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LETTERS:
D I W Phillips, C Osmond, Pat Doyle, David Leon, Noreen Maconochie, Susan Morton, Bianca de Stavola, Calum N Ross, Sheila Williams, and Richie Poulton
Twins and the fetal origins hypothesis
BMJ 1999; 319: 517 [Full text]

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Fetal growth retardation in twins: Jaakko Kaprio (30 August 1999)

The blood pressure of heavier and lighter twins: support for the fetal origin hypothesis?: Yin Bun Cheung (27 October 1999)

Fetal growth retardation in twins 30 August 1999

Jaakko Kaprio,
Professor of Public Health
Finnish Twin Cohort Study, Univ. of Helsinki
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Re: Fetal growth retardation in twins

Fetal growth of twins retarded in the third trimester
EDITOR - Williams and Poulton reported that twins (n=22) had a lower blood pressure than singletons (n=nearly 800)1. The result was criticised in letters by Phillips and Osmond2, and Doyle et al.3 with arguments that the growth rate of twins diverges from that of singletons 'very early in gestation, possibly during the first trimester'. The statements of the authors were based on three articles,4-6 none of which studied the first trimester - the last one in fact only third trimester (from 30 to 37 weeks' gestation).
An extensive review of the literature reveals that, beginning from the middle of the second trimester (15 gestational weeks), two studies4,7 show that the biparietal diameter (BPD) of twin fetuses are smaller than those of singletons throughout the latter half of the gestation, whereas 17 studies from the second or third trimester,8-20 including studies with large numbers of subjects from national data21-24 show that in terms of BPD, abdominal circumference (AC), femur length (FL), or birth weight (BW), there are no differences between twins and singletons to at least 28 gestational weeks. There are even a few studies where no difference between twins' and singletons' head, limb, or body size was found throughout the pregnancy. 25-27 In a study of nearly 3000 twin and singleton pregnancies,12 placental weight of twins was lower than that of singletons from 24 weeks onward. Thus, it is most likely that the notable divergence of twin growth from singleton growth starts in the beginning of the third trimester and then widens progressively towards the end of pregnancy. 21
It should be noted, however, that the birth weight deficit of approximately one kg observed in twins vs. singletons, is the result of both growth retardation and a more or less preterm birth. The early escape from the restrictive intrauterine environment may protect the twins from further growth delay.
Another issue to consider is that it is not necessarily the intrauterine environment that may shield twins from subsequent hypertension, but there may be postnatal differences between twins and singletons. 28
Back to the original study: 1 had there been a larger number of twins, it would have been interesting to know whether the subsequent blood pressures had differed a) in lower vs. higher birth weight twins, b) in MZ twins (being lighter at birth) vs. DZ twins, or c) in MZ twins discordant for birth weight.
Jaakko Kaprio, M.D. Professor of Public Health, University of Oulu
jaakko.kaprio@helsinki.fi
Kirsi H Pietil�inen, M.Sc. in nutrition, Med.Stud.
kirsi.pietilainen@helsinki.fi
Finnish Twin Cohort Study, Department of Public Health, University of Helsinki, P.O. Box 41, FIN-00014 University of Helsinki, FINLAND. Phone: +358 9 191 27 595, Fax +358 9 191 27 600
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3. Doyle P, Leon D, Maconochie N, Morton S, de Stavola B. Twins and the fetal origins hypothesis. Patterns of growth retardation differ in twins and singletons. BMJ 1999;319:517.
4. 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;135:727-730.
5. Wilson RS. Twins: measures of birth size at different gestational ages. Ann Hum Biol 1974;1:57-64.
6. Taylor GM, Owen P, Mires GJ. Foetal growth velocities in twin pregnancies. Twin Res 1998;1:9-14.
7. Divers WA, Hemsell DL. The use of ultrasound in multiple gestations. Obstet Gynecol 1979;53:500-504.
8. Kuno A, Akiyama M, Yanagihara T, Hata T. Comparison of fetal growth in singleton, twin, and triplet pregnancies. Hum Reprod 1999;14:1352-1360.
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growth in multiple gestations. Acta Genet Med Gemellol 1988;37:41-46.
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18. Schneider L, Bessis R, Tabaste JL, Sarramont MF, Japhet N. Foetal twin ultrasound biometry. Acta Genet Med Gemellol 1979;28:299-301.
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20. McKeown T, Record RG. Observations on foetal growth in multiple pregnancy in man. J Endocrinol 1952;8:386-401.
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The blood pressure of heavier and lighter twins: support for the fetal origin hypothesis? 27 October 1999

Yin Bun Cheung,
Medical Statistician
Department of Paediatrics and Clinical Trials Centre, University of Hong Kong
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Re: The blood pressure of heavier and lighter twins: support for the fetal origin hypothesis?

Williams and Poulton reported that twins had lower blood pressure than singletons.1 They challenged the fetal origin hypothesis partly on this ground. Doyle et al. criticised that their conclusion was based on only 22 twins.2 Kaprio suggested to analyse the blood pressure of heavier and lighter twins if possible.3 Using data from the 1970 British birth cohort study, I have analysed the blood pressure of twins (n=102) and singletons (n=5312) at age 16. The 102 twins consisted of 44 pairs of twins with valid data for both twin members and 14 alone twins. There is no information about types of zygotic twinning. Systolic and diastolic blood pressure were based on a single reading taken in a medical examination. The 1970 birth cohort study has been described elsewhere.4,5
Table 1 shows the means (95% confidence intervals) of birth weight and blood pressure of twins and singletons, adjusted for sex. As a whole group, twins had systolic and diastolic blood pressure similar to their singleton counterparts, despite the deficit in birth weight. Although there was only a difference of 0.3 kg in birth weight between the heavier and lighter twins, the heavier twins had systolic blood pressure of 2.2 mmHg lower than the lighter twins. Their diastolic blood pressure was 1.1 mmHg lower.
Table 1
------------------------------------------------------------ Multiplicity Birthweight* Systolic BP* Diastolic BP* ------------------------------------------------------------ Singletons 3.33 111.2 69.3 (3.31,3.34) (110.9,111.5) (69.0,69.5) Twins 2.41 111.5 69.2 (2.31,2.51) (109.2,113.8) (67.5,70.9) -heavier twins 2.58 110.2 68.6 (2.43,2.73) (106.7,113.7) (66.0,71.2) -lighter twins 2.28 112.4 69.7 (2.15,2.41) (109.4,115.5) (67.4,72.0) ------------------------------------------------------------ * adjusted for sex.

Using paired t-tests with adjustment for sex, the differences (95% confidence intervals) in systolic and diastolic blood pressure between the heavier and lighter twins were -1.0 mmHg (-3.9,1.8) and -1.7 mmHg (- 4.2,0.8), respectively.
In spite of statistical insignificance, the blood pressure of heavier and lighter twins gives some support to the fetal origin hypothesis. Studying the outcomes in twin pairs has the advantage of reducing confounding. Growth discordance in twins is a common phenomenon. This provides a research opportunity. Kaprio has suggested some strategies for the analyses.3 The comparability between singletons and twins have been discussed by others.3,6 Phillips and Osmond maintains that twins should be exempted from the fetal origin hypothesis.6 Their point should be better phased as twins should not be compared with singletons.
References
1. Williams S, Poulton R. Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study. BMJ 1999; 318: 897-900.
2. Doyle P, Leon D, Maconochie N, Morton S, de Stavola B. Twins and the fetal origins hypothesis. Patterns of growth retardation differ in twins and singletons. BMJ 1999;319:517.
3. Kaprio J. Fetal growth retardation in twins. eBMJ, 30 August 1999.
4. Chamberlain G, Philipp E, Howlett BC, Claireaux A. British Births: Vol. 1. The First Week of Life. London, Wm Heinemann, 1978.
5. Bynner J, Ferri E, Shepherd P. Twenty-something in the 1990s. Aldershot, Ashgate, 1997.
6. Phillips DIW, Osmond C. Twins and the fetal origins hypothesis. Many variables differ between twins and singleton infants. BMJ 1999;319:517.
Acknowledgement
Thanks are due to The Data Archive and the City University's Social Statistics Research Unit for access to the 1970 birth cohort data.