Dichorionic triamniotic triplets after two blastocysts transfer underwent multifetal pregnancy reduction: two case reports and literature review.

BACKGROUND: The increase in the rate of multiple pregnancies in clinical practice is associated with assisted reproductive technology (ART). Given the high risk of dichorionic triamniotic (DCTA) triplet pregnancies, reducing DCTA triplet pregnancies to twin or singleton pregnancies is often beneficial. CASE PRESENTATION: This article reports on two cases of DCTA triplet pregnancies resulting from two blastocyst transfers. Given the high risk of complications such as twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies, patients have a strong desire to preserve the dichorionic diamniotic (DCDA) twins. Multifetal pregnancy reduction (MFPR) was performed in both cases to continue the pregnancy with DCDA twins by reducing one of the MCDA twins. Both of the pregnant women in this report eventually gave birth to healthy twins at 37 weeks. CONCLUSIONS: For infertile couples with multiple pregnancies but with a strong desire to remain the DCDA twins, our report suggests that reducing DCTA triplets to DCDA twin pregnancies may be an option based on clinical operability and assessment of surgical difficulty.

Does Catch-Up Growth Come with a Cognitive Cost? Cognitive Outcome and Growth Patterns in Growth Discordant Identical Twins.

OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.

Intrauterine transfusion under fetal analgesia: the evaluation of perinatal outcomes.

Introduction: Intrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice. Materials and methods: Retrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected. Results: Altogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18-32 weeks), with no related preterm premature rupture of membranes (<48 h), or side effects from fetal analgesia. Gestational age at delivery was 33 weeks (26-41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery. Conclusion: Intrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication.

Sensitive detection of hemodynamic changes after fetoscopic laser photocoagulation by assessing intraventricular pressure difference in fetuses with twin-to-twin transfusion syndrome.

OBJECTIVES: To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography. METHODS: We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD. RESULTS: Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP. CONCLUSIONS: IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS.

The Number of Syncytial Knots and the Intensity of VEGF Expression in the Villi of the Monochorionic Diamniotic Placenta in Selective Fetal Growth Restriction.

A comparative study was carried out to analyze the number of syncytial knots and the intensity of expression of vascular endothelial growth factor (VEGF) in the villi of the monochorionic diamniotic placenta in pregnancies complicated by the syndrome of selective fetal growth restriction (sFGR). We performed a morphological analysis of 32 monochorionic diamniotic placentas after term delivery which were divided into two groups. The main group included the placentas of 15 puerperas whose pregnancies were complicated by sFGR. The control group included twin placentas of 17 puerperas without signs of sFGR. The number of syncytial knots was determined by histological studies, and the levels of VEGF expression in syncytiotrophoblast and capillary endotheliocytes of the placental villi were determined by immunohistochemical studies. The study showed an increase in the number of syncytial knots in the villi of the placental part of the fetus with sFGR which indicated the development of preplacental hypoxia. A significant increase in the level of VEGF expression in the syncytiotrophoblast and vascular endothelium of the villi should be considered as a manifestation of a compensatory adaptational response to hypoxia, though it is insufficient to prevent the development of sFGR.

The Role of MALAT1 in Regulating the Proangiogenic Functions, Invasion, and Migration of Trophoblasts in Selective Fetal Growth Restriction.

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects.

Co-Twin Prognosis After Single Intrauterine Fetal Death at a Tertiary Care Hospital in India: A Retrospective Observational Study.

INTRODUCTION: Twin pregnancy is associated with an increased risk of perinatal morbidity. Besides, if intrauterine death of a single twin occurs, it increases the morbidity of the surviving co-twin perinatally and postnatally. AIM:  The objective of this study was to determine the incidence of single intrauterine fetal death (SIUFD) in a twin pregnancy and fetal outcome defined in dimensions according to the complications in the surviving co-twin. MATERIAL AND METHODS: Data on twin pregnancies were collected retrospectively for a period of five years (from 2015 to 2019) from the labour room records of the Central Records Department (CRD) at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Cases with SIUFD were studied individually and neonatal follow-up was taken post delivery for up to three to eight years. Inclusion criteria were SIUFD in twin pregnancies after 14 weeks gestation, chorionicity pre-defined by early trimester ultrasonography. Exclusion criteria were higher-order pregnancy and monoamniotic twins. RESULTS: A total of 1246 (4.273%) twin deliveries were conducted in the study period. Of these, 107 (8.587%) pregnancies had SIUFD with co-twin surviving in utero. Among these, 77 (72%) were dichorionic diamniotic (DCDA) twin pregnancies and 30 (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The incidence of SIUFD was 8.5%. Preterm birth was the most common complication observed in our study and was found in 53.5% and 58.3% of participants in DCDA and MCDA twins, respectively. Early neonatal death (within 24 hours of life) of the surviving twin was found in 29.2% monochorionic twins with SIUFD. SIUFD at < 28 weeks gestation led to a greater number of early neonatal deaths of surviving twins. The incidence of neurodevelopmental disorders (cerebral palsy, developmental delay, epilepsy) in our population after birth was 7.5% (n=93). CONCLUSION: Twin pregnancies with SIUFD have an increased incidence of preterm labour, increased neonatal death of the surviving twin, and neurodevelopmental disorders (cerebral palsy, developmental delay, epilepsy). Monochorionicity and SIUFD at <28 weeks gestation are associated with increased neonatal deaths in co-twin. The Incidence of neurodevelopmental disorders is not directly associated with chorionicity, but developmental delay is more profoundly seen in the monochorionic group.

A case report of hepatic fetus-in-fetu: Approach to diagnosis.

Multiple theories have been proposed about the pathophysiology of Fetus-in-fetu (FIF). The most widely accepted theory is abnormal embryogenesis in diamniotic monochorionic pregnancies, in which a malformed parasitic fetus is found within the body of a twin host. Hepatic FIF has been reported in almost 1% of FIF cases, with only 2 case reports being published in the literature. This article presents the third case report of intrahepatic FIF. Additionally, we review the role of radiology in diagnosing these cases and guiding their proper management. This case report supports the monozygotic twin theory of FIF and the diagnostic dilemma of FIF vs. teratoma can be solved through collaborative work between radiologists and pathologists.

Society for Maternal-Fetal Medicine Consult Series #72: Twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Thirty percent of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared intertwin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia-polycythemia sequence, providing management recommendations based on the available evidence. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first-trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the intertwin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia-polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by posttreatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia-polycythemia sequence minimally require either middle cerebral artery Doppler peak systolic velocity values >1.5 and <1.0 multiples of the median in donor and recipient twins, respectively, or an intertwin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); and (14) consultation with a specialized fetal care center is recommended when twin anemia-polycythemia sequence progresses to a more advanced disease stage (stage ≥II) before 32 weeks of gestation or when concern arises for coexisting complications such as twin-twin transfusion syndrome (Best Practice).

Pre- and Periviable PPROM after Fetoscopic Laser Surgery: Are Survival Outcomes Better than We Think?

INTRODUCTION: Limited data exist regarding outcomes when pre- and periviable PPROM (PPROM ≤26 weeks of gestation) occurs as a complication of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). METHODS: This is a retrospective cohort study of FLS cases performed at a single institution between January 2015 and May 2021. Study inclusion was limited to patients with monochorionic-diamniotic twin pregnancies complicated by TTTS who underwent FLS. Patients were grouped by pPPROM status, and further stratified to those continuing with expectant management, and outcomes were compared between groups. The primary outcome was survival to live birth of at least one twin. RESULTS: During the study period, 171 patients underwent FLS and a total of 96 (56.1%) subjects satisfied inclusion criteria. Among included subjects, 18 (18.8%) experienced pPPROM after FLS and 78 (81.2%) did not. Baseline characteristics were similar between groups. Among patients with pPPROM, 11 (61.1%) pursued expectant management and 7 (38.9%) opted for pregnancy termination. Among expectantly managed subjects, median pPPROM-to-delivery interval was 47.0 days (6.0-66.0 IQR) with a median gestational age at delivery of 29+1 weeks (24 + 4-33 + 6 IQR). Rates of survival to live birth of at least one twin (90.9% vs. 96.2% p = 0.42) were similar between those with pPPROM undergoing expectant management and those without pPPROM. Dual survivorship (45.5% vs. 78.2%, p = 0.03), perinatal survival to live birth (68.2% vs. 87.2%, p = 0.05), and perinatal survival to newborn hospital discharge (59.1% vs. 85.9%, p = <0.01) were all significantly lower among those with pPPROM. Gestational age at delivery was lower among those continuing with pregnancies complicated by pPPROM (29 + 1 vs. 32+5 weeks, p = <0.01). CONCLUSION: Survival of at least one twin to live birth remained high among those pursing expectant management after experiencing post-FLS pPPROM, suggesting that the outlook after this complication is not necessarily poor. However, this complication was associated with lower chances of dual survival and greater prematurity.

Monochorionic Twin Complications and Fetoscopic Interventions.

Monochorionic twins are at risk for complications due to the presence of placental vascular anastomoses, including twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, and twin reversed arterial perfusion sequence. While ultrasound is the primary modality to screen for the development of these complications, MRI plays an important role in assessing monochorionic twin pregnancies for the development of other complications, such as neurologic injury. In this article, the authors review the ultrasound imaging findings associated with monochorionic twin complications, management options, and the role for MRI in these pregnancies.

Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial.

BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival. OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order. STUDY DESIGN: A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth. RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73-1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20-0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%. CONCLUSION: Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin's postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

Intertwin discordance of aldosterone levels in amniotic fluid with placental anastomoses in monochorionic twins: Insight into the pathophysiology of twin-to-twin transfusion syndrome.

INTRODUCTION: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin-angiotensin-aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF-ALD) levels. In addition, this study also examined the association between AF-ALD and the ALD levels in the umbilical cord blood (UCB-ALD) in monochorionic twins. MATERIAL AND METHODS: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin-to-twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF-ALD levels between the larger and smaller twins were analyzed. RESULTS: The AF-ALD levels showed a strong and significant positive correlation with UCB-ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF-ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). CONCLUSIONS: The AF-ALD levels reflect the UCB-ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS.

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

OBJECTIVES: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97). CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

Necrotizing enterocolitis in monochorionic twins: Insights from an identical twin model.

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002-2020 were retrospectively reviewed for NEC. Potential risk factors for NEC were studied. For within-pair comparison, outcomes were compared between affected and unaffected twins. Within-pair analyses showed that the twin with NEC had a lower birth weight compared to its unaffected co-twin (1100 (913-1364) vs. 1339 (1093-1755) grams). Median gestational age at birth and birth weight were lower in twin pairs in the NEC-group compared to the no-NEC group, 29.1 weeks (27.8-30.8) versus 33.6 (30.7-36.0) and 1221 g (1010-1488) versus 1865 (1356-2355) respectively. Twin pregnancies in the NEC-group were more often complicated by twin-to-twin transfusion syndrome compared to the no-NEC-group (70 % (14/20) vs. 49 % (472/962)), particularly when treated with amnioreduction. This unique population of identical twins confirms that preterm neonates with a relatively lower birth weight are more prone to develop NEC compared to their co-twin, regardless of other genetic, maternal and obstetrical factors.

Whole-genome sequences reveal zygotic composition in chimeric twins.

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.

OBJECTIVE: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally. METHODS: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally. RESULT: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05). CONCLUSION: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

OBJECTIVES: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. METHODOLOGY: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). RESULTS: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). CONCLUSION: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Perinatal outcomes and growth discordance of triplet pregnancies based on chorionicity: a retrospective cohort study.

BACKGROUND: The worldwide occurrence of triplet pregnancy is estimated to be 0.093%, with a natural incidence of approximately 1 in 8000. This study aims to analyze the neonatal health status and birth weight discordance (BWD) of triplets based on chorionicity from birth until discharge. METHODS: This was a retrospective study. We reviewed a total of 136 triplet pregnancies at our tertiary hospital between January 1, 2001, and December 31, 2021. Maternal and neonatal outcomes, inter-triplet BWD, neonatal morbidity, and mortality were analyzed. RESULTS: Among all cases, the rates of intrauterine death, neonatal death, and perinatal death were 10.29, 13.07, and 24.26%, respectively. Thirty-seven of the cases resulted in fetal loss, including 13 with fetal anomalies. The maternal complications and neonatal outcomes of the 99 triplet pregnancies without fetal loss were compared across different chorionicities, including a dichorionic (DC) group (41 cases), trichorionic (TC) group (37 cases), and monochorionic (MC) group (21 cases). Neonatal hypoproteinemia (P < 0.001), hyperbilirubinemia (P < 0.019), and anemia (P < 0.003) exhibited significant differences according to chorionicity, as did the distribution of BWD (P < 0.001). More than half of the cases in the DC and TC groups had a BWD < 15%, while those in the MC group had a BWD < 50% (47.6%). TC pregnancy decreased the risk of neonatal anemia (adjusted odds ratio [AOR] = 0.084) and need for blood transfusion therapy after birth (AOR = 0.119). In contrast, a BWD > 25% increased the risk of neonatal anemia (AOR = 10.135) and need for blood transfusion after birth (AOR = 7.127). TC pregnancy, MCDA or MCTA, and BWD > 25% increased neonatal hypoproteinemia, with AORs of 4.629, 5.123, and 5.343, respectively. CONCLUSIONS: The BWD differed significantly according to chorionicity. Additionally, TC pregnancies reduced the risk of neonatal anemia and need for blood transfusion, but increased the risk of neonatal hypoproteinemia. In contrast, the BWD between the largest and smallest triplets increased the risk of neonatal anemia and the need for blood transfusion. TC pregnancy, MCDA or MCTA, and BWD > 25% increased the risks of neonatal hypoproteinemia. However, due to the limited number of triplet pregnancies, further exploration of the underlying mechanism is warranted.