Results:
A total of 418 TTTS consecutive cases underwent laser surgery during the
study period at both institutions. UA PI of both donor and recipient
twins was available in 89.5% (374/418) of TTTS cases and DUAPI was
calculated in the latter cases. DUAPI was available in 96.4% (54/56),
99.2% (132/133), 81% (158/195), and 88.2% (30/34) of Quintero stage
I, II, III and IV cases, respectively. UA PI was recorded in only 65%
(34/52) of cases when the UA EDF was absent or reversed in either twin,
even though PI could be estimated in these cases. All cases where UA PI
was available in both twins were included in the study (n=374); 6.7%
(25/374) of these cases were lost to follow-up to 30 days of life,
leaving 349 cases for analysis. For the analysis, one participating
center contributed with 118 cases and the other one with 231 cases. TTTS
Quintero stage I or II was diagnosed in 176 cases and TTTS Quintero
stage III or IV was diagnosed in 173 cases. In the whole cohort, double
twin survival and survival of at least one twin to 30 days was observed
in 67% (234/349) and 90.3% (315/349), respectively. The demographic
and clinical characteristics according to Quintero stages and DUAPI
results are described in Tables 1 and 2.
ROC curve analysis demonstrated that higher inter-twin DUAPI was
associated with reduced dual infant survival to 30 days of life [area
under the curve (AUC): 0.67; p<0.001]. These results are
consistent with an earlier report at a single
institution9. Of note, ROC curve analysis demonstrated
that higher UA PI in donor twin, (AUC: 0.66; p<0.001) but not
in the recipient twin (AUC: 0.45; p=0.1), was also associated with
reduced dual infant survival to 30 days of life. These observations
suggest that the association of DUAPI with double infant survival in
TTTS cases undergoing laser surgery is primarily driven by UA PI in the
donor twin. We chose to use DUAPI instead of UA PI in the donor twin
because it does not have a significant correlation with gestational age
at ultrasonography (spearman’s rho correlation coefficient: -0.03;
p=0.6). As expected, UA PI in the donor twin had a significant
correlation with gestational age at ultrasonography (spearman’s rho
correlation coefficient: -0.16; p=0.02). Thus, the clinical use of UA PI
in the donor twin to predict infant survival in TTTS requires the use of
a normogram. In contrast, intertwin DUAPI does not change with
gestational age, and the use of a single cutoff (<0.4) is
simple to use.
The donor twin had higher UA PI that the recipient twin in 56.7%
(198/349) of TTTS cases and sFGR was identified in 21.5% (75/349) of
cases. Of note, in only 66.7% (50/75) of TTTS cases with sFGR, the
donor twin had higher UA PI than in the recipient twin; we anticipated
this proportion to be higher because of the known association of sFGR
with increased impedance to blood flow in the UA.
Significant differences in double twin survival to 30 days of life was
seen between DUAPI groups in the whole cohort [<0.4: 76.8%
(162/211) vs. ≥0.4: 52.2% (72/138); p<0.001] and in the
subgroup of women with TTTS Quintero stage I or II combined
[<0.4: 77.8% (105/135) vs. ≥0.4: 58.5% (24/41); p=0.015]
as well as in women with TTTS Quintero stage III or IV combined
[<0.4: 75% (57/76) vs. ≥0.4: 49.5% (48/97); p=0.001]
(see Table 2). Similar findings were observed when double twin survival
to 30 days of life was compared between the two DUAPI groups in TTTS
cases with Quintero stage I individually [<0.4: 88.1%
(37/42) vs. ≥0.4: 54.5% (6/11); p=0.02] or Quintero stage III
individually [<0.4: 80.3% (49/61) vs. ≥0.4: 50% (43/86);
p<0.001]. Among women with Quintero stages II or IV as
individual groups, those with a DUAPI <0.4 had higher double
twin survival to 30 days than those with a DUAPI ≥0.4, but these
differences did not reach statistical significance in either group
{Quintero stage II [<0.4: 73.1% (68/93) vs. ≥0.4: 60%
(18/30); p=0.1] or Quintero stage IV [<0.4: 53.3% (8/15)
vs. ≥0.4: 45.5% (5/11); p=0.6]}.
No significant differences in survival of at least one twin to 30 days
of life was seen between DUAPI groups in the whole cohort
[<0.4: 91% (192/211) vs. ≥0.4: 89.1% (123/138); p=0.6]
or in the subgroup of women with TTTS Quintero stage I or II combined
[<0.4: 91.9% (124/135) vs. ≥0.4: 90.2% (37/41); p=0.7]
or in women with TTTS Quintero stage III or IV combined
[<0.4: 89.5% (68/76) vs. ≥0.4: 88.7% (86/97); p=0.9]. In
a multivariable regression analysis, DUAPI <0.4 was not
associated with survival of at least one infant to 30 days [adjusted
odds ratio (aOR): 0.64, 95% confidence interval (CI): 0.19-2.2;
p=0.5] in the whole study cohort or in the subgroup analyses.
Intertwin DUAPI <0.4 was associated with a 3-fold to 3.5-fold
increase in double twin survival to one month of age in the regression
model of the whole cohort and the subgroup analysis (See Tables 3, 4 and
5). This was determined using DUAPI ≥0.4 as a reference when the
analysis was adjusted for confounding variables. Indeed, intertwin DUAPI
<0.4 was associated with increased survival of both twins to
one month of age in the whole cohort (aOR: 3.40; 95% CI: 2.02-5.70;
p<0.001) (Table 3), in the subgroup of women with TTTS
Quintero stage III or IV (aOR: 3.23; 95% CI: 1.52-8.85; p=0.002) (Table
4) as well as in those with TTTS Quintero stage I or II (aOR: 3.05; 95%
CI: 1.32-7.09; p=0.009) (Table 5). As anticipated, an additional
variable associated with increased double twin survival to one month of
age was gestational age delivery (See Tables 3, 4 and 5). In contrast,
neither Quintero staging nor any of the sonographic criteria used in
Quintero staging or sFGR were associated with infant survival when the
analysis was adjusted for confounding factors (See Tables 3, 4 and 5).
Similar findings were observed when the MVP of the donor (aOR: 0.91;
95% CI: 0.70-1.19; p=0.5) or recipient twin (aOR: 0.98; 95% CI:
0.89-1.10; p=0.8) were included as continuous variables in the
regression models.
There were significant differences in the proportion of women with
double infant survival to 30 days according to Quintero staging
[81.1% (43/53), 69.9% (86/123), 62.6 (92/147) and 50% (13/26) for
Quintero stage I, II, III and IV, respectively; p=0.002]. In contrast,
no significant differences were observed for survival of at least one
twin to 30 days according to Quintero staging [92.5% (49/53), 91.1%
(112/123), 90.5 (133/147) and 80.8% (21/26) for Quintero stage I, II,
III and IV, respectively; p=0.2]. The observation that Quintero
staging was associated with double infant survival in the univariate
analysis but not after the analysis was adjusted for DUAPI<0.4
and other confounders in the multivariable regression model (Table 3)
indicates that DUAPI <0.4 supersedes the Quintero
classification in the prediction of double infant survival to 30 days of
life in TTTS cases.