Selective Intrauterine Growth Restriction Research Articles

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia

BackgroundPreeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown.ResultsBy analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling.ConclusionsOur study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Clinical Outcome of Monochorionic Diamniotic Twins with Intrauterine Growth Restriction.

This study investigated the clinical outcome of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). International Peace Maternal and Child Health Hospital of Shanghai ultrasound database was investigated to identify all MCDA delivered from January 2013 to December 2017. After identifying 43 pairs of MCDA twins with sIUGR and 282 pairs of normal MCDA twins, we compared clinical outcomes between the two groups. Compared with normal twins, sIUGR fetuses had significantly shorter gestational age at delivery, smaller average birth weight of both twins, more significant intertwin difference in birth weight, lower Apgar scores, and higher intrauterine fetal demise (IUFD) rate, and smaller placental weight. The rate of abnormal umbilical cord insertions and abnormal blood flow in the ductus venosus (DV) and middle cerebral artery (MCA) is significantly higher in the sIUGR group. In addition, the subtype analysis of sIUGR groups indicated the poorest outcomes in type II with no significant difference between type I and III. MCDA twins with sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with abnormal umbilical cord insertions and blood flow in the DV and MCA. Clinical outcomes differed among the three types of sIUGR, with type II having the worst prognosis and the highest IUFD rate. · sIUGR generally exhibited limited clinical outcomes than normal MCDA twins.. · These limitations are mainly associated with blood flow of the DV and MCA.. · sIUGR with type II has the worst prognosis and the highest IUFD rate..

SFM Fetal Therapy Practice Guidelines: Bipolar Cord Coagulation

AbstractBipolar cord coagulation is modality available for the treatment of monochorionic diamniotic twins with any one of the following indications: discordant anomalous fetus, severe selective Intrauterine growth restriction (IUGR) (type 2 and type 3) in very preterm and premature fetuses, and selected cases of twin-twin transfusion syndrome when LASER photocoagulation is not feasible. Twin reversed arterial perfusion sequence with polyhydramnios and cardiac overload in pump twin, Multifetal reduction involving MCDA pair.

Outcome of monochorionic diamniotic twin pregnancy with selective intrauterine growth restriction, a single center study in China

IntroductionThis retrospective study aimed to evaluate clinical outcomes of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). Materials and methodsMCDA twins, either sIUGR and non-sIUGR, underwent expectant management from 2016 to 2019 in our hospital were included. sIUGR fetuses were classified into three types according to umbilical artery Doppler assessment. Non-sIUGR were considered as the control group. Outcomes were pregnancy outcomes and maternal complications. ResultsForty-three sIUGR (type I: 23; type II: 14, and type III: 6) and 282 non-sIUGR fetuses were included. The sIUGR group had a significantly earlier birth, lower birth weight of the twins, larger inter-twin weight difference, lower Apgar score of the twins, and higher intrauterine fetal death (IUFD) than the non-sIUGR group (all p < 0.001). The same trend was found in the sIUGR type II group compared to type I and III groups. A significantly lower gestational diabetes rate (p = 0.01) and placenta weight (p < 0.001), and higher proportions of abnormal placental umbilical cord insertion (p < 0.001), and ultrasound Doppler monitoring indicators (p = 0.006) were found in the sIUGR group than the non-sIUGR group. ConclusionsThe MCDA twins with sIUGR showed poorer outcomes than the non-sIUGR group. Doppler interrogation was a useful clinical marker for fetal outcome.

TET2-mediated DNA hydroxymethylation of TGFB1 is related to selective intrauterine growth restriction in monochorionic twin pregnancies

IntroductionSelective intrauterine growth restriction (sIUGR), which specifically occurs in monochorionic (MC) twins, usually has a poor prognosis and the underlying mechanisms are not well understood. It is an ideal model for exploring epigenetic-modified mechanisms for fetal development in MCDA twins due to eliminating the interference of different heritable backgrounds and intrauterine environments among individuals. MethodsThe levels of ten-eleven translocation 2 (TET2) and its upstream and downstream targets miR-29b-3p and transforming growth factor beta 1 (TGFB1) were determined using RT‒qPCR, western blotting, and immunohistochemistry. Using TET2 overexpression and knockdown methods, we investigated the role of TET2 in trophoblast functions. The regulatory relationships among TET2, miR-29b-3p, and TGFB1 were explored by cell migration assay, invasion assay, apoptotic ratio assays, Western blot, hMeDIP-qPCR and dual-luciferase assay. ResultsA consistent upregulation of TET2 and TGFB1 was observed in the smaller placental shares compared to the larger placental shares in sIUGR. Gain-of-function studies of TET2 in trophoblasts showed decreased cell invasion and increased apoptosis, whereas loss-of-function studies of TET2 rescued this effect. Mechanistic studies revealed that miR-29b-3p and TGFB1 were the upstream factor and downstream target of TET2, respectively. Furthermore, miR-29b-3p/TET2/TGFB1-smad was identified as a unique axis that regulates trophoblast invasion, migration, and apoptosis in a DNA hydroxymethylation-dependent manner. DiscussionWe elucidated the functional roles of TET2 and DNA hydroxymethylation in trophoblasts and identified a novel DNA regulatory mechanism, providing a basis for further exploration of DNA epigenetic regulatory patterns in sIUGR.

Fetal Outcomes and Prognostic Factors After Radiofrequency Ablation for the Selective Reduction in Complicated Monochorionic Multiple Pregnancies

Monochorionic pregnancies are responsible for some severe complications, and selective reduction of a single fetus can improve pregnancy outcomes. This study evaluated the fetal outcomes and procedure-related prognostic factors after radiofrequency ablation (RFA) in complicated monochorionic multiple pregnancies. This prospective cross-sectional study was conducted in an academic center from June 2020 to January 2022. The participants were 70 women with monochorionic multiple pregnancies who were candidates for selective fetal reduction by RFA. All participants' demographic data, RFA-related information, and pregnancy outcomes were evaluated and reported. The RFA procedure was successful in all participants. The most frequent RFA indications were twin-to-twin transfusion syndrome following selective intrauterine growth restriction. The mean gestational age at birth was 33.60±5.62 weeks. Also, 11 (15.7%) of the cases had preterm delivery up to 30 days after RFA. The total pregnancy loss rate was 12 (17.14%), and the total fetal survival rate after RFA was 82.85%. The mean time of the RFA procedure was 130.8±83.3seconds.The procedure was conducted easily in 31 (44.2%) cases. Althoughthe meantime of RFA procedure was longer in the not-easy group, the difference in surgery time was not significant (P=.296). There was no significant relationship (P=.623) between RFA indications and the gestational age of the remained fetus at delivery. The RFA needle was passed through the placenta in 18 (25.7%) cases. The mean gestational age at the delivery time was significantly lower in this group compared to their counterparts' gestational ages without needle placental passage (P=.030). Also, there was no significant correlation between gestational age at pregnancy termination and RFA cycles (P=.219). RFA is a relatively safe and minimally invasive procedure for the selective reduction of complicated monochorionic fetuses. Althoughmortality, premature membrane rupture, and preterm delivery are the potential risk factors for the remaining co-twin. According to this study, gestational age at the time of the procedure and passing the needle through the placenta can affect the outcome. Other procedure-related factors like easy- or hard-access procedures, and the number of RFA cycles are not significantly associated with gestational age at birth.

Surveillance of pregnancy outcome of monochorionic twins at Tu Du Hospital

Background: Monochorionic twins are a high risk pregnancy and are associated with special complications that are unique to sharing a placenta and because of the hemodynamic imbalance caused by placental vascular anastomoses. Therefore, the outcome of monochorionic twins is still being researched and reported to looking for the best evidence to perform the optimal interventions.&#x0D; Objectives: To describe the outcome of monochorionic twins to determine the proportion of special complications. Moreover, exploring the rate of fetal death in uterus, premature delivery, the successful vaginal birth in complicated monochorionic twins after bipolar cord coagulation.&#x0D; Materials and Methods: Case series report of monochorionic twins which was managed pregnancy and delivered at Tu Du hospital between January 2018 and January 2019, comprised 166 cases with 81 complicated monochorionic twin pregnancies.&#x0D; Results: The series comprised 85 uncomplicated monochorionic twins (51.2%) and 81 complicated cases (48.8%) with 15% twin-twin transfusion syndrome (TTTS) and 28.3% selective intrauterine growth restriction (sIUGR). Nineteen cases of bipolar cord coagulation perfomed included seven TTTS, eight sIUGR, three cases with serious malformation, and one twin reversed arterial perfusion sequence (TRAP).&#x0D; Conclusions: TTTS and sIUGR are complications unique to monochorionic twins and diagnosed in the early stage after 23 week’s gestation. Bipolar cord coagulation is an effective procedure in complicated monochorionic pregnancies to improve pregnancy outcome.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction

In perinatal medicine, intrauterine growth restriction (IUGR) is one of the greatest challenges. The etiology of IUGR is multifactorial, but most cases are thought to arise from placental insufficiency. However, identifying the placental cause of IUGR can be difficult due to numerous confounding factors. Selective IUGR (sIUGR) would be a good model to investigate how impaired placentation affects fetal development, as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors. Herein, we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins. Specifically, we identified a total of 5481 proteins, of which 233 were differentially expressed (57 up-regulated and 176 down-regulated) in IUGR twins. Bioinformatics analysis indicates that these differentially expressed proteins (DEPs) are mainly associated with cardiovascular system development and function, organismal survival, and organismal development. Notably, 34 DEPs are significantly enriched in angiogenesis, and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed. Moreover, we found decreased expression of metadherin (MTDH) in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro. Collectively, our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins, and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Analysis of typing conversion and perinatal outcomes in twins with selective intrauterine growth restriction of different subtypes

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.

Fetal Doppler in monochorionic pregnancies complicated by twin-to-twin transfusion syndrome and selective in utero growth restriction

BackgroundMonochorionic (MC) twin pregnancies may be complicated by placental pathologies that impact fetal cardiac function, such as twin-twin transfusion syndrome (TTTS) and selective intrauterine growth-restriction (sIUGR). In the TTTS, the unbalanced blood flow through placental anastomoses lead a recipient volume overload, hypertension and hypertrophic cardiomyopathy and the donor twin experiences hypovolemia and hypertension due to increased placental resistance and poor renal perfusion. When MC pregnancies were complicated by sIUGR, the increase of placental resistances lead to complex fetal compensatory mechanisms with redistribution of cardiac output to vital organs. Increased placental vascular resistances, hypoxia and hemodynamic compensation mechanisms lead to higher pre and/or afterload for both ventricles, right cardiac failure and eventually left cardiac failure observed just before fetal death. ObjectivesThe purpose of this study was to describe the anomalies of umbilical, ductal and aortic isthmic Doppler as well as left and right myocardial performance index (MPI) across various clinical phenotypes of MC twin pregnancies, uncomplicated or complicated by TTTS or sIUGR, in order to help differentiating these conditions and to improve the understanding of TTTS and sIUGR pathophysiology. Study designAortic isthmic systolic index (ISI), umbilical artery pulsatility index (UAPI), ductus venosus pulsatility index (DVPI), and MPI were studied in uncomplicated MC twins (control group) and cases of sIUGR or TTTS. ResultsThe measurements were obtained in 113 pregnancies (24 uncomplicated, 22 sIUGR, 51 TTTS). In comparison with controls, the sIUGR smaller twin sets had lower ISI and higher UAPI, and the larger twin had higher ISI. The TTTS donor and recipient had lower ISI, higher UAPI and DVPI. Compared to the co-twin, the ISI values were lower in the sIUGR smaller twin and the TTTS donor had lower ISI and MPI. Comparing TTTS and sIUGR, the recipient had higher DVPI and MPI than the sIUGR larger twin. ConclusionsThe Doppler anomalies observed in the smaller twin reflected increased placental blood flow resistance, presumably due to abnormal feto-fetal transfusion in TTTS and to unequal placental sharing in sIUGR. Early hemodynamic changes suggestive of cardiac overload in the recipient twin may help to differentiate TTTS and sIUGR.

A case of type III selective intrauterine growth restriction in a monochorionic twin pregnancy with a myriad of Doppler changes of the umbilical and vitelline arteries

Monochorionic twins have higher mortality rates than dichorionic twins. Selective intrauterine growth restriction (sIUGR) is a common complication found in monochorionic twins. We report such a case of type III sIUGR monochorionic twins. There was positive end-diastolic flow of umbilical arteries, which corresponded to type I sIUGR at 15 weeks. Then, the umbilical arteries showed persistently absent end-diastolic flow at 17 weeks which corresponded to type II sIUGR. Finally, the umbilical artery showed intermittent absent/reversed end-diastolic flow which corresponded to type III sIUGR. This case demonstrated a unique myriad of Doppler changes during the pregnancy, indicating its significance in being reported. The twins were delivered by caesarean section at 32 weeks and were developing well. Placental examination showed unequal placental sharing and the presence of an arterio-arterial anastomosis. These are characteristic findings of a type III sIUGR. Type III sIUGR may not be obvious at the initial examination but may only be obvious at later examinations.

Cord blood adiponectin and leptin concentrations in monochorionic twins with selective intrauterine growth restriction and their associations with childhood growth trajectories.

Being born with intrauterine growth restriction (IUGR) was associated with subsequent health issues later in life. However, the underlying role of adipokines in IUGR is unknown. To measure the adiponectin and leptin concentrations in the cord blood of monochorionic (MC) twins with selective IUGR (sIUGR) and evaluate their associations with childhood growth trajectories. Cord blood samples were collected from 22 pairs of MC twins with sIUGR and 20 pairs of normal MC twins. Adiponectin and leptin concentrations in cord blood were determined by ELISA. Data regarding perinatal outcomes and infantile growth trajectories from birth to 24 months were obtained. Only cord blood adiponectin concentrations were associated with IUGR (β -1.51, 95% CI -2.45, -0.57, p = 0.002), and cord blood leptin concentrations were significantly lower in sIUGR twins compared to normal twins (2.8 ± 1.6 vs. 6.4 ± 3.0, p < 0.001). Adiponectin concentrations were negatively associated with height increments from birth to 6 months (β -0.28, 95% CI -0.51, -0.06, p = 0.015). Leptin concentrations were negatively associated with weight at 6 and 24 months (β -0.12 95% CI -0.22, -0.02, p = 0.002; β -0.18 95% CI -0.33, -0.03, p = 0.019) and weight and height increments from birth to 6 months (β -0.17 95% CI -0.29, -0.06, p = 0.020; β -0.40 95% CI -0.81, -0.01, p = 0.037). Cord blood adiponectin concentrations were negatively associated with IUGR but did not predict childhood growth. Cord blood leptin concentrations were inversely associated with weight and height increments in the first 6 months.

Physical development of preterm monochorionic diamniotic twins at birth: retrospective cohort study

Background. Much controversy surrounds the estimation of anthropometric parameters in multiple newborns. In newborn monochorionic diamniotic twins, these parameters can be affected by specific antenatal complications.Objectives. To estimate the physical development parameters of preterm monochorionic diamniotic twins according to standards proposed within the INTERGROWTH-21st project, taking specific intrauterine complications into account.Methods. The anthropometric data were analyzed in 148 pairs of newborn monochorionic diamniotic twins, who were divided into three groups according to the presence of specific intrauterine complications: Group I (n = 56 pairs) — twin-to-twin transfusion syndrome (TTTS); Group II (n = 38 pairs) — selective intrauterine growth restriction (sIUGR); Group III (n = 58 pairs) — absence of the above-mentioned specific complications. The obtained data were statistically processed on a personal computer via variation statistics methods using Microsoft Excel spreadsheets (Microsoft, USA) and an online service available at https://medstatistic.ru.Results. Newborns with sIUGR (37–100.0%) and 26 (49.1%) donors fell into the category of newborns light for gestational age. Disharmonious (3–10th percentile) and markedly disharmonious (below the 3rd percentile) physical development at birth was most commonly observed in newborns with sIUGR and, to a lesser extent, in donors (OR — 9.2; 95% CI — 3.2–24.3; p &lt; 0.05), which was noted only occasionally in monochorionic twins from other groups. A combined decrease in the values of birth centiles for head circumference, body weight, and body length was found in 13 (35.1%) newborns with sIUGR and in 12 (22.6%) donors, which may mark the severity of antenatal complications and the development of neurological deficit.Conclusion. Monochorionic diamniotic twins include newborns having greater and lower body weights. In the newborn having a lower birth weight, specific complications associated with monochorionic multiple pregnancy result in body weight and length deficit, disharmonious development due to the lack of nourishment (22.6% in the TTTS group and 73.0% in the sIUGR group), as well as delayed head circumference growth in 56.8% of newborns with sIUGR.

Течение и исходы многоплодной беременности при монохориальной моноамниотической двойне

Aim: to evaluate the course and outcomes of monochorial monoamniotic (MCMA) twin pregnancy. Patients and Methods: this prospective study included 34 patients (a mean age 31.8±4.3 years) with MCMA twins for assessing the course of pregnancy and perinatal outcomes. The authors evaluated such criteria as the timing of delivery and the prenatal management of MCMA-twin pregnancy, as well as the perinatal outcomes and mortality. Monitoring of the pregnant women with umbilical cord entanglement was started at 16 weeks of gestation and included ultrasound examination every two weeks and after 26–28 weeks of gestation — two or three times a week coupled with cardiotocography for fetal assessment. Results: the study demonstrated a high prevalence of cervical insufficiency which was found in 10 (29.4%) MCMA twin pregnancies at 18 to 28 weeks of gestation. The diagnosis of umbilical cord entanglement was established in 16 (47.1%) patients, twin-twin transfusion syndrome (TTTS) – in 2 (5.9%) patients, and twin anemia-polycythemia syndrome (TAPS) – in 1 (2.9%) patient. The reported antenatal losses were 6 of 68 (8.8%) of fetuses. There were 7 perinatal losses of 68 MCMA-twin pregnancies (10.3%). The antenatal and perinatal losses in MCMA twins were caused by the following specific complications: TTTS, cord entanglement and hypoxia due to the selective intrauterine growth restriction (sIUGR). A preterm operative delivery was used in 29 (85.2%) patients with MCMA twins. Five (14.7%) patients did not have complications and it was possible to prolong the pregnancy to 36 weeks. Caesarean sections were carried out almost for all the pregnant women (33 (97.1%)). Conclusion: the antenatal and perinatal losses in MCMA twins are caused by the specific complications. These findings prove that patients with complicated MCMA twin pregnancies need to have a careful monitoring in Level III perinatal centers. Planned caesarean sections are recommended for all MCMA twin pregnancies. If complications are detected, a preterm operative delivery closer to week 35 of gestation will enable to increase the fetal survival rates and thus to improve the perinatal outcomes. Uncomplicated MCMA twin pregnancies can be prolonged to week 36 for improving the condition of newborn babies at the time of delivery. KEYWORDS: multifetal pregnancy, monochorial monoamniotic twin pregnancy, umbilical cord entanglement, neonatal outcome, twin-twin transfusion syndrome, selective intrauterine growth restriction, twin anemia-polycythemia syndrome. FOR CITATION: Kalashnikov S.A., Konoplyannikov A.G., Voskoboeva K.Yu. et al. The course and outcomes of monochorial monoamniotic twin pregnancy. Russian Journal of Woman and Child Health. 2023;6(1):6–12 (in Russ.). DOI: 10.32364/2618-8430-2023-6-1-6-12.

Amniotic fluid biomarkers of fetal stress response to cardiac dysfunction in twin-twin transfusion syndrome

Recipient twin (RT) cardiovascular changes in twin-twin transfusion syndrome (TTTS) are associated with increased mortality. This relationship is likely related to a cascade of pathophysiologic changes in the RT progressing to multisystem organ failure. We sought to evaluate biomarkers of inflammation, stress, and tissue injury within amniotic fluid (AF) of RTs undergoing selective fetoscopic laser photocoagulation (SFLP) for TTTS and examine their relationship with fetal echocardiographic findings. AF samples from RTs were obtained from 39 monochorionic-diamniotic pregnancies complicated by TTTS. Those without preoperative fetal echocardiograms or evidence of selective intrauterine growth restriction were excluded from analysis with 24 remaining samples. 15 commonly utilized clinical biomarkers for inflammation, stress, and tissue injury were assessed using a flow-cytometry based multiplex immunoassay. Fetal echocardiograms were performed prior to SFLP with myocardial performance index (MPI) utilized as a measure of cardiac dysfunction. Pearson’s correlation was used for data analysis. RT Left ventricular MPI (LV-MPI) ranged from 0.28-0.74, with 11/24 RTs demonstrating abnormal MPI for GA (Z-score > 2). RT AF cortisol (r = 0.4527, p = 0.020), IL-6 (r = 0.44, p = 0.025), CRP (r = 0.431, p = 0.028), and myoglobin (r = 0.401, p = 0.042) levels correlated with recipient left ventricular MPI (LV-MPI). AF cortisol strongly correlated with AF myoglobin (r = 0.576, p < 0.001). RT with abnormal LV-MPI exhibited significantly higher AF cortisol levels compared to those with normal LV-MPI (p = 0.029). RT amniotic fluid demonstrates markers of inflammation, stress and cardiac injury in recipient twins with cardiac dysfunction. These markers may be indicators of disease progression in TTTS secondary to cardiac dysfunction. The presence of these markers implicate stress and the immune response in the pathophysiologic response to cardiac dysfunction in TTTS.

Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2

Originally discovered in the circulation of pregnant women as a protein secreted by placental trophoblasts, the metalloprotease pregnancy-associated plasma protein A (PAPP-A) is also widely expressed by many other tissues. It cleaves insulin-like growth factor-binding proteins (IGFBPs) to increase the bioavailability of IGFs and plays essential roles in multiple growth-promoting processes. While the vast majority of the circulatory PAPP-A in pregnancy is proteolytically inactive due to covalent inhibition by proform of eosinophil major basic protein (proMBP), the activity of PAPP-A can also be covalently inhibited by another less characterized modulator, stanniocalcin-2 (STC2). However, the structural basis of PAPP-A proteolysis and the mechanistic differences between these two modulators are poorly understood. Here we present two cryo-EM structures of endogenous purified PAPP-A in complex with either proMBP or STC2. Both modulators form 2:2 heterotetramer with PAPP-A and establish extensive interactions with multiple domains of PAPP-A that are distal to the catalytic cleft. This exosite-binding property results in a steric hindrance to prevent the binding and cleavage of IGFBPs, while the IGFBP linker region-derived peptides harboring the cleavage sites are no longer sensitive to the modulator treatment. Functional investigation into proMBP-mediated PAPP-A regulation in selective intrauterine growth restriction (sIUGR) pregnancy elucidates that PAPP-A and proMBP collaboratively regulate extravillous trophoblast invasion and the consequent fetal growth. Collectively, our work reveals a novel covalent exosite-competitive inhibition mechanism of PAPP-A and its regulatory effect on placental function.

Perinatal and neurodevelopmental outcome in complicated monochorionic pregnancy after selective fetal reduction: radiofrequency ablation vs microwave ablation.

To summarize our experience in the application of radiofrequency ablation (RFA) and microwave ablation (MWA) for selective fetal reduction in complicated monochorionic pregnancies and compare the perinatal outcome of the two techniques. This was a retrospective study of data from a consecutive cohort of all monochorionic twin pregnancies that underwent selective fetal reduction with RFA or MWA at Peking University Third Hospital, Beijing, China from January 2012 to December 2018. All surviving cotwins were followed up to assess their neurodevelopment using the Age &amp; Stage Questionnaire, Chinese version. Perinatal and neurodevelopmental outcomes were compared between the RFA and MWA groups. We also fitted multivariable models to test the association between procedure-related factors and the main perinatal outcomes, including preterm birth (PTB) &lt; 37 weeks' gestation, intrauterine fetal death (IUFD) of the cotwin, adverse outcome (defined as occurrence of IUFD of the cotwin, termination of pregnancy or PTB &lt; 28 weeks) and overall survival. In total, 45 cases (42 twin and three triplet pregnancies) underwent RFA and 126 cases (105 twin and 21 triplet pregnancies) underwent MWA. The overall survival rates in monochorionic diamniotic twin pregnancies were similar between the RFA and MWA groups (61.0% vs 67.0%; P = 0.494). However, pregnancies whose indication for fetal reduction was selective intrauterine growth restriction or twin reversed arterial perfusion had higher overall survival rates (75.5% and 82.6%, respectively) compared with those in other indication groups. A total of 104 children were followed up (20 in the RFA group and 84 in the MWA group); four (20.0%) and eight (9.5%) children were assessed as having overall developmental delay in the RFA and MWA groups, respectively, with no significant difference between the two groups. Multivariable analyses showed that procedure indication, number of ablation cycles and gestational age at procedure were associated significantly with the main perinatal outcomes. RFA and MWA for selective fetal reduction in complicated monochorionic pregnancies can achieve similar overall survival rate and neurodevelopmental outcome, but MWA is associated with a lower risk of preterm birth. Moreover, procedure-related factors are associated significantly with perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Predictive values of first trimester ultrasound screening for twin-to-twin transfusion syndrome and selective intrauterine growth restriction in monochorionic twin pregnancies

Background: Monochorionic diamniotic (MCDA) twins are at significantly increased risk of perinatal morbidity and mortality due to shared placentation and the presence of inter-twin placental vascular anastomoses. Aim of the work: The main aim of this study was to validate first trimester ultrasound screening for twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies using the triad of nuchal translucency (NT), cord insertion site and inter-twin discordance in fetal size. Summary: We have demonstrated that NT and CRL were significantly higher in TTTS group than sIUGR group. And difference in NT, CRL and cord insertion site was identified as predictive markers for sIUGR and TTTS.

The effects of intrauterine growth on physical and intellectual development of one-year-old infants: a study on monochorionic twins with selective intrauterine growth restriction

This study aimed to evaluate physical and intellectual development of one-year-old infants of monochorionic twins with selective intrauterine growth restriction (sIUGR). A total of 31 pairs of sIUGR twins ageing 1 year old were included in the study. Each pair of sIUGR twins was divided into low birthweight-twin group (L-twin group) and high birthweight-twin group (H-twin group) according to twins’ birthweight. The differences in height, weight, head circumstance and body mass index (BMI) in each stage were statistically significant for all measures from birth until 1 year old (p < .05), and there was a disappointed catch-up growth in lighter twins. Psychomotor development index (PDI) and mental development index (MDI) at 1 year old were significantly different between the two groups (p < .05). Stepwise regression analysis showed that the effects of weight on both PDI and MDI were statistically significant (p < .05). Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants’ physical and intellectual development. Impact Statement What is already known on this subject? Selective intrauterine growth restriction in monochorionic twins increases the risks of intrauterine foetal demise, preterm birth, caesarean delivery and adverse neonatal outcomes, especially in the smaller foetus. What do the results of this study add? Previous studies have concentrated on the clinical management of sIUGR, while little attention has been paid to the growth and development of twins after birth. Given the adverse neurobiological effects of suboptimal nutrition on the brain development, it is important to determine whether IUGR causes long-term cognitive deficits and physical retardation. The current study has assessed the physical and intellectual development of one-year-old infants of monochorionic twins with sIUGR. What are the implications of these findings for clinical practice and/or further research? Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants’ physical and intellectual development. Further research on the longer-term effects of sIUGR is needed.