Fetal Articles of Interest

Articles

Fetal Risk Stratification and Outcomes in Children with Prenatally Diagnosed Lung Malformations: Results from a Multi-Institutional Research Collaborative[1] . Kunisaki SM, et al. Ann Surg. 2022 Nov 1;276(5):e622-e630.

Fetal congenital lung malformations (CLMs) are a common set of diseases referred to pediatric surgeons for prenatal consultation. Based on single center studies, congenital pulmonary airway malformation volume ratio (CVR) has been an important biomarker used for prognosis in counseling parents and decision-making around birthing location and fetal therapy, with a CVR of >1.6 being a risk factor of fetal or neonatal intervention.

This multi-institutional study re-evaluated CVR as a risk factor for fetal and neonatal outcomes. It found that an initial CVR of < 1.4 was the optimal threshold for very low risk of fetal hydrops and maximum CVR of < 0.9 indicated a low risk of requiring neonatal respiratory support. The study provides an updated algorithm for perinatal management of CLMs. The low rate of CVR measurements in this cohort (< 50%) demonstrates an opportunity for improved standardization and quality of care in the prenatal evaluation of CLMs.

Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI-FDA Meeting) [2]. Herzeg A, et al. J Clin Pharmacol. 2022 Sep;62 Suppl 1(Suppl 1): S36-S52.

Although there have been significant advances in fetal diagnosis and treatment of anatomic conditions, prenatal therapy for genetic conditions remains limited. Monogenic diseases are those that occur as a result of differences in a single gene and result in a variety of clinical manifestations. These diseases are often inherited. This review provides pertinent background information, rationale, and considerations for the use of prenatal somatic gene cell therapy (PSCGT) for the treatment of severe genetic diseases. PSCGT refers to in-utero gene replacement or editing of somatic cells. Preclinical data that highlight the promise of PSCGT have been shown in spinal muscular atrophy (SMA), Lysosomal storage diseases, Hemophilia A &B, hemoglobinopathies and cystic fibrosis. Gene therapies considered in this review article include: the use of antisense oligonucleotides (ASOs), gene replacement using a viral vector, gene editing, and gene activation or inhibition.

The authors describe criteria that should be met in order to consider a condition appropriate for PSCGT. These include a known natural history, effective means of diagnosis using routine screening, accurate means of prenatal molecular diagnosis, a clear indication that the benefits of PSCGT outweigh the risks of alternatives, and available expertise to perform the fetal interventions. The most relevant modes of delivery for PSCGT include intra-vascular, intra-amniotic, and intracerebroventricular injections.

PSCGT offers advantages over current strategies for gene therapy.  Given that PSCGT can be offered prenatally, it can be offered significantly earlier in the disease course, thus minimizing disease progression. It can also be used before the blood-brain barrier is formed, allowing the delivery of medications that would not otherwise cross this barrier. In addition, given that the fetal immune system is immature, PSCGT could result in minimal immune response, thus allowing for postnatal gene therapies. Lastly, PSCGT is likely less costly than current gene therapies.  This review also discusses potential risks of PSCGT such as the integration of viral vector genome with human genome, gene editing/replacement outside of the target gene, transduction of viral cells into germline, and maternal exposure to viral vectors. Procedural risks to consider include injury to umbilical vessels, bleeding, fetal bradycardia, and fetal demise.

The authors discuss important safety considerations including adverse event reporting, with fetal and maternal adverse events reported separately.  They also propose the need for a standard set of measures for PSCGT to evaluate its safety and efficacy. Lastly, the authors raise critical ethical considerations including issues of consent when the pregnant parent and non-pregnant parent are not in agreement, off-target effects of gene therapy on future offspring, costs and access to PSCGT.

Neonatal and Fetal Therapy of Congenital Diaphragmatic Hernia-related pulmonary hypertension [3]. De Bie FR, et al. Arch Dis Child Fetal Neonatal Ed. 2022 Sep;107(5):458-466. Epub 2021 Dec 24.

Congenital diaphragmatic hernia (CDH) is associated with significant neonatal mortality and morbidity, determined by the severity of pulmonary hypoplasia and pulmonary hypertension (PH). Although PH resolves in the majority of CDH patients in the neonatal period, those patients with refractory PH have worse outcomes. This comprehensive review explores the pathophysiology and interplay of pulmonary hypoplasia, pulmonary hypertension, and cardiac ventricular dysfunction. This review outlines evidence based multimodal treatment strategies in the treatment of CDH with particular emphasis on strategies to ameliorate PH.

Delivery room management includes early intubation and ventilation prior to cord clamping, if possible, to improve lung aeration, pulmonary blood flow and avoid hypoxia and acidosis. The principles of gentle ventilation are clearly delineated. A pressure-limited, volume-controlled ventilation strategy with permissive hypercapnia avoids barotrauma to the hypoplastic lung and avoids compromising pulmonary circulation.  In addition, evidence supports a lower FiO2 to achieve a preductal saturation >85% and post ductal saturation of >70% which reduces free radical release which can aggravate pulmonary vasoconstriction.

Optimizing cardiac output consists of adequate fluid resuscitation and use of dopamine and/or low dose epinephrine to support right ventricular function, and milrinone in the setting of left ventricular hypoplasia and dysfunction. Maintaining ductal patency may help reduce RV afterload. Pulmonary vasodilators may improve RV function, pulmonary circulation, and systemic oxygenation. Although inhaled nitric oxide is used in 62% of all neonates with CDH, current evidence suggests it is most beneficial in patients with preserved left ventricular function. Phosphodiesterase inhibitors, prostanoids, endothelial receptor antagonists, and calcium sensitizers are all treatment options and can improve function in certain patients. These therapies and the evidence for their use, as well as ongoing trials to prove efficacy, are discussed in this paper. 

Experimental strategies to improve pulmonary vasodilation, reverse remodeling, promote regeneration, and improve oxygenation are also reviewed. These include use of endothelial progenitor cells, tyrosine kinase inhibition, liquid ventilation, and others. Fetal therapies, including FETO and maternal sildenafil, as well as other more experimental synergistic agents are also discussed

Being small for gestational age is not an independent risk factor for mortality in neonates with Congenital Diaphragmatic Hernia: a multicenter study [4]. Zenilman A, et al. J Perinatol. 2022 Apr 21.

Neonates who are small for gestational age have overall increased morbidity and mortality. Various factors including prematurity, size of defect, low birth weight, and lung to head ratio have been demonstrated to correlate with outcomes for neonates with congenital diaphragmatic hernia. The impact of being small for gestational age on outcomes for neonates with congenital diaphragmatic hernias has not been fully evaluated.

The authors conducted a retrospective analysis of 589 neonates with CDH enrolled in the multicenter Diaphragmatic Hernia Research and Exploration, Advancing Molecular Science study. They compared the outcomes of neonates who were small for gestational age (n=90) to those appropriate for gestational age (n=499). Being small for gestational age was associated with worse outcomes on univariate analysis, but was not an independent risk factor on multivariate analysis.

Single Fetal Demise following Fetoscopic Ablation for Twin-to-Twin Transfusion Syndrome-cohort study, systematic review, and meta-analysis [5]. Mustafa HJ, et al. Am J Obstet Gynecol. 2022 Mar 4:S0002-9378(22)00164-8.

Fetoscopic laser photocoagulation improves survival in twin-twin transfusion syndrome. A number of studies have evaluated preoperative and operative risk factors associated with fetal demise, yet these results have varied between centers and a systematic review and meta-analysis have not yet been conducted.

The authors performed a retrospective cohort study of twin-twin transfusion cases that underwent fetoscopic laser photocoagulation at two fetal centers and evaluated risk factors for single fetal demise. They also performed a systematic review and meta-analysis of previously published papers. A total of 23 studies were included. The incidence of donor demise ranged from 10.9% to 35.8% and the incidence of recipient demise ranged from 7.3% to 24.5%. Abnormal umbilical artery flow, advanced stage, arterioarterial anastomoses, and low fetal weight were significant preoperative risk factors for single fetal demise. Sequential selective coagulation of vascular anastomoses was the only operative factor found to be protective against donor demise.

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018 [6].Bell EF, et al. JAMA. 2022 Jan 18;327(3):248-263.

Survival after preterm birth has improved in the past few decades. Data on the outcomes of children born extremally premature, before 25 to 26 weeks, is limited.

The authors used prospectively collected registry data for extremally premature infants (between 22 weeks and 27 weeks) born at 19 academic medical centers in the US between 2013 and 2018. Morbidity and mortality for these infants were compared to a similar cohort of infants born between 2008 and 2013. Premature infants born in 2013-2018 had a significantly higher survival to discharge of 78.3% compared to 76.0%. This increase was particularly notable for the most premature infants, with an increase in survival to discharge for infants born at 23 weeks from 32% in 2008-2013 to 49% in 2013-2018. In the 2013-2018 cohort a total of 48% of the surviving infants had no or mild NDI, for infants born at 23 weeks 31% had no or mild NDI.

Perinatal Outcome in Fetuses with Dislodged Thoraco-Amniotic Shunts [7]. Abbasi N, et al. Fetal Diagn Ther. 2021;48(6):430-439.

Insertion of fetal thoraco-amniotic shunts can improve survival in large fetal pleural effusions and macrocystic CPAMs. However, shunt migration or blockage can occur in up to 15% of cases, often necessitating a repeat procedure. There is limited data on the long-term management of dislodged shunts.   

A retrospective review of 211 fetuses undergoing thoraco-amniotic shunt placement was performed. Shunts were dislodged in 18 fetuses (8.5%). Of the 18 dislodged shunts, there were 7 cases of extrathoracic migration and 11 cases of intrathoracic migration. Of the 11 shunts with intrathoracic migration, 9 were left in situ without complication. This suggests retained intrathoracic shunts are well tolerated and may not require surgical removal.

TOTAL Trial for Severe Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia [8]. Deprest JA, et al. N Engl J Med. 2021 Jul 8;385(2):107-118. Epub 2021 Jun 8.

Fetal lung growth is stimulated by fetal occlusion. Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) in the fetus is demonstrated to have an acceptable safety profile for the mother. When compared to historical controls, neonatal survival among fetuses with CDH who underwent FETO is improved, but the risk of premature birth was higher.    

A randomized, prospective, multicenter study was performed to compare FETO to expectant prenatal care for fetuses with CDH and severe pulmonary hypoplasia. Enrollment was stopped after 80 patients for efficacy. Forty percent of infants in the FETO group survived to discharge from the NICU compared to 15% in the expectant care group. This increased survival persisted as 6 months of age. For fetuses with CDH with severe pulmonary hypoplasia FETO improves survival. 

Outcome of Twin-Twin Transfusion Syndrome according to Quintero stage of disease: Systematic Review and Meta-Analysis [9], Di Mascio et al. Ultrasound Obstet Gynecol. 2020 Dec;56(6):811-820.

The overall suspected survival rate after fetoscopic laser treatment for twin-twin transfusion syndrome (TTTS) is 50-70%. Laser therapy is considered the standard of care for Quintero stage II-IV TTTS.

This systematic review included 26 studies detailing 2699 twin pregnancies. Fetal survival in pregnancies complicated by TTTS was highest in Stage I and II. In Stage III and IV, survival of at least one twin remained high. In pregnancies complicated by Quintero stage I TTTS the rate of fetal survival of at least one twin was similar between different management strategies (expectant management, laser therapy, or amnioreduction). Amnioreduction was associated with a slightly higher rate of survival of both twins. Randomized control trials and long-term follow-up are necessary to provide further insight into the optimal management of stage I TTTS.

Prenatal assessment of Congenital Diaphragmatic Hernia at North American Fetal Therapy Network centers: A continued plea for standardization [10], Perrone et al. Prenat Diagn. 2021 Jan;41(2):200-206.

Prenatal assessment of congenital diaphragmatic hernia (CDH) includes ultrasound evaluation of the observed-to-expected lung-to-head ratio (o/e LHR). This is useful for prognostication, as o/e LHR inversely correlates with neonatal morbidity and an o/e LHR less than 25% may be used to select fetuses who could benefit from fetal endoluminal tracheal occlusion (FETO). Fetal MRI measurement of total fetal lung volume is also used to guide prenatal counseling. Currently, multiple methods to measure fetal lungs, both on ultrasound and on MRI, are used.

The authors conducted a survey of centers in the North American Fetal Therapy Network (NAFTNet) to evaluate fetal US and MRI practices. There was significant variation between centers in both US and MRI evaluation of fetal lungs. On US evaluation, only 58% of centers overall used the trace method, which is recommended by NAFTNet, to obtain LHR. Seventy-eight percent of centers overall used MRI for evaluation. There was variation between centers in the timing of MRI, ranging from < 24 weeks to 32-36 weeks, and in MRI lung volume calculation reference. There was increased consistency between the eleven centers that offered FETO, with 91% using the trace method in the US and 82% using fetal MRI. In response to the lack of uniformity in evaluation across fetal treatment centers, NAFTNet has developed a dedicated working group to standardize the prenatal prognostication and management of CDH.

Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society [11], Deprest et al. Fetal Diagn Ther 2020; 47(9):689-698.

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care including fetal diagnosis and therapy.

Reviews relevant recent information to allow optimize prenatal care delivery. Potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders are discussed as most fetal therapies are time-sensitive and cannot be delayed.

Summary of recommendations

  • Routine antenatal care should be adjusted by spacing out appointments and using telemedicine and home-based care. Ultrasound and noninvasive prenatal screening may also need re-arrangement.
  • If resources allow, there may be a place for generalized testing of pregnant women for SARS-CoV-2 infection. We do recommend testing prior to any operative procedure.
  • Pregnant women with SARS-CoV-2 infection may have a variable disease severity. It is uncertain whether they are at increased risk for COVID-19 disease. They should be managed based on the severity and nature of their complications. Cesarean delivery should be performed based on standard obstetric indications and considered in cases of septic shock or acute organ failure. Delivery may also facilitate maternal ventilation.
  • There is minimal and unconfirmed evidence for spontaneous vertical transmission. This risk theoretically may be increased by fetal procedures by disruption of either the feto-maternal barrier or the fetal skin. One should avoid transplacental instrument passage.
  • Fetal therapy is time-sensitive and hence should not be considered as elective care. In SARS-CoV-2 positive patients one may consider delaying an intervention to avoid surgical morbidity, provided the procedure can wait. This applies, in particular, to complex procedures under general anesthesia and in symptomatic patients. Conversely, life-saving minimally invasive procedures should continue.
  • Procedures of unproven fetal benefit should not be offered.
  • When caring for a neonate born to a mother with suspected or confirmed COVID-19, strict infection control measuresshould apply, including quarantine. Based on current data, the spectrum of COVID-19 infection in neonates is usually mild and their short-term outcomes are favorable.
  • Health care workers incur a significant risk of SARS-CoV-2 infection which is an argument for testing patients. When caring for suspected or SARS-CoV-2-positive patients, appropriate personal protective equipment should always be used.
  • The COVID-19 pandemic does not strike equally around the world. Centers must periodically review and adjust their approach to fetal therapy as demands and available resources change.
  • When consenting women with SARS-CoV-2 infection for fetal procedures of proven benefit, there is no autonomy-based ethical obligation to provide information about theoretical risks. Informed consent provides information about reasonable options and their benefits and risks and supports patient understanding and evaluation based on their own values and beliefs.
  • Termination of pregnancy is time sensitive and should not be considered as “elective.”
  • Registration of maternal and fetal outcomes is recommended because large cohort data will rapidly boost our knowledge.

Diagnostic and therapeutic procedures, estimated risks and benefits and position based on the current knowledge and available resources [11]

Procedure

Benefit to the fetus/mother

Theoretical risk of vertical transmission

Risk to healthcare provider

Maternal ICU need

Resource
Utilization

Recommendation

Amniocentesis

high

low

low

unlikely

minimal

offer to asymptomatic patients; others: consider delay if possible

Chorionic villus sampling

high

moderate

low

unlikely

minimal

offer to screen negative patients; delay to amniocentesis in symptomatic and screen-positive patients

Fetal blood transfusion

high

moderate

low

unlikely

moderate

offer to screen negative patients; adjust for symptomatic patients or screen positive patients if it cannot be delayed

Fetal cardiac procedures

unknown

moderate

low

unlikely

moderate

consider not offering

Fetal cystoscopy

unknown

moderate/high

low

unlikely

moderate

consider not offering screening

Laser for TTTS

high

low

low

unlikely

moderate

offer to screen asymptomatic patients; adjust for symptomatic patients or screen positive patients if it cannot be delayed

Selective feticide in monochorionic twins

variable

low

low

Unlikely

moderate

offer to screen asymptomatic patients; adjust for others

Spina bifida closure

high

high

moderate/high

low

high

delay if gestational age allows; if not, offer only to screen negative patients if sufficient local resources are available.

Thoraco-amniotic shunting

high

moderate/high

low

unlikely

moderate

offer to screen negative patients, adjust for symptomatic patients or screen positive patients if it cannot be delayed

Tracheal occlusion for CDH

unknown

low

low

unlikely

moderate

consider not offering screening

Vesico-amniotic shunting

low

moderate/high

low

unlikely

moderate

consider not offering screening

Ethical Challenges in Invasive Maternal-fetal Intervention [12], Austin et al. Semin Pediatr Surg. 2019;28(4):150819.

The field of maternal-fetal intervention is rapidly progressing and with it comes new and often complex ethical considerations that must be addressed.

Reviews the ethical issues that arise in maternal-fetal intervention and provides a list of recommended resources that any institution offering maternal-fetal intervention should have in place to meet the ethical obligations of such work.

Anhydramnios in the Setting of Renal Malformations: The National Institutes of Health Workshop Summary [13], Moxey-Mims et al. Obstet Gynecol 2018 Jun;131(6):1069-1079.

Anhydramnios is a lack of amniotic fluid surrounding the developing fetus defined as the deepest pocket of amniotic fluid measuring two cm or less in the second trimester. Anhydramnios due to fetal renal or urinary tract anomalies can result in severe pulmonary hypoplasia upon delivery. Amnioinfusion to restore amniotic fluid volume in pregnant women who carry a fetus with such anomalies may be a way to prevent pulmonary hypoplasia. This paper is a summary of a meeting of a panel of experts to further discuss this topic and to suggest an appropriate path to obtain meaningful research on the subject.

Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral Renal Agenesis [14], Sugarman et al. Obstet Gynecol 2018;131(1):130-134.

Legal and Ethical Issues in Fetal Surgery [15], Dickens et al. Int J Gynaecol Obstet 2011 Oct;115(1):80-3.

Weighing the Social and Ethical Considerations of Maternal-Fetal Surgery [16], Antiel et al. Pediatrics 2017 Dec;140(6).

Ethical Challenges in the New World of Maternal-Fetal Surgery [17], Antiel Semin Perinatol 2016 Jun;40(4):227-33.

Prevalence, Correlates, and Outcomes of Omphalocele in the United States, 1995-2005 [18], Marshall et al. Obstet Gynecol 2015 Aug;126(2):284-93.

Fetal MRI-Calculated Total Lung Volumes in the Prediction of Short-Term Outcome in Giant Omphalocele: Preliminary Findings [19], Danzer et al. Fetal Diagn Ther. 2012;31(4):248-53.

Management of Giant Omphaloceles: A Systematic Review of Methods of Staged Surgical vs. Nonoperative Delayed Closure [20], Bauman et al. J Pediatr Surg 2016 Oct;51(10):1725-30.

Giant Omphaloceles: Surgical Management and Perinatal Outcome [21], Akinkuotu et al. J Surg Res 2015 Oct;198(2):388-92.

Prenatal Steroids for Microcystic Congenital Cystic Adenomatoid Malformations [22], Curran et al. J Pediatr Surg 2010 Jan;45(1):145-50.

Cystic Adenomatoid Malformation Volume Ratio Predicts Outcome in Prenatally Diagnosed Cystic Adenomatoid Malformation of the Lung [23], Crombleholme et al. J Pediatr Surg 2002 Mar;37(3):338-8.

Congenital Lung Malformations: Informing Best Practice [24], Baird Ret al. Semin Pediatr Surg 2014 Oct; 23(5):270-7.

Gastroschisis outcomes in North America: a comparison of Canada and the United States [25], Youssef et al. J Pediatr Surg 2016 Jun;51(6):891-5.

Delivery planning for pregnancies with gastroschisis: findings from a prospective national registry [26], Al-Kaff et al. Am J Obstet Gynecol 2015 Oct;213(4):557.e1-8.

Effect of gestational age at birth on neonatal outcomes in gastroschisis [27], Carnaghan et al. J Pediatr Surg 2016 May;51(5):734-8.

Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial [28], Deprest et al. Semin Fetal Neonatal Med 2014 Dec; 19(6):338-48.

Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia [29], Jani et al. Ultrasound Obstet Gynecol. 2007 Jul;30(1):67-71.

Use of magnetic resonance imaging in prenatal prognosis of the fetus with isolated left congenital diaphragmatic hernia [30], Victoria et al. Prenat Diagn 2012 Aug;32(8):715-23.

Unique Considerations: Preterm Prelabor Rupture of Membranes in the Setting of Fetal Surgery and Higher Order Pregnancies [31], Forde et al. Obstet Gynecol Clin North Am 2020 Dec;47(4):653-669.

Fetal Surgery and Delayed Cord Clamping: Neonatal Implications [32], Frank et al. Crit Care Nurs Clin North Am 2018 Dec;30(4):499-507.

Postoperative imaging following fetal open myelomeningocele repair: The clinical utility of magnetic resonance imaging and sonographic amniotic fluid volumes in detecting suspected hysterotomy scar dehiscence [33], Seaman et al. Prenat Diagn 2020 Jan;40(1):66-70.

References

  1. Herzeg A, Almeida-Porada G, Charo RA, et al. Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI-FDA Meeting). J Clin Pharmacol. 2022;62 Suppl 1:S36-S52.  [PMID:36106778]
  2. De Bie FR, Avitabile CM, Joyeux L, et al. Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension. Arch Dis Child Fetal Neonatal Ed. 2022;107(5):458-466.  [PMID:34952853]
  3. Zenilman A, Fan W, Hernan R, et al. Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study. J Perinatol. 2022.  [PMID:35449444]
  4. Mustafa HJ, Javinani A, Goetzinger K, et al. Single fetal demise following fetoscopic ablation for twin-to-twin transfusion syndrome-cohort study, systematic review, and meta-analysis. Am J Obstet Gynecol. 2022.  [PMID:35257668]
  5. Bell EF, Hintz SR, Hansen NI, et al. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA. 2022;327(3):248-263.  [PMID:35040888]
  6. Abbasi N, Windrim R, Keunen J, et al. Perinatal Outcome in Fetuses with Dislodged Thoraco-Amniotic Shunts. Fetal Diagn Ther. 2021;48(6):430-439.  [PMID:33915545]
  7. Deprest JA, Nicolaides KH, Benachi A, et al. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N Engl J Med. 2021;385(2):107-118.  [PMID:34106556]
  8. Di Mascio D, Khalil A, D'Amico A, et al. Outcome of twin-twin transfusion syndrome according to Quintero stage of disease: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2020;56(6):811-820.  [PMID:32330342]
  9. Perrone EE, Abbasi N, Cortes MS, et al. Prenatal assessment of congenital diaphragmatic hernia at north american fetal therapy network centers: A continued plea for standardization. Prenat Diagn. 2021;41(2):200-206.  [PMID:33125174]
  10. Deprest J, Choolani M, Chervenak F, et al. Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society. Fetal Diagn Ther. 2020;47(9):689-698.  [PMID:32375144]
  11. Austin MT, Cole TR, McCullough LB, et al. Ethical challenges in invasive maternal-fetal intervention. Semin Pediatr Surg. 2019;28(4):150819.  [PMID:31451174]
  12. Moxey-Mims M, Raju TNK. Anhydramnios in the Setting of Renal Malformations: The National Institutes of Health Workshop Summary. Obstet Gynecol. 2018;131(6):1069-1079.  [PMID:29742659]
  13. Sugarman J, Anderson J, Baschat AA, et al. Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral Renal Agenesis. Obstet Gynecol. 2018;131(1):130-134.  [PMID:29215523]
  14. Dickens BM, Cook RJ. Legal and ethical issues in fetal surgery. Int J Gynaecol Obstet. 2011;115(1):80-3.  [PMID:21839453]
  15. Antiel RM, Flake AW, Collura CA, et al. Weighing the Social and Ethical Considerations of Maternal-Fetal Surgery. Pediatrics. 2017;140(6).  [PMID:29101225]
  16. Antiel RM. Ethical challenges in the new world of maternal-fetal surgery. Semin Perinatol. 2016;40(4):227-33.  [PMID:26804036]
  17. Marshall J, Salemi JL, Tanner JP, et al. Prevalence, Correlates, and Outcomes of Omphalocele in the United States, 1995-2005. Obstet Gynecol. 2015;126(2):284-93.  [PMID:26241416]
  18. Danzer E, Victoria T, Bebbington MW, et al. Fetal MRI-calculated total lung volumes in the prediction of short-term outcome in giant omphalocele: preliminary findings. Fetal Diagn Ther. 2012;31(4):248-53.  [PMID:22572017]
  19. Bauman B, Stephens D, Gershone H, et al. Management of giant omphaloceles: A systematic review of methods of staged surgical vs. nonoperative delayed closure. J Pediatr Surg. 2016;51(10):1725-30.  [PMID:27570242]
  20. Akinkuotu AC, Sheikh F, Olutoye OO, et al. Giant omphaloceles: surgical management and perinatal outcomes. J Surg Res. 2015;198(2):388-92.  [PMID:25918004]
  21. Curran PF, Jelin EB, Rand L, et al. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg. 2010;45(1):145-50.  [PMID:20105595]
  22. Crombleholme TM, Coleman B, Hedrick H, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg. 2002;37(3):331-8.  [PMID:11877643]
  23. Baird R, Puligandla PS, Laberge JM. Congenital lung malformations: informing best practice. Semin Pediatr Surg. 2014;23(5):270-7.  [PMID:25459011]
  24. Youssef F, Cheong LH, Emil S, et al. Gastroschisis outcomes in North America: a comparison of Canada and the United States. J Pediatr Surg. 2016;51(6):891-5.  [PMID:27004440]
  25. Al-Kaff A, MacDonald SC, Kent N, et al. Delivery planning for pregnancies with gastroschisis: findings from a prospective national registry. Am J Obstet Gynecol. 2015;213(4):557.e1-8.  [PMID:26116872]
  26. Carnaghan H, Baud D, Lapidus-Krol E, et al. Effect of gestational age at birth on neonatal outcomes in gastroschisis. J Pediatr Surg. 2016;51(5):734-8.  [PMID:26932253]
  27. Deprest J, Brady P, Nicolaides K, et al. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med. 2014;19(6):338-48.  [PMID:25447987]
  28. Jani J, Nicolaides KH, Keller RL, et al. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007;30(1):67-71.  [PMID:17587219]
  29. Victoria T, Bebbington MW, Danzer E, et al. Use of magnetic resonance imaging in prenatal prognosis of the fetus with isolated left congenital diaphragmatic hernia. Prenat Diagn. 2012;32(8):715-23.  [PMID:22674674]
  30. Forde B, Habli M. Unique Considerations: Preterm Prelabor Rupture of Membranes in the Setting of Fetal Surgery and Higher Order Pregnancies. Obstet Gynecol Clin North Am. 2020;47(4):653-669.  [PMID:33121651]
  31. Frank KM. Fetal Surgery and Delayed Cord Clamping: Neonatal Implications. Crit Care Nurs Clin North Am. 2018;30(4):499-507.  [PMID:30447809]
  32. Seaman RD, Cassady CI, Yepez Donado MC, et al. Postoperative imaging following fetal open myelomeningocele repair: The clinical utility of magnetic resonance imaging and sonographic amniotic fluid volumes in detecting suspected hysterotomy scar dehiscence. Prenat Diagn. 2020;40(1):66-70.  [PMID:31600420]
Last updated: November 30, 2022