Management, Outcome, Risk, and Expectation Classification for Structural Fetal Anomalies to Aid Antenatal Counseling: A Systematic Review

ABSTRACT

The aim of this study was to propose Management, Outcome, Risk, and Expectation (MORE) as a risk based stratification to aid in antenatal parental counseling and decision making through a systematic review of published literature. A Preferred Reporting Items for Systematic Reviews and Meta Analyses compliant systematic review was conducted to include articles that covered antenatal counseling of pediatric surgical conditions. The following information was solicited for each anomaly: primary organ syste*-m of involvement, single or multi system anomaly, natural history of the disease, standard management of the anomaly, need for antenatal intervention, and whether the anomaly requires any alteration in the obstetric management. Twenty two studies were identified fulfilling the inclusion criteria, between 1993 and 2023. Only two studies were found to have GRADE A recommendation and Level I evidence. Most of the studies were review articles/ survey, and 6 studies were found to be retrospective observational studies. Based on the analysis of the solicited information, the anomalies were stratified into a group subsequently maturing them into a simplified MORE classification scheme which stressed the importance of Management (10, 45.45%), Outcome (9, 40.90%), Risk (9, 40.90%), and Expectation (10, 45.45%) categories during antenatal counseling. MORE classification of fetal structural anomalies is a simple but comprehensive framework to assist the physicians and other medical personnel antenatal parental counseling and decision making.

INTRODUCTION

Congenital anomalies are reported to occur in 2%–4% of live births and account for 9% of global burden of surgical disease.[1,2] Ninety-four percent of the congenital anomalies occur in populations from low/middle-income countries (LMIC).[3] They are currently the fifth leading cause of death in children under 5 years of age globally.[4] Ninety-seven percent of such deaths occur in LMIC.[5] With the advances in screening and diagnostic armamentaria, a large proportion of these anomalies are now suspected or identified during the prenatal period. While the news of a pregnancy is often met with joy and excitement, the discovery of a congenital anomaly during this time can significantly impact the emotional experience of expectant parents. The revelation may lead to a mix of intense and conflicting emotions such as shock, grief, anger, guilt, anxiety, and distress.[5]

The expectant parents are faced with the ordeal of making decisions about the continuation of the pregnancy, potential interventions, and planning for the care of a child with special needs. The pediatric surgeons/obstetricians/fetal medicine specialists/geneticists are entrusted with the responsibility of counseling the affected family and navigating them through this situation. The current risk stratification of antenatally detected surgical anomalies broadly divides them into surgically correctable (where pregnancy is not terminated) and anomalies which are incompatible with life (where termination is advised).[6] The need of risk-based stratification of individual anomalies has been stressed frequently.[7] A detailed and comprehensive risk-based stratification, yet simple and useful at bedside is necessary to help health-care professionals offer targeted emotional yet scientific support and counseling to the aggrieved parents. A gradual and graded progression from a generic discussion to the specifics of the anomaly allows for more personalized and empathetic discussions about the potential challenges and outcomes.

Through this systematic review, the authors have proposed a risk-based stratification of fetal structural anomalies: Management, Outcome, Risk, and Expectation (MORE) to aid the medical personnel in counseling and decision-making.

MATERIALS AND METHODS

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review has been conducted across the published literature to enlist the different structural congenital malformations which may be diagnosed antenatally by ultrasonography or other screening investigations. PubMed (https://pubmed.ncbi.nlm.nih.gov/advanced/) was queried with the search strings, as depicted in Figure 1. Publications including reviews, trials, observational studies, case–control studies, or cohort studies were considered while case reports, case series, and letters to editor were excluded. Missing articles were identified through citations and reference tracking. A further search was conducted across online repositories for preprints, abstracts, and ongoing research. The WHO Reproductive Health Library was also scanned with the search strings.[8]

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram

The search results were filtered to include studies reporting in English language on human subjects only. Conditions which are not routinely dealt with by the pediatric surgeons were excluded from the scope of this study such as congenital heart diseases and metabolic, chromosomal, and genetic disorders. The search was augmented with additional searches conducted across standard textbooks for content relevant to the research question.

Data extraction and analysis

Data were extracted into Microsoft Excel (Microsoft^® Excel for Mac Version 16.55) and Microsoft Word (Microsoft^® Word for Mac Version 16.55). The common structural anomalies which could be diagnosed antenatally were identified, and the following information was solicited for each anomaly:

1. Primary organ system of involvement

2. Whether a single system is involved or is it a multi-system anomaly

3. Compatibility with life and natural history of the disease (whether the anomaly is life-threatening, known to be associated with other anomalies, possible of recurrence in subsequent pregnancies, etc.)

4. Standard management of the anomaly

   1. Whether the anomaly requires/is correctible with medical management or surgical correction
   2. Indication for surgery: Cosmetic, restoration of anatomy or functional
   3. Whether the anomaly requires a single or multiple surgeries

5. Whether the anomaly requires antenatal intervention

6. Whether the presence of the anomaly may alter the standard obstetric management.

Two reviewers (PG and VA) reviewed the potential abstracts and, if required, full texts of the search material to select the studies that appeared to be a “best fit” with stated objectives. Full articles of selected studies were reviewed in detail, and resolution of any disagreements was done in consultation with third author (RB). The result was assessed for each of the criteria and evaluated as recommended/not recommended/not available.

Quality of evidence was assessed according to GRADE guidelines.[9] Based on the insights from the review, a risk stratification-based MORE algorithm has been developed and herewith proposed for structural fetal anomalies to aid in the antenatal counseling of the affected families.

RESULTS

Twenty-two studies [Table 1] were identified fulfilling the inclusion criteria, between 1993 and 2023.[5,6,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30] Figure 1 depicts the PRISMA flowchart of the major studies considered for the synthesis. Most of the studies were review articles/survey and 6 studies were found to be retrospective observational studies.

Table 1.

Summary of the studies included in the systematic review

Authors	Year	Specialty	Type of article	Level of evidence	Recommendation	Study highlights	Input to the present study
Wilcox et al.[10]	1993	Pediatric surgery	Review article	V	D	Need for a comprehensive approach in parental counseling	Management, outcome, risk, and expectation
Crombleholme et al.[11]	1996	Pediatric surgery	Retrospective, observational study	III	C	Identifies the need of considerations such as referral of mother, site of delivery, type of delivery, and perinatal outcomes with different anomalies in a cohort of 4551 patients	Management
Miquel-Verges et al.[12]	2009	Pediatrics	Survey	V	D	Parents want realistic medical information, specific to their situation, provided in an empathetic manner and want to be allowed to hope for the best possible outcome	Expectation
Gagnon[13]	2009	Genetics	Review article	V	D	Need to identify the factors influencing antenatal management, postnatal outcome, and antenatal counseling and expand the scope of counseling measures	Management, outcome, risk, and expectation
Bischoff et al.[14]	2012	Pediatric surgery	Retrospective, cross-sectional study	III	C	Identifies the need of value-added counseling for anomalies having long-term consequences	Management, outcome, expectation
Lalatta and Tint[15]	2013	Genetics	Review article	V	D	Identify principles of reproductive autonomy, the major issues that ought to be discussed with the parents to minimize detrimental effects caused by unexpected finding	Expectation
Marokakis et al.[5]	2016	Pediatrics	Systematic review	I	A	Impact of prenatal counseling on psychological outcomes	Outcome
Deeney and Somme[16]	2016	Pediatric surgery	Review article	V	D	Highlights the need of prenatal counseling with respect to fetal intervention in select patients	Management
Akinkuotu et al.[17]	2016	Multidisciplinary	Retrospective comparative study	III	C	Identify risk stratification criteria for antenatally diagnosed CDH	Management, outcome, risk
Marokakis et al.[18]	2017	Pediatrics	Survey	V	D	While parents valued counseling, many continued to report unmet informational and psychological needs, identifying the need of shared decision-making	Expectation
Berman et al.[19]	2017	Pediatric surgery	Delphi consensus	V	D	Determined expert consensus to establish guidelines regarding perinatal management of CPAM and CDH using Delphi process and highlights the deficiency of a comprehensive classification system	Management, outcome, risk, and expectation
Sharma et al.[20]	2017	Pediatric surgery	Observational study	III	C	Analyzed the impact of counseling on antenatal congenital surgical anomalies and identify the factors affecting the outcome	Outcome
Wissanji and Puligandla[21]	2018	Pediatric surgery	Review article	V	D	Identification of outcome predictors and risk prognostication schemata for gastroschisis	Risk
Ramesh and Parvathi[22]	2020	Pediatric surgery	Review article	V	D	Need of incorporation of Genetic counseling	Management
Ioannides[23]	2021	Obstetrics	Review article	V	D	Need of incorporation of Genetic counseling	Management
Alshammari et al.[24]	2021	Pediatric surgery	Survey	V	D	Specialist counseling should focus on explaining postnatal management and should include practical aspects, especially concerning outpatient care	Expectation
Bendixen et al.[25]	2021	Pediatric surgery	Review article	V	D	Recommended to include parents in genetic analyses of exome/genome sequencing using a trio approach where the patient’s genome or exome is compared with sequences obtained from both of their biological parents	Risk
Coi et al.[26]	2022	Epidemiology	Meta-analysis	I	A	Pooling standardized data across 13 European congenital anomaly registries and the linkage to mortality data enabled reliable survival estimates which can be useful for clinical practice and parental counseling	Outcome
Kunisaki et al.[27]	2022	Pediatric surgery	Multicenter study	III	C	Risk stratification of congenital lung malformation	Risk
Sanderson et al.[28]	2022	Pediatrics	Survey	V	D	Identifies variability in prenatal counseling for CAKUT at different centers, highlighting the need of a uniform approach	Management, outcome, risk, and expectation
Walker et al.[29]	2023	Pediatric nephrology	Review article	V	D	Identify the need to counsel parents using a parent-focused, nondirected, and personalized approach	Expectation
Paladugu et al.[30]	2023	Obstetrics	Observational study	III	C	Risk stratification of urinary tract dilatation	Risk

CDH: Congenital diaphragmatic hernia, CAKUT: Congenital anomalies of the kidneys and urinary tract, CPAM: Congenital pulmonary adenomatoid malformation

A list of antenatally diagnosed common structural anomalies with emphasis on those which warrant involvement of pediatric surgeons was prepared. Only two studies were found to have GRADE A recommendation and Level I evidence.[5,26]

Management, Outcome, Risk, and Expectation classification for structural fetal anomalies

Based on the analysis of the solicited information, the list of anomalies was stratified into subgroups. Subsequently, the groups were matured into a simplified classification scheme. The MORE classification was developed which stresses the importance of Management (10, 45.45%), Outcome (9, 40.90%), Risk (9, 40.90%), and Expectation (10, 45.45%) categories during antenatal counseling. Therefore, the scheme of development of classification comprised four groups nomenclated incorporating characteristics (acronymized by Management (Antenatal), Outcome (Postnatal), Risk (In future Pregnancy), and Expectation (By Parents) – MORE) which are known to impact the overall decision-making algorithm [Table 2]. The four items of the MORE classification are explained as follows:

Table 2.

Management, Outcome, Risk, and Expectation classification for structural fetal anomalies to aid antenatal counseling

Items	Grade
	M1	M2	M3	M4	M5
Management (fetal)	Normal delivery at term may be safe at center booked	Antenatal intervention not indicated but maternal transfer to tertiary center recommended for safe delivery	Neonatal intervention may be necessary immediately after delivery	Fetal intervention to be considered explaining risks	Termination as an option for parents
Outcome (in later life)	O1	O2	O3	O4	O5
	Compatible with life, surgery may not be indicated/required	Compatible with normal life, correctible with single/multiple surgeries	Single/multiple surgeries but chronic disease/likely to be specially abled	Multiple systems affected, may be life threatening	Anomalies incompatible with life
Risk (for future pregnancy)	R1	R2			R3
	Low risk in future pregnancy	Risk unclear (further genetic testing/counseling may be needed)			Established risk for future pregnancy
Expectation (parents)	E1	E2			E3
	Elderly mother, precious baby (IVF); wants to continue pregnancy at all cost	No parental preference; No special considerations; parents fully open to suggestions			Parents keen for termination (family decision)

IVF: In vitro fertilization

• Management (obstetric) implies the timing, place and type of delivery, location of delivery, timing of intervention, and the need of termination

• Outcome implies the compatibility of the anomaly with a normal life, need of surgery, multiplicity of surgeries, and multiplicity of organs involved

• Risk implies the possibility of recurrence of the same or closely related anomalies in future pregnancies with a potential to influence the decision-making process

• Expectation implies the special parents and their social scenarios which are likely to affect the shared decision-making.

Based on the antenatal observations, the scenario can be labeled as M1-5, O1-5, R1-3, and E1-3 in different combinations.

The expected decision-making for various combinations is illustrated in Table 3.

Table 3.

Various clinical combinations and the counseling options which may be recommended to parents based on Management, Outcome, Risk, and Expectation

MORE category	MORE combination	Example
Continue pregnancy, good or fair prognosis	M1	Mild hydronephrosis UTD A1
	O1	Isolated soft markers such as choroid plexus cysts, echogenic cardiac foci, echogenic bowel
	R1
	E1
	O2
	R2
	E2
Shared decision-making	M2	Abdominal wall defect (low-risk types - exomphalos minor, perinatal gastroschisis)
		PUV/hydronephrosis without oligohydramnios
		Esophageal, duodenal, jejunoileal, and anorectal atresias
		Meconium ileus
		Enteric cysts and duplications
		Small intact meningocele
		Unilateral hydronephrosis
		Craniofacial, extremity, and chest wall deformities
		Cystic hygromas
		Small sacrococcygeal teratoma, mesoblastic nephroma, etc.
		Benign cysts: Ovarian, mesenteric, choledochal, etc.
	M4	PUV with complications/oligohydramnios
	O3	Myelomeningocele
	R2	Exstrophy bladder
	E2	Cleft lip and palate
	M3	PUV with severe oligohydramnios/anhydramniossss
	O3	Severe myelomeningocele/myeloschisis
	R2	Severe hydrocephalus
	E2	Large CPAM
		High-risk CDH
		Large sacrococcygeal teratoma
		Large cystic hygroma
		21 hydroxylase deficiency (Need to follow the evidence on indications/safety/feasibility/efficacy of fetal intervention)
	M4	VACTERL
	O4	Associated Major heart defect with a system anomaly
	R2
	E2
Termination is offered, final decision by parents	M5	Anencephaly
	O5	Bilateral PCKD
	R3	Bilateral renal agenesis
	E3	Eisenmenger’s syndrome/severe pulmonary hypertension
		Severe anomalies associated with confirmed chromosomal abnormalities (e.g., trisomy 13)

MORE: Management, Outcome, Risk, and Expectation, CDH: Congenital diaphragmatic hernia, PUV: Posterior urethral valve, PCKD: PolyCystic kidney disease, CPAM: Congenital pulmonary adenomatoid malformation, UTD A1: Urinary Tract Dilation Classification (Mild Category)

DISCUSSION

Between 3% and 6% of newborns may have congenital anomalies due to improvements in prenatal diagnosis, intervention, and counseling.[7] When a fetus is found to have a malformation during pregnancy, the parents are curious to understand about the fetus’s prognosis, the need for surgery, availability and necessity of antenatal management options, the need for termination of pregnancy, timing and mode of delivery, the kind of postnatal care warranted, and the long-term effects of the malformation. Addressing such concerns is often a team effort involving specialists from different dimensions including obstetricians, neonatologists, pediatric surgeons, radiologists, and geneticists. Physicians are legally and ethically obligated to provide accurate antenatal diagnoses and full disclosure to facilitate an informed decision-making process. Inaccurate or inadequate counseling may amount to negligence, potentially leading to liability for “wrongful birth” or “wrongful life” in many cases.[31] To some extent, the emotionality surrounding the ethical and legal issues involved with termination of pregnancy in “lethal” anomalies need to be overcome by distinguishing between the fetus destined to be brought to live birth (“the not-yet-born child/unborn patient’) from the fetus that will not be born alive.[32] While the counseling physician has a responsibility to offer a clear picture on lethal conditions to enable parents take the difficult decision of termination, the reverse also applies true. The counseling should reassure parents so that they avoid demanding termination for trivial anomalies.

The currently available risk stratification methods of antenatally detected surgical anomalies broadly divides them into surgically correctable (where pregnancy is not terminated) and anomalies which are incompatible with life (where termination is advised), which is based only on lethality and the termination rate of only about 5% and with that termination rate, neonatal mortality is about 7%.[6,33] As a result, the termination group constitutes a smaller subset, with the majority of antenatally detected surgical anomalies being correctable. This area remains a focus for exploring better measures for parental counseling.

Additionally, substantial evidence exists for stratifying the risk of individual anomalies, enabling an individualized approach toward one particular anomaly.[34,35,36,37,38]

However, there is a tendency to focus excessively on specific management plans which overshadows the overall action plan, like decisions regarding referral, delivery location, type and timing of intervention.[7] Therefore, during focused discussion and trouble-shooting related to decision-making and counseling of parents with antenatally detected congenital anomalies, experts strongly feel the need for a comprehensive bedside tool that could categorize anomalies based on outcomes and intervention strategies. Such a tool could serve as a bedside reference chart for both experts and students.

The MORE classification clearly divides the anomalies into a definite category based on outcome and management. This provides the clinicians, radiologists, obstetricians, neonatologists, and pediatric surgeons a bedside tool to categorize the anomaly and reach to a quick and most effective management plan keeping the outcome and risk in consideration. At present, there is no nationwide consensus regarding the antenatal counseling protocols. Due to the absence of any definite guidelines and the additional lacunae in the awareness regarding the appropriate antenatal counseling, the optimum benefits of neonatal and pediatric surgical advancements are not reaching the population.[39]

Fetal therapy, with its unique position in maternal-fetal medicine, has rapidly progressed from a novel idea or adaptation of existing technology to a standardized approach. However, challenges in conducting trials have hindered its validation and widespread clinical use.[40] Despite these obstacles, maternal-fetal surgery has become an international field with broad applications, though still under evaluation.[41] The MORE classification categorizes anomalies suitable for fetal intervention (M3), aiding researchers and clinicians in selecting interventions based on availability, expertise, and feasibility. Posterior urethral valve (PUV) with severe oligohydramnios/anhydramnios, severe myelomeningocele/myeloschisis, and severe congenital diaphragmatic hernia are suitable candidates, while others are suitable domains for further exploration.

Fetuses diagnosed with certain congenital anomalies prenatally should be delivered at a tertiary care center with facilities for neonatal surgery and pediatric intensive care. In the majority of cases, there is no indication for preterm delivery. Need of cesarean section is given a consideration in certain group of anomalies. However, no comprehensive classification is available, and the MORE classification provides a valuable tool to categorize patients to offer delivery by appropriate mode in a tertiary center (O2 category).[42] Cesarean delivery is generally indicated if the anomaly is associated with the risk of dystocia, bleeding, or disruption of a protective sac. Cesarean section (for fetal indication) should be reserved as the primary mode of delivery only for a select few congenital malformations, such as high-risk sacrococcygeal teratoma, congenital lung masses causing significant fetal compromise, fetal cerebral lesions, neural tube defects with a head circumference >40 cm or biparietal diameter ≥12 cm, gastroschisis with extracorporeal liver, or giant omphaloceles.[43] In large neck masses, ex utero intrapartum treatment procedure before cord clamping is recommended and this should involve maternal transfer to tertiary center where these facilities are available.[44]

“Isolated soft markers,” used to describe a soft marker that has been identified in the absence of any fetal structural anomaly, growth restriction, or additional soft marker following a detailed obstetrical ultrasound examination, which is a common scenario is kept under R0 in OMR stratification and does not warrant an invasive genetic screening.[45] However, there is a definite role of invasive genetic screening using chorionic villus sampling or amniocentesis for MORE category R2 [Table 2] for scenarios with uncertain risk in future pregnancy and likely to yield aneuploidy, chromosomal disorders, or a specific syndrome/association.[10,13,17,21,25,27,28,30,46] The MORE classification, therefore, provides an important guideline for indications of genetic screening which is either overused adding the financial, emotional, and fetal challenges or missed out completely leading to an incomplete evaluation.

The scientific classification has limitations of not taking into consideration certain special situations such as parental preferences, preciousness of pregnancy, and socioeconomic factors. In vitro fertilization (IVF) has been linked to a 25%–50% increased risk of birth defects, affecting various organ systems. These include cardiovascular anomalies (25%–40%), genitourinary anomalies (10%–60%), gastrointestinal anomalies (10%–20%), and musculoskeletal anomalies (10%–35%).[47] The decision-making process for parents of IVF-conceived children with severe anomalies differs from regular conceptions as these are precious babies for those parents. They may want to pursue with even O4M4 anomaly. The reverse is the situation in underprivileged families who may demand termination for facial abnormalities such as cleft lip. The MORE classification uniquely provides the crucial expectation category to address the concerns where shared decision-making is involved. Having standard risk stratification protects the health-care professionals from undue claims by parents later that their counseling led to a wrong decision to continue/terminate.[10,12,13,14,15,18,19,24,28,29]

Advances in technology have improved survival rates for critically ill neonates, but challenges remain for those born extremely premature or with complex conditions. Parents face tough decisions about the level of care their newborns should receive and when the burdens of treatment outweigh the benefits.[48] While guidelines suggest that parents’ values should guide these decisions, little is known about how parents form these values or how they are applied in these difficult situations. The parental decisions are guided by the severity of anomaly, long-term consequences, financial burden and security, parity, preciousness of pregnancy, and social structure.[49] Further research is needed to understand these processes better and improve value-based shared decision-making, ultimately enhancing satisfaction and reducing the potential for regret. The goal of antenatal consultation should rather be to adapt to parental needs and empower them through a personalized decision-making process, for which MORE classification can play a pivotal role.

Any risk stratification is marred by special scenarios, and so is the MORE classification. Selective termination for an anomalous twin in discordant twin pregnancy has been a special scenario in the era of in vitro techniques of fertilization. Diagnosis is typically confirmed in the second trimester using conventional prenatal techniques, making selective termination a second-trimester procedure.[50] Ethical issues around selective termination are significant and ongoing, including concerns about risks to the healthy twin. Although MORE classification characteristically includes multiple permutation and combination, there still exist certain areas which need special consideration.

Another limitation of MORE classification is lack of statistical validation. Further studies are required to methodically validate it and measure internal consistency using robust statistical measures. It still offers a broad categorical framework for clinicians to provide diverse counseling options to parents, facilitating ethical and informed decision-making regarding treatment versus termination.[51] Its numerous permutations and combinations may limit its specificity in decision-making. This is an initial effort to categorize and risk stratify congenital anomalies using a comprehensive yet straightforward template. This approach holds potential for future research, including assessing its impact on parents’ satisfaction after its systematic application in a cohort of the population.

Additionally, it can be a rich source of data for artificial intelligence which is significantly altering decision-making processes in various medical fields, including the realm of antenatal detection.[52] The grouping and classification of diseases in a single framework have the potential to pinpoint areas where deep learning, statistical algorithms, statistical analysis, and operational research can be applied through learning curves.

CONCLUSIONS

MORE classification of fetal structural anomalies is a simple but comprehensive framework to aid parental counseling and decision-making. It is likely to be a useful tool for physicians involved in antenatal counseling. Further research is needed to validate the usefulness of this system.

Key points

1. Existing risk stratifications broadly divide antenatally detected surgical anomalies into surgically correctable (where pregnancy is not terminated) and those which are incompatible with life (where termination is advised)

2. The parents often need a more detailed information on natural history of the fetal anomaly for informed decision-making. Obstetricians often seek the opinion of pediatric surgeons to aid them in the shared decision-making with parents before deciding on continuation/termination of pregnancy

3. MORE classification of fetal structural anomalies is a simple but objective framework to stratify the individual anomaly into a severity grid. It is likely to be a useful tool for physicians involved in antenatal counseling. Further research is needed to validate the usefulness of this system.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.