Comparison between the main models of prenatal education.
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\r\n\tEditors hope to build a line of transformative research based on the adaptation of energy and design solutions from natural models to technical models, using methodologies and solutions which will open new areas of work about how to solve efficiency requirements based on natural solutions honed by evolution. This process is based on creativity and forces researchers to think out of their boxes and open new scientific challenges. What drives the research is the urge to find alternative, more efficient solutions to tackle problems. Due to the wide range of possibilities offered by biodiversity’s tested solutions, the methodology prioritize (although not exclude) solution-based approaches.
Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. The study of such causal mutations is a central focus of cancer biology for two reasons; first is to reveal the molecular mechanisms of tumorigenesis, second is to provide insight in the development of novel therapeutic and diagnostic approaches. Although hundreds of genes are known to be mutated in cancers our understanding of mutational events in cancer cells remains incomplete (Futreal PA et al, 2004). This however has widely opened the field of cancer genomics studies which aims to provide new insights into the molecular mechanisms that lead to tumorigenesis.
As we are in the era of evidence-based molecular diagnosis, predictive testing, genetic counseling, gene-informed cancer risk assessment, and preventative and personalized medicine, therefore, studying the Mendelian genetics of the familial forms of cancer is one approach that can set up the basis for gene-informed risk assessment and management for the patient and family. Herein we selected a Mendelian genetics form of familial cancer such as hereditary tumor syndromic endocrine neoplasias caused by highly penetrant germline mutations leading to pheochromocytoma-paraganglioma syndromes. An example of such syndromes are autosomal dominant disorders; von Hippel-Lindau (VHL); Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. In the case of multiple endocrine neoplasia type 2 (MEN 2), gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumors. PTEN mutations in Cowden syndrome (CS), associated with breast, thyroid, and endometrial neoplasias. Identification and characterization of germline mutations in the predisposition genes of the great majority of these syndromes has empowered the clinical practice by the retrieved genetic information which guides medical management.
This review focuses specifically on the analysis of missense mutations in oncogenes and the tumor suppressor genes, though these genes can also be mutated through a variety of other mechanisms such as DNA amplification, translocation, and deletion. Unlike synonymous or silent mutations, which do not cause amino acid changes, missense mutations are non-synonymous amino acid substitutions that are typically caused by single-base nucleotide point mutations. However, many random missense mutations are not expected to alter protein function due to plasticity built into many amino acid residues.
Before proceeding into missense mutation in tumor suppressor gene we ought to introduce the "two hits" of Knudson\'s hypothesis. Alfred Knudson Jr in 1971 published his inspiring statistical analysis of the childhood cancer retinoblastoma where he found that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation (Knudson A. G. Jr, 1971). Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumors would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumors would develop late in life and in a unifocal manner. His observations led him to propose a two-hit theory of carcinogenesis. The "two hits" of Knudson\'s hypothesis, which has proved true for many tumors, recognized that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumor-suppressor genes (Ayerbes et al, 2008;.
Using the second generation sequencing approaches provided detailed information on the frequency and position of single point mutations as well as structural aberrations of cancer genomes such as small insertions and deletions, focal copy number alterations, and genomic rearrangementsm (Wood LD et al, 2007;. Jones S et al, 2008; Greenman C et al, 2007; Sjoblom T et al, 2006; Pleasance ED et al 2010a,b; Cancer Genome Atlas Research Network, 2008). The findings show that the complexity of each cancer genome is far greater than expected and that extensive variations exist between different cancer types as well as between different tumor samples of the same cancer type. Several recent studies have used the Catalogue Of Somatic Mutations In Cancer (COSMIC) database to discriminate oncogenes and the tumor suppressor genes by using the difference in their mutation patterns in order to understand oncogenesis and diagnose cancers (Forbes SA et al, 2008; Stehr H et al, 2011; Liu H, 2011). Such investigations at the systems level are currently being performed for many of oncogenes and the tumor suppressor genes as part of the Mutanom project (http://www.mutanom.org).
Stehr H et al study describes in a quantitative way, the opposing structural effects of cancer-associated missense mutations in oncogenes and tumor suppressors. Using COSMIC database (Forbes SA, 2008). Stehr H et al has assessed the effects of 1992 mutations cancer-associated mutations representing two common mechanisms through which tumorigenesis is initiated: via gain-of-function of oncogenes and loss-of-function of tumor suppressors (Vogelstein B et al, 1993). Then compared them to the effects of natural variants and randomized mutations. They focused on mechanisms of cancer mutations that have a consequence at the structural level. Another significant body of work has been published on consequences of mutations in a structural context (Ng PC, 2003, 2006; Ramensky V, et al, 2002; Wang Z et al, 2001; Karchin R et al, 2009). These studies differ in that either they focus on estimating the effects of individual mutations or they use different sets of disease mutations.
Studies of structural effects of mutations have found that disease mutations primarily occur in the protein core (Ramensky V, et al, 2002; Wang Z et al, 2001). This trend was confirmed only for the set of tumor suppressors. In contrast, core residues in oncogenes are significantly less often mutated than expected by chance. This is in agreement with Stehr H et al results for protein stability. Mutations located in the protein core are often destabilizing and result in loss-of-function. Thus, Stehr H et al data suggests that the loss-of-function of tumor suppressors is often caused by destabilization of the protein. They also suggested that specific mutations of functional sites that can either disable enzymatic activity and regulatory mechanisms or increase protein activity are often responsible for oncogene activation. Stehr H et al results show that the most frequently mutated types of functional sites in oncogenes are ATP and GTP binding sites and that the frequency of mutation is significantly higher than expected. This suggests that mutations of ATP and GTP binding sites are specific and common mechanisms of oncogene activation. Examples for such activating mutations near ATP binding sites have been described in the literature (Davies H et al, 2002; Shu HK et al, 1990, Jeffers M, et al, 1997).
Liu H et al investigated >120,000 mutation samples in 66 well-known tumor suppressor genes and oncogenes of the COSMIC database, and found a set of significant differences in mutation patterns (e.g., non-3n-indel, non-sense SNP and mutation hotspot) between them. They also developed indices to readily distinguish one from another and predict clearly the unknown oncogenesis genes as tumor suppressors (e.g., ASXL1, HNF1A and KDM6A) or oncogenes (e.g., FOXL2, MYD88 and TSHR). Based on their results, a third gene group was classified, which has a mutational pattern between tumor suppressors and oncogenes. The concept of the third gene group was thought to help in understanding gene function in different cancers or individual patients and to know the exact function of genes in oncogenesis.
von Hippel-Lindau (VHL) disease (MIM 193300) is a dominantly inherited familial cancer syndrome. It is caused by mutations in the VHL tumor suppressor gene with an incidence of 1:31-36000 live births worldwide across all ethnic backgrounds, with similar prevalence in both genders (Maher et al., 1991; Maher, et al.2004). The prevalence however was shown to be higher in some population withtin the same ethnicity such as 1:39 000 in South-West Germany and 1:53 000 in Eastern England (Maher ER et al, 1991; Neumann H et al, 1991). VHL is characterized by marked age-dependent penetrance and phenotypic variability. The factors that affect the actual clinical expression and tumor formation, including age of onset, tissue and organ-specific lesions, severity of lesions, and recurrence, are unknown. VHL main clinical manifestations are:
Hemangioplastoms of the central nervous system (CNS) which are typically located in the cerebellum, but can also occur at the brainstem, spinal cord, and rarely, at the lumbosacral nerve roots and supratentorial (Neumann et al., 1995). Retinal or CNS hemangioblastomas are often the earliest manifestations of VHL disease and the most common, occurring in up to 80% of patients (Maher et al., 1990b; Melmon and Rosen, 1964; Weil et al., 2003). VHL-associated cerebellar hemangioblastomas are diagnosed at a mean age of 29–33 years, much earlier than sporadic cerebellar hemangioblastomas (Hes et al., 2000a, 2000b; Wanebo et al., 2003). These lesions are rarely malignant, but enlargement or bleeding within the CNS can result in neurological damage and death (Pavesi et al., 2008). A lower incidence of CNS hemangioblastomas has been documented in specific ethnic populations (12% Finland (Niemela M et al., 1999); 5% German (Zbar B et al., 1999). Patients with cerebellar haemangioblastomas typically present with symptoms of increased intracranial pressure and limb or truncal ataxia (depending on the precise location of the tumor). Wanebo et al. (2003) showed most CNS hemangioblastomas were associated with cysts that were often larger than other hemangioblastomas.
Pheochromocytomas are endocrine neoplasias with intra- or extra-adrenal gland lesions that appear histologically as an expansion of large chromaffin positive cells, derived from neural crest cells (Lee et al., 2005). Seven to 18% of VHL patients are afflicted with pheochromocytomas (Crossey et al., 1994a; Garcia et al., 1997). The absence or present of this phenotype will type the VHL into type 1or 2 (A,B,C), respectively (Woodward ER et al., 1997; Hofstra RMW et al., 1996). Untreated pheochromocytomas can result in hypertension and subsequent acute heart disease, brain edema, and stroke.
Clear cell renal cell carcinoma (RCC) occurs in up to 70% of patients with VHL and is a frequent cause of death. 70% of VHL patients have the risk of developing RCC by 60 years old (Maher et al., 1990b, 1991; Whaley et al., 1994), at an average age of 44 years versus the average age of 62 years, at which sporadic RCC develops in the general population (http://www.umd.be/VHL/W_VHL /clinic.shtml). Renal cysts are common in VHL patients as well; however, unlike the completely benign cysts in the general population, renal cysts in VHL patients might degenerate into RCC (Kaelin et al., 2004). However, it is unlikely that RCC in all VHL patients originates from cysts, or that all cysts will eventually become malignant. RCC often overproduces VEGF, and thus can be very vascular (Berse et al., 1992; Sato et al., 1994; Takahashi et al., 1994).
VHL patient can also have low-grade adenocarcinomas of the temporal bone, also known as endolymphatic sac tumors (ELST), pancreatic tumor, and epididymal or board ligament cystadenomas (Gruber et al., 1980; Neumann and Wiestler, 1991; Maher et al., 2004; Kaelin et al., 2007). ELST in VHL cases can be detected by MRI or CT imaging in up to 11% of patients (Manski TJ, et al., 1997). Although often asymptomatic, the most frequent clinical presentation is hearing loss (mean age 22 years), but tinnitus and vertigo also occur in many cases. In addition to the inherited risk for developing cancer, VHL patients develop cystic disease in various organs including the kidney, pancreas, and liver (Hough et al., 1994; Lubensky et al., 1998; Maher et al., 1990b; Maher, 2004).
Tumor growth commonly cycled between growth and quiescent phases. Patients with numerous tumors experienced growth and quiescent phases simultaneously, suggesting that a combination of acquired genetic lesions and hormonal activity influence tumor growth.
Molecular genetic mutation and phenotypic clustering has allowed development of a clinical classification, although intra-familial variability is well recognized.
As mentioned previously VHL disease can be classified into VHL Type 1 or Type 2 depending on the phenotype. Type 1 describes those with typical VHL manifestations such as emangioblastomas and RCC, but does not include pheochromocytomas. Once a pheochromocytoma occurs the classification becomes Type 2. Type 2, accounting for 7–20% of VHL kindreds, is further subdivided into: (2A) pheochromocytomas and other typical VHL manifestations except RCC, (2B) the full spectrum of VHL disease including pheochromocytomas, RCC, and other typical VHL manifestation, and Type (2C) identifies those with familial risk of isolated pheochromocytoma (Gross D et al, 1996; Martin R, et al., 1998), although there are some kindreds without identified VHL mutation raising the possibility of another genetic locus (Woodward ER et al, 1997; Crossey et al., 1994b; Garcia et al., 1997; Mulvihill et al., 1997).
The morbidity of VHL disease depends on the organ system involved. For example, retinal hemangioblastomas can result in retinal detachment and/or blindness (Webster et al., 1999). Mortality is often due to either metastasis of RCC or complications of CNS hemangioblastomas (Filling-Katz et al., 1991; Maher et al., 1990b; Neumann et al., 1992); however, due to improved screening guidelines, life expectancy of VHL patients has improved.
The human VHL gene is a 10-kb region located on the short arm of chromosome 3 (3p25.3) (Richards et al., 1993) and consists of 3 exons (Kuzmin et al., 1995; Latif et al., 1993a, 1993b): Exon1 spans codons 1–113, exon 2 spans codons 114–154, and exon 3 spans codons 155–213. Two protein products are encoded by VHL: a 30-kDa full-length protein (p30, 213 amino acids, NM_000551.2 [variant 1 mRNA]) and a shorter protein product of 19-kDa (p19, 160 amino acids NM_198156.1 [variant 2 mRNA]), which is generated by alternative translation initiation at an internal methionine at position 54 (Blankenship et al., 1999). Although evolutionary conservation of VHL sequence is very strong over most of the pVHL19 sequence, the first 53 amino acids included in pVHL30 are less well conserved and functional studies suggest that the two pVHL isoforms have equivalent effects (Woodward ER et al, 2000; Iliopoulos O et al, 1998). The VHL mRNA and protein is widely expressed in both fetal and adult tissues (Richards FM et al., 1996; Corless CL et al., 1997) and can be found in all multicellular organisms examined to date without known similarity to other proteins (van M et al., 2001). Remarkable progress has been made in elaborating the function of pVHL and the role its inactivation plays in the pathophysiology of this disorder, including dysregulation of angiogenesis and tumor formation.
Given the lack of primary sequence homology to other proteins, the function of pVHL has been derived from studying pVHL interactors and associated proteins. Roles in oxygen-dependent angiogenesis, tumorigenesis, fibronectin matrix assembly and cytoskeleton organization, cell cycle control and cellular differentiation have been proposed. The N-terminal acidic domain of VHLp30 contains eight repetitions of a five-residue acidic repeat, which are absent in VHLp19. Phosphorylation of this acidic domain participates in tumor suppression and this domain binds the Kinesin-2 adaptor KAP3, thus mediating microtubule-binding (Lolkema et al., 2005, 2007). This domain is also responsible for binding metastasis suppressor Nm23H2, a protein known to regulate dynamin-dependent endocystosis (Hsu et al., 2006). Further downstream, the β-sheet domain (residues 63–154) binds HIF0a subunits at residues 65–117 and the α-helical domain (residues 155–192) binds the Elongin B and Elongin C (Elongin BC) complex at residues 158–184 (Feldman et al., 1999). Binding of pVHL to the Elongin BC is mediated by the chaperonin TRiC/ CCT. Elongin BC binding to pVHL requires TRiC, and VHL mutations causing defects in binding to Elongin BC are associated with VHL disease (Feldman et al., 1999). pVHL inactivation leads to an overexpression of hypoxia-inducible factor (HIF) and upregulation of its targets (vascular endothelial growth factor (VEGF), erythropoietin, transforming growth factor (TGF)-beta, alpha). Whether this is the sole etiologic factor causing characteristic VHL hemangioblastoma formation remains to be clarified. Evidence also suggests that pVHL inactivation alters fibronectin extracellular matrix formation, and that pVHL may participate in cellular differentiation and cell cycle control. Ongoing studies are directed at elaborating the biologic consequences that these pathways play in the angiogenesis and tumor formation central to VHL. Additionally, VHL protein has functions that are independent of HIF-1alpha and HIF-2alpha and are thought to be important for its tumor-suppressor action, assembly of the extracellular matrix, control of microtubule dynamics, regulation of apoptosis, and possibly stabilization of TP53 proteins (Frew IJ and Krek W. 2007).
Germline mutations, including large deletions/rearrangements, in the VHL gene, linked to 3p25-p26, are etiologic for virtually all VHL disease (Latif, F. et al., 1993; Stolle, C. et al., 1998; Zbar, B. et al., 1996). These VHL germline mutations may be also detected in patients with autosomal dominant familial non-syndromic phaeochromocytoma (Woodward ER et al., 1997; Neumann HP et al., 2002). Specific VHL missense mutations can cause an autosomal recessive form of polycythaemia without any evidence of VHL disease (AngSO et al., 2002; Gordeuk VR et al., 2004). Germ-line mutation confers genetic risk of tumor formation in concert with somatic second VHL allele loss or DNA methylation inactivation. However, somatic loss or inactivation of the wild-type vhl allele has been demonstrated in central nervous system (CNS) sporadic hemangioblastomas (Gnarra JR et al., 1994; Kanno H et al., 2000; Foster K et al., 1994; Herman JG et al 1994; Oberstrass J, et al., 1996; Tse J et al., 1997; Lee J-Y et al., 1998), in sporadic and VHL-associated renal cell carcinomas (RCCs) (Latif F et al, 1993; Shuin T et al., 1994; Phillips JL et al., 2001), pheochromocytoma (Bender BU et al., 2000; Linehan WM et al., 2001) and in endolymphatic sac tumors (ELSTs) (Vortmeyer AO et al., 2000).
More than 300 germline mutations have been identified in familial VHL. These occur throughout the coding region with only a few mutations appearing in multiple families (Zbar B et al., 1996; Beroud C et al., 1996). The new mutation rate has been estimated at between 3 and 20% (Latif F et al., 1993; Richard S et al., 1994; Schimke RN et al., 2000). Although decreased penetrance has been described (Maddock IF et al., 1994), comprehensive familial molecular data have not yet been reported to clarify this rate.
There has been limited correlation between specific mutation and phenotype, although some data on genotype-phenotype correlations have been reported (Neumann H et al., 1998; Hes F et al., 2000). Such correlations have revealed that certain missense mutations confer a high risk of pheochromocytoma (VHL type 1) whereas loss of pVHL through large deletions or nonsense-mediated decay appears to be incompatible with pheochromocytoma development (VHL type 2). [Chen et al., 1995; Cybulski et al., 2002; Glavac et al., 1996; Hes et al., 2000a, 2000b; Maher et al., 1996; Neumann and Bender, 1998; Ong et al., 2007; Zbar et al., 1996].
Interestingly, missense mutations causing amino acid changes on the surface of pVHL appear to have a higher risk for pheochromocytomas than missense mutations occurring deep within the protein; surface missense mutations also appear to have a higher risk for pheochromocytomas than deletions, nonsense, and frameshift mutations [Ong et al., 2007]. Thus, pheochromocytoma development appears to be related to an intact, but altered pVHL, which has seeded the hypothesis that these mutations may induce gain-of-function possibly through a dominant negative effect [Hoffman et al., 2001; Lee et al., 2005; Maher and Kaelin, 1997; Stebbins et al., 1999]. Nordstrom-O’Brien et al., 2010, analyzed 1548 VHL families and provided a wealth of data for genotype–phenotype correlations. They found 52% had missense mutations most frequently occurred at codons 65, 76, 78, 98, splice mutations at codon 155, 158, 161, 162, and 167. 13% had frameshift, 11% had nonsense, 6% had in-frame deletions/ insertions, 11% had large/complete deletions, and 7% had splice mutations. Mutations that predict absence of functional protein (deletion, frame-shift, nonsense, and splice) are associated in 96-97% of cases with type 1 phenotype and show an increased risk of RCC (including type 2b cases). This suggests that expressed dysfunctional protein may be required for pheochromocytoma formation. Missense mutations are associated with type 2 phenotype (hemangioblastoma and pheochromocytoma +/- RCC) in 69-98% of cases (Stolle C et al., 1998; Chen F et al., 1995; Zbar B et al., 1996). While Nordstrom-O’Brien et al., found 83.5% of VHL Type 2 families mainly had missense mutations. However, this is not as high as some studies, reporting up to 96% of those with pheochromocytomas to have missense mutations (Zbar et al., 1996). Nordstrom-O’Brien et al., found low percentage of VHL Type 2 families (0.5-7%) had other types of mutation such as nonsense, frameshift, splice, in-frame deletion/insertions, and partial deletions. The small percentage of nonsense and partial deletions along with the absence of complete deletions supports theories that an intact though altered pVHL is associated with pheochromocytomas. Stratifying missense mutations into those that resulted in substitution of a surface amino acid and those that disrupted structural integrity demonstrated that surface amino acid substitutions conferred a higher pheochromocytoma risk (Ong KR et al., 2007). Although loss of heterozygosity has been reported in endolymphatic sac tumors (ELST) tumors (Kawahara N et al., 1999; Vortmeyer AO et al., 1997) no predominant mutation has been identified.
It may be difficult, however, to predict functional biologic consequences from specific point mutations without direct functional assays as reported in recent RCC in-vitro mutation panel studies.
The recent characterization of the VHL protein crystal structure might suggests possible functional consequences of specific mutations. If we focus on the structure of the pVHL we can predict the effect of the mutation on the functionality of the pVHL and therefore the phenotype resulted. Mutation-specific dysfunction may depend on protein destabilization, altered interactor binding at the various pVHP binding domains or potential alteration in binding to other factors involved in tumor suppressor/activator activity. pVHL has two domains: an amino-terminal domain rich in β-sheet (the β-domain) and a smaller carboxyterminal α-helical domain (the α-domain). A large portion of the α-domain surface interacts with Elongin C, which binds to other members (e.g., Elongin B, Cul2, and Rbx1) of an SCF-like E3 ubiquitin-protein ligase complex as mentioned earlier. Obviously, loss of function VHL mutations prevents Elongin C binding and target ubiquitylation (Clifford et al., 2001). The β-domain on the other side has a macromolecular binding site targets the HIF-1α and HIF-2α regulatory subunits for proteasomal degradation. Whereas Type 1 and Type 2B mutations impair pVHL binding to Elongin C, Type 2A mutations map to the β-domain HIF-binding site and do not affect the ability of pVHL to bind Elongin C (Clifford et al., 2001). Therefore, classifying missense substitutions according to their predicted effect on pVHL structure enhances the ability to predict pheochromocytoma risk (Ong KR et al., 2007)
Nordstrom-O’Brien et al 2010 suggested that increased identification of new mutations and new patients with previously described mutations gives momentum to the search for the exact role of pVHL in its normal and mutated form. Understanding such functions and its association with specific mutations allows for identification of disease risks in individual patients. Such insight will offer improved diagnostics, surveillance, and treatment of VHL patients (Nordstrom-O’Brien et al., 2010).
Ongoing delineation of clinical subtypes may allow for better genotype-phenotype correlations, prediction of clinical progression and molecular mutation-directed clinical management. There is significant intra-familial difference in clinical expressivity and as of yet limited knowledge about modifiers of this phenotypic variation (Webster AR, et al, 1998). Prediction of the clinical course in any one patient based on molecular data is therefore difficult.
The paths that can lead women to become pregnant are multiple and not always happy [1]. Depending on the circumstances of life, the decision to accept a pregnancy may not be easy. The knowledge of being pregnant produces a feeling of ambivalence of whether I want it or not, in all women and their partners [2]. This feeling raises doubts about whether it is the right time, if you have the resources necessary to raise a child and if you are going to be able to play the role of mother or father [3]. Once the decision is made to continue with a pregnancy that the woman, or the woman and her partner accepts, it is necessary to advise the future parents about the care of the gestation, delivery and the puerperium. A personal work of bonding with the child must also be initiated, which lays the foundations for the development of the affective warp that every human being needs in order to fully develop. This element is so important that it is the axis of much international research on attachment and attachment in early childhood [4].
\nScience has shown that child health begins in the prenatal stage, in pregnancy, and this makes prenatal education very important. Everything from the mother’s diet to her emotions influences the future health of her child [5, 6]. So from the World Health Organization and from all related scientific societies education is promoted at this stage [7]. Prenatal education has ceased to be a concern of midwives and obstetricians to become a field of study that is approached from multiple disciplines, such as pediatrics, psychology and pedagogy. This makes it necessary for professionals to know the history of prenatal education and the main paradigms from which their study has been developed [8]. In this chapter, we are going to approach the evolution of health education for women and their partners in pregnancy.
\nThe objective of this work is to identify differences in approaching and methodology of the major schools of childbirth education.
\nIn the first quarter of 2019, a review was made of publications in the health sector in both Spanish and English, going back a maximum of 19 years. MeSH terms were selected that best reflect the objective of this work, these being: antenatal education, childbirth education, parenthood education, centering pregnancy/group care, pregnancy, prenatal care/methods and their equivalents in Spanish. The PubMed, Embase, Lilacs, Scielo, Cuiden, Cinhal and Cochrane databases were consulted. The websites of the main current antenatal education schools were reviewed and the relevant studies of the main European schools pre-2000 were located. Once the documents had been located, they were studied and analyzed using the comparative method. To conduct the analysis, a database was set up using Excel.
\nThe results have been structured in four sections:
Prenatal education before the twentieth century.
The beginning of prenatal health education.
The first large prenatal education schools, prenatal education schools.
The new prenatal education schools.
Until the twentieth century, women gave birth in their homes attended by midwives and accompanied by the women of the family and the environment [9]. According to anthropological studies, there are few cultures in which women separated from the group and were to give birth by themselves. There are references that cite some Eskimo and Indian tribes of North America. In general, childbirth was a common phenomenon in people’s lives. Women and girls, of all ages, had seen their mothers, sisters, daughters and/or neighbors give birth [10]. In this situation, birth should not have been as feared a moment as it is now. In her home, the woman in childbirth had greater prominence and control, but the mortality and morbidity rates were very high. In fact, today, in those parts of the world where women give birth without health care assistance, childbirth continues to be the first cause of death [11]. To remedy this situation, each culture has developed special care for pregnancy, childbirth and puerperium. This great variability of care is related to the eminently social nature of every human birth and the need for group survival [12]. These first cares constitute an informal prenatal education that occurred within social groups in a natural way.
\nAt the end of the twentieth century, great changes took place in the health sector, which gave another profile to hospitals. These had arisen from the hand of religious orders dedicated to charity. Over time they were developed, technified and became the great centers of training and development of medicine. At this time, the first maternities arose to serve the most disadvantaged women. Progressively, delivery assistance moves from homes to hospitals [13]. Women no longer had the opportunity to see their relatives give birth and lost ancestral control over their physiology and their natural knowledge of childbirth. In hospitals, seeking to improve perinatal outcomes, deliveries are intervened and instrumentalized. These interventions led to pain and anxiety for women in childbirth, so the need arose to look for ways to reduce pain [14]. As early as in 1870 James Young Simpson tries to apply chloromorphic anesthesia to childbirth. At the beginning of the century, studies were developed throughout Europe to achieve analgesia in childbirth with psychological means [13, 15, 16]. Obstetricians start prenatal education programs for childbirth. These early programs are the forerunners of the current Maternity/Paternity education programs.
\nIn Europe, the first models of prenatal education emerge in the first half of the century. Their sole object is to reduce the pain of women in childbirth and consist of only a few sessions. Gradually the programs expand their objectives and their sessions, and deal with pregnancy, the couple, bonding and the newborn.
\nThe schools of Charcot (Paris) and Berhein (Nancy) investigated clinical hypnosis [17, 18, 19]. In 1922 the obstetricians Schultze and Rhonhof proved that the introduction of educational sessions before childbirth reduced the time needed to achieve a hypnotic state. In 1923, Kogerer used post-hypnotic self-suggestion [20, 21]. These two techniques posed some difficulties so new methods were sought to relieve pain during labor [22].
\nIn 1932, the obstetrician Grantly Dick Read published “Natural Childbirth.” He viewed childbirth as a physiological phenomenon in which pain is created by fear which unleashes the defense mechanisms in the form of muscular tension. He formulated the Fear-Tension-Pain concept and developed a method featuring explanatory conversations, relaxation, breathing techniques and strategies that enhance trust in the healthcare team. He did not rate gymnastic exercises and warned against any muscle training. This concept has been disseminated worldwide and has undergone many changes [23, 24].
\nAt the same time, Drs. Velvoski, Platinov and Nikolaiev, who were working with hypnotic suggestion, were looking for new approaches (Obstetric Psychoprophylaxis) [25]. In accordance with Pavlov’s Classical Conditioning Theory, they concluded that pain in labor is a reaction conditioned by sociological and religious-cultural stimuli. They suggested de-conditioning the fear through aseptic language, relaxation (Schultze), positive thinking, the celebration of maternity and obstetric information [26]. To get the woman actively involved, they introduced breathing and muscle exercises [17, 27]. They came up with a simple and accessible method which encouraged its spread throughout Russia, Eastern Europe and China.
\nDr. Lamaze (1940) learned from the Russian school and was familiar with the English school. He created a more technical method that insisted on the need for a loving environment with the presence of a partner. His partner, Dr. Vellay, insisted on the therapeutic power of speech and the active role of the woman [28]. Later, in his book “Birth Without Violence” (1975), Leboyer popularized the creation of an environment of tranquility in the labor room and the submersion of newborns in a small bath of warm water; he is thus regarded as the precursor of water births [29].
\nIn 1955, the midwife Consuelo Ruiz presented her book “Labour Without Pain” featuring the new tendencies [30]. In 1956, Aguirre de Cárcer founded the school of “Obstetric Sophropedagogy or Maternal Education” and gave a substantial change from the focus of pain during labor for that of achieving a new sociocultural standard whereby both the woman and her partner would acquire the necessary knowledge to face labor with serenity, having diminished their fears, and experience this transcendental moment in their lives with full consciousness and satisfaction, as this experience will impact on the child by encouraging the development of the “Emotional Network” [31]. In 1959, the Compulsory Health Insurance entrusted her with a program and in 1986 Maternal Education was included in the service portfolio of the National Health System. This helped with its dissemination and facilitated significant further development [32].
\nIn the middle of the twentieth century, these first methods obtained good perinatal results, with which they developed and spread throughout the world [33]. Subsequently, multiple methods have emerged and, in every country, there are professionals concerned about improving care for women in childbirth and that disseminate this concept. Next, the emerging models that have a greater presence in the review are presented.
\nIn 1960 the International Childbirth Educators’ Association (ICEA) was founded, which further evolved the Lamaze method. It is a non-profit organization that promotes freedom of choice for women and their partners based on the informed knowledge of childbirth options. Its orientation is centered on maternity care and the care of the newborn by the family. It respects the individuality of the woman and her sense of autonomy [28, 34, 35].
\nIn 1965, Robert Bradley, in his book “Husband-Coached Childbirth,” claimed that the partner is the person who should ensure that the woman is in a safe, quiet environment and who should know her well enough to be able to help her in this process. He empowers fathers to ‘coach’ their partners with instructions, relaxation techniques and massages [36]. He was the pioneer of ‘father training’ (American Academy of Husband-Coached Childbirth).
\nIn 1970, Kabat-Zinn developed the Mindfulness-Based Childbirth and Parenting (MBCP) method at the University of Massachusetts Medical School, based on Mindfulness-Based Stress Reduction. This method emphasises the development of the conscience at a precise moment through meditation. The results indicate that this helps to reduce pregnancy-related depression and anxiety [37, 38]. It is also giving rise to new models such as “Centering Pregnancy®.”
\nIn the 1970s, Sheila Kitzinger reinstated the wisdom of a woman’s body in giving birth. The author of “Birth Your Way: Choosing Birth at Home or in a Birth Centre” proposes that women tune in to their contractions in the way they feel they achieve harmony and rhythm and acquire the knowledge to make their own decisions. The presence of the husband, the instructor and the midwife create a favorable environment for childbirth. Her partner, Janet Balaskas, created the Active Birth Movement and proposed the practice of yoga adapted to pregnancy [39].
\nIn the Netherlands, in the 70’s, a new approach to preparation for birth appeared: “Haptonomy,” which passed to France in 1978 by Frans Velman and later extended to Switzerland and Spain. Dr. Etienne Herbinet explains that haptonomic work is exercised on touch, on palpation in its affective aspect, on tactile contact as a means of communication. During preparation at birth the haptonomic approach can help future parents to have a more emotional perception of the baby to be born. Through touch they develop an active affective relationship between the mother, the father and the baby. The method helps to establish and develop a sense of paternity/maternity through affective contact with the baby [40].
\nIn 1975, in the United States, the percentage of pregnant women who used this type of practice was higher than 6–7% according to the program carried out under the name of “Prepared Childbirth” assumed by the “American Society for Psychoprophilaxis in Obstetrics” (2010) [41].
\nThe French obstetrician, Michel Odent (1977) popularizes birth in water and founds the “Primal Health Research Center.” He guides his work to help each woman choose the way she will give birth following her own instincts and respecting at all times the physiological process of childbirth. Author of numerous books, he postulates that the emotional situation of the pregnant mother is determinant in the psychological and physical future of the individual, and also points out the temporal importance of childbirth and the subsequent moments on the development of the person. He highlights the role of birth hormones (oxytocins and endorphins) and provides numerous investigations [42].
\nIn Rome, in 1984, Umberto Piscicelli, professor at the Catholic University of Rome, publishes his book “Respiratory Autogenic Training and Psychoprophylaxis in Obstetrics.” His method is known as “Respiratory Autogenic Training” or R.A.T. It is inspired by Schultz’s autogenous breathing, the laws of conditioning, group psychotherapy, relaxation therapy and his deep knowledge of psychosomatic medicine. Its objective is the psychological therapy of pain through its connections with uterine contractions, but also the correction of negative psychic aspects and non-adaptive behaviors. For this, the woman is given maximum autonomy to be the protagonist of her birth and is prepared to act in an environment full of stimuli [43].
\nIn the US, Barbara Harper, is one of the great scholars and disseminators of childbirth in water around the world. She founded Waterbirth International in 1987 after visiting Russia for the first time and sitting with Igor Charkovsky, where she was “influenced by her faith in the parturients and their babies” [44]. She has also worked extensively with Binnie Dansby in the early 1980s on cognitive learning and repressed experiences and memories of birth. She is a nurse, midwife, doula and perinatal educator. She has been Founder and Director of the World Association for Maternal and Child Health, and Founder and Director of Waterbirth International. She is recognized worldwide as an expert researcher and author of protocols for delivery in water since 1983 and responsible for the opening of and instituting policies for delivery in water in 140 hospitals in the United States.
\nIn 1990 Marie Mickey developed the Mongan Method, known as HypnoBirthing. Based on the premise that all women have within them the power to call on their natural instincts to achieve the best birth for their baby and for themselves, it works with mothers and families on birth expectations and taking a positive approach to the experience. It puts a lot of emphasis on language, breathing, relaxation, visualization and self-hypnosis and it highlights the fact that childbirth does not have to be painful [45].
\nIn 1992 a new method or program appears based on the affective bond with the baby: “intrauterine harmonization.” Dr. Thomas Verny and Pamele Weintraub prepare parents with music, deep relaxation, visualization and massage. They strengthen the bond between parents and children through dream induction, guided work with images, drawings, lullabies and words addressed to the child. The conflicts that future motherhood can arouse in parents are solved by examining their own childhood and positive thinking techniques [46].
\nIn 1998, Pam England and Rob Horowitz devised a holistic approach to the preparation for childbirth and the postpartum period, known as Birthing from Within. As well as information on childbirth and children’s upbringing, they also addressed introspection and self-discovery from the perspective of the woman’s own internal experience [47].
\nIn 2004, Dr. Wendy Anne McCarty, co-founder of the Masters and Doctorate programs of “Santa Barbara Graduate Institute” in Prenatal and Perinatal Psychology, reviewed 30 years of clinical research in this field. Her book, “Awareness of Welcome,” presents an integrated model of early development that was a reflection of the clinical results found in her research of prenatal and perinatal psychology. The transcendental aspects of consciousness and human rights from the beginning of life become the central thread of this holistic model. It is an integrating model of early human experience, learning, development and care (from before conception to early childhood) that includes our sensitive nature and integrates several fields such as theories of infant development, new clinical investigations of babies that incorporate a conscious state, prenatal psychology and perinatal, paternity practices and some ideas that make up the new physics sciences. The author affirms that the most important thing is to reconstruct our sensitive spiritual nature as well as our fundamental nature of Sensitive Human Beings [48].
\nMaternal and child health and the emotional attachment around birth are so important that they are the axis of multiple health guidelines worldwide [49], and the body of numerous international research [50]. However, despite the importance of prenatal education, according to the latest reviews, neither the results nor the best educational approaches are known [51, 52, 53, 54, 55, 56]. This situation makes it necessary to consider studying and analyzing the most representative prenatal education schools. For this, we must look for the paradigm that lies behind each school and know the methodology they use. This work is arduous because of the difficulty of finding detailed information about some schools. In order to make the comparison work more explicit, Tables 1–4 have been made. Schools that have not found a paradigm have not been included in them.
\nEducation models | \nMain elements of teaching | \nCharacteristics of the sessions | \nParadigm | \n
---|---|---|---|
Hypnosis (1922) | \n\n
| \n\n
| \n“Childbirth under hypnosis = painless childbirth” | \n
Read (1932) English school | \n\n
| \n\n
| \n“Fear of childbirth = pain.” | \n
Velvoski (1939) Russian School | \n\n
| \n\n
| \n“Childbirth = De-conditioning pain” | \n
Lamaze (1940) French school | \n\n
| \n\n
| \n“Childbirth = Preparedness” | \n
Aguirre de Cárcer (1956) Spanish School | \n\n
| \n\n
| \n“Childbirth = emotional encounter” | \n
Comparison between the main models of prenatal education.
The first large prenatal education schools.
Education models | \nMain elements of teaching | \nCharacteristics of the sessions | \nParadigm | \n
---|---|---|---|
International Childbirth Educators Association (ICEA) (1960) | \n\n
| \n\n
| \n“Childbirth = Family experience/informed choice” | \n
Robert Bradley (1965) | \n\n
| \n\n
| \n“Childbirth = Coaching fathers for childbirth“ | \n
Kabat-Zinn (1970) Mindfulness-Based Childbirth and Parenting | \n\n
| \n\n
| \n“Childbirth = awareness of birth and upbringing” | \n
Kitzinger (1970) Active Birth Mouvement | \n\n
| \n\n
| \n“Childbirth = No pain, Active childbirth movement” | \n
Velman (1970) Haptonomy | \n\n
| \n\n
| \n“Childbirth = develop a feeling of parenthood through touch” | \n
Comparison between the main models of prenatal education.
The new prenatal education schools [1].
Education models | \nMain elements of teaching | \nCharacteristics of the sessions | \nParadigm | \n
---|---|---|---|
Leboyer (1975) French school | \n\n
| \n\n
| \n“Childbirth = Baby fear” (non-violent birth) | \n
Michel Odent (1975) | \n\n
| \n\n
| \n“Childbirth = Recovering natural instincts. Personal and intimate experience” | \n
Piscicelli (1984) Respiratory autogenous training | \n\n
| \n\n
| \n“Childbirth = woman protagonist of her birth in an environment full of stimuli” | \n
“National Health System, Spain (1986) Maternal Education Program Spanish School | \n\n
| \n\n
| \n“Childbirth = emotional encounter” | \n
Harper (1987) Waterbirth | \n\n
| \n\n
| \n“Childbirth = Waterbirth | \n
Comparison between the main models of prenatal education.
The new prenatal education schools [2].
Education models | \nMain elements of teaching | \nCharacteristics of the sessions | \nParadigm | \n
---|---|---|---|
Mongan (1990) Hypnobirth | \n\n
| \n\n
| \n“Childbirth = Hypnobirth No pain” | \n
Verny (1992) “Intrauterine Harmonization” | \n\n
| \n\n
| \n“Childbirth = Intrauterine Harmonization” | \n
Horowitz (1998) “Birthing From Within” | \n\n
| \n\n
| \n“Childbirth = Self-discovery (birthing from within)” | \n
McCarty (2004) Welcome awareness | \n\n
| \n\n
| \n“Childbirth = Welcome awareness” | \n
Comparison between the main models of prenatal education.
The new prenatal education schools [3].
Given this multiplicity of methods, Walker affirms that we are at a crossroads [14]. Women and their partners have, in the developed world, more information opportunities on pregnancy and labor than ever before, but does this information really reach them in a way that they are capable of applying to their personal experience? Do we know which is the best educational method? Do we know which elements should be included in educational programs to obtain the best results? The professionals who work in antenatal education need to understand the current situation of women and be able to guide them in making informed decisions based on scientific evidence. It is also necessary to eradicate the current belief that technology and medical interventions guarantee the well-being and safety of women during childbirth. Therefore, education for women and their partners on care during pregnancy, labor and the postpartum period is still, in the twenty-first century, an issue of great concern in order to recover the experience of childbirth for women and to reinstate the birth of a human being as an integral part of the family experience from the beginning of the pregnancy [57].
\nThis work allows us to see how the first courses on “childbirth education,” “natural birth” and “painless labor,” in which the main approach was to reduce the pain for women in hospital childbirth, have evolved toward educational health programs in which. The main approach is maternal-infant health during pregnancy, labor and the postpartum period and the emotional bond with the newborn.
\nThe work describes the characteristics of the five main schools and of the main new models of antenatal education. The comparative analysis is the basis for identifying the similarities and differences of each of them. This will help professionals to choose the educational approach that best meets the characteristics of their environment. It can also lay the foundations for the design of research questions that remain unresolved, such as finding the best educational approaches and the best learning strategies in this environment [14, 49, 50, 51, 52, 53, 54, 55, 56]. The biggest limitation was restricting the search for works published in English and Spanish, as there may be schools in other languages that identify with different cultures. In the review, only three articles were found that analyzed the different models [8, 14, 33], so there is not a great deal of scientific literature with this approach for investigation. This means that the results offer the opportunity of thinking about the importance given to this subject, as health professionals, and the strategies we use to address and develop them. It also allows us to re-think the approach of antenatal education that underlies the care of women and their families at such a crucial point in life and health that is labor and the birth of a child. This can only be of benefit to health professionals, who will be able to provide more appropriate and efficient care, as well as to all future mothers and fathers who could receive a higher quality of medical attention.
\nAll the mothers and fathers who during the last 35 years have given me the opportunity to bring me closer to their moment of birth.
\nAll the academic and health institutions that have made this work possible.
\nThis work is an update of chapter two of the doctoral thesis: Fernández M. Preparation, validation and application of an evaluation tool for maternal education programs of the primary care centers of the Community of Madrid. Madrid: Comillas Pontifical University. 2012. Available from:
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