TOwards Prepared mums (TOP-mums), for a healthy start: A lifestyle intervention to reduce overweight and smoking in women with a pregnancy wish to prevent perinatal morbidity

The world suffers a global epidemic in non communicable diseases such as
diabetes mellitus, heart diseases and dyslipidaemia. Non-communicable diseases
can emerge because of exposure to an unhealthy lifestyle involving (second
hand) tobacco use, a lack of regular physical activity, and consumption of
diets rich in highly saturated fats, sugars and salt. The influences of
exposure to an unhealthy lifestyle can start very early in life, namely already
before and during pregnancy. Among the adverse lifestyle of women in
reproductive age, smoking and obesity are the most potentially modifiable
factors.

Obesity is detrimental for reproduction. Once pregnant, overweight and obese
women are at increased risk of pregnancy complications, including gestational
diabetes mellitus, pregnancy induced hypertension, preeclampsia and caesarean
delivery. Foetuses of overweight and obese pregnant women are at increases risk
of stillbirth, congenital anomalies and childhood obesity.

Smoking of the mother during pregnancy has several adverse effects for mother
and child. It not only reduces the fertility rate but also increases the risk
on spontaneous abortion, ectopic pregnancy, placental disorders, premature
rupture of membranes and higher rate of urinary tract infections. Moreover, the
risk on dysmaturity, prematurity, sudden infant death syndrome and asthmatic
disease greatly increases in the case of in utero exposure to cigarette smoke.

From a societal and clinical point of view there is an urgent need for an
intervention that break the vicious circle of transferring harmful lifestyle
influences from generation to generation. Therefore, this study will
investigate the effectiveness of an early-life intervention. The potential
beneficial health effects of a preconceptionally started lifestyle intervention
for mother and child are impressive. It may lead to better fertility, less
preeclampsia, less prematurity, less dysmaturity, less respiratory symptoms and
infections and a lower prevalence of childhood obesity.

The overall objective of the study is to investigate a lifestyle intervention
for women with a pregnancy wish or pregnant women in their first trimester, and
a high risk on perinatal morbidity because of (prepregnancy) overweight or
obesity. With an effective intervention directed towards healthy living,
including reduction of overweight or obesity and, if applicable, smoking
reduction, health problems in mothers and their offspring can be prevented.

The study design will be a randomised controlled trial regarding a lifestyle
intervention directed towards a healthy diet, adequate physical activity and,
if applicable, smoking reduction. A 1 : 1 randomisation will be applied. The
intervention group will receive the lifestyle intervention. The control group
will receive usual care and 1 recipe for a healthy meal per week. Block
randomisation will be stratified for the presence of different lifestyle
behavior factors: overweight (BMI 25.0-29.9 kg/m2), obesity (BMI >= 30.0 kg/m2),
overweight and smoking or obesity and smoking. The program and follow-up
continues during pregnancy, until 1 year after delivery.

The investigational treatment consists of a lifestyle intervention and will
directed towards a healthy diet, adequate physical activity and, if applicable,
smoking cessation. The program will start with a personal screening of the
women at the website of Slimmer Zwanger. The women receive information about
their unhealthy and healthy lifestyle habits, making visible with a figure and
supporting text. Thereafter, the coaching part of Slimmer Zwanger will start.
Through digital posts, women will get tips, tricks, rewards and recipes for
healthy meals. The advices are customised according to the results of the
personal screening and are offered at least three times a week.

The lifestyle intervention regarding a healthy diet and adequate physical
activity will be divided in two parts. First, women can participate in the
program of the Centre for Obesity and eating disorders Europe (CO-EUR). CO-EUR
is a second-line mental health institution and is specialised in treatment of
patients with obesity and eating disorders and their related comorbidities. The
treatment of CO-EUR is based on evidence based treatment methods. The short
program (4 months of duration) will be offered to the women participating in
this study.

Furthermore, the guidance consists of consultations with a dietician and a
physical activity program. During different phases in their life
(preconception, during pregnancy and postpartum), each phase will be
accompanied by specific lifestyle advices, and the women will be supported to
persevere the lifestyle changes they made earlier. The lifestyle intervention
targeted at overweight and obesity is based on the recommendations of the CBO
guideline *Diagnostics and treatment of obesity in adults and children* and
consists of a structured lifestyle program targeted at:
- Changing the dietary pattern;
- Stimulating physical activity of moderate intensity;
- Self-monitoring;
- Involvement of the partner.

Each woman will have her personal lifestyle coach. This personal coach will
have an overview over the lifestyle intervention and guide the women through
their personal program. Moreover, this personal coach is involved with the
smoking cessation coaching if smoking is present at inclusion. Smoking
cessation will be stimulated by coaching of the website of Slimmer Zwanger.
Moreover, the personal coach will stimulate the women to stop smoking by direct
feedback by use of carbon monoxide (CO)-measurements. The CO-gauger will show
the CO concentration in the blood of the foetus as well.

For the women, there are no associated risks in this study and the intervention
is non-invasive. The lifestyle intervention will be performed according to the
current guidelines and are under stringent supervision. Women in the
intervention group will visit the hospital, CO-EUR, dietician or sport
activities on a regular basis. This requires time and effort of the women. To
limit the burden as much as possible, the activities will be adapted as much as
possible to work and other activities of the women. Furthermore, the study
visits will be combined as much as possible with appointments with the midwife
or at the child well-being centre. Women that are randomised in the
intervention arm or who are pregnant at inclusion will attend the clinic for
4-12 extra visits in order to improve lifestyle, this will take around
11,5-19h. Moreover, they will be encouraged to participate in a physical
activity program). Women in the intervention group should adapt their lifestyle
in order to a healthier lifestyle. This will entail a certain degree of effort.
The control group will receive usual care. Therefore, they will not be
restrained from the standard care. They will not be restrained when they want
to search for guidance in improving their lifestyle. Subjects in the
intervention group are more likely to benefit from this research. The
intervention could have beneficial effects for the study population like
improving their health status, pregnancy rate and inducing less pregnancy and
delivery complications. Finally, not only the subjects in the intervention
group will benefit from this study but at the long term the global public
health as well. Data that will be collected, consisted of questionnaires (TFEQ,
EQ-5D-5L, Baecke questionnaire, smoking behaviour and health care cost
questionnaire), measurements of weight, anthropometry, blood pressure, CO
measurements (4-11times), body composition (2-4 times), glucose, insulin, lipid
profile and liver enzymes (3-7 times), OGTT (2-3 times), PWV and retinal image
(4-8 times) and urine cotinine (6-7 times) in the mother. Furthermore, samples
of microbial flora (faeces, vaginal swab and throat swab) will be collected
each 3 months and samples of breast milk will be collected at every visit
postapartum in case the mother is still breastfeeding (1-4x). The health risks
of most of the measurements are considered as negligible, since the methods are
routinely used in both research and in clinical practice.


The intervention and measurements will take place mainly in the mother during
the study. However, a part of the intervention is targeted on the child and a
couple of measurements will be executed in the children. The part of the
intervention that is targeted on the child will exists of advices to the
parents among nutrition and physical activity for their child. Examples of
these advices are the introduction of solid food and sufficient physical
activity. In usual care, these advices are already implemented in the child
well being centers. However, in the intervention group, these advices will be
reinforced. The child will not be exposed to risks. Moreover, in all children a
couple of measurements will be executed. In general, these measurements are
considered as a minimal burden and the health risks are negligible. In the
children, data collection will consist of 2 times a blood sample (of which 1
time is taken from the cord blood), and collection of the microbial flora
(faeces ) for 4 times.

We believe that the burden of the measurements will be compensated by the
social interest of the outcome of these measurements. With these measurements
we can study the effects of the lifestyle intervention on the health of the
mother and child. Moreover, with the data that will be collected, more insight
into the causes and relationships between the transition of harmful lifestyle
influences and the development of non-communicable diseases will be derived.
The lifestyle intervention is set up in that way, that implementation in usual
care would be very easy. When the lifestyle intervention will turn out to be
effective, this can be easy implemented in the already existing health care.
With this in mind, this study will contribute to the global public health.
Namely, not only the health of the mother will improve, but also the health of
the child will be guaranteed by an intervention that break the vicious circle
of transferring harmful lifestyle influences from generation to generation.