Hora Soltani

Anatomical, Physiological and Metabolic Changes with Gestational Age during Normal Pregnancy A Database for Parameters Required in Physiologically Based Pharmacokinetic Modelling

AbstractBackground: Pregnancy is associated with considerable changes in the physiological, anatomical and biochemical attributes in women. These may alter the exposure to xenobiotics between pregnant and non-pregnant women who receive similar doses, with implications for different susceptibility to environmental pollutants or therapeutic agents. Physiologically based pharmacokinetic (PBPK) models together with in vitro in vivo extrapolation (IVIVE) of absorption, distribution, metabolism and excretion (ADME) characteristics may capture the likely changes. However, such models require comprehensive information on the longitudinal variations of PBPK parameter values; a set of data that are as yet not available from a singular source. Aim: The aim of this article was to collect, integrate and analyse the available time-variant parameters that are needed for the PBPK modelling of xenobiotic kinetics in a healthy pregnant population. Methods: A structured literature search was carried out on anatomical, physiological and biochemical parameters likely to change in pregnancy and alter the kinetics of xenobiotics. Collated data were carefully assessed, integrated and analysed for trends with gestational age. Algorithms were generated to describe the changes in parameter values with gestational age. These included changes in maternal weight, the individual organ volumes and blood flows, glomerular filtration rates, and some drug-metabolising enzyme activities. Results: Articles were identified using relevant keywords, quality appraised and data were extracted by two investigators. Some parameters showed no change with gestational age and for others robust data were not available. However, for many parameters significant changes were reported during the course of pregnancy, e.g. cardiac output, protein binding and expression/activity of metabolizing enzymes. The trend for time-variant parameters was not consistent (with respect to direction and mono-tonicity). Hence, various mathematical algorithms were needed to describe individual parameter values. Conclusion: Despite the limitations identified in the availability of some values, the collected data presented in this paper provide a potentially useful singular resource for key parameters needed for PBPK modelling in pregnancy. This facilitates the risk assessment of environmental chemicals and therapeutic drug dose adjustments in the pregnant population.

A longitudinal study of maternal anthropometric changes in normal weight, overweight and obese women during pregnancy and postpartum

Many women associate one or more of their pregnancies with the development of adult obesity. Such an association has not been fully explored. This longitudinal study examines the changes in maternal anthropometric indices during pregnancy and postpartum. Seventy-seven pregnant subjects were investigated longitudinally at about 13, 25 and 36 weeks gestation, of whom forty-seven continued taking part into the postpartum period. Maternal weight, height and skinfold thickness (triceps, biceps, subscapular, suprailiac and mid thigh) were measured at each visit. Maternal fat mass was estimated from the conversion of the first four skinfold thicknesses. Maternal waist and hip circumferences were also measured at the first visit and 6 weeks and 6 months postpartum. Weight and fat gain during pregnancy (13-36 weeks gestation) was 10.9 (SD 4.7) kg and 4.6 (SD 3.3) kg (P < 0.001) respectively. A significant increase in fat mass from 13 weeks gestation to 6-months postpartum was observed (2.6 (SD 4.5), P < 0.001). The increased weight at 6-months postpartum, however, was not statistically significant (1.1 (SD 6.0) kg, P = 0.20). Based on BMI in early pregnancy, the subjects were divided into groups of underweight, normal weight, overweight and obese. The last three groups were compared using ANOVA. The obese group showed a significant difference in the pattern of changes in the skinfold thickness, waist:hip ratio and fat mass at the postpartum period, in comparison with the other two groups. In conclusion, there is a tendency in the obese group to develop central obesity at the postpartum period.

Discussions of findings from a Cochrane review of midwife-led versus other models of care for childbearing women: continuity, normality and safety

Health and Social Care Research Division, King’s College, London, UK Departement de Medecine Sociale et Preventive, Universite de Montreal, Montreal, Canada School of Nursing and Midwifery, Aras Moyola, National University of Ireland, Galway, Ireland Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UK Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry, UK Corresponding author at: NIHR King’s Patient Safety and Service Quality Research Centre, Florence Nightingale School of Nursing and Midwifery, Waterloo Bridge Wing, 150 Stamford Street, King’s College, London SE1 9NH, UK. E-mail address: jane.sandall@kcl.ac.uk (J. Sandall).

Factors Associated With Breastfeeding Up To 6 Months Postpartum in Mothers With Diabetes

OBJECTIVES To identify breastfeeding behavior in a group of women with diabetes and to determine factors that may influence breastfeeding rates in this population. DESIGN A 2-year retrospective study. SETTING Derby City General Hospital, Derby, UK. PARTICIPANTS Ninety-four women with diabetes. METHODS Data were collected using questionnaire and maternal clinical records. RESULTS Women with gestational diabetes mellitus intended to and breastfed more than women with type 1 and type 2 diabetes at 2 weeks postpartum (p<.05). Logistic regression showed that the type of diabetes was the most significant predictor of breastfeeding at birth (p<.05). At 1, 2, and 6 weeks and 4 months postpartum, maternal body mass index was negatively associated with breastfeeding (p<.05). At 6 months, socioeconomic status predicted breastfeeding (p<.05). CONCLUSION Type of diabetes is a significant predictor of breastfeeding initiation. At later stages of postpartum, maternal body mass index and socioeconomic status were significant predictors of infant feeding method. Identification of these factors can help in developing appropriate and timely interventions to more effectively promote breastfeeding.

Physiologically-based Pharmacokinetic (PBPK) Models for Assessing the Kinetics of Xenobiotics during Pregnancy: Achievements and Shortcomings

The physiological changes that occur in the maternal body and the placental-foetal unit during pregnancy influence the absorption, distribution, metabolism, and excretion (ADME) of xenobiotics. These include drugs that are prescribed for therapeutic reasons or chemicals to which women are exposed unintentionally from the surrounding environment. The pregnancy physiologically-based pharmacokinetic (p-PBPK) models developed for theoretical assessment of the kinetics of xenobiotics during pregnancy should take into account all the dynamic changes of the maternal and embryonic/foetal physiological functions. A number of p-PBPK models have been reported for pregnant animals and humans in the past 3 decades which have mainly been applied in the risk assessment of various environmental chemicals. The purpose of this review is to critically evaluate the current state of the art in p-PBPK modelling and to recommend potential steps that could be taken to improve model development and its application particularly in drug discovery and development for pregnant women, with potential implications for optimal drug treatment in pregnancy. The pregnancy-induced changes in physiology and pharmacokinetics, including metabolism, are reviewed to illustrate the basic alterations essential for pregnancy model development. A systemic search of the literature for existing p-PBPK models is carried out and the model structures, governing equations, methods of modelling growth, model validation/verification as well as model applications are highlighted. This review discusses benefits and limitations of the reported p-PBPK models so far and suggests areas for model improvement. The need for establishing databases on the system-related (biological, anatomical and physiological) and drug-related (physiochemical, affinity to enzymes and transpoorters) parameters for healthy and unhealthy pregnancies is particularly emphasized.

Maternal and perinatal health research priorities beyond 2015: an international survey and prioritization exercise.

BackgroundMaternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required.MethodsWe adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly.ResultsA list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies.ConclusionsKey research priorities in maternal and perinatal health were identified. The resulting ranked list of research questions provides a valuable resource for health research investors, researchers and other stakeholders. We are hopeful that this exercise will inform the post-2015 Development Agenda and assist donors, research-policy decision makers and researchers to invest in research that will ultimately make the most significant difference in the lives of mothers and babies.

Antenatal breast expression in women with diabetes: outcomes from a retrospective cohort study

BackgroundWomen with diabetes are sometimes advised to express breast milk antenatally to prepare for breastfeeding and to store colostrum for infant feeding in preventing or treating hypoglycaemia after the birth. The acceptability, risks and benefits of this practice have not been evaluated. This was aimed to investigate the pattern of antenatal breast expression uptake and its relationship with birth outcomes in women with diabetes.MethodsThis was part of a two year retrospective cohort study of pregnant women with diabetes (type 1, 2 and gestational diabetes) who gave birth during 2001–2003 in Derby Hospitals NHS Foundation Trust (n = 94). The information on the practice of antenatal breastfeeding expression and birth outcomes was collected via self-administered questionnaires and by examining maternity records.ResultsThirty-seven percent of women (35/94) recalled that they were advised to express antenatally and 17% did (16/94). The mean gestational age at birth for women who hand-expressed was lower than that for those who did not (mean difference (MD) (95% confidence intervals (CI)): -1.2 (−2.4 to 0.04), p = 0.06). A higher proportion of babies from the antenatal expression group were admitted to special care baby units (SCBU) (MD (95% CI): 21% (−3.9 to 46.3).ConclusionsLess than half the women who stated that they were advised to express, did so. There seems to be an indication that antenatal breast milk expression and lower gestational age at birth are associated. The trend of a higher rate of SCBU admission for babies from the breast milk expression group compared to those who did not express antenatally is of concern. An appropriately-powered randomised controlled trial is needed to determine the safety of this practice and its acceptability to women and health professionals before it can be recommended for implementation in practice.

Responses to gestational weight management guidance: a thematic analysis of comments made by women in online parenting forums

BackgroundThe National Institute for Health and Clinical Excellence (NICE) published guidance on weight management in pregnancy in July 2010 (NICE public health guidance 27: 2010), and this received considerable press coverage across a range of media. This offered an opportunity to examine how gestational weight management guidance was received by UK women.MethodsA thematic analysis was conducted of 400 posts made in UK-based parenting internet forums in the week following the publication of the NICE guidance. This allowed us to examine the naturally occurring comments from 202 women who posted about the guidance on public forums.ResultsThree main themes were identified and explored: i) Perceived control/responsibility ii) Risk perception iii) Confused messages.ConclusionsWomen differed in their perceptions of the level of control that they had over being overweight with some feeling responsible and motivated to maintain a healthy lifestyle. Others felt there were multiple factors influencing their weight issues beyond their control. There were reports of feeling guilty about the impact of weight on the growing baby and experiencing significant obesity stigma from the public and health professionals. Information about the risks of overweight and obesity in pregnancy were difficult messages for women to hear, and for health professionals to deliver. Women reported being confused by the messages that they received. Health messages need to be delivered sensitively to women, and health professionals need support and training to do this. Risk information should always be accompanied with clear advice and support to help women to manage their weight in pregnancy.

Maternal Obesity Management Using Mobile Technology: A Feasibility Study to Evaluate a Text Messaging Based Complex Intervention during Pregnancy

Background. Maternal obesity and excessive gestational weight gain (GWG) are on the rise with negative impact on pregnancy and birth outcomes. Research into managing GWG using accessible technology is limited. The maternal obesity management using mobile technology (MOMTech) study aimed at evaluating the feasibility of text messaging based complex intervention designed to support obese women (BMI ≥ 30) with healthier lifestyles and limit GWG. Methods. Participants received two daily text messages, supported by four appointments with healthy lifestyle midwife, diet and activity goal setting, and self-monitoring diaries. The comparison group were obese mothers who declined to participate but consented for their routinely collected data to be used for comparison. Postnatal interviews and focus groups with participants and the comparison group explored the interventions acceptability and suggested improvements. Results. Fourteen women completed the study which did not allow statistical analyses. However, participants had lower mean GWG than the comparison group (6.65 kg versus 9.74 kg) and few (28% versus 50%) exceeded the Institute of Medicines upper limit of 9 kg GWG for obese women. Conclusions. MOMTech was feasible within clinical setting and acceptable intervention to support women to limit GWG. Before further trials, slight modifications are planned to recruitment, text messages, and the logistics of consultation visits.

Global implications of evidence ‘biased’ practice: management of the third stage of labour

Increasing attention is being paid to the promotion of clinical and cost-effective care informed by the highest level of evidence to ensure health outcomes are optimised and access to health care is equitable. There are obvious advantages to these approaches, including increased awareness of the importance of rigorous methodology when conducting primary and secondary research, utilising methods which are systematic, robust, transparent and explicit. Evidence-based practice was introduced to replace the traditional approach of ‘this is how we have always done it’ as an underpinning for clinical practice. Ironically, however, the transition has not been straightforward and there have been criticisms of the way ‘evidence’ to support some areas of practice is perceived and applied in clinical settings. Anecdotally and based on personal experience, there are two main criticisms: 1. Acceptance of evidence without critique: Too much faith (or blind faith) in the process by which ‘evidence’ (authoritative or systematic) is produced. 2. Lack of holistic insight in the application of evidence: Employing ‘one size fits all’ policies ignoring individual needs for required care in conveyor-like processed care provision. To explore these criticisms, the example of management of the third stage of labour is used.