The HAPPY Study: Holistic Approach to Pregnancy and the First Postpartum Year

Recruitment: Dutch-speaking Caucasian women (or third generation women of other ethnic groups) who have their first prenatal visit are eligible to participate in the study from the early beginning of their pregnancy. Eligible pregnant women (and their partner) receive written and oral information about the study at their first prenatal visit. If women decide to participate, written informed consent will be obtained. Written informed consent includes participation in the study and inclusion of all obstetric data from the medical record form of the community midwife and obstetrician (including ultrasound data), a detailed delivery description and neonatal condition, and data of newborn screening (heel prick test).

Sample size calculation: The total amount of pregnancies in the area of the 17 community midwife practices is about 5,000 per year. With 10-15% non-Caucasian, 10-15% early abortion rate and 1.7% gemelli pregnancies, approximately 3,700 pregnant women will be eligible annually. Based on previous pregnancy-related research experiences of the last 20 years in this area, the response rate is expected to be high (70%) especially when no additional blood tests or interventions have to be performed. This will result in about 2,600 inclusions annually. During pregnancy, the rate of women moving outside the area is in general low which means that a number of 2,500 women are expected to finish the study protocol until delivery. After a pilot period of three months followed by a running-in period of three months, it is estimated that all midwife practices will collaborate within six months. Therefore, the period of recruitment will take 18 months to include 2,600 women.

Because different types of events with different prevalence rates might interfere with the sample size needed for appropriate statistics, the number of 2,500 women is estimated to meet the standard epidemiological criteria. With 2,500 participants, the following numbers of abnormal events are estimated to be found: 108 women with a foetus in breech position (4.3%), 185 preterm births (7.4%), 450 women (18%) will develop depression during pregnancy and 325-475 women (13-19%) will develop postpartum depression during the first postpartum year. According to thyroid function, the investigators will find 200 (8%) women with elevated titres of thyroid peroxidase antibodies (TPO-Ab) and 100 with thyrotrophin (TSH) levels > 2.5 IU/l. These numbers will allow statistical analysis with sufficient power. With an expected prevalence rate of 4-10% (breech, preterm birth, TPO antibodies, TSH > 2.5), a significance level of 5% and a power of 80%, 1,500-2,140 women need to be included (depending on the expected prevalence rate). In order to anticipate on (low) drop out, 2,600 women will be included.

Data collection:

• Questionnaires (eight questionnaires during the period between 12 weeks gestation and 12 months postpartum)
• Obstetric record form
• Standardized 20 weeks ultrasound (SEO)
• Blood analysis of thyroid function and HCG. The Primary Care laboratory of Eindhoven (Diagnostics voor U) will be responsible for collection of the blood samples and the ultrasounds. The Laboratory of clinical chemistry and haematology of the Máxima Medical Centre Veldhoven is responsible for analysis of TSH, free-thyroxin (FT4), TPO-Ab and HCG and storage of the blood samples. Since the additional tube of blood will be drawn during the regular blood assessment (which already needs a venipuncture), and the umbilical cord and the placenta normally are thrown away for destruction after birth, it can be stated that there are no additional interventions performed to either mother or the newborn within the HAPPY study.