A Prospective Longitudinal Study of Growth in Twin Gestations Compared with Growth in Singleton Pregnancies I. The Fetal Head

E. Albert Reece, MD, Shaul Yarkoni, MD, Mazen Abdalla, MD, Sandro Gabrielli, MD, Theodore Holford,. PhD, Theresa Z. O'Connor, MPH, John C. Hobbins, MD

Since the available data on growth in twin gestations have been derived from retrospective cross-sectional studies with varying results, a prospective longitudinal study was initiated to assess fetal head growth in twin gestations as compared to singleton pregnancies. In uncomplicated twin gestations, growth of the fetal head, based on the increment in growth over time and the rate of growth throughout pregnancy, was found

E

xtensive studies of fetal growth in singleton pregnancies have been conducted and have resulted in the establishment of normal growth profiles for multiple biometric parameters throughout pregnancy. 1 Many of these parameters are traditionally used to assess fetal growth in both singleton and multiple gestations. However, there is no agreement on whether the normative data derived from singleton pregnancies are appropriate for use in the evaluation of multiple gestations. Unfortunately, the available data on growth in twin gestations are derived primarily from retrospective cross-sectional studies with conflicting results and conclusions. 1-7 Jn an attempt to circumvent many of the problems inherent in cross-sectional studies and to characterize precisely the pattern of Received April 9, 1990, from the Section of Maternal-Fetal Med· icine, Department of Obstetrics and Gynecology and the Biostatistics Section, Department of Epidemiology and Public Health, Yale U ni ~ versity School of Medicine, New Haven, Connecticut. Revised man· uscript accepted for publication February 8, 1991. Address correspondence and reprint requests to Dr. E. Albert Reece, Department of Obstetrics and Gynecology, Temple University 3401 N. Broad Street, Philadelphia PA 19140.

not to be significantly different than in singleton pregnancies. In light of these findings, current nomograms derived from measurements obtained in singleton pregnancies remain useful for evaluating fetal head growth in twin gestations. KEY WORDS: Longitudinal, twin, singleton, growth. (/. Ultraso1111d Med 10:439, 1991)

growth in twin gestations, we initiated a prospective longitudinal study to assess fetal head growth in twin pregnancies in comparison with growth in singleton gestations.

MATERIALS AND METHODS Patients were recruited from private obstetrical practices in the community as well as from the outpatient obstetrical clinic at Yale-New Haven Hospital. After obtaining signed informed consent, patients underwent ultrasound examinations every 3 weeks from the 15th week of gestation until term, At the initial examination a careful determination was made as to the location of each twin; the presenting twin being designated twin A and the other, twin B. Subsequent examinations were conducted according to the original twin assignment. d db I Biometric parameters measure include iparieta diameter (BPD), occipitofronta) diameter (OFD), and head circumference (HC). f f The rate o increase in growth for a given eta) measurement for an individual midway between two

© 1991 by the American Institute of Ultrasound in Medicine• J Ultrasound Med 10:439- 443, 1991•0278-4297/91/ $3.50

440

J Ultrasound Med 10:439- 443, 1991

FETAL HEAD GROWTH

time points was calculated as the difference between the measurements at those two time points divided by the~ time difference, ie, [parameter (t(n) - parameter (t(11 - 1))1/[t(rz) - t(n - 1)], where parameter [t(n)] represents a particular fetal measurement at gestational age 1(11). The growth pattern was further categorized by the use of polynomial regression equations. Comparison was also made between fetal head growth in twins and growth in singleton pregnancies reported elsewhere. 8 The above comparison was performed us ~ ing multiple linear regression analyses, in which the following independent variables were included: fetal status (twin or singleton), gestational age (GA), the square of gestational age, interactions between twin and gestational age, and interactions between twin and the square of gestational age. Since measurements were obtained on each fetus multiple times, a variable representing a random effect for the fetus was included in the model. If no interactions between fetal status and gestational age or fetal status and the square of gesta· tional age were observed, then growth of twins relative to singletons was determined by the use of an F-test: F

=

Incremental growth patterns are shown in Figures lA, 2A, and 3A. The mean growth pattern of each measurement depicted in millimeters was best described by a second- or third-degree polynomial regression equation as shown below and depicted in Figures 1C, 2C, and JC: BPD

= -14.6773 +GA x

(2.22845)

+ GA 2

x (0.071095) + GA) x (-0.0015068)

Figure 1 A, Incremental growth of the BPD in twins and singletons across gestational age. The figure demonstrates that growth is significantly less in twin than in singleCon pregnancies. 8, Rate of growth of the BPD in twins and singletons throughout pregnancy. The figure shows no significant difference in the velocity between both groups. C, BPD in twins with fitted third-degree polynomial regression lines.

A.

100

•Normal O Twins

Mean square for twins Mean square error (MSE)

The MSE was modified to account for multiple examinations on each fetus, which were not given in a balanced manner. A correction was made by using the expected value of the MSE given for the random effect in the SAS PROC GLM program.9 The model used for this analysis included components of variance for intrasubject and intersubject variability. In cases in which the estimate of the intersubject variable was negative, a value of 0 was used. This, in effect, indicates use of the MSE to test for the effect of twin gestations in these instances, which turns out to be more conservative than the default used by SAS. Student's t-tests for paired samples were used to determjne whether significant differences existed between twin A and twin B groups.

9

15

11

21

24

27

30

33

38

39

Gellaliclnal Ago (wookl)

8.

12

•Normal OTwins

6

RESULTS 100

__ __

...............__..__...._....._...............

~.._

We examined 35 pregnant women with twin gestations and without medical complications longitudinally throughout the course of pregnancy for a total of 172 examinations with each patient receiving an average of 4.8 scans (range 3-9). Unfortunately, some patients did not comply with their follow-up appointments, and so the total number of scans was less than our target number. Because there was no statistically significant difference in the mean measurements between twin A or twin B, the analyses were performed on twin A only. The measurements done included BPD, OFD, and HC.

12

9

12

c. r . ..

t

~

'ZT 30 GellaliOnal Age (wookl)

15

11

21

24

33

..._~

•

39

7S• Mn'I- • tn• lfl.""°'* X GA•(·CUl50IJaX)XQAI

3

~

'l 11

10

~

!e

60

g

~.E

• Observed PjljjQ

40

• P1odidod Poinl1-

Q

lli 20"'-"'--L-~L---L-

10

1$

2(1

25

__

,_____..__~L---'

30

35

45

J Ultrasound Med 10:439-443, 1991

1so

REECE ET AL

A.

A.

400

~

• Normll

• Norm91

~

"E~~

.

a:; ~

• 110

:c

441

i;:Z:

.c '2

i" I! .. Cl~

..... ~.s

300

200

100

E

o...._..._....._.......__..__..__....._........__._.._..__._..... 3 15

6

9

15

12

18

21

2,

27

30

36

33

• i

39

B.

G•slalian11I Age Cw•tlll)

B.

....•t•

•Normal

I!-

0Twin1

~e

50

30 20

i~

·10

ll ...

·20

13 - ~

.i.5

24 27 30

e>.i!alianal Age (w•lk•)

40

u:; ~~ :h ll:z:

21

18

15

12

9

10 0 •Nalllllll

oTwint

·30 -40

·506

2--'1s'--1"-a-'21-2.._4_.21---'3'-o__...33__.3,_,_.39 1__,9..__1... •5 3.__...

350

130

e

1120

z.

110

~

100

C!

90

e

10

"

i

j

-...!.i

15 II 21 24 27 30 Gaslalion;al Ag• Cwaoks )

12

c.

n

1-1!

·:·.

· ~

~ il

5"""'~

60

so

..·:.

;;

40

~

30 20.___..__......._ 20 15 10

.

......._ 25

11111 11 ~

__..._ 30

• Observed Points • Pradi'1•d Point•

. .,,.,:. .·•.·. ·.i·: .. -1·.

:c

100

35

'0

'5

AG• (w1•k•l

+ GA x (7.05084) + GA2

x (-.069530)

= -132.7897 + GA x (18.22309) + GA2 x (-0.15708)

The F-test results for the linear, quadratic, and cubic terms are given in Table 1. The overall difference in incremental growth for both HC and OFD between twins and singletons was not significant. However, the incremental growth of the

10

Xa ~

39

J

-~t · ·.,·

;:;.~:

~

ii.Ii··.

200

150

......... .,

, :a.•

250

~.__

__,..___.._~

Figure 2 A, Incremental growth of the OFD in twins and singletons across gestational age, demonstrating no significant difference between twins and singletons. 8, Rate of growth of the OFD in twins and singletons throughout pregnancy. The figure shows no significant difference in the velocity between both groups. C, OFD in twins with fitted second-degree polynomial regre56ion lines.

OFD = -53.9499

.

~

•.

36

••'.'!!'··....·II ••

300

.s-ai ~

33

J• · 11t.tUGllDS • :SIO , C1111JDIMa5) KCA • ( · (l . \$7CdlleG~

!.

80

HC

9

.~

...'

...,..

~ ~:· I

• Ollsorvod Points • Prldic11d Points

__

_ _.__.....__.......__......._ ......... 15

20

2S

30

35

~~

40

45

G•Slatianal o\go (wHks )

Figure 3 A, Incremental growth of the HC in twins and singletons across gei;tational age, demonstrating no significant difference between twins and singletons. B, Rate of growth of the HC in twins and singletons throughout pregnancy. The figure shows no significant difference in the velocity between both groups. C, HC in twins with fitted second-degree polynomial regression lines.

biparietal diameter was found to be significantly less in twins when compared with singletons, although the difference in their mean values was only 1.88 mm. Results of the F· tests and adjusted means for these three parameters are shown in Table 2. The rate of growth for the three parameters (BPD, OFD, and HC) was also compared between twins and singletons and showed a slight decrease throughout pregnancy (Figs. 1B, 2B, and 3B). The growth rate assumed a linear relationship with gestational age for both OFD and HC, but a second-degree equation described the rate of growth for the BPD. There were,

442

JUltrasound Med 10:439- 443, 1991

FETAL HEAD GROWTH

Table 1; f-Test Results for the Linear, Quadratic, and Cubic Terms F-Test for f -Test for p f -Test for Linear Term P Value Quadratic Term PValue Cubic Term Value (OF)

(OF*)

BPD OFD

HC

5316.83 (1,119) :S0.0001 2074.18 (1,94) !S0.0001 763..44 (1,106) =s0.0001

118..47 (l,119) 45.79 (1,94) 9.04 (l,106)

:S0.0001 4.21 (1,119) 0.042 !S0.0001 1.10 (1,94) 0.296 =0.0033 0.63 (1,106) 0.429

OF, degrees of freedom,; BPD, biparietal diameter; OFD, occipitofrontal diameter; HC, head drcum· fe renc

~.

however, no significant differences between twins and singletons fot either BPD, HC or OFD as shown by the F-tests •n Table 3.

DISCUSSION This study did not find clinically important differences between twin and singleton pregnancies in growth of the fetal head as assessed by multiple parameters. Other studiesZ3 have found that the BPD growth in twins is similar to that in singletons until the third trimester when the BPDs of twins become smaller than singletons, with a significant difference observed after 27 weeks gestation. Similar findings were reported by Houlton in her study of 28 twin pregnancies. 4 Before 30 weeks gestation, she found no difference in BPD growth, but beyond 30 weeks, the growth rate between twins and singletons was similar in only 39% of the population and divergent in 61 %. Gottlicher et al ~ also found divergence in growth beyond the late second trimester. In a unique study, Grennert et aP compared each twin individually to singletons and found no significant difference between twin A and the singleton until after the 32nd week of gestation when the difference be.. came significant. In yet another study, Leveno et al6 studied 123 normal sets of twins and obtained multiple

BPD measurements between 16 and 40 weeks gestation, They found that the BPDs of twins were consistently smaller than those of singletons. From these results, the authors generated a nomogram that they proposed for use in the evaluation of growth in twin gestations. The above results are in sharp contrast to studies conducted by Crane et al7 and the current study. Crane et al7 retrospectively studied 135 consecutive twin pregnancies, obtaining BPD measurements in both fetuses and newborns. They found that in normal twin pregnancies, BPD growth in twins was similar to that in singletons throughout the pregnancy. Similarly, our results, collected in a prospective longitudinal manner, demonstrate that in uncomplicated twin pregnancies, growth of the fetal head is not significantly different from growth in singleton pregnancies. Although the incremental growth of the BPD was significantly less in twins as compared to singletons, growth of the head circumference was not significantly different. This discrepancy may be caused by a compression effect on the BPD because of fetal crowding, but such an effect would not alter the head drcumference size. The apparent compression effect of the BPD was not fully manifested in the OFD measurements. In fact, we observed no s.ignificant difference in the OFD between twins and singletons. In conclusion, the results of the present study show

Table 2: Incremental Growth of Fetal Head Measurement BPD OFD HC At 15-21 wk At 21-29 wk At~30 wk

DF

f -Test Value

P Value

Adjusted Mean Measurements• Twin

Singleton

(mm)

(mm)

Mean Ges· tational Age (wk)

1,95.52 1,110. .94

13.60 2.09