What’s new in the other journals?
Opioid addiction in pregnancy
Opioid addiction in pregnancy requires a comprehensive approach to improve maternal and neonatal outcomes. The use of methadone compared with no treatment or with medication-assisted withdrawal has proved successful but may leave the neonate with a withdrawal syndrome. This is correctly called Neonatal Abstinence Syndrome, which itself is dangerous with hyperirritability, weight loss and sometimes seizures that can be fatal.
The search for alternatives to methadone has led to a study comparing it with buprenorphine antenatally (Jones et al. N Engl J Med 2010;363:2320–31). Buprenorphine was similar to methadone in efficacy in controlling opioid intake in the mother but was superior in reducing the severity of the neonatal abstinence syndrome with the baby requiring less sedation for a shorter duration and fewer days in intensive care. The authors recommend its consideration as first-time treatment for opioid addiction in pregnancy.
Induction for growth restriction
Growth restriction is associated with poor obstetric outcomes, especially if it occurs early in the third trimester or in combination with obstetric disorders. However, it is also diagnosed at term where there may be no association with obstetric problems and this is precisely where clinical management dilemmas can arise. To try to address this issue a multi-hospital trial was conducted in the Netherlands to see if induction or expectant surveillance gave better results (Boers et al. BMJ 2010;341:c7087).
The Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT) took 4 years to recruit 600 women in 50 hospitals and allocated them to induction or expectant monitoring until spontaneous delivery. Monitoring included daily fetal movement counts, twice weekly cardiotocograph tracings and ultrasound plus measuring blood pressure, proteinuria, liver and renal function and full blood counts. About half of the pregnancies being watched needed induction but the rest had no worse outcomes than those allocated to induction.
The conclusion that can be drawn is that monitoring is as safe as induction but this has to be considered in the context of considerable resources, the inexact science of the true detection antenatally of growth restriction plus our present lack of any test to predict term stillbirths. The trial is a vote of confidence for high level surveillance but adds little to our understanding of the causes of growth restriction or its more accurate diagnosis.
Antenatal supplement outcomes
The value of supplements to pregnant women is much debated. Well-nourished mothers-to-be do not need prenatal supplements and indeed additional iron may be detrimental. Conversely in deprived areas, like Nepal, where micronutrients are in short supply there are advantages in adding antenatal supplements to the diet.
A study by Christian et al. (JAMA 2010;304:2716–23) over 7 years has shown that Nepalese children whose mothers received iron, folic acid and zinc supplements had superior intellectual and motor function skills compared with children whose mothers had been allocated to the control group in pregnancy. The researchers conclude that routine supplementation should be given to all antenatal clinic attendees in areas of high iron deficiency prevalence.
Vitamin A after delivery does not offer an advantage even in developing countries, having no effect on morbidity or mortality in seven different trials so the use of supplements is by no means a panacea (Gogia and Sachdev Int J Epidemiol 2010;39:1217–26).
In vitro fertilisation embryo transfer
It is 30 years since the first in vitro fertilisation baby was delivered and we are still learning about the technique. Initially, multiple embryos were transferred because it seemed the more that were introduced the better the chances of a pregnancy. It also reduced costs and risks in the woman as ovarian stimulation, egg harvesting and transfers were only carried out once. It was not originally understood that more embryos yielded a selection of more promising specimens and that cryopreservation and subsequent implantations gave good results.
The obstetric, financial, neonatal and social costs of twins or higher order multiple births were not taken into account whereas now these are weighed up when overall budgeting is calculated. It seems now that there is—statistically at least—a solution to the problem of single versus multiple transfers. McLernon et al. (BMJ 2011;341:c6945) reviewed the latest data and found that even two embryos transferred raised the risk of multiple births and obstetric complications above acceptable limits while single transfers lowered success rates considerably. However, transferring one embryo while freezing another for subsequent introduction after an unsuccessful first attempt, gave no loss in successful outcomes while reducing multiple pregnancy, prematurity and low birthweight delivery rates almost to normal.
This approach is logical but it has been slow to catch on, possibly because of ‘upfront’ costs, national public funding of assisted reproduction programmes or even national characteristics (Templeton BMJ 2011;341:c7083). Japan and Australia lead the way—with Sweden, Finland, Belgium and the Netherlands high on the list of those adopting this pragmatic approach. The USA is at the bottom of the list.
Fibroids in pregnancy
Fibroids are estimated to be present in 3% of pregnancies. Routine ultrasound in midpregnancy will detect the presence of fibroids but their significance on outcomes is unknown.
To shed light on the situation, Stout et al. followed up over 60 000 pregnancies and matched subsequent developments to the presence or absence of fibroids (Obstet Gynecol 2010;116:1056–63). Overall those women with fibroids had less optimal outcomes with results as follows (adjusted odds ratios with 95% CI): breech presentation 1.5 (1.3–1.9), placenta praevia 2.2 (1.5–3.2), caesarean section 1.2 (1.1–1.4), placental abruption 2.1 (1.4–3.0), preterm rupture of membranes 1.3 (1.0–1.7), preterm delivery <37 weeks 1.5 (1.3–1.8), preterm delivery <34 weeks 1.4 (1.0–1.8), intrauterine death 2.6 (1.5–4.5).
Most of these were significant associations so the discovery of fibroids places women at increased risk of adverse outcomes compared with women without fibroids. However, one should be careful not to jump from this to advising women not yet pregnant to have their fibroids removed ‘so as to reduce the risk during pregnancy’. Apart from adding the risk of scar rupture, there is at present no convincing evidence that removing fibroids before pregnancy reduces the risk of poor pregnancy outcome (Farquhar BMJ 2009;338:b126), and there is always the possibility of reducing fertility (because of adhesions) or even having to perform a hysterectomy, hence depriving the woman of her chances of carrying a pregnancy in the first place.
Reports that low-dose aspirin is advantageous in the primary prevention of various conditions raise interesting questions. In a climate of willingness to embark on ‘healthy alternatives’ it seems likely that aspirin will become increasingly popular as a prophylactic medication. Judging by Pat Public’s propensity to swallow supplements, it seems inevitable that aspirin will become one of the most bandwagoned pills of our generation.
Aspirin’s popularity comes from its established place in the secondary prevention of cardiac events in people who have suffered a myocardial infarction, reducing their risk of recurrence by 20%. There is now evidence of its protective effect in reducing the risk of colorectal cancers, also by 20%. In an aging population prone to these two major threats to longevity, it would seem unwise to predict anything but its increased usage.
But there is always caution to be exercised. The absolute numbers are small with the death rate from cancers reduced by 0.5% over 5 years and the numbers needed to treat 200. No doubt controlled trials will supply the final statistics but these are only due out next year with our present state of knowledge in equipoise (Moayyedi and Jankowski BMJ 2010;341:c7326).
Older women and men seek prevention and early diagnosis of the ills that they see looming to disrupt or curtail their expected longevity. Informed women have seen hormone therapy swing widely back from its promise of long-term, safe treatment against osteoporosis and cardiovascular disease, and the pendulum still has to settle—I predict more in its favour than the pessimistic views expressed in the first few years of this century.
They have also seen compelling question marks raised against screening mammography, no progress in the early diagnosis of ovarian cancer, and cervical cytology destined to play an ever decreasing role in genital cancer detection.
So how do concerned older women make a positive contribution to their own well being? There are obvious undisputed measures like smoking cessation, exercising, eating a mixed diet with little red meat, plenty of fruits, vegetables and nuts, maintaining a healthy weight and participating in active social and mental lifestyles (Hankinson et al. JAMA 2010;304:2603–10). Further measures are avoiding excessive alcohol intake, having regular health checks, medication adherence and possibly additives—like aspirin.
Aspirin does raise the risk of bleeding and this includes gastrointestinal bleeds, so its use needs to be accompanied by knowledge about its influence on normal parameters and routine testing—like faecal occult blood tests. This is a paradoxical issue because aspirin can cause bleeding, which might give rise to false-positive results, but it may reduce the incidence of cancers, leading to fewer genuine positive results, so clarity on the matter by research was sought by Brenner et al. (JAMA 2010;304:2513–20). The investigators noted the use of aspirin in a large group of middle- to old-aged people undergoing colonoscopy to see if it had an influence on the correlation between occult blood testing and the actual presence of cancers.
Their outcomes were reassuring and intriguing. Because aspirin lowers the bleeding threshold, it is quite possible that it ‘allows’ adenomas and polyps to bleed more readily than they would normally, thereby increasing the sensitivity of the occult blood test. This is precisely what the researchers found—with only a slight drop in specificity allowing them to say that low-dose aspirin does not hamper the immunochemical tests for occult blood in screening for colorectal malignancies, in fact it could be used as a temporary measure to enhance test performance, although that needs further investigation.
Low-dose aspirin looks promising as a primary preventative weapon and it appears far less risky than statins or blood-pressure-lowering agents at the present state of our knowledge. Aspirin is relatively safe, has widespread advantages and lets people feel they are doing something active about their health. Maybe it is the hope that one is ahead of the game, maybe countering the indulgent westernised culture that surrounds us, or just enjoying the placebo effect.