Nonpregnant Subjects Research Articles

Praziquantel for the treatment of schistosomiasis during human pregnancy.

In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praziquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach. Since 2006, two randomized controlled trials on the use of praziquantel during pregnancy have been conducted: one against S. mansoni in Uganda and the other against S. japonicum in the Philippines. In these trials, praziquantel treatment of pregnant women had no significant effect on birth weight, appeared safe and caused minimal side-effects that were similar to those seen in treated non-pregnant subjects. Having summarized the encouraging data, on efficacy, pharmacokinetics and safety, from these two trials and reviewed the safety data from non-interventional human studies, we recommend that all countries include pregnant women in praziquantel treatment campaigns. We identify the barriers to the treatment of pregnant women, in countries that already include such women in individual treatments and mass drug administration campaigns, and discuss ways to address these barriers.

Maternal Serum B-Cell Activating Factor Levels: Candidate Early Biomarker for Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. Early suppression of B-cell lymphopoiesis is necessary for a normal pregnancy. Dysregulation of factors critical to B-cell survival may result in pregnancy complications, including hypertension. In this prospective observational study at a single medical center, serum levels of BAFF (B-cell activating factor) were measured in pregnant participants at each trimester, at delivery, and postpartum and in nonpregnant controls at a single time point. Comparisons were made between nonpregnant and pregnant subjects and between time periods of pregnancy. First-trimester serum BAFF levels were further tested for association with hypertensive disorders of pregnancy. The study included 149 healthy pregnant women, 25 pregnant women with chronic hypertension, and 48 nonpregnant controls. Median first-trimester serum BAFF level (ng/mL) for healthy women (0.90) was lower than median serum BAFF levels for women with chronic hypertension (0.96; P=0.013) and controls (1.00; P=0.002). Serum BAFF levels steadily declined throughout pregnancy, with the median second-trimester level lower than the corresponding first-trimester level (0.77; P=0.003) and the median third-trimester level lower than the corresponding second-trimester level (0.72; P=0.025). The median first-trimester serum BAFF level was elevated in women who subsequently developed hypertension compared with women who remained normotensive (1.02 versus 0.85; P=0.012), with the area under the receiver operating characteristic curve being 0.709. First-trimester serum BAFF level may be an early and clinically useful predictor of hypertensive disorders of pregnancy.

The Endometriosis Fertility Index Is Useful for Predicting the Ability to Conceive without Assisted Reproductive Technology Treatment after Laparoscopic Surgery, Regardless of Endometriosis

Objective: The endometriosis fertility index (EFI) is a novel index for predicting pregnancy after surgery. We investigated the utility of the EFI for predicting the ability to conceive without assisted reproductive technology (ART) treatment after laparoscopic surgery. Methods: From July 2011 through December 2012, we recruited 133 infertile patients who underwent laparoscopy, and the EFI was calculated. After surgery, 55 of 133 achieved pregnancy without ART treatment. We evaluated the factors that predicted a naturally successful pregnancy and compared them between the pregnant and non-pregnant subjects. Results: On a univariate linear regression analysis, we found that a younger age, shorter duration of infertility, and higher EFI were positively associated with a successful pregnancy without ART after laparoscopic surgery (p < 0.05). According to 50th percentile EFI, the cutoff EFI predicting a successful pregnancy without ART was 7, the pregnancy rate in the high-EFI group (EFI; 8-10) was significantly higher than that in the low-EFI group (EFI ≤7; p < 0.05), but the duration to natural conception after surgery was similar between the 2 groups. Conclusion: The EFI possesses greater predictive power for a successful pregnancy with natural intercourse or intrauterine insemination in infertile patients, regardless of endometriosis, than the Revised-American Society of Reproductive Medicine classification.

Cannabis use during pregnancy: Pharmacokinetics and effects on child development.

The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with cannabis use, particularly for sensitive subgroups such as pregnant women, are difficult to define because of a paucity of dose-response data and the recent increase in cannabis potency. Although there is a large body of evidence detailing the mode of action of Δ9-tetrahydrocannabinol (THC) in adults, little work has focused on understanding how cannabis use during pregnancy may impact the development of the fetal nervous system and whether additional plant-derived cannabinoids might participate. This manuscript presents an overview of the historical and contemporary literature focused on the mode of action of THC in the developing brain, comparative pharmacokinetics in both pregnant and nonpregnant model systems and neurodevelopmental outcomes in exposed offspring. Despite growing public health significance, pharmacokinetic studies of THC have focused on nonpregnant adult subjects and there are few published reports on disposition parameters during pregnancy. Data from preclinical species show that THC readily crosses the placenta although fetal exposures appear lower than maternal exposures. The neurodevelopmental data in humans and animals suggest that prenatal exposure to THC may lead to subtle, persistent changes in targeted aspects of higher-level cognition and psychological well-being. There is an urgent need for well-controlled studies in humans and preclinical models on THC as a developmental neurotoxicant. Until more information is available, pregnant women should not assume that using cannabis during pregnancy is safe.

Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response.

Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs) are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1β and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF) as therapeutic option as PIF modulates Inflammation in pregnancy. Additionally, synthetic PIF (PIF analog) protects against multiple immune disorders. We used a LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss and increased the embryo weight significantly. We detected increased PIF expression in the placentae after LPS insult. The LPS induced serum and placenta cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well. In conclusion our results indicate that synthetic PIF protects against LPS induced fetal loss, likely through modulation of inflammatory response especially the inflammasome complex. Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562), therapeutic approach during pregnancy can be envisioned.

An evidence-based recommendation to increase the dosing frequency of buprenorphine during pregnancy

Dose-adjusted plasma concentrations of buprenorphine are significantly decreased during pregnancy compared with the nonpregnant state. This observation suggests that pregnant women may need a higher dose of buprenorphine than nonpregnant individuals to maintain similar drug exposure (plasma concentrations over time after a dose). The current dosing recommendations for buprenorphine during pregnancy address the total daily dose of buprenorphine to be administered, but the frequency of dosing is not clearly addressed. Based on buprenorphine's long terminal half-life, once-daily or twice-daily dosing has generally been suggested. The objective of the study was to assess the impact of dosing frequency on buprenorphine plasma concentration time course during pregnancy. We utilized 3 data sources to determine an optimal frequency for dosing of buprenorphine during pregnancy: data from a pharmacokinetic study of 14 pregnant and postpartum women on maintenance buprenorphine in a supervised clinical setting; data from pregnant women attending a buprenorphine clinic; and data from a physiologically based pharmacokinetic modeling of buprenorphine pharmacokinetics in nonpregnant subjects. Among the 14 women participating in the pharmacokinetic study during and after pregnancy, plasma concentrations of buprenorphine were <1 ng/mL (the theoretical concentration required to prevent withdrawal symptoms) for 50-80% of the 12 hour dosing interval while at steady state. Among 62 women followed up in a opioid agonist treatment program, in which dosing frequency is determined in part by patient preference, 10 (16%) were on once-daily dosing, 10 (16%) were on twice-daily dosing, 28 (45%) were on thrice-daily dosing, and 14 (23%) were on four-times-daily dosing. A physiologically based pharmacokinetic model in nonpregnant subjects demonstrated that dosing frequency has an impact on the duration over which the plasma concentrations are below a specified plasma concentration threshold. A more frequent dosing interval (ie, three-times-daily or four-times-daily dosing) may be required in pregnant women to sustain plasma concentrations above the threshold of 1 ng/mL to prevent withdrawal symptoms and to improve adherence.

THERMAL IMAGING AS AN ADJUNCT TOOL FOR IDENTIFYING FETAL GROWTH – A PILOT STUDY

Monitoring the fetal growth and diagnosing any possible abnormality plays a vital role in ensuring the healthy growth of a fetus. Certain health issues like Hyperthermia, Premature Rupture of Membranes (PROM) and Intrauterine Growth Restriction (IUGR) has to be diagnosed early. A pilot study comprising of 27 pregnant and 2 non-pregnant subjects was conducted to check the effectiveness of Thermal imaging in predicting the fetal growth. The heat dissipated by the fetus to the maternal abdominal wall is acquired as a surface thermal distribution. These images were processed qualitatively and quantitatively for better understanding. There was a consistent higher thermal pattern for pregnant women. A more pronounced temperature pattern is notable in the umbilical region that correlates with gestation age. However, as thermal pattern varies with age, gestation period and BMI, it is advisable to track the same person and compare the images for better assessment. This pilot study justifies the need for more elaborate study in building a database for classification and interpretation of thermogram to detect fetal abnormality with reduced human interpretation.

Effect of supervised exercise in groups on psychological well-being among pregnant women at risk of depression (the EWE Study): study protocol for a randomized controlled trial

BackgroundPregnant women with depression and/or anxiety prior to pregnancy are at higher risk of preterm birth, breastfeeding problems, postpartum depression, and disruption of the mother-infant attachment. It is well documented that exercise improves psychological well-being in nonpregnant subjects with symptoms of depression. However, in only a few small studies have researchers examined the effect of exercise on symptoms of depression among pregnant women. We hypothesize that physiotherapist-supervised group exercise for pregnant women at risk of antenatal depression increases their psychological well-being. This paper describes the study protocol of a randomized controlled trial (RCT) on a supervised group exercise intervention for pregnant women with a current or previous history of depression and/or anxiety.Methods/designThe RCT is being carried out at the Department of Obstetrics, Rigshospitalet, Copenhagen University Hospital, in the period 2016–2019. The inclusion criteria are pregnant women ≥18 years of age with depression and/or anxiety requiring treatment by a psychiatrist or a psychologist within the last 10 years and/or intake of antidepressants in the 3 months prior to conception and/or during pregnancy. The women must have appropriate Danish language skills, be pregnant with a single fetus, give written informed consent, and be at 17–22 gestational weeks when the intervention begins. The primary outcome is psychological well-being (the five-item World Health Organization Well-being Index). Secondary outcomes are symptoms of depression (Edinburgh Postnatal Depression Scale), functional ability (General Health Questionnaire), clinical symptoms of anxiety (State-Trait Anxiety Inventory), sleep quality and sleep disturbances (Pittsburgh Sleep Quality Index), and pregnancy and delivery outcomes. The intervention is supervised group exercise twice weekly for 12 weeks. The control group will receive standard antenatal care. On the basis of sample size calculation, a total of 300 women will be randomly assigned to either the intervention or the control group in a ratio of 1:1.DiscussionThe trial is expected to contribute to the body of knowledge used in planning antenatal care for pregnant women at risk of depression.Trial registrationClinicalTrials.gov, NCT02833519. Registered on 19 May 2016.

Provisional criteria for the diagnosis of hypertension in pregnancy using home blood pressure measurements

Most guidelines for the management of hypertension define it as a home blood pressure (HBP) value >135/85 mm Hg. However, there is no reference HBP value to diagnose hypertension in pregnant women. Therefore, in this study, we analyzed HBP measurements of pregnant women to determine whether it is appropriate to use the criteria for non-pregnant subjects for pregnant women. The participants of this study were 100 singleton pregnant women who visited our hospital between September 2013 and September 2016. We lent sphygmomanometers to the patients so they could measure their BP at home twice daily, and we measured their clinical BP when they visited the hospital. Six patients developed hypertensive disorders in pregnancy, whereas there were 63 women without hypertension or other complications that may affect BP. In the normotensive pregnant women, HBP values significantly correlated with the clinical BP values. HBP values equivalent to a clinical BP of 140/90 mm Hg, determined using the standard major axis method, were 120.8/83.5 mm Hg, 126.0/85.2 mm Hg and 136.3/89.3 mm Hg in the first, second and third trimesters, respectively. In normotensive pregnant women, HBP levels that indicate a risk of hypertensive disorder in pregnancy may be lower than 135/85 mm Hg before 28 weeks of gestation.

Relationship between maternal hemodynamics and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia and fetal growth restriction

A proper maternal cardiovascular adaptation to the pregnancy plays a key role for promoting an adequate uteroplacental perfusion, for ensuring normal fetal development and for preventing gestational hypertensive complications such as preeclampsia. This study aims to evaluate hemodynamic measurements obtained by noninvasive methods among preclamptic women with and without fetal growth restriction (FGR) and the relationship with plasma levels of natriuretic peptides. The study compared 98 pregnant women (n=48 with preeclampsia; n=50 normotensive pregnant women) and 50 nonpregnant normotensive control subjects undergoing anultrasonic cardiac output monitor (USCOM) and plasma assessment of atrial N-terminal pro B-type natriuretic peptide (NT-proBNP). The statistical analysis was carried out by analysis of variance and correlation analysis. Preeclampsia state is associated with increased vascular resistance (mean 1587±236 vs 978±153 dyn s cm-3) and lower cardiac output (mean 5.7±1.1 vs 6.78±0.8 l) and this hemodynamic state is associated with higher levels of NT-proBNP (mean 121.2±26.3 vs 42.5±11.4 pg ml-1); furthermore, we found an inverse correlation between maternal cardiac output and plasma levels of NT-proBNP only if preeclampsia is associated with FGR. The elevated NT-proBNP in preeclampsia may reflect ventricular stress and subclinical cardiac dysfunction worsening if FGR is present. This may have implications for the acute management of the preeclampsia and FGR women and for appropriately timed therapeutic interventions later in life.

Effects of dexamethasone on leukocytic responses in pregnant Yankasa ewes and Sahel does in Maiduguri, Nigeria

Effects of dexamethasone on leukocytic responses of pregnant Yankasa sheep and Sahel does were investigated. In addition to its anti-inflammatory properties, dexamethasone regulates broad variety of immune cell functions and immune mediator expression at the molecular level and has become subject of considerable interest in clinical immunology. It has been shown to cause leukocytosis involving neutrophilia, suppression of leukocyte blastogenesis and change lymphocyte subpopulation patterns. However, response to medication may differ among species and physiological status. The objective of the study was to compare and evaluate the effects of dexamethasone on leukocytic responses in pregnant Yankasa ewes and Sahel does. Fourteen adult Sahel goats comprising 12 does and 2 bucks and 14 Yankasa ewes comprising of 12 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injection was given at 0.25mg/kg body weight. Blood samples were collected on biweekly basis from each animal through the jugular vein on the same day with minimal excitement prior to feeding. Samples collected were used for the analysis of total white blood cell counts (WBC) and differential leukocyte counts (DLC) (neutrophils, eosinophils, lymphocytes, monocytes and basophils). Dexamethasone significantly (P&lt;0.05) increased total WBC and neutrophil counts in both pregnant Yankasa ewes and Sahel does, but decreased lymphocyte counts in both species. The leukocytic responses of pregnant Yankasa ewes and Sahel does to dexamethasone treatment were similar to reports by other workers in non-pregnant subjects. It was concluded that both species were sensitive to lymphopenic effects of dexamethasone and that pregnancy did not increase the susceptibility of the dam to dexamethasone with regard to leukocytic parameters.Keywords: Dexamethasone, Leukocytosis, Pregnant, Sahel does, Yankasa ewes

Covering the Cover

Covering the Cover

Bone Density Status and Vitamin D and Calcium Concentrations in Pregnant and Non-Pregnant Women

Background: The aim of this study was to analyse differences in bone density and vitamin D and calcium concentrations between pregnant and non-pregnant women. Methods: This was an analytical, cross-sectional study of women aged 30 years or over, residing in the Puskesmas Bangkalan district. The sample population was chosen at random and included 10 pregnant women in their third trimester and 10 non-pregnant women. This observational study consisted of an interview, a blood test, and a 24-hour recall. The concentration of serum vitamin D (25(OH)D) was measured by Gas Chromatography and a Photometric Test measured the concentration of serum calcium. Participant's bone density was measured by bone ultra sonometer. The data was analysed using the Mann-Whitney test and assessed ultraviolet-B exposure, bone density values, and consumption of vitamin D, calcium, energy, and protein. The Student t -test was used to analyse serum vitamin D and calcium concentrations. Results: There were no differences between the groups' serum vitamin D concentrations ( p = 0.946). However, there were significant differences between the groups' serum calcium concentrations ( p = 0.047) and bone density values ( p = 0.019). Conclusion s : A high prevalence of vitamin D deficiency (25(OH)D < 50 nmol/L) and insufficiency (25(OH)D < 80 nmol/L) was observed in both groups. The mean serum calcium concentrations and bone density values were lower in pregnant subjects than non-pregnant subjects.

Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype

Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14(+) cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.

Changes in qualitative and quantitative ultrasound assessment of the gastric antrum before and after elective caesarean section in term pregnant women: a prospective cohort study.

Ultrasound measurement of the antral cross-sectional area allows a quantitative estimate of gastric contents in non-pregnant adults, but this relationship may be affected by compression of the stomach exerted by the gravid uterus during pregnancy. This study aimed to assess differences in quantitative (Perlas score) and qualitative (antral cross-sectional area) ultrasound assessments of the gastric antrum performed immediately before and after caesarean section. Forty-three women having elective caesarean section performed under spinal anaesthesia were studied in the semirecumbent and semirecumbent-right lateral positions. Thirty-nine women showed no change in stomach contents using the Perlas score between the two measurement periods; four women showed a change, but by one grade only. The median (IQR [range]) antral cross-sectional area was 323 (243-495 [103-908]) mm2 before, and 237 (165-377 [112-762]) mm2 after, caesarean section in the semirecumbent position (p = 0.001); the comparable values in the semirecumbent-right lateral position were 418 (310-640 [161-1238]) mm2 and 362 (280-491 [137-1231]) mm2 (p = 0.09). The distance between the skin and the antrum, and the aorta and the antrum, decreased significantly in both positions after surgery. We suggest that our results indicate that stomach contents remain largely unchanged in women having elective caesarean section, but antral cross-sectional area decreases, especially in the semirecumbent position, related to a change in the position of the stomach within the abdomen. This implies that the relationship of antral cross-sectional area to volume of stomach contents, which has been determined for non-pregnant subjects, may not apply in term pregnant women.

Serum Immunoglobulin Changes in Pregnancy Complicated with Pre-Eclampsia and Diabetes in Nigerian Women

Objectives: Serum concentrations of IgA, IgG and IgM were determined in subjects with pre-eclampsia and gestational diabetes as compared to both apparently healthy pregnant and non-pregnant subjects resident in Port Harcourt, Nigerian. Materials and methods: A total of 200 femalesubjects comprising four groups of 50 subjects each were recruited into the study: healthy non-pregnant subjects (Group A); healthy pregnant subjects (Group B); subjects with pre-eclampsia (Group C) and subjects with gestational diabetesmellitus (Group D). All pregnant subjects were further subdivided into the appropriate semester according to gestational age of pregnancy. Venousblood samples were obtained and determined for immunoglobulins A, G and M with theturbidimetric immunoassay method usingan automated chemical analyzer. Results: Significant differences were observed in the values of the various types of immunoglobulins studied between healthy HIV sero-negative non-pregnant (group A) subjects and healthy HIV sero-negative pregnant (group B) subjects. Noteworthy is the observation that the values of both IgG and IgM were significantly higher while the values of IgA were significantly lower amongst the non-pregnant subjects in group A, compared to all the other pregnant subject groups: B, C and D (p<0.05). Furthermore, group B subjects were found to have significantly higher values of IgG and lower levels of IgM compared to groups C and D subjects (p<0.05). Values of IgA were significantly higher (P<0.05) in all pregnant groups compared to the non-pregnant subjects but highest in the GDM (group D) women.During the course of gestation, a graded decrease in the mean values of all three immunoglobulin classes was observed in the healthy pregnant group from the 1 st to 3 rd trimester. However, whereas a graded increase in mean IgA and IgM were observed in group C subjects across trimesters, mean IgG showed a similar graded but significant decrease (P<0.05). Also, the mean IgG decreased significantly in the pregnant diabetic (D) group in the 2 nd trimester,but that of IgM significantly increased in the 2 nd trimester. Conclusion: The observed changes in immunoglobulins A, G and M levels may be indicative of poorly transferred secondary immunity in the children born to pregnant diabetic and pre-eclamptic women, as well as pose complications related to indirect immune responses in these conditions.

Urinary congophilia in women with hypertensive disorders of pregnancy and preexisting proteinuria or hypertension

Congophilia indicates the presence of amyloid protein, which is an aggregate of misfolded proteins, that is implicated in the pathophysiologic condition of preeclampsia. Recently, urinary congophilia has been proposed as a test for the diagnosis and prediction of preeclampsia. The purpose of this study was to determine whether urine congophilia is present in a cohort of women with preeclampsia and in pregnant and nonpregnant women with renal disease. With the use of a preeclampsia, chronic hypertension, renal disease, and systemic lupus erythematosus cohort, we analyzed urine samples from healthy pregnant control subjects (n= 31) and pregnant women with preeclampsia (n= 23), gestational hypertension (n= 10), chronic hypertension (n= 14), chronic kidney disease; n= 28), chronic kidney disease with superimposed preeclampsia (n= 5), and chronic hypertension and superimposed preeclampsia (n= 12). Samples from nonpregnant control subjects (n= 10) and nonpregnant women with either systemic lupus erythematosus with (n= 25) and without (n= 14) lupus nephritis were analyzed. For each sample, protein concentration was standardized before it was mixed with Congo Red, spotted to nitrocellulose membrane, and rinsed with methanol. The optical density of the residual Congo Red stain was determined; Congo red stain retention was calculated, and groups were compared with the use of the Mann-Whitney test or Kruskal-Wallis analysis of Variance test, as appropriate. Congophilia was increased in urine from women with preeclampsia (median Congo red stain retention, 47%; interquartile range, 22-68%) compared with healthy pregnant control subjects (Congo red stain retention: 16%; interquartile range, 13-21%; P= .002), women with gestational hypertension (Congo red stain retention, 20%; interquartile range, 13-27%; P= .008), or women with chronic hypertension (Congo red stain retention, 17%; interquartile range, 12-28%; P= .01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant control subjects (Congo red stain retention, 17% [interquartile range, 12-28%] vs 16% [interquartile range, 13-21%], respectively; P= .72). Congophilia was present in pregnant women with chronic kidney disease (Congo red stain retention, 32%; interquartile range, 14-57%), being similar to values found in women with preeclampsia (P= .22) and for women with chronic kidney disease and superimposed preeclampsia (Congo red stain retention, 57%; [interquartile range, 29-71%; P= .18). Nonpregnant women with lupus nephritis had higher congophilia levels compared with nonpregnant female control subjects (Congo red stain retention, 38% [interquartile range, 17-73%] vs 9% [7-11%], respectively; P < .001) and nonpregnant women with systemic lupus erythematosus without nephritis (Congo red stain retention, 38% [interquartile range, 17-73%] vs 13% [interquartile range, 11-17%], respectively; P= .001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations, 0.702; 95% confidence interval, 0.618-0.770; P < .001). This study confirms that women with preeclampsia and chronic kidney disease without preeclampsia have elevated urine congophilia levels compared with healthy pregnant women. Nonpregnant women with lupus nephritis also have elevated urine congophilia levels compared with healthy control subjects. An elevated Congo Red stain retention may not be able to differentiate between these conditions; further research is required to explore the use of congophilia in clinical practice.

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH).

Pregnancy and the postpartum period are associated with an increased risk of venous thromboembolism (VTE). Over the past decade, new diagnostic algorithms have been established, combining clinical probability, laboratory testing and imaging studies for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the non-pregnant population. However, there is no such generally accepted algorithm for the diagnosis of pregnancy-associated VTE. Studies establishing clinical prediction rules have excluded pregnant women, and prediction scores currently in use have not been prospectively validated in pregnancy or during the postpartum period. D-dimers physiologically increase throughout pregnancy and peak at delivery, so a negative D-dimer test result, based on the reference values of non-pregnant subjects, becomes unlikely in the second and third trimesters. Imaging studies therefore play a major role in confirming suspected DVT or PE in pregnant women. Major concerns have been raised against radiologic imaging because of foetal radiation exposure, and doubts about the diagnostic value of ultrasound techniques in attempting to exclude isolated iliac vein thrombosis grow stronger as pregnancy progresses. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarise evidence from the available literature and aim to establish a more uniform strategy for diagnosing pregnancy-associated VTE.

Relationship of Circulating C5a and Complement Factor H Levels With Disease Control in Pregnant Women With Asthma.

Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257-3.052) ng/mL versus 1.84 (IQR 1.576-2.563), 1.783 (IQR 0.6064-2.786), and 2.024 (IQR 1.232-2.615) ng/mL, respectively (P = .02 in all cases). C5a correlated negatively with FEV1 (r = -0.44, P = .039) and FVC values (r = -0.64, P = .001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the non-pregnant asthma group (n = 12, r = 0.78, P = .004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9-1,224] and 910.7 [IQR 614.5-1076] μg/mL vs. 559.7 [IQR 388.7-783.1] μg/mL, P = .002 and P = .004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6-947.6] μg/mL, P = .10). Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma).

Lipid-lysine adducts and modified tyrosines as markers of oxidative stress in the second trimester of pregnancy and their association with infant characteristics.

Pregnancy is a physiological state accompanied by excessive levels of oxidative stress (OS), due to the increased demand and utilisation of oxygen. There is increasing evidence that maternally augmented OS exerts an adverse effect on pregnancy outcome. The aim of the present prospective study was to determine the association between the urinary concentration of relatively novel OS markers measured in the second trimester of pregnancy and the infant characteristics at birth. The maternal levels of urinary hexanoyl-lysine (HEL), propanoyl-lysine (PRL), dityrosine (DiY) and 3-nitrotyrosine (NY) were evaluated in generally healthy pregnant subjects to determine their association with birth weight, gestation at delivery and Apgar score. The observed levels of the markers were in agreement with those measured in healthy non-pregnant subjects in a previous study. A positive correlation was detected between HEL and PRL, as well as between HEL and DiY. Although the absence of a correlation between NY and the other markers has been previously noted in a non-pregnant population, a positive correlation in the pair PRL-NY (r=0.367; P<0.001) was observed in the present study. Maternal cigarette smoking was associated with increased urinary PRL levels (P=0.034). The most notable observation in the present study was that high levels of PRL and NY were associated with low Apgar scores at 1 and 5 min after birth (OR, 1.098 and 2.084 for PRL and NY, respectively; P<0.05). However, poor predictive accuracy was shown. For NY, the following results were obtained: Area under the curve (AUC), 0.818; sensitivity, 100%; specificity, 57%; positive predictive value (PPV), 11.54%; and negative predictive value (NPV), 100%. For PLR the values were as follows: AUC, 0.802; sensitivity, 100%; specificity, 62.6%; PPV, 13.05%; and NPV, 100%. DiY was negatively associated with preterm birth risk (OR=0.703; P=0.028). In conclusion, the results of the present study indicated the presence of OS in the second trimester of pregnancy, which was detected with damage to lipids and proteins and associated with an adverse Apgar score; however, the selected urinary markers exhibited poor positive predictive efficacy.