Pilot study of DEHP and BPA exposure during and after delivery, in mother and child

DEHP
Di(2-ethylhexyl)phthalate (DEHP) is a toxic organic molecule, with chemical
formula C6H4(C8H17COO)2 or C24H38O4. The compound is the most common of the
class of phthalate plasticisers. It is formed as a di-ester of phthalic acid
and the branched-chain 2-ethylhexanol. It is a colourless, viscous liquid with
a characteristic aroma. DEHP is hydrophobic/lipophilic and readily passes over
the placenta. It is also found in human breast milk.
Approximately 3 billion kilograms of DEHP are produced annually. DEHP is a low
cost product and is widely used as a plasticiser or softener in PVC products,
which may contain up to 40% DEHP. DEHP is also used as solvent and as fluid in
capacitors.
DEHP is banned in toys for children < 3 years of age in the European Union (EU
1999/815/EG). This is due to the fact that DEHP easily leaches out of PVC and
other plastics and is thought to be highly toxic to humans and environment. The
US Food and Drug Administration (FDA) only permits the use of DEHP in food
packaging for foods primarily containing water.
DEHP has traditionally been widely used as a plasticiser in medical devices.
Examples include intravenous tubing and bags, catheters, nasogastric tubes,
dialysis bags and tubing, blood bags and transfusion tubing, and endotracheal
ventilation tubes. Furthermore, it has been known for more than 30 years that
DEHP readily leaches out of these products, because it does not bind with the
plastic and subsequently, entering the human body.
At particular risk are neonates and the seriously ill child.

The Westfriesgasthuis has eliminated the use of PVC and DEHP-containing
products on the neonatal and pediatric wards. By doing so the hospital is a
forerunner in respect to other hospitals and health care institutions
throughout the Netherlands. However, PVC and DEHP-elimination has not (yet)
been realised for the rest of the hospital. We therefore expect women giving
birth in the hospital to be exposed to DEHP, resulting in perinatal exposure.
Additionally, the general population is exposed to DEHP in our homes, probably
via ambient exposure to DEHP-containing house dust. To our knowledge, no prior
studies have been performed to assess the perinatal exposure during birth, and
comparing the exposure on a maternity ward, operating theatre and home.

BPA
Bisphenol A (BPA) is an organic compound with chemical formula
(CH3)2C(C6H4OH)2. It is a colourless solid that is hydrophobic/lipophilic. It
is necessary for the production of polycarbonate polymers and epoxy. BPA is
known as a xenoestrogen, and has oestrogenic effects on humans and animals. The
US FDA issued a warning in 2010, wherein possible hazards to fetuses, infants,
and young children were stipulated. This was followed by Canada declaring BPA a
toxic substance. BPA has been banned for use in baby bottles in the European
Union, Canada, and recently the United States.
Bisphenol A is primarily used in the production of plastics since 1957. 21 At
least 3.6 million tonnes of BPA are used by manufacturers yearly. Polycarbonate
plastic, known from shatter-proof rulers, have traditionally also been used in
common products such as baby and water bottles, sports equipment, medical and
dental devices, dental fillings and sealants, CDs and DVDs, household
electronics, and eyeglass lenses. Bisphenol A was discovered in 1891 by Russian
chemist Aleksandr Dianin. In the early 1930s the British chemist Charles Edward
Dodds recognised BPA as a strong artificial oestrogen. At the time it was used
to enhance the growth of cattle and poultry and as an oestrogen replacement for
women. However, it was soon replaced by diethylstilbestrol (DES). Since the
1950s BPA has been used to harden polycarbonate plastics and make epoxy resin,
and in the lining of food and beverage containers.

While rodent studies conducted in the 1930s already showed toxicity effects, it
was not until recently that associations with negative health effects during
pregnancy and on development have been demonstrated. Early developmental
windows appear to be at greatest vulnerability and prenatal exposure has been
linked to later physical and neurological difficulties. BPA has been found in
96% of pregnant women in the U.S.
Similarly to DEHP, we expect women giving birth in the hospital to be exposed
to BPA, resulting in perinatal exposure. Additionally, the general population
is exposed to BPA in our homes. To our knowledge, no prior studies have been
performed to assess the perinatal exposure during birth, and comparing the
exposure on a maternity ward, operating theatre and home.

We seek to elucidate the perinatal exposures to DEHP and BPA with the intention
of providing evidence for policy makers and manufacturers. It is our hope that
less toxic products will be used in health care and in the general population
in the future. However, the laboratory testing costs are high and therefore a
pilot study will first be performed to elucidate whether the substances are
detectable in the urine of the mothers and children, and in the meconium and
amniotic fluid.

Primary Objective: is there a difference in exposure to DEHP and BPA at home,
in the delivery room and operating theatre?
a. The ambient concentrations in the home, delivery room and operating theatre
will be compared.
b. The DEHP and BPA levels in the pre- and post-delivery urine samples of the
mothers giving birth in a delivery ward and at home, will be compared with
mothers giving birth in an operating theatre.
c. The DEHP and BPA levels in the first urine samples of the neonates, born at
home will be compared to those born on a delivery ward or in an operating
theatre.
d. The DEHP and BPA levels in the meconium samples of the neonates, born at
home will be compared to those born on a delivery ward or in an operating
theatre.
Secondary Objective: is there a correlation between increasing exposure to
medical apparatus and increasing DEHP and BPA exposure in the mother and
newborn baby?
The registration forms of the medical apparatus used during the delivery will
be correlated to the DEHP and BPA exposures in the mothers and newborns.

This study is an open pilot explorative observational 3-arm cohort study. It is
currently unknown what the exposures of DEHP and BPA are in pregnant mothers
and newborn babies in the Netherlands. A total of 5 patients will be recruited
for each of the three settings for delivery: at home, on a delivery ward or on
an operating theatre. Consecutive multipara mothers-to-be will be approached by
their midwife or obstetrician, with the request to participate in the study. A
primary care midwife at Eva van Hoorn will be asked to recruit mothers-to-be.
All consecutive mothers-to-be planned for delivery in the Westfriesgasthuis
will be requested by their midwife or obstetrician, to participate in the
study. Inclusion will continue until 5 patients are included in each arm.
Patients dropping out of the study will be replaced by a following subject,
until the quota is achieved. The pilot study will run from 01-06-2014. Total
study duration for the participants is expected to be less than 48 hours (or
until the first urine sample and meconium of the neonate has been collected).
No further follow-up is planned but the participants may be approached in the
future for further research, upon their approval.

Standard medical care will continue to be provided. No variation from standard
care is required for the study, with the exception of the collection of the
urine, amniotic fluid and meconium samples. A total of 10 ml will be sufficient
for each sample. The mothers-to-be will be requested to collect a urine sample
prior to delivery and shortly thereafter. These samples will be collected in
glass containers. During delivery the midwife or obstetrician will be required
to collect amniotic fluid in a DEHP- and BPA-free syringe. The samples will be
transferred to glass containers for storage and analysis. After birth a DEHP-
and BPA-free urine collection bag will be applied to the neonate and removed as
soon as minimally 5 - 10 ml urine has been collected. The urine will be
transferred to a glass container for storage and analysis. A meconium sample
will be scooped from the diaper of the neonate and placed in a glass container
for storage and analysis. The registration of medical devices used will be done
by an attending nurse.
There are negligible risks associated with participation.