Maternal weight gain during pregnancy is associated with increasing birth weight. It is uncertain how much fat mass (FM) and fat-free mass (FFM) contributes to this association. The authors examined the influence of different maternal body composition parameters on birth weight. The study was confined to non-diabetic Caucasian women with a singleton pregnancy. Weight and height were measured in the first trimester. Maternal body composition was measured at 28 and 37 weeks using advanced bioelectrical impedance analysis. At delivery the baby was weighed and the clinical details recorded. Of the 178 women, the mean body mass index (BMI) was 28.2 kg/m2. Birth weight did not correlate with early pregnancy BMI but did correlate with gestational weight gain (r=0.230; p=0.002). Maternal FM did not correlate with birth weight, however maternal FFM did (r=0.247; p<0.001). An increase in maternal FFM and not FM correlated with birth weight (r=0.469; p<0.001). In non-diabetic pregnancies gestational weight gain, and not early pregnancy BMI, is the more important determinant of birth weight. Furthermore, it is the increase in maternal fat free mass and not fat mass that influences birth weight.
The purpose of this study was to profile sleep patterns during pregnancy according to body mass index (BMI) and to correlate labour outcomes with both BMI and hours sleep. Data were collected from 200 postpartum women detailing sleep characteristics before and during pregnancy. A validated sleep questionnaire was employed, which comprised of questions about sleep apnoea, snoring, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. Descriptive analyses were used. With advancing gestation, the mean (SD) number of hours sleep per night declined: pre-pregnancy 8.1 (SD 1.4); 1st trimester 8.3 (SD 1.8); 2nd trimester 7.7 (SD 1.7) and 3rd trimester 6.7 (SD 2.2). In the 18.5–24.9 BMI group, there was a marked difference in hours sleep per night from pre-pregnancy to 1st (8.6 h, p = 0.007), 2nd (7.9 h, p = 0.023) and 3rd (6.4 h, p = 0.000) trimesters in primiparous women. In the 25–29.9 BMI group, there was a difference from pre-pregnancy to 3rd trimester (p = 0.000). These changes were not reflected in a clinically significant difference in birth weight or mode of delivery.
In view of the coronavirus disease 2019 (COVID-19) pandemic and the predicted risk of severe infection in immunocompromised patients, chemotherapy protocols for patients with acute myeloid leukaemia (AML) have been modified in some patients to newer, less myelosuppressive regimens than standard induction chemotherapy. However, the modifications to treatment have occurred at such a considerable pace, due to the urgency of the pandemic, that optimal time points for measuring minimal residual disease (MRD) to assess disease response and monitor for relapse have not yet been established for the new regimens. Thus, decisions about duration of therapy and appropriate time points to intensify therapy prove very challenging. The combination of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax and the hypomethylating agent azacitidine (Ven-Aza) has recently been introduced as a treatment option for patients with AML during the COVID-19 pandemic, instead of the standard more intensive chemotherapy regimen of daunorubicin and cytarabine. It has been approved by the National Institute for Health and Care Excellence1 and was introduced in our institution on the 19 March 2020. The use of this combination of drugs in AML is based on evidence that it produces high rates of rapid and durable responses for patients who were not eligible for intensive chemotherapy.2 In particular, AML with nucleophosmin-1 (NPM1) mutations is shown to be particularly responsive to this combination of treatment.3, 4 Moreover, Ven-Aza can be used to treat persistent or rising NPM1 MRD levels after intensive induction chemotherapy.5 This combination of drugs is also well tolerated3, 6 and has a lower rate of death than that expected with induction chemotherapy,7 although to date there has not been a randomised trial to compare Ven-Aza directly with standard induction chemotherapy. However, reducing the intensity of chemotherapy now comes with new challenges, as it has to be applied rapidly to well-established protocols of MRD monitoring. This is illustrated in the case below of a 40-year-old male patient with NPM1-mutant AML. The NPM1 transcript level, as an MRD marker, is well established, particularly its level in peripheral blood, which has prognostic significance.8, 9 This patient presented to our institution on the 13 February 2020 with AML. His marrow showed 30% blasts which were CD34−CD33+CD13+HLADR+CD117+CD38+MPO+ by flow cytometry and that had a normal karyotype. Molecular typing showed that the marrow was positive for the NPM1 Type A mutation, and negative for the fms related receptor tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) and the FLT3 D835/I836 variant. He was initially treated with daunorubicin, cytarabine and gemtuzumab ozogamicin (Mylotarg) chemotherapy, which was complicated by a difficult course with haemophagocytic lymphohistiocytosis (HLH) and possible COVID-19 infection, although several nucleic acid tests for COVID-19 were negative. He was admitted to intensive care and treated with the interleukin 1 receptor antagonist anakinra, as described previously.10 He made a good recovery and was in complete morphological remission following regeneration of his blood counts. MRD using NPM1 transcript levels was measured using the reverse transcription quantitative polymerase chain reaction assay (RT-qPCR) comparing it to the reference ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) transcript levels as described by the UK National Cancer Research Institute AML Working Group.8 Following induction chemotherapy NPM1 transcript levels in the bone marrow were positive at 3 × 10−4 (sensitivity level of assay at 2·67 × 10−7). As a result of the COVID-19 pandemic, and the fact that this patient had a very serious complication during the intensive induction chemotherapy, this patient proceeded to cycle 2 with Ven-Aza combination therapy. This was uneventful and he was in complete morphological remission after cycle 2 with NPM1 mutation levels in the bone marrow at 5·98 × 10−5 (sensitivity level of 8·67 × 10−7). The NPM1 mutation levels in the peripheral blood at this point were negative (mutation level of 1·12 × 10−8, with sensitivity level of assay at 2.8 × 10−6). As NPM1 MRD levels at this time point and from this source of sample (peripheral blood after cycle 2) is established as having prognostic impact for patients with NPM1 mutant AML,8 this patient then proceeded to have cycle 3 chemotherapy with the same drug combination of Ven-Aza. The third course of chemotherapy was also uneventful. However, at the end of this course, although the peripheral blood NPM1 MRD level remains negative (2·13 × 10−7 with sensitivity level of assay of 7·36 × 10−7), the bone marrow NPM1 MRD level is still positive and higher than after cycle 2 (1·65 × 10−4 with assay sensitivity level of 2·01 × 10−6) (Fig 1). It is of concern that the bone marrow NPM1 MRD level is still positive and increasing, and this presents a significant challenge for the next therapeutic decision. This is because it is crucial to note that the time points of assessment of NPM1 MRD and the prognostic impact of each of these assessments as applied for this patient, were based on outcomes of patients having intensive standard chemotherapy during the AML17 trial (International Standard Randomised Controlled Trial Number ISRCTN55675535).8 There is no evidence yet to extrapolate these decision time points to patients being treated with the reduced intensity protocols with Ven-Aza. However, in view of the persistent and rising NPM1 MRD level in the bone marrow, and following multidisciplinary meeting review, we have decided to treat this patient with intensive chemotherapy using the fludarabine-idarubicin (FLA-IDA) protocol followed by allogeneic haematopoietic transplantation. Therefore, the impact of persistent bone marrow NPM1 MRD levels after cycle 2 of Ven-Aza needs to be reassessed in this new treatment regimen and whether treatment escalation needs to occur at a different time point to that of standard intensive treatment regimens. This question highlights the urgent need to collect the data of response rates and MRD levels of patients with AML treated on reduced intensity protocols and this will need to be addressed in future collaborative studies and randomised control trials. Nadine Farah, Richard Burt, Amr R. Ibrahim and Panagiotis D. Kottaridis wrote the manuscript. Robert Baker conducted the molecular NPM1 MRD analysis. Panagiotis D. Kottaridis is the consultant in charge of the patient. Panagiotis D. Kottaridis, Nadine Farah, Richard Burt, Amr R. Ibrahim were all involved in the clinical care of this patient. All authors reviewed and proofread the manuscript. The authors have no competing interests.
The purpose of this study was to examine the influence of obesity on vaginal birth after caesarean section, when body mass index (BMI) was based on the accurate measurement rather than self-reporting of maternal weight and height.
Study design
We enrolled women at their convenience after a sonogram confirmed an ongoing singleton pregnancy in the first trimester. Weight and height were measured digitally and BMI calculated. Clinical and demographic details were recorded prospectively.
Results
Out of 2300 women enrolled, 2209 subsequently delivered in the hospital a baby weighing 500 g or more. There were 50.5% (n=1161) primigravidas and 49.5% (n=1139) multigravidas. There were 188 women who had a previous delivery by caesarean section. The overall VBAC success rate in labour was 66.9%. Of the women that attempted a vaginal birth after previous caesarean section the success rate was 63.2% in Class 1 obese women and 80.0% in Class 2–3 obese women compared with 71.4% in women in the normal BMI category.
Conclusion
Our study showed that successful VBAC rates after one previous caesarean section are similar in obese (BMI>29.9 kg/m2) and non-obese women.
Prediction of hypertensive disease in pregnancy remains a challenge in modern obstetrics. Risk factor based screening, ultrasound and serum markers have been used with varying success. As pre-eclampsia would appear to occur due to changes in the vasculature, the vessel wall has been investigated as a predictor of hypertension in pregnancy. This study looked at pulse pressure wave analysis, using the diastolic portion of the cardiac cycle, in the prediction of hypertensive disease of pregnancy. Women were recruited from the antenatal clinic. Women with known cardiac disease were excluded. All women had pulse pressure waveform analysis performed in the first half of pregnancy. The primary outcome studied was the development of hypertensive disease of pregnancy. Pulse wave analysis was performed on 600 patients. The elasticity of the arterial vessel wall differed in hypertensive pregnancies and in particular in pregnancies subsequently complicated by pre-eclampsia. In early pregnancy, the mean arterial pressure (p=0.02), large artery elasticity (p=0.01), small artery elasticity (p=0.02) and systemic vascular resistance (p=0.02) were all significantly different in women who later developed pre-eclampsia compared to normal pregnancy. In pregnancies complicated by pregnancy induced hypertension, mean arterial pressure measurements were significantly different in early pregnancy but arterial elasticity did not differ. Pulse pressure waveform analysis may be a useful screening tool in the prediction of hypertensive disease and in particular, pre-eclampsia. Use of this technology in combination with other screening tools may aid in the selection of high risk pregnancy for more intensive antenatal care.
The use of body mass index (BMI) for the diagnosis of obesity has limitations, especially when comparing ethnic groups with different body proportions. The aim of this prospective study was to compare maternal body composition in early pregnancy between Caucasian Irish and Indian women. A total of 81 Indian women and 81 Irish Caucasian women were matched for age, parity and BMI. Maternal weight and height were measured, and body composition analysed using bioelectrical impedance. The Irish women were taller and weighed more than the Indian women (p < 0.001). At any given BMI, the Indian women had a higher total body fat percentage, visceral fat level and high fat percentage than the Irish women (p = 0.024, 0.001 and 0.001, respectively). Our findings suggest that lower BMI cut-offs should be used for screening for gestational diabetes mellitus in Indian women attending our antenatal services.
Changes in maternal blood pressure are seen in normal pregnancy. Mean arterial pressure falls until the end of the second trimester and then rises again to prepregnancy levels in the late third trimester. The aetiology of hypertensive disease of pregnancy remains elusive but may involve changes in the arterial vessel wall. We investigated what changes in arterial elasticity occur during pregnancy. Subjects were recruited from the antenatal clinic at their first visit to the hospital. Using the HDI/Pulsewave CR-2000 Research Cardiovascular Profiling System, we analysed the radial artery pulse pressure waveform on 660 occasions in 100 uncomplicated pregnancies between 8 and 40 weeks gestation. Reflective and capacitive arterial compliance was calculated from the pulse pressure waveform contour using a modified Windkessel model of the circulation (electrical analogue model). Centiles for artery elasticity throughout gestation were calculated and fitted using linear mixed effect modelling appropriate to longitudinal data. We found that reflective arterial compliance changes with advancing gestation. The median reflective arterial compliance is 7.6 ml/mm Hg×100 at 16 weeks gestation rising to a peak of 7.8 ml/mm Hg×100 at 20 weeks gestation and then declining to a median value of 5.8 ml/mm Hg×100 at 40 weeks gestation. We also found that capacitive artery elasticity only changes minimally with advancing gestation with a median value of 13.3 ml/mm Hg×10 at all gestations. Changes in small artery vessel wall elasticity are reciprocal to the changes in blood pressure throughout pregnancy. The increase in elasticity seen in the second trimester may contribute to the fall in mean arterial pressure. Further study is needed to clarify the aetiology of these physiological changes.
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