems included very mild difficulties (see “What was measured in the ORACLE Children Study” box), and most of the functioning problems reported by parents were minor

It was found that cerebral palsy in children was somewhat more common when women with signs of early labour did have antibiotics. In the Erythromycin Group, 3.3% of children had cerebral palsy compared with 1.7% of children whose mothers who did not have erythromycin. In the Co-amoxiclav Group, 3.2% of children had cerebral palsy compared with 1.9% of children whose mothers who did not have any co-amoxiclav 

Looking at it in more detail, the increase in the number of children with cerebral palsy was clearest in the group of women who had both antibiotics (co-amoxiclav and erythromycin together). In this group, 4.4% of children had cerebral palsy, though even here the numbers with cerebral palsy remain quite small.

Summary

The ORACLE trial has shown that the babies of women who had PPROM and received erythromycin had an improved outcome compared to those who did not have PPROM, including increasing the time to delivery, reduction of infection and improved respiratory function. The ORACLE Children Study however revealed that these early improved outcomes do not make a substantial difference to the children’s health and development long-term.
However, in those women who did not have PPROM, the study suggested that there may be a small increased risk of functional impairment and cerebral palsy in the children of women who took antibiotics because of early premature labour.
These findings do not mean that antibiotics are unsafe for use in pregnancy. Pregnant women showing signs of infection should be treated promptly with antibiotics

Ref:

http://www.le.ac.uk/oraclechildren 

http://www.rcog.org.uk/what-we-do/campaigning-and-opinions/statement/rcog-statement-oracle-children-study

http://www.rcog.org.uk/womens-health/clinical-guidance/preterm-prelabour-rupture-membranes-green-top-44

http://www.rcog.org.uk/womens-health/clinical-guidance/prevention-early-onset-neonatal-group-b-streptococcal-disease-green-