Direct injection of corticosteroids into the fetus compared with injection into the mother for improving fetal outcomes when the mother is at risk of preterm birth

What is the issue?

Babies born preterm (before 37 weeks of pregnancy) are at risk of dying, having bleeding into their brain and problems with their breathing because their lungs are not fully developed. Corticosteroid treatment given to the mother before early birth has been shown to be effective in preventing these problems and has become standard care in many countries. The common method of giving corticosteroid is by injecting into the mother's muscles. The corticosteroid treatment then transfers across the placenta (known as transplacental transfer) to the fetus. This treatment has its own risks, such as reducing fetal growth and brain development as well as increasing the baby's risks of diseases such as diabetes and high blood pressure. Injecting corticosteroid directly into the fetus is feasible with ultrasound guidance.

Why is this important?

Injecting corticosteroid directly into the fetus, instead of injecting into the mother's muscles, may prevent the risk of increased blood pressure, increased blood glucose levels, and susceptibility to sepsis in the mother. It may also reduce the amount of corticosteroid needed. However, it carries a risk of infection of the uterus and fetal injury, and may cause preterm labour and birth. We found that there have been no studies assessing the benefits and harms of direct injection into the fetus compared with injection into the mother.

What evidence did we find?

We searched for evidence on 25 October 2017 and we did not find any completed randomised controlled trials that assess the benefits and harms of direct injection of corticosteroid into the fetus compared with injection into the mother, for women who are at risk of preterm birth. We found two studies, but one was not a randomised controlled trial, and in the other study the methods were unclear, so we have contacted the study authors for further information.

What does this mean?

We need further studies to assess the effects of injecting corticosteroid directly to the fetus compared with injecting into the mother's muscles. The babies in these trials need to be followed up over a long period so that we can monitor the effects of corticosteroids on childhood development, including impairments or disabilities such as cerebral palsy. We need good-quality randomised trials, to establish if one method is better than the other.

Authors' conclusions: 

The available clinical studies carried out so far on animals and human have shown that direct intramuscular injection of corticosteroid into the fetus under ultrasound guidance is feasible, but data on health outcomes are lacking. Uncertainty therefore persists as to which method could provide better efficacy and safety. Randomised controlled trials are required focusing on the benefits and harms of transplacental versus direct fetal corticosteroid treatment. Until the uncertainties have been addressed, it is advisable to stay with the current standard of antenatal transplacental maternally-administered corticosteroid treatment.

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Background: 

Despite major advances in medical technology, the incidence of preterm birth remains high. The use of antenatal corticosteroid administered transplacentally, by intramuscular injection to women at risk of preterm birth, has reduced the incidence of respiratory distress syndrome and increased the survival rates of preterm infants. However, this intervention also comes with its own risks and side effects. Animal studies and early studies in pregnant women at risk of preterm birth have reported the use of an alternative route of administration, by direct intramuscular injection of corticosteroid into the fetus under ultrasound guidance, in an attempt to minimise the side-effect profile. Direct fetal corticosteroid administration may have benefits over maternal administration in terms of safety and efficacy.

Objectives: 

To assess if different routes of corticosteroid administration (maternal versus direct fetal) have effects on health outcomes for women and their babies.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (25 October 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 October 2017) and reference lists of retrieved studies.

Selection criteria: 

Randomised controlled trials comparing maternal with direct fetal routes of antenatal corticosteroid administration in women at risk of preterm birth.

Data collection and analysis: 

The two review authors independently assessed study eligibility. In future updates of this review, at least two review authors will extract data and assess the risks of bias in included studies. We will also assess the quality of the evidence using the GRADE approach.

Main results: 

We did not identify any eligible randomised controlled trials to include in this review.

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