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

BACKGROUND: Monochorionic (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. OBJECTIVES: The 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 DESIGN: Aortic 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. RESULTS: The 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. CONCLUSIONS: The 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.

Impact of Selective Fetal Growth Restriction on Laser Therapy Outcomes in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of this study was to determine if outcomes of fetoscopic laser photocoagulation in isolated twin-twin transfusion syndrome (TTTS) differ from TTTS with concomitant selective fetal growth restriction (sFGR). METHODS: This is a retrospective cohort study of all cases of TTTS treated at the CHU Sainte-Justine between February 2006 and January 2020. Data were collected from maternal, obstetrical, and neonatal chart review. RESULTS: A total of 149 patients were included in our study. Forty-seven patients (31.5%) had a pregnancy complicated by TTTS and sFGR. Mean gestational age at diagnosis and at treatment was 20+4 weeks and 20+6 weeks for TTTS alone, and 20+5 weeks and 21+2 weeks with concomitant sFGR. The presence of concomitant sFGR negatively impacted survival. Double survival in the TTTS + sFGR was 48.9% (23/47) versus 68.6% (70/102) in the TTTS-only group (p = 0.021). Fetal donor survival was 59.6% (28/47) in the TTTS + sFGR group and 84.3% (86/102) in the TTTS-only group (p = 0.001). However, the survival of at least one twin did not differ between the two groups: 93.6% (44/47) in the TTTS + sFGR group versus 92.2% (94/102) in the TTTS-only group (p = 0.751). The presence of type 2-3 sFGR (OR = 0.56; 95% CI 0.32-0.96, p = 0.033) and gestational age at laser therapy (OR = 1.17; 95% CI 1.01 = 1.36, p = 0.036) were independently associated with dual survival. CONCLUSION: sFGR is independently associated with decreased double survivorship at the expense of the donor in TTTS undergoing laser therapy. Type 2 or 3 sFGR and early gestational age at treatment are especially at risk. A larger cohort is needed to validate our results.

Calvarial doughnut lesions with bone fragility in a French-Canadian family; case report and review of the literature.

Calvarial Doughnut Lesions with Bone Fragility (CDL) is an autosomal dominant genetic disease, characterized by low bone mineral density, multiple fractures starting in childhood, and sclerotic doughnut-shaped lesions in the cranial bones. Aubé and colleagues described in 1988 a French-Canadian family of 12 affected members who had a clinical diagnosis of doughnut lesions of the skull, with pathological fractures, osteopenia, "bone in bone" in the vertebral bodies and squaring of metatarsal and metacarpal bones. Herein we study new members of this family. Sequential genetic testing identified a nonsense variant c.148C>T, p. Arg50⁎ in SGMS2 previously reported in other families. SGMS2 encodes Sphingomyelin Synthase 2, which produces Sphingomyelin (SM), a major lipid component of the plasma membrane that plays a role in bone mineralization. The nonsense variant is associated with milder phenotype. The proband presents with bone in bone vertebral appearance that had been defined uniquely in the first cases described in the same family. The proband's son was identified to carry the same variant, which makes him the sixth generation with the diagnosis of CDL. We also report that the same pathogenic variant was identified in another previously described family, from France. These reports further confirm the genetic basis of CDL, the recurrence of the same variant (p.Arg50*) in individuals of the same ancestry, and the variable penetrance of some of the clinical findings.

Prenatal presentation of glutaric aciduria type II: A case report with radiologic, clinical, biochemical, molecular, and pathological phenotyping.

We know that glutaric aciduria type II is an inborn metabolism. This case report highlights that polycystic kidneys with hepatomegaly in prenatal ultrasound are suggestive of glutaric aciduria type II and it identifies a new variant as pathogenic.

Expectant Management of Monochorionic-Triamniotic Triplets Complicated by Selective In Utero Growth Restriction: Report of 2 Cases.

The optimal management of monochorionic-triamniotic (MCTA) triplet pregnancies is not clearly established, and there is no literature to guide management of MCTA complicated with selective intrauterine growth restriction (sIUGR). This gap in knowledge and the concern for higher risk of severe complications have led some medical societies to recommend selective termination of nontrichorionic triplet pregnancies. We sought to report the favourable outcomes of two MCTA complicated by sIUGR expectantly managed at Sainte-Justine Hospital, Montreal, Canada. The first case is of a 42-year-old woman with spontaneous MCTA triplets diagnosed at 18 weeks with type II sIUGR who opted for expectant management. The second patient was a 22-year-old woman with a spontaneous MCTA triplet pregnancy diagnosed at 18 weeks with type III sIUGR. Our experience shows that close serial ultrasounds could potentially allow physicians to foresee fetal deterioration. In our opinion, expectant management should be considered as a management option for MCTA complicated by sIUGR.

Retrospective analysis of fetal vertebral defects: Associated anomalies, etiologies, and outcome.

Our objectives were to describe fetal cases of vertebral defects (VD), assess the diagnostic yield of fetal chromosomal analysis for VD and determine which investigations should be performed when evaluating fetal VD. We performed a retrospective chart review for fetuses with VD seen between 2006 and 2015. Cases were identified from CHU Sainte-Justine's prenatal clinic visits, postmortem fetal skeletal surveys, and medical records. Cases with neural tube defects were excluded. Sixty-six fetuses with VD were identified at a mean gestational age of 20 weeks. Forty-seven (71.2%) had associated antenatal anomalies, most commonly genitourinary, skeletal/limb, and cardiac anomalies. Thirteen mothers (19.7%) had pregestational diabetes (95% CI [10.1%-29.3%]). Fifty-three cases had chromosomal analysis. Three had abnormal results (5.6%): trisomy 13, trisomy 22, and 9q33.1q34.11 deletion. Thirty-four (51.5%) pregnancies were terminated, one led to intrauterine fetal demise and 31 (46.9%) continued to term. Of 27 children who survived the neonatal period, 21 had congenital scoliosis and 3 had spondylocostal dysostosis. Seven had developmental delay. In conclusion, prenatal evaluation of fetuses with VD should include detailed morphological assessment (including fetal echocardiogram), maternal diabetes screening, and chromosomal microarray if non-isolated. Our findings provide guidance about management and counseling after a diagnosis of fetal VD.

Renal functional markers in extremely premature infants with and without twin-twin transfusion syndrome.

OBJECTIVE: Describe renal function of preterm infants <29 weeks of gestational age (GA) with twin-twin transfusion syndrome (TTTS) who received laser therapy. DESIGN: Retrospective analysis of premature TTTS compared with dichorionic-diamniotic (di-di) twins from 2006 to 2015. Primary outcome was biomarkers of renal injury. RESULTS: Thirty-three TTTS-laser and 101 di-di newborns with similar GA at birth (26.4 ± 1.4 vs 26.9 ± 1.6 weeks, p = 0.07) were included. Creatinine and urea levels were higher in TTTS-laser group at day of life (DOL) 2-7 (123.5 ± 12.4 vs 75.8 ± 2 µmol/L, p = 0.0001 and 11.9 ± 1.1 mmol/L vs 8.7 ± 0.3 mmol/L, p = 0.0001) and DOL 8-14, (98.1 ± 14.2 vs 64.8 ± 2.3 µmol/L, p = 0.0001 and 9.1 ± 1.2 vs 5.4 ± 0.3 mmol/L, p = 0.0001). There was a significant effect of TTTS status on creatinine level at DOL 8-14. CONCLUSION: In extremely preterm with TTTS treated by laser, biomarkers of renal function were higher compared with di-di twins in the first 2 weeks of life.

Outcomes of extremely premature infants with twin-twin transfusion syndrome treated by laser therapy.

OBJECTIVE: To compare short-term and long-term outcomes of preterm infants born at <29 weeks of gestational age (GA) with twin-twin transfusion syndrome (TTTS) treated with laser therapy to preterm twin infants without TTTS. DESIGN: Retrospective case-control study comparing 33 preterm TTTS twins to 101 preterm diamniotic-dichorionic (di-di) twins born at our institution between 2006 and 2015. RESULTS: GA at birth were 26.4 ± 1.4 weeks (TTTS) and 26.9 ± 1.6 weeks (di-di) (p = 0.07). TTTS premature newborns were less exposed to antenatal steroids (p = 0.01), more frequently born by C-section (p = 0.005), received more surfactant therapy (p = 0.004, and were smaller for GA (p < 0.001). When adjusted for antenatal steroids and birth weight, TTTS status was not associated with increased mortality (HR 1.66, 95% CI 0.77-3.56, p = 0.20). No differences were found on neurodevelopmental outcomes at 18 months of corrected GA. CONCLUSION: Premature TTTS newborns treated with fetal laser therapy had similar survival and neurodevelopmental outcomes compared to preterm di-di twins without TTTS.

Factors associated to early intrauterine fetal demise after laser for TTTS by preoperative fetal heart and Doppler ultrasound.

OBJECTIVE: To determine the prognostic value of fetal Doppler and echocardiographic parameters for intrauterine fetal demise (IUFD) within 24 hours and within 1 week after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome. METHOD: This retrospective study correlated the preoperative hemodynamic and echocardiography parameters to the outcome in fetuses with twin-twin transfusion syndrome undergoing laser therapy. RESULTS: One hundred and twelve laser coagulations were performed between February 2006 and June 2015. The total (single and double) IUFD rate was 27.7%. Further, 59% of IUFD occurred within 24 hours and 74.4% occurred within 1 week after laser. The following were associated to IUFD within 24 hours: the middle cerebral arterial pulsatility index in the donor, abnormal umbilical artery (UA) end diastolic flow, increased middle cerebral artery peak systolic velocity, and right ventricular myocardial performance index (RV-MPI) z-score in the recipient. For IUFD within 1 week were the pulsatility index in the donor UA and the recipient abnormalities in UA, ductus venosus, middle cerebral artery-peak systolic velocity, and RV-MPI z-score. CONCLUSION: Following laser was early IUFD that was associated with Doppler findings suggesting donor cerebroplacental redistribution, and recipient overload cardiomyopathy, such as abnormal ductus venosus and UA Dopplers as well as an increase of RV-MPI.

Aortic Isthmus Flow Recording Predicts the Outcome of the Recipient Twin after Laser Coagulation in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. MATERIAL AND METHODS: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. RESULTS: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). DISCUSSION: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.

Impact of amniotic fluid "sludge" on the risk of preterm delivery.

OBJECTIVE: To evaluate the impact of amniotic fluid "sludge" (AFS) on the risk of preterm delivery and to describe the effect of antibiotic treatment in that situation. METHODS: Case-control study including singleton pregnancies with or without AFS, between 15-32 weeks of gestation. Factors associated with preterm delivery before 32 weeks, 34 weeks and 37 weeks were evaluated with univariate and multivariate logistic regression. Since all women with AFS in this study were treated with antibiotics, a historical comparison was performed with similar patients with AFS found before 2007 and not treated with antibiotics. RESULTS: AFS was observed in 90/1220 patients (7.4%). AFS was associated with shorter cervical length, greater body mass index, cervical cerclage and preterm birth before 28 weeks. However, after adjustment, AFS did not remain associated with preterm delivery before 32 or 34 weeks. The historical comparison suggested that azithromycin could significantly reduce the risk of preterm delivery before 34 weeks (odds ratio: 0.2; 95% CI: 0.04-0.92). CONCLUSIONS: AFS, treated with azithromycin, was associated with a higher risk of prematurity, but not independently after adjustment for cervical length and second trimester vaginal bleeding. Further studies need to evaluate the effect of antibiotics in pregnancies with AFS.