Anencephaly is a serious congenital malformation due to failure of the neural tube to close in the first weeks of pregnancy. A condition incompatible with life, the onset of which can be influenced by genetic, environmental and nutritional factors. Prevention with folic acid remains the most effective tool to reduce the risk today
Anencephaly is a rare and very serious congenital malformation that belongs to the group of neural tube defects. It can develop in the very first weeks of pregnancy, often when the woman does not yet know she is pregnant.
Precisely for this reason, talking about it in a clear and accessible way is essential: to inform, but above all to prevent and best support the couple.
What is anencephaly
We talk about anencephalus, fetal anencephaly or severe anencephaly when we indicate a condition in which the brain and skull bones do not develop correctly. For this reason it is sometimes described as a “brainless fetus” situation, although in reality a small part of the central nervous system, the brainstem, may be present.
Anencephaly is caused by a congenital defect of the neural tube, due to the failure of a structure, called the anterior neuropore, to close between the 23rd and 26th day after conception. This event involves the total or partial absence of the cranial vault, the cerebral hemispheres and the cerebellum.
The term comes from Greek and literally means “brainless”. It is a relatively rare condition, which affects approximately 1 in 1,000–2,000 pregnancies, affects females more than twice as often as males and has a multifactorial origin, with a combination of environmental, genetic and maternal health and lifestyle factors. This malformation is particularly widespread in some areas of China, Mexico, Turkey and the British Isles, probably due to a combination of dietary lifestyles and genetic characteristics of the native populations.
Neural tube defects
To understand what anencephaly is, we must start from the neural tube, an embryonic structure that forms very early, between the 17th and 30th day after the last ovulation. From this structure the brain and spinal cord originate, first through the process of “neurulation” (the initial neural plate folds and then closes) forming a hollow cylindrical tube. At this point the tube, starting from the center, closes at the two ends (neuropores), the front one from which the brain will originate and the rear one which will form the spinal cord.
When the neural tube does not close correctly, so-called “defects” appear, some of which are incompatible with life, such as anencephaly; others, such as meningocele or spina bifida, may instead be compatible and, in some cases, treatable.
During the first trimester of pregnancy, even before the diagnosis of anencephaly, a progression of events can be observed. In fact, acrania (absence of the cranial vault) is detected, which evolves into exencephaly (i.e. the growth of nervous tissue outside the skull) and finally into anencephaly towards the end of the first trimester.
Causes and risk factors
Anencephaly, as mentioned, has a multifactorial origin, meaning there is not a single cause, but a combination of genetic, clinical, environmental and behavioral factors, which together influence the appearance of mutations and the development of the organism, starting from conception.
The main and documented risk factor is the deficiency of folic acid, an essential vitamin for correct cell division and embryonic development, being involved in the process of DNA synthesis and in the correct functioning of the nervous system. An adequate intake of at least 400 mcg (0.4 mg) per day, combined with a healthy diet, reduces the risk of neural tube defects by up to 70%.
Other factors that may increase the risk of anencephaly include:
- Zinc deficiency. Zinc has the ability to regulate nerve cell growth factors.
- Insulin-dependent diabetes mellitus. Incorrect management of therapy and blood sugar levels interfere with embryonic development.
- Maternal obesity. During pregnancy, fat accumulation can induce an inflammatory state in the uterine environment, interfering with fetal neurodevelopment, metabolism and the formation of the immune system.
- Taking some medications. Some antiepileptics (valproic acid, carbamazepine), opioids (hydrocodone), antidepressants, high-dose antibiotics, and some antihypertensives, in addition to drug use, are related to the appearance of congenital neural tube defects.
- Exposure of the fetus to high temperatures. In the first weeks of pregnancy, hyperthermia, saunas and very hot baths in hot tubs, if frequent, have been associated with an increased risk.
- Genetic factors. Some variants, such as those of the MTHFR gene, which is involved in folate metabolism, interfere with neural development. In rare cases, familial forms of anencephaly are observed.
Clinical appearance and associated malformations
From a clinical point of view, anencephaly presents with recognizable characteristics: the face of the fetus typically appears flattened, with protruding eyes (exophthalmos), there is a chronic absence of bones with exposure of the nervous tissue and, in some even more serious cases, a cleft palate may be present.
Many malformations and congenital defects associated with anencephaly have been observed through autopsies; in most cases an absence of the adrenal glands was found. Cardiac defects, spinal anomalies, omphalocele (abdominal wall defect) and skeletal dysplasias (deficit in bone and cartilage development) may also be present.
Prenatal diagnosis
The diagnosis of anencephaly can occur as early as the first trimester of pregnancy. In fact, through an ultrasound between the 11th and 12th week, the absence of the cranial vault and the exposure of the brain structures to the amniotic fluid can be observed.
In the first trimester the so-called “Mickey Mouse” sign is visible, which subsequently evolves into the “frog” sign, when the structure of the head is completely flattened behind the face and the eyes are protruding. Tests may show an increase in the values of alpha-fetoprotein (AFP), a glycoprotein produced by the liver and the structure of the yolk sac, both in the blood (with the tri-test the values of AFP, beta-hCG and unconjugated estriol are detected, whose values, if high, indicate a risk of neural tube defects) and in the amniotic fluid (with amniocentesis).
Only in doubtful cases or in the presence of correlations with syndromes and other congenital defects can more advanced diagnostics be used, such as magnetic resonance imaging. Often it is also possible to observe an excessive accumulation of amniotic fluid (polyhydramnios), due to impaired fetal swallowing.
Genetic counseling plays a very important role in preventing the risk of anencephaly, as well as other neural tube defects, when there are previous cases. Recurrence in these cases has very low percentages (<5%), and is always correlated to the multifactorial nature and consistency of multiple risk factors. This is an important step to help parents understand the diagnosis and the implications, to calmly plan a pregnancy, improving where possible lifestyles, management of maternal chronic pathologies and related complications.
Prognosis
Anencephaly, unfortunately, is a condition incompatible with life. About 50% of fetuses die before birth, and among those that are born alive, survival is limited to a few hours or days. Only a minority of babies (about 32%) carried to term are born alive and with intensive care support they can survive from a week to a maximum of 2 or 3 months. However, a case is reported in the literature of a child who survived with anencephaly for up to 28 months, despite the absence of higher neurological functions and respiratory problems.
Treatment and assistance
There is no cure for anencephaly, in cases of survival the assistance is palliative and aims to support the newborn in the most humane and painless way possible. Treatment always includes hydration, nutrition and basic respiratory support, as well as trying to contain the frequent respiratory infections to which an anencephalic newborn is particularly subject. Intensive resuscitation is almost never an option as it does not change the prognosis.
Choice about continuing the pregnancy
Receiving a diagnosis of anencephaly is a very difficult experience emotionally, because it places parents faced with a complex choice: to continue or terminate the pregnancy, considering the high risk of prenatal death or in the first hours after birth.
This is a deeply personal decision, requiring accurate information and adequate multidisciplinary support. In these situations, clinical, psychological and emotional aspects are inevitably intertwined, just as the religious beliefs and ethical choices that the couple feels closest to their sensitivity can have an important role.
The role of professionals is to accompany parents along this path, offering clinical, psychological and practical support, respecting the decisions made by the couple and without judging attitudes.
Prevention
The prevention of anencephaly and, in general, of neural tube defects, occurs above all through the intake of folic acid before conception and during the first trimester of pregnancy. It has in fact been shown that this integration significantly reduces the risk of these malformations.
The guidelines recommend a dose of 0.4 mg per day for the general population and 4-5 mg per day for women who have already had a pregnancy with neural tube defects. In these cases, the higher dosage should be taken under medical supervision and started at least one month before seeking pregnancy.
In general, it is advisable to start supplementation at least 1-3 months before conception and continue until the 12th week of pregnancy, combining it with a diet rich in folate. Sources include, for example, green leafy vegetables, legumes, citrus fruits, dried fruit, liver, chicken and egg yolk, although cooking can reduce part of the folate content of foods.
Thanks to information campaigns, preconception counseling and, in some countries, the enrichment of folic acid in some elements (such as cereals), in recent years a significant reduction in cases of anencephaly and other neural tube defects has been observed globally.
Subsequent pregnancies and risk of recurrence
After a pregnancy in which the fetus has anencephaly, the risk of the condition recurring in a subsequent pregnancy is approximately 3%; It also increases the risk of other neural tube defects, such as spina bifida.
For this reason it is advisable to carry out a genetic consultation before a new pregnancy, together with correct folic acid supplementation and early checks.
These are particularly delicate topics, because they are linked to very painful experiences and complex eventualities. This is why it is essential that future parents can be accompanied with competence, attention and sensitivity throughout the entire process.
