Quantification of PEth to determine alcohol consumption by pregnant women, a prospective prevalence study

Alcohol consumption during pregnancy is known to cause damage to the unborn
child. It influences both the physical and neurobehavioral development of the
fetus. The (visible) effects and developmental problems of these children are
referred to as fetal alcohol spectrum disorder (FASD) or fetal alcohol syndrome
(FAS). FASD is characterized by a broad spectrum of symptoms, which are not
necessarily present at the same time or in the same extent. FAS is the most
serious variant of these disorders. Children with FAS meet the following
criteria: growth deficiency, three FAS facial dysmorphic signs, central nervous
system abnormalities (including cognitive and behavioural developmental
disorders and microcephaly), and maternal alcohol exposure . In North America,
FASD currently represent the leading cause of mental retardation, ahead of Down
syndrome and cerebral palsy . Although recent data are unknown for the
Netherlands, it is estimated that in the Netherlands every year at least 135
children are born with FAS and 400 with FASD. Today, health care providers
assume that these numbers are much higher because FAS and FASD are often
misdiagnosed.

To what extent low to moderate alcohol consumption does cause FASD or FAS still
remains unclear. However, there is a clear relation between excessive alcohol
consumption and FAS in children these women gave birth to. A study among
pregnant British women suggest that both pregnant women and women planning to
conceive, should be advised to abstain from alcohol. They state that even women
consuming 1-2 drinks up to two times a week are at risk of having babies with
reduced birth weight and born preterm, compared to women who abstained from
alcohol . They also found the effect of alcohol to the fetus to be the
strongest during the first trimester. On the contrary, a Dutch study found that
low-to-moderate alcohol consumption by pregnant women did not adversely affect
fetal growth characteristics. Although these studies show different results, it
is important to realise that they only focus on fetal growth and birth weight
and it is often difficult to diagnose FAS or FASD in those early stages of
life.

Another point to take into account is the fact that these studies on alcohol
consumption during pregnancy are based on questionnaires. When self-reporting
on alcohol consumption is compared with meconium testing for fatty acid ethyl
esters, a degradation product of alcohol, the meconium test was positive 4-13
times as often as would be expected on the self-reports. The inconsistency in
study results might be caused by unreliable data of self-reports. Therefore, a
reliable biomarker to detect alcohol consumption is highly desirable.

Phophatidylethanol (PEth) is a direct alcohol marker which is formed in the
cell membranes of red blood cells by means of phospholipase D. PEth is a very
specific metabolite, since it is formed exclusively in the presence of ethanol
and can therefore not be detected in non-drinkers. Furthermore, PEth remains
detectable in blood for an average period of at least two weeks. This offers
potential for retrospective detection of alcohol over a longer period. Such
analyses are desirable for pregnant women since they underreport to
questionnaires. When their alcohol consumption from even several weeks ago can
be objectified, these women can be offered special counselling programs. This
might prevent further alcohol consumption, will protect the fetus and therefore
reduce the number of children born with FAS and FASD. And even more important,
PEth can help us find possible relationships between alcohol consumption during
pregnancy and characteristics of the women that consume while pregnant. And
therewith we might be able to enter better education on women whom meet these
characteristics before they become pregnant.

Primary Objective:
-To explore the percentage of positive total PEth levels in blood, as a proxy
of alcohol consumption, in pregnant women during their first visit to the
obstetrics department.

Secondary Objectives:
To explore the distribution of POPEth, PLPEth and DOPEth levels in blood, as a
proxy of alcohol consumption, in pregnant women during their first visit to the
obstetrics department.

To analyse the association between positive total PEth levels in blood and
several patient characteristics (age, ethnicity, gravidity, parity, reported
alcohol consumption, gestational age, haemoglobin concentration and/or postal
code) in pregnant women during their first visit to the obstetrics department.

To analyse the association between POPEth levels, PLPEth levels and DOPEth
levels in blood and several patient characteristics (age, ethnicity, gravidity,
parity, reported alcohol consumption, gestational age, haemoglobin
concentration and/or postal code) in pregnant women during their first visit to
the obstetrics department.

Prospective prevalence study.
All pregnant women that visit the outpatient obstetrics department of Erasmus
MC and by whom routine laboratory testing is performed for the first time (new
pregnant women), regardless of their gestational age, will be included
anonymously in the study, unless opt-out. Analysis will be performed with means
of rest material.

Minimal.