Children follow-up study of PCOS women

Polycystic ovary syndrome (PCOS) is a complex and frequent disorder with a
heterogeneous clinical presentation varying throughout life, from birth up to
post-menopause. Although mostly known for its reproductive consequences, PCOS
is associated with metabolic abnormalities related to insulin resistance and
obesity. Children born from PCOS mothers are considered to be at risk for early
insulin resistance, leading to development of PCOS and metabolic abnormalities
in childhood and adolescence. Obesity and insulin resistance are considered as
states of low- and pro-inflammation associated with endothelial dysfunction. In
addition, it has been shown that endothelial dysfunction develops from the
first decade of life in response to genetic and environmental risk factors.
Therefore, offspring of women with PCOS may be at increased risk for vascular
disease later in life. Moreover, some evidence suggests that early life
respiratory disease also contributes to later life cardiovascular consequences.
The number of studies on offspring of PCOS mothers is low and a systematic
follow up of children born form PCOS mothers has not been performed yet. We
propose a systematic evaluation of cardiometabolic and pulmonary health
characteristics of children (aged 2,5-8 years) born from mothers diagnosed with
PCOS. A saliva sample will be performed to determine the biochemical androgenic
status of the children.
Mothers of these children have undergone standardized phenotyping prior to
conception; we will therefore be able to correlate the metabolic status of the
mother around the time of conception and the cardiometabolic and pulmonary
health of their offspring.

Primary objectives of the pilot study
• To determine childhood cardiovascular health in offspring of PCOS mothers and
to compare it with children from non-PCOS mothers.

Secondary objectives of the pilot study
• To compare cardiovascular risk factors between age groups
• To determine the childhood androgenic biochemical status in offspring of PCOS
mothers and to compare it with children from non-PCOS mothers
• To determine childhood pulmonary health in offspring of PCOS mothers and to
compare it with children from non-PCOS mothers
• To relate childhood cardiovascular health in offspring of PCOS mothers to
their mothers around time of conception

Future objective of the main study
To form a cardiovascular prediction model for children of PCOS mothers in a
longitudinal study.

Design: cross-sectional case-control study
Duration: 12 months
Setting: Single-centre study. Wilhelmina Children*s Hospital (WKZ) in Utrecht.

Since the pathogenesis of CVDs is known to start early in life and symptoms of
cardiovascular disease become present later in life, early factors associated
with the pathogenesis of CVDs have to be studied in children. Due to new
techniques (Luminex®) in the laboratories of the department of pediatric
immunology, it is now possible to study adipocytokines in small amounts of
serum.
It is believed that at the age of 5-8 years, blood sampling is minimally
invasive as the participants will probably understand the context and the aim
of the research. We therefore think that this blood sample to obtain
information on adipocytokines is justified in these children aged 5-8 years.
Subjects will have no benefit form participating to this study. The risks
associated with participation in this study are very small and the possible
complications are non-severe. Moreover, there is a risk of developing a
haematoma after the venous puncture. These risks have a short duration and are
non-severe.
The study related burden for the subjects will be minimized by using local
anaesthetics before the puncture will be conducted and a small needle will be
used. Moreover, the venous puncture will only be performed once. If the venous
puncture fails, the child will not be punctured for a second time, unless the
child and their parents give their permission.