Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia.

Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P  = 0.022, P  = 0.024, and P  = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P  = 0.024 and P  < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P  = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.

Prayer and meditation practices in the early COVID-19 pandemic: A nationwide survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

The safety of phthalate-containing medications used during pregnancy.

INTRODUCTION: Phthalates freely cross the placenta and have the potential to influence pregnancy outcomes, with evidence of an increased incidence of preterm birth, low birth weight, pregnancy loss, and gestational diabetes. There is no regulation of phthalate concentrations in medications, which is often found in enteric coatings. Ingestion of phthalate containing medication during pregnancy may result in materno-fetal harm. AREAS COVERED: Phthalate subtypes, sources of phthalate exposure, mechanisms of phthalate toxicity, associations between phthalate exposure and incidence of preterm birth, low birth weight, fetal growth, gestational diabetes, and placental development. EXPERT OPINION: There is robust evidence to link exposure to phthalates in medical products including preterm birth, gestational diabetes, pregnancy-induced hypertension, and miscarriage. Nevertheless, future studies need to address standardization to avoid the heterogeneity of current studies. In future, the use of naturally occurring biopolymers may be safer, and the role of vitamin D as an immune modulator also has promise.

Fibrinolytic Changes in Women with Preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a serious complication of pregnancy. The fibrinolytic system play crucial roles regarding placentation and evolution of PE. AIM: To study comprehensively components of the fibrinolytic system and fibrin lysability in women with PE. DESIGN AND METHODS: 117 women with PE and matched controls were included. Tissue type plasminogen activator (t-PA), plasminogen, PAI-1, plasmin inhibitor (PI), D-dimer, the fibrinolytic potential of dextran sulphate euglobulin fraction (DEF), PAI-2, polymere PAI-2, fibrin clot lysability, thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen were assessed. RESULTS: Women with PE had significantly increased concentrations of t-PA and PAI-1, whereas the plasma concentration of PAI-2 was significantly lower compared to controls, p < 0.0001. Polymere PAI-2 was detected in both groups. DEF, TAFI and fibrinogen were not different between the groups. D-dimer was significantly increased and plasminogen/PI together with fibrin clot lysability time decreased in the PE-group, p = 0.0004 p = 0.04, p = 0.03, p < 0.0001 respectively. CONCLUSION: This study demonstrates that PE is associated with an affected t-PA/PAI-1 system, decreased PAI-2 and increased fibrin lysability. Furthermore, PAI-2 has the potential to polymerize during pregnancy.

Depressed Kallikrein Generation in Women With Preeclampsia: A Matched Cross-Sectional Study.

Objective: The pathophysiology of preeclampsia is not fully understood. Disturbances in the contact system are associated with preeclampsia. Few studies have investigated the association between preeclampsia and alterations in the contact system in plasma. This study aims to elucidate whether this basic biological system is affected in preeclampsia using new methods focusing on the dynamic interactions and total capacity of the contact system in blood. Design: Cross-sectional study matching women with preeclampsia and controls without preeclampsia regarding age, pregestational body mass index, and gestational age at onset of the disease. Setting: Two Danish University hospitals. Sample: A cohort of 117 women with preeclampsia and 117 controls. Methods: The turnover and capacity of the contact system were determined with new methods. Paired t-test, Wilcoxon signed-pairs signed rank test, Mann-Whitney or Chi2-test were applied, as appropriate. Main Outcome Measurements: Kallikrein generation (peak kallikrein concentration and endogenous kallikrein potential), coagulation factor XII, prekallikrein, H-kininogen, cleaved H-kininogen, and complement C1 esterase inhibitor. Results: The endogenous kallikrein potential, peak kallikrein concentration, prekallikrein and cleaved H-kininogen were significantly lower in women with preeclampsia compared to the controls, p ≤ 0.005, whereas the concentration of coagulation factor XII, H-kininogen and complement C1 esterase inhibitor was not significantly different, p > 0.05. Conclusion: This study demonstrates significant reduction in kallikrein generating capacity, prekallikrein and cleaved H-kininogen indicating that the contact system is affected in preeclampsia suggesting a link to the pathophysiology of the disease.

The contribution of bacteriophages to the aetiology and treatment of the bacterial vaginosis syndrome.

Bacteriophages are obligate intracellular viruses that parasitize bacteria, making use of the host biosynthetic machinery. Bacterial vaginosis (BV) causes serious adverse sequelae, such as sexually transmitted infections, seroconversion to HIV positivity, and preterm birth. The aetiology of BV is multifactorial, and the vaginal microbiota, the response to antibiotics, and the phenotypic outcomes differ between cases. The choice of antibiotics to treat BV depends on the clinician's personal experience, which contributes to the poor outcome of BV treatment and high recurrence rate. In this review, we classify BV into two subtypes based on whether or not the BV case is sexually associated (potentially phage-related). An appropriate antibiotic can be selected on the basis of this BV-typing to optimise the short- and long-term effects of treatment. Not all Lactobacillus spp. are helpful or protective and some may sequestrate metronidazole, which mitigates its therapeutic efficacy. Phages, used therapeutically, could contribute to eubiosis by sparing beneficial species of Lactobacilli. However, Lactobacilli have an important role in maintaining vaginal eubiosis, so conventional wisdom has been that treatment of BV may benefit from metronidazole that conserves lactobacilli rather than clindamycin, which destroys lactobacilli. Furthermore, if the quality and quantity of vaginal lactobacilli are compromised by phage colonisation, as in the sexually transmitted subtype, eradication of lactobacilli with clindamycin followed by replacement by probiotics may be better therapeutically than metronidazole and reduce recurrence rates. Accordingly, the subtype of BV may provide a more scientific approach to antibiotic selection, which is absent in current clinical guidelines. We provide support for the role of bacteriophages in the aetiology, recurrence or failure to cure BV following treatment, through parasitic colonisation of lactobacilli that may be sexually transmitted and may be enhanced by other risk factors like smoking, a factor associated with BV.

Evaluation of'the Buddy Study', a peer support program for second victims in healthcare: a survey in two Danish hospital departments.

BACKGROUND: Healthcare professionals involved in adverse events may suffer severe physical and emotional distress in the aftermath. Adequate support is critical to an overall culture of safety for any healthcare institution. This study evaluates a formalised peer support program, 'the Buddy Study', in two Danish university hospital departments. The program consists of a 2-h seminar about second victims and self-selected buddies to provide peer support after adverse events. METHODS: The study design involved a cross-sectional survey comprised of two close-ended questionnaires evaluating the Buddy Study seminar (Q1) and the Buddy Study program (Q2), along with two open-ended questions and three individual interviews for more elaborate answers. RESULTS: Out of the 250 HCPs employed in both departments, 191 midwives, physicians, and nursing assistants completed Q1 and 156 completed Q2. The seminars were evaluated positively; 91.6% were satisfied with the overall content of the seminar, and 69.1% agreed that insight into how other people may react to adverse events has helped them contain their own reactions or emotions. Assessments of having the Buddy Study program in the department or using or being used as a buddy were more diverse, yet overall positive. Three benefits of the program were identified: the program i) has encouraged an open and compassionate culture; ii) has caused attentiveness to the wellbeing of colleagues; and iii) the self-selected buddy relationship has created a safe space for sharing. Additionally, three challenges or shortcomings were identified: i) although peer support is valuable, it should not stand alone; ii) informal peer support is already in place, hence making a formalised system redundant; and iii) the buddy system requires continuous maintenance and visibility. CONCLUSIONS: The overall evaluation of the Buddy Study program was positive, suggesting that this type of formalised peer support may contribute to a rapid and accessible second-victim support program in healthcare institutions. A key principle for the Buddy Study program is that relationships are crucial, and all buddy relationships are based on self-selection. This seems to offer a safe space for health care professionals to share emotional vulnerability and professional insecurity after an adverse event.

Public-health risks from tea drinking: Fluoride exposure.

AIMS: Due to new evidence on fluoride neurotoxicity during early life, this study examined maternal exposure to fluoride through tea consumption in a low-fluoride region and measured fluoride releases from commercially available teas (tea bags and loose teas) to determine the need to limit fluoride exposure. METHODS: Maternal urine fluoride (MUF) concentrations were measured in spot urine samples (N=118) from first-trimester pregnant women and in prepared tea infusions made with deionised water from 33 brand teas and 57 loose-tea products, as determined by the direct method of using a fluoride-selective electrode. RESULTS: The fluoride concentration in the local drinking water supplies ranged from 0.10 to 0.18 mg/L, and the creatinine-adjusted MUF ranged from 0.09 to 1.57 mg/L. Seventeen per cent of the women were daily tea drinkers, and their MUFs were higher than those with no consumption (p=0.002). The fluoride concentration from tea bags ranged from 0.34 to 2.67 mg/L, while loose teas showed 0.72-4.50 mg/L (black), 0.56-1.58 mg/L (oolong), 1.28-1.50 mg/L (green), and 0.33-1.17 mg/L (white tea). CONCLUSIONS: Fluoride exposure among pregnant women increases with tea consumption, with likely risks of developmental neurotoxicity to their children. As the fluoride release from tea varies widely, the fluoride concentration should be indicated on tea packages in order to allow consumers to make informed decisions on minimising their fluoride exposure.

Listeriosis in pregnancy: An umbrella review of maternal exposure, treatment and neonatal complications.

BACKGROUND: Listeria monocytogenes is a commonly found organism in processed and prepared food and the disease of listeriosis is associated with a high morbidity and mortality. Compared with the general population, the risk of being diagnosed with listeriosis increases during pregnancy. Listeriosis can lead to miscarriage, spontaneous preterm labour and preterm birth, stillbirth and congenital neonatal infections. OBJECTIVES: We conducted a universal review of listeriosis in pregnancy and in the newborn. SEARCH STRATEGY: The EMBASE, PubMed, Cinahl and Web of Science databases were searched for systematic reviews indexed before 1 December 2020. SELECTION CRITERIA: Any systematic reviews evaluating the prevalence, treatment, diagnosis and effects of listeriosis during pregnancy and up to 4 weeks postnatally were included. DATA COLLECTION AND ANALYSIS: Eligibility assessment, data extraction and quality assessment by the Methodological Quality Assessment of Systematic Reviews (AMSTAR-2) were performed in duplicate. MAIN RESULTS: We identified 397 citations of which nine systematic reviews comprising 330 studies and 487 patients' reviews were included. Most systematic reviews (seven of nine) were of moderate to high quality. Prevention in pregnant women was based on adherence to strict dietary recommendations, such as reheating leftovers until steamed and avoiding unpasteurised dairy products. Listeriosis infections were likely to occur in the third trimester (66%) rather than in the first trimester (3%) of pregnancy. Symptoms are mostly fever and other flu-like symptoms, such as fatigue. Diagnosis was primarily made by culture of the pathogen. Intravenous amoxicillin or ampicillin were first-line treatment. CONCLUSIONS: Listeriosis, a rare but serious infectious disease in pregnancy, can cause devastating consequences for the fetus and newborn. Appropriate preventative treatment should be initiated during early pregnancy to avoid complications. TWEETABLE ABSTRACT: Listeria is commonly found in processed and prepared food. Prevention is the best way to avoid listeriosis during pregnancy.

Concerns about transmission, changed services and place of birth in the early COVID-19 pandemic: a national survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The outbreak of the COVID-19 pandemic caused great uncertainty about causes, treatment and mortality of the new virus. Constant updates of recommendations and restrictions from national authorities may have caused great concern for pregnant women. Reports suggested an increased number of pregnant women choosing to give birth at home, some even unassisted ('freebirth') due to concerns of transmission in hospital or reduction in birthplace options. During April and May 2020, we aimed to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concern related to changes in maternity services due to the pandemic, and iii) implications for choice of place of birth. METHODS: We conducted a nationwide cross-sectional online survey study, inviting all registered pregnant women in Denmark (n = 30,009) in April and May 2020. RESULTS: The response rate was 60% (n = 17,995). Concerns of transmission during pregnancy and birth were considerable; 63% worried about getting severely ill whilst pregnant, and 55% worried that virus would be transmitted to their child. Thirtyeight percent worried about contracting the virus at the hospital. The most predominant concern related to changes in maternity services during the pandemic was restrictions on partners' attendance at birth (81%). Especially nulliparous women were concerned about whether cancelled antenatal classes or fewer physical midwifery consultations would affect their ability to give birth or care for their child postpartum.. The proportion of women who considered a home birth was equivalent to pre-pandemic home birth rates in Denmark (3%). During the temporary discontinue of public home birth services, 18% of this group considered a home birth assisted by a private midwife (n = 125), and 6% considered a home birth with no midwifery assistance at all (n = 41). CONCLUSION: Danish pregnant womens' concerns about virus transmission to the unborn child and worries about contracting the virus during hospital appointments were considerable during the early pandemic. Home birth rates may not be affected by the pandemic, but restrictions in home birth services may impose decisions to freebirth for a small proportion of the population.

[Treatment of incidentally found group B streptococcus in urine of pregnant women].

Group B streptococcus (GBS) is a group of naturally occurring bacteria that colonises the anogenital region of every third pregnant woman. From the anogenital region they can colonise the urine and cause bacteriuria. It is well documented that treatment of GBS-bacteriuria with more than 104 colony forming units per millilitre (CFU/ml) reduces the risk of maternal and neonatal morbidity. There is, however, no clear evidence as summarised in this review that GBS-bacteriuria more than 104 CFU/ml increases the risk of maternal and neonatal morbidity which is why no treatment is warranted.

Exposure to perfluoroalkyl substances and blood pressure in pregnancy among 1436 women from the Odense Child Cohort.

BACKGROUND: Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes. OBJECTIVES: To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia. METHODS: 1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC-MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model. RESULTS: All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: -0.13; 1.08) and 0.36 mmHg (-0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (-0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found. DISCUSSION: The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.

Blood Pressure and Angiogenic Markers in Pregnancy: Contributors to Pregnancy-Induced Hypertension and Offspring Cardiovascular Risk.

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P<0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P<0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted ß coefficients (95% CI) for predicting systolic blood pressure (SBP): -3.18 (-4.66 to -1.70) mm Hg, for predicting diastolic blood pressure (DBP): -2.48 (-3.57 to -1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

Blood pressure and hypertension during pregnancy in women with polycystic ovary syndrome: Odense Child Cohort.

INTRODUCTION: The aim of this study was to compare blood pressure and prevalence of pregnancy-induced hypertension in women with polycystic ovary syndrome and the reference group throughout pregnancy. MATERIAL AND METHODS: This retrospective study was part of the prospective study Odense Child Cohort. Pregnant women were recruited from January 2010 to December 2012. Blood pressure was measured in 200 women with polycystic ovary syndrome and in 2197 in the reference group. Main outcome measures were blood pressure and pregnancy-induced hypertension. Pregnancy-induced hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg occurring after gestational week 20 at two separate visits. Mann-Whitney U test and Chi-square test were used to test differences between women with polycystic ovary syndrome and the reference group. Associations between polycystic ovary syndrome status (PCOS; the reference group) and blood pressure were tested using random mixed-effect linear regression analyses with subjects as random effect to comply with repeated blood pressure measurements. RESULTS: Median blood pressure was comparable in women with polycystic ovary syndrome and the reference group throughout pregnancy: systolic blood pressure 116 (111-123) vs 119 (112-124) (P = .06), diastolic blood pressure 72 (69-77) vs 73 (69-78) (P = .23) and mean arterial pressure 87 (83-93) vs 88 (84-92) (P = .13). In first trimester where systolic blood pressure was lower in polycystic ovary syndrome, median systolic blood pressure was 116 (111-123) vs 119 (112-124) mmHg (P = .04). The prevalence of pregnancy-induced hypertension was similar in polycystic ovary syndrome and the reference group: 17/200 (8.5%) vs 178/1997 (8.9%) (P = .84). Regression analyses showed no significant associations between polycystic ovary syndrome and blood pressure. CONCLUSIONS: Blood pressure and prevalence of pregnancy-induced hypertension were comparable in pregnant women with polycystic ovary syndrome and the reference group.

Normal-range urinary albumin excretion associates with blood pressure and renal electrolyte handling in pregnancy.

Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na+ reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na+, K+, Cl-, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted ß coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na+, K+, and Cl-, with adjusted ß coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: -0.25 (-0.35 to -0.14), -5.06 (-6.81 to -3.30), and -0.28 (-0.41 to -0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.

Recent advances in cultivation-independent molecular-based techniques for the characterization of vaginal eubiosis and dysbiosis.

"The bacterial vaginosis syndrome" has significant adverse effects for women and babies, including preterm birth and increased risk of acquisition of sexually transmitted infections and HIV. Currently, the gold standard for diagnosis is Gram stain microscopy of vaginal secretions, which is not readily available, is somewhat subjective, and does not differentiate between the likely different subtypes of vaginal dysbioses that may have different etiologies, microbiology, responses to antibiotics, and phenotypic outcomes. With new information from molecular-based, cultivation-independent studies, there is increasing interest in the use of molecular techniques for the diagnosis of bacterial vaginosis. We reviewed the current evidence on and the rationale behind the use of molecular techniques for the diagnosis of bacterial vaginosis. We found a number of commercially available molecular diagnostic tests, a few of which have US Food and Drug Administration (FDA) and/or Conformité Européenne in vitro diagnostic (CE-IVD) approval, and we have compared their performance with respect to sensitivities and specificities. Molecular-based tests have the advantage of objectivity, quantification, detection of fastidious organisms, and validity for self-obtained vaginal swabs. The performance of the molecular tests against standard microscopy is impressive, but further education of users on interpretation is needed. Bacterial vaginosis is the major cause of vaginal dysbiosis and should be recognized for the threat it is to women's genital tract health. Quantitative assessment of microbial abundance, the diversity of other organisms present, specific primers for gene sequence regions, and clades and biovars of target microbes should be recognized and incorporated into future molecular diagnostic tests to better differentiate between vaginal eubiosis and dysbiosis.

Management and monitoring of opioid use in pregnancy.

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure.