GROWTH AND DEVELOPMENT OF TWINS OF DISSIMILAR SIZE AT BIRTH

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GROWTH

AND

DEVELOPMENT

OF

TWINS

OF

DISSIMILAR

SIZE

AT

BIRTH

S. Gorham Babson, M.D., John Kangas, Ph.D., Norton Young, Ph.D.,

and James L. Bramhall, M.B., Ch.B.

Crippled Children’s Division and Departments of Pediatrics, Medical Psychology, and Clinical Pathology

of the University of Oregon Medical School and Emanuel Hospital, Portland, Oregon

(Submitted July 25; accepted for publication October 15, 1963.)

Presented in part at the 10th International Congress of Pediatrics.

Supported by the Crippled Children’s Division of the University of Oregon Medical School. ADDRESS: (S.G.B.) Department of Pediatrics, University of Oregon Medical School, Portland 1, Oregon.

PEDIATRICS, March 1964

ARTICLES

I

NFANTS undersized for their gestational

age have been reported by many

ob-servers.1-6 Approximately 2% of infants born

at term in the United States of America

weigh 2,500 gm or less and 0.25% of term

infants weigh under 2,050 gm.4

Observa-tions made in our Prematurity Study Clinic

suggested that infants born near term who

were undersized at birth failed to match

the later mental and physical development

of infants of comparable birth weight with

shorter gestation periods.

There is uncertainty among investigators

as to the ultimate outcome of these runted#{176}

but not grossly malformed infants. Some

authors report these infants to be

indistin-guishable from normal babies by 4 to 6

months of age.4’3 Otherse, have

sug-gested that poor fetal growth may be

asso-ciated with failure to achieve maximum

later mental and physical development.

Drillien,b0 in her report on the development

of small premature infants, lists six

ex-amples of twins in five of which the smaller

twin had inferior intelligence at an average

age of 63 years. Bowen and Hepner’12

studying placental abnormalities mention nine runted infants who showed continued

stunting in physical growth through one

*The term, “runt,” is being used in the tra-ditional sense of an unusually small biological product, relative to expectation, and without spe-cification of etiological mechanism(s).

year of age. McCance,13 reviewing animal

experiments states, “The failure of a young

animal to catch up with its fellows or

litter-mates for a long time and indeed its

ten-dency at first to lag further and further

behind after a nutritional setback before

birth is a common experience with many

species.” He further remarks,”... It would

appear that the younger the animal the

more serious a nutritional setback will be,

and permanent effects from under-nutrition

during fetal life are a distinct possibility.”

Twins discrepant in weight at birth

pres-ent an experimental opportunity for

evalu-ating the later effects of intrauterine

growth retardation. The factors of

gesta-tional age, racial background, maternal

health, and nutrition would l)e equated.

Genetic factors would be reduced in the

dizygotic and eliminated in the

mono-zygotic pairs. Differences in psychosocial

environment would also be reduced.

SAMPLE

A search was made for surviving sets of

dissimilar-sized twins in the records of two

Portland, Oregon, hospitals from 1950 to

1958. Only twin sets were selected in which

the runt met the arbitrary criteria of having

been at least 25% smaller than the co-twin

and having weighed less than 2,000 gm at

birth. The records of approximately 40,000

(2)

pairs of twins of ‘hom 11 met the criteria.

At the University of Oregon Medical

School Premature Unit the neonatal

rec-ords showed that one or both infants of 87

pairs of twins had been referred. Nine of

these pairs from six different hospitals

ful-filled the study criteria. These admissions

to the Medical School Premature Unit were

believed to have been referred for

eco-nomic reasons, a factor which should not

produce intrapair bias. Nevertheless, the

possibility of selective referral on the basis

of suspected neonatal problems in one twin

cannot be excluded in the referred pairs.

Of the twenty pairs fulfilling the criteria,

eighteen have been traced and sixteen pairs

were available for this study. These

chil-dren

ranged

in age from 4 years, 5 months,

to 10 years, 11 months (median of 8%

years) at the time of examination. Fourteen

sets were white, one set Negro, and one set

of Japanese extraction. Eight sets were

female, four sets male, and four sets were

mixed. Nine pairs were monozygotic as

determined by physical similarity and

blood typing.

The average birth weight of the runted

group

was 1.61 kg (range 0.95-1.99 kg) in

contrast to the nonrunt group mean of 2.47

kg (range 1.64-3.12 kg). This represents

a mean difference of 0.86

kg

or nearly 2 lb.

The runts weighed one-third less on the

average than their co-twin at birth.

Infants of decreasing size may be

ex-pected to have an increasing percentage of

birth weight loss.14 It is of interest that the

average postnatal weight loss in the runted

twins was 0.09 kg (6.6% of their birth

weight)

compared to 0.22

kg

(9.2% of their

birth weight) in the co-twin group. Pick5

reported a similar limitation of weight drop

in a case report

of

three small term infants.

The

smaller twin was born first in 9

of

the 16 sets. There were 11

cephalic

and

5

breech deliveries in both runted and

non-runted groups. Two runts were male and

2 female in the 4 sets

of unlike

twins. No

major differences between groups in

neo-natal complications were found in the

nursery records.

METHOD

Each set of twins was examined by a

pediatrician, clinical psychologist, speech

pathologist, and clinical pathologist.

Infor-mation on the order of births and birth size

was withheld from the examiners.

The examinations included a pediatric

history and physical examination with

an-thropometric measurements. Inspection of

physical characteristics and color

photo-graphs was used for the determination of

zygosity. On the similar appearing twins,

blood typing was carried through nine

anti-sera: anti-A, anti-B, anti-C, anti-D, anti-E,

anti-c, anti-e, anti-M, anti-N, and anti-K

sera. Intelligence was measured by the

Stan-ford-Binet, Form L-M.15

Communication was assessed from both

physical and language aspects. The oral

structures were compared by inspection.

Oral diadochokinesis was timed for distinct

one-, two-, and three-syllable sequences.

Judgments of speech articulation were

made by using phonetic analysis of the

child’s response on a standard articulation

inventory. Hearing was measured by

pure-tone screening audiometry at 15 decibels,

and in the case of the youngest pair, by

speech audiometry. Judgments of language

differences were obtained using

compre-hension items such as association of objects

with

functions and sentence understanding,

and communication items such as sentence

length,

complexity,

syntax, and fluency.

The Peabody Picture Vocabulary Test16

was used to estimate verbal intelligence by

the child’s ability to identify pictures in

response to verbal request.

On quantitative measures, the obtained

paired comparison differences between

runts and their co-twins were evaluated

statistically by testing the mean of a

popula-tion of differences.17 All significance levels

cited refer to one-tailed tests unless noted

otherwise.

RESULTS

Table I presents the raw data derived

from the birth records and the

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TABLE II

PoYSIcAL DIFFERENCES BETWEEN

16 TWIN SIBLING P.snts

TABLE III

INTELLIGENCE DIFFERENCES BETW EEN

16 TWIN SIBLING P.siirs

Test

4tnnford-Binet Form L-M

I’eal)o(ly Picture %ocabular

Mean I.Q. Difference

Runts 96.53 6.73 Nonrunts 103.00

Hunts 91.63 Nonrunts 94.13 . 30

#{149}t p 5.46 <.053 1.73 -.03 Variable Runt Supe-nor 14*

* Sign Test. Walker & I,ev, Statistical Inference,

Henry bit &Co., 1953, 430-431.

t One pair too young to be evaluated.

ARTICLES

331

Mean

- .

I ariabie Difference.

avon rig

.\onrunl

I p

Ueight (cm) 4.34 3.86 <.005 Weight (kg) 3.95 5.49 <.000.5

Uead Circumference

(cm) 1.34 4.80 <.0005

Physical differences between the twin

sibling pairs in height, weight, and head

circumference are shown in Table II. The

mean differences on all three variables favor

the nonrunt group to a highly significant

degree. Four children had important

physi-cal defects. They were all runts from

mono-zygotic pairs. The defects were: a patent

ductus arteriosus (corrected), bilateral

zonu-lar cataracts, fusion of the ribs with

scolio-sis, and a monoplegia. The nonrunts had no

comparable deformities.

Shown in Table III are intellectual

dif-ferences between the twin siblings. The

nonrunts as a group show an average

ad-vantage of more than six I.Q. points over

their runted twins on the Stanford-Binet

Intelligence Scale. The mean difference

favoring the nonrunt is statistically

signifi-cant on both of the intelligence measures

used. *

Table IV shows the results of

compari-sons made between runt and nonrunt

groups on speech and language variables.

Judgments of language proved significantly

different between runt and nonrunt siblings

below the 5% level. The other aspects which

relate to production of speech sounds,

speed of articulatory movement, and size

and shape of oral structures were not

sta-* The differences remain statistically significant

when evaluated by the Wilcoxon Matched-Pairs

Signed Ranks Test, a nonparametric statistic which

makes no assumptions concerning the shape of the

distribution of difference scores, S. Siegel:

Non-parametric Statistics for the Behavioral Sciences,

New York: McGraw-Hill, 1956, pp. 75-83.

tistically different between twin siblings.

Hearing was screened and was normal in

all subjects.

Although the runt and nonrunt groups

are almost evenly divided in their

respec-tive proportions of first- and second-born

children, it is possible to analyze for the

effects of birth order on current height,

weight, head circumference, and

intelli-gence. These differences between first and

second born were not statistically

signifi-cant and are summarized in Table V.

Nine of the 16 sets of twins were judged

to be monozygotic, according to physical

characteristics and identity of the blood

types performed. These 9 pairs offer an

even more precise opportunity to evaluate

the effects of runting, since all genetic

variation would be controlled within each

twin pair. Despite this small subgroup size,

the average differences favoring the

non-flint on the quantitative measures remain

TABLE IV

SPEECH EXAMINATION C0uPARIS0N BET\VEEN

16 TWIN SIBLING P.s1105

Non-Runt !.ren

Supe-nor

Language 3 11 2 .03

Articulation 3 8 5

-Oral Diadochokinesi.sf 7 7 1

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-* Based on eight pairs.

TABLE V

PHYsICAL AND INTELLECTUAL DIFFERENCES BETWEEN FIR.ST AND SECOND BORN TWIN SIBLINGS

No. Pairs = 16

Variable Mean Difference Favoring Second Born I p* Height (cm) Weight (kg)

Head Circumference (con)

Binet I.Q. 0.84 0.88 0. 2 -0.88 <1 <1 <1 <1

-* A two-tailed test and the .05 significance level used.

statistically significant and of equal or

larger magnitude than in the total group.

Oral diadochokinesis, which previously

showed no trend reaches a statistically

significant level of non-runt superiority in

the monozygotic sub-sample. Table VI

summarizes these comparisons.

CONCLUSIONS

It has been shown that twin pairs can

vary markedly in birth size, and that such

pairs still show significant differences at a

median age of 8% years. These data

con-firm and extend the observations of Bowen

and 12 and Engleson et al.#{176}that

intrauterine growth retardation is associated

with retardation of subsequent growth.

The number of important defects in the

smaller of the twin pairs is consistent with

the data of Warkany et al.’ and Rumboltz

et al. in their reports of an increased

in-cidence of anomalies in children having

had intrauterine growth retardation.

The data also indicate a detrimental

re-lationship between intrauterine runting

and intellectual development. This finding

is in accord with the intellectual differences

apparent in six sets of twins of dissimilar

birth weight listed by Drillien.b0 The work

of Engleson et al. comparing children

dysmature at birth and control children

also found intellectual measures to be

among the discriminating variables.

The language behavior of the nonrunt

group proved to be statistically superior

to the runted group, while factors of speech

sound production, speed of articulation,

and oral structures were not different. It

is of interest to note that runting had a

closer association with the more subtle and

higher order aspects of

communication-those most closely associated with language

and intellect-than with the motor or

pro-duction aspects of speech. The lack of

differences in articulation and motor speech

behavior may be related to the unique

speech environment in a home with twins.

Since Smith’9 has suggested that

intra-uterine stunting may have a genetic

com-ponent, it is of interest to note that the

physical and intellectual disadvantages of

the runt group continued to be exhibited

when only monozygotic pairs are

con-sidered. Birth order was of no significance.

Our data would support the discussion of

Price,20 that natal environment markedly

affects the development of twins. He warns

of interpretations of twin differences based

on post-natal environment, unless

intra-uterine variations have been carefully

eliminated.

SUMMARY

Birth records of a large private hospital and admissions records of a premature re-ferral center, covering the period 1950 to

TABLE VI

PHYSICAL AND INTELLEcTUAL DIFFERENCES BETWEEN

9 MONOZYGOTIC TWIN SIBLING PAIRS

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1958 were reviewed. Twenty pairs of

sur-viving twins were found in which the

smaller twin weighed less than 2,000 gm

and was at least 25% less than the weight of

the larger twin at birth. Sixteen of these

twenty pairs of twins were examined at a

median age of 8% years.

Comparisons were made between the

group composed of the smaller members

of the twin sets and the group of their

co-twins. A highly significant difference

was present in height, head circumference,

and weight. Significant differences in

in-telligence as measured by the

Stanford-Binet and Peabody Picture Vocabulary

Test, and in the judged level of language

comprehension and expression were found.

No significant difference was found

be-tween the groups in respect to articulation,

oral structures, oral diadochokinesis or

auditory acuity.

Four of the children had important

phys-ical defects. Each child was the smaller

member of a monozygotic twin set.

Birth order showed no relationship to

weight at birth or to subsequent

develop-ment.

A subgroup composed of monozygotic

twins was studied. Results comparable to

those for the total study group were

ob-tained.

REFERENCES

1. Clifford, S. H.: Postmaturity with placental

dysfunction. J. Pediat., 44:1, 1954.

2. Sj#{246}stedt, S., Engleson, G., and Rooth, G.:

Dysmaturity. Arch. Dis. Child., 33:123,

1958.

3. Soderling, B.: Pseudo-prematurity, Acta

Paediat., 42:520, 1953.

4. Rumboltz, W. L., Edwards, M. C., and Mc-Googan, L. S.: The small full term infant

and placental insufficiency. Western J.

Surg., 69:53, 1961.

5. Pick, W.: Malnutrition of the newborn sec-ondary to placental abnormalities. New

Engi. J. Med., 250:905, 1954.

6. Gruenwald, P. : Letter to the Editor: Full

term and low birth weight. PEDIATRICS, 29:

333, 1962.

7. Colman, H. J., and Rienzo, J.: The small full

term baby. Obstet. Gynec., 19:87, 1962.

8. Baird, Sir Dugald: The contribution of

obstet-rica! factors to serious physical and mental

handicap in children. Obstet. Gynaec. Brit.

Emp., 66:749, 1959.

9. Engleson, G., Rooth, C., and T#{246}rnblom, NI.: A

follow-up study of dysmature infants. Arch.

Dis. Child., 38:62, 1963.

10. Drillien, Cecil Mary: The incidence of mental and physical handicaps in school age chil-dren of very low birth weight. PEDIATRICS,

27:452, 1961.

11. Bowen, Mary, and Hepner, R.: Placental

in-sufficiency and growth. J. Dis. Child., 98:

567, 1959.

12. Hepner, R., and Bowen, Mary: The placenta

and the fetus. J.A.M.A., 172:427, 1960.

13. McCance, R. A.: Food, growth, and time.

Lancet, 11:671, 1962.

14. Silverman, W. A.: Dunham’s Premature

In-fants. 3rd Ed., New York: Paul A. Hoeber,

Inc., 1961, pp. 530-538.

15. Terman, L. M., and Merrill, M. N.:

Stanford-Binet Intelligence Scale. Boston: Houghton

Mifihin Co., 1960.

16. Dunn, L. M.: Manual for the Peabody Picture

Vocabulary Test. Philadelphia: American

Guidance Service, Inc., 1959.

17. Walker, H., and Lev, J.: Statistical Inference.

New York: Henry Holt, 1953, pp. 151-154.

18. Warkany, J., Monroe, B., and Sutherland,

Betty: Intra-uterine growth retardation.

Amer. J. Dis. Child., 102:127, 1961.

19. Smith, C. A.: Prenatal and neonatal nutrition.

PEDIATRICS, 30:145, 1962.

20. Price, B.: Primary basis in twin studies. A

re-view of perinatal and natal

difference-pro-ducing factors in monozygotic pairs. Amer.

J. Hum. Genet., 2:293, 1950.

Acknowledgment

It is our pleasure to acknowledge the help

pro-vided in this study by Mrs. Sue Underwood, RN.,

Premature Follow-up Nurse; Miss Jeanne Carol

Hopkins, B.S., MT. (ASCP), Research Assistant;

Miss Gwen Amel, RN., Nursery Supervisor of

Emanuel Hospital, and Miss Barbara Goffeney,

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1964;33;327

Pediatrics

S. Gorham Babson, John Kangas, Norton Young and James L. Bramhall