Should obstetric mortality be an inalienable right?

BACKGROUND: Obstetricians often times find themselves in a conflict of right and duty with their patients, when these patients refuse recommended treatment. On the one hand, the obstetrician, aiming to fulfil the duty of care, recommends a treatment in the best interest of the woman. The woman, on the other hand, exercising her right of self-determination and autonomy, declines the recommended treatment. MATERIALS AND METHODS: A search was conducted for literature, articles and case reports on the subject on PubMed/MEDLINE and Google Scholar using the keywords: medical ethics, medical law, obstetric mortality, maternal medicine, foetal medicine, patient autonomy, informed consent, right to life and right to liberty. RESULTS: Opinions have historically differed on whether maternal or foetal rights should be deferred to in situations where pregnant women refuse obstetric interventions. So also have legal decisions on the issue. The general consensus is, however, to respect a woman's refusal of recommended medical treatment, in deference to her right of self-determination and autonomy. The obstetric outcomes in such instances are however, often times, unfavourable. CONCLUSION: The ethics of patient care in the face of conflicting rights deserves renewed examination and discourse.

Analysis of a maternal health medicines pipeline database 2000-2021: New candidates for the prevention and treatment of fetal growth restriction.

OBJECTIVE: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally. DESIGN: Landscape analysis. SETTING: Global (focus on low- and middle-income countries, LMICs). SAMPLE: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction. METHODS: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive. MAIN OUTCOMES MEASURES: Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility. RESULTS: Of the 444 unique candidates in the database across all five pregnancy-related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l-arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high-potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega-3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP). CONCLUSIONS: l-Arginine, aspirin and vitamin D are promising, high-potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future.

Interventions to enhance medication adherence in pregnancy- a systematic review.

BACKGROUND: Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. METHODS: Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. RESULTS: Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/- counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect  of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. CONCLUSIONS: There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes.

Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles.

BACKGROUND: The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs. METHODS: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass. RESULTS: The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols. CONCLUSIONS: This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.

Postpartum haemorrhage and associated factors among mothers who gave birth in South Gondar Zone public health facilities, Ethiopia: a cross-sectional study.

BACKGROUND: Postpartum haemorrhage is one of the direct and the leading causes of maternal morbidity and mortality. There are many risk factors of postpartum haemorrhage, which vary in different settings. Therefore, the purpose of this study was to assess postpartum haemorrhage and associated factors among mothers who gave birth in public health facilities. METHODS: A cross-sectional study was employed from 17 November 2019 to 15 February 2020. The study participants were selected using a systematic sampling technique. The data were entered and cleaned using EpiData V.3.1 then exported to SPSS V.20 for analysis. Factors associated with postpartum haemorrhage were selected for multiple logistic regression at the probability value (p value) of less than 0.2 in the χ2 analysis. Statistically significant associated factors were identified at probability value (p value) less than 0.05 and adjusted OR (AOR) with a 95% CI. RESULTS: The mean age of participants was 31.3 (SD ±5.7) years. This study found that the prevalence of postpartum haemorrhage was 13.6% (67). Age of participants (AOR 12.5, 95% CI 4.0 to 38.6), disrespectful maternity care (AOR 8.4, 95% CI 3.2 to 22.0), labour induction and augmentation (AOR 6.97, 95% CI 2.34 to 20.8), the prolonged second stage of labour (AOR 9.9, 95% CI 2.6 to 37.1) and no antenatal care visit (AOR 10.1, 95% CI 3.4 to 29.7) were statistically significant associated factors of postpartum haemorrhage. CONCLUSIONS: The prevalence of postpartum haemorrhage is high. The age of the participants, disrespectful maternity care, labour induction and augmentation, the prolonged second stage of labour and no antenatal care visit were independent predictors of postpartum haemorrhage.

Impact of maternal iron deficiency anaemia on the expression of the newly discovered multi-copper ferroxidase, Zyklopen, in term placentas.

In the present study, we investigated the effect of maternal iron deficiency anaemia (IDA) on expression of the newly discovered iron transporter, Zyklopen in term placenta, in 200 pregnant women. Placental expression of Zyklopen was studied by mRNA analysis and immunohistochemistry for the protein. In addition neonatal anthropometric parameters were also analysed. 58.8% of 200 subjects were anaemic. Both Zyklopen mRNA as well as protein expression in the placenta showed a statistically significant increase with increasing severity of anaemia. Although all the neonatal anthropometric parameters were lower in newborns of anaemic mothers, none showed any statistical significance. Zp mRNA levels did not show any significant correlation with newborn and placental parameters (except newborn skinfold thickness and head circumference). Similar to mRNA expression, Zp IHC expression correlated positively, albiet non-significantly, with newborn length and Hb levels, the correlation was however negative with birth weight, head circumference, mid-arm circumference unlike the mRNA expression, where it positively correlated with the above parameters. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both mRNA and protein levels in term placenta, in maternal IDA.IMPACT STATEMENTWhat is already known on this subject? Iron deficiency anaemia (IDA) in a pregnant mother can lead to anaemia in the developing foetus; which is frequently observed to be of lesser severity than that in the mother. Recently a copper-containing oxidase called Zyklopen was discovered which was involved in iron efflux in BeWo cells. The gene encoding Zyklopen has been identified with a putative C-terminal membrane-spanning sequence and high sequence identitical to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate multicopper ferroxidase (MCF). Protein expression of this new MCF was observed in multiple diverse mouse tissues, including placenta and mammary gland.What do the results of this study add? Zyklopen protein immunohistochemical expression showed a statistically significant increase with increasing severity of anaemia. Similarly, placental mRNA expression of the Zyklopen gene was observed to be higher in anaemic mothers when compared to non-anaemic mothers. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both protein and mRNA levels in term placenta, in maternal IDA.What are the implications of these findings for clinical practice and/or further research? This study will help us to understand better, the increased potential for influx of iron from mother to foetus in the condition of maternal iron deficiency. This study will help to determine how placental iron transport proteins can be regulated in response to maternal and neonatal iron status and will further our existing knowledge on relationships between maternal and neonatal iron status and mechanisms by which placental iron transport is modified in relation to these parameters.

Socio-behavioural determinants of maternal near miss: a prospective case control study from a tertiary care centre of India.

Near miss occurs in far greater numbers than maternal deaths and allows a more robust quantification on risk factors and determinants of life-threatening complications. A 'Three delay model' has been proposed in identification of causes of near miss and maternal deaths. There may be delay in seeking and obtaining health care: delay in recognising danger signs and deciding to reach source of care, delay in reaching appropriate source of care and delay in obtaining appropriate and adequate treatments. We compared various delays between near miss cases (n = 100) and controls (n = 200). Women who fulfilled criteria of near miss were taken as cases. Women who had obstetrical complications like near miss but were managed successfully and did not reach near miss state were labelled as controls. Near miss were then compared with maternal death. For normally distributed measurable data, outcome was compared using Student's t-test, for non-normally distributed/ordinal data, outcome was compared using Mann-Whitney's test. For categorical/classified data, association with outcome was analysed using Chi-Square test/Fisher's exact test.Delay in all three levels was seen among the groups. Lack of knowledge, non-availability of decision maker, and concern of cost of transport were main contributors of these delays.Impact StatementWhat is already known on this subject? Nonavailability of healthcare and low socio-economic status strongly correlate with maternal morbidity and mortality.What do the results of this study add? Lack of knowledge, non-availability of the decision maker, and concern of cost of transport were the main contributors of delay in seeking medical care. Majority of the cases of near miss were attributed to poor utilisation of health resources, ignorance and lack of emergency obstetric care at the primary level.What are the implications of these findings for clinical practice and/or further research? Patient and attendant education to ensure follow-up visits, recognise danger signs and report without undue delay, compliance to dietary modifications, medications given needs to be addressed at every visit to reduce the impact of socio-behavioural determinants on maternal near miss and mortality which are preventable in majority of cases.

Maternal serum pregnancy-associated plasma protein-A concentration at 11-14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities.

To evaluate maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels at 11-14 weeks of gestation and preeclampsia risk in women with common congenital anatomic uterine abnormalities (AUAs). First trimester screening markers were compared between 12 AUA pregnancies, 60 age matched controls and 12 cases of early preeclampsia. PAPP-A level and birth weight were significantly lower in AUA compared to control and early preeclampsia group (p<.001). Preeclampsia was absent in the AUAs pregnancies group. Birth weight were similar in AUA group when we compared AUA and control group regarding weeks of gestation at delivery and lower but not significantly, when we compared AUA and early preeclampsia group. Our findings suggest that AUA pregnancies are associated with low first trimester maternal serum PAPP-A concentrations not predictive of susceptibility to preeclampsia.Impact statementWhat is already known on this subject? During first trimester screening for preeclampsia based on maternal pregnancy-associated plasma protein A (PAPP-A) levels, various parameters are used, such as the somatometric characteristics of pregnant woman, single or multiple pregnancy, smoking status, family history, diabetes, hypertension and measurement of blood pressure and uterine artery Dopplers.What do the results of this study add? Our pioneer study revealed that there is drastic difference in PAPP-A concentration in women with common anatomic uterine abnormalities (AUAs), in comparison with their age matched control women with normal uterus.What are the implications of these findings for clinical practice and further research? Based on our results, uterine anatomical deviations, is another factor which must be taken in account for preeclampsia risk calculation and further clinical consultation and follow up in those pregnancies. Lower PAPP-A levels in AUA cases is a weak predictor of susceptibility to preeclampsia and could be associated to smaller placental size rather than poor placentation and in future research the calculation of the uterine cavity functional dimension may lead to a more accurate clinical assessment.

The Late Effects of Pregnancy on Aortic Dimensions in Patients with Marfan Syndrome.

While the immediate effects of pregnancy on aortic dimension in patients with Marfan syndrome (MFS) have been evaluated, the late effects of subsequent pregnancies in these patients are less known. For this purpose, we evaluated 2 groups of women with MFS who were under specialized care in our institution. Group A included 23 women with MFS who experienced 55 pregnancies; group B included 12 nulliparous MFS patients. Patients in group A were similar in age (36.13 ± 5.6 years vs. 34.25 ± 6.54 years, p = 0.41) and follow-up time (group A 6.05 ± 3.56 years and group B 4.92 ± 3.37 years, p = 0.37). Baseline aortic root diameters as well as the aortic root diameters at follow-up visits were similar between groups (35.60 ± 4.42 vs. 35.08 ± 3.82 mm, p = 0.73, and 37.57 ± 4.66 vs. 37.33 ± 4.83 mm, p = 0.89, respectively). The aortic root diameter increased by 0.5 (0, 2) mm in group A and 1 (0, 4.5) mm in group B (p = 0.54). The rate of aortic dilation per year of follow-up was similar between the groups (0.34 ± 0.52 mm/year in group A vs. 0.55 ± 0.75 mm/year in group B [p = 0.52]). Chronic medical treatment was similar in both groups. Patients in both groups were treated similarly with ß-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. In summary, subsequent pregnancies in patients with MFS were not associated with an increase in the rate of aortic root dilation in these patients.

Maternal childbirth-related mortality in the last 40 years in Turin, Italy: the impact of universal health coverage on inequalities in a developed country.

The aim of this study was to investigate social disparities in childbirth-related mortality in women (CRM) in Italy during 1972-2013, a period characterised by important changes in the organisation of healthcare services. The relationship between education and CRM was assessed using a Poisson regression model adjusted for age, area of birth and year of delivery.The risk of dying from childbirth related causes was more than double for less educated women when compared to women with better education (RR 2.3; 95% CI 1.1-3.9). CMR was almost 2.5 times higher in 1971-1979 than in the universalistic coverage period (1980-2013): RR 2.6, 95% CI 1.4-4.6. CMR in Turin has decreased in the last 40 years and this success is probably the result of the development of our public health system and of specific health facilities for pregnant women but free access to maternal care alone is not sufficient to erase inequalities.IMPACT STATEMENTWhat do we already know? Mother mortality due to childbirth-related causes has significantly decreased in the last 40 years and the development of the public health system is likely to have contributed to this success.What do the results of this study add? This study shows that, although there has been good progress in pregnancy and partum assistance, inequalities in the incidence of mortality from childbirth-related causes still exists even in a high-income country such as Italy.What are the implications of these findings for clinical practice and/or further research? The results are useful both for clinicians and for policy-makers as it suggests that the assessment of socioeconomic factors should be taken into account by clinicians along with other risk factors. Furthermore, community interventions targeted at more vulnerable women should be implemented to improve the use of healthcare and pre-partum facilities.

Can oxytocin augmentation modify the risk of epidural analgesia by maternal age in cesarean sections?

INTRODUCTION: Maternal age is an established risk factor for cesarean section; epidural analgesia and oxytocin augmentation may modify this association. We investigated the effects and interactions of oxytocin augmentation, epidural analgesia and maternal age on the risk of cesarean section. MATERIAL AND METHODS: In all, 416 386 nulliparous women with spontaneous onset of labor, ≥37 weeks of gestation and singleton infants with a cephalic presentation during 2000-2011 from Norway and Denmark were included [Ten-group classification system (Robson) group 1]. In this case-control study the main exposure was maternal age; epidural analgesia, oxytocin augmentation, birthweight and time period were explanatory variables. Chi-square test and logistic regression were used to estimate associations and interactions. RESULTS: The cesarean section rate increased consistently with advancing maternal age, both overall and in strata of epidural analgesia and oxytocin augmentation. We observed strong interactions between maternal age, oxytocin augmentation and epidural analgesia for the risk of cesarean section. Women with epidural analgesia generally had a reduced adjusted odds ratio when oxytocin was used compared with when it was not used. In Norway, this applied to all maternal age groups but in Denmark only for women ≥30 years. Among women without epidural, oxytocin augmentation was associated with an increased odds ratio for cesarean section in Denmark, whereas no difference was observed in Norway. CONCLUSIONS: Oxytocin augmentation in nulliparous women with epidural analgesia is associated with a reduced risk of cesarean section in labor with spontaneous onset.

MBRRACE in simulation: an evaluation of a multi-disciplinary simulation training for medical emergencies in obstetrics (MEmO).

The majority of maternal deaths in the UK are due to pre-existing or new-onset medical conditions, known as 'indirect deaths'. The MBRRACE report identified serious gaps in clinicians' human factors skills, including communication, leadership and teamwork, which contributed to maternal death. In response, we developed the first multi-disciplinary simulation-based training programme designed to address Medical Emergencies in Obstetrics (MEmO). Employing a mixed methods design, this study evaluated the educational impact of this training programme on the healthcare staff (n = 140), including the medical doctors (n = 91) and the midwives (n = 49). The training improved participants' clinical management of medical deterioration in pregnancy (p=.003) alongside improving their human factors skills (p=.004). Furthermore, participants reported the translation of these skills to their routine clinical practice. This flexible training is responsive to the changing national needs and contextualises the MBRRACE findings for healthcare staff. It is a promising avenue for reducing the rates of in-direct death in pregnancy. Impact statement What is already known on this subject? The majority of maternal deaths in the UK are due to pre-existing or new-onset medical conditions. The management of medical conditions in pregnancy relies on a multi-professional approach. However, serious gaps in clinicians' human factors skills, highlighted by the MBRRACE report, may contribute to maternal death. What do the results of this study add? This study evaluated the first multi-disciplinary, simulation-based training programme designed to address Medical Emergencies in Obstetrics (MEmO). Training significantly improved participants' management of medical deterioration in pregnancy and human factors skills, particularly in the areas of leadership, communication and teamwork. Moreover, the participants learning translated into their clinical practice. What are the implications of these findings for clinical practice and/or further research? The delivery of multi-disciplinary team training for all healthcare staff involved in the complex management of medical conditions in pregnancy can help develop a greater understanding of others' professional roles, and demonstrate the importance of interprofessional teamwork. Furthermore, it provides the space to reflect on team working approaches, including the leadership and professional autonomy, and their potential impact on patient care. Future research should evaluate the impact of this training on the objective outcome measures of medical emergencies in pregnancy.

Survey on knowledge, attitude, acceptance and related factors among pregnant women in Thailand regarding antenatal thalassaemia screening.

Thalassaemia is a common haematologic health condition in Southeast Asian countries (SEA) including Thailand. Reducing the birth of new thalassaemia cases is an effective method to control disease. The background level of knowledge and attitude of pregnant women on the disease influences their decision to perform antenatal screening. Unfortunately, the information about pregnant women's knowledge and attitude on antenatal thalassaemia screening in a developing country such as Thailand is lacking. We therefore conducted this cross-sectional study to examine patients' knowledge and to evaluate the factors which influence the patient's knowledge and attitude on antenatal thalassaemia screening. 1006 pregnant women who attended antenatal care at the Maha Chakri Sirindhorn Medical Center, Faculty of Medicine, Srinakharinwirot University, Ongkharak, Nakhon Nayok, Thailand were enrolled. We found that women's knowledge on antenatal thalassaemia screening is low. A maternal age of ≥35 years was associated with a higher level of knowledge. A higher level of education and multigravidity, a family history of thalassaemia and a positive level of attitude were found more likely to have higher scores for knowledge. A higher level of education and level of knowledge score were also more likely to have a positive attitude score, but multigravidity negatively affected the attitude score. Effective counselling should be monitored among women with a lower levels of education, those with no family history of thalassaemia, and in primigravidas. Lastly, a concurrent Down syndrome screening or foetal sex determination may be useful incentives to encourage the decision to undergo screening. Impact statement What is already known about this subject? Screening for the paternal and maternal thalassaemia carrier status is important for reducing the incidence of severely thalassaemia-affected children. Poorer education and receiving genetic counselling for the first time were the predictive factors for the low post-counselling knowledge in genetic counselling before second trimester genetic amniocentesis. What do the results of this study add? Pregnant women's knowledge of antenatal thalassaemia screening was low. We found that pregnant women aged ≥35 years had a higher level of knowledge. Women with a higher level of education, multigravidity, the presence of a family history of thalassaemia and a positive attitude were more likely to have higher scores for knowledge. A higher level of education and level of knowledge score were also more likely to have a positive attitude score but multigravidity negatively affected the attitude score. The encouraging factors, such as an adjunctive Down syndrome screening or foetal structural screening or foetal sex determination may be useful as the incentive tools. What are the implications of these finding for clinical practice and/or further research? The awareness of a possible incorrect understanding is important for the antenatal counselling in the developing countries. Intensive monitoring of effective counselling using a post-counselling test should be scheduled. The methods of effective counselling for antenatal thalassaemia in developing countries should be evaluated.

Prophylactic magnesium sulphate in prevention of eclampsia in women with severe preeclampsia: randomised controlled trial (PIPES trial).

Optimum dose, route and duration of use of prophylactic magnesium sulphate in women with severe pre-eclampsia is still controversial. We compared the efficacy and safety of 'low-dose Dhaka' regime with 'Loading dose only' regime for seizure prophylaxis in severe preeclampsia using a randomised controlled trial in 402 women. The incidence of eclampsia in the 'low-dose Dhaka' regime group was 1.49% and that in the 'Loading dose only regime' was 2.98% (p = .321). In the low-dose Dhaka regime, injection site abscess and respiratory depression occurred in one woman each. Neonatal outcomes such as Apgar score at 5 minutes (5.0% vs. 8.05% p = .251) and perinatal mortality (20.4% vs. 21.9%, p = .724) were similar in both groups. Loading dose only regime may be considered an effective alternative regime for the prevention of eclampsia in women with severe preeclampsia. Impact statement What is already known on this subject: Efficacy of therapeutic short regime magnesium sulphate in eclampsia has already been reported. Data regarding prophylactic short regime in women with preeclampsia is sparse. What the results of this study add: We have shown that short regime of magnesium sulphate using only the loading dose in the prevention of seizure in preeclampsia is an effective alternative to the low-dose Dhaka regime. What the implications are of these findings for clinical practice and/or further research: The short regime is less resource-intensive. Further larger studies are needed to confirm the efficacy of this short regime and to establish its cost-effectiveness.

Longitudinal hemodynamics in acute phase of treatment with labetalol in hypertensive pregnant women to predict need for vasodilatory therapy.

OBJECTIVE: Hypertensive pregnant women who do not respond to treatment with labetalol to control blood pressure (BP), but require vasodilatory therapy, progress rapidly to severe hypertension. This could be delayed by early recognition and individualized treatment. In this study, we sought to create prediction models from data at presentation and at 1 h and 24 h after commencement of treatment to identify patients who will not have a sustained response to labetalol and therefore need vasodilatory therapy. METHODS: The study population comprised 134 women presenting with hypertension at a UK hospital. Treatment with oral labetalol was administered when BP was > 150/100 mmHg or > 140/90 mmHg with systemic disease. BP and hemodynamic parameters were recorded at presentation and at 1 h and 24 h after commencement of treatment. Labetalol doses were titrated to maintain BP around 135/85 mmHg. Women with unresponsive BP, despite labetalol dose maximization (2400 mg/day), received additional vasodilatory therapy with nifedipine. Binary logistic and longitudinal (mixed-model) data analyses were performed to create prediction models anticipating the likelihood of hypertensive women needing vasodilatory therapy. The prediction models were created from data at presentation and at 1 h and 24 h after treatment, to assess the value of central hemodynamics relative to the predictive power of BP, heart rate and demographic variables at these intervals. RESULTS: Twenty-two percent of our cohort required additional vasodilatory therapy antenatally. These women had higher rates of severe hypertension and delivered smaller babies at earlier gestational ages. The unresponsive women were more likely to be of black ethnicity, had higher BP and peripheral vascular resistance (PVR), and lower heart rate and cardiac output (CO) at presentation. Those who needed vasodilatory therapy showed an initial decrease in BP and PVR, which rebounded at 24 h, whereas BP and PVR in those who responded to labetalol showed a sustained decrease at 1 h and 24 h. Stroke volume and CO did not decrease during the acute phase of treatment in either group. The best model for prediction of the need for vasodilators was provided at 24 h by combining ethnicity and longitudinal BP and heart rate changes. The model achieved a detection rate of 100% for a false-positive rate of 20% and an area under the receiver-operating characteristics curve of 0.97. CONCLUSION: Maternal demographics and hemodynamic changes in the acute phase of labetalol monotherapy provide a powerful tool to identify hypertensive pregnant patients who are unlikely to have their BP controlled by this therapy and will consequently need additional vasodilatory therapy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVO: Las embarazadas hipertensas que no responden al tratamiento con labetalol para el control de la presión arterial (PA), pero que requieren terapia vasodilatadora, evolucionan rápidamente hacia una hipertensión severa. Ésta se puede retrasar mediante un diagnóstico precoz y un tratamiento individual. En este estudio se ha tratado de crear modelos de predicción a partir de datos al inicio del tratamiento y al cabo de 1 hora y de 24 horas después del mismo, para identificar a las pacientes que no mostrarán una respuesta constante al labetalol y que por lo tanto necesitarán terapia vasodilatadora. MÉTODOS: La población de estudio incluyó 134 mujeres con hipertensión en un hospital del Reino Unido. El tratamiento con labetalol por vía oral se administró cuando la PA fue >150/100 mm de Hg o >140/90 mm de Hg con enfermedad multisistémica. Se registró la PA y los parámetros hemodinámicos tanto al inicio como al cabo de 1 h y de 24 h después del inicio del tratamiento. Las dosis de Labetalol se ajustaron para mantener la PA en torno a los 135/85 mm de Hg. Las mujeres cuya PA no produjo respuesta, a pesar de haberles administrado la dosis máxima de labetalol (2400 mg/día), recibieron terapia vasodilatadora adicional con nifedipino. Se realizaron análisis de datos mediante logística binaria y longitudinal (modelo mixto), para crear modelos de predicción con los que pronosticar la probabilidad de la necesidad de terapia vasodilatadora en mujeres hipertensas. Los modelos de predicción se crearon a partir de datos al inicio y al cabo de 1 hora y 24 horas del tratamiento, para evaluar el valor de los parámetros hemodinámicos principales con respecto a la capacidad predictiva de la PA, la frecuencia cardíaca y las variables demográficas en estos intervalos. RESULTADOS: El 22 % de la cohorte necesitó terapia vasodilatadora adicional antes del parto. Estas mujeres tuvieron tasas más altas de hipertensión grave y neonatos más pequeños en edades gestacionales más tempranas. Las mujeres que no respondieron al tratamiento fueron con más frecuencia de raza negra, tuvieron la PA y la resistencia vascular periférica (RVP) más alta, y la frecuencia cardíaca y el gasto cardíaco (GC) más bajos al inicio del tratamiento. Aquellas que necesitaron terapia vasodilatadora mostraron un descenso inicial de la PA y la RVP, que se recuperó al cabo de 24 h, mientras que la PA y la RVP en las que respondieron al labetalol mostraron una disminución constante al cabo de 1 h y de 24 h. El volumen sistólico y el GC no disminuyeron durante la fase aguda del tratamiento en ninguno de los grupos. El mejor modelo para la predicción de la necesidad de vasodilatadores se obtuvo a las 24 h mediante la combinación de la etnia con los cambios longitudinales de la PA y la frecuencia cardíaca. El modelo alcanzó una tasa de detección del 100% para una tasa de falsos positivos del 20% y un área bajo la curva de características operativas del receptor de 0,97. CONCLUSIÓN: Los datos demográficos maternos y los cambios hemodinámicos en la fase aguda de la monoterapia con labetalol constituyen una herramienta poderosa para identificar a las pacientes embarazadas hipertensas con pocas probabilidades de que se les pueda controlar su PA mediante esta terapia y que por lo tanto necesitarán terapia vasodilatadora adicional. : 、(blood pressure,BP),。。,1 h24 h,。 : 134。BP>150/100 mmHgBP>140/90 mmHg。1 h24 hBP。,BP135/85 mmHg。BP,()。logistic(),。1 h24 h,,BP、。 : 22%。。,BP(peripheral vascular resistance,PVR),(cardiac output,CO)。BPPVR,24 h,1 h24 hBPPVR。CO。24hBP。100%,20%,0.97。 : ,BP。.

Longitudinal maternal hemodynamics in pregnancies affected by fetal growth restriction.

OBJECTIVE: Fetal growth restriction (FGR) is a powerful determinant of poor perinatal outcome. From our previous work in pregnancies at high risk of development of hypertension we found impaired cardiovascular adaptation early in gestation in those destined to deliver growth-restricted infants. In this study, we monitored serially maternal hemodynamics from the first to third trimester in a similar high-risk cohort, in order to determine whether this distinct hemodynamic profile found at presentation persisted throughout pregnancy in those complicated by FGR. METHODS: This was a prospective observational study based at a specialist antenatal hypertension clinic at a tertiary hospital in London. Maternal hemodynamics were evaluated serially using a non-invasive bioreactance method in pregnant women referred to the clinic with a history of chronic hypertension or a history of hypertensive disorder in a previous pregnancy. Differences in maternal hemodynamic parameters were compared between women who delivered a baby with a birth weight ≥ 10th vs < 10th percentile and ≥ 5th vs < 5th percentile. RESULTS: Eighty-four pregnant women were included in the study. Mean gestational age at presentation was 14.3 weeks. Sixteen women delivered babies with a birth weight < 10th percentile and 11 with a birth weight < 5th percentile. In pregnancies with a birth weight ≥ 10th percentile, longitudinal maternal hemodynamics showed a pattern consistent with well-established physiological changes in pregnancy, i.e. a reduction in vascular resistance and an increase in cardiac output with advancing gestation until mid-pregnancy. However, women who delivered babies with a birth weight < 10th percentile showed a static pattern with no change during gestation and lower cardiac output and higher peripheral vascular resistance. Similar differences were seen when the 5th percentile was used to discriminate between appropriately-grown and growth-restricted babies. CONCLUSION: Serial assessment of maternal hemodynamics in high-risk women identifies distinctive trends associated with pregnancies destined to deliver babies with birth weights < 10th and < 5th percentiles. These pregnancies have a suppressed and static maternal cardiac output and stroke volume, and have consistently raised peripheral vascular resistance. This suggests that, in women with chronic hypertension or a history of hypertensive disorder in a previous pregnancy, FGR is associated with a primary and persistent failure of maternal cardiovascular adaptation in pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.