Fetal Diagnosis and Therapy最新文献

Introduction: Hereditary pyropoikilocytosis (HPP) is a rare genetic disorder causing severe fetal anemia, often leading to hydrops fetalis. This study evaluates intrauterine blood transfusion (IUT) efficacy and associated genetic mutations in Northeastern Thai patients.

Methods: Eight fetuses with hydrops fetalis were identified between 17 and 30+6 weeks' gestation, with initial hematocrit levels of 8.7-16.7%.

Results: IUTs were performed at 20-36 weeks, guided by fetal hematocrit, middle cerebral artery peak systolic velocity, and fetal hemodynamic status. Five cases progressed uneventfully following IUTs, although three resulted in premature delivery. Four cases reached term, with two infants born at normal weight and two at low birth weight. Among premature cases, three had birth weights below the 10th percentile for gestational age, and one had normal weight. Five patients remain transfusion dependent. Genetic analysis revealed homozygous spectrin Providence in 4 patients, homozygous spectrin Buffalo in 1, compound heterozygous spectrin Providence/Buffalo in 2, and spectrin Providence with SPTB c.6171_6182delinsACCCCAGCT (novel) in 1. Three cases developed severe complications, including severe birth asphyxia, persistent pulmonary hypertension, and multiple organ failure, leading to death.

Conclusions: This study identified SPTB gene mutations associated with HPP. Early detection of hydrops fetalis caused by severe anemia, along with confirmation of the underlying genetic mutation, is essential for timely and effective clinical intervention. Intrauterine transfusion remains a viable therapeutic option to sustain pregnancy and enhance fetal survival. Further research is needed to refine the management strategies for HPP-associated hydrops fetalis and to improve perinatal outcomes.

Introduction: Recent technological advances in fetal medicine have led some investigators to reconsider ventriculoamniotic shunting for fetal hydrocephalus, an intervention that was attempted in the 1980s but was abandoned due to perceived lack of effect. The objective of this manuscript describes outcomes after induction of hydrocephalus followed by ventriculoamniotic shunt placement and postmortem analysis in the ovine model.

Methods: Mixed-breed fetal sheep underwent induction of hydrocephalus by injection of BioGlue® into the cisterna magna at ∼85 days gestation followed by ventriculoamniotic shunt placement at ∼100 days gestation. Brains were inspected by transcranial ultrasound at the time of shunt placement and after delivery using the ventricle to hemisphere ratio (VHR). The VHR at the time of shunting was compared to the VHR at end of study. Pathologic analysis was performed on gestational age-matched normal brains, shunted brains, and unshunted hydrocephalic controls.

Results: Twenty-five fetal sheep underwent induction of hydrocephalus. Two fetuses were lost immediately. Of the 23 remaining fetuses, 20 (87%) developed hydrocephalus. Five fetuses served as hydrocephalic controls. Eighteen fetuses who developed hydrocephalus were assessed for a VHR by transcranial ultrasound at the time of shunt placement. The mean VHR was 0.71. Of the 20 fetuses that developed hydrocephalus, 12 underwent shunt placement. Eight shunted fetuses were available for VHR and pathologic analysis at end of study. The mean VHR at the time of shunt placement was compared to the VHR at end of study (n = 8, 0.70 ± 0.10 vs. 0.50 ± 0.16, p = 0.016). Histologically, shunted brains had better neuropreservation than unshunted hydrocephalic controls.

Conclusion: Hydrocephalus was induced in 87% of fetal sheep using this model. In an ovine model, ventriculoamniotic shunting both decreased the degree of hydrocephalus sonographically and improved brain histology compared to hydrocephalic controls. These findings demonstrate proof of concept in the animal model and support ongoing research in cerebrospinal fluid diversion for fetal obstructive hydrocephalus.

Introduction: Both a low and an increased body mass index (BMI) are risk factors for surgical complications. It is less clear whether they also affect the outcomes of fetoscopic procedures. In this manuscript, we aimed to assess the effect of maternal BMI on operative and pregnancy outcomes following fetoscopic laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS).

Methods: We retrospectively reviewed all patients with twin pregnancies complicated by TTTS treated with fetoscopic laser surgery at the Ontario Fetal Centre, Toronto, over a 24-year period. Demographic and procedural data as well as pregnancy and delivery outcomes were prospectively collected as part of our quality control program. Patients were divided into 6 groups for BMI at the time of surgery: BMI <20, 20-24.9, 25-29.9, 30-34.9, 35-39.9, and ≥40 kg/m2. Collected variables included demographics, operative characteristics, operative complications, obstetric complications, twin anemia-polycythemia sequence, TTTS recurrence, intrauterine (fetal) death, gestational age at delivery, and survival. Outcomes of all groups were compared to the "normal weight" reference cohort (BMI: 20-24.9 kg/m2).

Results: Of 1,012 patients in our database, 859 were twin pregnancies treated with laser for TTTS. Pregnancy outcomes were available for 515. Of all patients, 47% were categorized as normal weight, 3% were underweight, 25% were obese, and 5% had a BMI of >40 kg/m2. Patients with a higher BMI had higher parity (p = 0.0001), longer cervical length (p = 0.008), and a significantly higher TTTS stage (p = 0.0003) at the time of surgery. There were no significant differences between groups in terms of surgical or anesthetic characteristics or perinatal complications.

Conclusion: BMI does not significantly affect operative or perinatal outcomes in patients undergoing fetoscopic laser ablation for severe TTTS, despite being at a higher stage at diagnosis.

Introduction: Dilated colon or rectum on fetal imaging raises concern for underlying anorectal malformation (ARM) or Hirschsprung's disease (HD).

Methods: We evaluated pregnant women referred to a dedicated fetal center between 2006 and 2024 for suspected fetal rectal/colonic dilation. Findings by ultrasound and magnetic resonance imaging were compared to neonatal outcomes. Those with a statistically significant association with postnatal distal bowel abnormality were identified by univariate analysis and used to formulate a risk score.

Results: A total of 18/47 (38.2%) patients had normal imaging. A total of 29/47 (61.7%) demonstrated persistent "prominence" (15/29) or "dilation" (14/29) of the fetal colon/rectum. Seven male fetuses with large bowel dilation/prominence were diagnosed postnatally with an imperforate anus. None had HD. Compared to the no-ARM group, ARM patients were more likely to have earlier initial referral imaging; imaging noting persistent bowel dilation/prominence; imaging with an abnormal amniotic fluid level, meconium signal, bowel echogenicity, or anal sphincter; enterolithiasis; or concern for VACTERL (all p ≤ 0.035). These 8 variables were used to create a risk score to diagnose ARM with 100% sensitivity and specificity in our cohort.

Conclusion: Fetal imaging showing a dilated colon/rectum is rarely pathologic. When targeted imaging does not reveal any features predictive of pathology, reassurance may be provided to families and providers.

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease associated to low survival disease into adulthood. The appearance of the cystic fibrosis transmembrane conductance regulator (CFTR) therapy has revolutionized the management and the prognosis of these patients with an improvement in the pancreatic and lung function with a much better quality of life. More women with CF are considering being mothers. Other clinical scenario is the prenatal diagnosis of fetus with CF. Three case reports have been published, suggesting that CFTR therapy during pregnancy in fetuses affected by CF might prevent prenatal meconium ileus (MI), which are the one who have a higher risk of gastrointestinal morbidity and long-term complications.

Case presentation: We present 2 cases in which the diagnosis of CF occurred during intrauterine life and treatment with CFTR therapy was administered to healthy pregnant women in order to reduce the risk MI in their fetuses. In both cases, the diagnosis suspicion was by ultrasound findings with a genetic confirmed diagnosis by amniocentesis. In the first case, the mother received the CFTR therapy during 5 weeks and MI was not developed by the newborn. In the second one, the mother received the treatment only for a week and MI could not be avoided.

Conclusion: This clinical situation has special ethical considerations, since a drug is being administered through compassionate use to a woman who does not need it. The fundamental reason is the lack of authorization for the use of these drugs in newborns but in adults. We hope that these 2 clinical cases, together with those already published, will increase the knowledge and experience of using this drug in this context helping with the management of pregnant women with fetuses affected by CF in order to reduce associated complications.

Introduction: Currently, risk stratification criteria and indications for early postnatal resection of high-risk congenital lung malformations (CLM) are not universally accepted. In this study, we sought to characterize prenatal risk factors and outcomes associated with early postnatal resection in prenatally diagnosed CLMs.

Methods: Retrospective cohort study of patients seen at the Fetal Care Center from January 2014 to December 2023. Categorical data were analyzed with chi-square calculations. Receiver operating characteristic curves were generated for optimal CPAM volume ratio (CVR) and imaging cutoff values associated with hydrops development and/or need for early resection.

Results: Of the 204 patients analyzed, 10.2% (21/204) patients underwent early postnatal resection. Hydropic fetuses required early resection significantly more than non-hydropic fetuses (33.3% vs. 5.0%, p < 0.001). A greater number of early resection patients had macrocystic lesions compared to non-early resection patients (76.2% vs. 12.3% p < 0.001). A maximum CVR ≥1.66 was highly predictive of early postnatal resection (AUC = 0.90; 95% CI = 0.84-0.96). An initial CVR <0.88 indicated a low likelihood of developing hydrops (negative predictive value = 98.6%).

Conclusion: Prenatally, hydrops, macrocysts, and a maximum recorded CVR ≥1.66 are associated with early postnatal resection. Hydrops development is unlikely with an initial CVR <0.88.

Introduction: This study evaluated fetal MRI lung measurements with ECMO use and survival of prenatally diagnosed CDH.

Methods: This was a retrospective chart review of 113 patients from January 2012 to December 2023 with prenatally diagnosed congenital diaphragmatic hernias. Lung measurements from prenatal MRIs, infant ECMO use, and survival were analyzed to determine optimal cut-off value for outcome prediction.

Results: Patients were categorized as mild (10.1%, n = 11), moderate (34.3%, n = 37), and severe (55.6%, n = 60). Mortality was 29.2% (n = 33), and 52.2% (n = 59) required ECMO. Patients undergoing FETO (n = 11) were excluded from statistical analysis. Median change in total lung volume, ipsilateral lung, and contralateral lung from early to late gestation MRI was 15.1 mL (IQR: 9.3-21.7), 1.5 mL (IQR: 0.1-3.1), and 13.4 mL (IQR: 8.1-18.34), respectively. Optimal cut-off values, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each volume parameter in terms of predicting ECMO use and mortality. Ipsilateral and contralateral lung growth below the cut-off significantly predicted ECMO use (p < 0.05). There was no significance for any cut-offs predicting mortality.

Conclusion: Lung volume growth measured by MRI in prenatally diagnosed CDH may be a useful predictor of ECMO use and mortality.

Introduction: The aim of this study was to assess the clinical utility of low-set ears (LSE) as a novel 2D-ultrasound marker for the prenatal detection of chromosomal anomalies.

Methods: A multicenter cohort study including 1,331 singleton pregnancies between 11+2 and 34+6 weeks of gestation was conducted in the two participating centers to determine the performance of LSE as an aneuploidy marker. LSE was defined as a dichotomous marker using a newly defined axial plane of the fetal head in 2D ultrasound. Intra- and interobserver variability were assessed to ensure marker reliability. Efficacy in predicting chromosomal anomalies was assessed using LSE alone or in combination with aneuploidy screening.

Results: A new axial plane of the fetal head, defined by both lenses and the cerebellum, was adopted for LSE detection. Intra-observer concordance Kappa index for LSE measurement was 1.0, and 0.82 for interobserver reliability. LSE could be assessed in 99% of the studied fetuses and was detected in 30 (2.3%) fetuses: in 19 (86%) of the 22 fetuses with chromosomal anomalies, in all cases (5/5, 100%) with other genetic anomalies, and in six (18%) of the 34 malformed fetuses without a genetic disorder. In one (3.3%) of the fetuses, LSE was not confirmed postnatally while the remaining 29 fetuses had an adverse outcome. When LSE was combined with aneuploidy screening, the detection rate of chromosomal anomalies remained the same and specificity increased from 89% to 100%.

Conclusions: Our study supports using LSE as a potential 2D-ultrasound marker for chromosomal anomaly detection. Studies with a larger sample size and in high-risk populations are warranted to prove its clinical utility before this marker can be included in prenatal screening protocols.

Introduction: The clinical phenotypes associated with 1q21.1 deletion or duplication syndromes vary considerably among individuals, and the underlying mechanisms remain poorly elucidated. Moreover, data on prenatal ultrasound findings in fetuses carrying these copy number variants are still limited. This study aimed to preliminarily evaluate the association between prenatal phenotypic features and 1q21.1 deletion/duplication syndromes.

Methods: A retrospective analysis was performed on 16 cases diagnosed with 1q21.1 deletions and 13 cases with 1q21.1 duplications, employing single nucleotide polymorphism arrays (SNP-arrays).

Results: The deletion fragment sizes of the 16 deletion cases ranged from 1.30 Mb to 2.18 Mb, with the overlapping region located at 146.5 Mb to 147.5 Mb, encompassing nine OMIM genes such as ACP6, BCL9, and CHD1L. The fragment sizes of the 13 duplication cases ranged from 0.87 Mb to 3.87 Mb, with the overlapping region located at 146.5 Mb to 147.0 Mb, encompassing a total of 4 OMIM genes, namely, BCL9, CHD1L, FMO5, and PRKAB2. Among the 16 fetuses with deletions, eight exhibited ultrasound-detected abnormalities. Specifically, three fetuses had urinary tract malformations, four were diagnosed with fetal growth retardation, three displayed lateral ventricle enlargement, and one had aortic stenosis. Of the 13 fetuses with duplication, six were found to have ultrasound abnormalities, including four fetuses with cardiovascular malformations, one fetus with fetal growth retardation, one fetus with widened posterior fossa, and one fetus with widened lateral ventricle. Among the 16 fetuses identified with deletions, nine pregnancies were electively terminated, while seven pregnancies were carried to term, resulting in normal births. During follow-up, one child was diagnosed with epilepsy, and another exhibited delays in language and motor development. In the cohort of 13 fetuses with duplications, four pregnancies were terminated, and nine proceeded to term, yielding normal births. However, follow-up assessments revealed that one child experienced hearing impairment and another demonstrated speech delays.

Conclusion: This study suggests that fetuses with prenatal 1q21.1 deletions may be associated with malformations of the urinary system, whereas those with 1q21.1 duplications are likely associated with cardiac malformations. For fetuses diagnosed with 1q21.1 deletions or duplications who present with a normal phenotype prenatally, it is essential to conduct close monitoring of their neurodevelopmental trajectory postnatally.