Anencephaly of the brain in the fetus

Among the intrauterine malformations, there is such a type of irreversible violation of fetal brain embryonic morphogenesis as anencephaly. In ICD-10, this defect is attributed to congenital anomalies of the nervous system with the code Q00.0.

Epidemiology

According to medical statistics, fetal anencephaly is one of the most common types of neural tube defects, and in the United States about three pregnancies per 10 thousand are annually complicated by this anomaly. Although these figures do not take into account gestations interrupted by a miscarriage.

In the UK, such defects were found in 2.8 infants per thousand live births and in 5.3 cases per thousand spontaneously terminated pregnancies (for a period of at least eight weeks). [1]

And according to EUROCAT (European Commission for the Epidemiological Monitoring of Congenital Anomalies), over the course of 10 years (2000-2010), the total prevalence of anencephaly was 3.52 per 10 thousand live births. After prenatal diagnosis, of all pregnancies, 43% were interrupted for medical reasons. [2], [3]

Causes of the anencephaly

Three weeks after fertilization - during the  development of the human embryo  - neurulation occurs, that is, the formation of the neural tube, which is the germ of the brain and spinal cord.

A key cause of anencephaly in neural tube dysraphia is a violation of its closure at the fourth to fifth week of embryonic development. This anomaly occurs when the rostral end of the neural tube of the embryo, which forms the head of the fetus and transforms into the brain, remains open. This makes it impossible to further develop the basic structures and tissues of the brain.

A fetal anencephaly is characterized by the absence of hemispheres and, accordingly, the cortex and the neocortex of the brain that provides the highest functions of the central nervous system, as well as the bones of the cranial vault and the skin covering them. [4]

Risk factors

Embryonic morphogenesis is a very complicated process, therefore, not all probable risk factors for its violation leading to anencephaly have been identified so far.

It was found that with a  lack of folic acid  - pteroylglutamic acid (or vitamin B9), necessary for the synthesis of purine and pyrimidine bases of certain amino acids and DNA - neural tube defects, in particular, anencephaly and spinal cleavage, are observed much more often.

See details -  What causes folic acid deficiency?

In addition, the risk of impaired intrauterine development of the brain may be associated with:

• genetic problems (since the appearance of an anencephalus in the family increases the likelihood of this anomaly in subsequent pregnancies to 4-7%);
• persistent maternal viral infections;
• uncontrolled diabetes mellitus, other endocrine pathologies and obesity;
• the negative impact of the environment, in particular, ionizing radiation, provoking spontaneous mutations;
• teratogenic effects of chemicals, including narcotic, as well as alcohol and drugs.

More information - Injection of toxic substances into pregnancy and the fetus

Pathogenesis

Closing an already formed neural tube occurs 28-32 days after conception, and researchers see the pathogenesis of anencephaly as a violation of the formation of an embryo of the central nervous system of the fetus even when the neural plate is formed (between 23 and 26 days after conception), with which, in fact, the stage begins neurula, ending with the closure of the plate into the neural tube.

The essence of the violation of the morphogenesis of the brain in the embryo with this anomaly is that the opening of the neural tube channel (neuropore) at the front end of the embryo remains open.

Further, the neural tube bends with the formation of protrusions for the formation of differentiated nerve stem cells of the anterior, middle and hindbrain. And for the formation of the cerebral hemispheres (end brain), the pterygoid plate of the midbrain should expand. But since the front neuropore did not close in time, the formation of the skull acquires an abnormal character, and the morphology of the brain tissue changes, losing its functions.

Given the leading role in embryonic development and control of the formation of fetal organs and tissues, homeosis or homeotic genes (HOX genes or morphogens) that are located on different chromosomes and contain DNA sequences encoding protein transcription factors, the possibility of impairment of neurulation at the gene level should be considered. [5]

Symptoms of the anencephaly

Despite the individual appearance of newborns, there are clear external signs of children with anencephaly.

Immediately after childbirth, the first signs of this birth defect are visible: a deformed baby's skull with missing bones of its arch - the occipital or parietal; a partial absence of the frontal bone or, less commonly, the temporal bone is also possible. There are no cerebral and cerebral hemispheres, and in a skin-free defect of the skull there may be exposed tissue (glia), or the existing structures - the brain stem, the incompletely formed basal nuclei of the forebrain - are covered with a thin membrane of connective tissue. [6]

Another external sign is the eyeballs that stand out prominently from the orbits, which is explained by the underdevelopment of the frontal bone of the skull, which forms the upper edge of the eye sockets.

In 80% of cases, other congenital anomalies do not accompany anencephaly, but cleavage of the soft palate (cleft palate) may be observed. [7]

Complications and consequences

Infants with this malformation of the brain usually die during childbirth or shortly after birth, since the central nervous system does not function with such an anomaly of the brain (there are only some basic reflexes, and not always). And experts note 100% mortality among babies with anencephaly.

On rare cases of longer life - at the end of the publication.

Diagnostics of the anencephaly

A  prenatal diagnosis is performed, and the diagnosis of fetal anencephaly can be made during pregnancy - in the early stages.

This can be done by visualization - instrumental diagnostics using ultrasonography.

Anencephaly is detected on ultrasound - in the form of an open neural tube defect during an ultrasound examination of the fetus at the 12th week of pregnancy. In this case, polyhydramnion (an excess of amniotic fluid) is often observed. Therefore, their analysis may be necessary -  amnioscopy and amniocentesis .

In the future, if the pregnancy did not terminate spontaneously, during an  ultrasound of the fetus

Anencephaly, microcephaly, and hydrocephalus of the fetus are differentiated, since with  microcephaly the  skull is underdeveloped in the presence of convolutions having an abnormal width. And in the case of  dropsy of the brain in a newborn  or congenital hydrocephalus, the size of the head is increased.

In addition, for a period of 13-14 weeks, an analysis of alpha-fetoprotein in the blood of  pregnant women is needed , since in the presence of anencephaly in the fetus, the level of this specific embryonic protein is always increased. 

Differential diagnosis

Differential diagnosis is carried out, first of all, with the occipital cerebral hernia of the newborn (encephalocele), which occurs due to a partially uncovered cranial vault; microhydranencephaly, the lobar type of  holoprosencephaly , schizocephaly.

Treatment of the anencephaly

Treatment of anencephaly in a baby - in cases when he is alive after birth - is palliative, since this defect is irreversible.

Prevention

Although not all etiological factors leading to anencephaly are known, numerous studies have proven the effectiveness of folic acid intake  in planning pregnancy : with a daily dose of 0.8 mg.

Also see -  Folic Acid During Pregnancy

Forecast

A logical question arises: how long do people live with anencephaly? Regarding the life expectancy of infants with this congenital anomaly, the prognosis cannot be at least any long-term positive...

According to British obstetricians, a little more than 70% of newborns lived in a very short time after birth (from a few hours to two to three days), and only 7% lived for about four weeks. Then death came from cardiorespiratory collapse - cessation of breathing and cardiac arrest. [8], 

However, there have been several cases in which surviving children with anencephaly, after being born, lived for longer periods of time.

For example, the girl Angela Morales from Providence (Rhode Island, USA) lived for 3 years and 9 months, at the age of two months she underwent surgery to close the opening on the occipital part of the skull, since there was a constant leakage of cerebrospinal fluid.

A boy Nicolas Cox, born in Pueblo (Colorado, USA), lived two months longer.

And Jackson Emmett Buell (born August 2014 in Orlando, Florida) with the absence of 80% of the brain (including the cerebral hemispheres) and most of the skull, is still alive. But his diagnosis is microhydranencephaly, and he has a brain stem and thalamus not damaged, and there are also some cranial nerves.