8 Fetal Alcohol Spectrum Disorder: Embryogenesis Under …
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and Sokol 2011; Andersen et al. 2012). For first trimester spontaneous abortion, alcohol intake can increase the risk fivefold from the general population, while alcohol
drinking can increase the risk of stillbirth threefold and can reach 40% of at risk
pregnancies depending upon the amount of alcohol ingested, the pattern of drinking,
and the developmental stage of the fetus. From the detailed description and definition
of the viable births with FAS, it became clear these individuals represented the most
severely affected among the viable cases of fetal alcohol exposure.
A spectrum of developmental abnormalities induced by prenatal alcohol exposure
have been described (Chaudhuri 2000; Caputo et al. 2016; Gupta et al. 2016; Chudley 2018). Individuals with FAS exhibit neurodevelopmental abnormalities, including central nervous system (CNS) and craniofacial malformations, microcephaly,
and intrauterine growth restriction (IUGR) (Fig. 8.1). They also suffer from behavioral anomalies affecting mental capacity, behavior, social interactions, judgment
and concentration ability (Fig. 8.2).
The CNS is the main target of alcohol. Malformations in the CNS include brain
malformations affecting size, anatomical changes, neuronal connectivity and cell
death. In the majority of alcohol-affected individuals, the CNS defects also manifest
as functional deficits involving cognitive and mental disabilities, including reduced
intellectual capacity, learning disorders, poor memory, attention deficit, and multiple
deficiencies with information processing. Alcohol-affected individuals also exhibit
behavioral problems, including difficulty in school, poor social skills, impulsiveness, jitteriness, aggressiveness, and hyperactivity. It is commonly accepted, but
marginally understood that a number of factors like gestational age at the time of
exposure, the amount of alcohol, concurrent drug abuse, and the genetic background
of the mother and fetus affect the phenotypic manifestation, i.e. severity, of FASD
(Riley et al. 2011).
In addition to the neurodevelopmental defects, many individuals with severe FAS
also present other organ malformations or malfunctions in kidneys, heart, lungs and
other tissues (Fig. 8.1) (Guerri et al. 2009; Popova et al. 2016). Heart malformations, including atrial or ventricular septal defects and aortic and pulmonary artery
anomalies are observed in the more severely affected FASD individuals (Fig. 8.1).
Microphthalmia and inner-ear defects are also observed, and although they are considered part of the CNS, eye and ear malformations could arise by CNS-independent
mechanisms. Among other targets are the skeleton, with fusion of the vertebral bodies
or their posterior elements (scoliosis), thoracic cage abnormalities, and limb defects
(including mildly shortened or missing digits, curvature of the digits (clinodactyly),
radioulnar synostosis and carpal fusions) (González 1979; Herrmann et al. 1980;
Cremin and Jaffer 1981; Smith et al. 1981; Sreenathan et al. 1984; Tsukahara and
Kajii 1988). Renal abnormalities are also observed, including malrotation of the
kidney, neurogenic bladder and ureteropelvic obstruction. Alcohol can also cause
intrauterine or fetal growth restriction (IUGR or FGR), i.e. small size or weight for
gestational age (Mills et al. 1984; Arfsten et al. 2004; Banakar et al. 2009; Williams
et al. 2015).
Based on the developmental defects and the behavioral and cognitive anomalies
described, we can summarize that individuals with a partial form of FAS (pFAS)
203
and Sokol 2011; Andersen et al. 2012). For first trimester spontaneous abortion, alcohol intake can increase the risk fivefold from the general population, while alcohol
drinking can increase the risk of stillbirth threefold and can reach 40% of at risk
pregnancies depending upon the amount of alcohol ingested, the pattern of drinking,
and the developmental stage of the fetus. From the detailed description and definition
of the viable births with FAS, it became clear these individuals represented the most
severely affected among the viable cases of fetal alcohol exposure.
A spectrum of developmental abnormalities induced by prenatal alcohol exposure
have been described (Chaudhuri 2000; Caputo et al. 2016; Gupta et al. 2016; Chudley 2018). Individuals with FAS exhibit neurodevelopmental abnormalities, including central nervous system (CNS) and craniofacial malformations, microcephaly,
and intrauterine growth restriction (IUGR) (Fig. 8.1). They also suffer from behavioral anomalies affecting mental capacity, behavior, social interactions, judgment
and concentration ability (Fig. 8.2).
The CNS is the main target of alcohol. Malformations in the CNS include brain
malformations affecting size, anatomical changes, neuronal connectivity and cell
death. In the majority of alcohol-affected individuals, the CNS defects also manifest
as functional deficits involving cognitive and mental disabilities, including reduced
intellectual capacity, learning disorders, poor memory, attention deficit, and multiple
deficiencies with information processing. Alcohol-affected individuals also exhibit
behavioral problems, including difficulty in school, poor social skills, impulsiveness, jitteriness, aggressiveness, and hyperactivity. It is commonly accepted, but
marginally understood that a number of factors like gestational age at the time of
exposure, the amount of alcohol, concurrent drug abuse, and the genetic background
of the mother and fetus affect the phenotypic manifestation, i.e. severity, of FASD
(Riley et al. 2011).
In addition to the neurodevelopmental defects, many individuals with severe FAS
also present other organ malformations or malfunctions in kidneys, heart, lungs and
other tissues (Fig. 8.1) (Guerri et al. 2009; Popova et al. 2016). Heart malformations, including atrial or ventricular septal defects and aortic and pulmonary artery
anomalies are observed in the more severely affected FASD individuals (Fig. 8.1).
Microphthalmia and inner-ear defects are also observed, and although they are considered part of the CNS, eye and ear malformations could arise by CNS-independent
mechanisms. Among other targets are the skeleton, with fusion of the vertebral bodies
or their posterior elements (scoliosis), thoracic cage abnormalities, and limb defects
(including mildly shortened or missing digits, curvature of the digits (clinodactyly),
radioulnar synostosis and carpal fusions) (González 1979; Herrmann et al. 1980;
Cremin and Jaffer 1981; Smith et al. 1981; Sreenathan et al. 1984; Tsukahara and
Kajii 1988). Renal abnormalities are also observed, including malrotation of the
kidney, neurogenic bladder and ureteropelvic obstruction. Alcohol can also cause
intrauterine or fetal growth restriction (IUGR or FGR), i.e. small size or weight for
gestational age (Mills et al. 1984; Arfsten et al. 2004; Banakar et al. 2009; Williams
et al. 2015).
Based on the developmental defects and the behavioral and cognitive anomalies
described, we can summarize that individuals with a partial form of FAS (pFAS)