A total of 262 consecutive TTTS cases were treated via SLPCV between March 2006 and May 2011. Of the 262 twin gestations, 242 (92%) had at least one neonatal survivor and 185 (71%) had dual survivors at 30 days. All demises prior to 30 days after birth, whether intrauterine (N=78) or in the neonatal period (N=19), were excluded from the analysis. Of the 427 “total survivors”, 137 were delivered at a gestational age of less than 32 weeks, and 134 of those had routine cranial ultrasounds. Of the remaining 290 30-day survivors that were born at or beyond 32 weeks' gestation, 108 had cerebral imaging due to other clinical indications, and 182 had no clinical indication for imaging and thus did not undergo an imaging procedure. Thus, among our sample, 242 “high-risk survivors” had delivery, demographic, 30-day survivorship, and imaging information available for analysis (see ).
Flow diagram of study cohort. TTTS = twin-twin transfusion syndrome; GA = gestational age.
Among the entire cohort of 427 survivors, 46 (10.8%) had a documented cerebral lesion and 18 (4.2%) had a documented severe lesion if survivors with only grade I–II IVH and/or nonspecific echogenicity were excluded. All survivors with a documented cerebral lesion (N=46) had a cranial ultrasound except for one who had magnetic resonance imaging only. Of the 45 survivors with a cranial ultrasound, 12 had an additional follow-up magnetic resonance imaging and 2 others had follow-up computed tomography scan. Among the 242 “high-risk survivors” indicated for cerebral imaging, the rates for any cerebral lesion and severe cerebral lesion were 19.0% and 7.4%, respectively. In this sub-group of “high-risk survivors”, the prevalence of any cerebral lesion and severe cerebral lesion in the survivors born between 24 to <28 weeks was 44.7% and 18.4%; between 28 and <32 weeks was 20.8% and 7.3%; and 32 weeks or greater was 8.3% and 3.7%, respectively (see ).
Prevalence of any cerebral lesion and severe cerebral lesion after laser surgery for TTTS in the “high-risk survivors” according to gestational age at birth. GA=gestational age.
presents descriptive statistics for the risk factors and outcomes by donor/recipient status and overall for the “high-risk survivors”. Multiple lesions were found in several of these survivors. Documented severe lesions included: grade III or IV IVH (N=6; 2.5%), PVL (N=7; 3%), ventriculomegaly/hydrocephalus (N=6; 2.5%), microcephaly (N=1; 0%), Dandy-Walker cyst (N=1; 0%), and bilateral or multiple choroid plexus cysts (N=1; 0%). No survivors were diagnosed with single or multiple infarctions. There were seven survivors with residual anastomoses; among these, two had grade I–II IVH and one had a co-twin with an intrauterine fetal demise (IUFD) but no lesions. None of the survivors with residual anastomoses had severe lesions. No significant difference in the rate of any cerebral lesion were noted in the sub-group of “high-risk survivors” with an IUFD (7.7%) compared to those with dual survivors (20.4%, p=0.18). Similarly, no difference in prevalence of severe cerebral lesions were detected in these two sub-groups (3.8% vs. 7.9%, p=0.70, respectively).
Descriptive statistics of donors, recipients, and both in “high-risk survivors” (N=242).
Using the multilevel modeling approach, it is possible to compute an intraclass correlation that represents the proportion of total variation in the outcome present at each level of the model. The intraclass correlation of the empty model for any lesion (i.e., a multilevel model with no predictors) was 0.259, indicating that roughly a quarter of the variation in any lesion development outcome was attributable to pregnancy-level, rather than individual-level, effects, demonstrating the need to account for both sources of variation in modeling survivor outcomes. A series of multilevel logistic regression models were then conducted in Mplus to investigate the relationships, if any, between individual- and pregnancy-level risk factors and likelihood of any lesion. presents the unadjusted regression model results from a series of analyses in which each risk factor for any lesion was tested in the model one-at-a-time. Higher birth weight (kg) (OR=0.12, 95% CI=[0.04,0.34], p<0.001) and later gestational age at birth (OR=0.73, 95% CI=[0.63,0.85], p<0.001) were protective. The binary indicator of prematurity defined as birth <32 weeks (OR=4.95, 95% CI=[1.91,12.81], p=0.001) and < 28 weeks (OR=6.25, 95% CI=[2.16–18.07], p=0.001) were significant risk factors for development of any lesion in the “high-risk survivors”.
Unadjusted multilevel regression results describing independently tested individual-level and pregnancy-level characteristics of any cerebral lesion in “high-risk survivors”.
Subsequently, the effects of all potential individual- and pregnancy-level risk factors were modeled simultaneously in a multivariate multilevel regression model. Separate models were run including either gestational age at birth or the prematurity indicator. In the multivariate model, only birth weight (OR=0.11, 95% CI=[0.04,0.31], p<0.001) remained a significant risk factor for any lesion development. Curiously, triplet pregnancy (OR=0.20, 95% CI=[0.04,0.98], p<0.05) became significantly associated with a lower odds of any lesion after controlling for the variance associated with low birth weight. After accounting for the variance explained by these predictors in the adjusted model, 18.4% of the variation in the occurrence of any lesion remained at the pregnancy rather than individual level.