Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Fetal Care Nursing-The Birth of a Specialty.

With the rapid growth of specialized fetal care centers (FCCs) across the United States, a new area of nursing practice has emerged. Fetal care nurses provide care in FCCs to pregnant persons experiencing complex fetal conditions. This article describes the unique practice of fetal care nurses necessitated by the complexity of perinatal care and the provision of maternal-fetal surgery in FCCs. The Fetal Therapy Nurse Network has played a significant role in the evolution of this nursing practice and will serve as a platform for the generation of core competencies and the development of a potential specialty certification for fetal care nurses.

Outcomes of Monochorionic, Diamniotic Twin Pregnancies with Prenatally Diagnosed Intertwin Weight Discordance.

OBJECTIVE: Monochorionic, diamniotic (MCDA) twin pairs are predisposed to various pregnancy complications due to the unique placental angioarchitecture of monochorionicity. Few studies have evaluated the outcomes of weight-discordant MCDA pairs without selective fetal growth restriction (SFGR) or the risk factors for development of SFGR. This study aims to describe the natural history of expectant, noninvasive management of weight-discordant MCDA twins and to evaluate risk factors associated with progression to SFGR. STUDY DESIGN: This was a retrospective cohort study at a single, tertiary care center in the United States. All MCDA twins with isolated intertwin weight discordance (ITWD) ≥ 20% diagnosed before 26 weeks' gestational age (GA) were included. The primary outcome of descriptive analyses was overall pregnancy outcome, incorporating both survival to delivery and GA at delivery, as defined by the North American Fetal Therapy Network. The secondary outcome was SFGR in one twin (defined as estimated fetal weight < 10% for GA) and factors associated with this progression. Only those with fetal ultrasound (US) within 4 weeks of delivery were included in this secondary analysis. RESULTS: Among 73 MCDA pairs with ITWD, 73% had a good pregnancy outcome, with dual live delivery at a median GA of 33 weeks. Among the 34 pairs with adequate US follow-up, 56% developed SFGR. There were no differences in GA at delivery or discordance at birth between those who did and those who did not develop SFGR. There was a nonsignificant association between increasing ITWD at diagnosis and subsequent development of SFGR. CONCLUSION: Expectant, noninvasive management can be considered in MCDA twin pregnancies with ITWD ≥ 20% diagnosed before 26 weeks. This approach is associated with a good pregnancy outcome in the majority of cases, even after the development of SFGR in the smaller twin. KEY POINTS: · Nearly 75% of weight-discordant mo/di twins have a good pregnancy outcome.. · Weight-discordant mo/di twins deliver at a mean gestational age of 33 weeks without invasive therapy.. · Noninvasive management should be considered for weight-discordant mo/di twins..

The Use of Sequential Integrated Screening to Stratify Risk in Monochorionic-Diamniotic Twin Pregnancies.

OBJECTIVE: This study aimed to identify differences in sequential integrated screening and early ultrasound markers in monochorionic/diamniotic (MC/DA) pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) and unequal placental sharing (UPS). STUDY DESIGN: Retrospective cohort study of MC/DA pregnancies evaluated between January 2012 and July 2017 at the University of California San Francisco. MC/DA pregnancies with ultrasound surveillance up to 26 weeks who participated in the California Prenatal Screening Program (CPSP) were included. Pregnancies with structural or genetic anomalies were excluded. UPS was defined as an intertwin growth discordance ≥20%. Intertwin nuchal translucency (NT) discordance was calculated by the absolute value of the difference of the NT of cotwins. Kruskal-Wallis or ANOVA testing was performed where appropriate, and negative binomial regression models were chosen to test for differences in mean biomarker levels by outcome group. RESULTS: A total of 191 MC/DA pregnancies were included; 85 were affected by TTTS, 35 by UPS, and 71 controls. Significant differences in intertwin NT discordance in pregnancies complicated by TTTS and UPS compared with controls (p = 0.007) were found. TTTS cases had a mean NT discordance greater than two times that of controls (p = 0.04), while UPS cases had a value more than three times greater (p = 0.003). There was a statistically significant difference in mean second trimester human chorionic gonadotropin (hCG) between the cohorts (p = 0.0002) with TTTS cases having a mean second trimester hCG value 1.5 greater than both controls (p < 0.001) and UPS cases (p = 0.001). Analysis showed a significant difference in mean second trimester inhibin between the three cohorts (p = 0.029). Pregnancies complicated by UPS had a mean second trimester inhibin 1.5 times greater than controls (p = 0.010). CONCLUSION: Our study shows that there are unique differences in early ultrasound and sequential integrated serum markers between MC/DA gestations complicated by TTTS and UPS versus those unaffected. KEY POINTS: · Differences exist in sequential integrated screening markers in monochorionic-diamniotic twin pregnancies.. · Early risk stratification of monochorionic-diamniotic twin pregnancies may be possible.. · Sequential integrated screening testing can provide useful information to clinicians when evaluating monochorionic-diamnitoic twin pregnancies..

Utility of chromosomal microarray for diagnosis in cases of nonimmune hydrops fetalis.

PURPOSE: Chromosomal microarray (CMA) is recommended in the diagnostic evaluation of cases with fetal structural anomalies when invasive testing is pursued. However, the utility of CMA for nonimmune hydrops fetalis (NIHF) specifically is not well known. Our objective was to describe the overall yield of CMA in the diagnostic evaluation of NIHF, comparing isolated cases to those with concurrent structural anomalies. METHODS: This was a retrospective cohort study of all prenatally diagnosed NIHF cases evaluated at the University of California, San Francisco from 2008 to 2018. NIHF due to twin-twin transfusion syndrome was excluded. RESULTS: There were 131 cases of prenatally diagnosed NIHF. In 43/44 cases with a CMA performed, results were categorized as normal or likely benign. One case was found on CMA to have a large pathogenic duplication of 21p11.2q22.3, which could have been detected by karyotype and was consistent with a diagnosis of Down syndrome. There was no incremental yield demonstrated for CMA over karyotype. CONCLUSIONS: Among a cohort of prenatally diagnosed NIHF cases, CMA did not identify any copy number variants beyond those detectable by karyotype, and the vast majority of CMAs were normal. These results suggest that CMA has low diagnostic utility for NIHF.

Fetal Congenital Pulmonary Airway Malformation: The Role of an Objective Measurement of Cardiomediastinal Shift.

OBJECTIVE: To examine the relationship between cardiomediastinal shift angle (CMSA) and adverse perinatal outcomes and hydrops in cases of congenital pulmonary airway malformation (CPAM). STUDY DESIGN: This retrospective study evaluated CPAM cases referred to our institution from 2008 to 2015. The primary outcome was a composite score for adverse perinatal outcome. CMSA was measured for each case and evaluated for its association with the primary outcome. The prediction accuracy of CMSA for adverse perinatal outcome was assessed using receiver operator characteristic (ROC) curves. RESULTS: Eighteen (21.2%) of the 85 cases experienced an adverse perinatal outcome. Increases in CMSA were associated with adverse perinatal outcomes and hydrops in bivariate analyses. Adjusted analyses found each 10-degree increase in CMSA to be associated with increased odds of an adverse perinatal outcome (adjusted odds ratio [aOR] 2.2, 95% confidence interval [CI]: 1.4-3.3) and hydrops (aOR 3.0, 95% CI: 1.5-6.1). CMSA performed well and was comparable to CPAM volume ratio in predicting adverse perinatal outcomes (area under the curve 0.81 and 0.84, respectively). CONCLUSION: We describe a novel measurement of mediastinal shift in cases of CPAM and its relationship with adverse perinatal outcomes and hydrops. These findings may shape the evaluation and management of CPAMs, improve our understanding of their prognosis, and influence patient counseling.

Stage I Twin-Twin Transfusion Syndrome: Outcomes of Expectant Management and Prognostic Features.

OBJECTIVE: This article describes the natural history of stage I twin-twin transfusion syndrome (TTTS) including risk of progression to higher stage TTTS and pregnancy outcomes, and to identify risk factors for progression. STUDY DESIGN: Retrospective cohort study of monochorionic diamniotic (MCDA) twin pregnancies from 2006 to 2016 with expectantly managed Quintero stage I TTTS. RESULTS: A total of 30 MCDA twin pregnancies with expectantly managed stage I TTTS were identified. Of these, eight (26.7%) progressed to higher stage TTTS. Median gestational age (GA) at diagnosis for those that progressed was 18.9 ± 2.9 weeks versus 21.4 ± 3.4 weeks in those that remained stable (p = 0.06). Presence of an arterioarterial (A-A) anastomosis was assessed for 20/30 patients, and eight A-A were identified. Of those, 7/8 (87.5%) remained stable. In the complete cohort, a tiny or transiently visible bladder was noted in seven donor twins. Of these, 4/7 (57.1%) progressed. Excluding one termination, 47/58 (81.0%) fetuses survived. CONCLUSION: With expectant management of stage I TTTS, nearly three-fourths of pregnancies remain stable and most have survival of ≥ 1 twin. A-A anastomoses were not associated with progression to higher stage TTTS, whereas earlier GA at diagnosis or a small or intermittently visible donor bladder may herald greater risk of progression.

Utility of chromosomal microarray in anomalous fetuses.

OBJECTIVE: The objective of this study was to determine the association of copy number variants (CNV) with perinatal outcomes among fetuses with sonographic abnormalities. METHODS: This was a retrospective cohort study of anomalous fetuses evaluated at a single fetal center, who underwent chromosomal microarray (CMA) testing. Pathogenic CNV or variants of uncertain significance were classified as abnormal. The primary outcome of perinatal death was compared among fetuses with normal vs abnormal CMA. Secondary outcomes included preterm birth, small for gestational age birth weight, and death prior to discharge. The odds ratio (OR) of perinatal death was determined, adjusting for potential confounders. RESULTS: Of 280 fetuses, 60 (21.4%) had abnormal CMA results-21 (35.0%) were classified as pathogenic, 39 (65.0%) were variants of uncertain significance. Among 212 (75.7%) continuing pregnancies, abnormal CMA was not associated with increased odds of perinatal death (adjusted OR 0.81, 95% CI 0.34-1.93), after adjustment for the presence of hydrops and specific anomalies. The overall frequency of perinatal death was 21.2%. No differences in secondary outcomes were observed. CONCLUSIONS: Abnormal CMA was not associated with increased odds of perinatal death in this cohort. Fetal CNV are common among fetal center patients; such fetuses are at high risk of perinatal death irrespective of CMA results.

Prenatal Diagnosis of Congenital Diaphragmatic Hernia: Does Laterality Predict Perinatal Outcomes?

OBJECTIVE: The objective of this study was to examine laterality as a predictor of outcomes among fetuses with prenatally diagnosed congenital diaphragmatic hernia (CDH). METHODS: This is a retrospective cohort study of pregnancies with CDH evaluated at our center from 2008 to 2016 compared cases with right-sided CDH (RCDH) versus left-sided CDH (LCDH). The primary outcome was survival to discharge. Secondary outcomes included ultrasound predictors of poor prognosis (liver herniation, stomach herniation, lung area-to-head circumference ratio [LHR]), concurrent anomalies, hydrops, stillbirth, preterm birth, mode of delivery, small for gestational age, use of extracorporeal membrane oxygenation, and length of stay. Terminations and stillbirths were excluded from analyses of neonatal outcomes. RESULTS: In this study, 157 (83%) LCDH and 32 (17%) RCDH cases were identified. Survival to discharge was similar (64 vs. 66.4%, p = 0.49) with regard to laterality. RCDH had higher rates of liver herniation (90.6 vs. 72%, p = 0.03), hydrops fetalis (15.6 vs. 1.3%, p < 0.01), and lower LHR (0.87 vs. 0.99, p = 0.04). LCDH had higher rates of stomach herniation (69.4 vs. 12.5%, p < 0.01). Rates of other outcomes were similar in univariate analyses. Adjusting for microarray abnormalities, the odds for survival to discharge for RCDH compared with LCDH was 0.93 (0.38-2.30, p = 0.88). CONCLUSION: Compared with LCDH, fetuses with RCDH had higher rates of adverse ultrasound predictors, but equivalent survival.

Polyhydramnios Affecting a Recipient-like Twin: Risk of Progression to Twin-Twin Transfusion Syndrome and Outcomes.

OBJECTIVE: The significance of polyhydramnios of one twin in the absence of oligohydramnios of the cotwin in monochorionic diamniotic (MCDA) twin pregnancies (polyhydramnios affecting a recipient-like twin [PART]) is unknown. Our aim is to assess the risk of progression to twin-twin transfusion syndrome (TTTS) with PART, progression to ≥ stage II TTTS, and neonatal survival. STUDY DESIGN: This study was a retrospective cohort study of MCDA twin pregnancies with PART evaluated at a referral center from 2008 to 2015. RESULTS: Sixty-four MCDA twin pregnancies with PART were identified. Fifteen (23.4%) progressed to TTTS, including 10 (15.6%) who progressed to ≥ stage II TTTS. Three pregnancies were terminated and one underwent selective reduction by radiofrequency ablation. Overall survival was 113 out of 128 (88.3%). Of those who remained stable, 91.8% (N = 45) had survival of both neonates. In multivariate analysis, the presence of arterioarterial (A-A) anastomosis by in utero Doppler ultrasound was associated with decreased risk of progression to TTTS (odds ratio: 0.12, p = 0.03, 95% confidence interval: 0.02-0.78). CONCLUSION: Most MCDA twin pregnancies with PART do not progress to TTTS and have a favorable prognosis. Progression rates are higher than observed in uncomplicated MCDA twins; however, so close surveillance is warranted. The presence of an A-A anastomosis appears to confer decreased risk of progression to TTTS.

Non-Immune Hydrops Fetalis: Do Placentomegaly and Polyhydramnios Matter?

OBJECTIVES: Polyhydramnios and placentomegaly are commonly observed in nonimmune hydrops fetalis (NIHF); however, whether their ultrasonographic identification is relevant for prognosis is controversial. We evaluated outcomes of fetal or neonatal death and preterm birth (PTB) in cases of NIHF alone and in those with polyhydramnios and/or placentomegaly (P/PM). METHODS: We conducted a retrospective cohort of singletons with NIHF evaluated between 1994 and 2013. Nonimmune hydrops fetalis was defined as 2 or more abnormal fluid collections, including ascites, pericardial effusion, pleural effusion, and skin edema. Primary outcomes were intrauterine fetal demise (IUFD) and neonatal death. Secondary outcomes were PTB (<37, < 34, and <28 weeks) and spontaneous PTB. Outcomes were compared between cases of NIHF alone and NIHF with P/PM. RESULTS: A total of 153 cases were included; 21% (32 of 153) had NIHF alone, and 79% (121 of 153) had NIHF with P/PM. There was no significant difference in neonatal death (38.1% versus 43.0%; P = .809) between the groups. Intrauterine fetal demise was seen more frequently in NIHF alone (34.4% versus 17.4%; P = .049). Nonimmune hydrops fetalis-with-P/PM cases were more likely to deliver before 37 weeks (80.0% versus 57.1%; P = .045) and before 34 weeks (60.0% versus 28.6%; P = .015) and to have spontaneous PTB (64.4% versus 33.3%; P = .042). Adjusted odds ratios accounting for the etiology of NIHF supported these findings, with the exception of IUFD. CONCLUSIONS: Compared to NIHF alone, pregnancies with NIHF and P/PM had a lower risk of IUFD and were at increased risk of PTB (<37 and <34 weeks) and spontaneous PTB. This information may help providers in counseling patients with NIHF and supports the need for close antenatal surveillance.

Diastolic Cardiac Pathology and Clinical Twin-Twin Transfusion Syndrome in Monochorionic/Diamniotic Twins.

OBJECTIVE: to identify differences in echocardiographic profiles of monochorionic/diamniotic pregnancies with early or mild twin-twin transfusion syndrome (TTTS), compared to monochorionic/diamniotic twins affected only by discordant growth or discordant fluid. STUDY DESIGN: retrospective evaluation of sonograms and echocardiograms of twin pregnancies referred for suspected TTTS. RESULTS: 112 monochorionic/diamniotic pairs were studied. 41 did not have/develop TTTS, 61 had Stage I/II TTTS. Ten developed TTTS after initially not meeting criteria. TTTS recipients had a higher rate of venous Doppler or tricuspid inflow abnormalities than purported "recipients" in non-TTTS pregnancies (86% vs. 37%, P<0.001). TTTS recipients had shorter tricuspid inflow duration/RR intervals than non-TTTS fetuses (32+/-6% versus 37+/-4%, P<0.001). Logistic regression and recursive partitioning identified shorter tricuspid inflow duration, longer isovolumic relaxation, and ductus venosus abnormality associated with TTTS. CONCLUSION: Diastolic pathology, specifically shorter tricuspid inflow duration, may be considered a hallmark of TTTS distinguishing these pregnancies from other monochorionic/diamniotic twin complications.