Preventing Birth Defects: Understanding Teratogenic Factors

Preventing Birth Defects: Understanding Teratogenic Factors

Source: INTERPSIQUIS. 2004

Author: Iris. M. Motta, BA in Psychology

Professor JTP, Universidad Argentina John F. Kennedy

Secretary of Neuropsychology Postgraduate Course in Dynamics of the University Kennedy

Company Secretary of Biopsychopedagogy, Argentina

Email: imotta@fibertel.com.ar

Keywords: Teratogenic Factors, Prevention, Defects in the Developing Embryo

Summary

The biopsychosocial health of a person rests largely on proper embryonic and perinatal development. For this to be possible, it is necessary to implement effective primary prevention strategies. Many of these strategies depend on global health policy, but many relate to knowledge and awareness of the need for behavioral changes designed to improve living conditions in general and during the gestational period in particular.

Health professionals cannot ignore the factors that alter normal development, as the consequences, whether predominantly biotic, psychological, or social-cognitive, affect the whole existence of those who suffer. Therefore, for the purpose of exercising effective therapeutic actions, but primarily for the purpose of avoiding their needs as much as possible, we propose, without pretense of completeness, to explore the wide range of factors that can produce malformations and/or Central Nervous System dysfunction.

The Role of Prophecy and Prevention in Health

From ancient times, humanity has been concerned about the future. In all cultures, there have been social characters who are assigned the gift of prophecy. These characters served the important role of calming the mind from the anxiety generated by uncertainty. In current usage, the word “prophet” is defined as “one who predicts the future.” In our Judeo-Christian culture, these characters are not lacking. The Bible is perhaps the greatest exponent of stories in which a person “is called and has the duty to call others,” who tells the people what will happen. But saving a few exceptions that were revelations by supernatural means, the vast majority of them were brought by God to draw attention to data perceptible in the reality of the moment whose consequences were disastrous, logical, and obvious because they contradicted the divine law, but they were not noticed by the people. When Jeremiah anticipated the catastrophe that was looming on Jerusalem, ending with the conquest of King Nebuchadnezzar and the subsequent captivity in Babylon, he reprimanded the people about the need to reverse the behaviors of idolatry that had become more prevalent and were explicitly forbidden. Thus, they had a primarily defensive role.

Today, there is much scientific data that can be considered to avoid an enormous amount of future damage. Cardiovascular risk factors and stroke are known and reported, many standards and elements that make transport safer have been developed, etc. But there has also been enormous progress in the discovery of factors that influence the occurrence of developmental disorders. Prospective parents have many expectations about their unborn child. They wonder about who will inherit their eyes, what hair color they will have, and surely, they also worry about their future health.

Not everything is known, but much is known, and much can be prevented. Health professionals, in a broad sense as defined by the WHO, must be the first to see clearly the evidence of the need for more effective primary prevention against the occurrence of large stocks in the fullness of their potential to contribute to a healthier humanity. Many of the factors that cause disabilities of various types are unknown, and for them, we can do little, but a lot is known, and still, adequate measures are not taken to avoid them. Often, these measures depend on health-policy decisions that exceed us in particular, but we cannot afford that such measures are not carried out due to our ignorance. The popular saying states: “There is none so deaf as he who will not hear,” and the evidence is clear.

The word noxa is a substantivization of harmful (Latin nocivus: harmful, injurious) [1]. Noxae may be of several types depending on the time of the cycle in which they appear. Thus, there are post-natal noxae (trauma, infection, etc.) that cause injuries in specific tissues. But there are also those that affect normal gestational development.

Henceforth, we will try to make an approach, which is not exhaustive, to those factors that may harmfully be involved in the embryonic development of the human.

The word Teratogenesis comes from the Greek “teratos,” meaning monster. The original meaning of the word refers to gross structural malformations, although the current concepts of this term have been extended to include more subtle developmental abnormalities such as delayed intrauterine development, behavioral disorders, and other functional deficiencies. The meaning of the word indicates the nature of the ancient beliefs which attributed the divine or satanic intervention, hybridization with other species, or a terrifying experience of pregnant women as the leading role in its genesis, in contrast to the multifactorial etiology accepted today.

Defining Teratogens and Their Impact

In this way, we define a teratogen as any chemical, physical agent, infectious or deficiency state, acting during the embryonic or fetal period, that can produce morphological or functional impairment. Teratology is the science that studies the causes, mechanisms, and manifestations of abnormal fetal development from the structural and functional perspectives.

The term strain or deformation is used to indicate a change in the shape, size, or position of a structure that had a normal early development (clubfoot, congenital hip dislocation). The term disruption is sometimes used to indicate the failure or interruption of the development of a previously well-formed structure (formation of cracks). Dysplasia should be used only when there is an abnormal tissue of an organ or structure. However, many times these terms are used interchangeably.

An estimated 2-4% of newborns have congenital anomalies as major structural changes, increasing the percentage to 8-10% if we consider development up to 5 years. This is because many teratogens, by their nature or by the time of pregnancy in which they appeared, have functional consequences that do not manifest until later. Despite the importance of knowledge for prevention and/or treatment of the consequences, both medical and social, the causes are unknown in 40-70% of cases of congenital malformations. This suggests that existing teratogens are actually much more varied than what science can tell. It is known that hereditary diseases account for 15-20%, chromosomal disorders for 5%, and environmental factors such as exposure to drugs for 2-4%. The rest is caused by congenital infections and systemic diseases [2].

Moreover, in most cases, medical consultations occur when the woman knows or suspects that she is pregnant, and several weeks have passed, so much has already happened in the process of cell differentiation, and many noxae may have acted negatively.

There is a branch of Teratology, Experimental Teratology, which, together with Embryology, makes constant efforts to expand the range of known teratogenic factors and thus improve the possibilities for prevention. However, animal testing has not always successfully extrapolated the results to humans because, as pointed out by Wilson in the basic principles of teratology of his famous treatise “Environment and Birth Defects,” susceptibility to a teratogen depends on the genotype of the embryo and how this interacts with environmental factors. Proof of this is the infamous thalidomide, a drug used between 1959 and 1965 in pregnant women to treat anxiety and nausea. Its teratogenic effects, consisting of defective limb development, could not be foreseen because in certain species used for experimentation, malformations in rabbits and mice appeared only at high doses, never administered in humans. Even more so, in other species such as dogs and cats, the malformations never occurred. At this time, there are numerous medical associations in open protest against the return of thalidomide to pharmacies (as in the U.S. it was prohibited after the terrible marketing findings) because it has proven useful in treating certain complications of leprosy. These associations argue that once released, its sale will be very difficult to control.

Critical Periods of Fetal Development

The mechanisms of teratogenesis are essentially reparative cell death without regeneration, the delay of mitosis, the delay of differentiation, or vascular physical constraints and the inhibition of cell migration.

The moment of maximum vulnerability for the developing fetus is between 17 and 57 days after fertilization, i.e., the first 10 weeks after the last menstrual period in women with regular cycles. During that time, cellular organization, differentiation, and organogenesis occur. Any harmful agent will have a teratogenic effect on the organs that are developed at that time. During this critical period, a phenomenon of “all-or-nothing” occurs, i.e., any aggression on the fetus during the first 4 weeks will result in an abortion, while later, birth defects usually occur without spontaneous abortion.

We will see that many of the factors that we can produce subsequent malformations and dysfunctions of varying severity. One is low birth weight. On this point, it is important to make some considerations now because these patients are a relatively new pediatric population, and this is because, with the advancement of medical science, children who in another era would have died now survive. But this opens a new vista to interdisciplinary work because, in many cases, they develop neurological disorders that cover a wide spectrum ranging from severe to relatively overlapped (minor or soft signs). Low birth weight can be produced by premature delivery or intrauterine growth retardation. These children are more likely to have respiratory and cardiovascular disorders, a high incidence of stroke, difficulty in regulating body temperature, and an increased risk of infections. In neuropsychological research, a history of low birth weight has been found in a high percentage of patients with soft neurological signs, with various types of alterations, attention, and visoperception being the most commonly affected functions. They are followed by the involvement of language and motor skills. There is also evidence that their IQ is directly proportional to the length of the gestational period and inversely proportional to neuroanatomical abnormalities [3, 4, 5].

Family History and Genetic Factors

Family history obtained before pregnancy is a very important aspect to consider in the prevention of potential anomalies. The age of the mother, when more than 35 years, increases the risk of genetic diseases such as Down syndrome and other chromosomal abnormalities, whereas when the father is over 60 years of age, it increases the risk of Achondroplasia (an anomaly in the growth of the bones that produces one of the most common types of dwarfism). The existence of congenital or genetic diseases in the family has a tendency to recur. Belonging to certain ethnic groups may influence the onset of certain diseases: sickle cell anemia is prevalent among people of African origin, Tay-Sachs disease is common in people of European Jewish origin, thalassemia is common in certain Mediterranean communities, the cystic fibrosis gene occurs in a specific case in every 20 people of European origin, etc. In epidemiological studies of Multiple Sclerosis, it has been found that the prevalence is much higher in populations with a Scandinavian background. Many of these diseases can be detected early. These prospective parents at risk should be informed of the available evidence for diagnosis before pregnancy.

Teratogenic mechanisms are better known in chromosomal alterations that are the basis of heredity defects. The most common chromosomal abnormality is mutation, consisting of changing the sequence of nucleotides in the DNA molecule. Another type of chromosomal abnormality is causing chromosome breakage or nondisjunction or abnormal crossovers so that the normal process of DNA repair can be modified. Altering the number of chromosomes (monosomy or trisomy, such as Down Syndrome) is also a cause of birth defects. The types of genetic alterations that can cause birth defects are estimated at more than 400 [6].

All these genetic changes are often presented as proteins that differ phenotypically from normal and cause different diseases depending on the type of protein that is affected. Phenylketonuria is caused by inactivation of the enzyme that catalyzes the conversion of phenylalanine to tyrosine in the diet, producing mental retardation, microcephaly, congenital heart disease, and low birth weight. Cystic Fibrosis is caused by a defective version of a membrane protein. Duchenne Muscular Dystrophy is given by altering structural proteins that prevent the normal functioning of the muscles, causing progressive weakening with prostration and death when muscles fail to serve the respiratory system. Fragile X chromosome syndrome is the most common form of hereditary mental retardation. The typical clinical features are: long face, prominent ears, muscular hypotonicity, macroorchidism (in men older than 8 years), learning difficulties ranging from specific disorders to moderate mental retardation, hyperactivity, behavioral problems, and autism. The cause is a mutation in a single gene that leads to the absence of a protein (FMRP) with an important function in the brain [7].

Interaction of Genetic and Environmental Factors

While it is true that there are thousands of diseases that result from genetic alterations in which the heritability is clearly determinable as autosomal (recessive or dominant) or sex-linked clinical phenotype, the fact remains that they are much more common diseases caused by genetic factors interacting with the environment. These are produced, as we shall see later, by ionizing radiation, chemical agents (medicines, food additives, agricultural or industrial use, carcinogenic agents), infectious agents, etc.

Chemical Agents and Their Effects

Most of the things we think can act negatively on pregnancy, unfortunately, really do.

  • Smoking during pregnancy increases the risk of spontaneous abortion, fetal malformations, premature delivery, and low birth weight infants. The mechanism of action of snuff is the inactivation of hemoglobin for carbon monoxide, reducing the irrigation by placental vasoconstrictive action of nicotine, and changes in appetite. In addition, cigarette smoke contains tar and toxic gases such as carbon monoxide and cyanide. Many researchers recognize adverse neurobehavioral effects are usually milder than the growth retardation, but more important epidemiologically.
  • Alcohol consumption during pregnancy results in fetal sequelae ranging from hyperactivity to mental retardation, without forgetting the fetal malformations, stillbirth, fetal growth retardation, abortions, and premature detachment of the placenta [8]. Intrauterine growth is more affected by continuous consumption, resulting in symmetric intrauterine growth retardation (weight, height, and head circumference affected) if during the first trimester. If in the second or third trimester, weight is more affected, and there is a greater likelihood of recovery. Instead, the central nervous system deteriorates further with the consumption of large amounts. Occasional nerve cells are not capable of recovery, and structural alterations and functional vary by time of exposure. The emergence of so-called Fetal Alcohol Syndrome (FAS) occurs at an average of 200 gr. alcohol daily, but with 60-80 gr. there is a decrease in birth weight. The characteristics of this syndrome are prenatal growth retardation or postnatal microcephaly with severe central nervous system including neurological impairment, developmental delay, behavioral deficits, and abnormal facial features such as small palpebral fissures, thin upper lip, maxillary hypoplasia, palpebral ptosis, small and upturned nose, flat face, and facial elongation. Although the physical characteristics change a little with the growth in children with FAS, behavioral abnormalities persist throughout life [9]. These include: attention deficit disorder, low IQ, and impulsivity. The Massachusetts General Hospital in Boston conducted a study that concluded that there are a number of women carrying some form of the gene that governs the processing of alcohol in which tolerance to it is greater, so that if consumers could do so in larger quantities before feeling the effects, this increases the chance that the baby is born with FAS [10]. Alcohol is one of the factors that must put special emphasis on prevention, especially as the social diffusion of consumption means that many women do not consider it dangerous.
  • It was long debated the effect of caffeine and its effect on the fetus. Several studies have shown that eating a couple of cups of coffee or tea without risk to the fetus. The consumption of soft drinks or chocolate with equivalent amounts of caffeine can be consumed during pregnancy. However, a study in Prague in 1997 indicates that habitual moderate consumption of caffeine is associated with low birth weight.

Effects of Drug Addiction During Pregnancy

Drug addiction [11, 12, 13] should be avoided, especially during pregnancy.

  • Smoking marijuana causes deformities of the sperm and is teratogenic at high doses in experimental animals.
  • Cocaine favors the placenta through its vasoconstrictor action with increased blood. As a low molecular weight, it diffuses rapidly from the placenta to the fetus, who has high toxicity due to immaturity of the liver. Teratogenic effects of cocaine use during pregnancy are not described as a classic syndrome because they can be multiple and nonspecific. These can be cranio-spinal malformation (hydrocephalus, porencephaly, cefalomalacia, encephalocele, myelomeningocele, hypoplasia of the corpus callosum, parietal lobe cleft), face (oro-orbital unilateral cleft, cleft lip, cleft palate, facial palsy, ptosis, skin blemishes, etc.), heart (auricular defects and ventricular septum, transposition of great vessels, pulmonary artery stenosis, hypoplastic right heart syndrome, right ventricular hypertrophy, cardiomegaly), genitourinary, and gastrointestinal (ileal atresia, inguinal hernia, agenesis kidney, polycystic kidneys, undescended testes, hydrocele), neurological (irritability, increased muscle tone, abnormal reflexes, anorexia, sleep disorders) and osteoarticular (shortening of limbs, polydactyly, syndactyly).
  • Heroin use can cause fetal growth retardation and fetal anomalies, and whether women share needles or have sexual promiscuity runs the risk of infection by the AIDS virus. However, most neonatal therefore recognized the use of opiates, especially heroin, is the withdrawal syndrome that occurs at birth, which is seen in up to 75% of newborns in this group during the first 48 hours of life. It is reported that the prevalence is high in these children of ADHD and specific learning disorders, which are generally better compensated for the children of addicts who have been adopted at an early age [14]. This suggests the importance of sound stimulation to tap the potential effects of neuronal plasticity. The appearance of this syndrome is dependent on the daily maternal dose.
  • LSD produces malformations and chromosomal abnormalities.
  • Amphetamines are stimulants with effects on the sympathetic nervous system to produce the release of norepinephrine by the presynaptic terminal so that, although a link between the consumption of amphetamines and fetal malformations or other abnormalities at low doses has not been proven, by vasoconstrictor and hypertensive effect are potentially producing alterations in placental and secondarily, abruptio placenta, abortion, prematurity, and low birth weight newborns. A withdrawal syndrome has been submitted after birth in exposed children, which is characterized by abnormal sleep, tremors, hypertonia, irritability, vomiting, sucking desperately, tachypnea, and visual disturbances, up to 8 days after birth.

Industrial Solvents and Other Chemicals

You should also take into account the common use of certain chemicals such as industrial solvents (e.g., Benzene). Among the uses of these is the manufacture of medicines, dyes, detergents, plastics, explosives, and in the synthesis of other aromatics. Also as a parasiticide in wounds (veterinary) and solvent lacquers, waxes, and oils. In gasoline, it is used as an antiknock. These solvents have effects such as anencephaly, hydrocephalus, meningocele, agenesis of corpus callosum, ear anomalies, skeletal malformations of the spine, cleft palate, polydactyly, and vascular defects. In some cases, they are abortifacients. Its mechanism of action, in general, relates to certain chemical reactions with cellular macromolecules such as proteins, lipids, DNA, and RNA, inactivating specific protein receptors, damaging cell membranes, and triggering mutagenic reactions [15]. Many of these chemicals are part of everyday compounds, and due to their low cost and their impact on various systems, they are used as inhalant drugs (e.g., glue) [16].

Another example of this type of element is polychlorinated biphenyls (PCBs), used as an insulator and coolant in electrical and high voltage installations. It is among the 12 most dangerous pollutants, and at high temperatures, it is five million times more toxic than cyanide. Several studies have shown that prenatal exposure to these substances produces cognitive and behavioral impairment in the long run [17]. In 1976, it was banned in the U.S. and Europe, and the World Health Organization (WHO) warned about its carcinogenic effects [18].

Pesticides and Their Impact

Since the end of the 2nd World War and the growth of the agro-industry, pesticide use has increased exponentially. However, even many FAO countries have no legislation on their distribution and use, despite the existence of a large amount of data that point to their dangerous effects on different body systems, particularly the nervous system [19]. Several years ago, the Committee on Agriculture of the U.S. Senate made a decision: 52 pesticides banned in this country by the Environmental Protection Agency (most causing birth defects) would be exported to third-world countries whose legislation does not protect the population against them. Agent Orange (used in the Vietnam War as a chemical weapon) arrived in Argentina between 1976 and 1983 to be used as a defoliant in snuff cultures. Not only is it cumulatively toxic to the farmer, but it also accumulates in the groundwater so that their action exceeds that which is directly over the farm workers. Even today, in the crops of the Province of Misiones, other highly toxic pesticides are used by inexperienced personnel. In the same province, there are entire populations whose descendants have noticeable deformities and/or mental retardation ranging from moderate to severe.

Dr. Hugo DeMaio, Director of the Center for Children’s Hospital Myelodysplasia Posadas, told a news program: “They (farmers) are instructed about intoxication. They know they have to be careful because it can poison, and poisoning can kill or cure. What they do not know is that with the use of these chemicals, their adipose tissue is contaminated, and they will be a carrier because it is not degradable, he and his descendants. It’s going to change genetic information, and the child will have a disability or a malformed child or cancer. That they do not know because he does not say” [20].

Medications and Their Teratogenic Risk

Drugs may cause fetal abnormalities, and therefore any prescription medication must be consumed under medical supervision. The Food and Drug Administration (FDA) has categorized the U.S. teratogenic risk of different drugs [21]:

  • CAT. A: Controlled studies in women have demonstrated no risk to the fetus during the 1st trimester, and there seem to be no further signs of toxicity. Examples are certain thyroid hormones, some asthma drugs, and topical corticosteroids.
  • CAT. B: Animal studies have shown no teratogenic risk, but there are no controlled studies in women. Examples are acetaminophen (non-opioid analgesic), morphine (analgesic), some antiemetics, antifungals, penicillins, and some anti-infectives.
  • CAT. C: Studies in animals have shown adverse effects. Should be given only if the potential benefit justifies it. Examples are antihypertensives, antimalarials, amebicides, aspirin, diazepam (anxiolytic), carbamazepine (antiepileptic), lidocaine (local anesthetic), amphetamine (stimulant), methylphenidate (stimulant), some antiemetics, laxatives, anti-inflammatories, some antibiotics, immunoglobulin, antiviral, some vaccines, anti-spasticity, and muscle relaxants.
  • CAT. D: There is clear evidence of teratogenicity, but the benefit of its use is acceptable despite the risk (e.g., in case of extreme situations in which the life of the mother and the baby is threatened). As an example, we quote: antihypertensive drugs, imipramine (antidepressant), lithium (antipsychotic), risperidone (antipsychotic), alprazolam (anxiolytic), phenobarbital (hypnotic), pentobarbital (hypnotic), diuretics, anticoagulants, tetracycline, antineoplastic, and some anti-inflammatories.
  • CAT. X: Studies in animals or humans have demonstrated fetal abnormalities, and the risk of their use exceeds the benefit. They are contraindicated in pregnant women or those who potentially could be. As examples, we cite: quinine (antimalarial), triazolam (anxiolytic/hypnotic), androgens, estrogens, progestogens, some thyroid hormones, some corticosteroids, glycerol (cough suppressant), misoprostol (antiulcer), some acne, and antipsoriatic.

Physical Agents: Injuries, Compressions, and Radiation

Among the physical factors, we must consider all types of injuries and compressions (e.g., those produced by uterine tumors), which also directly harm the baby and can cause placental abruption.

Another factor is the physical type of radiation. Injuries due to these can be produced by 2 mechanisms [22]:

  1. Direct mechanism: the energy released alters cellular links, causing an alteration of DNA and structural proteins.
  2. Indirect mechanism: the interaction with photons that release free radicals that damage DNA, water, and membranes, being able to produce alterations in mitosis (inhibition, increase, etc.) mutations or cell necrosis.

The effects of radiation depend on the dose, frequency, and type of tissue most vulnerable at the time of receipt.

According to the time of exposure, the effects are variable:

  • Preimplantation Embryo: death.
  • Introduction to 9 weeks: malformations even at doses several exploratory.
  • 9 weeks at birth: CNS functional impairment and increased player and leukemia and brain tumors.
  • Postnatal Period: delays in development and bone growth, eye abnormalities, and alterations in dentition.

It was precisely the interest in detecting DNA damage in people exposed to varying levels of radiation, such as Hiroshima survivors and their descendants, that in 1984 the U.S. government sponsored an international conference for scientists to examine the effects of factors environmental mutagens. But to know the abnormalities in the genetic code, it was necessary to first know the normal genetic code. Under this, Renato Dulbecco, Nobel Prize winner for his pioneering work on oncogenic viruses, proposed in 1986 that the international scientific community determine the normal sequencing of human DNA. Thus emerged the Human Genome Project [23]. But humans think that we cannot construct something positive without starting the destruction: nuclear weapons from being developed from the 2nd World War, in which the heat generated by the explosion of Hiroshima left carved figures of civilian casualties in the walls [24], to weapons currently used by NATO and the U.S. (and over 40 other countries although they deny) [25] is what the experts called depleted uranium armament. Depleted Uranium is nothing other than wastes from nuclear power plants and proved to be an excellent penetrator of armor and bunkers, as well as waste, is free. But despite NATO reports stating that it has no risk, it has been proven that they carry warheads that are pyrophoric and loose particles in the path, which remain in the air as the medium of uranium oxide step. The movement of these particles in the air has no boundaries so that radioactive contamination, after years, will spread across the globe and reach all people. Remember that only considering the U238 (which is the most toxic included in the EU) the time it takes to lose only half of its radioactivity is 4,500 million years. This contamination will increase cancers, immunodeficiencies, and other diseases, but above all, it will produce genetic damage [26]. Against this background, the images of a planet of mutants will no longer be just a creative idea of the scripts of science fiction films.

Maternal Nutritional Status

Among environmental factors, the mother’s diet is an important factor to consider. During pregnancy, a desirable body weight gain, harmonious and progressive, should occur. The diet should contain sufficient amounts of carbohydrates, protein, and essential fatty acids. The calorie intake should be sufficient, but not exaggerated: between 2200 and 2500 calories a day with an appropriate amount of vitamins. However, the adjustment should be made by the doctor according to the peculiarities of the pregnant woman. These needs are met by the usual diet in developed countries. When these requirements are not met, fetal undernutrition and hypoxia occur, and from this, fetal malnutrition increases the risk of neurologic and intellectual difficulties. Nutritional insults during critical stages of prenatal or postnatal [27] result in alterations in the histogenesis of nerve tissue [28]. Abnormalities in neurogenesis have been reported, with stem cells being particularly vulnerable. The anomalies caused by protein-calorie malnutrition in gliogenesis, cell migration, cell differentiation, and formation of neuronal circuits at critical periods of development would be of great importance. Disorders in synaptogenesis have an impact on a deficit in brain plasticity in malnourished subjects [29], which lead to poor roads and circuit training, with consequent behavioral and learning deficits [30, 31, 32]. This is an issue of utmost importance if we want to do prevention, and poverty rates have increased alarmingly in our country. The unfavorable economic and educational conditions put low-income populations in a position to perpetuate the disadvantages when they “inherit” their descendants the frank intellectual limitations, when they are not condemned to an early death [33].

On the other hand, a recent prospective study conducted in Helsinki on 7086 subjects determined the increased risk of developing schizophrenia or schizotypal those which showed low height and weight at birth due to maternal malnutrition [34].

Doctors also warn about the implementation of pure vegetarian diets as it may cause a deficiency of vitamin B12, whose main source is meat, milk, and eggs.

Several groups of Consumer Protection have made their voices heard about the potential danger of the use of GM food. According to their studies, while not really been able to demonstrate its teratogenic action, production companies have not clearly demonstrated the absence of long-term risk [35].

The excessive increase of weight and gestational diabetes promotes the birth of obese children. Gestational diabetes develops in 1-3% of pregnancies, but their frequency may increase in specific populations (e.g., Mexican, Asian, Indian). Metabolic disorders of the mother during embryogenesis are linked to birth defects. Research conducted at the University of Boston in the eighties said that women who developed gestational diabetes had twice as likely to give birth to children with such anomalies regarding pregnant women without diabetes. However, the researchers also suggest that diabetes during pregnancy is not in itself a risk factor for chromosomal defects, since these are formed in early states of pregnancy, but it is an indicator of pre-existing risk factors [36]. In the case of uncontrolled type 1 diabetes during early pregnancy, the chances of giving birth to deformed babies is 4 times higher than in those cases where the disease is controlled [37].

Importance of Folic Acid and Other Nutrients

Furthermore, weight loss diets are contraindicated during pregnancy because of the risk of ketosis and neurological disorders in the fetus.

It is thought that vitamin supplements are not necessary when you consume a balanced diet, with the exception of the consumption of iron and folic acid, as it has been shown to prevent 70% of the defects in the neural tube (NTD). The most common NTD is anencephaly (skull with no brain) and spina bifida (meningocele and myelomeningocele), which are malformations of the vertebrae that allow the exposure of the spinal cord. These are serious conditions, and 50% of children die during the first days of life. Those who survive do so with great consequences. In populations where the diet was supplemented with folic acid, a decrease in other birth defects such as cleft lip, cleft palate, and some heart deformations has also been observed [38]. In some countries, like the U.S., the addition of folic acid in flour and cereals is regulated, which is critical if we are to prevent the occurrence of these severe malformations. Because the neural tube closes between 25 and 28 days of gestation, it is useless to take folic acid when it is known that the woman is pregnant, as this usually happens after that period. [39]

The use of some other dietary supplements must also be put in brackets. For example, zinc, used to reduce the risk of low birth weight in third-world populations where the diet is rich in fiber and very low in animal protein, has been studied in the United Kingdom. The conclusions reached after studying a group of children aged 13 months whose mothers took zinc during pregnancy and a control group are not conclusive regarding the declining level of psychocognitive development but note that children in the control group had a higher degree of development [40].

Disorders Related to Medical Problems



Another source of problems is called blood incompatibility. There are two types of incompatible blood: blood group incompatibility and Rh incompatibility. ABO incompatibility or group occurs when the mother is group O and the father of group A, B or AB. Rh incompatibility occurs when the father is Rh positive and the mother is Rh negative. The Rh incompatibility problem is that the mother when in contact with the blood of Rh-positive baby, produces antibodies against fetal red blood cells. These antibodies cross the placenta and cause destruction of the baby’s red blood cells, causing anemia, increased bilirubin, heart failure and even fetal death. However, only 5% of women have alloimmunization (development of antibodies against the Rh factor). In these pregnancies must always do a good prenatal care, in which the doctor should order a special test called the Coombs test to verify whether mother has antibodies. If the result is negative should be placed a vaccine for pregnant women to prevent the form, and then again after delivery if the baby is Rh positive.

Psychosocial health of the mother is not a minor issue. In case of unwanted pregnancy or lack of a social network containment and specific stress-producing situations, can cause high levels of anxiety and distress that accompany the state of pregnancy and generate somatic changes that indirectly affect child (maternal hypertension, impaired vagal, changes in appetite, nausea, vomiting, etc.).. For researchers, it is clear that stress affects the possibility of premature labor, but to what degree. However, it is known that stress can cause increased secretion of steroids on the matrix and thus stimulate the cellular receptors that control uterine contraction and relaxation, leading to increased risk of preterm delivery [41]. A sad example recounted the March 26 war correspondent of the newspaper Clarin in Baghdad said that hospitals began to serve pregnant women with spontaneous abortions for fear of the bombing. In a maternity hospital, in a single day, there were 9 cases and only two babies survived [42].

Before the occurrence of a pregnancy is advisable to check the immunity of women to those diseases which can be problematic if gestation. It is therefore recommended to check the degree of immunity against rubella and chickenpox, and if necessary to prevent pregnancy vaccination within 3 months. You should verify if the woman has received doses of tetanus vaccine in the past 10 years. It is also recommended to vaccinate people at risk of infection with hepatitis B before they become pregnant. If the woman is at risk of contracting the HIV virus should be recommended for testing before pregnancy or as early if it is already in place, but today is a routine examination of suspected pregnancy.

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Rubella: is a highly contagious disease caused by a virus which is transmitted to the baby and it produces infection. This virus causes fetal malformations when the mother gets the disease in the first trimester. The risk of fetal infection depends on the gestational age: 61% when infection occurs in the first 4 weeks of pregnancy, 26% if it occurs between 5 and 8 weeks, and 8% when it occurs between 9 and 12 weeks . Fetal abnormalities are loss of hearing (60-75%), eye defects such as cataracts (50-90%), heart (40-85%) and psychomotor retardation (25-40%). Other changes are intrauterine growth retardation and hepatosplenomegaly.

Chickenpox is a highly contagious viral disease transmitted by blood to the fetus through the placenta. When fetal disease occurs early in pregnancy can cause birth defects and at the end of the third trimester of pregnancy (especially if the baby is born within 5 days after infection of the mother) is also dangerous for the baby, since the 25-50% of infants develop a severe form of chickenpox, with a mortality rate of 30%.

Toxoplasmosis: a zoonosis, meaning that the animals can transmit to humans. It is caused by a parasite called Toxoplasma gondii and the disease can occur in an acute or chronic. The transmission of toxoplasmosis to the fetus occurs if the mother becomes infected during pregnancy acute. In the mother toxoplasmosis is not dangerous, the infection is usually mild or no symptoms. If acute infection occurs during the first two months of pregnancy rarely occurs infection of the fetus because the placenta acts as a “barrier.” In general, most people already had the disease unwittingly and immunoglobulin G values that are measured will always remain positive.

The triad of signs suggesting congenital toxoplasmosis: chorioretinitis, intracranial calcifications and hydrocephalus. However, many children born with toxoplasmosis have no signs at birth and later develop visual and learning disabilities.
Preventive measures include not eating raw or undercooked meat or unpasteurized milk, wear gloves when gardening or any place where they can find cat droppings and wash fruits and vegetables [43].

Syphilis: the risk of transplacental infection depends on the stage of maternal infection and the stage of pregnancy when the mother is infected. The newborn who has syphilis presented characteristic skin lesions, growth retardation and have a look “old.” Some develop meningitis, hydrocephalus, or seizures, and others may show mental retardation. Some do not show signs early and the disease remains dormant. When it manifests late paresis, and optic atrophy shows that sometimes causes blindness. A rare sequel is the poor development of the jaws resulting facies of “bulldog.”

Gonorrhea can cause conjunctivitis, blindness and widespread infection in the baby. If the mother is infected it is subjected to antibiotic treatment.
Women with metabolic endocrine disease should be evaluated before they become pregnant.

Hiperfenilaninemia: This condition is characterized by an increased level of phenylalanine in blood and is produced by the lower conversion of phenylalanine to tyrosine, which is a consequence of the abnormal functioning of laenzima converter. Classical PKU is best known, the enzyme it does not work, what is the most severe form of the disease. In atypical phenylketonuria and mild, there is some activity of the enzyme and therefore are less severe [44].


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It is important to rule out their presence during pregnancy because if the mother has this disease, is more likely to have a baby with mental retardation, microcephaly, congenital heart disease and low birth weight, however, this risk depends on the level of phenylalanine in blood. On the other hand, is a disease that is inherited as an autosomal recessive trait.

Within the framework of preventive, PKU is a disease that can be detected after 48 hours of life until the sixth day of life with the simple analysis of one drop of blood drawn from the baby’s heel. In fact, in the Republic of Argentina there is a national law, No. 23,413, 23,874 and its modification by decree 1316/94 and Resolution 508/96 reporting obligation to perform tracking for early detection of congenital hypothyroidism and phenylketonuria. However, due to budget or simple lack of responsibility, lots of clinics and hospitals do not perform the study, contrary to the law [45]. The seriousness of this lack of compliance increases when taking into account dietary treatments and avoids the severe mental retardation occurs. Thus, the child can live a completely normal life.

Maternal diabetes: potentially serious complications during pregnancy can cause stillbirth and neonatal mortality.

Infants of diabetic mothers are usually large, high weight (4 kg. Or more), which present crisis of cyanosis (bluish color of mucous membranes by hypoxia), hypoglycemic seizures, abnormal movements by hypocalcemia, etc. At times can cause malformations of varying severity.
Hypothyroidism: In general, pregnant women with hypothyroidism is normal even reported improvement of hypothyroidism. However, in the case of severe hypothyroidism is more likely to develop complications such as preeclampsia anemia, abruption, and low birth weight newborns.

On the other hand, the appearance of the newborn infants of mothers with hypothyroidism is healthy without evidence of thyroid problems, however it is important to be studied to rule out congenital hypothyroidism, which if untreated can lead to mental retardation.
Maternal Hyperthyroidism: Babies with minor nervous system disorders, hyperkinesis, sensory disorders, hydrocephalus, microcephaly. Additional studies may indicate fetal hypermetabolism occurs, for example., Tachycardia. They can also be preterm deliveries.

Women with epilepsy who take anticonvulsant drugs, are at risk of 2 to 3 times more likely to have a baby with birth defects than women who do not have epilepsy. Part of this is due to medication, but women who have epilepsy and are no longer taking medication, have a risk of 1 to 2 times higher than the general population to have a baby with congenital malformations. The cause of the increased risk is not completely known. There may be common genes for epilepsy and congenital malformations, or perhaps a specific effect of drugs, or a predisposition to the effect of the drug. Some researchers are working to find ways to identify those who may be more susceptible to the influence of drugs.

The most common malformations are cleft lip, cleft palate and congenital heart disease. But it is important to remember that women with epilepsy have a probability of more than 90% chance of having a normal baby.
It is very important to seizure control with minimal dose possible. Pregnancy is not the right time to discontinue or change the medication, but the neurologist should monitor drug levels in blood because the pharmacokinetics is often changed due to changes in gastric acidity, fetal growth and increased interstitial tissue [46].


Cytomegalovirus: Being the most common cause of perinatal infection, as it is transmitted to the fetus through the placenta (between 0.5 – 2% of all infants), the CMV is a virus belonging to the family of herpes. It is excreted in the urine, semen, cervical secretions and saliva, so that the transmission path can be sexual, respiratory, or by contact with infected urine or saliva. 10% of children born with congenital infection suffer from a syndrome that includes low birth weight, intracranial calcifications, mental and motor retardation, hepatosplenomegaly, hemolytic anemia, microencephaly, chorioretinitis, sensorineural deficits, jaundice and thrombocytopenic purpura.


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It is also necessary to create awareness of the importance of regular monitoring for the prevention of diseases during pregnancy. Some of the most important are:

Hypertension: fetal prognosis is directly related to the reduction of blood volume to the circuit uteroplacental cash. Fetal death is usually secondary to hypoxia and is usually preceded by intrauterine growth retardation.


Preeclampsia: is the presence of high blood pressure in a pregnant woman, accompanied by loss of protein in the urine. It occurs in approximately 7 to 10% of pregnancies. Although its cause is unknown, it is known that there are factors that make a pregnant woman to have more risks than other to develop preeclampsia. These include being primigravida (first pregnancy), primigravida early (less than 16 years) or years (30 years), obesity, black and pre-pregnancy medical conditions such as hypertension, diabetes and kidney disease. Among its complications are reported decreased platelets, which can be isolated or part of a syndrome called HELLP (alteration in liver enzymes, low platelets and red blood cell destruction).

Some authors believe that 50% of cases may be related to maternal age and that 12% may be associated with the father.A team from New York University School of Medicine conducted a study whose results indicate that when the parent has between 35 and 44 years, the risk of preeclampsia is 24% higher than if the parent has between 25 and 34. While no one knows the mechanism by which this factor influences the risk, which may result suggests that sperm may be damaged more by genetic mutations associated with aging or environmental causes, such as radiation, heat or pesticides [47 ].


Eclampsia: Alteration of pregnancy that causes epileptic seizure hits that are not attributed to another cause, hypertension and renal failure, among other symptoms. Yet its exact cause is unknown but sometimes appears after a preeclampsia have not been able to control.

This disease is related to abortions, mental retardation, brain damage, epilepsy and diffuse neurological damage. The cause of these changes is the reduced delivery of oxygen to the fetus by placental vessel spasm.
Chronic urinary tract infections: Pregnancy causes mechanical and functional changes in the urinary tract which facilitates the bacteriuria and the ascent of microorganisms into the kidney. May arise due to infectious diseases in the fetus transplacentally from systemic infections. Is associated with an increased incidence of preterm delivery, premature rupture of membranes, low birth weight and intrauterine growth retardation [48].


Placental dysfunction syndrome: In it, the placenta, membranes or umbilical cord develop abnormally and affect fetal growth. It can cause severe prematurity and respiratory disorders as well as irreversible neurological damage.


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HIV: Transmission of the virus in utero has long been demonstrated in many studies [49, 50], being the most common source of infection in children under 15 years. It is also possible the infection during delivery. The most common is postnatal transmission through breast milk. According to the National Human Retroviruses the Ministry of Health of Argentina, in our country have reported cases 1441 to 2002, representing 7% of total reported cases [51]. Although since 1997 in our country’s National AIDS Standard Perinatal, which indicates the obligation to offer pregnant women HIV serology, the administration of antiretroviral therapy according to protocol PACTG 076 and avoidance of breastfeeding, the curve of cases of HIV in children under 13 years has not decreased enough.

Children who acquire the virus prenatally have varied signosintomatología: recurrent infectious syndromes, HIV encephalopathy, whose key feature is the delay with the purchase of maturational patterns of the acquired or loss, hyperreflexia, microcephaly and cerebral palsy. If not diagnosed and treated promptly, your survival will not exceed 6 to 9 months [52]. 50-70% of children infected in the peripartum. While most of them asymptomatic evolves, it should be noted that careful examination data are significant: children who are sick are less serious in a very diligent, have difficulty achieving the expected height and weight for their age and present difficulties learning, including academic failure [53] and behavioral disorders that often are ascribed to the light to other causes.


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b. Fonolla Puerta, A. Teratology: Preventive Medicine. V Conference of Preventive Medicine and Public Health. Universidad Complutense de Madrid.Julio 1999


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