most common presentation of fetus with anencephaly

Anencephaly

Children's hospital of philadelphia, what is anencephaly.

Anencephaly is a condition present at birth that affects the formation of the brain and the skull bones that surround the head. Anencephaly results in only minimal development of the brain. Often, the brain lacks part or all of the cerebrum (the area of the brain that is responsible for thinking, vision, hearing, touch, and movement). There is no bony covering over the back of the head and there may also be missing bones around the front and sides of the head.

What causes anencephaly?

Anencephaly is a type of neural tube defect that occurs in about one of 10,000 pregnancies in the U.S. each year. The actual number is unknown because many of these births result in miscarriages. According to the CDC, one in every 4,859 newborns in the United States has this condition.

During pregnancy, the human brain and spine begin as a flat plate of cells, which rolls into a tube, called the neural tube. If all or part of the neural tube fails to close, leaving an opening, this is known as an open neural tube defect, or ONTD. This opening may be left exposed or covered with bone or skin.

Anencephaly and spina bifida are the most common ONTDs, while encephaloceles (where there is a protrusion of the brain or its coverings through the skull) are much rarer. Anencephaly occurs when the neural tube fails to close at the base of the skull, while spina bifida occurs when the neural tube fails to close somewhere along the spine.

ONTDs happen to couples without a prior family history of these defects in the vast majority of cases. ONTDs result from a combination of genes inherited from both parents, coupled with environmental factors. For this reason, ONTDs are considered multifactorial traits, meaning many factors , both genetic and environmental, contribute to their occurrence.

Once a child has been born with an ONTD in the family, the chance for an ONTD to happen again is increased by 4 to 10 percent. It is important to understand that the type of neural tube defect can differ the second time. For example, one child could be born with anencephaly, while the second child could have spina bifida.

What are the symptoms of anencephaly?

The following are the most common symptoms of anencephaly. However, each child may experience symptoms differently. Symptoms may include:

Absence of bony covering over the back of the head

Missing bones around the front and sides of the head

Folding of the ears

Cleft palate. A condition in which the roof of the child's mouth does not completely close, leaving an opening that can extend into the nasal cavity.

Congenital heart defects

Some basic reflexes, but without the cerebrum, there can be no consciousness and the baby cannot survive

The symptoms of anencephaly may resemble other problems or medical conditions. Always consult your child's doctor for a diagnosis.

How is anencephaly diagnosed?

The diagnosis of anencephaly may be made during pregnancy, or at birth by physical examination. The baby's head often appears flattened due to the abnormal brain development and missing bones of the skull.

Diagnostic tests performed during pregnancy to evaluate the baby for anencephaly include the following:

Alpha-fetoprotein. A protein produced by the fetus that is excreted into the amniotic fluid. Abnormal levels of alpha-fetoprotein may indicate brain or spinal cord defects, multiple fetuses, a miscalculated due date, or chromosomal disorders.

Amniocentesis. A test performed to determine chromosomal and genetic disorders and certain birth defects. The test involves inserting a needle through the abdominal and uterine wall into the amniotic sac to retrieve a sample of amniotic fluid.

Ultrasound (also called sonography). A diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels.

Blood tests

Treatment of the newborn with anencephaly

There is no cure or standard medical treatment for anencephaly. Treatment is supportive.

Experiencing the loss of a child can be very traumatic. Grief counseling services are available to help you cope with the loss of your child.

Future pregnancies

Genetic counseling may be recommended by the doctor to discuss the risk of recurrence in a future pregnancy as well as vitamin therapy (a prescription for folic acid) that can decrease the recurrence for ONTDs. Extra folic acid, a B vitamin, if taken one to two months prior to conception and throughout the first trimester of pregnancy, has been found to decrease the reoccurrence of ONTDs for couples who have had a previous child with an ONTD. The CDC also recommends to avoid smoking and drinking alcohol during pregnancy.

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Fetology: Diagnosis and Management of the Fetal Patient, 2e

Chapter 7: Anencephaly

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SONOGRAPHIC FINDINGS
DIFFERENTIAL DIAGNOSIS
ANTENATAL NATURAL HISTORY
MANAGEMENT OF PREGNANCY
FETAL INTERVENTION
TREATMENT OF THE NEWBORN
SURGICAL TREATMENT
LONG-TERM OUTCOME
GENETICS AND RECURRENCE RISK
Full Chapter
Supplementary Content

Accounts for approximately one-half of all cases of neural tube defects.

Incidence is approximately 0.3/1000 births. Maternal risk factors include Hispanic ethnicity, pregestational diabetes, obesity, and hyperthermia.

First trimester sonographic findings include a reduced crown-rump length, and the “Mickey Mouse” sign in the coronal view. Second trimester findings include an absent upper cranial vault and no cerebral tissue above the level of the orbits.

Differential diagnosis includes amniotic bands, ruptured encephalocele, and iniencephaly.

Approximately a quarter of affected pregnancies are complicated by polyhydramnios.

Consider prenatal karyotype if associated anomalies present. If anencephaly is isolated, consider postnatal karyotype.

Condition is uniformly fatal postnatally. Only 7% of fetuses die in utero.

Preconceptual folic acid (4 mg/day) significantly decreases recurrence if anomaly is isolated and not due to a chromosomal or single-gene disorder.

Anencephaly [congenital absence of a major portion of the brain, skull, and scalp ( Medical Task Force on Anencephaly, 1990 )] is the most severe and single most common prenatally detected neural tube defect ( Goldstein and Filly, 1988 ). Although the cerebral hemispheres can develop in this condition, any exposed brain tissue is subsequently destroyed (see Chapter 13 ). This produces a hemorrhagic, fibrotic mass of neurons and glia, with no functional cortex. The brainstem and cerebellum may be spared. Despite the severe brain abnormalities, the facial bones and base of the skull are nearly normally formed. The frontal bone, however, is always absent and the brain tissue is always abnormal.

Anencephaly is sometimes divided into two subcategories. The milder form is known as meroacrania, which describes a small defect in the cranial vault covered by the area cerebrovasculosa. The more severe form is holoacrania, in which the brain is completely absent.

Van Allen et al. (1993) proposed that multisite neural-tube closure provides the best explanation for neural tube defects in humans. The closure sites are most likely controlled by separate genes expressed during embryogenesis. These authors hypothesized that the majority of neural tube defects could be explained by a failure of fusion of one of the closures or their contiguous neuropores. Anencephaly results from failure of closure site 2 for meroacranium and closures 2 and 4 for holoacranium. Folate deficiency is thought to affect the closures of sites 2 and 4. This hypothesis has been demonstrated in humans with more than one neural tube defect ( Pantzar et al., 1993 ).

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Second Opinion

most common presentation of fetus with anencephaly

Anencephaly in Children

What is anencephaly in children?

Anencephaly is a condition that is present at birth (birth defect). It affects the brain and skull bones. With this condition, the brain is not fully formed. It often lacks part or all of the cerebrum. The cerebrum is the area of the brain used for thinking, seeing, hearing, touch, and movement. There is also no bone on the back of the head. Bones may also be missing on the front and sides of the head. Anencephaly is a type of neural tube defect. It occurs in about 3 of 10,000 pregnancies in the U.S. each year. The exact number is not known because many of these pregnancies end in miscarriages. This condition most often leads to death in days or weeks.

What causes anencephaly in a child?

During pregnancy, the brain and spine begin as a flat plate of cells. This plate rolls into a tube called the neural tube. The tube is completely formed 28 to 32 days after conception. If all or part of the neural tube fails to close, this leaves an opening. The opening is called an open neural tube defect. The opening in the tube may be left exposed. Or it may be covered with bone or skin. Anencephaly is when the neural tube fails to close at the base of the skull.

Neural tube defects may be caused by genes passed on from both parents and by environmental factors. Some of these factors include obesity, uncontrolled diabetes in the mother, and some prescription medicines. In most cases, a child with a neural tube defect has no family history of this problem.

Which children are at risk for anencephaly?

Once a child with a neural tube defect has been born in the family, the chance that this problem will happen in another child rises to 1 in 25. The type of neural tube defect can differ the second time. For example, one baby could be born with anencephaly. A second baby could have spina bifida instead. Children born to mothers taking certain medicines are at risk of anencephaly. It is important to talk with your healthcare provider about the safety of your medicines when pregnant. Don't stop or change your medicines without first talking with your healthcare provider.

What are the symptoms of anencephaly in a child?

Symptoms can occur a bit differently in each child. They can include:

No bones on the back of the head

Missing bones on the front and sides of the head

Large areas of brain missing

Folding of the ears

Split in the roof of the mouth (cleft palate)

Congenital heart defects

The symptoms of anencephaly can be like other health conditions.

How is anencephaly diagnosed in a child?

The diagnosis of anencephaly may be made during pregnancy. Tests done during pregnancy to check for anencephaly include:

Blood test. A test called a quad screen measures 4 substances in the mother's blood to see if there is an increased risk for neural tube defects and other problems. This test is done between 16 and 18 weeks of pregnancy. It measures levels of alpha-fetoprotein (AFP) and other things in the blood. AFP is a protein made by the baby growing in the womb. If a baby has an open neural tube defect, the AFP level in the mother's blood will be higher than normal. The test isn’t conclusive. But it can show if your baby is at risk for an open neural tube defect. The test can show if you need more testing. It is advised that this blood test be offered to all pregnant women.

Prenatal ultrasound. This imaging test uses high-frequency sound waves and a computer to make images of blood vessels, tissues, and organs. Ultrasounds let healthcare providers see the internal organs as they function. They also show blood flow through blood vessels. Prenatal ultrasound may be able to find an open neural tube defect. Your provider may also use ultrasound to look at other organs and body systems of the baby.

Amniocentesis. This test looks at a small sample of the fluid that surrounds the baby in the womb. The healthcare provider uses a long, thin needle to reach the amniotic sac. He or she takes the sample of fluid and checks it for AFP. The test may not be able to find small or closed defects.

After birth, a diagnosis is made by physical exam. The baby's head often appears flattened because of the abnormal brain growth and missing bones of the skull.

How is anencephaly treated in a child?

There is no cure or standard treatment for anencephaly. Treatment is supportive. This means efforts are made to keep the baby as comfortable as possible. Anencephaly most often leads to death in days or weeks. Grief counseling services are available to help parents cope with the loss of their child.

How can I help prevent anencephaly in my child?

The neural tube closes 28 to 32 days after a baby is conceived. This is before many women are aware that they are pregnant. Normal brain and spinal cord development may be affected during these first 3 to 8 weeks of pregnancy by:

Not enough vitamins such as folic acid and other nutrients

Using prescription medicine or alcohol

Being around hazardous chemicals and other substances

Genetic problems

Researchers have found that a woman who gets enough folic acid (vitamin B-9) can help lower the risk for neural tube defects. Folic acid is found in some leafy green vegetables, nuts, beans, citrus fruits, and fortified breakfast cereals. It is recommended that all women of childbearing age take a multivitamin that has folic acid. Folic acid is in prenatal vitamins. Getting this vitamin before a woman knows she is pregnant and early in pregnancy is most important.

If you have had a child with a neural tube defect, your healthcare provider may recommend taking a larger amount of folic acid before your next pregnancy. Your provider may tell you to take this extra amount for 1 to 2 months before conception and then through the first trimester.

Your healthcare provider may also advise genetic counseling. You can discuss with a counselor the risk for a neural tube defect in a future pregnancy. Also talk with your provider about getting a prescription for folic acid to lower the risk for another open neural tube defect.

When should I call my child’s healthcare provider?

Call the healthcare provider if your child has:

Symptoms that don’t get better, or get worse

New symptoms

Key points about anencephaly in children

Anencephaly is a condition that is present at birth (birth defect). It affects the brain and skull bones. The brain is not fully formed. There is also no bone on the back of the head. Bones may also be missing on the front and sides of the head.

Anencephaly most often leads to death in days or weeks.

Anencephaly is a type of neural tube defect. Neural tube defects are caused by genes passed on from both parents and by environmental factors.

You may need tests while you are pregnant to check for anencephaly in your growing baby.

If you have had a child with a neural tube defect, your healthcare provider may recommend taking a larger amount of folic acid before your next pregnancy.

Your healthcare provider may also advise genetic counseling. You can discuss with a counselor the risk for a neural tube defect in a future pregnancy.

Tips to help you get the most from a visit to your child’s healthcare provider:

Know the reason for the visit and what you want to happen.

Before your visit, write down questions you want answered.

At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.

Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.

Ask if your child’s condition can be treated in other ways.

Know why a test or procedure is recommended and what the results could mean.

Know what to expect if your child does not take the medicine or have the test or procedure.

If your child has a follow-up appointment, write down the date, time, and purpose for that visit.

Know how you can contact your child’s provider after office hours. This is important if your child becomes ill and you have questions or need advice.

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Management Options and Outcomes

Of those fetuses with anencephaly, a small portion will die while still in the uterus ( intrauterine fetal demise or stillbirth ). Approximately 25% will have excessive amniotic fluid around the fetus ( polyhydramnios ). Polyhydramnios may cause extra stretching of the uterus resulting in preterm contractions. Sometimes, these patients require cesarean section because the fetus is breech. These infants will die in the immediate newborn period.

If prenatal screening is performed to detect spinal cord ( neural tube ) defects, the maternal serum alpha-fetoprotein level ( MSAFP ) will be significantly elevated in 90% of fetuses with anencephaly (Medical Task Force on Anencephaly, 1990). A detailed ultrasound examination is indicated for all patients with significantly elevated MSAFP levels. If there are no other abnormalities and the anencephaly is considered isolated, then a test to determine if there is a chromosomal abnormality may be recommended ( amniocentesis ). The chromosomes represent the instructions for how a fetus should form. It is quite likely that the chromosomes will be normal. Most fetuses with anencephaly deliver around 37 weeks of gestation (Melnick and Myrianthopoulos,1987). Because pregnancy with a fetus with anencephaly carries an increased medical risk for the mother, prospective parents may be offered the opportunity to terminate, especially if the diagnosis is made prior to 24 weeks of gestation. Cesarean delivery is indicated only for maternal health considerations or, perhaps, if the fetus is breech.

Candidacy for Fetal Treatment

There is no fetal intervention recommended for anencephaly.

Newborn Care

The diagnosis of anencephaly can be confirmed on physical examination when the following criteria are met: a large portion of the skull is absent, the scalp is absent over the skull defect, and a hemorrhagic, fibrotic mass of tissue is exposed to the environment. The newborn will seem unconscious because the upper brain portions ( cerebral hemispheres) are absent or not functioning. The parts that control the breathing, heartbeat and body temperature will be functional. The newborn has reflex responses to pain. Most newborns will die within the first few hours or days of life, though about 10% may live up to one week.

Surgical Management

Surgical treatment is not applicable in anencephaly.

Additional Information

The major issue in long-term outcome is the potential use of anencephalic fetuses or infants as organ donors. Difficulties exist, however, because of the traditional means of determining brain death for organ donors. For babies with anencephaly, the diagnosis of brain death depends on documentation of disappearance of previously existing brainstem functions ( i.e., breathing or spontaneous movements ), Most major organs from anencephalic infants are smaller than average for body size and have often not formed appropriately. Therefore, these organs might not be able to be donated.

A family history of spina bifida and/or anencephaly is one of the strongest risk factors for recurrence. Most cases of anencephaly have a recurrence risk of between 2% and 5% following a single case (Medical Task Force on Anencephaly, 1990). Some cases of anencephaly are associated with chromosomal abnormalities such as trisomies 13 and 18, and triploidy. For women who have previously had a fetus or infant affected with anencephaly, the Centers for Disease Control and Prevention (CDC) recommends increasing the intake of folic acid to 4000 mcg (4mg) per day beginning at least 1 month prior to conception (Committee on Genetics,1999).

A Difficult Diagnosis

The Fetal Health Foundation was founded by parents seeking hope for a fetal diagnosis. We try to provide accurate medical information, support, and hope. In the case of a diagnosis like this, we also want to offer resources that can help parents make the most of their time with their child.

Global prevalence of congenital anencephaly: a comprehensive systematic review and meta-analysis

Nader Salari 1 ,
Behnaz Fatahi 2 ,
Reza Fatahian 3 ,
Payam Mohammadi 4 ,
Adibeh Rahmani 5 ,
Niloofar Darvishi 2 ,
Mona Keivan 6 ,
Shamarina Shohaimi 7 &
Masoud Mohammadi ORCID: orcid.org/0000-0002-5722-8300 8

Reproductive Health volume 19 , Article number: 201 ( 2022 ) Cite this article

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Anencephaly is a fatal congenital anomaly characterized by the absence of brain hemispheres and cranial arch. Timely preventive measures can be taken by knowing the exact prevalence of this common neural tube defect; thus, carried out through systematic review and meta-analysis, the present study was conducted to determine the worldwide prevalence, incidence and mortality of anencephaly.

Cochran’s seven-step instructions were used as the guideline. Having determined the research question and inclusion and exclusion criteria, we studied MagIran, SID, Science Direct, WoS, Web of Science, Medline (PubMed), Scopus, and Google Scholar databases. Moreover, the search strategy in each database included using all possible keyword combinations with the help of “AND” and “OR” operators with no time limit to 2021. The I 2 test was used to calculate study heterogeneity, and Begg and Mazumdar rank correlation tests were employed to assess the publication bias. Data were analyzed by Comprehensive Meta-Analysis software (Version 2).

In this study, the statements of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) were used. In the first stage, 1141 articles were found, of which 330 duplicate studies were omitted. 371 articles were deleted based on the inclusion and exclusion criteria by reviewing the title and abstract of the study. 58 articles were removed by reviewing the full text of the article because it was not relevant to the research. 360 studies with a sample size of 207,639,132 people were considered for the meta-analysis. Overall estimate of the prevalence, incidence and attenuation of anencephaly worldwide were 5.1 per ten thousand births (95% confidence interval 4.7–5.5 per ten thousand births), 8.3 per ten thousand births (95% confidence interval 5.5–9.9 per ten thousand births), 5.5 per ten thousand births (95% confidence interval 1.8–15 per ten thousand births) respectively the highest of which according to the subgroup analysis, belonged to the Australian continent with 8.6 per ten thousand births (95% confidence interval 7.7–9.5 per ten thousand births).

The overall prevalence of anencephaly in the world is significant, indicating the urgent need for preventive and treating measures.

Plain Language summary

Anencephaly is a fatal congenital anomaly characterized by the absence of brain hemispheres and cranial arch. Cochran’s seven-step instructions were used as the guideline. Having determined the research question and inclusion and exclusion criteria, we studied MagIran, SID, Science Direct, WoS, Web of Science, Medline (PubMed), Scopus, and Google Scholar databases. Moreover, the search strategy in each database included using all possible keyword combinations with the help of “AND” and “OR” operators with no time limit to 2021. Out of 1141 initial articles found, and after excluding repetitive ones in various databases and those irrelevant to inclusion criteria, 360 studies with a sample size of 207,639,132 people were considered for the meta-analysis. Overall estimate of the prevalence, incidence and attenuation of anencephaly worldwide were 5.1 per ten thousand births (95% confidence interval 4.7–5.5 per ten thousand births), 8.3 per ten thousand births (95% confidence interval 5.5–9.9 per ten thousand births), 5.5 per ten thousand births (95% confidence interval 1.8–15 per ten thousand births) respectively the highest of which according to the subgroup analysis, belonged to the Australian continent with 8.6 per ten thousand births (95% confidence interval 7.7–9.5 per ten thousand births). The overall prevalence of anencephaly in the world is significant, indicating the urgent need for preventive and treating measures.

Peer Review reports

Neural Tube Defects (NTDs) are considered the most common congenital anomalies of the central nervous system (CNS) [ 1 ], and the second most serious ones after inborn heart defects [ 2 ]. Non-spontaneous neural tube closure between the 3rd and 4th weeks of intrauterine growth is considered as the leading cause of this defect [ 1 ]. Regarding the etiology of these defects, most cases are attributed to the interaction between different genes and environmental factors, known as a multifactorial inheritance [ 3 ]. Studies indicate that immediate family members are more at risk compared to others; in other words, if a child is born with NTD, the risk of recurrence in future pregnancies is between 25 and 50 times higher than in general cases [ 4 , 5 , 6 ]. Moreover, diabetes mellitus, using valproic acid to treat epilepsy during pregnancy, obesity, zinc deficiency, hyperthermia, and folate deficiency are all predisposing factors for neural tube defects [ 7 , 8 ].

Though being significantly various in different geographical areas, the incidence of NTD is generally around 1 in 1000 live births or (NTD affects about 1 in 1000 live births on average, however this varies greatly by area.) [ 4 , 9 ]. Pathologically, neural tube defects vary from a small, uncomplicated opening in the posterior canal of the vertebrae to the failure of the entire neural tube to close, leading to the most severe type of defect that is craniorachischisis [ 10 ]. The most recurring cases include anencephaly, spina bifida, and encephalocele [ 10 ].

Anencephaly is a fatal congenital malformation characterized by the absence of hemispheres of the brain and cranial arch [ 11 ]. Anencephaly is the most common CNS disorder in the Western world, occurring 37 times more frequently in women than men [ 12 ]. Babies born with such defects generally die at birth or shortly thereafter while newborns with spina bifida and encephalocele require special medical care and surgery to survive [ 13 ]. Prevalence of anencephaly mortality (100%), compared to Spina bifida (7%) and encephalocele (46%), is significantly higher [ 14 ]; thus, anencephaly is considered as a taxing burden on public health worldwide that may lead to significant human resources loss [ 15 ].

Frog-like appearance, short neck, bulging eyes, and large tongue are characteristic features of infants with anencephaly [ 16 ]. About 12% of cases of anencephaly are associated with other structural abnormalities [ 17 ], including Cleft lip, cleft palate, clubfoot and omphalocele (Anencephaly is linked to additional structural abnormalities in around 12% of cases [ 17 ], such as cleft lip, cleft palate, clubfoot, and omphalocele) [ 16 ]. Anencephaly was the first congenital anomaly to be detected by ultrasound, and it can be diagnosed at weeks 12–13 of pregnancy while preventive measures include controlling known risk factors and offering medical counseling to couples about termination of pregnancy [ 16 ]. Previous studies have demonstrated that anencephaly is a multifactorial process that is controlled by genes and numerous other environmental factors. However, recent studies reveal that folic acid supply before and in the early stages of pregnancy (1 to 3 months before pregnancy and up to 12 weeks of gestation) can dramatically prevent anencephaly and reduce its prevalence by 50–70% [ 18 ]. The U.S. Public Health Service and the Food and Nutrition Council of the Institute of Medicine, along with the National Research Council, recommend that all women of childbearing potential can take 0.4 mg of folic acid daily to reduce the risk of developing neural tube defects [ 19 , 20 ].

Annually, about 300,000 babies are born with neural tube defects, resulting in 88,000 deaths and 8.6 million lifelong disabilities [ 21 ]. The occurrence of anencephaly varies over time and geographically. For instance, the prevalence of this defect in northern Iran in 1998–2005 was estimated at 12 per 10,000 births [ 22 ] while In Texas, the United States, 2.81 per 10,000 births during 1999–2003 were reported [ 23 ]. The prevalence of anencephaly based on data collected from (EUROCAT) member countries during the years 2000 and 2010, was estimated at 3.52 per 10,000 births [ 24 ].

Considering the importance of anencephaly as the most severe type of neural tube defect, and its detrimental effects on the quantity and quality of patients’ and parents’ life, and regarding the serious health, psychological, social and economic costs for the individual and society, accurate identification of patients is of great importance to organize health care services and implement preventive measures. In addition, because of various statistics on the prevalence of anencephaly and the worldwide absence of a comprehensive investigation capable of analyzing the outcomes of these studies, the present research was conducted through a systematic review and meta-analysis to shed light on the prevalence, incidence and mortality of anencephaly worldwide.

The present systematic review and meta-analysis was conducted based on the Cochrane 7-step approach, including: research question selection, inclusion and exclusion criteria, article identification, study selection, study quality evaluation, data extraction, and analysis and interpretation of findings [ 25 ]. In this study, the statements of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) were used [ 26 ].

Research question and keyword determination

According to the research question “How has the prevalence, incidence and mortality of anencephaly changed worldwide?” the following were defined:

The study population (Population) included patients with anencephaly, result (Outcome) comprised the prevalence of anencephaly, date of publishing the first related article until March 23, 2021 was specified as the time range (Time or Duration), and type of study (study design) included cross-sectional studies (descriptive, descriptive-analytical). Keywords were extracted from the MeSH browser. Keywords related to the studied population (P): Anencephaly, Congenital Absence of Brain, Anencephalus, Anencephalia, Incomplete Anencephaly, Partial Anencephaly, Hemicranial Anencephaly, Aprosencephaly and Keywords related to outcome were (O), Prevalence, outbreak.

Inclusion and exclusion criteria according to the research question

Cross-sectional population-based studies (descriptive, descriptive-analytical) that reported the prevalence of anencephaly in different parts of the world, published in Persian and English with full texts available included in the study. Analytical, interventional, conferential, and group-case studies irrelevant to the research question and studies that were not in English or did not have English abstracts were excluded from the investigation.

Article identification

To review the literature, two Persian databases, including MagIran and SID, and four international ones, Science Direct, Web of Science (WoS), Medline (PubMed), and Scopus, were selected. The Google Scholar scientific search engine was considered for final review while no time limit was set for the search to retrieve relevant results; thus, all articles published up to March 23, 2021 were reviewed. Searching was limited to studies published in Persian and English and strategy in each database was determined using Advanced Search (Advance Search) with the help of all possible keyword combinations with the help of AND and OR operators. For example, searching strategy in the PubMed database was determined as follows:

(prevalence [Title/Abstract] OR outbreak [Title/Abstract]) AND (Anencephaly [Title/Abstract] OR Congenital Absence of Brain [Title/Abstract] OR Anencephalus [Title/Abstract] OR Anencephalia [Title/Abstract] OR Incomplete Anencephaly [Title/Abstract] OR Partial Anencephaly [Title/Abstract] OR Hemicranial Anencephaly [Title/Abstract] OR Aprosencephaly [Title/Abstract]).

In order to access the latest published studies, an alert was created on a number of important databases, including PubMed and Scopus, to check if new articles were published during the study. Also, in order to access all related studies, the sources of articles that met the inclusion criteria were manually reviewed. To avoid error, all steps of article search, study selection, qualitative evaluation and data extraction were performed independently by two researchers (BF and ND). If there was a difference of opinion among the researchers regarding the inclusion of the article in the study, in order to avoid the risk of biased selections for specific studies, first a final agreement was reached through discussion and in some cases with the participation and opinion of a third party (MM).

Selection of studies based on inclusion and exclusion criteria

The information of all articles found in each database was transferred to EndNote X8 software. After completing the search in all the databases, duplicate articles were excluded. Then, in order to avoid the risk of prejudice in selecting studies, the names of the authors and the titles of the journals of the articles were removed and a checklist was prepared based on the titles and abstracts of the studies. In the next step, two authors (N.D. and B.F.) independently examined the title and abstract of the research and eliminated irrelevant papers based on the inclusion and exclusion criteria. Studies with no full text were not considered for the systematic review and meta-analysis process. The full text of all remaining articles was then evaluated. Studies that did not meet the inclusion criteria based on the research question were out listed.

Qualitative evaluation of studies

Qualitative evaluation of studies was performed using the Newcastle–Ottawa Scale, the NOS assigns a maximum of 9 points for the three areas of study group selection, group comparison, and exposure and outcome for the case and group studies [ 27 ]. Based on this, articles were classified as high quality (≥ 5) and low quality (< 5).

Extracting the data

After selecting the studies to enter the systematic review and meta-analysis process, the data were extracted and the studies were summarized. An electronic checklist was prepared for this purpose. The various items on the checklist included: the surname of the first author, year of publication and year of the report, sample size, number of patients, prevalence, incidence and mortality of patients.

Statistical analysis

To analyze and combine the results of different studies, in each study, the prevalence of anencephaly was considered as the probability of two-sentence distribution and its variance was calculated through two-sentence distribution. Heterogeneity of studies was assessed using I 2 test. A Random effect model was used in case of I 2 index above 50%. In this model, parameter changes between studies are also considered in the calculations, so it can be said that the results of this model in heterogeneous conditions can be more generalized than the model with a fixed effect. Due to the large sample size investigated in the study, Begg and Mazumdar rank correlation test was used at a significance level of 0.1 to check the publication bias. Data were analyzed using Comprehensive Meta-Analysis (Version 2) software.

Summary of how articles entered the meta-analysis

In this study, the statements of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) were used [ 26 ]. In the first stage, 1141 articles (1104 articles in international, 9 articles in Persian databases and 28 studies in reviewing article sources) were found, of which 330 duplicate studies were omitted. 811 studies entered the screening stage and 371 articles were deleted based on the inclusion and exclusion criteria by reviewing the title and abstract of the study. In the next stage (competency assessment), out of the remaining 440 studies from the screening stage, 58 articles were removed by reviewing the full text of the article because it was not relevant to the research. The quality evaluation of 382 articles included in this study was performed using the STROBE checklist, of which 22 studies had poor methodological quality and were deleted. Thus, 360 related studies entered the process of systematic review and meta-analysis (Fig. 1 ) [ 28 ].

Preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) flow diagram

General characteristics of the studies:

The total sample size of the prevalence studies was 169,407,738 people. The studies were published between 1969 and March 23, 2021. The lowest sample size was related to the study of Castilla-17 et al. (1985) with 1623 people in [ 29 ] Colombia and the highest sample size was related to the study of James et al. (1993) with 15,487,449 people in the USA [ 30 ]. The surname of the first author, year of publication and year of reporting, place of study, maternal age, sample size, number of cases, prevalence, incidence and attenuation of anencephaly reported in Tables 1 , 2 and 3 .

The result of the I 2 test for the prevalence of anencephaly in different parts of the world indicates a significant heterogeneity between studies (I 2 = 99.9), so the data were analyzed by meta-analysis using a random effects model. Due to the high heterogeneity of the studies, sensitivity analysis was performed and the effect of each study on the final result and the degree of heterogeneity were evaluated. Based on Begg and Mazumdar rank correlation tests, the publication bias in the studies with less than 0.1% was not observed. (P = 0.105) (Table 4 ).

As a result of the combination of studies, the overall estimate of the prevalence of Anencephaly in the world will be 5.1 per ten thousand births (95% confidence interval 4.7–5.5) based on the random effects model (Table 4 ).

According to different reports of Anencephaly prevalence in different parts of the world, subgroup analysis by different continents (Asia, Europe, USA, Africa and Australia) is reported in Table 2 , which has the highest prevalence in Australia with 8.6 per ten thousand births (confidence interval). 95%: 7.7–9.5) (Table 4 ).

Incidence and mortality of Anencephaly were 8.3 per ten thousand births (95% confidence interval 5.5–9.9) and 5.5 per ten thousand births (95% confidence interval 1.8–15) respectively (Table 5 ).

Neural tube defects (NTDs) are a major congenital structural disorder of the brain and spinal cord that occurs early in pregnancy as a result of defective neural tube closure [ 9 ], including abortion, stillbirth, and lifelong disability, as well as high emotional, psychological and economic consequences (138). Many factors, including radiation therapy, drugs, malnutrition, chemicals, and genetic determinants (mutations in folate-responsive or folate-dependent pathways) can adversely affect CNS growth during pregnancy and cause neural tube defects [ 12 ].

Anencephaly, which is the partial or complete absence of the brain and skull [ 3 ] is one of the most common forms of NTD. The fetus with anencephaly dies or will die in the first few hours after birth [ 9 ]. Exposure to methotrexate, aminopterin and valproic acid, maternal characteristics, race, ethnicity, geography, nutritional, biological and poor economic conditions are all risk factors for anencephaly [ 121 , 122 ].

According to the present systematic review and meta-analysis, the overall prevalence of anencephaly in the world was 5.1 per ten thousand births. The highest prevalence of anencephaly was related to the study of RICHARDS et al. [ 57 ] with 230.69 infants with anencephaly per ten thousand births and the lowest prevalence was related to the study of Castilla et al. [ 31 ] with zero cases per ten thousand births. The most comprehensive study in terms of sample size was the study of James et al. (1993) with 15,487,449 people in the USA [ 32 ] that reported the prevalence of anencephaly at 3.89 per thousand births. Also, the present study estimated the risk of incidence and death due to anencephaly: 8.3 per ten thousand births and 5.5 per ten thousand births worldwide. Bhide et al. (2013) reported the prevalence of anencephaly in India at 2.1 per thousand births through 19 studies [ 123 ]. A meta-analysis and systematic review by Bitew et al. (2020) reported the prevalence of NTD in Ethiopia. 63.3 per ten thousand births [ 124 ]. Our study is almost in line with these studies and regarding the cause of minor differences between the present study and these studies, we can point out that the number of articles studied in the present study is more (121 articles in the present study versus 19 articles in the study of Bhide et al.) And also, the present study has examined patients with different races and geographical regions in the world.

Due to the change in population structure in different countries and different reports of the prevalence of anencephaly, the need for a detailed study of the prevalence of this defect in different continents in order to pay more attention to the process and its consequences seems inevitable. Therefore, according to the analysis of subgroups according to different continents, the highest prevalence of anencephaly is related to the continent of Australia with 8.6 per ten thousand births and the lowest belongs to the Americas with 4.3 per thousand births.

The results show that in addition to genetics, various environmental factors can also be involved in the development of anencephaly. So far, folic acid is the most important factor in preventing neural tube defects. Reports suggest the use of periovulation fulate supplements significantly reduces the risk of recurrence of anencephaly and other neural tube defects [ 125 ].

Regarding the serious nature of anencephaly and its high mortality, genetic counseling, folic acid supplements and prenatal diagnosis of neural tube defects are extremely important or (Given the seriousness of anencephaly and its high mortality rate, genetic counseling, folic acid supplements, and prenatal detection of neural tube abnormalities are critical.). This defect can be diagnosed by screening AFP (alpha-fetoprotein) with a combination of ultrasound and amniocentesis between 14 and 16 weeks of gestation [ 3 , 5 ]. These studies can provide useful information to health care providers and enrich health care interventions and improve the quality of services and life [ 126 ].

Limitations

One of the limitations of this study is that some samples were not based on random selection. Also, non-homogeneous reporting of articles, non-homogeneous method of implementation, and unavailability of the full text of the papers presented at the conference can be added. Such conditions can justify the high heterogeneity reported in the studies, and therefore, if these limitations and differences in the studies did not exist, the heterogeneity analysis could be less.

The results of this study demonstrate that the prevalence of anencephaly in the world is high; therefore, it is necessary for physicians and specialists to emphasize the importance of preventive as well as control and treatment strategies.

Availability of data and materials

Datasets are available through the corresponding author upon reasonable request.

Abbreviations

Neural Tube Defects

Scientific Information Database

Medical Subject Headings

Web of Science

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

Strengthening the reporting of observational studies in epidemiology for cross-sectional study

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Acknowledgements

This study is the result of research project No. 4000613 approved by the Student Research Committee of Kermanshah University of Medical Sciences. We would like to thank the esteemed officials of the center for financing this study.

By Deputy for Research and Technology, Kermanshah University of Medical Sciences (IR) (4000613). This deputy has no role in the study process.

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Nader Salari

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

Behnaz Fatahi & Niloofar Darvishi

Department of Neurosurgery, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Reza Fatahian

Department of Neurology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Payam Mohammadi

Julius Wolff Institute, Chatite, Berlin, Germany

Adibeh Rahmani

Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Mona Keivan

Department of Biology, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia

Shamarina Shohaimi

Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran

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NS and BF and ND contributed to the design, MM statistical analysis, participated in most of the study steps. MM and RF and PM and MK prepared the manuscript. MM and ND and BF and AR and PM and SHSH assisted in designing the study, and helped in the, interpretation of the study. All authors read and approved the final manuscript.

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Salari, N., Fatahi, B., Fatahian, R. et al. Global prevalence of congenital anencephaly: a comprehensive systematic review and meta-analysis. Reprod Health 19 , 201 (2022). https://doi.org/10.1186/s12978-022-01509-4

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Anencephaly

Anencephaly is characterized by a total (holo) or partial (mero) absence of the brain with absence of the cranial vault (calvaria) and covering skin.

Fig. 2. Anencephaly

Photograph sources: Latin American Collaborative Study of Congenital Malformations (ECLAMC); CDC–Beijing Medical University collaborative project.

Type – holoanencephaly (panel a: total absence) is the most common type of anencephaly; meroanencephaly (panel b: partial absence).
Covering – no skin covering residual brain tissue or cranial vault (calvarium).

Prenatal. Anencephaly is diagnosed prenatally but should always be confirmed postnatally. Use programme rules (standard operating procedures [SOPs]) to decide whether to accept or not accept prenatal diagnoses without postnatal confirmation (e.g. in cases of termination of pregnancy or unexamined fetal death).

Postnatal. The newborn examination confirms the diagnosis and will distinguish anencephaly from the other anomalies of the brain and cranium.

Clinical and epidemiologic notes

Eyes are normally formed; bulging is a result of absence of the frontal portion of the cranial vault.
Cerebellum, brain stem and spinal cord are intact.
Craniorachischisis characterized by anencephaly plus rachischisis, a contiguous upper spine defect without meninges covering the neural tissue.
Amniotic band or limb-body wall spectrum, which have other findings (facial schisis, limb and ventral wall anomalies, bands) and allow the differentiation from typical anencephaly

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Anencephaly

Anencephaly is absence of the cerebral hemispheres. It is usually accompanied by a defect in the formation of the skull posteriorly, leaving the back of the head without skeletal protection.

In anencephaly, the residual brain tissue consists of highly malformed neural tissue, which may be exposed completely or thinly covered with skin. Parts of the brain stem and spinal cord also may be missing or malformed. Infants are stillborn or die within days or weeks.

Treatment of anencephaly is palliative only.

Hydranencephaly is a type of anencephaly.

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Exencephaly – Anencephaly Sequence and its Sonographic Features

Anencephaly represents the most common neural tube defect. It’s incidence is approximately 1:1000 with female predominance (4:1) and geographical variability.

Introduction

Anencephaly represents the most common neural tube defect. It’s incidence is approximately 1:1000 with female predominance (4:1) and geographical variability. 1,2 The etiology of anencephaly closely mirrors that of spina bifida. The condition results from the failure of the rostral (cephalic) neuropore to close. Sonographic as well as pathologic evidence points to a close link between exencephaly (also frequently referred to as "acrania") and anencephaly. It has been proposed that the brain tissue of exencephalics may gradually degenerate due to the exposure to amniotic fluid in combination with mechanical trauma. This wearing down of the brain stroma produces the classic anencephalic features with flattened brain remnants behind the prominent orbits. This hypothesis is supported by animal studies, pathologic analysis of exencephalic brain stroma when compared with cerebrovasculosa 2 , as well as observations on ultrasonography combined with amniotic fluid cytology. 3

Ultrasound Findings

Reliable sonographic diagnosis of anencephaly is usually possible in early second trimester (10-14wks GA) 4 . Conventional 2D ultrasound is accurate in diagnosing anencephaly 5 and the sensitivity is virtually 100% after 14wks GA 6 . 3D sonography has been shown to be equally effective in detecting anencephaly. 7

On ultrasound, the cranial vault (bony calvarium) is symmetrically absent. Rudimentary brain tissue (area cerebrovasculosa) is covered by a membrane, but not bone (Figure 1,2). This be seen protruding from the base of the skull in the early second trimester, and gradually degenerates until the appearance of the head is completely flattened behind the facial structures. Facial views reveal frog-like appearance with prominent bulging eyeballs (Figure 3,4). Associated polyhydramnios usually develops in the second trimester and is likely due to absent or ineffective fetal swallowing (Figure 3). High degree of fetal activity is often observed. 1,2,6

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What’s Happening When the Pregnancies Are Not Terminated in Case of Anencephalic Fetuses?

Emre ekmekci.

a Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynecology, Sanliurfa Education and Research Hospital, Sanliurfa,Turkey

Servet Gencdal

b Department of Obstetrics and Gynecology, Ataturk Education and Research Hospital, Izmir Katip Celebi University, Izmir, Turkey

To review the obstetric outcomes of pregnancies with anencephalic fetuses when these pregnancies are not terminated and ongoing.

A retrospective chart review is made of the cases with a prenatal diagnosis of anencephaly and who were opted to continue the pregnancy in 1-year period. The evaluated data included gestational age at diagnosis, gestational age at birth, labor induction rates, cesarean delivery rates, stillbirth, shoulder dystocia rate, antepartum and postpartum hemorrhage.

A total of 28 cases that were selected from 87 cases with the diagnosis of anencephaly are included in the study. The average gestational age at diagnosis was 18 weeks. The average gestational age at birth was 31 weeks (range 23 - 37 weeks). Stillbirths were reported in 32% (9/28). Polyhydramnios developed at six patients and two of them required amniodrainage due to severe polyhydramnios. Vaginal birth was achieved in 67% (19/28) of the patients. Labor induction was applied at total 17 patients and one of them had gone to cesarean section due to failed induction. There were two cases of shoulder dystocia. Nine patients had gone to cesarean delivery. Any other complication was not encountered.

Conclusions

Parents should be counseled in detail about continuation of an anencephalic pregnancy before making their decision. The information about “what an anencephalic pregnancy can lead”' should be given. The redundant cesarean deliveries, polyhydramnios and associated complications, obstetrical hemorrhage risk should be discussed with patients. It should also be emphasized that these maternal risks are for the sake of a non-life expectant baby.

Introduction

Anencephaly is a lethal condition, which is part of the neural tube defect (NTD) spectrum. It is a serious developmental defect of the central nervous system. The brain and cranial bones are grossly malformed. Cerebral and cerebellar structures are reduced or grossly malformed, but the hindbrain is present. The etiology seems to be caused by genetic and environmental factors; however, many of which remains unknown. Its prevalence at birth ranges from 1 in 5,000 to 1 in 2,000 [ 1 , 2 ]. The prevalence at birth has great geographic variation, with especially high rates in the British Isles, China, Mexico, and Turkey [ 3 ]. The widespread use of ultrasound has led to earlier bonding of parents to their unborn children because that’s very traumatic for parents to terminate babies that they have become attached.

If the anencephalic pregnancy is not terminated prenatally or diagnosis is not made prior to birth, live born infants typically survive less than 1 day [ 4 ]. It is an important aspect to address all the potential possibilities of maternal outcomes with parents, especially in case of pregnancy termination is not or no longer an option. The decision about pregnancy termination is associated with parents’ religious beliefs and restricted legal termination rules, in addition to other factors such as late detection of the anomaly and delayed fetal anatomy scans. Commonly, the major reason for continuation of pregnancy is the request of parents due to religious beliefs.

In our study, we aimed to review the obstetric outcomes after the continuation of pregnancies with anencephalic fetuses, to review the obstetric impact and natural history of anencephalic pregnancies, and to define the maternal risks in the continuation of pregnancies with non-life expectant babies.

Materials and Methods

This is a retrospective chart review of all prenatal diagnoses of anencephaly, made in Sanliurfa Education and Research Hospital, Sanliurfa, Turkey, in a 1-year period between May 2017 and April 2018. The unit is a busy tertiary center in the east of Turkey, which receives referral patients from the region, with about 35 - 40,000 deliveries per year. Also an important aspect of the hospital is that a great amount of health care is being provided to Syrian refugees due to the intensity of the Syrian refugees in the region. Approval and permission for the study regarding the provision of patient data were obtained from the institution (registration number: 96537014-00-3876). The study design is in accordance with the Helsinki Declaration (Association 2014), and conformed with the Committee on Publication Ethics Guidelines. The diagnosis of anencephaly was made through prenatal ultrasound by the same physician (Ekmekci E) and confirmed in postnatal neonatal examinations. The ultrasound device used was a Voluson E8 system (GE Healthcare, Milwaukee, WI) with an RAB 4 - 8-MHz transabdominal probe. Multiple gestations are not included in study.

All parents were informed about the fetal status through detailed oral disclosure with photographs of sample anencephalic babies, and all were given the option of pregnancy termination, irrespective of gestational age. There is no restriction for termination of pregnancy in Turkey in cases of confirmed lethal or severe fetal anomalies with the approval of the hospital ethics board. Twenty-eight women who do not accept termination and opted to continue pregnancy were selected for the study. Pregnancies were followed up to 37 weeks of pregnancy; if labor did not start spontaneously, labor induction was started.

Outcome variables included gestational age at diagnosis, gestational age at birth, induction of labor, cesarean delivery, live births, stillbirths, shoulder dystocia, polyhydramnios, antepartum hemorrhage (APH), and postpartum hemorrhage (PPH). Polyhydramnios was defined as ultrasound estimation of amniotic fluid if the deepest vertical pocket is ≥ 8 cm and defined as severe polyhydramnios if ≥ 16 cm.

Eighty-seven anencephaly cases from 27,754 deliveries were enrolled in the study during the 1-year period. A total of 3,885 deliveries were carried by Syrian refugees, 31 of which were anencephalic fetuses. The average maternal age was 27 years (range, 17 - 46 years). The median parity was 3 (range, 0 - 8). Thirteen percent (12/87) of the patients were primigravida. Three women had a history of previous anencephalic pregnancies. No other risk factors were identified. The mean gestational age at diagnosis was 18 weeks (range, 11 - 36 weeks). Forty-nine pregnancies were terminated after the diagnosis, according to family request.

Twenty-eight patients were rejected termination of pregnancy and opted for continuation of pregnancy, 11 (39%) of whom were Syrian refugees. The average gestational age at birth was 31 weeks (range, 23 - 37 weeks). Stillbirths were reported in 32% (9/28), 68% of the fetuses (19/28) were alive; however, all died within the first week of life. One baby was alive for 5 days in the neonatal intensive care unit, the remainder died in the first hour after delivery. The median gestational age of pregnancies with stillbirth was 27 weeks. The average birth weight was 1,526 ± 946 g (range, 450 - 3,170 g).

Vaginal birth was achieved in 68% (19/28) of the patients. Cesarean section (CS) was performed in nine patients (32%); seven patients had previous uterine surgery, one patient had a transverse presentation after membrane rupture at 32 weeks, and one patient had failed labor induction. Spontaneous labor was started in nine (32%) patients, two of them were underwent CS due to previous uterine surgery. Twelve (42%) patients reached 37 weeks with live fetuses and pregnancy was terminated during this week. Labor induction was performed in a total of 18 (64%) patients. Six (21%) patients developed polyhydramnios, and of these, two women were required serial amniodrainages due to severe polyhydramnios that was causing maternal dyspnea during follow-up. Amnioreduction was repeated twice for two patients.

Two (11%) vaginal deliveries were complicated by shoulder dystocia; both could be delivered vaginally by rotational maneuvers. One PPH was occurred due to uterine atony, which was resolved with medication and was not required surgery. There were no surgical complications associated with CS. There were no maternal postnatal complications. The complications associated with ongoing anencephalic pregnancies are listed in Table 1 . The outcomes of the pregnancies are reported in a flow diagram in Figure 1 .

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Outcome of anencephalic pregnancies in the study.

In this study, we evaluated the outcome of anencephalic pregnancies and aimed to describe the redundant maternal risks for a non-viable baby. The major risk for the mother was redundant cesarean deliveries.

There is great geographic variation in the prevalence of fetal anencephaly and neural tube defects. Although this study was not a prevalence study, approximate prevalence can be calculated by using the annual birth numbers of the hospital. In a 1-year period, the total number of births was 27,754 in our hospital. If this is used for calculation, the prevalence is 3.1 per 1,000 live births. This prevalence is significantly higher compared with the reported prevalence in the literature. Obeid et al reported the prevalence as 3.52 per 10.000 live births on the basis of the surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT) [ 5 ]. There is a great variation in the prevalence compared to worldwide in our area. Also, in Northern Iran which is a close region to our area, the prevalence was reported as 12 per 10,000 live births, that’s very high again compared to worldwide, in a cross-sectional hospital-based study published in 2010 [ 6 ]. This significantly high prevalence may be misleading due to the non-homogenous study population, but the prevalence seems higher than the general population. The hospital is a tertiary center and accepting referral patients from the region. Also, there is an intensity of Syrian refugees in the region (about 500,000 Syrian refugees live in Sanliurfa province). Another aspect is that, in a recent study from the north west of Turkey, the prevalence of anencephaly is reported as 2.1 per 10,000 live births, which is similar to general worldwide data [ 7 ]. This great geographical variation at the prevalence of condition in the same country and same health policies cannot be only associated with environmental factors. Also, racial and genetic factors should be taken into account. We feel that further large population based studies are required to investigate this high prevalence in the region.

Another interesting aspect was about the prevalence of anencephaly in Syrian refugees. In this period, the total number of births of Syrian refugees was 3,885. Thirty-one anencephalic pregnancies were diagnosed among the Syrian refugees. The prevalence was 8 in 1,000 births (31/3885). Three pregnancies had a history of previous anencephalic pregnancies. Rates are very high when compared to world average and rates from the hospital. This may be evidence of destructive effects of environmental factors on the developing fetus, like war and malnutrition.

Although anencephalic fetuses are non-viable and termination of pregnancy is the most logical approach; due to religious beliefs, pregnancies are not being terminated commonly, compared to the usual. In Turkey, there is no restriction for pregnancy termination with an anencephalic fetus, but 32% (28/87) of patients were not terminated their pregnancies, primarily due to religious beliefs. When these pregnancies are ongoing, patients are subjected to various pregnancy complications specific to anencephalic pregnancies, in addition to general pregnancy complications.

The prenatal detection of anencephaly with ultrasound is high and reliable in the 10 - 14 weeks scan [ 8 , 9 ]. In our study, the mean gestational age for the diagnosis of anencephaly was 18 weeks and the earliest gestational age was 11 weeks. Blaas et al reported that diagnosis of anencephaly could be made as early as the ninth week of pregnancy [ 10 ]. Almost all anencephalic fetuses can be diagnosed during the first trimester screening of 11 - 14 weeks. The sensitivity is 100% in the second trimester screening sonography.

In our study population, six (21%) patients required amnioreduction due to severe polyhydramnios. Polyhydramnios was also a significant prenatal complication in our study, as other authors have also found [ 1 ]. Obeidi et al reported that one-quarter of anencephalic pregnancies were complicated by polyhydramnios in their study [ 2 ]. The rate of stillbirth in our anencephaly fetuses was 32%. Al-Obaidly and Obeidi et al reported 40% and 42% stillbirth rates, respectively, in their studies during follow-up of anencephalic fetuses [ 2 , 11 ]. Induction of labor might carry an increased risk for CS [ 12 ]. However, in our study, there were no differences in achieving vaginal birth in women who were induced compared with women who had spontaneous labor.

Shoulder dystocia in anencephalic pregnancies is an expected complication that can be attributed to diminished head size, which cannot dilate the cervix enough to deliver the fetal trunk and shoulders [ 13 ]. The shoulder dystocia rate was 2/19 (11%) in our study and all were relieved with rotational maneuvers. None of the patients in our study were diabetic, that supports that anencephaly could be solely itself a risk factor for shoulder dystocia.

The majority of maternal risks after an ongoing anencephalic pregnancy are associated with compulsory cesarean operations for non-viable babies. The risk of repeated CS should be addressed in women with a previous uterine scar, especially in anencephalic pregnancies because the risk about the prolongation of pregnancy to upper gestational age is increased due to fetal hypothalamic-pituitary axis dysfunction [ 14 ]. In our study, seven (25%) patients required CS due to previous uterine surgery, and two were underwent CS due to malpresentation and failed labor induction. In our clinic our management protocol is to follow anencephalic pregnancies up to 37 weeks and then to start the delivery. Therefore, we had no post-term pregnancies.

Although our study represents a shorter period of time than similar reports on this issue, our study population had a large cohort for this area. We could establish the outcomes of all patients because our hospital is the referral center for the region and all high-risk pregnancies are followed in our center. A major strength of our results is that, the study population contains patients who were all given the option to terminate pregnancies but opted to continue their pregnancies. There was no governmental restriction for pregnancy termination.

Study limitations

The limitation of our study is its retrospective nature; however, all medical data were directly achieved from case notes and other hospital records. Another limitation of our study is that we did not follow pregnancies to term due to the fact they were all terminated at 37 weeks. The pregnancies were not left to their natural course. On the other hand, there is no consensus in the literature regarding the time for termination of ongoing pregnancies with anencephalic fetuses.

In this study, our intention was not to discuss the ethical and moral issues in the management of anencephalic pregnancies, but rather to report the outcomes of a large number of cases complicated with anencephalic fetuses. We would like to draw attention to this problem, which is very common in our region for health professionals caring for patients with anencephalic pregnancies. The leading morbidity associated with ongoing anencephalic pregnancies seems to be associated with redundant cesarean deliveries. Also, polyhydramnios and postpartum hemorrhage are less frequent complications that should be kept in mind. These findings should assist in counseling parents more appropriately about the possible complications of ongoing anencephalic pregnancies and outcomes of these pregnancies.

Acknowledgments

None to declare.

Financial Disclosure

There has been no significant financial support for this work that could have influenced its outcome.

Conflict of Interest

We confirm that there are no known conflicts of interest.

Informed Consent

Author contributions.

Study conception and design: Ekmekci E and Gencdal S. Acquisition of data: Ekmekci E and Gencdal S. Analysis and interpretation of data: Ekmekci E and Gencdal S. Drafting of manuscript: Ekmekci E. Critical revision: Ekmekci E and Gencdal S.

COMMENTS

Embryology, Anencephaly
Anencephaly is a pathology of development characterized by a fetus that has no calvarium, with a lack of most or all of the fetus' brain tissue.[1] Anencephaly belongs to a collective group known as neural tube defects (NTD) and is a result of the neural tube failing to close in its rostral end during fetal development.[2] While the central nervous system (CNS) is developing in a fetus, the ...
Exencephaly-anencephaly Sequence
The main differential diagnoses are amniotic bands and severe microcephaly. In amniotic band sequence, the most common defects are those involving the fetal extremities that can result in constrictions and amputations. However, severe craniofacial defects, such as anencephaly, have been reported in approximately one-third of cases of amniotic ...
Anencephaly
Anencephaly is a type of neural tube defect that occurs in about one of 10,000 pregnancies in the U.S. each year. The actual number is unknown because many of these births result in miscarriages. According to the CDC, one in every 4,859 newborns in the United States has this condition. During pregnancy, the human brain and spine begin as a flat ...
Anencephaly: What It Is, Causes, Signs & Prevention
Anencephaly. Anencephaly is a fatal birth defect. It occurs when the fetal brain and skull don't develop in your uterus as expected. Babies born with the condition die within a few hours or days. Most pregnancies end in miscarriage. You can lower your risk by taking the recommended dose of folic acid before and during pregnancy.
Facts about Anencephaly
What is anencephaly? Anencephaly is a serious birth defect in which a baby is born without parts of the brain and skull. It is a type of neural tube defect (NTD). As the neural tube forms and closes, it helps form the baby's brain and skull (upper part of the neural tube), spinal cord, and back bones (lower part of the neural tube ...
Anencephaly
Anencephaly [congenital absence of a major portion of the brain, skull, and scalp (Medical Task Force on Anencephaly, 1990)] is the most severe and single most common prenatally detected neural tube defect (Goldstein and Filly, 1988).Although the cerebral hemispheres can develop in this condition, any exposed brain tissue is subsequently destroyed (see Chapter 13).
PDF Anencephaly
anencephaly die before birth or within a few hours or days after birth. Frequency Anencephaly is one of the most common types of neural tube defect, affecting about 1 in 1,000 pregnancies. However, most of these pregnancies end in miscarriage, so the prevalence of this condition in newborns is much lower. An estimated 1 in 10,000
Anencephaly
Anencephaly is a condition present at birth that affects the formation of your baby's brain and the skull bones that surround the head. Anencephaly results in only minimal development of the baby's brain. Often, the brain lacks part or all of the cerebrum, the area of the brain that is responsible for thinking, vision, hearing, touch, and movement.
Anencephaly in Children
Anencephaly is a condition that is present at birth (birth defect). It affects the brain and skull bones. With this condition, the brain is not fully formed. It often lacks part or all of the cerebrum. The cerebrum is the area of the brain used for thinking, seeing, hearing, touch, and movement. There is also no bone on the back of the head.
Anencephaly
Anencephaly is a condition in which major portions of the brain, skull, and scalp are absent. It is the most severe and single most common prenatally detected spinal cord ( neural tube) defect (Goldstein and Filly, 1988). Although the upper portions of the brain ( the cerebral hemispheres) can develop in this condition, any exposed brain tissue ...
Global prevalence of congenital anencephaly: a comprehensive systematic
Anencephaly is a fatal congenital anomaly characterized by the absence of brain hemispheres and cranial arch. Timely preventive measures can be taken by knowing the exact prevalence of this common neural tube defect; thus, carried out through systematic review and meta-analysis, the present study was conducted to determine the worldwide prevalence, incidence and mortality of anencephaly.
Anencephaly
Anencephaly is a lethal condition and is often an isolated, non-syndromic anomaly. Eyes are normally formed; bulging is a result of absence of the frontal portion of the cranial vault. Cerebellum, brain stem and spinal cord are intact. Additional clinical tips: Anencephaly can be confused with: Craniorachischisis characterized by anencephaly ...
Anencephaly
Reviewed/Revised Jul 2023. Anencephaly is absence of the cerebral hemispheres. It is usually accompanied by a defect in the formation of the skull posteriorly, leaving the back of the head without skeletal protection. In anencephaly, the residual brain tissue consists of highly malformed neural tissue, which may be exposed completely or thinly ...
Anencephaly © The Author(s) 2010
anencephaly, acrania, lethal anomalies. Anencephaly is absence of the scalp, skull, cranial vault, and cerebral hemispheres. It is the most common neural tube defect and occurs in 1/1000 pregnancies.1 The condi-tion is incompatible with life, and management for liveborns is supportive only.
Exencephaly
Ultrasound Findings. Reliable sonographic diagnosis of anencephaly is usually possible in early second trimester (10-14wks GA) 4. Conventional 2D ultrasound is accurate in diagnosing anencephaly 5 and the sensitivity is virtually 100% after 14wks GA 6. 3D sonography has been shown to be equally effective in detecting anencephaly. 7.
Anencephaly: Overview, Pathophysiology, Causes
Overview. Anencephaly is a serious developmental defect of the central nervous system in which the brain and cranial vault are grossly malformed. The cerebrum and cerebellum are reduced or absent, but the hindbrain is present. Anencephaly is a part of the neural tube defect (NTD) spectrum. This defect results when the neural tube fails to close ...
Anencephaly
Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. 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. Strictly speaking, the Greek term translates as "without a brain" (or totally ...
Anencephaly
Anencephaly is one of the most common neural tube defects. Neural tube defects are birth defects that affect the tissue that becomes the spinal cord and brain. Anencephaly occurs early in the development of an unborn baby. It results when the upper part of the neural tube fails to close. The exact cause is not known.
Face and Brow Presentation
Fetal anomalies such as hydrocephalus, anencephaly, and neck masses are common risk factors and may account for as many as 60% of cases of face presentation. For example, anencephaly is found in more than 30% of cases of face presentation. Fetal thyromegaly and neck masses also lead to extension of the fetal head.
What's Happening When the Pregnancies Are Not Terminated in Case of
The prenatal detection of anencephaly with ultrasound is high and reliable in the 10 - 14 weeks scan [8, 9]. In our study, the mean gestational age for the diagnosis of anencephaly was 18 weeks and the earliest gestational age was 11 weeks. Blaas et al reported that diagnosis of anencephaly could be made as early as the ninth week of pregnancy ...

Anencephaly

What causes anencephaly?

What are the symptoms of anencephaly?

How is anencephaly diagnosed?

Treatment of the newborn with anencephaly

Future pregnancies

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Chapter 7: Anencephaly

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What is anencephaly in children?

What causes anencephaly in a child?

Which children are at risk for anencephaly?

What are the symptoms of anencephaly in a child?

How is anencephaly diagnosed in a child?

How is anencephaly treated in a child?

How can I help prevent anencephaly in my child?

When should I call my child’s healthcare provider?

Key points about anencephaly in children

Related Topics

Management Options and Outcomes

Candidacy for Fetal Treatment

Newborn Care

Surgical Management

Additional Information

A Difficult Diagnosis

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Global prevalence of congenital anencephaly: a comprehensive systematic review and meta-analysis

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Research question and keyword determination

Inclusion and exclusion criteria according to the research question

Article identification

Selection of studies based on inclusion and exclusion criteria

Qualitative evaluation of studies

Extracting the data

Statistical analysis

Summary of how articles entered the meta-analysis

General characteristics of the studies:

Limitations

Availability of data and materials

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Anencephaly

Fig. 2. Anencephaly

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Anencephaly

Exencephaly – Anencephaly Sequence and its Sonographic Features

What’s Happening When the Pregnancies Are Not Terminated in Case of Anencephalic Fetuses?

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