Materials and Methods
A retrospective study was conducted of 628 consecutive monochorionic diamniotic pregnancies referred for evaluation of possible TTTS at the Los Angeles Fetal Therapy Program (Keck School of Medicine, University of Southern California) from June 2006 to June 2013. Indication for referral was clinical suspicion of TTTS by the referring Maternal-Fetal Medicine specialist. At our center, each patient underwent a consultative ultrasound that consisted of a detailed anatomic survey and measurement of the amniotic fluid MVP for each twin. A diagnosis of TTTS was made if the MVP of amniotic fluid measured ≤2 cm in the donor’s sac and ≥8 cm in the recipient’s sac. Patients with TTTS were staged based on the Quintero staging system.
The diagnosis of iPoly was established if the MVP measured ≥8 cm in one sac and >2 and <8 cm in the other sac. The fetus with increased amniotic fluid volume was labeled the ‘iPoly twin,’ and the one with a normal MVP was labeled the ‘co-twin.’ Patients diagnosed with iPoly were counseled about the high-risk nature of their pregnancy, but that they did not meet surgical criteria for TTTS. Patients were followed by their referring physician with weekly or twice weekly ultrasound examinations. If criteria for TTTS or symptomatic polyhydramnios (defined as maternal discomfort, respiratory embarrassment, preterm labor, and/or significant cervical shortening) were met at a later time, the patient was referred back to our center for reevaluation and possible treatment.
Information that was gathered at our center and prospectively recorded in a database for each case included: maternal demographics, Quintero Stage of TTTS, findings of consultative ultrasound including estimated fetal weight, MVP, cervical length and fetal Doppler values, gestational age at diagnosis and at laser surgery, and number of amnioreductions. Intrauterine growth restriction (IUGR) was defined as estimated fetal weight <10%. Delivery information including gestational age at delivery, perinatal survival, and birthweight was obtained prospectively by the research team via acquisition of medical records and telephone inquiry of the referring providers and the patient.
Patient characteristics and outcome data were analyzed univariately, and those patients who did and did not develop TTTS were compared. The primary outcome was the development of TTTS; all other outcomes were considered secondary. Medians are expressed with ranges. Analyses of continuous variables were performed with Kruskal-Wallis testing; analyses of categorical variables were performed using χ 2 testing with Yates correction or Fisher exact testing if appropriate. Those patient characteristics associated with the TTTS group ( P < .20) were examined using multivariable logistic regression models for the development of TTTS. Odds ratios (ORs) and 95% confidence intervals (95% CI) are expressed. All analyses were performed using SAS statistical software (version 9.2; SAS Institute Inc., Cary, NC). This study was approved by the institutional review board of the University of Southern California, and complied with all patient protection criteria stipulated therein.
Results
Of the 628 consecutive patients with monochorionic diamniotic pregnancies that were evaluated in the study period, 74 (11.8%) met criteria for iPoly. All patients had prenatal data available for analysis. Seventy-one patients had monochorionic diamniotic twins, 2 patients had pregnancies that were dichorionic triamniotic, and 1 had a pregnancy that was trichorionic quadamniotic. None of these higher order gestations progressed to TTTS. The presence of higher order multiples was not associated with the development of TTTS as demonstrated by a nonsignificant P value of .5161. Of these higher order multiples, the triplet gestations delivered at 30.4 and 31.6 weeks whereas the quadruplet gestation delivered at 31.0 weeks; the 30-day perinatal survival rate for these newborns was 100% (10/10).
Patients with iPoly were subsequently analyzed as 2 separate groups. There were 22 (29.7%) patients who eventually developed TTTS and 52 (70.3%) patients who did not develop TTTS. Patient characteristics are described in Table 1 . No patient in the iPoly cohort elected to undergo umbilical cord occlusion or pregnancy termination.
| Patient characteristic | All iPoly patients (n = 74) | iPoly patients who developed TTTS (n = 22) | iPoly patients who did not develop TTTS (n = 52) | P value a |
|---|---|---|---|---|
| Maternal age, y b | 30.0 (17–47) | 32.0 (18–42) | 30.0 (17–47) | .4521 |
| Race, n (%) | .4375 | |||
| Asian | 6 (8.1) | 2 (9.1) | 4 (7.7) | |
| Black | 4 (5.4) | 1 (4.6) | 3 (5.8) | |
| Hispanic | 30 (40.5) | 7 (31.8) | 23 (44.2) | |
| White | 26 (35.1) | 11 (50.0) | 15 (28.8) | |
| Unknown | 8 (10.8) | 1 (4.6) | 7 (13.5) | |
| Multiparous | 47 (63.5) | 14 (63.6) | 33 (63.5) | > .99 |
a TTTS and non-TTTS are the comparison groups for the listed P values
As seen in Table 2 , in the 22 patients with iPoly who subsequently developed TTTS, Quintero Stage I was diagnosed in 8 (36.4%), Stage III in 12 (54.5%), and Stage V in 2 (9.1%). Subclassification of the 12 Stage III patients according to which fetus had critically abnormal Doppler examinations revealed that only the donor was affected in 3 (Stage III Donor), only the recipient in 7 (Stage III Recipient), and both donor and recipient in 2 gestations (Stage III Donor/Recipient). The median number of days from diagnosis of iPoly at consultation ultrasound to TTTS was 11 (2-68) days ( Figure ). The 30-day perinatal survival rate of at-least-one twin in this group was 81.8% (18/22). In the subgroup of 19 (86.4%) patients who subsequently underwent laser surgery, laser surgery was performed at a median gestational age of 20.6 (16.6-28.7) weeks, and 16 (84.2%) had 30-day survival of at-least-one twin. In the remaining 3 TTTS patients that did not undergo laser surgery, 2 had a fetal demise (thus excluding them from laser surgery) and 1 was diagnosed with Stage I TTTS at 28 weeks and was managed with amnioreduction. Outcome data for these patients are as follows: the Stage I patient delivered at 36.7 weeks with two 30-day survivors, 1 Stage V patient delivered a donor twin at 23.6 weeks who remained alive at 30 days, and the other Stage V patient had IUFD of the donor twin at 24.7 weeks with same-day termination of the pregnancy.
| Patient characteristic | iPoly patients who developed TTTS (n = 22) |
|---|---|
| Diagnosis in days from isolated polyhydramnios a to TTTS | 22/22 11.0 (2–68) |
| Laser surgery | 19 (86.4%) |
| GA at laser surgery a | 19/22 20.6 (16.6–28.7) |
| Quintero stage | |
| Stage I | 8 (36.4%) |
| Stage II | 0 (0%) |
| Stage III | 12 (54.6%) |
| Stage IV | 0 (0%) |
| Stage V | 2 (9.1%) |
In the remaining 52 patients with iPoly who did not progress to TTTS, the median gestational age at diagnosis of iPoly was 21.7 (17.9-26.1) weeks followed by delivery at 34.1 (22.1-38.4) weeks. Forty of these patients were managed expectantly and 12 underwent subsequent amnioreductions. The amnioreductions were performed either by a single provider at our fetal care center or the patient’s referring Maternal-Fetal Medicine specialist. Of those who underwent amnioreductions, 5 were due to maternal discomfort and 7 due to signs of preterm labor. The 30-day survival of at-least-one twin in this group was 93.0% (40/43), with no 30-day survivorship data available for 9 patients. Among these 9 patients, 5 had both twins born alive, 1 had only the iPoly twin born alive, and the remaining 3 patients had unknown live birth status.
As seen in Table 3 , the median maximum vertical pocket of amniotic fluid for the iPoly twin was not statistically different between those who did and did not develop TTTS (9.20 [8.0–13.9] cm vs 10.00 [8.0–20.4] cm; P = .1931). However, there was a statistically significant difference in gestational age at the time of diagnosis of iPoly when comparing the TTTS and non-TTTS groups (18.9 [16.1–25.1] weeks vs 21.7 [17.9–26.1] weeks; P = .0001). Also of significance was the rate of co-twin IUGR in the TTTS and non-TTTS groups (45.5% vs 19.3%; P = .0425). There were no differences in Doppler measurements of the middle cerebral artery, ductus venosus, umbilical artery, and vein between the 2 groups. The median cervical length was longer in the TTTS vs non-TTTS group (4.4 cm vs 3.7 cm; P = .0060) but in multivariate logistic regression analysis, cervical length was not found to be a risk factor.
| Patient characteristic | iPoly patients who developed TTTS (n = 22) | iPoly patients who did not develop TTTS (n = 52) | P value |
|---|---|---|---|
| GA (wks) at diagnosis of iPoly a | 18.9 (16.1–25.1) | 21.7 (17.9–26.1) | .0001 |
| Diagnosis of iPoly at GA <20 wks | 15 (68.2%) | 11 (21.2%) | .0002 |
| Co-twin MVP a | 3.30 (2.1–7.2) | 3.25 (2.2–6.7) | .3874 |
| iPoly twin MVP a | 9.20 (8.0–13.9) | 10.0 (8.0–20.4) | .1931 |
| Co-twin weight percentile a | 14.5 (1.0–66.0) | 24.5 (1.0–89.0) | .0186 |
| iPoly twin weight percentile a | 52.0 (11.2–98.0) | 63.8 (3.0–99.0) | .2980 |
| IUGR of co-twin | 10 (45.5%) | 10 (19.3%) | .0425 |
| IUGR of iPoly twin | 0 | 2 (3.9%) | > .99 |
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