The impact of laser therapy on fetal growth discordance in twin-to-twin transfusion syndrome

Objectives: to evaluate the impact of laser therapy on inter-twin discordance in twin-to-twin transfusion syndrome (TTTS). Methods: biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight were prospectively collected during a five-year period (1999 to 2004). The inter-twin discordance was expressed as a percentage of the largest twin's measurements. The measurements were made the day before laser, twice following laser and after delivery. The mean values of discordance in measurements and in fetal weight were calculated. ANOVA was used to compare mean values. Results: the mean (SD) discordance for BPD, HC, AC, FL and estimated fetal weight the day before laser were 8.53% (5.28), 8.75% (2.76), 16.19% (4.85), 12.92% (5.13) and 28.50% (6.46) respectively. At the at 2nd ultrasound assessment after surgery were 4.37% (3.55), 3.73% (2.71), 8.90% (4.42), 6.61% (4.99) and 19.11% (8.01) respectively; and at birth the weight discordance was 18.55% (8.74). There was a significant decrease in discordance for HC and AC for each ultrasound assessment. Conclusions: there was a decrease in fetal growth discordance following laser therapy in TTTS. These changes might be related to re-adaptation of blood flow following laser therapy.


Palavras-chave Transfusão Feto-fetal, Coagulação
por laser, Fetoscopia interval between the ultrasound measurements was of at least two weeks. 10Estimated fetal weight was calculated using Hadlock et al. 9 formula: log10 (EFW)=1.326+0.0107(HC)+0.0438(AC)+0.158(FL)-0.00326(AC×FL).At the time of laser therapy, Quintero's stages and umbilical Doppler were collected in each case.Laser surgery was performed as previously described. 11he inter-twin discordance in BPD, HC, AC, FL and estimated fetal weight (mean+/-SD) were calculated for each pair and expressed as a percentage of the larger twin's measurements [100 x (larger twin's measurement-smaller twin's measurement) / Larger twin's measurement].
Normality of the distribution of measurements was tested using a Shapiro-Wilks test (p>0.05).The ANOVA Post Hoc Test was used to compare the mean values of intertwine discordances at the day before laser with the mean values at the 1st and 2nd ultrasound assessment and after birth, respectively.All calculations were performed using the SPSS software package (release 10.0, SPSS Inc., Chicago, IL, USA).For all tests used, a value of p<0.05 was considered statistically significant.
The mean discordance in HC, AC, FL and estimated fetal weight one day before laser, at 1st and 2nd ultrasound assessment and at birth are shown in Table 1.
There was a significant difference (p<0.05) in HC and AC between ultrasound assessment the day before laser and at 1st and 2nd assessment following laser, respectively.The decrease in discordance for

Introduction
Birthweight discordance can affect up to a quarter of twin gestations and is a critical factor in the management of those pregnancies. 1,2The discordance is calculated as the intrapair weight difference, expressed as a percentage of the larger twin's weight. 3The incidence of discordance is directly related to the definition used.Most published studies have used a birth weight difference of 15% to 25 %. 3 Twin-to-Twin Transfusion Syndrome (TTTS) is often associated with growth discordance between Donors and Recipients. 2 Around 20% of monochorionic twins develop TTTS. 4,55][6][7][8] Laser therapy is the most effective first line treatment of TTTS; however, its effect on fetal growth has not been evaluated to date.
We aimed to evaluate the impact of laser therapy on inter-twin discordance in TTTS by serial assessment of fetal biometry measures and estimated fetal weight between fetuses following surgery when both fetuses were born alive.

Methods
This study included all live-born neonates born after 24 weeks of gestation from pregnancies complicated by TTTS and treated by laser therapy before 26 weeks'during a five-year period (1999 to 2004).
TTTS was diagnosed with the association of severe polyhydramnios defined by a deepest pool above 80mm (recipient twin) showing a distended bladder, and oligohydramnios defined by a deepest pool below than 20mm (donor twin) showing small or no bladder on ultrasound.
Only pregnancies in which we performed laser therapy and when both infants were born alive were included in the study.Cases that needed repeat-laser or another treatment were not included.Gestational age was established on the basis of best obstetric estimate including last menstrual period and firsttrimester ultrasound.All pregnancies were diagnosed to be monochorionic and diamniotic by ultrasound examination at 6-14 weeks of gestation.
Ultrasound examination was performed on the day before laser and twice following surgery.Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL) were collected prospectively. 9The BPD, FL and estimated fetal weight became significant only after the second assessment following laser (Table 2, Figures 1 and 2).arterial perfusion (TRAP) sequence. 15This study suggests that the inter-twin discordance decreases after laser therapy in successful cases leading to the birth of two liveborn twins.The incidence of intrauterine fetal death increases with increasing fetal weight discordance in twins at of the same sex.2,16TTTS carries a high mortality mainly related to intra-uterine death and severe preterm delivery.Early fetal death following laser can be related to perioperative factors, such as placental abruption, hemorrhage or infection.Late fetal death may be related to either recurrence of TTTS or severe growth restriction.
][19][20][21] The design of our study does not allow to draw these definitive conclusions on the effect of laser therapy on fetal growth.These changes in fetal growth could also have occurred in a control group without laser therapy.However, an untreated control group with severe TTTS before 26 weeks' is unlikely to allow double survival.González-Quintero et al. 8 have shown that early fetal growth discordance diagnosed as early as 20 weeks, increases with advancing gestation until birth and Rodis et al. 17 reported similar findings in their study by concluding that twins who ultimately become discordant exhibit demonstrable differences as early as 23 to 24 weeks.Fetal weight discordance at birth was 18% and compares favorably with the results from Duncombe et al. 22 who reported 34% discordance in birth weight in a series of 69 TTTS, treated with amnioreduction and septostomy.Our results suggest that fetoscopic laser surgery of the chorionic plate may influence the natural history of fetal discordance caused by TTTS.Indeed the mean estimated fetal weight discordance went down from 28% at 21weeks'before laser to 18% at the time of delivery.This decrease was already significant at 28 weeks'at second assessment after laser.The overall reduction in estimated fetal weight discordance throughout gestation was over 30%.
Following laser therapy in TTTS, there is a decrease in fetal growth discordance.These changes might be related to the readjustment in blood flows following laser therapy.

Discussion
Both the presence of inter-twin anastomoses and unequal placental sharing are likely to be the main causes for fetal growth discordance and amniotic fluid imbalance to develop in TTTS. 5 Established treatments of TTTS include serial amnioreduction and laser therapy.2][13] Endoscopic laser ablation is feasible in pregnancies that are complicated by severe fetofetal transfusion syndrome and appears to be associated with improved perinatal outcome. 14Laser coagulation of the umbilical cord vessels is an effective method of treating monozygotic twin pregnancies with reversed Figura 2Fetal discordance across time Changes in fetal discordance over time.