Department of Obstetrics and Gynaecology, Catholic University, School of Medicine, 00168 Rome, Italy
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Abstract |
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Key words: birth weight discordance/growth restriction/pre-eclampsia/twin pregnancy
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Introduction |
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The present study was carried out to verify whether twin pregnancies complicated by pre-eclampsia are associated with: (i) negative fetal outcome in terms of low birth weight and preterm delivery; (ii) higher rate of inter-twin weight discordance; and (iii) higher prevalence of SGA compared with normotensive twin pregnancies.
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Materials and methods |
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The study population was of ethnic uniformity due to the large predominance of white Italians (97%). During the time period covered by this study, no policy of special antenatal clinical care was enforced for twin gestations other than encouraging bed rest. Across all subjects, the indications for planning delivery were: severe pre-eclampsia according to ACOG (American College of Obstetricians and Gynecologists, 1986), presence of fetal distress as indicated by fetal heart rate recording, oligo-anhydramnios, premature rupture of membranes, cholestasis in presence of a mature lecithin/sphingomyeline ratio, chorionamnionitis or any other general obstetric indication. The finding of intrauterine fetal discordance was not an indication for planned delivery if not associated with other signs of fetal distress. In case of intrauterine demise of one fetus, delivery was immediately planned after 27 weeks gestation, when placentation was monochorial, or as soon as lecithin/sphingomyeline ratio was more than 2 when the placentation was dichorial. Corticosteroids were used to accelerate fetal lung maturation in both pre-eclamptic and normotensive twin pregnancies.
For the purpose of data analysis, information was extracted from the records and entered into a personal computer database. Information included aspects of prenatal care, previous medical history, complications, intrapartum care, delivery, fetal outcome and post-partum course. Data entries were then accumulated and organized in tabular form on a spreadsheet database. Case notes on the twins were reviewed with reference to birth weight differences, birth order and sex combination. In each case, the membrane separating the amniotic sacs had been examined to determine whether it was monochorionic or dichorionic. In the case of same sex twins and fused placentae, the membranes separating the amniotic sacs were microscopically examined by our pathologists to exclude the presence of chorionic tissue. Although examination of the placentae and membranes is not the most accurate way to diagnose specific twin type, the margin of error was considered negligible and other methods were not used. Where clinical and ultrasound evidence of twintwin transfusion syndrome was available, a difference in haemoglobin concentration of 5 g/dl at birth was considered as corroborative when the placental type was monochorionic.
Eighty-nine per cent of all pregnancies during the study period under consideration were evaluated with routine ultrasound in the early second trimester. No correction was made when significant differences (more than 7 days) were not evident in comparing gestational age between ultrasound and last menstrual period. A case was excluded from analysis in the absence of ultrasound or when this was only performed near delivery with uncertain information on gestational age.
SGA was diagnosed as a birth weight lower than the 10th percentile according to either a national standard curve for singleton births (Gagliardi et al., 1975) or a recently elaborated standard curve for twin births from white population (Cohen et al., 1997
).
Inter-twin birth weight difference was reported as weight discordance. Twin A was defined as first born and twin B as second born. The absolute weight discordance (AWD) between two twins was defined as heavier twin minus lighter twin and expressed in grams. The percentage weight discordance (PWD) was defined as (heavier twin lighter twin)x100/(the heavier of the two) and expressed as a percentage. Signed percentage weight discordance (SPWD) was defined as (twin A twin B)x100/(the heavier of the two twins) and expressed as signed percentage. The latter, unlike other measures of weight discordance, indicates which twin is heavier according to delivery order. The twin B/twin A SGA rate ratio was calculated to allow a direct comparison of frequencies between the two groups of twin pregnancies.
Statistical analysis included the Student's t-test for comparison of averages, the Wilcoxon rank sum test for comparison of medians when the distribution of the data was not normal and the 2 or Fisher's exact test when appropriate for comparison of frequencies. P values < 0.05 (two-tailed) were considered significant. A power analysis was performed for statistical inference. The value reported in the tables represents the power of the statistical test used to detect the observed difference between two sample mean values or frequencies. This value is derived from assessing
= 0.05 and a sample size of 76 when the t-test is used (Glanz, 1987
) or a 5.3 ratio (400/76) when the
2 is applied (Marascuilo and McSweeney, 1977
).
Power determination in regression analysis was obtained according to Cohen (Cohen, 1977) by using the Fisher z transformation for the critical value of r and for sample r. Survival statistics and plots were obtained by using the KaplanMeier non-parametric method and the P value was obtained through the log rank (MantelCox). Multiple comparisons with Bonferroni correction were used to isolate differences between groups. All computations were performed on an Apple Macintosh Performa 6400/200 with appropriate software (Microsoft Excel, Abacus StatView).
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Results |
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Discussion |
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The higher rate of SGA neonates in pre-eclamptic twin pregnancies suggested more detailed analysis of the birth weight characteristics in each twin pregnancy. Despite a total birth weight difference of about 200 g between the two study groups (not significant), some significant differences were found in inter-twin weight discordance however expressed (whether as absolute or percent or signed percent). Like other studies (Taylor et al., 1998), in normotensive twin pregnancies no significant differences were observed in the birth weight within pairs at any week. While lack of significance could be ascribed to a type II error, it still indicates that if a mean size difference should exist, it would be negligible. In twin pregnancies with pre-eclampsia this difference became clear. It has previously been reported that early onset pre-eclampsia in singleton pregnancies was associated with higher frequency of SGA neonates (Ferrazzani et al., 1990
). Similarly, in twin pregnancies it was observed that early onset pre-eclampsia was associated with a higher degree of percentage discordance as a consequence of lower size in second twins. It is important to note that in our sample the median time interval between the first observation of proteinuria and delivery was 3 days (range 025). So early onset pre-eclampsia was approximately coincident with early birth.
Observed from a different point of view, the findings argue that growth discordance higher than 25% was associated with lower gestational age at delivery in both pre-eclampsia and normotensive twin pregnancies. No other authors have observed this relationship between growth discordance and gestational age (Blickstein et al., 1987; Taylor et al., 1998
), probably because they studied only normotensive twin pregnancies where this association is much less evident. Since this was a retrospective study, it was not possible to control for timing of delivery and factors that may have contributed to the decision to deliver preterm twins. All twin pregnancies during the study period, regardless of indication for delivery were considered. To a certain extent we were able to minimize some of these concerns by documenting a comparable gestational age distribution in both groups.
Twin pregnancies with more than 25% growth discordance were delivered (or had to be delivered) earlier. The low gestational age at delivery in the presence of severe percent weight discordance could be related to the high rate of SGA among second twins. This association was much more evident in pre-eclampsia than in normotensive twin pregnancies, probably because in women with pre-eclampsia there is an increased likelihood of the second twin being SGA. It is well known that in twin pregnancies, second twin outcome is more jeopardized than the first (Friedman et al., 1977; Essel and Opai-Tetteh, 1994
). The findings of this study confirm this assertion by indicating that the rate of SGA and stillbirth increased in second twins in both groups. However, even if not in a significant manner, the stillbirth rate in pre-eclampsia was almost double that in normotensive twin pregnancies. It seems reasonable to consider this as relevant to the higher rate of SGA among second twins in pre-eclampsia.
The findings of this study highlight that when both twins are SGA without discordance, delivery is closer to term in normotensive pregnancy. On the other hand, when both twins are AGA without discordance, delivery is more distant from term. The paradox is only apparent and only evident when SGA is defined according to the singleton growth curve. In fact, it is well known that the birth weight of an uneventful twin pregnancy progressively diverges from singleton median birth weight as it approaches term. In other words, neonates born from an uncomplicated twin pregnancy at term are SGA when compared to singleton standards. When the week of delivery is earlier, birth weight may still be within normal limits for singleton standards. The reason for a premature delivery when both twins are AGA could simply be ascribed to premature labour, the most frequent complication in twin pregnancies. In pre-eclampsia there was no significant relationship between the occurrence of SGA neonates and duration of gestation, probably because the maternal indication for timing of delivery could have interfered with the natural evolution of pregnancy.
In conclusion, the rate of inter-twin birth weight discordance is similar between pre-eclamptic and normotensive pregnancies. In the presence of similar gestational weeks at delivery, pre-eclampsia shows a higher rate of SGA among second twins than in normotensive pregnancies. In both pre-eclamptic and normotensive twin pregnancies, earlier delivery weeks were related to birth weight discordance >25% or to the concomitant occurrence of SGA second twin and discordance >25%, but not to the presence of SGA second twin alone. These associations were more strongly evident in pre-eclampsia.
The term SGA, deriving from a statistical concept, does not distinguish normal and healthy fetuses that have a weight below the 10th percentile from those who are small because of intrauterine malnutrition. The `healthy SGA' could be defined as the neonate being constitutionally small with no deprivation of in-utero nutrients, and the `at-risk SGA' could be identified as the malnourished fetus that is small because of in-utero deprivation of nutrients and oxygen, as a consequence of placental insufficiency. In pre-eclampsia placental insufficiency is frequently observed and it can be associated with endothelial activation and damage (Myatt et al., 1997; Daniel et al., 1998
). In the light of the findings by other authors (Blickstein and Lancet, 1988
), indicating that the smallest discordant twin delivered at term has normal outcome, the data presented here suggest that also in twin pregnancies there are two types of SGA neonates: healthy (probably constitutional) and at risk (malnourished). In general, the `healthy SGA' neonate can be identified in twin pregnancies where one (generally the first presenting) or both twins are under the 10th percentile and pregnancy can end close to term. The `at-risk SGA' neonate is to be found prevalently among second twins when growth discordance is evident.
Prospective studies are needed to confirm the findings of this study.
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Notes |
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References |
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Submitted on May 17, 1999; accepted on September 27, 1999.