We investigated the prospective risk of unexpected IUD in MCDA pregnancies with structurally normal fetuses, uncomplicated by TTTS or IUGR, which has not to our knowledge been reported in the literature to date. Population-based twin studies provide little information of relevance to this question, as they fail to stratify for chorionicity, fail to distinguish complicated from uncomplicated twin pregnancies, and record gestational age not at fetal death but at delivery, often many weeks later [20
]. Indeed the prospective risk of stillbirth in twins overall has yet to be addressed in the literature. Older studies in both singletons and twins have concentrated on overall risks of fetal death as a proportion of total births, or weekly rates, rather than deriving prospective risks by gestation as a function of continuing pregnancies [22
]. We have previously applied the latter approach to singletons to illustrate how prospective risk declines with gestational age and is a more useful measure both for patient counselling and timing of delivery, as it expresses the risk of fetal death at any particular point in gestation for the remainder of the pregnancy [18
Sebire et al. suggested that the main risk of fetal death in MC pregnancies was before 24 wk, as after this, the rate of perinatal loss was only slightly higher in MC than in DC pregnancies (4.9% versus 2.8% of pregnancies) [3
]. This, however, was a referral population with a high incidence of TTTS and other pathologies, and no recent ultrasound in many cases, and so is not comparable with our study of otherwise uncomplicated MCDA pregnancies which suffered an unexpected death within 2 wk of a normal scan.
Our data suggest instead that even intensively monitored, apparently healthy MCDA pregnancies remain at substantial risk of IUD after 24 wk (4.6% of pregnancies and 3.3% of fetuses). IUDs after 24 wk occurred in the third trimester, and predominantly after 32 wk of gestation, at which time the prospective risk of subsequent IUD was 1/23 pregnancies. Our findings provide useful information for counselling parents with MCDA pregnancies, and notwithstanding the limitation of small numbers, may be used to inform decisions regarding the optimal timing of delivery.
Analysis of the antenatal findings on fortnightly scans shows that deaths after 24 wk occurred unassociated with any antenatal evidence of either TTTS or IUGR, and thus were unexpected. Only two of the seven pregnancies complicated by an IUD had a definite cause at autopsy. Late onset TTTS is rare but not unknown, and here seems to have been unpredictable. Recent case reports [25
] suggest that thrombosis of a previously patent compensatory anastomosis, either AAA or reverse arteriovenous, can result in haemodynamic imbalance and thus acute onset TTTS, as suggested in one of the two cases in this study. The fetal deaths in the present study occurred despite strategies aimed at preventing them, specifically, fortnightly ultrasound and Doppler surveillance in a tertiary fetal medicine unit, and elective delivery at 36–37 wk).
We acknowledge a number of limitations of our study. First, there is the retrospective nature of the analysis. Notwithstanding this, clinical and ultrasound findings were entered prospectively into our database, and we reviewed all cases entered over the 12-y period since its inception. Second, caution is advised in view of small numbers. However, this is the first series to our knowledge to report this outcome in otherwise normal MCDA twins, and the deaths were spread relatively evenly over the study period.
Third, there is a lack of comparative data in other twin pregnancies. Use of a DC control group was precluded by they fact that our protocol for DC pregnancies differs from that for MCDA pregnancies, as in most centres, with DC monitoring performed outside the fetal medicine unit and at less frequent intervals (every 4 wk rather than every 2 wk), and with elective delivery 1 to 2 wk later than for MCDA pregnancies. In terms of complicated MC twin pregnancies, few with TTTS or IUGR and two live fetuses remain undelivered after 32 wk. We chose not to use the brain:liver ratio as an indicator of IUGR at post-mortem because of its insensitivity [27
]. Birth weights were also not used as an indicator of discordant IUGR in view of the variable interval from death to diagnosis, and the even greater interval between death and delivery (up to several weeks) following single IUD, in which varying degrees of post-mortem weight loss and continued growth of the surviving twin might confound measured birth weights.
Our findings have a number of clinical implications. The high rate of unexpected third trimester fetal death might be obviated by a range of preventative strategies. One would be to increase the frequency of monitoring. Although growth is only usefully measured every 2 wk, more frequent surveillance could include amniotic fluid volume and distribution, and fetal Doppler waveforms. This might allow earlier identification of the occasional case of late onset TTTS, and thus prevention of IUD through timely delivery. However, it is not clear how more frequent monitoring would prevent unexplained IUDs, just as this strategy does not appear to prevent them in singleton pregnancies [28
Another preventative approach might be earlier delivery. Complicated MCDA twin pregnancies, such as those with TTTS or abnormal umbilical artery Doppler, are already delivered in many centres at 32 wk. At this stage neonatal survival is now comparable to that at term [30
]. Minor neonatal morbidity is still likely at 32 wk, but the chance of major respiratory and neurological problems is reduced substantially by administration of antenatal steroids [32
]. Elective vaginal delivery would increase the chance of failed induction, but there is an increasing view that elective caesarean section is preferable to preterm induction of labour in MCDA twin pregnancies, both to avoid a caesarean section being performed as an emergency and to obviate the risks of acute intertwin transfusion during labour [33
]. Accepting that elective delivery of all MC twins at 32 wk would carry an attendant neonatal morbidity, the complications of iatrogenic prematurity could be lessened if an intermediate gestation were chosen, e.g., 34 wk. Although neonatal morbidity would be reduced, so would the number of fetal deaths prevented. Acknowledging the limitation of small numbers in this study, 80% of fetal deaths at 32 wk or greater and 60% at 34 wk or greater, respectively, would have been prevented if fetuses were delivered before these gestation time points. When expressed per pregnancy, one case of IUD would be prevented for every 23 MC pregnancies delivered at 32 wk and one for every 30 pregnancies at 34 wk. The above figures underestimate the potential gain of such strategy, because single IUD in MCDA pregnancy also exposes the surviving co-twin to a substantial risk of brain injury and thus long-term handicap from acute intertwin transfusion [6
Major neurodevelopmental sequelae are now rare in otherwise well babies delivered after 32 wk. MC twins are at increased risk of cerebral palsy compared to DC twins, but this is mainly prior to 32 wk and in pregnancies complicated by TTTS and IUGR [34
]. Prematurity per se is not considered responsible for the high risk of neurological morbidity in MC twins, but rather the haemodynamic imbalance unique to MC placentation [36
]. Thus, uncomplicated MC twins should not be at substantially increased risk of neurological sequelae from elective premature delivery at or after 32 wk. Indeed, elective delivery may reduce their risk of neurodevelopmental injury, as single IUD in MC twins is a well-established risk factor for cerebral palsy [6
In conclusion, apparently uncomplicated MCDA pregnancies remain at substantial risk of fetal loss as they approach 32 wk of gestation, whereafter one in 23 (4.3%) will suffer an unexpected IUD. This risk is exacerbated by the 40%–50% risk of co-twin death or neurological injury following a single IUD [6
]. If our findings are confirmed in other observational series, our suggestion that earlier delivery might prevent this adverse outcome could be tested by randomised trial.
As mothers wait longer to have children and more of them make use of reproductive technologies (medications that stimulate egg production and ripening, and in vitro fertilization, for example), multiple pregnancies (mostly twins and triplets) have become a lot more common. Such pregnancies carry a higher risk for mothers and fetuses, and obstetricians have developed more involved regimens of check-ups and tests to minimize those risks.
Why Was This Study Done?
Guidelines for how to best manage multiple pregnancies are still under development. This study looked at how the risk of complications changed from 24 weeks of pregnancy (the earliest time point after which preterm babies can survive) on throughout the last trimester.
What Did the Researchers Do?
They looked at identical (monozygotic) twins that shared a common placenta but had their own amniotic sac (the sac that holds the protective liquid called amniotic fluid that surrounds the fetus inside the uterus). Twins with these characteristics make up about two-thirds of all monozygotic twins. The researchers studied the records of one United Kingdom hospital that specializes in fetal care over a 12-year period (from 1992 to 2004) and looked at the clinical details and ultrasound scan records.
What Did They Find?
Of a total of 480 completed identical twin pregnancies with shared placentas, 151 were found to be uncomplicated; that is, both fetuses seemed normal and healthy on all of their regular check-up scans (done every two weeks). In seven of those 151 pregnancies, however, either one or both of the fetuses died late during pregnancy, without any prior warning signs.
What Does This Mean?
Despite intensive surveillance of women during pregnancy, this particular group of pregnant women experienced a substantial rate of unexpected fetal death. The numbers in this study are small, however, and this is only one study (one needs to be careful about drawing conclusions based on one small study). In addition, the study was not designed to test a specific question but just looked at the records retrospectively. For all of these reasons, it is not clear whether these results are representative of what happens in general.
Larger studies need to test whether this risk of fetal death late in pregnancy among identical twins sharing a placenta is common. If follow-up studies confirm the preliminary results here, it might be worth delivering such twins prematurely (that is, at around 32 weeks of pregnancy), when the risks associated with premature birth are relatively small compared to the risk of losing one or both of the fetuses after that date.
Additional Online Resources
Information about different types of multiple pregnancies, screening guidelines, and possible complications can be found at the following sources.