55
Anrc. Hum. Genet., Lond. (1979), 43, 55
Printed in Great Britain
Maternal height and twinning BY G. CORNEY," D. SEEDBURGH," B. THOMPSON,t D. M. CAMPBELL,$ I. MAcGILLIVRAY~AND D. TIMLINS
* MRC Human Biochemical Genetics Unit, The Galton Laboratory,
University College London,
T MRC Medical Sociology Unit, Institute of Medical Sociology, Aberdeen, $ Department of Obstetrics and Gynaecology, University of Aberdeen and 3 Medical Computer Centre, Westminster Hospital, London INTRODUCTION
Various studies have indicated that there is a positive correlation between maternal height and the rate of twinning in a population. This was first suggested by Tchouriloff in 1877 as a result of his observations that men rejected from military service because of small stature came from various parts of Europe in which the rate of twinning was known to be low. A relationship between body size and litter size exists in various species (MacArthur, 1941 ; Thomson & Thomson, 1949) and further studies in man have confirmed the association (Torgersen, 1951 ; Anderson, 1956 ; Campbell, Campbell & MacGillivray, 1974). Nylander (1975u, c ) has shown this to be specifically with dizygotic twinning. I n 1972 we reported that the combined birth weights of dizygotic (DZ) twins were heavier than those of monozygotic (MZ) pairs (Corney, Robson & Strong, 1972). Since birth weight is known to be positively correlated with maternal height both in singletons and twins (Cawley, McKeown 8: Record, 1954; McKeown & Record, 1954) we suggested that the mothers of DZ twins might be taller than the mothers of MZ twins. This does not predict the relationship between the height of either group with the mothers of singletons. As MZ twinning is not appareiitlj- affected by recognizable environmental or genetical factors (Nylander, 1975 b ) , it can perhaps best be regarded as a chance event, and the mothers of MZ twins thus not different in their general characteristics from the mothers of singletons. Data to test these hypotheses have not previously been available. I n this paper we present an analysis of maternal height and zygosity data from the Oxford area and also from Aberdeen and north-east Scotland.
Composition of twin samples Oxford. The details of this study have been reported previously (Corney, Robson & Strong, 1968; Corney et al. 1972), but the size of the sample for this analysis has been increased by the addition of some pairs which were discarded in the previous analysis because they did not fulfil the rigid criteria then used for the determination of zygosity. For present purposes less uniform criteria have been applied with regard to the range of genetic markers used and a quantitative assessment of the probability of dizygosity for each pair alike for all markers substituted as the criterion for inclusion. Aherdeen and north-east Scotland. A survey similar to that carried out in the Oxford area was started at the Aberdeen Maternity Hospital in 1968, the period of study for this particular analysis extending from August 1968 to June 1973. All twin confinements in Aberdeen City and Suburbs take place in this hospital and also nearly three-quarters of those from other parts of north-east Scotland. The organization and methods of collection of the umbilical cord 0003-4800/i9/0000-4307 $02.00
0 1979 University College London
56
G. CORNEYAND
OTHERS
blood specimens and placentae were similar to those used in the Oxford survey. A technician specifically allocated t~ this project identified the placental membrane relationships and sent the specimens of cord blood and placentae to London for determination of zygosity. Zygosity Difference in sex or in one or more of the genetic markers (red cell antigens and genetically determined enzymes in red cells and placental tissue) was taken as evidence of dizygosity. In all prospective studies of newborn twins so far reported, twins with monochorionicplacentation hax-e been found to be alike in sex and all markers tested (Corney, 1975) and therefore such placentation was accepted as adequate evidence for monozygosity. Pairs which were alike for all markers hut tlicliorionic were accepted as JiZ when the statistical probability of dizygosity was less than 0.02. The methods used for this calculation have been described previously (Corney 8: Robson, 1975). The proportion of DZ pairs (see Tables 1 and 2) in Oxford (219/307 = 71 yo)is similar t o that in Aberdeen and north-east Scotland (179/267 = 67 yo)and comparable with findings from similar sur\-e)’s i n England and white populations in the United States (Corney, 1975).
X a fPr n CI 1 he igii t d o h In the Oxford area maternal height data were available in the hospital notes for only 307 (4996) mothers of the twin deliveries which we originally reported. This was because height was not regnlarly measured in some of the hospitals. The relative proportion of DZ and JiZ pairs is unchanged. The control population, namely the mothers of singletons delivered during the same period, was identified by taking four adjacent entries (two preceding and two following) from the delivery room registration of each twin birth. Height was available for only 640 such mothers. This was again because not all were measured and because it was necessary to exclude the non-Caucasians. The practice for measurement was similar in all three hospitals, namely to the nearest quarter-inch and recorded thus in the hospital notes. For this study individual measurements were converted t o centimetres and adjusted t o one decimal place. Measurement of height is routine practice for mothers attending Aberdeen Maternity Hospital with the exception of emergency admissions. During the period 1968-72 height in this hospital was also measured t o the nearest quarter-inch. Individual measurements for mothers of twins were conrerted to centimetres and adjusted to a single decimal place. Height information on a large population of mothers of singletons from Aberdeen City and Suburbs was available for this period. The mean height, which was originally expressed in inches has been converted to centimetres for this stuclS. Maternal height data in centimetres for singletons tleli\-rred in north-east Scotland outside the Aberdeen (city and suburbs) area are available for the period 1870-4 from records kept by the Scottish Home and Health Department.
RESULTS
Tlir mean maternal height for the mothers of twins and singletons from the surveys are giren in Table 1 (Oxford) and Table 2 (dberdeen and north-east Scotland). As there are significant differences between these areas the data hare been presented separately. A x2 test
Maternal height and twinning
57
Table 1. Mean maternal height for twin pairs and singletons in the Oxford Survey
Twin pairs
Number
Mean maternal height (cm)
S.D.
219 88 640
163.2 161.5 161.7
6.88 5.72 6.39
DZ MZ
Singletons
Table 2. Mean maternal height for twin pairs and singletons in the Aberdeen Survey City
Suburbs r----A-- 7
7-----A----7
Maternal height (cm) Kumber Twin pairs DZ MZ Singletons
Maternal height (cm)
( . __7 A S.D. Number Mean
80 43 12,762
I 60.0
160.6
6.16 5'47
18 3
158.2
5.96
2,405
7
Mean
S.D.
161.2 159.6
8.15 6.03
159'4
5.78
Xorth-east Scotland r------~-------
Maternal height (cm) 7
Number Twin pairs DZ MZ Singletons
'
81 42 20,439
Mean
S.D.
161.4 160.0 160.1
5-40 5'51 6.23
Table 3. Signi$mnce probabilities for t tests for difference in heigh,ts of mothers of DZ and M Z twin pairs and those of singletons
Oxford DZ 'u.MZ DZ v. Singletons MZ v. Singletons
Aberdeen I City Suburbs
0'02
0.30
0'002
0'0002
0.86
0.05
0.38 0.17 0.94
North-east Scotland
0.09 0.016 0.93
for homogeneity (Smith, 1969) within the Aberdeen data (Table 2) showed a marked difference between the singletons ( x 2 = 774.0). For this reason the data are listed separately. DZ and MZ data for these three groups were homogeneous although the numbers involved were t'oo small to draw firm conclusions. Unpaired t tests were applied to investigate whether the heights of the MZ twin, DZ twin and singleton mothers were drawn from the same population, or if they represented different populations. The results of three comparisons, DZ v. MZ, DZ v. singletons and MZ v. singletons are listed in Table 3. I n the DZ v. singletons and DZ v. MZ cases, the probabilities are I-tailed as we are predicting the direction of the differences; in the MZ v. singletons comparisons, the probabilities are 2-tailed.
58
G. CORXEYASD
OTHERS
DISCUSSIOS
Our original hypothesis was partly that mothers of D Z twins might be taller than those of &I% pairs. Such a clifference in height (1.7 em) has been found in Oxford (see Table 1) and also (1.4 em) in the data from north-east Scotland (see Table 2). Significance tests are given in Table 3. I n Aberdeen City, however, the difference between D Z and MZ mothers is less, 0.6 ern, albeit in the expected direction, but not statistically significant. Since there was no indication of appreciable heterogeneity for the DZ-MZ comparisons, it is appropriate to combine the observed differences into a single estimate by using a weighted mean and the resulting DZ-MZ difference in maternal height is 1.03 0-74 em. On the whole, therefore, the data support the hypothesis and it is possible that an increase in maternal height might contribute to the difference in combined weight between D Z and MZ pairs. There is no obvious explanation for the rather small difference found in Aberdeen City. Although the detailed birth weight analysis for this survey has not yet been published, a preliminary analysis confirms that the birth weight difference between D Z and MZ pairs found in the Oxford survey is present in north-east Scotland, where the maternal height difference has also been demonstrated. and not in Aberdeen City where the difference in birth weight between DZ and MZ pairs is not statistically significant. These results are therefore consistent in terms of the relationship hetween birth weight and maternal height, but do not help to explain the reason for thr. apparent difference between Aberdeen City and the rest of north-east Scotland. The scbcontl part of the hypothesis was that, whereas mothers of DZ pairs represent a different po~)ulationin height, JIZ t n in mothers resemble the general population in stature. Mothers of I)% twins arc significantly taller than those of singletons in Oxford, Aberdeen City and t Scotland thus confirming that they do represent a separate group. The combined data for the Scottish survey gives n mean difference of 1.77 0.44 em. Mothers of N Z pairs do not differ appec.iably in height from those of singletons in Oxford and north-east Scotland. This I:, not, lio.r\erei~.the case in Aberdeen City as J l Z twin mothers there are significantIy tallei than those of singletons. The combined figure for the Scottish survey is 0.85 f 0-59 em. 7’11~most tltfinite finding, therefore, is that the mothers of DZ twins are a recognizable groul). tliffering in height from other mothers. This is a direct confirmation of Nylander’s (1!3iI. 1 U i . 5 0 , r ) conclusion based on studies showing that the DZ twinning rate is positively correLtted with maternal height. Milham (1964) suggested that the various influences then knon t i to be associated with DZ twinning, advancing maternal age, number of previous b i r t h independent of age, and ethnic group, might all be attributable to rariations in pituitary function. Sylancler (19’73. 1974, 1975b) has also shown that in Xigeria amongst the Yoruba woniw, d i o hare tlic highest known rate of diz-gotic twinning in the world, mothers of twins have higher swum gonadotrophin levels than mothers of singletons, thus establishing a relationship in a particular population between quantitative variation in gonadotrophins and t v inrting, d i i c h would support Milham‘s theory. The effect of body size may also originate in tl-ir, I’ituitary glan(l its JlacArthnr (1941) suggested. Land (1970) has shown that there is a poiitire correlation ill the mouse between body \wight and ovulation rate with its associated tlcxtci i , i i n a n t q , follicle-stimiilatiiig liornioi~eactiritv and ovarian sensitiITity. Thus, the associtit ioii \it incr.cah.cd iiiaternal height with tlizygotic tn inning demonstrated here may be yet i ()t 1 I I 1 a t i j fi>
Anrc. Hum. Genet., Lond. (1979), 43, 55
Printed in Great Britain
Maternal height and twinning BY G. CORNEY," D. SEEDBURGH," B. THOMPSON,t D. M. CAMPBELL,$ I. MAcGILLIVRAY~AND D. TIMLINS
* MRC Human Biochemical Genetics Unit, The Galton Laboratory,
University College London,
T MRC Medical Sociology Unit, Institute of Medical Sociology, Aberdeen, $ Department of Obstetrics and Gynaecology, University of Aberdeen and 3 Medical Computer Centre, Westminster Hospital, London INTRODUCTION
Various studies have indicated that there is a positive correlation between maternal height and the rate of twinning in a population. This was first suggested by Tchouriloff in 1877 as a result of his observations that men rejected from military service because of small stature came from various parts of Europe in which the rate of twinning was known to be low. A relationship between body size and litter size exists in various species (MacArthur, 1941 ; Thomson & Thomson, 1949) and further studies in man have confirmed the association (Torgersen, 1951 ; Anderson, 1956 ; Campbell, Campbell & MacGillivray, 1974). Nylander (1975u, c ) has shown this to be specifically with dizygotic twinning. I n 1972 we reported that the combined birth weights of dizygotic (DZ) twins were heavier than those of monozygotic (MZ) pairs (Corney, Robson & Strong, 1972). Since birth weight is known to be positively correlated with maternal height both in singletons and twins (Cawley, McKeown 8: Record, 1954; McKeown & Record, 1954) we suggested that the mothers of DZ twins might be taller than the mothers of MZ twins. This does not predict the relationship between the height of either group with the mothers of singletons. As MZ twinning is not appareiitlj- affected by recognizable environmental or genetical factors (Nylander, 1975 b ) , it can perhaps best be regarded as a chance event, and the mothers of MZ twins thus not different in their general characteristics from the mothers of singletons. Data to test these hypotheses have not previously been available. I n this paper we present an analysis of maternal height and zygosity data from the Oxford area and also from Aberdeen and north-east Scotland.
Composition of twin samples Oxford. The details of this study have been reported previously (Corney, Robson & Strong, 1968; Corney et al. 1972), but the size of the sample for this analysis has been increased by the addition of some pairs which were discarded in the previous analysis because they did not fulfil the rigid criteria then used for the determination of zygosity. For present purposes less uniform criteria have been applied with regard to the range of genetic markers used and a quantitative assessment of the probability of dizygosity for each pair alike for all markers substituted as the criterion for inclusion. Aherdeen and north-east Scotland. A survey similar to that carried out in the Oxford area was started at the Aberdeen Maternity Hospital in 1968, the period of study for this particular analysis extending from August 1968 to June 1973. All twin confinements in Aberdeen City and Suburbs take place in this hospital and also nearly three-quarters of those from other parts of north-east Scotland. The organization and methods of collection of the umbilical cord 0003-4800/i9/0000-4307 $02.00
0 1979 University College London
56
G. CORNEYAND
OTHERS
blood specimens and placentae were similar to those used in the Oxford survey. A technician specifically allocated t~ this project identified the placental membrane relationships and sent the specimens of cord blood and placentae to London for determination of zygosity. Zygosity Difference in sex or in one or more of the genetic markers (red cell antigens and genetically determined enzymes in red cells and placental tissue) was taken as evidence of dizygosity. In all prospective studies of newborn twins so far reported, twins with monochorionicplacentation hax-e been found to be alike in sex and all markers tested (Corney, 1975) and therefore such placentation was accepted as adequate evidence for monozygosity. Pairs which were alike for all markers hut tlicliorionic were accepted as JiZ when the statistical probability of dizygosity was less than 0.02. The methods used for this calculation have been described previously (Corney 8: Robson, 1975). The proportion of DZ pairs (see Tables 1 and 2) in Oxford (219/307 = 71 yo)is similar t o that in Aberdeen and north-east Scotland (179/267 = 67 yo)and comparable with findings from similar sur\-e)’s i n England and white populations in the United States (Corney, 1975).
X a fPr n CI 1 he igii t d o h In the Oxford area maternal height data were available in the hospital notes for only 307 (4996) mothers of the twin deliveries which we originally reported. This was because height was not regnlarly measured in some of the hospitals. The relative proportion of DZ and JiZ pairs is unchanged. The control population, namely the mothers of singletons delivered during the same period, was identified by taking four adjacent entries (two preceding and two following) from the delivery room registration of each twin birth. Height was available for only 640 such mothers. This was again because not all were measured and because it was necessary to exclude the non-Caucasians. The practice for measurement was similar in all three hospitals, namely to the nearest quarter-inch and recorded thus in the hospital notes. For this study individual measurements were converted t o centimetres and adjusted t o one decimal place. Measurement of height is routine practice for mothers attending Aberdeen Maternity Hospital with the exception of emergency admissions. During the period 1968-72 height in this hospital was also measured t o the nearest quarter-inch. Individual measurements for mothers of twins were conrerted to centimetres and adjusted to a single decimal place. Height information on a large population of mothers of singletons from Aberdeen City and Suburbs was available for this period. The mean height, which was originally expressed in inches has been converted to centimetres for this stuclS. Maternal height data in centimetres for singletons tleli\-rred in north-east Scotland outside the Aberdeen (city and suburbs) area are available for the period 1870-4 from records kept by the Scottish Home and Health Department.
RESULTS
Tlir mean maternal height for the mothers of twins and singletons from the surveys are giren in Table 1 (Oxford) and Table 2 (dberdeen and north-east Scotland). As there are significant differences between these areas the data hare been presented separately. A x2 test
Maternal height and twinning
57
Table 1. Mean maternal height for twin pairs and singletons in the Oxford Survey
Twin pairs
Number
Mean maternal height (cm)
S.D.
219 88 640
163.2 161.5 161.7
6.88 5.72 6.39
DZ MZ
Singletons
Table 2. Mean maternal height for twin pairs and singletons in the Aberdeen Survey City
Suburbs r----A-- 7
7-----A----7
Maternal height (cm) Kumber Twin pairs DZ MZ Singletons
Maternal height (cm)
( . __7 A S.D. Number Mean
80 43 12,762
I 60.0
160.6
6.16 5'47
18 3
158.2
5.96
2,405
7
Mean
S.D.
161.2 159.6
8.15 6.03
159'4
5.78
Xorth-east Scotland r------~-------
Maternal height (cm) 7
Number Twin pairs DZ MZ Singletons
'
81 42 20,439
Mean
S.D.
161.4 160.0 160.1
5-40 5'51 6.23
Table 3. Signi$mnce probabilities for t tests for difference in heigh,ts of mothers of DZ and M Z twin pairs and those of singletons
Oxford DZ 'u.MZ DZ v. Singletons MZ v. Singletons
Aberdeen I City Suburbs
0'02
0.30
0'002
0'0002
0.86
0.05
0.38 0.17 0.94
North-east Scotland
0.09 0.016 0.93
for homogeneity (Smith, 1969) within the Aberdeen data (Table 2) showed a marked difference between the singletons ( x 2 = 774.0). For this reason the data are listed separately. DZ and MZ data for these three groups were homogeneous although the numbers involved were t'oo small to draw firm conclusions. Unpaired t tests were applied to investigate whether the heights of the MZ twin, DZ twin and singleton mothers were drawn from the same population, or if they represented different populations. The results of three comparisons, DZ v. MZ, DZ v. singletons and MZ v. singletons are listed in Table 3. I n the DZ v. singletons and DZ v. MZ cases, the probabilities are I-tailed as we are predicting the direction of the differences; in the MZ v. singletons comparisons, the probabilities are 2-tailed.
58
G. CORXEYASD
OTHERS
DISCUSSIOS
Our original hypothesis was partly that mothers of D Z twins might be taller than those of &I% pairs. Such a clifference in height (1.7 em) has been found in Oxford (see Table 1) and also (1.4 em) in the data from north-east Scotland (see Table 2). Significance tests are given in Table 3. I n Aberdeen City, however, the difference between D Z and MZ mothers is less, 0.6 ern, albeit in the expected direction, but not statistically significant. Since there was no indication of appreciable heterogeneity for the DZ-MZ comparisons, it is appropriate to combine the observed differences into a single estimate by using a weighted mean and the resulting DZ-MZ difference in maternal height is 1.03 0-74 em. On the whole, therefore, the data support the hypothesis and it is possible that an increase in maternal height might contribute to the difference in combined weight between D Z and MZ pairs. There is no obvious explanation for the rather small difference found in Aberdeen City. Although the detailed birth weight analysis for this survey has not yet been published, a preliminary analysis confirms that the birth weight difference between D Z and MZ pairs found in the Oxford survey is present in north-east Scotland, where the maternal height difference has also been demonstrated. and not in Aberdeen City where the difference in birth weight between DZ and MZ pairs is not statistically significant. These results are therefore consistent in terms of the relationship hetween birth weight and maternal height, but do not help to explain the reason for thr. apparent difference between Aberdeen City and the rest of north-east Scotland. The scbcontl part of the hypothesis was that, whereas mothers of DZ pairs represent a different po~)ulationin height, JIZ t n in mothers resemble the general population in stature. Mothers of I)% twins arc significantly taller than those of singletons in Oxford, Aberdeen City and t Scotland thus confirming that they do represent a separate group. The combined data for the Scottish survey gives n mean difference of 1.77 0.44 em. Mothers of N Z pairs do not differ appec.iably in height from those of singletons in Oxford and north-east Scotland. This I:, not, lio.r\erei~.the case in Aberdeen City as J l Z twin mothers there are significantIy tallei than those of singletons. The combined figure for the Scottish survey is 0.85 f 0-59 em. 7’11~most tltfinite finding, therefore, is that the mothers of DZ twins are a recognizable groul). tliffering in height from other mothers. This is a direct confirmation of Nylander’s (1!3iI. 1 U i . 5 0 , r ) conclusion based on studies showing that the DZ twinning rate is positively correLtted with maternal height. Milham (1964) suggested that the various influences then knon t i to be associated with DZ twinning, advancing maternal age, number of previous b i r t h independent of age, and ethnic group, might all be attributable to rariations in pituitary function. Sylancler (19’73. 1974, 1975b) has also shown that in Xigeria amongst the Yoruba woniw, d i o hare tlic highest known rate of diz-gotic twinning in the world, mothers of twins have higher swum gonadotrophin levels than mothers of singletons, thus establishing a relationship in a particular population between quantitative variation in gonadotrophins and t v inrting, d i i c h would support Milham‘s theory. The effect of body size may also originate in tl-ir, I’ituitary glan(l its JlacArthnr (1941) suggested. Land (1970) has shown that there is a poiitire correlation ill the mouse between body \wight and ovulation rate with its associated tlcxtci i , i i n a n t q , follicle-stimiilatiiig liornioi~eactiritv and ovarian sensitiITity. Thus, the associtit ioii \it incr.cah.cd iiiaternal height with tlizygotic tn inning demonstrated here may be yet i ()t 1 I I 1 a t i j fi>
