Cerebral palsy   Antibiotics in Pregnancy

Cerebral palsy link to antibiotics given during premature birth

Giving antibiotics to pregnant women going into premature labour increases the risk of cerebral palsy in the child, research has found.

Rebecca Smith, Medical Editor
18 Sep 2008

Children born to mothers given a combination of two antibiotics in an attempt to stop them giving birth prematurely had an almost three fold higher risk of developing cerebral palsy, a long term study of more than 4,000 pregnant women found.

The drugs each increased the risk when given singly but to a lesser degree, the Oracle study carried out by the University of Leicester and others found.

Children whose mothers had the antibiotics were also more likely to have problems such as having to wear glasses, struggling to walk around the block and difficulties with day to day problem solving at age seven.

The results only apply to women who went into premature labour but whose waters had not broken and who had no obvious signs of infection.

It was thought that a undetectable infection could have started the labours early and doctors theorised that giving antibiotics would clear the infection and stop a premature birth.

The Oracle study randomly assigned women going into labour to have the antibiotics erythromycin, Co-amoxiclav, both drugs together, or a double dummy drug. After seven years the children were followed up and in those children born to mothers who received both drugs, 25 had cerebral palsy or 4.4 per cent of the group compared with 12 with cerebral palsy or 1.6 per cent of those born to mothers who received dummy drugs.

Of the children born to mothers who had erythromycin 42.3 per cent had some functional problems compared to 38.3 per cent who did not have erythromycin, which equates to an 18 per cent increased risk.

Over 4,000 women involved in the study were asked to be kept informed of the results and have received letters but those whose children have problems will not know if they received the real antibiotics or the dummy drug unless they contact the researchers.

A helpline has also been set up.

Experts said there is no risk to pregnant women taking antibiotics if they have an infection and in those cases the drugs can be life saving.

But doctors should not prescribe antibiotics for women with no sign of infection when they go into premature labour and the Department of Health has written to those in the field to inform them of the results.

It is not thought that the drugs are damaging the child rather that they are stopping the premature labour but failing to clear an infection so the child remains in a 'toxic environment' for longer.

Another group of women who went into premature labour but whose waters had broken and received antibiotics showed no harmful affects.

The results were a surprise to the researchers who were expecting to find that the short-term benefits of giving erythromycin would be translated into long-term benefits for the children.

It is thought that doctors have already stopped prescribing antibiotics in these situations.

In an accompanying editorial in The Lancet, Prof Philip Steer, of Chelsea and Westminster Hospital in London and Dr Alison Bedford Russell at Warwick Medical School, said: "The lessons to be learned seem clear; contrary to popular opinion (might as well give them, they don't do any harm), antibiotics are not risk-free. There are good reasons not to give them in association with threatened preterm labour unless there is clear evidence of infection."


The Lancet: ORACLE studies

New data to inform clinical practice around preterm labour

Long-term follow-up data on the effects of antibiotics in pregnant women experiencing premature labour and the developmental effects on their children were published by The Lancet on Sept 18, 2008.
The original ORACLE trial published in 2001 investigated the effect of two antibiotics given around preterm labour. The ORACLE follow-up findings have important implications for the clinical management of pregnant women experiencing preterm birth, and were presented at a press conference on Sept 16, 2008.

ORACLE I: 2008
Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial
S Kenyon, K Pike, DR Jones, P Brocklehurst, N Marlow, A Salt, DJ Taylor - (DOI: 10.1016/S0140-6736(08)61202-7)
Full Text

Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial
S Kenyon, K Pike, DR Jones, P Brocklehurst, N Marlow, A Salt, DJ Taylor - (DOI: 10.1016/S0140-6736(08)61203-9)
Full Text

A Comment also published on Sept 18, 2008, assesses the two ORACLE papers:
Antibiotics in preterm labour­the ORACLE speaks
AR Bedford Russell, PJ Steer - (DOI: 10.1016/S0140-6736(08)61248-9)
Full Text