OBJECTIVE: Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS).
METHODS: 46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire.
RESULTS: From the parents\' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, β=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, β=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, β=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001).
CONCLUSIONS: Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents\' perspective on the smaller twins\' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome.
This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome.
In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned.
The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups were observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity.
In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks\' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS.
A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus.
A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks\' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings.
A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Twin pregnancy is associated with increased perinatal mortality and morbidity, but long-term neurodevelopmental outcome remains underinvestigated. The primary objective of this study was to investigate the incidence of adverse neurodevelopment after 1 year of age in complicated monochorionic diamniotic (MCDA) twin pregnancies compared with uncomplicated twin pregnancies.
This was a prospective cohort study conducted at St George\'s University Hospital NHS Foundation Trust, London, UK. Women with a twin pregnancy culminating in at least one surviving child, aged between 12 and 60 months (corrected for prematurity) at the time of assessment, were invited to complete the relevant Ages and Stages Questionnaire® version 3 (ASQ-3) test. The two study groups were: (1) complicated MCDA twin pregnancies, including those with twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, twin reversed arterial perfusion sequence and/or single intrauterine demise; and (2) uncomplicated MCDA and dichorionic diamniotic twin pregnancies. The primary outcome measure was an abnormal ASQ-3 score, defined as a score of more than 2 SD below the mean in any one of the five domains. Mixed-effects multivariable logistic regression analysis was performed to determine whether a complicated MCDA twin pregnancy was associated independently with an abnormal ASQ-3 score.
The study included 174 parents who completed the questionnaire for one or both twins; therefore, 327 ASQ-3 questionnaires were available for analysis. Of those, 117 (35.8%) were complicated MCDA twin pregnancies and 210 (64.2%) were controls. The overall rate of an abnormal ASQ-3 score in children born of a complicated MCDA twin pregnancy was nearly double that of those from uncomplicated twin pregnancies (14.5% vs 7.6%; P = 0.056). Children born of a complicated MCDA twin pregnancy had a significantly higher rate of impairment in the gross-motor domain compared with the control group (8.5% vs 2.9%; P = 0.031). Complicated MCDA twin pregnancies that underwent prenatal intervention had a significantly higher rate of abnormal ASQ-3 score compared with those that did not undergo prenatal intervention (28.1% vs 1.7%; P < 0.001). On multilevel logistic regression analysis, complicated MCDA twin pregnancy was an independent predictor of abnormal ASQ-3 score (adjusted odds ratio, 3.28 (95% CI, 3.27-3.29); P < 0.001).
This study demonstrates that survivors of complicated MCDA twin pregnancies have a higher rate of adverse neurodevelopmental outcome, independently of prematurity. Long-term neurodevelopmental follow-up in these pregnancies can ensure timely and optimal management of those affected. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS) and to identify risk factors for ROP development.
METHODS: This retrospective cohort study included 147 TTTS twin pairs managed between 2002 and 2022 and eligible for ROP screening. Primary outcomes were any stage ROP and severe ROP. Secondary outcomes were hemoglobin at birth, red blood cell transfusions, mechanical ventilation days, postnatal steroids, and neonatal morbidity. Donor status was defined as having polyhydramnios pre-laser.
RESULTS: Rates of any stage ROP (23% vs. 14%) and severe ROP (8% vs. 3%) were significantly higher in donors compared to recipients. Donors received a higher number of blood transfusions (1 [±1.9] versus 0.7 [±1.5]). Five factors were univariately associated with any stage ROP: donor status (odds ratio [OR] 1.9; 95% CI 1.3-2.9), lower gestational age (GA) at birth (OR 1.7; 95% CI 1.4-2.1), small for GA (OR 2.1; 95% CI 1.3-3.5), mechanical ventilation days (OR 1.1; 95% CI 1.1-1.2), and blood transfusions in phase 1 (OR 2.3; 95% CI 1.2-4.3). Three factors were independently associated with any stage ROP: donor status (OR 1.8; 95% CI 1.1-2.9), lower GA at birth (OR 1.6; 95% CI 1.2-2.1), and mechanical ventilation days (OR 1.1, 95% CI 1.0-1.1). Donor status was univariately associated with severe ROP (OR 2.3, 95% CI 1.1-5.0).
CONCLUSIONS: Any stage ROP and severe ROP are detected twice as frequently in donors compared to recipients. Increased awareness for ROP is needed in donors, especially those with lower GA at birth and longer duration of mechanical ventilation.

UNASSIGNED: To compare the outcomes of dichorionic triamniotic (DCTA) triplets with that of monochorionic diamniotic (MCDA) twin gestations undergoing fetoscopic laser surgery (FLS) for treatment of twin-to-twin transfusion syndrome (TTTS).
UNASSIGNED: Retrospective cohort study of prospectively collected data of consecutive DCTA triplet and MCDA twin pregnancies with TTTS that underwent FLS at two fetal treatment centers between 2012 and 2020. Preoperative, operative and, postoperative variables were collected. Perinatal outcomes were investigated. Primary outcome was survival to birth and to neonatal period. Secondary outcomes were gestational age (GA) at birth and procedure-to-delivery interval. Literature review was conducted in which PubMed, Web of Science, and Scopus were searched from inception to September, 2020.
UNASSIGNED: Twenty four sets of DCTA triplets were compared to MCDA twins during the study period. There were no significant differences in survival (no survivor, single, or double survivors) to birth and to the neonatal period of the MC twin pairs of the DCTA triplets vs MCDA twins. Median GA at delivery was approximately three weeks earlier in DCTA triplets compared to MCDA twins (28.4 weeks vs 31.4 weeks, p = .035, respectively). Rates of preterm birth (PTB) less than 32 and less than 28 weeks were significantly higher in DCTA triplets compared to twins (<32 weeks: 70.8% vs 51.1%, p = .037, respectively, and <28 weeks: 37.5% vs 20.8%, p = .033, respectively).
UNASSIGNED: Perinatal survival including fetal and neonatal are comparable between DCTA triplets and MCDA twins. However, this might have resulted from the small sample size of the DCTA triplets. GA at delivery is earlier in triplets, which could be due to the nature of triplet gestation rather than to the laser procedure itself.

Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders.
This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment).
Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0).
As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk.
The Dutch Heart Foundation.

To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity.
This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated.
The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses.
This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

UNASSIGNED: Twin-twin transfusion syndrome (TTTS) is a severe prenatal complication of monochorionic diamniotic twins (MCDA). If left untreated, TTTS is associated with a high risk of neonatal death and neurological complications. Various treatment methods for TTTS have been proposed, but fetoscopic laser surgery (FLS) is currently the primary treatment for TTTS in global fetal medicine centers. The objective of this study was to evaluate the outcome of TTTS following FLS treatment at Hanoi Obstetrics and Gynecology Hospital (HOGH), a new fetal medicine center in Vietnam.
UNASSIGNED: A prospective study of a series of 33 consecutive TTTS cases prior to 26 weeks of gestation subjected to FLS at HOGH in Vie-tnam between September 2019 to July 2021. Neonates were monitored for at least six months after birth.
UNASSIGNED: The survival rate of at least one fetus reached 84.85%. No short-term neurological complications have been reported upon follow-up of the newborn up to six months after birth. There were three stillbirth cases (9.09%), one case of preterm ruptured membra-nes (PROM) (3.03%) after seven days of surgery and three cases of recurrent TTTS after surgery using the Solomon technique (25%). No maternal complications were observed. The mean gestational age at birth was 33.76 ± 4.52 weeks, with a mean interval of 12.24 ± 6.67 weeks between intervention and delivery. Nine cases (30%) were born prematurely before 32 weeks. Additionally, 60% of recipients and nearly 90% of donors weighed less than 2500 grams.
UNASSIGNED: FLS leads to high survival rates for fetuses with TTTS. FLS seems to be an effective therapeutic option for TTTS before 26 weeks of gestation.

Complete coagulation of the vascular equator (as in the Solomon technique) has been suggested to reduce postoperative complications such as twin anemia polycythemia syndrome and the recurrence of twin-twin transfusion syndrome following fetoscopic laser coagulation of chorionic vessels for twin-twin transfusion syndrome.
We aimed to evaluate the benefit of this technique on perinatal outcomes compared with selective ablation of anastomoses.
We conducted a monocentric retrospective study comparing selective laser coagulation of anastomoses to the Solomon technique from January 2006 to August 2020. To adjust for potential confounders, the cases operated by selective surgery were matched to the cases operated with the Solomon technique according to the gestational age at laser therapy, placental localization, and Quintero stage using propensity score matching.
With a total of 994 cases, 399 matched pairs were included in the analysis. Compared with selective ablation, the Solomon technique was associated with significantly improved survival: the overall twin survival at delivery and discharge was 72% vs 79% (P=.003) and 69% vs 75% (P=.006), respectively; the double twin survival rate at discharge was 55% vs 65% (P=.02), respectively, and the rate of intrauterine death dropped from 18% to 12% (P=.003), respectively. The Solomon technique significantly reduced the rate of twin anemia polycythemia syndrome (10% vs 4%; P=.02), leading to fewer secondary rescue procedures (13% vs 7.3%; P=.01). However, the Solomon technique was associated with an increased risk of preterm rupture of membranes, especially at early gestational ages (3.8% vs 11%; P<.001 for preterm rupture of membranes <24 weeks). Among the survivors at delivery, both the groups had similar gestational ages at birth. Both neonatal mortality and severe neurologic morbidity were similar in both the groups. However, an increased risk of bronchopulmonary dysplasia was found in the Solomon group (4.5% vs 12%; P<.001).
Although the risk of preterm premature rupture of membranes has increased, the introduction of the Solomon technique has significantly improved perinatal outcomes in pregnancies affected with twin-twin transfusion syndrome.