Some birth defects can be diagnosed before birth through ultrasound, amniocentesis, or chronic villus sampling [CVS]. Most women have blood tests to screen for their risk of having a baby with a specific birth defect, such as Down syndrome and
spina bifida. While it does not usually lead to a cure for the baby's birth defect, prenatal diagnosis can prepare the parents emotionally and help them prepare for a child with a birth defect. In other cases a birth defect is diagnosed after birth through physical examination or a blood test that screens for several disorders in newborns. A
preconception examination, also known as a preconception visit, is one of the best ways to ensure a healthy pregnancy. The goals are to assess your overall health and identify any risk factors that can complicate a pregnancy. A preconception examination can include any of the following: A doctor will assess the medical history of both of your biological parents to see if any family member has had medical problems such as
high blood pressure, diabetes, or mental retardation. A doctor will assess any possible genetic disorders that can be passed down to your child; some genetic disorders can be detected by blood tests before pregnancy. Personal Medical History: to determine if you have any medical
conditions that may require special care during pregnancy [anemia, epilepsy, diabetes, high blood pressure]; to gather information about previous surgeries; and to obtain information about past pregnancies such as complications, losses, and length of gestation. To assess immunity to diseases such as
rubella [German measles] that can cause miscarriage or birth defects, a vaccine can be given at least three months prior to conception to provide immunity. Infection screening determines if a woman has a sexually transmitted infection, a
urinary tract infection, or another type of infection that can be harmful to her or to the fetus. Most birth defects cannot be cured. Treatment focuses on managing the symptoms. In some cases, however, there are ways to treat specific birth defects. Gene therapy replaces a gene that is either missing or defective.
Severe combined immunodeficiency diseases [SCID] are a group of very rare diseases for which gene therapy has been used.How are birth defects diagnosed?
What is a preconception examination?
Family medical history
Genetic testing
Vaccination status
Infection screening
What are the treatment options for birth defects?
Gene therapy
Enzyme replacement therapy
Enzymes are proteins for which genes code. So when a gene is mutated and does not produce the gene product, an enzyme is missing or defective. One way to treat this type of genetic defect is to replace the enzyme that the gene is not producing. An example of a condition for which enzyme replacement therapy has been developed is Gaucher disease.
Prenatal treatment
Some birth defects can be diagnosed and treated before birth. Prenatal surgery, for instance, can treat babies with urinary tract blockages and rare lung tumors.
How we care for birth defects
The Maternal Fetal Care Center is one of a handful of comprehensive fetal care centers in the United States, and the only one in New England. The MFCC treats, supports, and manages complicated fetal anomalies. Its doctors were the world's first to perform life-saving cardiac interventions, such as treating heart problems in utero. The center is also advancing treatments for congenital diaphragmatic hernia, a condition in which a baby is born with a hole in the diaphragm or no diaphragm at all.
Open access peer-reviewed chapter
Submitted: November 8th, 2019 Reviewed: April 16th, 2020 Published: June 17th, 2020
DOI: 10.5772/intechopen.92580
Abstract
Congenital anomalies present with significant financial, social, and moral issues and questions to the family and society and are difficult to rehabilitate. In utero exposure to teratogenic agents and infection are the two most important causes of nongenetic acquired anomalies presenting at birth. Teratogens such as drugs, adverse maternal conditions, and toxins are environmental factors that cause permanent structural or functional malformations or death of the embryo or fetus. Teratogens may cause significant congenital anomalies if encountered during the organogenesis period of 3–8 weeks of fetal life, which is the stage of tissues and organs formation, whereas minor morphological and functional disorders may occur with exposure during the fetal period of first 2 weeks. TORCH group infections [toxoplasmosis, others, rubella, cytomegalovirus, and herpes] are the most serious infectious diseases during pregnancy due to the severity of possible embryo-fetal lesions. With expanding scientific knowledge and clinical experience about the association of these toxins and infections with significant, at times crippling congenital anomalies, the avoidance of exposure to pregnant mothers has become the most important part of their prevention and management.
Keywords
- teratogens
- drugs
- toxins
- alcohol
- smoking
- congenital infections
- cytomegalovirus
Mehmet Semih Demirtaş*
- Department of Pediatrics, Aksaray University Education and Research Hospital, Aksaray, Turkey
*Address all correspondence to:
1. Introduction
In utero exposure to teratogenic agents and infection are the two most important causes of nongenetic, acquired anomalies presenting at birth. The fetal response and susceptibility to such agents are variable, and the effects depend on the type, timing, and duration of intrauterine exposure [1, 2] [Figure 1]. The end results of such exposures may be organ system malformations; aberrations in organ growth, function, and development; and even death. The developmental stage of organogenesis, which is characterized by rapid cellular differentiation and migration, is the most vulnerable period, as the actively dividing cells are highly sensitive to the adverse effects of noxious agents [3]. The effects of teratogens during the preimplantation embryonic phase of the first two postconceptional weeks might present as all or none, as the uterine implantation of a defective embryo may fail and the pregnancy end with undetected abortion, thus nullifying the possibility of congenital malformations [4, 5] [Figure 1].
Figure 1.
Sensitivity to teratogens during pregnancy.
Congenital anomalies are health problems that are difficult to rehabilitate. They generate high treatment costs and might bring on huge financial and moral burdens to the family and society. According to the congenital anomalies survey conducted by the World Health Organization [WHO] in 193 countries in 2010, 270,000 of the 3.1 million newborn deaths were caused by congenital anomalies [6]. In the United States, 2–3% cases of the 3–5% of children born with birth defects are attributed to environmental or iatrogenic teratogen exposure during the intrauterine [IU] life [7]. Most of the teratogen-induced anomalies are preventable.
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2. Teratogenic agents
Teratogens may cause significant congenital anomalies if encountered during the organogenesis period of 3–8 weeks of fetal life, which is the stage of tissue and organ formations [Figure 1]. Minor morphological and functional disorders may occur with exposure during the fetal period of the first 2 weeks [8]. Multiple factors come into play for the teratogens to impart their effects. These are the genetic specifications of the conceptus, the dose and duration of exposure, and the mechanism of action of the offending agent. Teratogens effectuate primarily by disrupting cell-specific biochemical metabolism and by compromising blood circulation which lead to cell death. They can destroy and deplete essential nutrients, block enzyme activities, disrupt mitosis, interfere with nucleic acid functions, and derange membrane functions, osmolar balance, and energy production [9, 10]. Genetic differences in response to teratogens have been documented and may be due to the presence of genetic polymorphisms in the activities of enzymes involved in the excretion of toxic substances [11]. Animal studies have shown differences in the susceptibility to teratogen-induced damage within the same as well as between different species. Fetal hydantoin syndrome is detected in 5% of embryos exposed to phenytoin [PTN], and about 30% of them show some congenital anomalies, while more than half display no teratogenic effects [12]. Aspirin, corticosteroids, and some vitamins are teratogenic in mice and rats, but not in humans. Cleft palate and cleft lip are more common in mice with consanguineous matings [13].
2.1 Drugs
Drugs can directly affect the product of conception and cause malformation and/or embryo-fetal demise. They can impair the fetal development by compromising the transplacental transfer of nutrients and oxygen from the mother. They may diminish fetal blood supply and initiate premature myometrial contractions resulting in premature birth [14]. Drugs can play roles in the intrauterine development of gene-encoding proteins, thereby altering transcription regulation signals which adversely affect embryogenesis [15]. Drugs can exert their effects at different stages of cell development, namely, replication, proliferation, gene expression, signal transduction, programmed cell death, and cell migration [Table 1] [16, 17].
| Phenytoin | Organogenesis [18–60 days] | Fetal hydantoin syndrome, facial cleft, cognitive impairment |
| Lithium | Organogenesis [18–60 days] | Ebstein’s anomaly |
| Warfarin | Second part of the first trimester [6–9 weeks] | Nasal hypoplasia, limb hypoplasia, optic atrophy, bone abnormalities, neurological impairment |
| Amphetamines | All trimester | Cleft palate, heart defects, intestinal atresias, and structural brain abnormalities |
| Sodium valproate | Organogenesis [18–60 days] | Neural tube defect, cleft palate, atrial septal defect, hypospadias, polydactyly, craniosynostosis |
| Cyclophosphamide | Organogenesis [18–60 days] | Skeletal and ocular defects, cleft palate |
| Aminopterin | Organogenesis [18–60 days] | CNS, limb, and skeletal defects |
| ACE inhibitors | Second. or third trimester [13th week term] | Craniofacial abnormalities, neonatal renal failure, pulmonary hypoplasia |
| Benzodiazepines | Organogenesis [18–60 days] | Cleft lift and palate abnormalities |
| Lithium | First trimester | Ebstein’s anomaly |
Table 1.
Some teratogenic drugs and their effects.
2.1.1 Phenytoin
Although the exact pathogenesis of phenytoin [PTN] embryo toxicity is unclear, some possible mechanisms have been proposed [18]. Phenytoin acts as a membrane stabilizer by inhibiting sodium [Na] and calcium [Ca] channels, as a result of which free radicals are released and cause endothelial damage, myocardial depression, bradycardia, and consequently fetal hypoxia. Phenytoin induces cytochrome P450 activation which results in the release of teratogenic free radicals, sourced via the metabolism of epoxides, folate, and vitamin K in the liver [19, 20]. Phenytoin, like other antiepileptic agents, namely, valproic acid [VPA] and vigabatrin, induces carnitine deficiency in the fetus which may lead to cardiomyopathies and ventricular septum defects [21]. Infants born to women with mutations in the methylenetetrahydrofolate reductase [MTHFR] gene are at an increased risk for fetal hydantoin syndrome as its protein products compromise the metabolism of phenytoin and/or its metabolites. Free radicals released as intermediate metabolites of phenytoin bind to deoxyribonucleic acid [DNA], proteins, and lipids and adversely affect the neurodevelopment. The wide variation in the presentation of anomalies related to PTN may be due to the genetic differences in the formation of free radicals, drug clearance, and repair mechanism. Fetal hydantoin syndrome can be seen in approximately 5–10% of infants with in utero exposure to phenytoin, whereas incomplete clinical syndrome can be seen in about one third of them [22]. The characteristic features of fetal hydantoin syndrome include microcephaly, craniofacial anomalies, hypertelorism, flattened nasal root, ptosis, wide mouth, cleft palate-lip, cardiac defects, urogenital malformations, and hypoplastic distal phalanx and nails. There is also an increased risk of neural tube defects [NTD] as this antiepileptic reduces fetal serum folate levels [23].
2.1.2 Valproic acid
Depending upon the dose and duration, the in utero exposure to VPA may increase the incidence of congenital malformations in neonates by 2–16 times [24]. The teratogenic effects of VPA on the fetus are typically caused by maternal ingestion of drug in doses over 1000 mg/day. However, adverse effects can be seen at lower doses of 500 mg/day as well. In one study, the rate of major congenital malformations with fetal exposure to VPA via maternal medication in the doses of