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1.  Knowledge about safe motherhood and HIV/AIDS among school pupils in a rural area in Tanzania 
Background
The majority of adolescents in Africa experience pregnancy, childbirth and enter motherhood without adequate information about maternal health issues. Information about these issues could help them reduce their pregnancy related health risks. Existing studies have concentrated on adolescents' knowledge of other areas of reproductive health, but little is known about their awareness and knowledge of safe motherhood issues. We sought to bridge this gap by assessing the knowledge of school pupils regarding safe motherhood in Mtwara Region, Tanzania.
Methods
We used qualitative and quantitative descriptive methods to assess school pupils' knowledge of safe motherhood and HIV/AIDS in pregnancy. An anonymous questionnaire was used to assess the knowledge of 135 pupils ranging in age from 9 to 17 years. The pupils were randomly selected from 3 primary schools. Underlying beliefs and attitudes were assessed through focus group interviews with 35 school children. Key informant interviews were conducted with six schoolteachers, two community leaders, and two health staffs.
Results
Knowledge about safe motherhood and other related aspects was generally low. While 67% of pupils could not mention the age at which a girl may be able to conceive, 80% reported it is safe for a girl to be married before she reaches 18 years. Strikingly, many school pupils believed that complications during pregnancy and childbirth are due to non-observance of traditions and taboos during pregnancy. Birth preparedness, important risk factors, danger signs, postpartum care and vertical transmission of HIV/AIDS and its prevention measures were almost unknown to the pupils.
Conclusion
Poor knowledge of safe motherhood issues among school pupils in rural Tanzania is related to lack of effective and coordinated interventions to address reproductive health and motherhood. For long-term and sustained impact, school children must be provided with appropriate safe motherhood information as early as possible through innovative school-based interventions.
doi:10.1186/1471-2393-7-5
PMCID: PMC1868762  PMID: 17456230
3.  Inflammatory pathways in the mechanism of parturition 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S7.
Increasing evidence suggests that parturition is an inflammatory process. In this brief overview, inflammatory events occurring in association with parturition, and the mechanism by which they may contribute to labour and delivery will be discussed. Mention will be made of how this information may be of use in regulating the timing and the onset of parturition.
doi:10.1186/1471-2393-7-S1-S7
PMCID: PMC1892064  PMID: 17570167
4.  Reductionist and system approaches to study the role of infection in preterm labor and delivery 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S9.
A substantial number of patients with preterm labor and delivery do not show clinical signs of infection, however, it is the subclinical form which is the main causative factor and often results in premature delivery. The hitherto commonly applied methods of inflammation detection are based either on potentially hazardous amniocentesis or still insufficient inflammation-related protein measurement in the serum or other biological fluids.
The advent of new "omics" technologies has led to a paradigm-shift in experimental approach which tends to primarily generate rather than form hypotheses. This has resulted in a surge of wealth of data composed of sets of individual or clusters of new genes and proteins that can be of potential importance as new markers of inflammation leading to preterm labor. It is hoped that as a result of those new methodologies the overall perception of medical research and practice would gradually change from reductionist to systems approach. Despite several successes of reductionism in the diagnosis and treatment of preterm labor it seems that system-based methodology would contribute to a more favorable personalized rather than one-for-all patient assistance. In this review we present the current knowledge on this new attractive field of medical studies with emphasis on early detection of infection related with preterm labor.
doi:10.1186/1471-2393-7-S1-S9
PMCID: PMC1892066  PMID: 17570169
5.  Measuring perinatal complications: methodologic issues related to gestational age 
Background
Perinatal outcomes differ by week of gestational age. However, it appears that how measures to examine these outcomes vary among various studies. The current paper explores how perinatal complications are reported and how they might differ when different denominators, numerators, and comparison groups are utilized.
Conclusion
One issue that can clearly affect absolute rates and trends is how groups of women are categorized by their gestational age. Since most perinatal outcomes can only occur in women and neonates who have delivered, using the number of pregnancies delivered (PD) as the denominator of outcomes is appropriate. However, for an outcome such as antepartum stillbirth, all women who are pregnant at a particular gestational age are at risk. Thus, the denominator should include all ongoing pregnancies (OP). When gestational age is used by week this means using both deliveries during a particular week plus those women who deliver beyond the particular week of gestation in the denominator. Researchers should be careful to make sure they are utilizing the appropriate measure of perinatal complications so they do not report findings that would be misleading to clinicians, patients, and policy makers.
doi:10.1186/1471-2393-7-18
PMCID: PMC2075508  PMID: 17760989
6.  Induction of labour versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks (the PPROMEXIL-trial) 
Background
Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries.
Methods/Design
We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring.
The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling.
Discussion
This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis.
Controlled clinical trial register
ISRCTN29313500
doi:10.1186/1471-2393-7-11
PMCID: PMC1934382  PMID: 17617892
7.  A translational approach to studying preterm labour 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S8.
Preterm labour continues to be a major contributor to neonatal and infant morbidity. Recent data from the USA indicate that the number of preterm deliveries (including those associated with preterm labour) has risen in the last 20 years by 30%. This increase is despite considerable efforts to introduce new therapies for the prevention and treatment of preterm labour and highlights the need to assess research in this area from a fresh perspective. In this paper we discuss i) the limitations of our knowledge concerning prediction, prevention and treatment of preterm labour and ii) future multidisciplinary strategies for improving our approach.
doi:10.1186/1471-2393-7-S1-S8
PMCID: PMC1892065  PMID: 17570168
8.  New research models and novel signal analysis in studies on preterm labor: a key to progress? 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S6.
Preterm labor affects up to 20% of pregnancies, is considered a main cause of associated neonatal morbidity and mortality and is responsible for neonatal care costs of multimillion euros. In spite of that, the commercial market for this clinical indication is rather limited, which may be also related to high liability. Consequently, with only a few exceptions, preterm labor is not in the orbit of great interest of the pharmaceutical industry. Coordinated effort of research community may bring the change and help required to reduce the influence of this multifactorial syndrome on society. Between the novel techniques that are being explored in a SAFE (The Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network) group, there are new research models of preterm labor as well as novel methodology of analysis of biological signals. In this article, we briefly describe new clinical and nonclinical human models of preterm labor as well as summarize some novel methods of data processing and analysis that may be used in the context of preterm labor.
doi:10.1186/1471-2393-7-S1-S6
PMCID: PMC1892063  PMID: 17570166
9.  Preterm labour detection by use of a biophysical marker: the uterine electrical activity 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S5.
Background
The electrical activity of the uterine muscle is representative of uterine contractility. Its characterization may be used to detect a potential risk of preterm delivery in women, even at an early gestational stage.
Methods
We have investigated the effect of the recording electrode position on the spectral content of the signal by using a mathematical model of the women's abdomen. We have then compared the simulated results to actual recordings. On signals with noise reduced with a dedicated algorithm, we have characterized the main frequency components of the signal spectrum in order to compute parameters indicative of different situations: preterm contractions resulting nonetheless in term delivery (i.e. normal contractions) and preterm contractions leading to preterm delivery (i.e. high-risk contractions). A diagnosis system permitted us to discriminate between these different categories of contractions. As the position of the placenta seems to affect the frequency content of electrical activity, we have also investigated in monkeys, with internal electrodes attached on the uterus, the effect of the placenta on the spectral content of the electrical signals.
Results
In women, the best electrode position was the median vertical axis of the abdomen. The discrimination between high risk and normal contractions showed that it was possible to detect a risk of preterm labour as early as at the 27th week of pregnancy (Misclassification Rate range: 11–19.5%). Placental influence on electrical signals was evidenced in animal recordings, with higher energy content in high frequency bands, for signals recorded away from the placenta when compared to signals recorded above the placental insertion. However, we noticed, from pregnancy to labour, a similar evolution of the frequency content of the signal towards high frequencies, whatever the relative position of electrodes and placenta.
Conclusion
On human recordings, this study has proved that it is possible to detect, by non-invasive abdominal recordings, a risk of preterm birth as early as the 27th week of pregnancy. On animal signals, we have evidenced that the placenta exerts a local influence on the characteristics of the electrical activity of the uterus. However, these differences have a small influence on premature delivery risk diagnosis when using proper diagnosis tools.
doi:10.1186/1471-2393-7-S1-S5
PMCID: PMC1892062  PMID: 17570165
10.  Functional genomics of the pregnant uterus: from expectations to reality, a compilation of studies in the myometrium 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S4.
Background
Studies on the human myometrium have reported on different microarrays containing different sets of genes or ESTs. However each study profiled only a small number of patients due to various constraints. More profiling information would be an addition to our knowledge base of parturition.
Methods
We compiled from five human studies, transcriptional differences between the non pregnant myometrium (NP), preterm myometrium (PTNIL), term myometrium not in labor (TNIL) and term myometrium in labor (TIL). Software modules developed by the Draghici's group at Wayne State University (Detroit, MI, USA) were used to propose a hierarchical list of several KEGG pathways most likely adjusted to changes observed in microarray experiments.
Results
The differential expression of 118 genes could be dispatched in 14 main KEGG pathways that were the most representative of the changes seen in NP and PTNIL, versus TNIL or TIL. Despite the potential of multiple pitfalls inherent to the use of the microarray technology, gene module analysis of the myometrial transcriptome reveals the activation of precise signaling pathways, some of which may have been under evaluated.
Conclusion
The remodelling and maturation processes that the uterus undergoes in pregnancy appear clearly as phenomena which last during the full course of gestation. It is attested by the nature of the main signaling pathways represented, in the comparison of the PTNIL versus TNIL uterus. Comparatively, the onset of labor is a phenomenon which remains less well characterized by these methods of analysis, possibly because it is a phenomenon occurring in too short a window to have been grasped by the studies carried out up to now.
doi:10.1186/1471-2393-7-S1-S4
PMCID: PMC1892061  PMID: 17570164
11.  Overview. Preterm labour: mechanisms and management 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S2.
Preterm birth remains a major cause of perinatal mortality and long term handicap in surviving infants. This is one of the most important clinical problems in Europe and across the world. While some preterm births are iatrogenic, associated with severe complications of pregnancy (e.g. hypertensive disorders, antepartum haemorrhage, infection), or the result of multiple pregnancies following assisted reproduction, a high proportion of preterm births occur following spontaneous preterm labour of unknown cause. Early intervention in this group of women would have a significant impact on neonatal mortality and morbidity figures. However, the endocrine changes preceding parturition in women remain elusive and this makes it difficult to predict spontaneous labour at term, let alone preterm labour. Moreover our understanding of myometrial physiology remains rudimentary, limiting our options to devise improved pharmacological strategies to control uterine contractility when this is indicated. There is a need for concerted European and international research efforts to improve our knowledge of the mechanism of labour in women, to identify diagnostic markers to predict preterm labour and to develop uterine selective drugs to inhibit uterine contractions in a safe and efficient manner. This aim will be achieved by multidisciplinary research efforts from academics and industry, using traditional laboratory and clinical research methods, as well as novel technologies.
doi:10.1186/1471-2393-7-S1-S2
PMCID: PMC1892059  PMID: 17570162
12.  Clinical aspects of cervical insufficiency 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S17.
Fetal loss is a painful experience. A history of second or early third trimester fetal loss, after painless dilatation of the cervix, prolapse or rupture of the membranes, and expulsion of a live fetus despite minimal uterine activity, is characteristic for cervical insufficiency. In such cases the risk of recurrence is high, and a policy of prophylactic cerclage may be safer than one of serial cervical length measurements followed by cerclage, tocolysis and bed rest in case of cervical shortening or dilatation. In low risk cases, however, prophylactic cerclage is not useful. There is a need for more basic knowledge of cervical ripening, objective assessment of cervical visco-elastic properties, and randomized controlled trials of technical aspects of cervical cerclage (e.g. suturing technique).
doi:10.1186/1471-2393-7-S1-S17
PMCID: PMC1892058  PMID: 17570161
13.  Tocolytic effect of a selective FP receptor antagonist in rodent models reveals an innovative approach to the treatment of preterm labor 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S16.
Background
Management of preterm labor by tocolysis remains an unmet medical need. Prostaglandins play a major role in regulation of uterine activity and in molecular mechanisms of human labor and parturition. There is some circumstantial evidence that prostaglandin F2α by action through the prostaglandin receptor subtype FP is effective in key events during labor uterine contraction, rupture of membranes and cervical dilation. This role of FP is briefly reviewed. In this study, we tested the hypothesis that an orally active and selective FP antagonist may arrest labor and delay parturition in animal models.
Methods
We examined the effects of a small molecule selective antagonist of the FP receptor (AS604872) in inhibition of spontaneous uterine contraction in pregnant rat near term. We tested AS604872 for its ability to delay preterm birth in a mouse model in which the anti-progestin agent RU486 triggered parturition.
Results
By oral or intravenous dosing AS604872 reduced markedly and dose-dependently the spontaneous uterine contractions in late-term pregnant rats at gestational days 19–21. In pregnant mice, AS604872 delayed the preterm birth caused by RU486 administration. The effect was dose-dependent with a significant increase in the mean delivery time of 16 and 33 hours at oral doses of 30 mg/kg and 100 mg/kg, respectively, in the case of labor triggered at gestational day 14. In both models AS604872 appeared more effective than the β-agonist ritodrine.
Conclusion
The tocolytic activity displayed by a selective FP receptor antagonist supports a key role for the FP receptor in the pathophysiology of premature birth and demonstrates the therapeutic potential of an FP antagonist for the treatment of preterm labor cases in which uterine hyperactivity plays a dominant role.
doi:10.1186/1471-2393-7-S1-S16
PMCID: PMC1892057  PMID: 17570160
14.  Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs? 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S14.
The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the β3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour.
doi:10.1186/1471-2393-7-S1-S14
PMCID: PMC1892055  PMID: 17570158
15.  Alternative splicing: an important mechanism for myometrial gene regulation that can be manipulated to target specific genes associated with preterm labour 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S13.
Considerable effort has been expended in attempting to distinguish genes that contribute to initiating the onset of term and preterm labour (PTL) from those that change in expression as a consequence of the progression of labour. The ability to define more clearly the genes involved in triggering labour contractions should lead to the development of new effective and safer strategies to prevent preterm birth. There is ample evidence to suggest that specific genes are co-ordinately regulated within the upper and lower regions of the myometrium prior to and during parturition and many of these genes are regulated by alternative pre-mRNA splicing. This mini-review highlights that expression of a range of different splicing factors, with defined roles in pre-mRNA splicing, is both temporally and spatially regulated within the uterine smooth muscle during pregnancy and labour. Moreover, several of these splicing factors play key roles in controlling the differential expression of specific regulatory proteins involved in uterine signalling and uterine quiescence. In addition, antisense morpholino oligonucleotide manipulation of pre-mRNA splicing may have potential in defining and targeting uterine pro-labour genes and thus contribute to the development of new therapeutic approaches to prevent PTL.
doi:10.1186/1471-2393-7-S1-S13
PMCID: PMC1892054  PMID: 17570157
16.  PDE4 as a target in preterm labour 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S12.
Cyclic nucleotide phosphodiesterases (PDE) are the enzymes catalyzing the hydrolysis and inactivation of the second messengers, cAMP and cGMP. Eleven PDE families are described to date, and selective inhibitors of some PDEs families are currently used in clinic for treating cardiovascular disorders, erectile dysfunction, and pulmonary hypertension. Isoforms of the PDE4 family are involved in smooth muscle contraction and inflammation. PDE4 selective inhibitors are currently in clinical trials for the treatment of diseases related to inflammatory disorders. Because of their myorelaxant properties, we first examined their expression in human myometrium and uncover an increased expression of one specific isoform, PDE4B2, in the near-term myometrium as compared to myometrium in the nonpregnant state. Using human myometrial cells in culture, we demonstrated that PDE4B2 can be induced by its own substrate, under the control of one of the major utero-contractile agonists, PGE2, itself upregulated by the proinflammatory cytokine IL-1β. Functionally, augmentation of global PDE4 activity decreases the ability of β-adrenergic agonists (the most commonly used tocolytic drugs) to inhibit myometrial contraction at the end of pregnancy and during pathophysiological situations, such as persistent intrauterine inflammation which is a major cause of very preterm delivery. Currently exploring the anti-inflammatory properties of PDE4 inhibitors in gestational tissues, we recently demonstrated the ability of these drugs to block a persistent inflammatory response of the foetal membranes in Humans and to prevent inflammation-driven preterm delivery and foetal demise in mice. These data open up a new therapeutical strategy to prevent inflammation-induced preterm delivery and its sequelae in very preterm infants.
doi:10.1186/1471-2393-7-S1-S12
PMCID: PMC1892053  PMID: 17570156
17.  Protein kinase C and human uterine contractility 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S11.
Abnormalities in uterine contractility are thought to contribute to several clinical problems, including preterm labor. A better understanding of the mechanisms controlling uterine activity would make it possible to propose more appropriate and effective management practices than those currently in use. Recent advances point to a role of the protein kinase C (PRKC) family in the regulation of uterine smooth muscle contraction at the end of pregnancy. In this review, we highlight recent work that explores the involvement of individual PRKC isoforms in cellular process, with an emphasis on the properties of PRKCZ isoform.
doi:10.1186/1471-2393-7-S1-S11
PMCID: PMC1892052  PMID: 17570155
18.  Cyclic AMP signalling pathways in the regulation of uterine relaxation 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S10.
Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications.
doi:10.1186/1471-2393-7-S1-S10
PMCID: PMC1892051  PMID: 17570154
19.  Barusiban suppresses oxytocin-induced preterm labour in non-human primates 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S15.
Background
Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin V1A/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored.
Methods
Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg kg-1 h-1) or fenoterol (3 μg kg-1 h-1) were administered.
Results
Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU kg-1 h-1, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163).
Conclusion
The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term.
doi:10.1186/1471-2393-7-S1-S15
PMCID: PMC1892056  PMID: 17570159
20.  Towards understanding the myometrial physiome: approaches for the construction of a virtual physiological uterus 
BMC Pregnancy and Childbirth  2007;7(Suppl 1):S3.
Premature labour (PTL) is the single most significant factor contributing to neonatal morbidity in Europe with enormous attendant healthcare and social costs. Consequently, it remains a major challenge to alleviate the cause and impact of this condition. Our ability to improve the diagnosis and treatment of women most at risk of PTL is, however, actually hampered by an incomplete understanding of the ways in which the functions of the uterine myocyte are integrated to effect an appropriate biological response at the multicellular whole organ system. The level of organization required to co-ordinate labouring uterine contractile effort in time and space can be considered immense. There is a multitude of what might be considered mini-systems involved, each with their own regulatory feedback cycles, yet they each, in turn, will influence the behaviour of a related system. These include, but are not exclusive to, gestational-dependent regulation of transcription, translation, post-translational modifications, intracellular signaling dynamics, cell morphology, intercellular communication and tissue level morphology.
We propose that in order to comprehend how these mini-systems integrate to facilitate uterine contraction during labour (preterm or term) we must, in concert with biological experimentation, construct detailed mathematical descriptions of our findings. This serves three purposes: firstly, providing a quantitative description of series of complex observations; secondly, proferring a database platform that informs further testable experimentation; thirdly, advancing towards the establishment of a virtual physiological uterus and in silico clinical diagnosis and treatment of PTL.
doi:10.1186/1471-2393-7-S1-S3
PMCID: PMC1892060  PMID: 17570163
21.  Use pattern of maternal health services and determinants of skilled care during delivery in Southern Tanzania: implications for achievement of MDG-5 targets 
Background
Almost two decades since the initiation of the Safe motherhood Initiative, Maternal Mortality is still soaring high in most developing countries. In 2000 WHO estimated a life time risk of a maternal death of 1 in 16 in Sub- Saharan Africa while it was only 1 in 2800 in developed countries. This huge discrepancy in the rate of maternal deaths is due to differences in access and use of maternal health care services. It is known that having a skilled attendant at every delivery can lead to marked reductions in maternal mortality. For this reason, the proportion of births attended by skilled health personnel is one of the indicators used to monitor progress towards the achievement of the MDG-5 of improving maternal health.
Methods
Cross sectional study which employed quantitative research methods.
Results
We interviewed 974 women who gave birth within one year prior to the survey. Although almost all (99.8%) attended ANC at least once during their last pregnancy, only 46.7% reported to deliver in a health facility and only 44.5% were assisted during delivery by a skilled attendant. Distance to the health facility (OR = 4.09 (2.72–6.16)), discussion with the male partner on place of delivery (OR = 2.37(1.75–3.22)), advise to deliver in a health facility during ANC (OR = 1.43 (1.25–2.63)) and knowledge of pregnancy risk factors (OR 2.95 (1.65–5.25)) showed significant association with use of skilled care at delivery even after controlling for confounding factors.
Conclusion
Use of skilled care during delivery in this district is below the target set by ICPD + of attaining 80% of deliveries attended by skilled personnel by 2005. We recommend the following in order to increase the pace towards achieving the MDG targets: to improve coverage of health facilities, raising awareness for both men and women on danger signs during pregnancy/delivery and strengthening counseling on facility delivery and individual birth preparedness.
doi:10.1186/1471-2393-7-29
PMCID: PMC2222241  PMID: 18053268
22.  Assessing fetal growth impairments based on family data as a tool for identifying high-risk babies. An example with neonatal mortality 
Background
Low birth weight is associated with an increased risk of neonatal and infant mortality and morbidity, as well as with other adverse conditions later in life. Since the birth weight-specific mortality of a second child depends on the birth weight of an older sibling, a failure to achieve the biologically intended size appears to increase the risk of adverse outcome even in babies who are not classified as small for gestation. In this study, we aimed at quantifying the risk of neonatal death as a function of a baby's failure to fulfil its biologic growth potential across the whole distribution of birth weight.
Methods
We predicted the birth weight of 411,957 second babies born in Denmark (1979–2002), given the birth weight of the first, and examined how the ratio of achieved birth weight to predicted birth weight performed in predicting neonatal mortality.
Results
For any achieved birth weight category, the risk of neonatal death increased with decreasing birth weight ratio. However, the risk of neonatal death increased with decreasing birth weight, even among babies who achieved their predicted birth weight.
Conclusion
While a low achieved birth weight was a stronger predictor of mortality, a failure to achieve the predicted birth weight was associated with increased mortality at virtually all birth weights. Use of family data may allow identification of children at risk of adverse health outcomes, especially among babies with apparently "normal" growth.
doi:10.1186/1471-2393-7-28
PMCID: PMC2233632  PMID: 18045458
23.  Costs and consequences of treatment for mild gestational diabetes mellitus – evaluation from the ACHOIS randomised trial 
Background
Recommended best practice is that economic evaluation of health care interventions should be integral with randomised clinical trials. We performed a cost-consequence analysis of treating women with mild gestational diabetes mellitus by dietary advice, blood glucose monitoring and insulin therapy as needed compared with routine pregnancy care, using patient-level data from a multi-centre randomised clinical trial.
Methods
Women with a singleton pregnancy who had mild gestational diabetes diagnosed by an oral glucose-tolerance test between 24 and 34 weeks' gestation and their infants were included. Clinical outcomes and outpatient costs derived from all women and infants in the trial. Inpatient costs derived from women and infants attending the hospital contributing the largest number of enrolments (26.1%), and charges to women and their families derived from a subsample of participants from that hospital (in 2002 Australian dollars). Occasions of service and health outcomes were adjusted for maternal age, ethnicity and parity. Analysis of variance was used with bootstrapping to confirm results. Primary clinical outcomes were serious perinatal complications; admission to neonatal nursery; jaundice requiring phototherapy; induction of labour and caesarean delivery. Economic outcome measures were outpatient and inpatient costs, and charges to women and their families.
Results
For every 100 women with a singleton pregnancy and positive oral glucose tolerance test who were offered treatment for mild gestational diabetes mellitus in addition to routine obstetric care, $53,985 additional direct costs were incurred at the obstetric hospital, $6,521 additional charges were incurred by women and their families, 9.7 additional women experienced induction of labour, and 8.6 more babies were admitted to a neonatal nursery. However, 2.2 fewer babies experienced serious perinatal complication and 1.0 fewer babies experienced perinatal death. The incremental cost per additional serious perinatal complication prevented was $27,503, per perinatal death prevented was $60,506 and per discounted life-year gained was $2,988.
Conclusion
It is likely that the general public in high-income countries such as Australia would find reductions in perinatal mortality and in serious perinatal complications sufficient to justify additional health service and personal monetary charges. Over the whole lifespan, the incremental cost per extra life-year gained is highly favourable.
Trial Registration
Australian Clinical Trials Registry ACTRN12606000294550
doi:10.1186/1471-2393-7-27
PMCID: PMC2241640  PMID: 17963528
24.  Assessment of social psychological determinants of satisfaction with childbirth in a cross-national perspective 
Background
The fulfilment of expectations, labour pain, personal control and self-efficacy determine the postpartum evaluation of birth. However, researchers have seldom considered the multiple determinants in one analysis. To explore to what extent the results can be generalised between countries, we analyse data of Belgian and Dutch women. Although Belgium and the Netherlands share the same language, geography and political system and have a common history, their health care systems diverge. The Belgian maternity care system corresponds to the ideal type of the medical model, whereas the Dutch system approaches the midwifery model. In this paper we examine multiple determinants, the fulfilment of expectations, labour pain, personal control and self-efficacy, for their association with satisfaction with childbirth in a cross-national perspective.
Methods
Two questionnaires were filled out by 605 women, one at 30 weeks of pregnancy and one within the first 2 weeks after childbirth either at home or in a hospital. Of these, 560 questionnaires were usable for analysis. Women were invited to participate in the study by independent midwives and obstetricians during antenatal visits in 2004–2005. Satisfaction with childbirth was measured by the Mackey Satisfaction with Childbirth Rating Scale, which takes into account the multidimensional nature of the concept. Labour pain was rated retrospectively using Visual Analogue Scales. Personal control was assessed with the Wijma Delivery Expectancy/Experience Questionnaire and Pearlin and Schooler's mastery scale. A hierarchical linear analysis was performed.
Results
Satisfaction with childbirth benefited most consistently from the fulfilment of expectations. In addition, the experience of personal control buffered the lowering impact of labour pain. Women with high self-efficacy showed more satisfaction with self-, midwife- and physician-related aspects of the birth experience.
Conclusion
Our findings focus the attention toward personal control, self-efficacy and expectations about childbirth. This study confirms the multidimensionality of childbirth satisfaction and demonstrates that different factors predict the various dimensions of satisfaction. The model applies to both Belgian and Dutch women. Cross-national comparative research should further assess the dependence of the determinants of childbirth satisfaction on the organisation of maternity care.
doi:10.1186/1471-2393-7-26
PMCID: PMC2200649  PMID: 17963491
25.  How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study 
Background
In 1998, mandatory folic acid fortification of white flour and select cereal grain products was implemented in Canada with the intention to increase dietary folate intakes of reproducing women. Folic acid fortification has produced a dramatic increase in blood folate concentrations among reproductive age women, and a reduction in neural tube defect (NTD)-affected pregnancies. In response to improved blood folate concentrations, many health care professionals are asking whether a folic acid supplement is necessary for NTD prevention among women with high blood folate values, and how reliably high RBC folate concentrations predict folate intakes shown in randomized controlled trials to be protective against NTDs. The objective of this study was to determine how predictive blood folate concentrations and folate intakes are of each other in a sample of well-educated lactating Canadian women exposed to high levels of synthetic folate.
Methods
The relationship between blood folate concentrations and dietary folate intakes, determined by weighed food records, were assessed in a sample of predominantly university-educated lactating women (32 ± 4 yr) at 4-(n = 53) and 16-wk postpartum (n = 55).
Results
Median blood folate concentrations of all participants were well above plasma and RBC folate cut-off levels indicative of deficiency (6.7 and 317 nmol/L, respectively) and all, except for 2 subjects, were above the cut-off for NTD-risk reduction (>906 nmol/L). Only modest associations existed between total folate intakes and plasma (r = 0.46, P < 0.001) and RBC (r = 0.36, P < 0.01) folate concentrations at 16-wk postpartum. Plasma and RBC folate values at 16-wk postpartum correctly identified the quartile of folate intake of only 26 of 55 (47%) and 18 of 55 (33%) of subjects, respectively. The mean RBC folate concentration of women consuming 151–410 μg/d of synthetic folate (2nd quartile of intake) did not differ from that of women consuming >410 μg/d (3rd and 4th quartile).
Conclusion
Folate intakes, estimated by food composition tables, and blood folate concentrations are not predictive of each other in Canadian lactating women exposed to high levels of folate. Synthetic intakes > 151–410 μg/d in these women produced little additional benefit in terms of maximizing RBC content. More studies are needed to examine the relationship between blood folate concentration and NTD risk. Until data from such studies are available, women planning a pregnancy should continue to consume a daily folic acid supplement of 400 μg.
doi:10.1186/1471-2393-7-25
PMCID: PMC2231404  PMID: 17961229

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