Pregnant Subjects Research Articles

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.

Factors affecting cell-free DNA fetal fraction: statistical analysis of 13,661 maternal plasmas for non-invasive prenatal screening

BackgroundThe identification of cell-free fetal DNA (cffDNA) facilitated non-invasive prenatal screening (NIPS) through analysis of cffDNA in maternal plasma. However, challenges regarding its clinical implementation become apparent. Factors affecting fetal fraction should be clarified to guide its clinical application.ResultsA total of 13,661 pregnant subjects with singleton pregnancies who undertook NIPS were included in the study. Relationship of gestational age, maternal BMI, and maternal age with the cffDNA fetal fraction in maternal plasmas for NIPS was investigated. Compared with 13 weeks (12.74%) and 14–18 weeks group (12.73%), the fetal fraction in gestational ages of 19–23 weeks, 24–28 weeks, and more than 29 weeks groups significantly increased to 13.11%, 16.14%, and 21.17%, respectively (P < 0.01). Compared with fetal fraction of 14.54% in the maternal BMI group of < 18.5 kg/m2, the percentage of fetal fraction in the group of 18.5–24.9 kg/m2 (13.37%), 25–29.9 kg/m2 (12.20%), 30–34.9 kg/m2 (11.32%), and 35–39.9 kg/m2 (11.57%) decreased significantly (P < 0.01). Compared with the fetal fraction of 14.38% in the group of 18–24 years old, the fetal fraction in the maternal age group of 25–29 years old group (13.98%) (P < 0.05), 30–34 years old group (13.18%) (P < 0.01), 35–39 years old group (12.34%) (P < 0.01), and ≥ 40 years old (11.90%) group (P < 0.01) decreased significantly.ConclusionsThe percentage of fetal fraction significantly increased with increase of gestational age. Decreased fetal fraction with increasing maternal BMI was found. Maternal age was also negatively related to the fetal fraction.

The pattern of serum zinc and its contributing factors among third trimester pregnant women in Urmia, Iran, 2018

Purpose The deficiency or excess of serum zinc in pregnancy may threaten the health of the mother and the fetus. The purpose of this study is to determine the pattern of serum zinc in pregnant women covered by Urmia urban health centers and its association with some nutritional and clinical determinants in the third trimester, from July to December 2018. Design/methodology/approach In this analytic cross-sectional study, of six selected health centers in Urmia, 400 pregnant women subjects who were in their third trimester were recruited in a simple random manner. The nutritional, demographic, clinical data as well as fasting blood samples were taken from each of the subjects. The data were analyzed using chi-square, independent t-test and logistic regression tests. Findings The study revealed that about 3 per cent of pregnant women had zinc deficiency, 70.2 per cent were normal and 26.8 per cent had high serum zinc levels. In 388 pregnant women (72.4 per cent with normal serum zinc and 27.6 per cent with high serum zinc), binary logistic regression model showed that high concentration of serum zinc was directly associated with dietary intake zinc (OR: 2.252; 95 per cent CI: 1.85-2.74), supplement zinc (OR: 7.823; 95 per cent CI: 3.676-16.649) and total intake magnesium (OR: 1.005; 95 per cent CI: 1.000-1.01) and inversely associated with frequent reproductive cycling (OR: 0.739; 95 per cent CI: 0.569-0.959). Originality/value Pregnant women in Urmia probably have high concentrations of serum zinc, and it is likely related to consumption of the zinc supplementation. Supplementation programs need to be scaled up for pregnant women that take inadequate dietary zinc.

Some haematological parameters among pregnant women of African descent attending antenatal clinic in Sokoto North Western Nigeria.

Pregnancy is the fertilization and development of one or more offspring, known as an embryo or foetus in a woman's uterus. Pregnancy is a critical stage of development during which maternal nutrition can strongly influence obstetric and neonatal outcomes. The aim of this study was to determine the effect of pregnancy on the full blood count parameters of pregnant women of African descent residing in Sokoto, North Western Nigeria. This case-control study investigated 74pregnant subjects and 22non-pregnant controls. The mean age and income of the subjects were 28.00 ± 8.295 and 2760.42 ± 7975.178 respectively. Haematological parameters were determined using a fully automated 5-part differential haematology analyzer (Model Mythic 22-CT, Orpheee, Switzerland). Results obtained of pregnant subjects were compared with that of non-pregnant controls. The prevalence of anaemia (Hb < 11g/dl) and thrombocytopenia (Platelet count < 140 × 109/L) was 58.11% and 6.75% respectively among the pregnant subjects. The mean haemoglobin, PCV, platelet and red cell count were significantly lower among the pregnant subjects (10.7 ± 0.13g/dl and 31.4 ± 0.38%, 252.7 ± 14.35 × 109/L and 3.7 ± 0.04) compared to the non-pregnant controls (12.2 ± 0.44g/dl, 36.2 ± 1.17 %, 362.7 ± 36.51 × 109/L and 4.3 ± 0.11) (p= 0.004, 0.001, 0.009 and 0.000) respectively. There were no significant differences in the total white blood cell count between the pregnant subjects (5.3 ± 0.22) and non-pregnant controls (4.6 ± 0.59) (p= 0.267). The Neutrophils count was significantly higher among the pregnant subjects (42.6 ± 3.06) compared to the non-pregnant controls (20.0 ± 2.33) (p= 0.000). This study has shown that pregnancy has a significant effect on some haematological parameters of women of African descent. The results of this research work indicates the need to routinely monitor the full blood count, anaemia and thrombocytopenia among pregnant women of African descent.

Study of hematological parameters in anemia in pregnancy

Background: To evaluate the major hematological parameters and morphological typing in anemic pregnant females and correlation of the above findings with the trimester and gravid status of the patient. Material and Methods: This study was conducted on 250 pregnant women attending antenatal OPD having hemoglobin level less than 11 gm/dl in 1st and 3rd trimesters and less than 10.5 gm/dl in the 2nd trimester. Age, gravida, trimester, educational status of each pregnant subject was noted as well as grading and morphological typing of anemia was done. Results: Maximum number of cases were found in age group of 21-30 years i.e. 79.2% (198 cases out of 250 cases). Maximum number of cases of anemic pregnant subjects were primigravidae i.e. 42%. Highest percentage of anemia was in third trimester i.e. 52.4% (131 out of 250 cases). Among all morphological types microcytic hypochromic anemia was most predominant i.e. 89.2%. Moderate anemia was the predominant grade of anemia i.e. 67.6% (169 out of 250). On correlating age group with grade of anemia, moderate anemia was found to be predominant among all age groups. Out of 169 cases of moderate anemia, 74 cases (43.8%) were in 21-25 age group. Conclusion: All the four factors i.e. age, gravida, trimester and educational status were correlated with grade and morphological type of anemia. Microcytic hypochromic anemia was the predominant morphological type of anemia in all age ranges, all gravidae and all trimesters. There was statistically significant association between age and morphological type of anemia.

Serum amphiregulin and cerebellin-1 levels in severe preeclampsia

Purpose Preeclampsia is a form of hypertensive disorders of pregnancy and defined as the presence of new-onset hypertension and proteinuria or other end organ damage occurring after 20-week gestation. Preeclampsia can be a destructive process that can cause maternal and infant mortality. The exact etiopathogenesis of preeclampsia is still undefined. We aimed to compare serum amphiregulin and cerebellin-1 levels of severe preeclampsia patients with healthy pregnant women and healthy control subjects. Materials and methods A total of 88 women were enrolled in this study. Patients diagnosed with severe preeclampsia were group 1 (n = 28), healthy non-pregnant normotensive women group 2 (n = 30), and healthy pregnant women group 3 (n = 30). The participants in each group were matched for age. Pregnant women in groups 1 and 3 were also matched for gestational age. Serum amphiregulin and cerebellin-1 levels were measured using ELISA. Results Serum amphiregulin levels were 3413 ± 1.38 ng/ml (1748–7739), 8510 ± 7213 ng/ml (2019–24,000), and 6580 ± 5360 ng/ml (2484–24,000) in preeclampsia patients, controls and healthy pregnant women, respectively. Amphiregulin levels were significantly lower in preeclampsia patients than healthy pregnant women (p=.008) and controls (p = .015). Amphiregulin levels were similar between healthy controls and healthy pregnant women (p = 1.00). Cerebellin-1 levels were 222.039 ± 92.681 pg/ml (138,580–557,757) in preeclamptic patients, 537.043 ± 525.117 pg/ml (150,432–1,600,000) in controls and 415.091 ± 436.580 pg/ml (137,284–1,600,000) in healthy pregnant women. Cerebellin-1 levels were similar among groups (p = .272). Serum amphiregulin and cerebellin-1 levels were significantly and positively correlated with each other in preeclampsia patients (r = 0.693, p < .001), controls (r = 0.882, p < .001), and healthy pregnant women (r = 0.591, p = .001). Serum level of amphiregulin ≤3590 pg/ml had a sensitivity of 67.9% and specificity of 63.3% in the diagnosis of preeclampsia (AUC: 0.751; p = .001). Conclusions Serum amphiregulin decreases in severe preeclampsia patients.

Individual variation in simulated fetal SAR assessed in multiple body models.

We generate 12 models from 4 pregnant individuals to evaluate individual differences in local specific absorption rate (SAR) for differing body habitus and fetal and maternal positions. Structural MR images from 4 pregnant subjects (including supine and left-lateral maternal positions) were manually segmented to create 12 body models by rotating the fetus, modifying the fat content, and altering the maternal arm position in 1 of the subjects. Electromagnetic simulations modeled at 3 Tesla determined the average and peak local SAR in the maternal trunk, fetus, fetal brain, and amniotic fluid. We observed a significant range of fetal and maternal peak local SAR across the models (maternal trunk: 19.14-44.03 watts/kg, fetus: 9.93-18.79 watts/kg, fetal brain 3.36-10.3 watts/kg). We found that maternal body habitus changes introduced a significant variation in the maternal peak local SAR but not the fetal local SAR. However, the maternal position (either rotating the mother to left-lateral position or altering the arm position) introduced changes in fetal peak local SAR (range: 11.9-17.9 watts/kg). Rotating the fetus also introduced variation in the fetal and fetal brain peak local SAR. The observed variation in SAR emphasizes the need for more anatomical models to enable better safety management of individuals during fetal MRI, including a wider range of gestational ages.

Preliminary evaluation of dynamic glucose enhanced MRI of the human placenta during glucose tolerance test.

To investigate dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) MRI as a means to non-invasively image glucose transport in the human placenta. Continuous wave (CW) CEST MRI was performed at 3.0 Tesla. The glucose contrast enhancement (GCE) was calculated based on the magnetization transfer asymmetry (MTRasym), and the DGE was calculated with the positive side of Z-spectra in reference to the first time point. The glucose CEST (GlucoCEST) was optimized using a glucose solution phantom. Glucose solution perfused ex vivo placenta tissue was used to demonstrate GlucoCEST MRI effect. The vascular density of ex vivo placental tissue was evaluated with yellow dye after MRI scans. Finally, we preliminarily demonstrated GlucoCEST MRI in five pregnant subjects who received a glucose tolerance test. For human studies, the dynamic R2* change was captured with T2*-weighted echo planar imaging (EPI). The GCE effect peaks at a saturation B1 field of about 2 μT, and the GlucoCEST effect increases linearly with the glucose concentration between 4-20 mM. In ex vivo tissue, the GlucoCEST MRI was sensitive to the glucose perfusate and the placenta vascular density. Although the in vivo GCE baseline was sensitive to field inhomogeneity and motion artifacts, the temporal evolution of the GlucoCEST effect showed a consistent and positive response after oral glucose tolerance drink. Despite the challenges of placental motion and field inhomogeneity, our study demonstrated the feasibility of DGE placenta MRI at 3.0 Tesla.

Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones.

Cholecystokinin (CCK) is an important neuro-intestinal peptide hormone produced by the enteroendocrine I-cells in the upper part of small intestine. Protein- and fat-enriched food plays an important role in triggering CCK secretion from the intestine. Carbohydrates stimulate only small amounts of CCK release. The CCK-1 receptor (CCK-1R) is largely localized in the gallbladder, sphincter of Oddi, pancreas, small intestine, gastric mucosa, and pyloric sphincter, where it is responsible for CCK to regulate multiple digestive processes including gallbladder contraction, pancreatic secretion, small intestinal transit, and gastric emptying. Accumulated evidence clearly demonstrates that CCK regulates gallbladder and small intestinal motility through CCK-1R signaling cascade and the effect of CCK-1R on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. Disruption of the Cck or the Cck-1r gene in mice significantly increases the formation of cholesterol gallstones by disrupting gallbladder emptying and biliary cholesterol metabolism, as well as promoting intestinal absorption of cholesterol. Abnormalities in gallbladder motility function in response to exogenously administered CCK are found primarily in patients with cholesterol gallstones. Patients with pigment gallstones display an intermediate degree of gallbladder motility defect without gallbladder inflammation and enlarged fasting gallbladder. Dysfunctional gallbladder contractility has been found under several conditions such as pregnancy, obesity, diabetes, celiac disease, and total parenteral nutrition although gallstones are not observed. The gallbladder-specific CCK-1R-selective agonist may lead to an efficacious novel way for preventing gallstone formation by promoting gallbladder emptying, particularly for pregnant women and subjects with dysfunctional gallbladder motility function such as celiac patients, as well as patients with total parenteral nutrition.

İkinci ve üçüncü trimester gebelerde artırılmış derinlik optik koherens tomografi ile koroid kalınlık ölçümü

Aim: Evaluation of choroid thickness in 2nd and 3rd trimester pregnancies by Enhanced Depth Imaging –EDI Optic Coherence Tomography (OCT). Patients and Methods: In this study, the subfoveal, 2 mm nasal, 2 mm temporal choroidal thicknesses of both eyes in 40 pregnant and 40 non-pregnant (control) women were evaluated. The pregnant women were categorized in 2 groups, 20 being 16-24 weeks pregnant (second trimester) and 20 being 24-39 weeks pregnant (third trimester). The average age of the pregnant women and non-pregnant women was calculated as 27.4±5.8 and 26.9±7.1, respectively. Results: The choroid thicknesses in the pregnant women were recorded by EDI-OCT as follows; right eye subfoveal 295.3±51.8μm, 2 mm nasal 242.4±49.2μm, 2 mm temporal 252.3±52.9μm and left eye subfoveal 298.4±66.7μm, 2 mm nasal 251.5±54.7μm, 2 mm temporal 263.6±64.3μm. The control group was recorded as follows; right eye subfoveal 307.8±64.5μm, 2 mm nasal 267.6±54.2μm, 2 mm temporal 292.9±50.9μm and left eye subfoveal 295.3±71.3μm, 2 mm nasal 269.6±63.7μm, 2 mm temporal 292.0±59.5μm. The comparison of the choroid thicknesses in the pregnant subjects and the control group shows that the thickness in the 2 mm nasal (p=0.032) and 2 mm temporal (p=0.001) areas of the right eye and 2 mm temporal (p=0.044) area of the left eye is significantly different. No significant difference was observed in the other areas (p&amp;gt;0.05) Conclusions: In this study, choroidal thickness measurement with EDI OCT was found to be thinner in pregnant patients compared to similar age group.

A cross sectional study to assess the sFlt-1:PlGF ratio in pregnant women with and without preeclampsia

BackgroundPreeclampsia is a multisystem disorder characterized by vascular endothelial malfunction occurring after 20 weeks of gestation. Placental soluble fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic factor and placental growth factor (PlGF) is a potent angiogenic factor. The imbalance between these factors during placenta and fetal development has been shown to play a role in endothelial damage in preeclampsia.Preeclampsia is the leading cause of maternal mortality in Nepal. This study was designed to compare the sFlt1:PLGF ratio in pregnant women with and without preeclampsia attending Tribhuvan University Teaching Hospital (TUTH).MethodAn observational cross-sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving forty-four subjects with preeclampsia and forty-four age- and gestational-week-matched normal pregnant subjects as controls. Blood pressure, urinary protein levels, serum sFlt-1 levels, serum PlGF levels and the sFlt-1:PlGF ratio was compared in both the cases and control. The concentrations of sFlt-1 and PlGF were measured with commercially available ELISA kits. SPSS ver. 20.0 was used to analyze the data.ResultsThere was no significant difference in age or gestational age in either study group. The ratio of the sFlt-1 and PlGF concentrations was significantly higher in women with preeclampsia (31.6 ± 9.6) than in the controls (3.2 ± 1.3). Likewise, diastolic blood pressure was significantly associated (p-value 0.000), whereas the severity of proteinuria was not associated (p-value 0.773) with the sFlt-1:PlGF ratio in women with preeclampsia. The significantly higher ratio (35.51 ± 8.1 versus 25.4 ± 8.7) was found in women with preeclampsia who developed complications than the group of women with preeclampsia who did not develop complication.ConclusionThe sFlt-1:PlGF ratio is significantly higher in Nepalese women with preeclampsia than in normal controls and this finding can be applied for further planned clinical trials.

Study on the mechanism of microRNA-210 regulating the immune pathogenesis of Treg cells in preeclampsia

Objective The aim of this study was to evaluate the number of Treg cells in preeclampsia (PE) patients, to explore the expression levels of microRNA-210 (microRNA-210) and forkhead box p3 (Foxp3) genes in preeclampsia, and to reveal the regulatory mechanism of microRNA-210 and Foxp3 in preeclampsia. Methods Serum levels of cytokines [interleukin (IL)-6, IL-10, IL-17, and transforming growth factor-beta 1 (TGF-β1)] were detected with enzyme-linked immunosorbent assay (ELISA). 29 patients with late-onset preeclampsia (≥36 weeks of gestation), 27 pregnant women with normal uncomplicated pregnancies (≥36 weeks of gestation) and 20 healthy non-pregnant women were enrolled in the study. Reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect mRNA expression for maternal placenta retinoic acid-related orphan receptor C (RORc), Foxp3, and miR-210. Foxp3 protein expression was evaluated by Western blot. Results ⑴ The serum levels of IL-6, IL-17 and TGF-beta 1 in preeclampsia patients were significantly higher than those in normal pregnant women, and the level of Treg cytokine IL-10 was lower than that in normal pregnant women (P<0.05). ⑵ The percentage of CD4+ CD25+ CD127-/CD4+ T cells in peripheral blood of preeclampsia patients was significantly lower than that of normal pregnancy group and healthy non-pregnant women (P<0.001). ⑶ The mRNA expression of Foxp3 in placenta of preeclampsia patients was significantly lower than that of normal pregnant women, RORc in preeclampsia patients was significantly higher than that of normal pregnant women, and the expression of microRNA210 in preeclampsia patients was enhanced (P<0.01). ⑷ Consistent with mRNA expression results, lower protein expression levels of Foxp3 was observed in patients with PE compared with normal pregnant subjects. Conclusions Treg cells decreased in preeclampsia patients and Treg/Th17 imbalance existed in preeclampsia patients, which regulate maternal immune tolerance to fetuses. The expression of Foxp3 in placenta of preeclampsia patients was significantly decreased, which was correlated with the expression of microRNA-210. Key words: MicroRNAs; T-lymphocytes, regulatory; Pre-eclampsia; Forkhead transcription factors

Circulating soluble LR11, a differentiation regulator for vascular cells, is increased during pregnancy and exaggerated in patients with pre-eclampsia

BackgroundPre-eclampsia is a pregnancy-specific disease characterized by onset of hypertension and proteinuria, sometimes progressing into damaging other organs. Here, we investigated the pathological significance of the soluble fragment of LR11 (sLR11), a cell differentiation regulator, in comparison to circulating IL-6 and TNF-α, in pre-eclampsia. MethodsThe study was conducted in a cross-sectional research design with fourteen pre-eclampsia patients and fifty healthy pregnant subjects. Pre-eclampsia was defined as hypertensive disorders in pregnancy at over 20 weeks of gestation with proteinuria. ResultsPlasma levels of sLR11 as well as IL-6 in pre-eclampsia were increased compared with those in the healthy pregnant subjects at the first, the second, and the third trimester. Receiver operating characteristic analysis for the detection of pre-eclampsia among third-trimester subjects showed that the areas under the curves of sLR11 and IL-6 were equivalent. sLR11 and IL-6 correlated positively with TNF-α in healthy pregnant subjects. In the pre-eclampsia patients, there was neither a correlation between sLR11 and IL-6 nor between sLR11 and TNF-α. ConclusionssLR11 increases during pregnancy, with levels further exaggerated in pre-eclampsia, and may be related to the pathology of pre-eclampsia.

Fetal heart detection based wide area network technology with wireless sensor transmission

Fetal heart detection technology, especially in remote areas, has so far been manual and lacks facilities for monitoring fetal safety. This results in many pregnant women at risk of labor, so early detection of fetal heart conditions becomes important. Development of fetal heart detector technology based on wide area network technology that is able to provide real-time monitoring results and is connected to the proposed wireless sensor network transmission. Its integration with smartphones makes it easy to use in rural and remote areas. The design of this monitoring system called detector of fetal abnormalities technology has the advantage of sending medical data for pregnant women and fetal heart conditions to families and to health care centers for pregnant women in large cities or obstetricians. Visualization of data in image, graphic and text, can be used as a digital-based maternal and fetal health detector tool. In the initial trial, fetal heart rate data from 4 pregnant subject were evaluated and obtained results with an average curation of 94%.

Hepcidin as a diagnostic biomarker of iron deficiency anemia during pregnancy

Objectives Hepcidin hormone production is suppressed in the case of iron deficiency. The role of hepcidin as a hormone in iron metabolism along with its diagnostic cut-off values and its sensitivity and specificity among pregnant women with iron deficiency anemia (IDA) was examined in this study. Methods In this case-control study, three groups of pregnant subjects were included according to the following criteria: cases/patient group: pregnant women with IDA based on, Hb < 11.5 g/dl, S ferritin < 10 ng/ml, TS%<15%; positive control group: pregnant women with non-IDA based on, Hb < 11.5 g/dl, S ferritin > 10 ng/ml, TS%>15%; and negative control group: included non-anemic apparently healthy pregnant women based on, Hb > 11.5 g/dl, S ferritin > 10 ng/ml, TS%>15%. Results The serum hepcidin was significantly lower in pregnant women with IDA (0.34 ng/ml) compared to its level in pregnant women with non-IDA (23.48 ng/l) and apparently healthy pregnant women (13.86 ng/ml; p<.001). The study found a significant correlation between serum hepcidin and iron deficiency-related parameters with adjustment for study groups (p<.01). Moreover, the study found that serum hepcidin has good sensitivity in the range of 0.49–0.76 ng/ml (80.6–83.3%) and good specificity (76.2%) over positive IDA. Similar results were found for serum hepcidin over negative control group (0.49–0.83 ng/ml; sensitivity: 80.6–83.3%; specificity: 75.8–78.8%). Conclusions This study suggests that serum hepcidin is superior to hemoglobin, serum iron, serum ferritin, TS, and TIBC as an indicator of IDA in pregnant women. Study register 24012018-1 on 24 January 2018.

Effect of N-Acetyltransferase 2 Genotype on the Pharmacokinetics of Hydralazine During Pregnancy.

Hydralazine, an antihypertensive agent used during pregnancy, undergoes N-acetylation primarily via N-acetyltransferase 2 (NAT2) to form 3-methyl-1,2,4-triazolo[3,4-a]phthalazine (MTP). To characterize the steady-state pharmacokinetics (PK) of hydralazine during pregnancy and evaluate the effects of NAT2 genotype on hydralazine and MTP PK during pregnancy, 12 pregnant subjects received oral hydralazine (5-25mg every 6 hours) in mid- (n=5) and/or late pregnancy (n=8). Serial blood samples were collected over 1 dosing interval, and steady-state noncompartmental PK parameters were estimated. Subjects were classified as either (rapid acetylators, n=6) or slow acetylators (SAs, n=6) based on NAT2 genotype. During pregnancy, when compared with the SA group, the RA group had faster weight-adjusted hydralazine apparent oral clearance (70.0±13.6 vs 20.1±6.9 L/h, P<.05), lower dose-normalized area under the concentration-time curve (AUC; 1.5±0.8 vs 5.9±3.7 ng·h/mL, P<.05), lower dose-normalized peak concentrations (0.77±0.51 vs 4.04±3.18 ng/mL, P<.05), and larger weight-adjusted apparent oral volume of distribution (302±112 vs 116±45 L/kg, P<.05). Furthermore, the MTP/hydralazine AUC ratio was ∼10-fold higher in the RA group (78±30 vs 8±3, P<.05) than in the SA group. No gestational age or dose-dependent effects were observed, possibly because of the small sample size. This study describes for the first time, the PK of oral hydralazine and its metabolite, MTP, during pregnancy, and confirmed that the PK of oral hydralazine is NAT2 genotype dependent during pregnancy.

A simulation study on the effect of optimized high permittivity materials on fetal imaging at 3T.

PurposeOne of the main concerns in fetal MRI is the radiofrequency power that is absorbed both by the mother and the fetus. Passive shimming using high permittivity materials in the form of “dielectric pads” has previously been shown to increase the B1+ efficiency and homogeneity in different applications, while reducing the specific absorption rate (SAR). In this work, we study the effect of optimized dielectric pads for 3 pregnant models.MethodsPregnant models in the 3rd, 7th, and 9th months of gestation were used for simulations in a birdcage coil at 3T. Dielectric pads were optimized regions of interest (ROI) using previously developed methods for B1+ efficiency and homogeneity and were designed for 2 ROIs: the entire fetus and the brain of the fetus. The SAR was evaluated in terms of the whole‐body SAR, average SAR in the fetus and amniotic fluid, and maximum 10 g‐averaged SAR in the mother, fetus, and amniotic fluid.ResultsThe optimized dielectric pads increased the transmit efficiency up to 55% and increased the B1+ homogeneity in almost every tested configuration. The B1+‐normalized whole‐body SAR was reduced by more than 31% for all body models. The B1+‐normalized local SAR was reduced in most scenarios by up to 62%.ConclusionSimulations have shown that optimized high permittivity pads can reduce SAR in pregnant subjects at the 3rd, 7th, and 9th month of gestation, while improving the transmit field homogeneity in the fetus. However, significantly more work is required to demonstrate that fetal imaging is safe under standard operating conditions.

Sequencing shorter cfDNA fragments improves the fetal DNA fraction in noninvasive prenatal testing

Sequencing cell-free DNA in maternal plasma is an effective noninvasive prenatal testing technique that has been used in fetal aneuploidy screening worldwide. However, its clinical application is limited by the low fetal fraction (<4%) of cell-free DNA in many singleton pregnancies, which usually results in screen failures or no calls. In addition, dizygotic twin contributions of cell-free DNA into the maternal circulation can vary by 2-fold, complicating the quantitative diagnosis of fetal aneuploidy. We performed semiconductor sequencing of shorter fragments (107-145 bp) of circulating cell-free DNA to improve the fetal DNA fraction at lower uniquely mapped reads (1-8.5 MB) to reduce the probability of no calls. We identified 2903 plasma samples from pregnant women, including 86 dizygotic twin pregnancy, that were collected at a single prenatal diagnostic center between October 2015 and July 2018. Size-selection noninvasive prenatal testing for fetal aneuploidy was applied to 2817 plasma samples (1409 male and 1408 female fetuses) and 86 dizygotic twins using noninvasive prenatal testing with and without size selection. Shorter fragment size was the key factor affecting fetal fraction in multivariable linear regression models as well as to validate the accuracy of the size selection for noninvasive prenatal testing. Analysis of 1409 male fetuses by multivariable linear regression showed that maternal age, body mass index, number of pregnancies, average cell-free DNA size, maternal plasma cell-free DNA concentration, library concentration, and multiple gestation were negatively correlated with fetal fraction. Conversely, gestational age and uniquely mapped reads were positively correlated with fetal fraction. Compared with ≤120 bp cell-free DNA fragments, mean fetal fraction differences were -3.57% (95% confidence interval, -5.95% to -1.19%), for 121-130 bp, -9.52% (95% confidence interval, -11.89% to -7.14%) for 131-140 bp, and -14.47% (95% confidence interval, -18.37% to -10.58%) for ≥141 bp (Ptrend < .0001). These results were statistically significant after multivariable adjustments in models for fetal fraction. Meanwhile, results from 86 dizygotic twins showed that the size selection increased the fetal fraction by ∼3.2-fold, with 98.8% of samples reaching a fetal fraction >10%. Improved detection accuracy was also achieved. Sequencing shorter cell-free DNA fragments is a reasonable strategy to reduce the probability of no calls results because of low fetal fraction and should be recommended to pregnant subjects.

Changes in bone metabolic profile associated with pregnancy or lactation

Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

Of Pregnancy and Dairy Cows: Entanglements of Materiality, Pregnancy and the Farmed Animal in Helena Granström’s ”Skördebrev”

Abstract This article centres on the literary representation of the pregnant body in the short story Skördebrev by Helena Granström. The short story interlocks the narration of the pregnant experience with narration from the perspective of a dairy cow on a farm, thus negotiating the dominating discourses surrounding farmed animals and human pregnancy. The article investigates these matters by discussing the relations between the characters, the farmed animals and the farmed landscape as portrayed in the short story, and in doing this, examines what the relations convey about the portrayal of human, non-human and pregnant corporeality and identity in the text. It does this using Stacy Alaimo’s term trans-corporeality, Karen Barad’s notions of intra-action and Ann-Sofie Lönngren’s adaption of this theory to literary analysis. The article suggests that the text offers an understanding of the material situatedness of the literary pregnant subject and the dairy cow as partly shared and argues that it shows the potential of literary representation to articulate these intersecting positions. In doing this, it suggests that the text negotiates the societal power structures that are at play in the Western cultural understanding of pregnancy as well as in the farming environment, in an ethical and political manner.