SIMPLE: implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study.

BACKGROUND: Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives). METHODS: An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs. DISCUSSION: This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child. TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT01261676.

Characterization of the human CD34+ hematopoietic progenitor cell compartment during the second trimester of pregnancy.

BACKGROUND AND OBJECTIVES: Characterization of the different sites of fetal hematopoiesis during the second trimester of pregnancy can provide important information for the timing of in utero stem cell transplantation (SCT), as an experimental treatment for congenital hematologic disorders. DESIGN AND METHODS: We analyzed the distribution of the different hematopoietic precursor cells in fetal blood, liver, bone marrow (BM), spleen and thymus from 66 fetuses between the ages of 13 to 23 weeks of gestation by flow cytometry and culture of hematopoietic progenitor cells (HPC) in semi-solid media. RESULTS: During the second trimester the percentages of CD34+ cells did not change and were 4.0% (1.0-12.0%) (median [min.-max.]) in blood, 16.5% (3.0-32.0%) in BM, 6.0% (2.0-16.0%) in liver, 5.0% (2.0-14.0%) in spleen, and 1.1% (0.9-3.0%) in the thymus. Each tissue contained all subsets of CD34+ cells at various levels. Within the CD34+ population, in BM the main sub-population was CD34+CD19+ (38% (11-67%)), in thymus CD34+ CD7+ (83% [45-98%]), and in blood and liver CD34+ CD33+ (57% (30-80%) and 48% (20-82%), respectively). In all tissues approximately 1 % of nucleated cells were non-committed CD34+ CD38- cells. The frequencies of both committed CD34+ cells and non-committed CD34+ CD38- cells were constant from 13 to 23 weeks in fetal blood, BM, liver and spleen. The frequencies of cultured HPC were high in fetal liver, low in fetal BM, and increasing in fetal blood. INTERPRETATION AND CONCLUSIONS: During the second trimester of gestation, all CD34+ subsets were present in each hematopoietic compartment at different levels. An exchange of stem cells between organs is likely, but no major shift of the hematopoietic stem cell compartment from the liver to other hematopoietic organs was found during the mid-trimester. No arguments for a specific time window for performing in utero SCT were found, but if engraftment of donor stem cells in the human fetus is influenced by competition of endogenous stem cells or fetal immune competence, in utero SCT should be performed as early as possible during fetal development.

Magnetic resonance imaging of fetal bone marrow for quantitative definition of the human fetal stem cell compartment.

Magnetic resonance imaging (MRI) can be used to distinguish bone marrow (BM) from cartilage and may therefore be used to measure BM volume in intact bones. We used MRI to measure the total human fetal BM volume in intact fetuses during the second trimester of pregnancy and determined the contribution of the individual bones to the total compartment. The total BM volume ranged from 934 microL at 17 to 18 weeks to 4563 microL at 22 to 23 weeks of gestation. The largest contributor to the total BM volume was the spine, constituting 26.4% +/- 2.7% of the total volume. By analyzing leukocyte content and percentages of CD34+ cells, lymphocytes, granulocytes, and monocytes of determined volumes, absolute numbers of these cell populations in BM could be measured. The cellular composition of the BM compartment did not significantly change throughout the second trimester of gestation. Absolute white blood cell counts per fetus increased from 111 x 10(6) at 16 to 17 weeks to 1229 x 10(6) at 21 to 22 weeks. The absolute numbers of CD34+ cells increased from 25 x 10(6) at 16 to 17 weeks to 256 x 10(6) at 21 to 22 weeks. Similar analysis of liver and spleen revealed comparable absolute numbers of CD34+ cells in BM and liver throughout the second trimester of gestation. In fetal liver, CD34+ cells differentiate into red cells, myeloid cells, and platelets, while lymphopoiesis mainly occurs in BM or spleen. Combining MRI and cell counts provides a method to quantify specific cell populations in fetal compartments. This study may enable better evaluation of fetal diagnostics and therapies.