[Clinical Efficacy and Nursing Care of Fetal Intrauterine Blood Transfusion: Previous Experience Review].

Objective: To summarize the clinical efficacy and nursing experience of intrauterine blood transfusion (IUT) treatment for fetal anemia cases. Methods: The clinical data of 4 fetal anemia cases receiving IUT in Beijing Obstetrics and Gynecology Hospital, Capital Medical University between 2020 and 2022 were collected. Four pregnant women aged 24-38 years were included in the study. They carried fetuses with anemia of unknown causes. The four pregnant women developed anxiety after they were informed of the diagnosis of fetal anemia. One-on-one psychological counseling before the IUT procedure and one-on-one companionship over the course of the surgery were provided for the pregnant women. In addition, they were closely monitored for blood transfusion reactions. Postprocedural observation of the puncture site and 24-hour monitoring of the newborns were also conducted. Results: The four pregnant women underwent 1-3 times of IUT in the second and third trimesters, with the minimum gestational age at the time of IUT being 25 + weeks and the blood transfusion volume being 20-107 mL/time. Two pregnant women experienced irregular uterine contractions during IUT in the third trimester. Other than that, all other IUT treatments were successful. After IUT, there was a significant improvement in fetal hemoglobin, peak systolic velocity of the middle cerebral artery (MCA-PSV), and cardiothoracic area ratio. One case did not give birth in our hospital and the outcome of the fetus was not known. The other three fetuses achieved good outcomes. Conclusion: Positive preprocedural psychological counseling for pregnant women, close intraoprocedural and postprocedural pregnancy monitoring, and the prevention of maternal and fetal complications are the key to improving the clinical efficacy of IUT and achieving a good fetal outcome.

Fetal Alloimmune Hemolytic Anemia (AHA) as a Potential Target for Transamniotic Fetal Immunotherapy (TRAFIT).

PURPOSE: Fetal alloimmune hemolytic anemia (AHA) resulting from maternal antibodies against fetal erythrocytes may require fetal administration of immunoglobulin-G (IgG) via invasive methods. IgG can reach the fetal circulation after transamniotic fetal immunotherapy (TRAFIT). We sought to both develop a model of AHA and to test TRAFIT as a potential treatment. METHODS: Sprague-Dawley fetuses (n = 113) received intra-amniotic injections on gestational-day 18 (E18, term = E21) of either saline (control; n = 40), anti-rat-erythrocyte antibodies (AHA; n = 37), or anti-rat-erythrocyte antibodies plus IgG (AHA + IgG; n = 36). At term, blood was procured for red blood count (RBC), hematocrit, or ELISA for inflammatory markers. RESULTS: There was no difference in survival [95% (107/113)] across groups (p = 0.87). Both hematocrit and RBC were significantly lower in the AHA group than controls (p < 0.001). Although still significantly lower than controls (p < 0.001), both hematocrit and RBC significantly increased in AHA + IgG group compared to AHA alone (p < 0.001). Pro-inflammatory TNF-α and IL1-ß were significantly elevated from controls in the AHA group, but not in AHA + IgG (p < 0.001-0.159). CONCLUSIONS: Intra-amniotic injection of anti-rat-erythrocyte antibodies can reproduce manifestations of fetal AHA, constituting a practical model of this disease. Transamniotic fetal immunotherapy with IgG reduces anemia in this model and may emerge as a new minimally invasive means of treatment. TYPE OF STUDY: Animal and laboratory study. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Prenatal management of fetal anemia due to pyruvate kinase deficiency: A case report.

BACKGROUND: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of glycolysis, leading to congenital hemolytic anemia, which can occur during the neonatal period. STUDY DESIGN AND METHODS: We report the prenatal management of fetal anemia related to PK deficiency in a family with a severe proband. RESULTS: The couple had a first child born with hydrops, whose PK deficiency was diagnosed at 18 months of life. He was treated with allogeneic bone marrow transplantation. The second child was free from disease. For the third pregnancy, the amniocentesis revealed a PK deficiency. Weekly ultrasound monitoring of the middle cerebral artery velocity allowed the detection of severe fetal anemia. Two intrauterine red blood cell transfusions (IUTs) were performed, raising the fetal hemoglobin from 6.6 to 14.5 g/dl at 28 weeks' gestation and from 8.9 to 15.3 g/dl at 31 weeks. A hematopoietic stem cell allograft was discussed prenatally but not chosen, as it would not have significantly changed the perinatal prognosis. The patient delivered a 2730 g girl at 37 weeks, with hemoglobin of 13.6 g/dl. The child presented with neonatal jaundice treated with phototherapy and received postnatal transfusions. DISCUSSION: When a proband is identified in a family, fetal investigation is warranted, to set up third-trimester ultrasound surveillance and perinatal management. In case of fetal severe anemia of unknown etiology, the workup on fetal blood sampling before IUT should comprise the search for erythrocytes enzymopathies, such as PK deficiency. IUTs allow safer full-term delivery in cases with PK deficiency.

20 years review of antenatal diagnosis of haemoglobin Bart's disease and treatment with intrauterine transfusion.

OBJECTIVE: To review prenatal diagnosis and outcome of alpha thalassaemia major through universal antenatal screening. METHOD: This was a retrospective study on ultrasound features, antenatal diagnosis, in-utero intervention and long term outcome of pregnancies at risk of Haemoglobin Bart's hydrops foetalis syndrome attending prenatal diagnosis from 2000 to 2019 at Tsan Yuk Hospital in Hong Kong. RESULTS: Among 390 foetuses from 373 at-risk pregnancies, 122 (31%) prenatal invasive procedures were performed and 65 affected foetuses were diagnosed antenatally. For foetuses with ultrasound features of anaemia, the diagnostic yield of BHFS was 73%. Cardiomegaly carried a positive predictive value of 65.2% while its absence had the highest negative predictive value (96.0%). Three women having affected foetuses continued pregnancy and received intrauterine transfusion beginning 20 weeks of gestation. All babies were born alive and non-hydropic. They were managed with regular transfusion and cured by haematopoietic stem cell transplantation. CONCLUSIONS: Absence of ultrasound features of anaemia had high negative predictive value for alpha thalassaemia major. Couple at risk of having affected foetus could be offered serial ultrasound surveillance. Invasive testing for pregnancies with features of foetal anaemia provided high diagnostic yield. Intrauterine transfusion corrected foetal anaemia and allowed long term transfusion free survival without significant neurological sequelae following postnatal transplant therapy.

Fetoscopic Balloon Dilation and Stent Placement of Congenital High Airway Obstruction Syndrome Leading to Successful Cesarean Delivery.

INTRODUCTION: Without fetal or perinatal intervention, congenital high airway obstruction syndrome (CHAOS) is a fatal anomaly. The ex utero intrapartum treatment (EXIT) procedure has been used to secure the fetal airway and minimize neonatal hypoxia but is associated with increased maternal morbidity. CASE PRESENTATION: A 16-year-old woman (gravida 1, para 0) was referred to our hospital at 31 weeks gestation with fetal anomalies, including echogenic lungs, tracheobronchial dilation, and flattened diaphragms. At 32 weeks, fetoscopic evaluation identified laryngeal stenosis, which was subsequently treated with balloon dilation and stent placement. The patient developed symptomatic and regular preterm contractions at postoperative day 7 with persistent sonographic signs of CHAOS, which prompted a repeat fetoscopy with confirmation of a patent fetal airway followed by Cesarean delivery under neuraxial anesthesia. Attempts to intubate through the tracheal stent were limited and resulted in removal of the stent. A neonatal airway was successfully established with rigid bronchoscopy. Direct laryngoscopy and bronchoscopy confirmed laryngeal stenosis with a small tracheoesophageal fistula immediately inferior to the laryngeal stenosis and significant tracheomalacia. A tracheostomy was then immediately performed for anticipated long-term airway and pulmonary management. The procedures were well tolerated by both mom and baby. The baby demonstrated spontaneous healing of the tracheoesophageal fistula by day of life 7 with discharge home with ventilator support at 3 months of life. CONCLUSION: Use of repeated fetoscopy in order to relieve fetal upper airway obstruction offers the potential to minimize neonatal hypoxia, while concurrently decreasing maternal morbidity by avoiding an EXIT procedure. Use of the tracheal stent in CHAOS requires further investigation. The long-term reconstruction and respiratory support of children with CHAOS remain challenging.

Antenatal Three-Dimensional Printing for Ex Utero Intrapartum Treatment Procedures.

BACKGROUND: Prenatal ultrasonography allows for timely identification of fetal abnormalities that can have an effect on securing the neonatal airway at delivery. We illustrate the role of antenatal three-dimensional printing in cases with fetal airway obstruction. CASE: We present two cases that highlight the utility of a three-dimensional printing technique to aid in ex utero intrapartum treatment procedures during cesarean delivery. CONCLUSION: Three-dimensional printing plays a complementary role to standard imaging options in optimizing presurgical planning, prenatal parental counseling, personalized patient care, and education of the multidisciplinary team in cases of fetal congenital airway obstruction.

Current perspective and scope of fetal therapy: part 1.

Fetal therapy term has been described for any therapeutic intervention either invasive or noninvasive for the purpose of correcting or treating any fetal malformation or condition. Fetal therapy is a rapidly evolving specialty and has gained pace in last two decades and now fetal intervention is being tried in many malformations with rate of success varying with the type of different fetal conditions. The advances in imaging techniques have allowed fetal medicine persons to make earlier and accurate diagnosis of numerous fetal anomalies. Still many fetal anomalies are managed postnatally because the fetal outcomes have not changed significantly with the use of fetal therapy and this approach avoids unnecessary maternal risk secondary to inutero intervention. The short-term maternal risk associated with fetal surgery includes preterm labor, premature rupture of membranes, uterine wall bleeding, chorioamniotic separation, placental abruption, chorioamnionitis, and anesthesia risk. Whereas, maternal long-term complications include risk of infertility, uterine rupture, and need for cesarean section in future pregnancies. The decision for invasive fetal therapy should be taken after discussion with parents about the various aspects like postnatal fetal outcome without fetal intervention, possible outcome if the fetal intervention is done, available postnatal intervention for the fetal condition, and possible short-term and long-term maternal complications. The center where fetal intervention is done should have facility of multi-disciplinary team to manage both maternal and fetal complications. The major issues in the development of fetal surgery include selection of patient for intervention, crafting effective fetal surgical skills, requirement of regular fetal and uterine monitoring, effective tocolysis, and minimizing fetal and maternal fetal risks. This review will cover the surgical or invasive aspect of fetal therapy with available evidence and will highlight the progress made in the management of fetal malformations in last two decades.

Current perspective and scope of fetal therapy: part 2.

Fetal therapy has been defined as any therapeutic intervention either invasive or noninvasive for correcting or treating any fetal malformation or condition. Invasive fetal therapy have its own set of maternal and fetal complications and invasive approach is not feasible in many of fetal conditions that are candidate for fetal therapy. Many such fetal conditions have been treated successfully by medical or noninvasive management. In medical fetal therapy, mothers are treated with medications which are transferred to fetus through placenta and exert positive effect on the fetus, thus avoiding complications that are seen secondary to invasive fetal therapy. The fetal conditions that have been managed with medical therapy includes fetal and neonatal alloimmune thrombocytopenia, neural tube defect, congenital adrenal hyperplasia, perinatal infections, respiratory distress syndrome, inborn error of metabolism, and congenital cystic adenomatoid malformation. This review will cover the medical or noninvasive aspect of fetal therapy and will highlight the progress made in the management of these fetal conditions.

In Utero Fetal Therapy: Stem Cells, Cell Transplantation, Gene Therapy, and CRISPR-Cas9.

In utero fetal therapy offers the opportunity to prevent and treat diseases with a cellular or genetic basis. Components of successful fetal treatment include isolation of a replacement cell population, in utero stem cell transplantation, cell engraftment with fetal immune tolerance, and ongoing cell function. Fetal gene therapy with CRISPR-Cas9 represents an exciting potential therapy for genetic diseases not amenable to gene supplementation via adenoviral vector transduction. These fetal therapies have unique ethical and safety considerations. Clinical trials for in utero cell therapy are underway, as additional discoveries in stem cell biology and gene therapy move closer to clinical translation.

Potential Benefits of Bovine Colostrum in Pediatric Nutrition and Health.

Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing enterocolitis (NEC), short-bowel syndrome, and mucositis). Human trials and animal studies (mainly in piglets) are reviewed to assess the scientific evidence of whether BC is a safe and effective antimicrobial and immunomodulatory nutritional supplement that reduces clinical complications related to preterm birth, infections, and gut disorders. Studies in infants and animals suggest that BC should be supplemented at an optimal age, time, and level to be both safe and effective. Exclusive BC feeding is not recommended for infants because of nutritional imbalances relative to human milk. On the other hand, adverse effects, including allergies and intolerance, appear unlikely when BC is provided as a supplement within normal nutrition guidelines for infants and children. Larger clinical trials in infant populations are needed to provide more evidence of health benefits when patients are supplemented with BC in addition to human milk or formula. Igs and other bioactive factors in BC may work in synergy, making it critical to preserve bioactivity with gentle processing and pasteurization methods. BC has the potential to become a safe and effective nutritional supplement for several pediatric subpopulations.

Cardiac rhabdomyoma with hydrops fetalis: Prenatal management by abdominal drainage.

OBJECTIVE: We described a case of fetal cardiac rhabdomyoma complicated by hydrops. And we discussed our approach during pregnancy. CASE REPORT: A 23-year-old woman primigravida was referred at 29 weeks of gestation (WG) to prenatal unit for a large hyperechogenic intracardiac mass associated with fetal hydrops. An intrauterine peritoneo-amniotic shunt was placed. Complete regression of ascites and pericardial effusions were observed after 34 WG with drain in good position. CONCLUSION: Cardiac rhabdomyoma is the most common prenatal cardiac tumor. These tumors are benign, asymptomatic and spontaneously regress after birth. However, in some cases, these tumors may cause severe obstructions on the fetal heart and need specific treatment.

Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. CONCLUSIONS: The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive fetal electrocardiography ameliorates fetal outcome in chorioangioma: A case report.

 Chorioangioma is a rare vascular placental tumour. Large chorioangiomas are known to have many maternal and perinatal complications. The case of placental chorioangioma detected via ultrasound is presented. This paper is focused on non-invasive fetal electrocardiography (NI-FECG) clinical use for diagnosing fetal anemia in chorioangioma.A 22-year-old primigravida was admitted to the department of fetomaternal medicine at 30 weeks of gestation. She had threatened preterm labour, polyhydramnios, and breech presentation. The large echogenic mass of 77 mm×66 mm×83 mm, located in the uterine bottom, protruded into the amniotic cavity, and connected to the marginal sinus of the placenta was determined via ultrasound. The sinusoidal pattern of beat-to-beat variations was diagnosed via NI-FECG in spite of normal blood flow velocity in the fetal middle cerebral artery. Therefore, NI-FECG was superior in the detection of fetal anemia. The female baby weighing 1500 g and measuring 42 cm in length, with a head circumference of 30 cm and Apgar score 3⟶5, was delivered by caesarean section. The baby had severe anemia and respiratory distress syndrome.NI-FECG was a good option for the clinician for the timely and accurate diagnosis of fetal anemia and fetal compromise in placental chorioangioma.

A novel two-component, expandable bioadhesive for exposed defect coverage: Applicability to prenatal procedures.

BACKGROUND/PURPOSE: We sought to test select properties of a novel, expandable bioadhesive composite that allows for enhanced adhesion control in liquid environments. METHODS: Rabbit fetuses (n = 23) underwent surgical creation of spina bifida on gestational day 22-25 (term 32-33 days). Defects were immediately covered with a two-component tough adhesive consisting of a hydrogel made of a double network of ionically crosslinked alginate and covalently crosslinked polyacrylamide linked to a bridging chitosan polymer adhesive. Animals were euthanized prior to term for different analyses, including hydraulic pressure testing. RESULTS: Hydrogels remained adherent in 70% (16/23) of the recovered fetuses and in all of the last 14 fetuses as the procedure was optimized. Adherent hydrogels showed a median two-fold (IQR: 1.7-2.4) increase in area at euthanasia, with defect coverage confirmed by ultrasound and histology. The median maximum pressure to repair failure was 15 mmHg (IQR: 7.8-55.3), exceeding reported neonatal cerebrospinal fluid pressures. CONCLUSIONS: This novel bioadhesive composite allows for selective, stable attachment of an alginate-polyacrylamide hydrogel to specific areas of the spina bifida defect in a fetal rabbit model, while the hydrogel expands with the defect over time. It could become a valuable alternative for the prenatal repair of spina bifida and possibly other congenital anomalies. TYPE OF STUDY: N/A (animal and laboratory study). LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Delivery technologies for in utero gene therapy.

Advances in prenatal imaging, molecular diagnostic tools, and genetic screening have unlocked the possibility to treat congenital diseases in utero prior to the onset of clinical symptoms. While fetal surgery and in utero stem cell transplantation can be harnessed to treat specific structural birth defects and congenital hematological disorders, respectively, in utero gene therapy allows for phenotype correction of a wide range of genetic disorders within the womb. However, key challenges to realizing the broad potential of in utero gene therapy are biocompatibility and efficiency of intracellular delivery of transgenes. In this review, we outline the unique considerations to delivery of in utero gene therapy components and highlight advances in viral and non-viral delivery platforms that meet these challenges. We also discuss specialized delivery technologies for in utero gene editing and provide future directions to engineer novel delivery modalities for clinical translation of this promising therapeutic approach.

Antenatally detected liver and biliary pathology.

Liver and biliary pathology in the neonate are rare and include a broad range of structural, neoplastic, infectious, genetic, and metabolic diseases. While most conditions present postnatally, antenatal detection is increasing given recent advances in antenatal imaging capabilities. In certain structural or obstructive liver diseases, antenatal detection now proves essential to help guide treatment and prevent morbidity. We review the epidemiology, pathophysiology, common antenatal diagnostic findings, and recommendations for surgical liver and biliary pathology in the neonate.

Prenatal ultrasound and magnetic resonance evaluation and fetal outcome in high-risk fetal tumors: A retrospective single-center cohort study over 20 years.

INTRODUCTION: Fetal tumors are rare and usually followed by poor outcome. We describe our single-center experience with fetal tumors evaluated by ultrasound and magnetic resonance imaging (MRI). Our aims were to evaluate mortality and morbidity including long-term outcome and to determine which ultrasound and MRI characteristics were helpful for pre- and perinatal management. MATERIAL AND METHODS: We conducted a retrospective analysis on prenatally diagnosed tumors between 1998 and 2018. Poor outcome included fetal or neonatal death and survival with serious illness. MRI addressed tumor morphology (sacrococcygeal teratomas), compromise of surrounding structures (head and neck tumors) and early depiction of brain alterations specific to tuberous sclerosis (rhabdomyomas). RESULTS: Of 68 pregnancies, 15 (22%) were terminated and eight children (8/53, 15%) died pre- or postnatally. Of the 45 survivors (45/68, 66%), 24 (24/45, 53%) were healthy, eight (8/45, 18%) had a minor illness and 13 (13/45, 29%) a serious illness. Diffusion- and T1-weighted MRI reliably predicted tumor morphology in teratomas. To detect head and neck tumors critical to airway obstruction, MRI was superior to ultrasound in delivery planning. Rhabdomyomas were frequently associated with tuberous sclerosis, regardless of their number or size in ultrasound; MRI could depict specific brain alterations from the early third trimester onwards. For several rare tumors, MRI provided critical differential diagnoses that could not be clearly displayed in ultrasound. CONCLUSIONS: The rate of survivors with serious long-term illness among fetuses with prenatal diagnosis of a tumor was high. MRI is specifically helpful for risk stratification in fetal teratomas and delivery planning in head and neck tumors.