What’s new in the other journals?
These snippets are extracts from a monthly service called the Journal Article Summary Service. It is a service that summarises all that is new in obstetrics and gynaecology over the preceding month. If you would like to know the details of how to subscribe, please email the editor Athol Kent at firstname.lastname@example.org or visit the website http://www.jassonline.com.
Antioxidants and pre-eclampsia
In any group of low-risk nulliparous women, about 7% will develop pre-eclampsia. As the disease carries considerable maternal and fetal jeopardy, interventions to prevent its initiation or progression are being keenly sought. Vitamins that reduce oxidative stress given early in pregnancy have mixed records of success but enjoy good pathophysiological grounds to be promising candidates for prevention.
The underpinning hypothesis of the condition is that abnormal placentation leads to an inflammatory-type response with endothelial dysfunction giving rise to the clinical syndrome. The mechanisms whereby the biochemical upset leads to the maternal manifestations may be through oxidative stress, which in turn is caused by the generation of free radicals by the placental hypoperfusion. This theory is supported by the reduction of buffering anti-oxidants found in the tissues of women with pre-eclampsia so there are reasonable foundations for a randomised trial of the antioxidants vitamins C and E to prevent or alleviate the illness.
Roberts et al. (NEJM 2010;362:1282–91) conducted a carefully monitored trial of daily supplementation with 1000 mg vitamin C plus 400 iu vitamin E or placebo to 10 000 women with uncomplicated first pregnancies starting between 9 and 16 weeks of gestation. It took 5 years to complete and the endpoints were severe pregnancy-induced hypertension or evidence of organ/tissue damage in the mother or suboptimal fetal outcomes.
The results showed that supplementation did not materially affect either maternal or perinatal outcomes.
The study deserves comment because it provides point-of-entry data about a large group of US women as well as the outcomes that their compatriots can expect.
The trial itself recruited 10 000 women from a pool of 30 000 candidates who had the following characteristics:
- • a mean age of 23 years, about 5 years younger than many equivalent populations in European countries
- • an average body mass index of 25, which does not reflect the overall (USA) rate of being overweight or obese, which afflicts two-thirds of women in the that country
- • most of the participants had received formal education for 12 years
- • 15% were smokers
- • three-quarters were already taking some form of vitamin supplementation
- • their mean blood pressure at entry was 110/65.
Their obstetric outcomes were of interest too:
- • the gestational age at delivery was 39 weeks with a birthweight of 3250 g
- • 10% were born before 37 completed weeks and 3% before 32 weeks of gestation
- • perinatal mortality was approximately 12 per 1000 from 20 weeks onwards
- • the primary caesarean section rate was 25%
- • the antepartum haemorrhage rate was 2%
- • the mean hospital stay was 2 days.
Although supplementation with vitamins C and E did not prove successful the researchers completed a ‘never to be repeated’ piece of research providing intriguing statistics about the pregnancies of Middle America.
H1N1 flu and pregnancy
The 2009 influenza (H1N1 or Flu A or Swine flu) epidemic had special impact on pregnant women. Irrespective of gestational age they appear to have suffered from more profound consequences of the illness with higher morbidity and mortality than matched nonpregnant women. A report from the USA traces the severity and interventions that took place at the height of the epidemic last year (Siston et al. JAMA 2010;303:1517–25).
Although influenza (H1N1) was characterised as a self-limiting uncomplicated infection it was classified by the World Health Organization as a level 6 epidemic, the highest level of alert in June 2009, triggering widespread surveillance and reaction. Among the groups targeted for special care were pregnant women and comprehensive data were gathered from the USA on the treatment and outcomes of this cohort.
Overall, pregnant women are more at risk of the complications of H1N1 Flu and are more likely to be admitted to intensive care than nonpregnant women. Although they constitute only 1% of the US population they accounted for 5% of deaths from H1N1 Flu. The data on 800 pregnant women admitted to hospitals showed that the majority were in the second half of their pregnancy and responded well to early antiviral treatment. Most had antiviral medication initiated within 2 days of the onset of symptoms and this appears to have been effective. Also recommended are seasonal and Flu vaccines which are safe even in the first trimester. Despite possible over-reaction to the epidemic (Watson BMJ 2010;340:c1904) obstetricians must be aware of the increased risk to pregnant women and act decisively in recommending vaccinations for maternity staff as well as patients.
More breast screening data
Routine breast cancer mammography data continue to accumulate. Some are positive and some negative so it seems that the debate will run and run.
On the positive side, Duffy et al. (J Med Screening 2010;17:25–30) claim that screening in the UK works if a 20-year view is taken. If 1000 women are followed between 50 and 70 years of age, then those screened will have ‘lives saved’ compared with those not screened. About six per 1000 will have death from breast cancer prevented. They accept that there will be harms—overtreatment of false positives that turned out not to be malignant—but these are fewer (2 per 1000 over 20 years) than the lives saved so the ‘benefits of screening outweigh the harms’. It is acknowledged that their figures are at odds with other recently published records.
On the negative side, a Danish group report on the natural experiment that is ongoing in their country (Jörgensen et al. BMJ 2010;340:c1241). Two areas, Copenhagen and Funen county, introduced routine mammography screening in the early 1990s whereas the rest of the country (about 80%) did not have screening introduced. Initial results showed a decrease in deaths in the screened areas but long-term mortality rates show no difference between the 20% screened and the 80% unscreened population. All mortality rates have come down in women up to the age of 75 years, in keeping with other European countries where some nations have routine programmes and others do not. The authors say the improved statistics can more likely be explained by better treatment than by routine screening mammography.
Treatment for recurrent miscarriage
About 5% of women experience two or more miscarriages. Very few of these women have a cause identified for the failure of their pregnancies but empirically they are often treated in a subsequent pregnancy ‘in case’ they have a thrombophilia or antiphospholipid syndrome—for which there is evidence that antithrombotic therapy is useful.
Despite aspirin and low-molecular-weight heparin being safe to use in early pregnancy there is no direct proof that prescribing these drugs to treat recurrent miscarriage is beneficial. To rectify this lack of data Kaandorp et al. (NEJM 2010;362:1586–96) treated over 300 women with a history or recurrent miscarriages with aspirin alone, aspirin plus low-molecular-weight heparin, or placebo. The results yielded 60–70% live birth rates in all three groups where pregnancies were achieved so the trial was stopped on the basis of futility.
Greer (NEJM 2010;362:1630–1) quotes a Scottish study giving similar outcomes and states that antithrombotic interventions should not be advocated for the treatment of unexplained recurrent miscarriage. It remains unwise to use any therapy in pregnancy unless it can be shown, on balance, to be beneficial so this advice should be heeded.
The world of genetics has been resounding with the news of the ‘creation of life’ in The J Craig Venter Institute in the USA. Synthetic biology has always been concerned with reading genetic codes but now Gibson et al. (Science doi:10.1126/science.1190719) have succeeded in writing new code.
What they did was to take the DNA from a bacterium and modify the sequence of its strands of DNA. The modified DNA was built up to form a chromosome in a yeast cell and the synthetic chromosome was transferred back to the original bacterium whose own chromosomes had been removed. The bacterium then started making proteins dictated by the modified DNA. It was able to replicate itself and after about 30 divisions there was little to identify the original organism and a new species emerged.
Although the process depends on bacteria and yeast cells to get it going the scientists have created ‘the first self-replicating cell on the planet whose parent is a computer’. The media have had a field day, dubbing the bacterium Synthia and challenging the inventor’s intention to patent this new life-form. The ethics and financial implications are considerable.
Synthetic biology holds the promise of allowing vaccines to be produced in a fraction of the time taken at present or even producing algae with hydrocarbon-fuel-producing capacity. This latter quest is Venter’s priority, in which synthetic algae could capture carbon dioxide and turn it into a compound similar to petrol—a project that has already attracted multimillion dollar backing.
Whether Synthia is a newly created life-form, a new species or just a variation, it is clear that it has not evolved over the 3 billion years of earth’s existence and has not been required to overcome the hazards of natural selection—which is both intriguing and sobering. However the achievement is viewed, it does mark the crossing of a boundary not previously possible and asks new questions so, in that sense, it is good science.