Twins and the fetal origins hypothesis

British Medical Journal, August 21, 1999

Many variables differ between twins and singleton infants

EDITOR--Williams and Poulton report that their 22 adolescent twins had lower blood pressure than singletons.[1] They interpret their data as being contrary to the fetal origins hypothesis because they presume that twins, being small at birth, would tend to have higher rather than lower blood pressure in later life. As twins have different patterns of fetal growth from singletons, however, they were specifically excluded from the fetal origins hypothesis.[2]

There are several reasons why the low birth weight of twins may not have the same significance as intrauterine growth retardation in singleton births. Ultrasound evidence suggests that twins down regulate their growth rate early in gestation, possibly during the first trimester.[3] Studies in fetal lambs suggest that early down regulation of fatal growth protects against growth retardation induced by undernutrition in later gestation.[4] Finally, the metabolic and endocrine changes associated with growth retardation in singleton infants, including hypoinsulinaemia, are not observed in twins.[5]

D I W Phillips consultant physician diwp@mrc.soton.ac.uk

C Osmond senior scientist Medical Research Council Environmental Epidemiology Unit (University of Southampton), Southampton General Hospital, Southampton SO16 6YD

[1] Williams S, Poulton R. Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study. BMJ 1999;318:897-900. (3 April.)

[2] Barker DJP. Fetal origins of coronary heart disease. BMJ 1995;311:171-4.

[3] Leveno KJ, Santos-Ramos R, Duenhoelter JH, Reisch JS, Whalley PJ. Sonar cephalometry in twins: a table of biparietal diameters for normal twin fetuses and a comparison with singletons. Am J Obstet Gynecol 1979;135:727-30.

[4] Harding J, Liu L, Evans P, Oliver M, Gluckman PD. Intrauterine feeding of the growth retarded fetus: can we help? Early Hum Devel 1992;29:193-7.

[5] Van Assche FA, Aerts L. Holemans K. Low birthweight and ischaemic heart disease. Lancet 1994;343:731-2.

Patterns of growth retardation differ in twins and singletons

EDITOR--Williams and Poulton[1] and an accompanying editorial by Susser and Levin[2] challenged the fetal origins hypothesis with some vigour. Both articles emphasise the finding that twins had lower blood pressure than singletons. They argue that this provides crucial evidence against the fetal origins hypothesis as it would predict the opposite effect given that twins have slower growth rates in utero than singletons and are lighter at birth.

Although we applaud the intention to test the hypothesis rigorously, the line of argument is unconvincing. Firstly, the conclusion rests on 22 twins only. Moreover, these may not be representative of all twins in the population. Indeed, examination of the distribution of birth weight in these twins indicates that there may be missing individuals at very low birth weight ([is less than] 1500 g). Secondly, the data as a whole (singletons and twins combined) show a negative association between birth weight and blood pressure at age 9 years and thus support the fatal origins hypothesis. This is given far less prominence than the twin finding. Thirdly, and most importantly, the notion that growth impairment in twins is similar to other forms of fatal growth impairment is questionable. Divergence in fetal growth rates between twins and singletons occurs very early in gestation[3 4] Reduced size at birth in the population as a whole results primarily from growth faltering in late gestation, as the rapidly increasing nutritional demands of the fetus exceed supply. If it is this later type of growth impairment that is associated with programming blood pressure and cardiovascular disease, then the early reduction of growth rate in twins may not be associated with increases in blood pressure.

Given the weight of evidence in support of a negative association between birth weight and blood pressure,[5] twins may be interesting exceptions to the rule. As such, studying why they are different from singletons may help to reveal the mechanisms underlying fetal programming of later blood pressure.

Pat Doyle senior lecturer in epidemiology p. doyle@lshtm.ac.uk

David Leon reader

Noreen Maconochie lecturer

Susan Morton research student

Bianca de Stavola senior lecturer London School of Hygiene and Tropical Medicine, London WC 1E 7HT

[1] Williams S, Poulton R. Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study. BMJ 1999;318:897-900. (3 April.)

[2] Susser M, Levin B. Ordeals for the fetal programming hypothesis BMJ 1999;318:885-6. (3 April.)

[3] Wilson RS. Twins: measures of birth size at different gestational ages. Ann Hum Biol 1974; 1:57-64.

[4] Taylor GM, Owen R Mires GJ. Foetal growth velocities in twin pregnancies. Twin Res 1998; 1:9-14.

[5] Law CM, Shiell AW. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens 196; 14:935-41.