Hubbry Logo
AnencephalyAnencephalyMain
Open search
Anencephaly
Community hub
Anencephaly
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Anencephaly
Anencephaly
Anencephaly
View on Wikipedia
from Wikipedia

Anencephaly
Illustration of an anencephalic fetus
SpecialtyMedical genetics; pediatrics
SymptomsAbsence of the cerebrum and cerebellum
Risk factorsFolic acid deficiency
PreventionMother taking enough folic acid
PrognosisDeath typically occurs within hours to days after birth
Frequency1 in 4600 in the U.S.
Photos of anencephalic baby at first (A) and second years (B) of age.
Photos of an anencephalic newborn.

Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development.[1] It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception.[2] Strictly speaking, the Greek term translates as "without a brain" (or totally lacking the inside part of the head), but it is accepted that children born with this disorder usually only lack a telencephalon,[3] the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc., are all lacking.[4] With very few exceptions,[5] infants with this disorder do not survive longer than a few hours or days after birth.

Anencephaly is a severe neural tube defect typically considered incompatible with prolonged postnatal survival, and as such, surgical intervention is not commonly indicated.[6]

Signs and symptoms

[edit]

The National Institute of Neurological Disorders and Stroke (NINDS) describes the presentation of this condition as follows: "A baby born with anencephaly is usually blind, deaf, unaware of its surroundings and unable to feel pain. Although some individuals with anencephaly may be born with a main brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining awareness of their surroundings. Reflex actions such as breathing and responses to sound or touch may occur."[4]


A side view of an anencephalic fetus
A front view of an anencephalic fetus
X-ray of an anencephalic stillborn baby

Causes

[edit]

Folic acid has been shown to be important in neural tube formation since at least 1991,[7][8] and as a subtype of neural tube defect, folic acid may play a role in anencephaly. Studies have shown that the addition of folic acid to the diet of women of child-bearing age may significantly reduce, although not eliminate, the incidence of neural tube defects. Therefore, it is recommended that all women of child-bearing age consume 0.4 mg of folic acid daily,[4] especially those attempting to conceive or who may possibly conceive, as this can reduce the risk to 0.03%.[9] It is not advisable to wait until pregnancy has begun, since, by the time a woman knows she is pregnant, the critical time for the formation of a neural tube defect has usually already passed. A physician may prescribe even higher dosages of folic acid (5 mg/day) for women having had a previous pregnancy with a neural tube defect.[9]

Neural tube defects can follow patterns of heredity, with direct evidence of autosomal recessive inheritance.[10] As reported by Bruno Reversade and colleagues, the homozygous inactivation of the NUAK2 kinase leads to anencephaly in humans.[11] Animal models indicate a possible association with deficiencies of the transcription factor TEAD2.[12] A woman who has had one child with a neural tube defect such as anencephaly has about a 3% risk of having another child with a neural tube defect,[13] as opposed to the background rate of 0.1% occurrence in the population at large.[14] Genetic counseling is usually offered to women at a higher risk of having a child with a neural tube defect to discuss available testing.[15]

An infant with anencephaly and acrania

It is known that people taking certain anticonvulsants and people with insulin-dependent diabetes have a higher risk of having a child with a neural tube defect.[16]

Relation to genetic ciliopathy

[edit]

Until recently, medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying set of medical symptoms that are clinically visible in the disorders. Anencephaly is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and, thus, offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome, and some forms of retinal degeneration.[17]

Diagnosis

[edit]
Ultrasound image of fetus with anencephaly

Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal serum alpha-fetoprotein (AFP screening)[18] and detailed fetal ultrasound[19] can be useful for screening for neural tube defects such as spina bifida or anencephaly.

Meroanencephaly

[edit]

Meroanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a median cranial defect, and a cranial protrusion called area cerebrovasculosa. Area cerebrovasculosa is a section of abnormal, spongy, vascular tissue admixed with glial tissue ranging from simply a membrane to a large mass of connective tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid plexuses.[20]

Holoanencephaly

[edit]

The most common type of anencephaly, where the brain has entirely failed to form, except for the brain stem. Infants rarely survive more than one day after birth with holoanencephaly.[20]

Craniorachischisis

[edit]
Main article: Rachischisis

The most severe type of anencephaly where area cerebrovasculosa and area medullovasculosa fill both cranial defects and the spinal column. Craniorachischisis is characterized by anencephaly accompanied by bony defects in the spine and the exposure of neural tissue as the vault of the skull fails to form.[20][21] Craniorachischisis occurs in about 1 of every 1000 live births, but various physical and chemical tests can detect neural tube closure during early pregnancy.[22]

Prognosis

[edit]

There is no cure or standard treatment for anencephaly. Prognosis is extremely poor, as many anencephalic fetuses do not survive birth and infants that are not stillborn will usually die within a few hours or days after birth from cardiorespiratory arrest.[4]

In 2023, Menekse and colleagues reported what they described as the first surgical procedure performed on an infant with anencephaly who survived beyond the neonatal period. The case involved a multidisciplinary approach and neurosurgical intervention aimed at improving the patient's quality of life.[4]

Epidemiology

[edit]

In the United States, anencephaly occurs in about 1 out of every 4600 births.[23] Rates may be higher among Africans with rates in Nigeria estimated at 3 per 10,000 in 1990 while rates in Ghana estimated at 8 per 10,000 in 1992.[24] As of 2005, rates in China were estimated at 5 per 10,000.[24]

A high anencephaly rate of 19.7 per 10,000 live births was found in 1990/1991 in Brownsville, Texas. A cluster of cases made national headlines[25] and prompted a public health investigation and the Texas Neural Tube Defect Project. It was found, that neural tube defects in general, including spina bifida, and encephalocele had been occurring in Mexican-American women undetected for years in the area.[26] Subsequently, multiple risk factors were found, foremost folic acid deficiency, low serum vitamin B12, high serum homocysteine levels, and obesity independently contributed to risk. Increasing dietary folate intake had a protective effect.[27]

Research has suggested that, overall, female babies are more likely to be affected by the disorder.[28]

Ethical issues

[edit]

Organ donation

[edit]

One issue concerning anencephalic newborns is organ donation. Initial legal guidance came from the case of Baby Theresa in 1992, in which the boundaries of organ donation were tested for the first time.[29] Infant organs are scarce, and the high demand for pediatric organ transplants poses a major public health issue. In 1999, it was found that for American children under the age of two who are waiting for a transplant, 30–50% die before an organ becomes available.[29]

Within the medical community, the main ethical issues with organ donation are a misdiagnosis of anencephaly, the slippery slope argument, that anencephalic neonates would rarely be a source of organs, and that it would undermine confidence in organ transplantation.[30] Slippery slope concerns are a major issue in personhood debates, across the board. In regards to anencephaly, those who oppose organ donation argue that it could open the door for involuntary organ donors such as an elderly person with severe dementia. Another point of contention is the number of children who would actually benefit. There are discrepancies in statistics; however, it is known that most anencephalic children are stillborn.[30]

Proposals have been made to bypass the legal and ethical issues surrounding organ donation. These include waiting for death to occur before procuring organs, expanding the definition of death, creating a special legal category for anencephalic infants, and defining them as non-persons.[31]

In the United Kingdom, a child born with anencephaly was reported as the country's youngest organ donor. Teddy Houlston was diagnosed as anencephalic at 12 weeks of gestation. His parents, Jess Evans and Mike Houlston, decided against abortion and instead proposed organ donation. Teddy was born on 22 April 2014, in Cardiff, Wales, and lived for 100 minutes, after which his heart and kidneys were removed. His kidneys were later transplanted into an adult in Leeds. Teddy's twin, Noah, was born healthy.[32]

Brain death

[edit]

There are four different concepts used to determine brain death: failure of heart, failure of lungs, whole brain death, and neocortical death.[citation needed]

Neocortical death, similar to a persistent vegetative state (PVS), involves loss of cognitive functioning of the brain. A proposal by law professor David Randolph Smith,[33] in an attempt to prove that neocortical death should legally be treated the same as brain death, involved PET scans to determine the similarities. However, this proposal has been criticized on the basis that confirming neocortical death by PET scan may risk indeterminacy.[34]

Pregnancy termination

[edit]

Anencephaly can be diagnosed before delivery with a high degree of accuracy. Although anencephaly is a fatal condition, the option of abortion is dependent on the abortion laws in the jurisdiction.[35] According to a 2013 report, 26% of the world's population reside in a country where abortion is generally prohibited.[35][36] In 2012, Brazil extended the right of abortion to mothers with anencephalic fetuses. This decision, however, received vocal disapproval from several religious groups.[37]

[edit]

The case of baby Theresa was the beginning of the ethical debate over anencephalic infant organ donation.[29] The story of baby Theresa remains a focus of basic moral philosophy. Baby Theresa was born with anencephaly in 1992. Her parents, knowing that their child was going to die, requested that her organs be given for transplantation. Although her physicians agreed, Florida law prohibited the infant's organs from being removed while she was still alive. By the time she died nine days after birth, her organs had deteriorated past the point of being viable.[38]

United States uniform acts

[edit]

The Uniform Determination of Death Act (UDDA) is a model bill, adopted by many US states, stating that an individual who has sustained either 1) irreversible cessation of circulatory and respiratory functions or 2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. This bill was a result of much debate over the definition of death and is applicable to the debate over anencephaly. A related bill, the Uniform Anatomical Gift Act (UAGA), grants individuals and, after death, their family members the right to decide whether or not to donate organs. Because it is against the law for any person to pay money for an organ, the person in need of an organ transplant must rely on a volunteer.[35]

There have been two state bills that proposed to change current laws regarding death and organ donation. California Senate Bill 2018 proposed to amend the UDDA to define anencephalic infants as already dead, while New Jersey Assembly Bill 3367 proposed to allow anencephalic infants to be organ sources even if they are not dead.[35][39]

Research

[edit]

Some genetic research has been conducted to determine the causes of anencephaly. It has been found that cartilage homeoprotein (CART1) is selectively expressed in chondrocytes (cartilage cells). The CART1 gene to chromosome 12q21.3–q22 has been mapped. Also, it has been found that mice homozygous for deficiency in the Cart1 gene manifested acrania and meroanencephaly, and prenatal treatment with folic acid will suppress acrania and meroanencephaly in the Cart1-deficient mutants.[40][41]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Anencephaly

View on Grokipedia
from Grokipedia
Anencephaly is a lethal congenital characterized by the failure of the anterior neuropore to close during the third and fourth weeks of gestation, resulting in the absence of the , cerebral hemispheres, and overlying tissue. This malformation arises from disrupted , the embryonic process forming the , leaving only rudimentary structures and exposing neural tissue to . Affected fetuses exhibit characteristic physical features, including a frog-like appearance due to the exposed remnants and lack of bones. The of anencephaly involves multifactorial interactions between genetic predispositions and environmental factors, with metabolism disruptions playing a central causal role; periconceptional supplementation with 0.4 mg of folic acid daily has been empirically shown to prevent up to 70% of cases in randomized trials and population studies. Incidence rates vary globally but have declined in regions with mandatory folic acid fortification of food, such as a reported U.S. figure of approximately 1 in 4,600 pregnancies, though precise contemporary statistics reflect ongoing surveillance challenges post-fortification. Prenatal diagnosis via typically occurs in the first trimester, revealing the hallmark and exencephaly, prompting informed parental decisions including elective termination in many jurisdictions. Prognosis is invariably fatal, with live-born infants surviving mere hours to days due to respiratory insufficiency and absence of higher brain function, underscoring the defect's incompatibility with sustained postnatal life. Despite preventive advances, residual cases highlight gaps in universal folic acid access and underscore the need for causal interventions targeting underlying metabolic pathways beyond supplementation alone.

Definition and Pathophysiology

Neural Tube Closure Defect

Anencephaly represents a severe arising from the incomplete closure of the anterior neuropore during primary . The , which develops into the brain and , begins forming from the around days 18 to 21 post-fertilization in human embryos. Closure initiates at the midpoint of the neural groove and proceeds bidirectionally, with the anterior neuropore typically sealing by day 25 at the 18- to 20-somite stage. Failure in this anterior closure process exposes nascent neural tissue to the amniotic environment, triggering degeneration of structures and inhibiting calvarial . The cellular and molecular mechanisms underlying neural tube closure involve coordinated processes such as apical constriction of neuroepithelial cells, convergent extension to elongate the , and interkinetic nuclear migration to regulate proliferation. These events, driven by signaling pathways including planar cell polarity and dynamics, must align precisely for fusion of the folds at the midline. In anencephaly, disruptions—often multifactorial—prevent this fusion at the cranial end, resulting in exencephaly (an exposed, malformed ) that progresses to anencephaly through tissue and resorption by the fourth week of . Unlike , which stems from posterior neuropore failure around day 28, anencephaly's rostral defect precludes development, leaving only rudimentary remnants. This defect is invariably lethal, as the absence of a functional cranium and precludes viability beyond the perinatal period. Embryological studies confirm that closure completion by the end of the fourth gestational week underscores the narrow window for intervention, with no postnatal repair possible due to the foundational nature of the malformation.

Anatomical and Neurological Consequences

Anencephaly results in the complete or partial absence of the calvarium, the upper portion of the , leaving neural tissue exposed without protective bony covering or overlying . This defect arises from failed closure of the rostral , leading to degeneration of structures and replacement of cerebral hemispheres with a vascular, hemorrhagic mass known as area cerebrovasculosa. The and often the are absent or severely reduced, while elements such as the may persist but undergo secondary degeneration due to lack of mechanical protection and vascular insufficiency. Neurologically, the absence of the cerebral cortex precludes any capacity for consciousness, perception, or higher cognitive function, rendering affected infants permanently unconscious. Brainstem-mediated reflexes, including spontaneous respiration, sucking, swallowing, and responses to stimuli, may be variably present, though often incomplete; for instance, in one series of cases, pupillary light reflexes were absent in over half, and oculocephalic responses failed in approximately 50%. These rudimentary functions are insufficient for sustained viability, as the profound structural deficits prevent organized neural integration or adaptation to extrauterine life. Associated cranial nerve and special sense organ malformations further impair reflexive capabilities.

Causes and Risk Factors

Genetic and Familial Predispositions

Anencephaly exhibits a familial aggregation pattern, with siblings of affected individuals facing a recurrence of 2-5%, representing approximately a 50-fold increase over the general incidence. This elevated risk persists even after accounting for environmental factors like supplementation, suggesting a substantial heritable component. Family history of defects (NTDs), including anencephaly, remains one of the strongest known risk factors, with empirical recurrence rates for subsequent pregnancies after an affected estimated at around 3%. Genetic studies indicate that anencephaly arises from complex, multifactorial inheritance rather than single-gene Mendelian patterns, with estimates attributing 60-70% of NTD risk to genetic factors. Genome-wide association and linkage analyses have identified modest contributions from variants in folate metabolism pathways, such as the MTHFR gene encoding methylenetetrahydrofolate reductase, which impairs homocysteine remethylation and may interact with nutritional status. Other candidate genes include PAX3, involved in neural crest development and neurulation; GJA1 (encoding connexin 43 for cell communication); and extracellular matrix components like LAMA5 (laminin-α5) and integrins. Rare chromosomal anomalies, such as trisomies or deletions, occur in about 0.66% of cases but do not account for the majority. Evidence points to maternal genetic effects influencing susceptibility, including sex-influenced traits and imprinting, as recurrence risks vary by parental origin of the defect. Despite over 200 genes implicated in NTD models, human studies reveal no high-penetrance loci for isolated anencephaly, underscoring polygenic architecture and gene-environment interplay. Whole-exome sequencing in affected families has occasionally identified de novo or rare variants in genes like TRIM36 or MARCKSL1, but these explain only sporadic cases. Population-level genetic may differ by , with higher NTD rates in certain groups potentially linked to variations.

Environmental and Nutritional Influences

during the periconceptional period is a well-established nutritional for anencephaly, as it impairs closure occurring between days 21 and 28 post-fertilization. Periconceptional supplementation with 400-800 micrograms of folic acid daily reduces the incidence of s, including anencephaly, by 50-70%, according to randomized controlled trials and population-level data from programs. Mandatory folic acid of grains in the United States since 1998 has correlated with a 20-30% decline in rates, including anencephaly. Higher maternal intakes of other micronutrients, such as thiamin, betaine, iron, and , have been associated with reduced anencephaly risk in case-control studies, potentially through synergistic effects on one-carbon metabolism and critical for development. However, evidence for these associations is observational and weaker than for , with no causal confirmation from intervention trials. Environmental exposures implicated include high nitrate levels in , which elevate anencephaly risk via potential interference with metabolism or , as observed in cohort studies from agricultural regions. Maternal exposure to ambient particulate matter (PM10) before and during early pregnancy increases odds of anencephaly, likely due to inflammatory or hypoxic effects on embryogenesis, per epidemiological analyses in polluted areas. Certain teratogenic medications, notably valproic acid used for , heighten risk by antagonizing pathways, with relative risks exceeding 10-fold in exposed pregnancies. These factors interact with genetic susceptibilities, but isolated environmental causation remains unproven absent .

Multifactorial Interactions

Anencephaly results from multifactorial interactions involving multiple genetic variants of low and environmental exposures that disrupt closure during embryogenesis. These interactions follow a threshold liability model, wherein cumulative genetic susceptibility combined with suboptimal environmental conditions exceeds a developmental threshold, leading to failure of cranial neuropore closure. Genetic contributions are estimated to account for approximately 70% of (NTD) etiology, with environmental factors modulating the final outcome by influencing processes such as metabolism and cellular signaling. Key gene-environment interactions center on maternal folate status and polymorphisms in folate pathway genes. For instance, the MTHFR C677T variant impairs metabolism, elevating levels and reducing 5-methyltetrahydrofolate availability, which heightens NTD risk particularly in mothers with low dietary folate intake; periconceptional folic acid supplementation mitigates this risk more effectively in wild-type individuals than in homozygous TT carriers, where residual susceptibility persists. Similarly, variants in genes like FOLR1 (encoding folate receptor alpha) interact with suboptimal folate levels to impair folate to the , as evidenced by associations between FRα polymorphisms and increased NTD incidence in folate-deficient populations. Other loci, including those in planar (PCP) pathways (e.g., VANGL1, VANGL2), exhibit interactions with teratogens like valproic acid, which disrupts convergent extension movements essential for neural tube folding. Maternal conditions such as , , and further exemplify multifactorial dynamics by altering epigenetic regulation and , which compound genetic vulnerabilities; for example, diabetic pregnancies show elevated NTD rates that are partially attenuated by folic acid but persist due to hyperglycemia-induced disruptions in sonic hedgehog signaling interacting with predisposing alleles. Empirical evidence from family recurrence s (2-5% after one affected pregnancy) and geographic variations—higher in low-folate regions despite —underscores driven by these polygenic-environmental synergies rather than single causal loci. While folic acid has reduced NTD by 20-50% globally since the , incomplete prevention (e.g., 20-30% residual cases) highlights ongoing interactions where genetic resistance or additional unmitigated factors like anti-epileptic drugs sustain .

Diagnosis

Prenatal Screening Techniques

Prenatal screening for anencephaly relies on non-invasive techniques such as imaging and maternal serum (MS-AFP) testing, which detect indicators of defects early in . is the cornerstone method, offering high sensitivity for visualizing the absence of development. MS-AFP screening complements by identifying elevated protein levels associated with open defects. Fetal performed between 10 and 14 weeks of can reliably detect anencephaly through characteristic findings like the "frog face" appearance or lack of echogenic cranial structures, with sensitivity rates of 100% when a targeted examination is conducted. By 14 weeks, accuracy approaches 100%, enabling early identification that distinguishes anencephaly from similar conditions such as . Second-trimester scans further confirm these features, with overall detection rates exceeding 99% across studies of structural anomaly screening. MS-AFP testing, typically conducted between 15 and 21 weeks, measures levels in maternal blood, which are markedly elevated in anencephaly due to leakage from the exposed neural tissue. This biochemical screen detects approximately 85-90% of anencephaly cases before 24 weeks, though false positives can occur from factors like gestational dating errors or multiple gestations, necessitating follow-up. Integrated approaches combining MS-AFP with or multiple serum markers, such as the quad screen, enhance overall screening efficacy for defects. Advanced ultrasound modalities, including three-dimensional imaging, may improve diagnostic precision over two-dimensional scans, achieving sensitivities above 92% for anomalies, though routine use is not universally standardized. Non-invasive prenatal testing (NIPT) for does not directly screen for anencephaly but may be offered concurrently in comprehensive protocols. These techniques enable timely counseling, with prenatal rates for anencephaly approaching 100% in settings with routine anomaly scans.

Postnatal Confirmation and Subtypes

Postnatal confirmation of anencephaly occurs primarily through of the newborn, which reveals the diagnostic features of a missing calvaria (), exposed or absent cerebral hemispheres, and often a flattened or frog-like cranial appearance due to underdeveloped tissue. This examination distinguishes anencephaly from similar cranial anomalies, such as acalvaria or , by confirming the specific absence of vault bones and structures. In instances where prenatal suspicion exists but confirmation is needed postnatally, radiographic studies like skull X-rays or computed can verify the skeletal defects, though these are secondary to the overt clinical presentation. Anencephaly is classified into subtypes based on the extent of cranial involvement and associated spinal defects. Holoacrania (or holoanencephaly) represents the complete form, with total absence of the and brain above the , often accompanied by orbital and microstomia. Meroacrania (or meroanencephaly) involves partial absence, preserving some superior brain tissue. A further distinction includes craniorachischisis, where anencephaly coexists with extensive spinal (open along the spine), comprising up to 10-20% of cases in some series and worsening prognosis due to compounded exposure of neural elements. These subtypes reflect varying degrees of failed anterior neuropore closure during embryogenesis, around days 23-26 post-fertilization.

Prognosis and Clinical Management

Expected Survival and Outcomes

Anencephaly is incompatible with sustained life due to the absence of major structures, resulting in inevitable either or shortly after birth. Approximately 75% of affected pregnancies end in , with the remainder involving live births followed by rapid demise. Among live-born infants, beyond a few hours or days is exceptional, as , inability to regulate vital functions, and exposure of neural tissue lead to swift deterioration. Studies indicate that over 85% of live-born cases result in within the first 24 hours, with fewer than 5% surviving beyond one week. No curative interventions exist, and outcomes uniformly involve palliative measures focused on comfort rather than prolongation of life. Infants exhibit profound neurological impairment, lacking , sensory responses, or the capacity for independent feeding or . While rare cases of prolonged survival—such as one unassisted instance lasting 28 months—have been documented, these defy typical expectations and do not alter the uniformly lethal , with anencephaly considered 100% fatal within the first year in standard . Maternal and fetal monitoring post-diagnosis prioritizes ethical considerations, including options for pregnancy continuation or termination, but postnatal viability remains negligible.

Supportive and Palliative Approaches

Supportive and palliative approaches for infants with anencephaly prioritize comfort measures and family-centered care, given the absence of curative options and the condition's near-uniform , with most affected neonates surviving only hours to a few days postnatally. Care plans typically involve multidisciplinary teams, including neonatologists, specialists, social workers, and chaplains, to address physiologic stability, symptom relief, and psychosocial needs through parallel planning that accommodates both potential short-term survival and end-of-life support. Immediate postnatal management focuses on non-invasive comfort interventions, such as drying the , providing skin-to-skin contact for thermal regulation and , and applying protective dressings like moist or hats over exposed neural tissue to prevent or . Pain and distress assessment uses validated neonatal scales, with initial reliance on non-pharmacologic methods including positioning, , and facilitated parental holding; pharmacologic agents like or are administered judiciously if reflexive responses suggest discomfort, though cerebral absence limits conscious perception. Invasive procedures, such as or resuscitation, are generally withheld to avoid prolonging futile suffering, aligning with guidelines emphasizing physiologic stability without aggressive prolongation. Some families elect hospital-based care in a private room to facilitate memory-making, such as or footprint impressions, alongside discussions of or if viable; others pursue home discharge under oversight for extended bonding, though this entails challenges like managing cranial defects, potential seizures, or feeding via breastmilk expression without enteral tubes. Home settings require parental education on basic monitoring, but outcomes reveal gaps, including limited bereavement-trained providers and inconsistent post-death follow-up, with only isolated cases of prolonged survival exceeding weeks under such care. Bereavement support extends to parents through counseling, referrals to organizations like Antenatal Results and Choices, and respect for cultural preferences in rituals. Integrated frameworks advocate holistic elements, including anticipatory guidance from prenatal diagnosis, of parental , and continuity across antenatal, delivery, and neonatal phases to mitigate trauma and foster dignified closure. These approaches underscore empirical focus on observable comfort indicators over speculative neurologic function, given the brainstem's minimal viability and lack of cortical activity.

Epidemiology

Prevalence and Incidence Rates

A global and published in 2022 estimated the overall of congenital anencephaly at 5.1 cases per 10,000 births (95% : 4.7–5.5), incorporating data from multiple regions and accounting for both live births and stillbirths, with regional attenuation due to prenatal and elective termination ranging from negligible to substantial. This rate reflects baseline incidence before widespread interventions, though methodological variations in ascertainment—such as inclusion of terminated pregnancies or reliance on registries—affect comparability across studies. Higher rates persist in low-resource settings with limited folic acid access, underscoring environmental modifiable factors over purely genetic ones. In the United States, birth prevalence stands at approximately 1.9 cases per 10,000 live births (or 1 in 5,246), a figure derived from national surveillance data and attributable to mandatory folic acid fortification of enriched cereal grains implemented in 1998, which reduced rates by an estimated 20–50%. This translates to roughly 700 affected infants annually, though prenatal detection via —achieving sensitivity over 90% by 18–20 weeks —often leads to non-viable outcomes not captured in live birth statistics. European rates, from registry-based studies, hover similarly low at 1–2 per 10,000 in fortified or supplemented populations but elevate to 3–5 per 10,000 in areas with inconsistent measures. Incidence, measured as diagnosed cases per total conceptions or early pregnancies, exceeds birth globally due to embryonic lethality and terminations; for instance, pre-fortification U.S. data from the 1990s indicated rates up to 4 per 10,000 pregnancies, halved post-intervention. Temporal trends show declines in high-income countries since the 2000s, but stagnation or increases in under-fortified regions like parts of (up to 9 per 10,000 in recent urban cohorts) highlight disparities tied to socioeconomic access rather than inherent population differences.

Demographic and Geographic Patterns

Anencephaly exhibits a marked predominance, with a -to-male of approximately 4:1 across global studies. This sex disparity aligns with broader patterns in defects, where fetuses are more frequently affected, potentially due to differences in embryonic development or genetic susceptibility. In the United States, prevalence varies significantly by maternal race and . Rates are highest among births, followed by non- white births, with the lowest rates observed among non- births; for instance, between 1995 and 2002, populations showed elevated incidence prior to widespread folic acid impacts. ethnicity remains a key predictor, alongside factors such as maternal age, parity, and residence near borders like the U.S.- boundary, where environmental or dietary influences may contribute. American Indian/ Native populations also display higher rates of certain defects, including anencephaly, often exceeding non- rates by 50% or more. Geographically, anencephaly prevalence demonstrates substantial variation worldwide, estimated at a global average of 5.1 per 10,000 births (95% CI: 4.7–5.5). Hotspots include regions like northern (up to 12 per 10,000 births from 1998–2005), , and parts of northern , where rates historically exceeded 10 per 10,000 before interventions. In , EUROCAT registry data from 2000–2010 report lower rates of 3.52 per 10,000 births, reflecting better prenatal screening and nutritional policies. African countries show heterogeneous prevalence, ranging from 1 to 4.7 per 1,000 births in meta-analyses, with higher burdens in low-resource settings lacking . These patterns underscore the role of socioeconomic, dietary, and genetic factors in regional disparities, with declines observed post-folic acid mandates in fortified areas.

Prevention

Folic Acid Supplementation Efficacy

Periconceptional supplementation with folic acid reduces the risk of defects (NTDs), including anencephaly, by addressing implicated in neural tube closure failure during embryogenesis. The Medical Research Council () Vitamin Study, a 1991 multicenter double-blind randomized trial involving 1,817 women with prior NTD-affected pregnancies, demonstrated that 4 mg daily folic acid from one month before conception through the 12th gestational week lowered NTD recurrence by 72% (4 recurrences in the folic acid group versus 21 in the or multivitamin-without-folic-acid groups; 0.28, 95% CI 0.12-0.68). This efficacy held specifically for anencephaly and subtypes within NTDs. For primary prevention of first-occurrence NTDs, a 1992 Hungarian randomized of 4,753 women planning found periconceptional multivitamins containing 0.8 mg folic acid (plus other micronutrients) yielded zero NTD cases among 2,474 supplemented participants, compared to six cases (three anencephaly, three ) in 2,477 trace-vitamin controls, indicating near-complete prevention in that cohort ( approaching 0, though limited by small event numbers). Observational and cohort studies corroborate that even lower doses (0.4 mg daily) achieve 50-70% risk reduction for NTDs, including anencephaly, when initiated preconceptionally or in early . The U.S. Preventive Services Task Force (USPSTF) 2023 recommendation for 0.4-0.8 mg daily folic acid supplementation in all persons planning or capable of draws from updated , including meta-analyses of randomized and observational showing consistent NTD prevention without serious harms at these doses. interventions, such as mandatory grain fortification starting in 1998, have reduced U.S. NTD prevalence by 28-35%, with similar declines in anencephaly rates, attributing causality to elevated folate levels. Efficacy varies by baseline folate status, (e.g., MTHFR polymorphisms), and timing, preventing most but not all folate-sensitive cases, as 20-30% of NTDs involve non-folate pathways.

Public Health and Policy Measures

Public health strategies to prevent anencephaly, a severe (NTD), emphasize periconceptional folic acid intake, as adequate maternal levels during early embryogenesis reduce NTD risk by up to 70% in high-risk cases and 50% overall. In the United States, the Centers for Disease Control and Prevention (CDC) recommends that all women capable of becoming pregnant consume 400 micrograms (mcg) of folic acid daily from fortified foods and/or supplements, a guideline originating from the 1992 U.S. Service recommendation to address the preconception timing of closure. The U.S. Preventive Services Task Force reinforces this with a Grade A recommendation for 0.4 to 0.8 mg daily supplementation in the periconceptional period for primary prevention. Mandatory folic acid of enriched products, implemented nationwide in the U.S. on January 1, 1998, has contributed to a 19% to 35% decline in NTD , including anencephaly, by increasing average daily intake across the population without relying solely on voluntary supplementation. Comparable mandatory in , introduced in 1998, correlated with a significant reduction in NTD rates from 1.58 per 1,000 births pre-fortification to lower levels post-implementation. These policies demonstrate the efficacy of population-level interventions over individual supplementation alone, though residual NTD cases persist due to factors like non-compliance or genetic predispositions. Globally, the (WHO) endorses 400 mcg daily folic acid supplementation for women from the start of attempts to conceive until 12 weeks of gestation, alongside efforts to achieve optimal population folate concentrations above 906 nmol/L to maximize NTD prevention. However, mandatory remains uneven, with only about 25% of preventable and anencephaly cases averted worldwide due to limited adoption in low- and middle-income countries, where NTD burdens are highest. campaigns, such as those by the CDC and WHO, promote awareness of these measures, but gaps in implementation highlight the need for broader policies to equitably reduce anencephaly incidence.

Research Directions

Genetic and Developmental Studies

Anencephaly results from the failure of anterior closure during , occurring between embryonic days 23 and 26 after fertilization, leading to the absence of the , cerebral hemispheres, and overlying . This defect exposes the and remnants of neural tissue to , resulting in degeneration and the characteristic "frog-like" appearance. Developmental studies in mammalian models, including mice and humans, highlight that cranial neural tube closure requires precise coordination of cellular behaviors such as convergent extension, apical constriction of neuroepithelial cells, and interkinetic nuclear migration to elevate and fuse neural folds. Disruptions in these biomechanically driven processes, often modeled in mice targeting genes like those in the planar cell polarity pathway (e.g., Vangl2), recapitulate exencephaly, the murine equivalent of human anencephaly. Genetic studies underscore a multifactorial involving gene-environment interactions, with no single locus accounting for most cases; instead, polygenic risk combines with teratogenic exposures like or maternal . The methylenetetrahydrofolate reductase (MTHFR) gene, encoding an enzyme critical for and homocysteine remethylation, harbors the common C677T polymorphism (rs1801133), where homozygosity reduces enzyme activity by up to 70%, elevating risk by impairing one-carbon necessary for closure. Population-based case-control studies, including those from the and , report odds ratios of 2-7 for MTHFR 677TT in anencephaly-affected pregnancies, particularly in regions with low folate fortification prior to 1998 mandates. Beyond MTHFR, rare monogenic forms implicate mutations in genes regulating cytoskeletal dynamics and signaling; for instance, homozygous loss-of-function variants in TRIM36 disrupt organization in neuroepithelial cells, causing autosomal recessive anencephaly in consanguineous families, as identified in a 2017 whole-exome sequencing study of 48 affected fetuses. Other candidates include variants in SLC19A1 ( transporter) and components of the Sonic Hedgehog pathway, though genome-wide association studies (GWAS) yield limited hits due to the condition's lethality and small sample sizes, emphasizing the need for larger cohorts integrating rare variant burden analysis. Epigenetic factors, such as altered in -related genes, further modulate risk, with maternal serum levels inversely correlating with defect incidence in prospective cohorts. These findings, drawn from peer-reviewed genetic consortia like those in the Neural Tube Defect Genetics Group, affirm that while folic acid supplementation mitigates many cases, unresolved genetic heterogeneity persists in supplementation failures.

Prevention and Intervention Trials

Trials evaluating prevention strategies for anencephaly, a severe (NTD), have built on established folic acid interventions by investigating adjunct therapies for cases resistant to folic acid alone. A pilot , the Prevention of Neural Tube Defects by (PONTI) study conducted from 2003 to 2014, assessed the safety and feasibility of combining 2 g daily myo- with 5 mg folic acid versus folic acid plus in 116 women at high risk for NTD recurrence (prior affected ). No NTDs, including anencephaly, occurred in either arm, though the small sample size precluded efficacy conclusions; the regimen was well-tolerated with minor gastrointestinal side effects in 18% of the inositol group. Larger trials have not advanced due to recruitment challenges, but preclinical evidence from folate-resistant mouse models indicates myo-inositol prevents up to 90% of NTDs by supporting closure signaling pathways independent of metabolism. Intervention trials targeting diagnosed anencephaly remain absent from registries like , reflecting the condition's incompatibility with viable postnatal repair due to absent cerebral hemispheres and inevitable brainstem failure. Standard management is limited to palliation, with no experimental therapies demonstrating survival beyond hours to days in most cases. A single 2023 case report described microsurgical cranial closure with duraplasty and flap reconstruction in a 3-week-old anencephalic twin, enabling 37 months of supportive care (including ventilation and hormones) without immediate complications, but this untested approach highlights ethical barriers to trialing such high-risk procedures given uniform lethality. Stem cell approaches, successful in fetal trials for tissue regeneration, have not been adapted for anencephaly's profound absence, remaining preclinical for NTDs broadly. Future trials may integrate genetic risk profiling from studies like the Genetics of and Anencephaly project to refine periconceptional prevention.

Organ Procurement and Donation Debates

The prospect of procuring organs from anencephalic infants has sparked ethical and legal debates since the , centered on the tension between the dead donor rule—which prohibits harvesting organs from living individuals—and the urgent need for pediatric transplants. Anencephalic neonates, lacking and cerebral hemispheres but often retaining brainstem function, exhibit spontaneous respiration and circulation for hours to days post-birth, precluding immediate declaration of under standard whole-brain criteria. Proponents argue that these infants' inevitable demise and parental willingness to donate could yield viable organs like hearts, livers, and kidneys for other infants, potentially addressing the scarcity of donors under 1 year old, where waitlist mortality exceeds 20%. Opponents contend that altering death criteria for anencephalics risks eroding the uniform definition of death, potentially incentivizing premature interventions or pressuring families, and violates causal principles by linking organ retrieval to hastened demise rather than independent physiological failure. Historical efforts, such as the 1989 protocol to maintain anencephalics on ventilators until brain death for donation, were abandoned after two cases yielded no usable organs due to physiological instability. In the Baby Theresa case in , courts rejected harvesting organs from a living anencephalic infant, affirming that congenital malformation alone does not constitute , as reflexes persisted. Subsequent proposals explored donation after circulatory death (DCD), withdrawing support and harvesting post-asystole, but outcomes remain limited; a 2017 review of 17 U.S. cases found elective feasible in 4 of 5 attempts, yet no transplants succeeded due to rapid organ ischemia. The American Medical Association's evolving guidance, from a 1990 moratorium to conditional permissibility in 1995 if voluntary and non-coercive, underscores professional caution, prioritizing adherence to existing standards over ad hoc redefinitions. Today, anencephalic donation is not routine, with fewer than 100 potential U.S. cases annually deemed insufficient to justify protocol changes, and ethical consensus holds that infants must meet standard somatic or criteria before procurement to avoid commodifying non-viable lives. Empirical data indicate typically occurs within 7-10 days, by which time thoracic organs suffer irreversible damage from exposure or support withdrawal, rendering hearts unusable in over 90% of scenarios. Legislative responses, including a 1988 Harvard report and state-level inquiries, have reinforced prohibitions absent national consensus, prioritizing definitional integrity over marginal gains in transplant rates.

Pregnancy Continuation vs. Termination

Upon prenatal diagnosis of anencephaly, typically confirmed via ultrasound between 11 and 14 weeks gestation or later with fetal MRI if needed, parents face the choice of pregnancy termination or continuation, informed by the condition's invariably lethal prognosis. Anencephalic fetuses lack cerebral hemispheres and a functional forebrain, rendering survival beyond a few hours or days post-birth impossible, with approximately 75% stillborn and the remainder succumbing rapidly due to respiratory failure and brainstem dysfunction. Termination rates following diagnosis range from 59% to 100% across studies, influenced by gestational age at detection, regional laws, and parental factors, with higher rates observed earlier in pregnancy (e.g., 48.5% at 10-12 weeks). In jurisdictions permitting it, such as many U.S. states and European countries, termination is often pursued via induction of labor or dilation and evacuation, minimizing maternal risks like hemorrhage or infection compared to carrying to term, though ethical debates persist over late-term procedures despite the fetus's non-viability. For parents electing continuation, perinatal palliative care programs provide multidisciplinary support, including serial ultrasounds to monitor (affecting up to 50% of cases and risking preterm labor), maternal , and psychosocial counseling to facilitate and preparation. Outcomes of continued pregnancies include a 30-42% rate and, among live births (about 72%), median survival of under 24 hours, with rare cases exceeding one week but none achieving sustained viability. Cesarean deliveries, comprising up to 70% in some cohorts, are discouraged unless medically necessary for , as they elevate risks without benefiting the ; vaginal delivery with comfort measures post-birth, such as skin-to-skin contact and if desired, aligns with goals of dignity and closure. Studies report that while initial emotional distress is profound, continuation can enable positive maternal experiences, such as holding the , potentially aiding long-term bereavement compared to abrupt termination, though empirical data on comparative trajectories remain limited and vary by individual beliefs. Decisions hinge on parental values, including religious convictions prohibiting termination (e.g., in Catholic doctrine viewing direct abortion as impermissible even for lethal anomalies) and access to hospice resources, with counseling emphasizing factual prognosis over unsubstantiated hope. In regions with restrictive abortion laws, continuation predominates, but even there, up to 58% opt for termination when available, underscoring the weight of empirical non-viability in shaping choices. Post-decision support, including genetic counseling for recurrence risk (2-5% without folic acid intervention), is standard regardless of path.

Brain Death Criteria and Personhood

Brain death criteria, as established by medical consensus such as the 1981 President's Commission guidelines and subsequent updates, require irreversible cessation of all functions of the entire , including the , confirmed through clinical tests like absence of pupillary and corneal reflexes, gag response, and an apnea test demonstrating no spontaneous respiration at PaCO₂ >60 mmHg. In neonates with anencephaly, these criteria are rarely met at birth because, despite the absence of cerebral hemispheres and , residual function often persists, enabling primitive reflexes, spontaneous respiration, and cardiovascular activity for hours to weeks post-delivery. Clinical studies of liveborn anencephalic infants have documented cases where full , including failure, was confirmed after an observation period of at least 48 hours, correlating with neuropathologic findings of extensive , though such determinations remain exceptional due to the condition's variability. The application of brain death standards to anencephalic neonates has fueled debates on whether "whole brain" criteria should apply or if a narrower "cerebral death" threshold—focusing only on higher brain absence—sufficies, given the empirical futility of cerebral function in anencephaly. Proponents of redefinition argue that anencephalics are biologically equivalent to brain-dead patients, as the missing forebrain precludes consciousness, sentience, or potential for recovery, rendering prolonged support ethically questionable. However, opponents cite risks of diagnostic error, the dead donor rule prohibiting organ procurement from living patients, and precedents where brainstem-mediated survival (e.g., up to 10-14 days with ventilation) delayed viable organ use, as seen in 1980s-1990s trials where harvested organs from presumed anencephalic donors failed due to non-death status. Personhood considerations in anencephaly intersect these criteria, with ethical analyses questioning whether organisms lacking cerebral structures qualify as entitled to full moral protections against utilitarian organ harvesting. From a biological standpoint, anencephalic infants represent organisms with integrated bodily functions but no capacity for relational or future-directed agency, prompting some bioethicists to equate their status to that of brain-absent entities, ineligible for predicates like to non-futile care. Counterarguments, grounded in ontological views of as inherent to human life from fertilization, reject functionalist metrics, asserting that empirical activity evidences ongoing organismal integrity, thus barring preemptive death declarations or experimental protocols that prioritize recipients over donors. Legal precedents in the U.S., such as Virginia's abandoned proposal for anencephalic-specific death laws, upheld standard criteria to avoid eroding public trust in transplantation systems, emphasizing verifiable irreversibility over condition-specific exceptions.

Judicial and Legislative Responses

In the United States, judicial responses to anencephaly have primarily addressed conflicts over organ donation from anencephalic infants and obligations to provide life-sustaining treatment. In the 1992 Florida Supreme Court case In re T.A.C.P., parents sought to declare their anencephalic newborn legally dead to enable organ donation while the infant retained brainstem function, including spontaneous respiration and heartbeat. The court ruled that anencephaly alone does not constitute death under Florida law, which requires either irreversible cessation of circulatory and respiratory functions or whole-brain death, rejecting redefinition of death based on prognosis or deformity to preserve the dead donor rule. Similarly, in the 2000 case involving infant Theresa Ann Pearson (Baby Theresa), the Florida Supreme Court upheld that an anencephalic infant is not legally dead until cardiopulmonary functions cease, denying parental requests for pre-mortem organ harvesting despite the infant's inevitable demise within days. The 1994 federal appeals court decision in In the Matter of compelled a Virginia hospital to provide to an anencephalic infant with recurrent respiratory failure, interpreting the Emergency Medical Treatment and Active Labor Act (EMTALA) to require stabilization of acute symptoms like breathing difficulties, irrespective of the underlying futile condition of anencephaly. The ruling emphasized statutory mandates over medical futility arguments, leading to prolonged ventilation until the infant's death two years later from complications, though it did not alter criteria. These cases underscore courts' adherence to established death definitions, preventing without violating ethical norms against harvesting from living persons. Legislatively, efforts to facilitate anencephalic organ donation have faltered due to concerns over redefining or eroding trust in transplantation systems. The American Medical Association's Council on Ethical and Judicial Affairs has opposed using anencephalic newborns as donors absent standard brain or somatic criteria, citing risks to the dead donor rule and public confidence in . No federal U.S. legislation has amended the to include anencephaly as a death equivalent, and state laws generally align with whole-brain or cardiopulmonary standards. Regarding pregnancy management, post-2022 Dobbs v. Jackson overturning Roe v. Wade, many U.S. states enacted near-total abortion bans without exceptions for lethal fetal anomalies like anencephaly, complicating terminations even when viability is impossible. For instance, Kentucky's 2022 law lacks provisions for anencephaly, forcing affected women to carry to term or travel out-of-state, as illustrated by cases where parents faced legal barriers despite confirmed non-viability. Texas's restrictions similarly exclude fetal anomalies, permitting abortions only for maternal life-threatening conditions, not prognostic ones. Some states, like Florida, include exceptions for "fatal" anomalies post-six weeks, but interpretation remains contested, often requiring judicial or medical board approval. Internationally, Brazil's Supreme Federal Court in 2012 rejected blanket decriminalization of abortions for anencephaly, upholding therapeutic exceptions only for maternal health risks rather than fetal condition alone. These frameworks prioritize jurisdictional definitions of viability and maternal rights over uniform accommodation for anencephaly.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK545244/
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC6511489/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7864317/
  4. https://pubmed.ncbi.nlm.nih.gov/2072886/
  5. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5113a1.htm
  6. https://www.cdc.gov/birth-defects/about/neural-tube-defects.html
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC11103198/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC9575217/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC4023229/
  10. https://www.ncbi.nlm.nih.gov/books/NBK557414/
  11. https://www.ncbi.nlm.nih.gov/books/NBK542285/
  12. https://emedicine.medscape.com/article/1181570-overview
  13. https://pmc.ncbi.nlm.nih.gov/articles/PMC5325323/
  14. https://www.medlink.com/articles/anencephaly-and-other-neural-tube-defects
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC8884297/
  16. https://www.cdc.gov/birth-defects/about/anencephaly.html
  17. https://my.clevelandclinic.org/health/diseases/15032-anencephaly
  18. https://medlineplus.gov/genetics/condition/anencephaly/
  19. https://www.nejm.org/doi/full/10.1056/NEJM199003083221006
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC4239538/
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC2758708/
  22. https://stacks.cdc.gov/view/cdc/106266/cdc_106266_DS1.pdf
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC11412643/
  24. https://www.sciencedirect.com/science/article/pii/S1875957225000828
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC2981339/
  26. https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1126209/full
  27. https://www.mdpi.com/2227-9059/10/5/965
  28. https://publications.aap.org/pediatrics/article/104/2/325/62434/Folic-Acid-for-the-Prevention-of-Neural-Tube
  29. https://jamanetwork.com/journals/jama/fullarticle/2807739
  30. https://onlinelibrary.wiley.com/doi/10.1002/bdra.23068
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC2929981/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC2770490/
  33. https://www.sciencedirect.com/science/article/abs/pii/S0013935120306502
  34. https://pmc.ncbi.nlm.nih.gov/articles/PMC8565987/
  35. https://pubmed.ncbi.nlm.nih.gov/34040637/
  36. https://pubmed.ncbi.nlm.nih.gov/22692891/
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC7614420/
  38. https://www.annualreviews.org/doi/10.1146/annurev-nutr-071714-034235
  39. https://www.sciencedirect.com/science/article/pii/S0022316622153848
  40. https://pmc.ncbi.nlm.nih.gov/articles/PMC8143787/
  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC9138472/
  42. https://rarediseases.org/rare-diseases/anencephaly/
  43. https://www.sciencedirect.com/science/article/abs/pii/S0070215322001089
  44. https://www.ncbi.nlm.nih.gov/books/NBK593617/
  45. https://www.birthdefectsresearch.org/primer/Screen-Prenatally.asp
  46. https://radiopaedia.org/articles/anencephaly?lang=us
  47. https://pubmed.ncbi.nlm.nih.gov/75505/
  48. https://fetalmedicine.org/fmf/1997_14.pdf
  49. https://pmc.ncbi.nlm.nih.gov/articles/PMC11079979/
  50. https://medlineplus.gov/lab-tests/alpha-fetoprotein-afp-test/
  51. https://jamanetwork.com/journals/jama/fullarticle/394421
  52. https://www.womenandinfants.org/services/medical-screening/afp-plus-quad-test
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC8462195/
  54. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1265090/full
  55. https://archive.cdc.gov/www_cdc_gov/ncbddd/birthdefects/surveillancemanual/chapters/chapter-4/chapter4-2a.html
  56. https://archive.cdc.gov/www_cdc_gov/ncbddd/birthdefects/surveillancemanual/quick-reference-handbook/anencephaly.html
  57. https://www.chop.edu/conditions-diseases/anencephaly
  58. https://www.childrenshospital.org/conditions/anencephaly
  59. https://www.brainfacts.org/diseases-and-disorders/neurological-disorders-az/diseases-a-to-z-from-ninds/anencephaly
  60. https://www.nature.com/articles/s41372-018-0227-3
  61. https://pubmed.ncbi.nlm.nih.gov/6705433/
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC5093842/
  63. https://www.gov.uk/government/publications/anencephaly-description-in-brief/anencephaly-information-for-parents
  64. https://fn.bmj.com/content/110/3/236
  65. https://pmc.ncbi.nlm.nih.gov/articles/PMC10562587/
  66. https://pubmed.ncbi.nlm.nih.gov/34185728/
  67. https://reproductive-health-journal.biomedcentral.com/articles/10.1186/s12978-022-01509-4
  68. https://link.springer.com/content/pdf/10.1186/s12978-022-01509-4.pdf
  69. https://www.cdc.gov/birth-defects/data-research/facts-stats/index.html
  70. https://onlinelibrary.wiley.com/doi/10.1002/bdra.23400
  71. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a2.htm
  72. https://bmjpublichealth.bmj.com/content/3/2/e001489
  73. https://pmc.ncbi.nlm.nih.gov/articles/PMC8660872/
  74. https://europepmc.org/article/pmc/pmc1012737
  75. https://publications.aap.org/pediatrics/article/116/3/580/68437/Decline-in-the-Prevalence-of-Spina-Bifida-and
  76. https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3016.2008.00975.x
  77. https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2014.302098
  78. https://www.dovepress.com/risk-factors-of-anencephaly-a-casecontrol-study-in-dessie-town-north-e-peer-reviewed-fulltext-article-PHMT
  79. https://www.nature.com/articles/s41598-021-02966-w
  80. https://pubmed.ncbi.nlm.nih.gov/1677062/
  81. https://www.nejm.org/doi/full/10.1056/NEJM199911113412012
  82. https://www.nejm.org/doi/full/10.1056/NEJM199212243272602
  83. https://pmc.ncbi.nlm.nih.gov/articles/PMC9875360/
  84. https://jamanetwork.com/journals/jama/fullarticle/2807740
  85. https://www.cdc.gov/folic-acid/index.html
  86. https://www.cdc.gov/mmwr/preview/mmwrhtml/00019479.htm
  87. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/folic-acid-for-the-prevention-of-neural-tube-defects-preventive-medication
  88. https://jamanetwork.com/journals/jama/fullarticle/193937
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC3257747/
  90. https://www.nejm.org/doi/full/10.1056/NEJMoa067103
  91. https://publichealthreviews.biomedcentral.com/articles/10.1186/s40985-018-0079-6
  92. https://www.who.int/tools/elena/interventions/folate-periconceptional
  93. https://www.who.int/news-room/events/detail/2017/10/15/default-calendar/WHO-CDC-symposium-guidelines-folate-concentrations-prevent-neural-tube-defects
  94. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X2200213-3/fulltext
  95. https://pubmed.ncbi.nlm.nih.gov/37103517/
  96. https://pubmed.ncbi.nlm.nih.gov/38169713/
  97. https://journals.biologists.com/dev/article/144/4/552/48315/Neural-tube-closure-cellular-molecular-and
  98. https://pmc.ncbi.nlm.nih.gov/articles/PMC2727639/
  99. https://www.sciencedirect.com/science/article/pii/S0002929707615249
  100. https://pmc.ncbi.nlm.nih.gov/articles/PMC3385168/
  101. https://academic.oup.com/hmg/article/26/6/1104/2901825
  102. https://www.sciencedirect.com/science/article/abs/pii/S0009898124021089
  103. https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.2643
  104. https://pmc.ncbi.nlm.nih.gov/articles/PMC4825100/
  105. https://www.nature.com/articles/nm0197-60
  106. https://www.childneurologyfoundation.org/disorder/anencephaly/
  107. https://pmc.ncbi.nlm.nih.gov/articles/PMC10036067/
  108. https://health.ucdavis.edu/news/headlines/worlds-first-stem-cell-treatment-for-spina-bifida-delivered-during-fetal-surgery--/2022/10
  109. https://clinicaltrials.gov/study/NCT00636233
  110. https://jamanetwork.com/journals/jama/fullarticle/388595
  111. https://jamanetwork.com/journals/jama/fullarticle/392525
  112. https://pubmed.ncbi.nlm.nih.gov/2586397/
  113. https://pmc.ncbi.nlm.nih.gov/articles/PMC2722973/
  114. https://law.justia.com/cases/florida/supreme-court/1992/79582-0.html
  115. https://journals.lww.com/transplantjournal/abstract/2017/08002/anencephalic_infants_as_organ_donors_after.107.aspx
  116. https://journalofethics.ama-assn.org/article/considering-organ-donation-anencephalic-neonates/2004-08
  117. https://journals.sagepub.com/doi/abs/10.1097/JPS.0000000000000299
  118. https://pediatricethicscope.org/article/life-prolonging-therapies-in-a-case-of-anencephaly/
  119. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6060
  120. https://www.sciencedirect.com/science/article/abs/pii/S0020729208002105
  121. https://pmc.ncbi.nlm.nih.gov/articles/PMC4589245/
  122. https://www.perinatalhospice.org/faqs
  123. https://pmc.ncbi.nlm.nih.gov/articles/PMC6469884/
  124. https://pubmed.ncbi.nlm.nih.gov/16827827/
  125. https://www.sciencedirect.com/science/article/abs/pii/S0266613818303735
  126. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.8649
  127. https://epublications.marquette.edu/cgi/viewcontent.cgi?article=1980&context=lnq
  128. https://pubmed.ncbi.nlm.nih.gov/2206156/
  129. https://www.sciencedirect.com/science/article/pii/088789949090113F
  130. https://pubmed.ncbi.nlm.nih.gov/11651985/
  131. https://digitalcommons.nyls.edu/cgi/viewcontent.cgi?article=1144&context=journal_of_human_rights
  132. https://theconversation.com/what-is-personhood-the-ethics-question-that-needs-a-closer-look-in-abortion-debates-182745
  133. https://pubmed.ncbi.nlm.nih.gov/11653953/
  134. https://pmc.ncbi.nlm.nih.gov/articles/PMC5606434/
  135. https://law.justia.com/cases/federal/appellate-courts/F3/16/590/492033/
  136. https://www.practicalbioethics.org/shared-decision-making-and-advance-care-planning/end-of-life-ethics/case-study-baby-k/
  137. https://www.cnn.com/2023/07/07/health/kentucky-abortion-anencephaly
  138. https://www.texastribune.org/2022/09/20/texas-abortion-ban-complicated-pregnancy/
  139. https://19thnews.org/2024/10/floridas-abortion-ban-fetal-anomalies/
  140. http://socialsciences.scielo.org/scielo.php?script=sci_arttext&pid=S0104-026X2008000100004
Add your contribution
Related Hubs
User Avatar
No comments yet.