Finding the cause and applying the insights toward prevention and treatment forms
the ultimate goal of most disease research. This strategy has been successfully used
to make diseases like Scurvy and Smallpox, a history. The impact of this research
during the last few years has been nothing less than miraculous. More and more people
are living longer with healthy and productive lives, well into the 80's and 90's.
Discovery of the cause(s) of disease(s) however is a demanding, time consuming, and
expensive exercise. Also, there is no guarantee for success. Yet, even the modest
success in search for causes have the potential to change the outcome and perception.
Early diagnosis of a number of cancers for example is now viewed as treatable with
reasonable chance of recovery. Also, some heart diseases are being managed and treated
with high rate of success. Given this record of success, the research on disease causations
continues to increase and the results have begun to pay increasing dividend. Unfortunately,
there are cases of diseases where even full understanding of the cause has not resulted
in the prevention or treatment of some common and devastating diseases. One such disease
is the fetal alcohol spectrum disorder (FASD).
FASD is caused by the exposure of developing fetus to alcohol via maternal drinking
during pregnancy (Jones and Smith, 1973). It represents the biggest single cause of
mental retardation and developmental disabilities among babies born in the Western
World (Barry et al., 2009). In the U.S. more than 50,000 babies are born with FASD
every year (May and Gossage, 2001) and the annual cost of treating FASD in Canada
and U.S. exceeds $6 and $8 billions, respectively (Lupton et al., 2004; Popova et
al., 2013). Although, the prevention of FASD is a high priority, the failure to prevent
it is attributed to our alcohol culture. Most people drink for social and recreational
purposes. Others are addicted to alcohol.
As it stands, there is no consensus on whether there is a “safe” limit for alcohol
consumptions during pregnancy. Recent research involving animal (mice) models has
shown that continuous exposure of low-to-moderate dose of alcohol during pregnancy
impacts behavioral and cognitive outcomes of resulting pups (Kleiber et al., 2011)
and even a single binge dose of alcohol at any time during pregnancy results in alterations
in gene expression (Kleiber et al., 2012, 2013) and associated FASD related phenotypes.
Furthermore, the molecular alterations may be initiated and maintained for life by
alcohol's effect on epigenetic features that includes DNA methylation (Laufer et al.,
2013). The results on animal models argue that clinical features of FASD represent
“tip of the iceberg.” They are also backed by results on humans. For example, exposure
of human embryonic stem cells to low alcohol can alter gene expression leading to
the abnormal development of prefrontal cortex (Krishnamoorthy et al., 2010). Also,
fetal alcohol exposed school children show “a small but potentially important detrimental
effect” on educational outcomes (Zuccolo et al., 2013) as well as generalized deficit
of conceptualization (Quattlebaum and O'Connor, 2013).
We feel that such results deserve due consideration given that Royal College of Obstetrics
and Gynecologists (Royal College of Obstetrician and Gynaecology, 2006) states that,
“there is no evidence of harm from low levels of alcohol consumption, defined as no
more than one or two units of alcohol once or twice a week.” Also, “there is considerable
doubt as to whether infrequent and low level of alcohol consumption during pregnancy
convey any long-term harm”—in other words they suggest a safe amount of alcohol consumption
in pregnancy. Unfortunately, this limit has not been defined and may vary from individual
to individual. Individual women process alcohol differently. Also, the age of the
mother, the timing and regularity of the alcohol ingestion, and whether the mother
has eaten any food while drinking may be important. We argue that there is no logistic
evidence to define this limit. What is needed is to undertake thorough studies on
neurodevelopment and assess the significance of such factors as maternal and fetal
genotype, stress during pregnancy and childbirth, prenatal drinking patterns (mild,
medium, heavy), post-natal environment, and socioeconomic status, as most of these
may contribute to the manifestation of the effect of prenatal alcohol on the newborn.
We note that some of these studies will be problematic if not impossible on humans.
The rational question is “does no evidence of harm from low levels of alcohol consumption
means 100% exclusion of the possibility of any harm to the fetus?” To the best of
our understanding the answer is “no.”
The issue is particularly problematic as there is a rise in heavy drinking by young
people, particularly women. Often, it is framed, as freedom of choice or “a single
drink will not harm.” Not surprisingly, 1 in 8 adult women and 1 in 5 high school
girls binge drink (CDC, 2013) and there is ample evidence from animal experiments,
which argue for a life-long effect of even a single exposure of alcohol during pregnancy.
The developing brain is a sequential, multistage, closely orchestrated, and highly
sensitive to stresses. Also, any aberration could lead to life-long abnormality. For
now, it is prudent to prevent a brain disorder than to attempt to ameliorate or cure
it. Preventing a single case of FASD will save the society $1 million. More importantly
it will save a productive life. The business as usual model is not helpful. It continues
to result in births with alcohol effects. Any harm caused by prenatal alcohol is currently
not reversible. It will affect the child for life.
With the current knowledge of what causes FASD it is prudent to stay on the safe side
and avoid any drinking during and around the pregnancy. FASD is an alcohol problem.
It is possible to prevent this calamity by avoiding alcohol during pregnancy and the
time is now! FASD is a preventable disease—by not drinking during pregnancy. On the
other hand, finding “cure” will be much more challenging, costly and time taking.
It is critical to undertake active measures to reduce the occurrence of this disorder
by a message of “no alcohol dose is guaranteed to be 100% safe for the embryo/fetus.”
Also, “no time during pregnancy is 100% safe to drink.” Any adult has the right to
drink if they so wish. Also, every child has the right to be born healthy!
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.