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  • Athol Kent

Antiepileptic drugs in pregnancy

It has long been believed that some antiepileptic drugs constitute a danger to the fetus. Generally, women who suffer from epilepsy should stay on their medication during pregnancy because of the negative effects of seizures on mother and fetus. Certain agents are teratogenic but more subtle effects at lower doses may occur although they are less readily detectable. A new study by Meador et al. (NEJM 2009;360:1597–605) is of considerable value in guiding prescribing.

The authors followed up the offspring of women taking single antiepileptic drugs (carbamazine, lamotrigine, phenytoin or valproate) at the age of three years and measured their neuro-developmental scores. Using IQ as the cognitive marker and after adjusting for maternal IQ, they found that the children exposed to valproate had scores six points lower than for carbazamine, seven points lower than for phenytoin and nine points lower than for lamotrigine. The association between valproate and IQ was dose dependent. This impairment of cognitive function should persuade women of childbearing age with epilepsy not to use valproate as their first-choice drug.

China’s one child policy

China’s one child per family policy was introduced in 1979. A decade earlier the fertility rate was six but this had dropped to three by the time the policy began and it reached 1.7 in the mid 1990s where it has stabilised (Liu & Zhang BMJ 2009;338:899–90).

The Chinese have prospered while controlling their population but it has had social and gender repercussions. Over-cosseting or spoiling single children can lead to sociological dysfunction while the cultural preference for sons, like other East Asian countries, has resulted in selective abortion of female fetuses and a skewed male to female sex ratio.

The sex ratio is expressed as the number of males to 100 females and is explored by Zhu et al. (BMJ 2009;338:920–3) who found that in 2005 there were more than a million excess births of boys. Of the total population under the age of 20 years, males exceeded females by 32 million so, even if the present ban on selective terminations is enforced, the normalisation of ratios will take decades to be achieved. As more and more women in urban areas claim to prefer smaller families with no sex preferences, changes are anticipated but not before huge social imbalances will work their way through a biased population.

Family planning in the UK

Unintended pregnancies are expensive. Obstetric services are costly, as are terminations of pregnancy, of which there are nearly 200 000 in the UK annually. It is calculated that the cost benefit of family planning services is more than £10 for every £1 spent by the NHS.

Perhaps economic considerations are going to play increasingly important roles in individual and policy decisions. What gives value for money as well as reliability will be a significant factor, so long-acting, reversible contraceptive methods will be very much part of the future family planning landscape.

Attempts have been made to quantify cost-effectiveness using literature reviews, but real-world comparisons between methods are scarce. Lipetz et al. from Wales (Contraception 2009;79:304–9) compared the 3-year progestogen implant (Implanon®) with oral contraceptives in a case-controlled study. The implant which is subdermally inserted by a doctor releases etonogestrel over 36 months before requiring replacement and is considered more cost-effective than depot injections and copper or progestogen-releasing intrauterine devices. Calculations at 1, 2 and 3 years against oral contraceptives proved revealing, with the implant being superior at all three time intervals.

Since implants give lower pregnancy rates than oral contraceptives and nurse insertion can be readily learnt, the unit cost may come down while acceptance may increase, making this method an important option in developed and developing countries.

Ovarian cancer screening

Ovarian cancer is the most lethal of gynaecological cancers, presenting late and having a poor prognosis. This makes it an ideal candidate for screening in the anticipation of early detection and life-saving intervention and hopes were high for positive results from the large trial using serum CA 125 and transvaginal ultrasound as the screening tools (Partridge et al. Obstet Gynecol 2009;113:775–83).

A total of 35 000 women who were middle-aged and healthy were allocated to undergo the two screening modalities annually or ‘usual care’. The number of women having both tests positive—an overall positive result—was <1 per 1000 during any given year of the trial. These women had laparotomies but only 1 in 20 turned out to have ovarian cancer.

Even if one accepts this enormous screening effort plus the chances of a negative operation, there was still another vital question to be answered. Were the early cancers found amenable to successful intervention? Regrettably, fully 80% of those detected were already advanced lesions so the screening made no difference to the life expectancy of these women.

We remain unable to pick up—at an early enough stage—the 4 per 10 000 post-menopausal women who will develop ovarian cancer. The results of this study show that screening the general population for ovarian cancer cannot be justified, using the tools presently at our disposal.

Eating in labour

What women are allowed to eat during labour varies considerably. There is little evidence to support nil per mouth, water only, fluids only or a light diet but this does not prevent the holding of strong views.

If there are major obstetric complications with the likelihood of a general anaesthetic being necessary, different rules may apply but most women would like the choice of something comforting and nutritious to eat. A study by O’Sullivan et al. from London (BMJ 2009;338:880) suggests little harm can come from a low-fat, low residue diet in uncomplicated labours. Allocating women to eating or water-only did not affect spontaneous delivery rates or any other outcomes, so maybe there is an argument in favour of a relaxed policy towards oral intake in labour.

Obesity and pregnancy risk

The prevalence of obesity among pregnant European women is 20%. This is a three-fold increase over the last two decades and these women should be considered high-risk antenatally, intrapartum and postpartum. When recording a woman’s weight and height, this should be carried out objectively as relying on her version may lead to errors. If you take the patient’s word at booking, more than half will under-report their weight and throw out the Body Mass Index calculation (Fattah et al. Euro JOG & Repro Bio 2009;144:32–4).

Meat and mortality

Eating a lot of red meat is bad for you. Data from an American mega-study of half a million people show that those eating the most red or processed meat have ‘modest increases in total mortality, cancer mortality and cardiovascular mortality’ (Sinha et al. Arch Int Med 2009;169:562–71). This is euphemistically put but the message is clear for men and women between the ages of 50 and 70 years—any sort of increase in mortality risk is unlovely—so the less red and processed meat you eat the better your survival chances.

Endometrial cancer is linked to obesity and the avoidance of being overweight is associated with a lowered risk. It now seems that diet is also implicated, as indicated by a study from Italy (Bravi et al. AJOG 2009;200:293–6) in which they find a decreased risk in women on diets high in vegetables, grains and coffee but an increased risk for red meat eaters.

Coffee consumption—or at least high or increased consumption—does not get approval as far as breast cancer is concerned. A meta-analysis by Tang et al. (AJOG 2009;200:290–2) suggests borderline significance so it seems prudent to advocate moderate intake only.

Health kick

Middle-aged men benefit from physical exercise. This is unsurprising but the duration required for it to kick-in is long and the degree of benefit is unexpectedly large.

Byberg et al. from Sweden (BMJ 2009;338:936) followed up men for 35 years, starting at the age of 50 years, and compared those who exercised regularly with those who did not. It took a decade before clear benefits in mortality became apparent but when they did start to show they were substantial. Mortality rates per 1000 person years were 27, 24 and 18 in the low, moderate and high physical activity groups. These substantial reductions were on a par with the effect of kicking the habit of smoking.

Will it be the same for women?

The Polypill

The principle of the Polypill is simple. Put five drugs known to reduce cardio-vascular risk into a single pill and give it to middle-aged people to prevent cardio-vascular disease. It is a great idea. It was proposed more than 5 years ago by Wald & Law (BMJ 2003;326:1419–24) but somehow it has never caught on—or maybe it was not a good proposition commercially.

The concept is back in favour with an Indian generic manufacturer making the running (The Indian Polycap Study Lancet 2009;373:1341–52). The capsule being tested contained three blood pressure reducing agents, a statin to lower cholesterol and a low-dose of aspirin to attenuate coagulation. The actual ingredients are an angiotension-converting enzyme inhibitor (ramipril 5 mg), a beta blocker (atenolol 50 mg), a diuretic (hydrochlorthiazide 12.5 mg), the statin (simivastin 20 mg) and aspirin 100 mg.

In their clinical trial they report this combination lowered blood pressure between 5–8 mmHg, reduced LDL cholesterol by 0.7 mmol/l, slowed heart rates by 7 beats/minute and decreased urinary thromboxane B2 (a marker of prostinoid activity). The Polypill or, in this case the Polycap, was well-tolerated and the drug combinations were not antagonistic.

The overall reduction in cardio-vascular risk is estimated to be between 50% and 75% for largely healthy people. Imagine the combination of the Polypill and hormone replacement therapy.

Will this be the next big controversy in preventative medication?