Tests for neural tube defects include ultrasound examination and measurement of maternal serum alpha-fetoprotein (MSAFP). Second trimester ultrasound is recommended as the primary screening tool for NTDs, and MSAFP as a secondary screening tool. This is due to increased safety, increased sensitivity and decreased false positive rate of ultrasound as compared to MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) and amniotic fluid acetylcholinesterase (AFAChE) tests are also used to confirming if ultrasound screening indicates a positive risk. Often, these defects are apparent at birth, but acute defects may not be diagnosed until much later in life. An elevated MSAFP measured at 16–18 weeks gestation is a good predictor of open neural tube defects, however the test has a very high false positive rate, (2% of all women tested in Ontario, Canada between 1993 and 2000 tested positive without having an open neural tube defect, although 5% is the commonly quoted result worldwide) and only a portion of neural tube defects are detected by this screen test (73% in the same Ontario study). MSAFP screening combined with routine ultrasonography has the best detection rate although detection by ultrasonography is dependent on operator training and the quality of the equipment.

In 1996, the United States Food and Drug Administration published regulations requiring the addition of folic acid to enriched breads, cereals, flour and other grain products. It is important to note that during the first four weeks of pregnancy (when most women do not even realize that they are pregnant), adequate folate intake is essential for proper operation of the neurulation process. Therefore, women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risks of serious birth defects.

In Canada, mandatory fortification of selected foods with folic acid has been shown to reduce the incidence of neural tube defects by 46%.

Women who may become pregnant are advised to get 400 micrograms of folic acid daily. Women who have previously given birth to a child with a neural tube defect may benefit from a supplement containing 4.0 mg/5.0 mg in the UK mg daily, following advice provided by their doctor.

Open spina bifida can usually be detected during pregnancy by fetal ultrasound. Increased levels of maternal serum alpha-fetoprotein (MSAFP) should be followed up by two tests – an ultrasound of the fetal spine and amniocentesis of the mother's amniotic fluid (to test for alpha-fetoprotein and acetylcholinesterase). AFP tests are now mandated by some state laws (including California). and failure to provide them can have legal ramifications. In one case, a man born with spina bifida was awarded a $2-million settlement after court found his mother's OBGYN negligent for not performing these tests. Spina bifida may be associated with other malformations as in dysmorphic syndromes, often resulting in spontaneous miscarriage. In the majority of cases, though, spina bifida is an isolated malformation.

Genetic counseling and further genetic testing, such as amniocentesis, may be offered during the pregnancy, as some neural tube defects are associated with genetic disorders such as trisomy 18. Ultrasound screening for spina bifida is partly responsible for the decline in new cases, because many pregnancies are terminated out of fear that a newborn might have a poor future quality of life. With modern medical care, the quality of life of patients has greatly improved.

The most accurate method of diagnosis is prenatal screening through real-time fetal images. However, since maternal body habitus leads to diagnostic difficulties using this method, MRI and sonography are the most commonly used technique since there is no exposure to ionizing radiation. At the beginning of the second trimester, the central nervous system (CNS) and anatomic structures of the fetus can be clearly visualized and the characteristic malformations of iniencephaly, such as a shortened trunk, marked lordosis in the cervicothoracic vertebrae, absence or partial absence of the occipital squama, abnoramal fusion of vertebrae, closed vertebral arches, formation of an encephalocele (for iniencephaly apertus), and dorsiflexion of the head in respect to the spine, can be precisely diagnosed as well as the severity and location established. Once established, further decisions can be made with regard to terminating the pregnancy or providing a plan of adequate postnatal care.

Phase contrast-MRI is an imaging method which is more sensitive than MRI for analysis of the pulsatile CSF flow in the ventricular system. This method takes multiple images of the ventricles within one cardiac cycle to measure the flow of CSF running past the area of acquisition. If no flow is seen, this is a reliable diagnosis of aqueductal stenosis as it implies that there is a blockage of CSF.

Ultrasonography can be used in utero to diagnose aqueductal stenosis by showing dilation of the lateral and third ventricles. A retrospective study found that diagnosis can be made as early as 19 weeks of gestation, and that on average diagnosis is made at 33 weeks. Unfortunately, prenatal diagnosis still has a poor prognosis even with immediate treatment upon birth.

An omphalocele is often detected through AFP screening or a detailed fetal ultrasound. Genetic counseling and genetic testing such as amniocentesis are usually offered during the pregnancy.

MRI is considered the best method of detecting aqueductal stensosis because it can visualize the entire length of the aqueduct, can clearly depict tumors, and can show ventricle enlargement or other deformations. It is helpful in determining the extent of the aqueductal obstruction, particularly when multiple masses or lesions are present, and thereby aids in determining the most appropriate treatment method (i.e. surgery, shunt, or ETV). When constructive interference in steady state (CISS) or fast imaging employing steady-state acquisition (FIESTA) sequence are used, subtle abnormalities or partial obstructions in the aqueduct can be depicted in the MRI. For example, CISS can be used to determine if a thin membrane interfering with CSF flow is present.

It is recommended that women who may become pregnant take 400 micrograms of folic acid daily.

There is neither a single cause of spina bifida nor any known way to prevent it entirely. However, dietary supplementation with folic acid has been shown to be helpful in reducing the incidence of spina bifida. Sources of folic acid include whole grains, fortified breakfast cereals, dried beans, leaf vegetables and fruits.

Folate fortification of enriched grain products has been mandatory in the United States since 1998. The U.S. Food and Drug Administration, Public Health Agency of Canada and UK recommended amount of folic acid for women of childbearing age and women planning to become pregnant is at least 0.4 mg/day of folic acid from at least three months before conception, and continued for the first 12 weeks of pregnancy.

Women who have already had a baby with spina bifida or other type of neural tube defect, or are taking anticonvulsant medication, should take a higher dose of 4–5 mg/day.

Certain mutations in the gene "VANGL1" have been linked with spina bifida in some families with a history of the condition.

Since many of the characteristics of iniencephaly, such as congenital retroflexion of the spine and fusion of the cervical vertebrae, are shared with other disorders, key differences are important to note.

While anencephaly experiences a partial to total lack of the neurocranium, iniencephaly does not. In anencephaly, the retroflexed head is not covered with skin while in iniencephaly, the retroflexed head is covered with skin entirely. Cervical vertebrae are malformed and reduced in iniencephaly while they are almost normal in anencephaly.

Even though KFS does experience malformed cervical vertebra due to failure of segmentation during early fetal development, there is not retroflexion of the head as seen in iniencephaly. While iniencephaly clausus is fatal, KFS is not and can be surgically corrected. Therefore, it is crucial to correctly diagnose KFS and not mistake it for iniencephaly clausus.

Encephaloceles of the face are generally classified as nasofrontal, nasoethmoidal, or naso-orbital, however, there can be some overlap in the type of encephalocele. They can also appear along any part of the cranial vault as they result from abnormal closure of cranial bones; the most common location for enncephaloceles is the occipital region. If the bulging portion contains only cerebrospinal fluid and the overlying membrane, it may be called a meningocele. If brain tissue is present, it may be referred to as a meningoencephalocele.

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

AVSDs can be detected by cardiac auscultation; they cause atypical murmurs and loud heart tones. Confirmation of findings from cardiac auscultation can be obtained with a cardiac ultrasound (echocardiography - less invasive) and cardiac catheterization (more invasive).

Tentative diagnosis can also be made in utero via fetal echocardiogram. An AVSD diagnosis made before birth is a marker for Down syndrome, although other signs and further testing are required before any definitive confirmation of either can be made.

The syndrome is generally diagnosed clinically shortly after birth. The infant usually has respiratory difficulty, especially when supine. The cleft palate is often U-shaped and wider than in cleft palate that is not associated with this syndrome.

A VSD can be detected by cardiac auscultation. Classically, a VSD causes a pathognomonic holo- or pansystolic murmur. Auscultation is generally considered sufficient for detecting a significant VSD. The murmur depends on the abnormal flow of blood from the left ventricle, through the VSD, to the right ventricle. If there is not much difference in pressure between the left and right ventricles, then the flow of blood through the VSD will not be very great and the VSD may be silent. This situation occurs a) in the fetus (when the right and left ventricular pressures are essentially equal), b) for a short time after birth (before the right ventricular pressure has decreased), and c) as a late complication of unrepaired VSD. Confirmation of cardiac auscultation can be obtained by non-invasive cardiac ultrasound (echocardiography). To more accurately measure ventricular pressures, cardiac catheterization, can be performed.

A chest x-ray will be given to determine the size of the heart and the blood vessels supplying blood to the lungs.

There is no cure or standard treatment for anencephaly and the prognosis for patients is death. Most anencephalic fetuses do not survive birth, accounting for 55% of non-aborted cases. Infants that are not stillborn will usually die within a few hours or days after birth from cardiorespiratory arrest.

Four recorded cases of anencephalic children surviving for longer periods of time are Stephanie Keene (better known as Baby K) of Falls Church, Virginia, USA, who lived for 2 years 174 days; Vitoria de Cristo, born in Brazil in January 2010 and surviving until July 17, 2012; Nickolas Coke of Pueblo, Colorado, USA, who lived for 3 years and 11 months, and died October 31, 2012; and Angela Morales, from Providence, Rhode Island, who live for 3 years and 9 months, and died December 16 2017.

In almost all cases, anencephalic infants are not aggressively resuscitated because there is no chance of the infant's ever achieving a conscious existence. Instead, the usual clinical practice is to offer hydration, nutrition, and comfort measures and to "let nature take its course". Artificial ventilation, surgery (to fix any co-existing congenital defects), and drug therapy (such as antibiotics) are usually regarded as futile efforts. Some clinicians and medical ethicists view even the provision of nutrition and hydration as medically futile.

A color flow and doppler imaging is used to help confirm the presence as well as evaluate the severity of ASD and MS.

Treatment is with neonatal surgical repair, with the objective of restoring a normal pattern of blood flow. The surgery is open heart, and the patient will be placed on cardiopulmonary bypass to allow the surgeon to work on a still heart. The heart is opened and the ventricular septal defect is closed with a patch. The pulmonary arteries are then detached from the common artery (truncus arteriosus) and connected to the right ventricle using a tube (a conduit or tunnel). The common artery, now separated from the pulmonary circulation, functions as the aorta with the truncal valve operating as the aortic valve. Most babies survive this surgical repair, but may require further surgery as they grow up. For example, the conduit does not grow with the child and may need to be replaced as the child grows. Furthermore, the truncal valve is often abnormal and may require future surgery to improve its function.

There have been cases where the condition has been diagnosed at birth and surgical intervention is an option. A number of these cases have survived well into adulthood.

Although there are several classifications for VSD, the most accepted and unified classification is that of Congenital Heart Surgery Nomenclature and Database Project.

The classification is based on the location of the VSD on the right ventricular surface of the inter ventricular septum and is as follows:

This condition may be visible, after about 26 weeks, on an ultrasound. On antenatal USG, the finding of an absent or small stomach in the setting of polyhydramnios was considered a potential symptom of esophageal atresia. However, these findings have a low positive predictive value. The upper neck pouch sign is another sign that helps in the antenatal diagnosis of esophageal atresia and it may be detected soon after birth as the affected infant will be unable to swallow its own saliva. Also, the newborn can present with gastric distention, cough, apnea, tachypnea, and cyanosis. In many types of esophageal atresia, a feeding tube will not pass through the esophagus.

This condition takes several different forms, often involving one or more fistulas connecting the trachea to the esophagus (tracheoesophageal fistula).

Children affected with PRS usually reach full development and size. However, it has been found internationally that children with PRS are often slightly below average size, raising concerns of incomplete development due to chronic hypoxia related to upper airway obstruction as well as lack of nutrition due to early feeding difficulties or the development of an oral aversion. However, the general prognosis is quite good once the initial breathing and feeding difficulties are overcome in infancy. Most PRS babies grow to lead a healthy and normal adult life.

The most important medical problems are difficulties in breathing and feeding. Affected infants very often need assistance with feeding, for example needing to stay in a lateral(on the side) or prone(on the tummy) position which helps bring the tongue forward and opens up the airway. Babies with a cleft palate will need a special cleft feeding device (such as the Haberman Feeder). Infants who are unable to take in enough calories by mouth to ensure growth may need supplementation with a nasogastric tube. This is related to the difficulty in forming a vacuum in the oral cavity related to the cleft palate, as well as to breathing difficulty related to the posterior position of the tongue. Given the breathing difficulties that some babies with PRS face, they may require more calories to grow (as working of breathing is somewhat like exercising for an infant). Infants, when moderately to severely affected, may occasionally need nasopharyngeal cannulation, or placement of a nasopharyngeal tube to bypass the airway obstruction at the base of the tongue. in some places, children are discharged home with a nasopharyngeal tube for a period of time, and parents are taught how to maintain the tube. Sometimes endotracheal intubation or tracheostomy may be indicated to overcome upper respiratory obstruction. In some centers, a tongue lip adhesion is performed to bring the tongue forward, effectively opening up the airway. Mandibular distraction can be effective by moving the jaw forward to overcome the upper airway obstruction caused by the posterior positioning of the tongue.

Given that a proportion of children with Robin sequence will have Stickler syndrome, it is important that a child with PRS have an evaluation by an optometrist or ophthalmologist in the first year of life looking for myopia that can be seen in Stickler syndrome. Because retinal detachment that can occur in Stickler syndrome is a leading cause of blindness in children, it is very important to recognize and be thoughtful of this diagnosis.

The most well-known classification was the fourfold system developed by Collett and Edwards in 1949. Collett/Edwards Types I, II, and III are distinguished by the branching pattern of the pulmonary arteries:

- Type I: truncus -> one pulmonary artery -> two lateral pulmonary arteries

- Type II: truncus -> two posterior/posterolateral pulmonary arteries

- Type III: truncus -> two lateral pulmonary arteries

The "Type IV" proposed in 1949 is no longer considered a form of PTA by most modern sources.

Another well-known classification was defined by Van Praaghs in 1965.

Before birth, openings in the abdomen can usually be detected by a detailed ultrasound or AFP screening. In addition to the ultrasound or AFP scanning, it is also necessary for children with this defect to be checked for other birth defects because genetic disorders are usually associated with some of the abdominal wall defects. In looking for other genetic disorders that may be associated, Genetic counseling and further genetic testing, such as amniocentesis, are offered.