Department of Obstetrics and Gynecology, Hôpital Antoine Béclère, Assistance Publique Hopitaux de Paris, Université Paris XI, 92140 Clamart, France
1 To whom correspondence should be addressed. e-mail: francois.audibert{at}abc.ap-hop-paris.fr
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: birth weight discordance/embryo reduction/growth restriction/twin birth
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Data were obtained from the obstetric and perinatal databases for all pregnancies, and ultrasound reports and individual charts were reviewed for all cases with birth weight discordance or embryo reduction. Overall, 358 sets of dichorionic twins were included. Six cases were excluded because of intra-uterine fetal death at 4 weeks before birth. Indeed, birth weight discordance was obviously present in these cases, and we have considered that keeping these cases would have biased the definition of our study groups (weight discordance could be a cause or a consequence of fetal death). None of these excluded cases had undergone embryo reduction procedure. Another six cases were excluded because of missing data, leaving 346 dichorionic pregnancies for the final study group.
Birth weight discordance, expressed as a percentage, was determined as 100(A-B)/A, where A was the birth weight of the heavier twin and B was the birth weight of the lighter twin (Cooperstock et al., 2000). Small for gestational age (SGA) newborns were defined by a birth weight <10th percentile for gestational age (Leroy and Lefort, 1971
; Keen and Pearse, 1985
). Discordant sets of twins were defined by a birth weight discordance >20%.
Statistical analysis was performed using Stata 7.0 software (Stata Corporation, College Station, TX, USA). Univariate analysis was performed by 2-test for categorical variables and by two-tailed t-test for numerical variables. Multivariate analysis was done by stepwise forward logistic regression, with a P value of
0.25 for entry into the model. The following variables were either previously demonstrated to be associated to growth restriction or were found to be associated with discordance in the univariate analysis and were therefore included in the model: maternal age >35 years, nulliparity, ovulation induction, IVF (including ICSI and oocyte donation), embryo reduction, fetal or neonatal malformation. A P-value < 0.05 was considered significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Table I compares the characteristics of pregnancies, according to the presence or absence of birth weight discordance. Among discordant twins, the rate of pregnancies obtained by ART was higher than among concordant twins (72 versus 60%, P = 0.053). The rate of embryo reduction was significantly higher in discordant twins (14.7 versus 6.6%, P = 0.03). Moreover, the risk of birth weight discordance increased with greater initial number of embryos [20.2% (64/317), 28.6% (6/21), 57.1% (4/7) and 100% (1/1) respectively for an initial number of two (no reduction), three, four, and five embryos, P = 0.02]. Data on outcome of pregnancies according to birth weight discordance are given in Table II. Perinatal mortality and morbidity were significantly increased in the presence of discordance. Birth weight discordance was associated with a four-fold increased risk of neonatal mortality, and a two-fold increased risk of neonatal intensive care unit (NICU) admission. When comparing reduced versus non-reduced pregnancies, we found a significantly higher incidence of birth weight discordance, but no difference was noted in the incidence of small for gestational age new-borns, in one or both twins. Moreover, birth weights did not differ significantly between reduced and non-reduced pregnancies (Table III). We calculated the number needed to harm with the formula 1/(0.0380.02) = 5.5, which means that, based on our results, 56 procedures of reductions might give rise to one more discordant twin set. In multivariate analysis, embryo reduction was the only significant and independent risk factor for the occurrence of birth weight discordance (Table IV).
|
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Several limitations of this study must be acknowledged: this is a retrospective study conducted in a single tertiary perinatal centre, and our population may not reflect the general twin population, due to a high rate of ART, and to a high rate of pregnancies referred because of complications (this bias concerns our whole population, not only the subset of those twins born after embryo reduction). However, the proportion of discordant twin pregnancies in our population is consistent with other reports using the same definition of birth weight discordance. Indeed, Hanley et al. 2002 found a discordance in 61/341 (17.9%) of dichorionic pregnancies in a recent study. In the same way, Torok et al. note that 26/136 (19.1%) of non-reduced dichorionic pregnancies showed a birth weight discordance of
20% (Torok et al., 1998
). All these studies might be concerned by the same selection bias but, to our knowledge, there is no available population-based data about birth weight discordance in dichorionic twins.
We focused our attention towards growth discordance rather than intrauterine growth restriction, because discordance raises a difficult challenge in choosing the appropriate time for delivery. Indeed, the decision to deliver twins prematurely when only one twin appears compromised may result in unnecessary prematurity and subsequent morbidity for the other twin. While several studies emphasise the clinical importance of growth discordance in twins (Hollier et al., 1999; Cooperstock et al., 2000
), others conclude that prematurity and low-birth-weight, not birth weight discordance, are the greatest threat to the new-born twin (Patterson and Wood, 1990
; Fraser et al., 1994
).
It is not clear whether the association we found between embryo reduction and growth discordance is causative; however, we believe that we controlled for the major bias that could generate such an association. The mechanisms by which birth weight discordance might be caused by embryo reduction remain unclear and warrant further research. The hypothesis of uterine imprinting determined early in gestation is proposed by Evans et al. 2001. This early imprinting might persist after the reduction, thus limiting the functional placental territory dedicated to the adjacent fetus. Another possible cause of growth restriction in one twin is the local inflammatory response that could be developed at the contact of the reduced sac. However, there are currently no studies to confirm this hypothesis.
We conclude that multifetal pregnancy reduction should now be considered an independent epidemiological risk factor for birth weight discordance in twins, a condition associated with a poor perinatal outcome. Therefore, ultrasound monitoring of twin pregnancies resulting from reduction should be encouraged. In addition, further studies examining the outcome of reduced pregnancies should include the issue of discordance in their results. Finally, our findings add further concern about infertility therapy risks, and emphasise the need for preventing high-order multiple pregnancies.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Blickstein, I., Goldman, R.D. and Mazkereth, R. (2000) Risk for one or two very low birth weight twins: a population study. Obstet. Gynecol., 96, 400402.
Cooperstock, M.S., Tummaru, R., Bakewell, J. and Schramm, W. (2000) Twin birth weight discordance and risk of preterm birth. Am. J. Obstet. Gynecol., 183, 6367.[CrossRef][ISI][Medline]
DAlton, M.E. and Simpson, L.L. (1995) Syndromes in twins. Semin. Perinatol., 19, 375386.[ISI][Medline]
Evans, M.I., Berkowitz, R.L., Wapner, R.J., Carpenter, R.J., Goldberg, J.D., Ayoub, M.A., Horenstein, J., Dommergues, M., Brambati, B., Nicolaides, K.H., et al. (2001) Improvement in outcomes of multifetal pregnancy reduction with increased experience. Am. J. Obstet. Gynecol., 184, 97103.[CrossRef][ISI][Medline]
Fraser, D., Picard, R., Picard, E. and Leiberman, J.R. (1994). Birth weight discordance, intrauterine growth retardation and perinatal outcomes in twins. J. Reprod. Med., 39, 504508.[ISI][Medline]
Hanley, M.L., Ananth, C.V., Shen-Schwarz, S., Smulian, J.C., Lai, Y.L. and Vintzileos, A.M. (2002) Placental cord insertion and birth weight discordancy in twin gestations. Obstet. Gynecol., 99, 477482.
Hollier, L.M., McIntire, D.D. and Leveno, K.J. (1999) Outcome of twin pregnancies according to intrapair birth weight differences. Obstet. Gynecol., 94, 10061010.
Keen, D.V. and Pearse, R.G. (1985) Birthweight between 14 and 42 weeks gestation. Arch. Dis. Child., 60, 440446.[Abstract]
Kogan, M.D., Alexander, G.R., Kotelchuck, M., MacDorman, M.F., Buekens, P., Martin, J.A. and Papiernik, E. (2000) Trends in twin birth outcomes and prenatal care utilization in the United States, 19811997. JAMA, 284, 335341.
Leroy, B. and Lefort, F. (1971) Poids et taille des nouveau-nés à la naissance. Rev. Fr. Gynecol. Obstet., 66, 391396.[Medline]
Martin, J. and Park, M. (1999) Trends in twin and triplet births. Natl Vital Stat. Rep., 47, 116.
OBrien, W.F., Knuppel, R.A., Scerbo, J.C. and Rattan, P.K. (1986) Birth weight in twins: an analysis of discordancy and growth retardation. Obstet. Gynecol., 67, 483486.[Abstract]
Patterson, R.M. and Wood, R.C. (1990). What is twin birthweight discordance? Am. J. Perinatol., 7, 217219.[ISI][Medline]
Petterson, B., Blair, E., Watson, L. and Stanley, F. (1998) Adverse outcome after multiple pregnancy. Baillieres Clin. Obstet. Gynecol., 12, 117.[ISI][Medline]
Schieve, L., Meikle, S., Ferre, C., Peterson, H., Jeng, G. and Wilcox, L. (2002) Low and very low birth weight in infants conceived with use of assisted reproductive technology. N. Engl. J. Med., 346, 731737.
Silver, R.K., Helfand, B.T., Russell, T.L., Ragin, A., Sholl, J.S. and MacGregor, S.N. (1997) Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: a case-control study. Fertil. Steril., 67, 3033.[CrossRef][ISI][Medline]
Torok, O., Lapinski, R., Salafia, C.M., Bernasko, J. and Berkowitz, R.L. (1998) Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples. Am. J. Obstet. Gynecol., 179, 221225.[ISI][Medline]
Ville, Y., Hyett, J., Hecher, K. and Nicolaides, K. (1995). Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N. Engl. J. Med., 332, 224227.
Submitted on August 29, 2002; accepted on October 23, 2002.