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Preterm birth intervention.

Fully three-quarters of preterm births occur spontaneously. In situations where some predisposing factors can be identified, there are primary, secondary and neonatal interventions available to reduce mortality and morbidity. Individualised maternal care, the use of steroids antenatally, surfactant postnatally--together with improved neonatal care--make a difference. The secondary manoeuvres of tocolysis and prolongation of gestation are less well evidence based but appear better researched than primary prevention. On this score, there is new evidence about repeat courses of antenatal steroids. It has been established that their use does reduce mortality rates, respiratory distress and intraventricular haemorrhage but that weekly courses are associated with reduced birth weight and increased numbers of small-for- gestational-age infants. These side-effects together with developmental concerns have contraindicated serial administration of these agents. However, less clear is the use of a 'rescue' course under specific circumstances. Garite et al. (AJOG 2009; 200: 248-250) looked at the outcomes of infants whose mothers received steroids but who did not deliver within 2 weeks of this initial management. Where the pregnancy was <30 weeks gestation, membranes were intact and, in the obstetrician's opinion, delivery was imminent--a second rescue course or placebo was administered.

They found the rescue course to be beneficial in terms of neonatal outcomes without detrimental effects of low birth weight, growth restriction or reduced head circumferences.

One of the few primary preventive measures with potential is the use of progesterone in high-risk situations (Tita and Rouse, AJOG 2009; 200: 219-224). There are two types of progesterone in clinical practice:

Natural progesterone. Doses ranging from 90 mg to 400 mg of natural progesterone per day are administered as a vaginal gel from mid-pregnancy. The vaginal route excludes the hepatic first-pass effects, and it appears that the anatomical proximity to the uterus also has dose-related benefit. There are very few side-effects of sleepiness, fatigue or headache which can occur with oral use.

17-alpha-hydroxyprogesterone. This is a synthetic progesterone given in doses from 25 mg to 1 000 mg by intramuscular injection in schedules from weekly to thrice weekly. Side-effects, although common, are mild and are restricted to the injection sites. There are no reports of genital anomalies or gender-role alterations in children up to 4 years of age.

The indications for the use of progesterone are:

* History of preterm birth. Women with a history of spontaneous preterm birth have been incorporated in progesterone/placebo trials and the results have been promising. Positive outcomes of longer gestation, higher birth weight with lower mortality and morbidity rates in up to 50% of cases are reported with singleton pregnancies.

* Short cervix. Clinical trials have been published on the use of progesterone in women found to have a short cervix on routine screening. Those with a cervix <15 mm in length and who received progesterone had superior outcomes to those in the placebo arms in terms of delay in delivery and neonatal outcomes.

* Arrested preterm labour. Studies using progesterone after the inhibition of preterm labour are not robust. Some encouraging outcomes are reported but more convincing studies are required before routine clinical practice can be advised.

* Multiple pregnancy. Previous trials have found no advantages in the use of progesterone in multiple pregnancies. It therefore comes as no surprise that the latest study confirms these findings. The Study of Progesterone for the Prevention of Preterm Birth in Twins (STOPPIT) research in the UK was a placebo-controlled trial using 90 mg of progesterone daily per vaginam from 24 weeks (Norman et al. Lancet 2009; 373: 2034-2040). These pregnancies constituted 1.5% of all their deliveries but had stillbirth rates of 15 per 1 000 and neonatal mortality rates of 20 per 1 000, so improvements through the prolongation of gestation would be welcome. There were no improved outcomes in terms of fetal or neonatal wellbeing, so progesterone cannot be advised for use in uncomplicated twin pregnancies.

Athol Kent

Editor
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Title Annotation:THE BEST OF THE REST: A summary of some of the best recent landmark articles from the international journals
Author:Kent, Athol
Publication:South African Journal of Obstetrics and Gynaecology
Article Type:Editorial
Geographic Code:6SOUT
Date:Aug 1, 2009
Words:643
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