Lucy Mackillop

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia A Prospective Multicenter Study

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

European evidenced-based consensus on reproduction in inflammatory bowel disease

Inflammatory bowel diseases (IBD) typically affect patients in their reproductive years. It has been shown that reproductive issues are of key concern to IBD patients,1 especially women.2 In this respect, it is important to note that IBD patients remain voluntary childless more frequently than non-IBD controls.1,3,4 A recent study reported that IBD patients refrain from having children due the concerns about the adverse reproductive outcome.1 Fear of side-effects of the medication on the child and medical advice given by physicians, were the most important reasons for voluntary childlessness in this study. The treatment of IBD patients wishing to conceive is surrounded with uncertainties both for the parents to be and the treating physician. This guideline is developed to address these uncertainties and to promote a European perspective on reproduction in inflammatory bowel disease patients. The strategy to reach consensus involved the following steps: 1. The development of questions that should be covered by these pregnancy guidelines. Participants were asked to review these questions and when necessary to adjust or add questions. 2. The participants met in London in November to agree on the questions 3. The participants performed a systematic literature search of their topic with the appropriate key words using Medline/Pubmed and the Cochrane database, as well as their own files. The evidence level was graded (Table 1) according to the Oxford Centre for Evidence-Based medicine 5. 4. Provisional statements of the participants were written and the participants met in Prague in February 2010 to agree on the statements. This was done by projecting the statements and revising them on screen until a consensus was reached. Consensus was defined as agreement by > 80% of the participants. Each recommendation was graded as stated above. 5. The final document on each topic was written by the …

Systemic Lupus Erythematosus

Systemic lupus erythematosus is an autoimmune connective-tissue disorder with a wide range of clinical features, which predominantly affects women, especially from certain ethnic groups. Diagnosis is based on clinical assessment supported by investigations, including the finding of autoantibodies. Treatments range from antimalarial agents to corticosteroids and immunosuppressive agents. This Seminar draws attention to advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues. New therapeutic approaches, such as biological agents and mycophenolate mofetil, will also be discussed.

Unique blood pressure characteristics in mother and offspring after early onset preeclampsia.

Risk of hypertension in mother and offspring after preeclampsia is greater if preeclampsia develops early in pregnancy. We investigated whether those who develop early onset disease have unique adverse blood pressure characteristics. One hundred forty women were studied 6 to 13 years either after a pregnancy complicated by preeclampsia (45 women with early onset preeclampsia before 34 weeks gestation and 45 women with late-onset preeclampsia) or after a normotensive pregnancy (50 women). Forty-seven offspring from these pregnancies also participated. Data on maternal antenatal and postnatal blood pressures were extracted from maternity records and related to peripheral, central, and ambulatory blood pressure measurements in later life. Compared with late-onset preeclampsia, early onset preeclampsia was associated with higher diastolic blood pressure 6 weeks postnatally (86.25±13.46 versus 75.00±5.00 mm Hg, P<0.05), a greater increase in blood pressure relative to booking blood pressure over the subsequent 6 to 13 years, and higher nocturnal systolic and diastolic blood pressures in later life (111.07±13.18 versus 101.13±11.50 mm Hg, P=0.04, and 67.00±7.25 versus 58.60±5.79 mm Hg, P=0.002). Furthermore, at age 6 to 13 years their offspring had higher systolic blood pressure compared with those born to late-onset preeclampsia (96.27±7.30 versus 88.39±7.57 mm Hg, P=0.005). Mothers who developed early onset preeclampsia, and the offspring of that pregnancy display specific adverse blood pressure characteristics later in life. These are not evident in mothers and offspring after late-onset preeclampsia or normotensive pregnancy.

Starvation ketoacidosis in pregnancy

Starvation ketosis outside pregnancy is rare and infrequently causes a severe acidosis. Placental production of hormones, including glucagon and human placental lactogen, leads to the insulin resistance that is seen in pregnancy, which in turn increases susceptibility to ketosis particularly in the third trimester. Starvation ketoacidosis in pregnancy has been reported and is usually precipitated by a period of severe vomiting. Ketoacidosis is likely to have important implications for fetal survival as ketoacidosis in women with type 1 diabetes mellitus is associated with intrauterine death. This article features four cases of women with vomiting in the third trimester of pregnancy associated with a severe metabolic acidosis. The mechanism underlying ketogenesis, the evidence for accelerated ketogenesis in pregnancy and other similar published cases are reviewed. A proposed strategy for management of these women is presented.

Pregnancy Plus: Systemic lupus erythematosus

Systemic lupus erythematosus in pregnancy brings risks for the mother, and possible harm to the fetus if the disease is treated. This article discusses the challenges of management

Development of a real-time smartphone solution for the management of women with or at high risk of gestational diabetes.

Background: Gestational diabetes mellitus (GDM) is defined as new onset or recognition of glucose intolerance in pregnancy. Evidence supports tight blood glucose regulation to prevent adverse maternal and fetal outcomes. Finger-prick blood glucose (BG) testing with frequent clinic review remains the most common method of managing diabetes in pregnancy. The prevalence of GDM is rising globally, pressuring resource-limited services. Objectives: We have developed an intuitive, interactive, reliable, and accurate management system to record BG measurements and deliver management of GDM remotely. Methods: Following an initial scoping phase, a prototype software application was developed using an Android smartphone with BG meter linkage via Bluetooth. A custom website was built for clinician review of the data transmitted by the smartphone. After system refinement, further evaluation was undertaken for usability and reliability in a 48-patient service development project. Results: Women used the system for an average of 13.1 weeks. In all, 19 686 BG measures were transmitted, 98.6% of which had a meal tag. A total of 466 text messages were transmitted. A mean of 30 BG readings per woman per week were transmitted, and 85% of women submitted the minimum requirement of 18 readings per week. Discussion: We have developed a novel, real-time, smartphone-based BG monitoring management system that allows clinician review of real-time patient-annotated BG results. Results indicate high usage and excellent compliance by women. Conclusion: Robust clinical, economic, and satisfaction evaluations are required. To address these requirements, we are currently conducting a randomized controlled pilot trial.

Acceptability and User Satisfaction of a Smartphone-Based, Interactive Blood Glucose Management System in Women With Gestational Diabetes Mellitus

Background: The increase in gestational diabetes mellitus (GDM) is challenging maternity services. We have developed an interactive, smartphone-based, remote blood glucose (BG) monitoring system, GDm-health. Aims: The objective was to determine women’s satisfaction with using the GDm-health system and their attitudes toward their diabetes care. Methods: In a service development program involving 52 pregnant women (September 2012 to June 2013), BG was monitored using GDm-health from diagnosis until delivery. Following birth, women completed a structured questionnaire assessing (1) general satisfaction, (2) equipment issues, and (3) relationship with the diabetes care team. Responses were scored on a 7-point Likert-type scale. Reliability and validity of the questionnaire were assessed using statistical methods. Results: Of 52 women, 49 completed the questionnaire; 32 had glucose tolerance test confirmed GDM (gestation at recruitment 29 ± 4 weeks (mean ± SD), and 17 women previous GDM recommended for BG monitoring (18 ± 6 weeks). In all, 45 of 49 women agreed their care was satisfactory and the best for them, 47 of 49 and 43 of 49 agreed the equipment was convenient and reliable respectively, 42 of 49 agreed GDm-health fitted into their lifestyle, and 46 of 49 agreed they had a good relationship with their care team. Written comments supported these findings, with very positive reactions from the majority of women. Cronbach’s alpha was .89 with factor analysis corresponding with question thematic trends. Conclusions: This pilot demonstrates that GDm-health is acceptable and convenient for a large proportion of women. Effects on clinical and economic outcomes are currently under investigation in a randomized trial (clinicaltrials.gov NCT01916694).

Telemedicine Technologies for Diabetes in Pregnancy: A Systematic Review and Meta-Analysis

Background Diabetes in pregnancy is a global problem. Technological innovations present exciting opportunities for novel approaches to improve clinical care delivery for gestational and other forms of diabetes in pregnancy. Objective To perform an updated and comprehensive systematic review and meta-analysis of the literature to determine whether telemedicine solutions offer any advantages compared with the standard care for women with diabetes in pregnancy. Methods The review was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Randomized controlled trials (RCT) in women with diabetes in pregnancy that compared telemedicine blood glucose monitoring with the standard care were identified. Searches were performed in SCOPUS and PubMed, limited to English language publications between January 2000 and January 2016. Trials that met the eligibility criteria were scored for risk of bias using the Cochrane Collaborations Risk of Bias Tool. A meta-analysis was performed using Review Manager software version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). Results A total of 7 trials were identified. Meta-analysis demonstrated a modest but statistically significant improvement in HbA1c associated with the use of a telemedicine technology. The mean HbA1c of women using telemedicine was 5.33% (SD 0.70) compared with 5.45% (SD 0.58) in the standard care group, representing a mean difference of −0.12% (95% CI −0.23% to −0.02%). When this comparison was limited to women with gestational diabetes mellitus (GDM) only, the mean HbA1c of women using telemedicine was 5.22% (SD 0.70) compared with 5.37% (SD 0.61) in the standard care group, mean difference −0.14% (95% CI −0.25% to −0.04%). There were no differences in other maternal and neonatal outcomes reported. Conclusions There is currently insufficient evidence that telemedicine technology is superior to standard care for women with diabetes in pregnancy; however, there was no evidence of harm. No trials were identified that assessed patient satisfaction or cost of care delivery, and it may be in these areas where these technologies may be found most valuable.

Prescribing in pregnancy and during breast feeding: using principles in clinical practice

Prescribing in pregnancy often causes uncertainty and anxiety for the clinician and may lead to the omission of necessary treatment. Many drugs have inadequate data to assure safety, and therefore the clinician is left with a dilemma as to where the balance of risks and benefits lie with respect to the mother and her fetus. Understanding under what circumstances women can be prescribed medication and using principles of prescribing in pregnancy to further clarify the potential risks will aid good clinical decision-making. An appreciation of the available resources and the conviction to find the best available evidence will best serve the patient and her fetus. Teratogenicity refers to the potential for a drug to cause fetal malformations and affects the embryo 3–8 weeks after conception. Teratogenic drugs are associated with an increased risk of malformations, but the majority of babies are born with no abnormalities. In addition, approximately 2–3% of infants are born with major malformations with no association with maternal medication, and this and other confounding factors need to be addressed during counselling of a woman. Fetotoxicity refers to the functional changes that can occur to the fetus as a result of medication in the second and third trimesters. These effects are more subtle and more difficult to assess and therefore there are fewer data to support or refute these types of associations. For the majority of drugs, the neonatal dose from breast feeding is a fraction of the dose exposure in utero.