Effect of COVID-19 on antenatal care: experiences of medical professionals in the Netherlands.

BACKGROUND: COVID-19 has greatly affected the delivery of all health care services globally. Antenatal care is one area of care that has been impacted, despite the fact that attending antenatal check-ups is essential for pregnant women and cannot be postponed. Little is known about how exactly ANC provision has changed in the Netherlands, or how the changes have impacted midwives and gynaecologists providing those services. METHODS: This study used a qualitative research design to investigate changes in individual and national practice following the onset of the COVID-19 pandemic. The study involved a document analysis of protocols and guidelines for ANC provision to evaluate how those changed following the onset of the COVID-19 pandemic and semi-structured interviews with ANC care providers (i.e., gynaecologists and midwives). RESULTS: Guidance was issued by multiple organizations, during the pandemic, on how to approach the risk of infection in pregnant women, recommending several changes to ANC to protect both pregnant women and ANC providers. Both midwives and gynaecologists reported changes in their practice. With less face-to-face consultations happening, digital technologies became critical in the care of pregnant women. Shorter and fewer visits were reported, with midwifery practices adjusting their guidelines further than hospitals. Challenges, with high workloads and lack of personal protective equipment were discussed. CONCLUSIONS: The COVID-19 pandemic has had an immense impact on the health care system. This impact has had both negative and positive effects on the provision of ANC in the Netherlands. It is important to learn from the current COVID-19 pandemic and adapt ANC, as well as health care systems as a whole, to be better prepared for future health crises and ensure continuous provision of good quality care.

COVID-19 has affected the delivery of healthcare services globally. Antenatal care is one of the healthcare services that has been impacted on a global scale. Little is known about how antenatal care provision has changed in the Netherlands during the pandemic period. Our project focuses on examining the effects of COVID-19 on existing antenatal care protocols, as well as the impacts on antenatal care providers, such as midwives and gynaecologists. This knowledge can be beneficial in adapting antenatal care provision in times of health emergencies, to be better prepared and more resilient. This research uses a qualitative approach to investigate changes in practice following COVID-19 pandemic. It involves 20 antenatal care providers, working in the Netherlands, which took part in semi-structured interviews, and 9 national protocols and guidelines which were analysed. This study indicates that antenatal care changed at different levels in the Netherlands. Many changes show that antenatal care is an essential service, which should not be cut back, but it should be implemented, to be prepared for a future health emergency.

Definition and Quantification of Three-Dimensional Imaging Targets to Phenotype Pre-Eclampsia Subtypes: An Exploratory Study.

Pre-eclampsia is a severe placenta-related complication of pregnancy with limited early diagnostic and therapeutic options. Aetiological knowledge is controversial, and there is no universal consensus on what constitutes the early and late phenotypes of pre-eclampsia. Phenotyping of native placental three-dimensional (3D) morphology offers a novel approach to improve our understanding of the structural placental abnormalities in pre-eclampsia. Healthy and pre-eclamptic placental tissues were imaged with multiphoton microscopy (MPM). Imaging based on inherent signal (collagen, and cytoplasm) and fluorescent staining (nuclei, and blood vessels) enabled the visualization of placental villous tissue with subcellular resolution. Images were analysed with a combination of open source (FIJI, VMTK, Stardist, MATLAB, DBSCAN), and commercially (MATLAB) available software. Trophoblast organization, 3D-villous tree structure, syncytial knots, fibrosis, and 3D-vascular networks were identified as quantifiable imaging targets. Preliminary data indicate increased syncytial knot density with characteristic elongated shape, higher occurrence of paddle-like villous sprouts, abnormal villous volume-to-surface ratio, and decreased vascular density in pre-eclampsia compared to control placentas. The preliminary data presented indicate the potential of quantifying 3D microscopic images for identifying different morphological features and phenotyping pre-eclampsia in placental villous tissue.

Optimizing the Comet Assay-Based In Vitro DNA Repair Assay for Placental Tissue: A Pilot Study with Pre-Eclamptic Patients.

The comet assay-based in vitro DNA repair assay has become a common tool for quantifying base excision repair (BER) activity in human lymphocytes or cultured cells. Here, we optimized the protocol for studying BER in human placental tissue because the placenta is a non-invasive tissue for biomonitoring of early-life exposures, and it can be used to investigate molecular mechanisms associated with prenatal disorders. The optimal protein concentration of placental protein extracts for optimal damage recognition and incision was 2 mg protein/mL. The addition of aphidicolin did not lead to reduced non-specific incisions and was, therefore, not included in the optimized protocol. The interval between sample collection and analysis did not affect BER activity up to 70 min. Finally, this optimized protocol was tested on pre-eclamptic (PE) placental tissues (n = 11) and significantly lower BER activity in PE placentas compared to controls (n = 9) was observed. This was paralleled by a significant reduction in the expression of BER-related genes and increased DNA oxidation in PE placentas. Our study indicates that BER activity can be determined in placentas, and lower activity is present in PE compared with healthy. These findings should be followed up in prospective clinical investigations to examine BER's role in the advancement of PE.

The association between decidual vasculopathy and abnormal uterine artery Doppler measurement.

INTRODUCTION: Placental syndrome is an umbrella term encompassing the clinical phenotypes of preeclampsia and fetal growth restriction, and is associated with high maternal and neonatal morbidity. In women with placental syndrome, histologicl examination of the uteroplacental unit commonly demonstrates pathological lesions, such as decidual vasculopathy. Decidual vasculopathy are pathological changes in the spiral arteries, which are associated with adverse outcome in preeclampsia and long-term maternal cardiovascular health. The relation between placental syndrome phenotypes and placental pathology has been previously demonstrated; however, the role of uteroplacental Doppler measurements as a link between placental syndrome phenotypes and the underlying placental pathology is still unclear. We hypothesized that decidual vasculopathy is associated with abnormal uteroplacental Doppler profiles and ultrasound placental parameters, independent of clinical phenotype. MATERIAL AND METHODS: We performed a retrospective analysis of data from a prospective cohort of pregnancies with placental syndrome, as well as cases without hypertensive disease or fetal growth restriction. The study group was divided into women with decidual vasculopathy on histologic analysis of placental specimen and those without the lesions. Outcome parameters included maternal and fetal Dopplers, estimated fetal weight, placental weight and thickness, placental lacunae and abnormal placental calcification. RESULTS: Compared with the women without the lesions (n = 91), the group with decidual vasculopathy (n = 25) had a higher mean uterine artery pulsatility index (1.70 vs 0.81, p < 0.001) and uterine artery pulsatility index percentile (>p99 vs p67, p < 0.001). Decidual vasculopathy was associated with abnormal uterine artery Doppler profile (defined as pulsatility index p > 95 and/or bilateral notch) (82%) compared with women without the lesions (33%) (odds ratio [OR] 9.3, 95% CI 2.4-36.0), which remained significant after adjusting for possible confounding factors preeclampsia, tobacco use and gestational age at birth (OR 7.1, 95% CI 1.3-39.1). Decidual vasculopathy was not associated with fetal Doppler abnormalities or placental parameters and only modestly so with lower cerebroplacental ratio (p = 0.036). CONCLUSIONS: Histologic decidual vasculopathy is associated with abnormal uterine artery Doppler, independent of clinical phenotype during pregnancy.

Preconceptional evaluation of women with recurrent pregnancy loss: the additional value of assessing vascular and metabolic status.

BACKGROUND: A majority of recurrent pregnancy loss cases (RPL) remains unexplained. We hypothesized that complications in vascular and metabolic status may guide towards underlying problems that also predispose to RPL and that the number of pregnancy losses is related. METHODS: A retrospective study in 123 women with either a history of low-order RPL (2-3 pregnancy losses) or high-order RPL (≥ 4 pregnancy losses) and 20 women with a history of uncomplicated pregnancy (controls) was performed. Vascular status was assessed by measuring hemodynamic parameters, determining abnormal parameters and analyzing their contribution to the circulatory risk profile (CRP). In a similar way, metabolic status was assessed. Metabolic parameters were measured, used to determine abnormal parameters and analyzed for their contribution to the metabolic syndrome (MetS). RESULTS: No major differences were observed in vascular or metabolic parameters between women with RPL and controls. There was no relation with the number of pregnancy losses. However, when analyzing the presence of abnormal constituents, more than 80% of women with RPL had at least one abnormal constituent of the CRP. While only 27% had one or more abnormal constituent of the MetS. CONCLUSIONS: The presence of abnormal circulatory factors prior to pregnancy, and to lesser extent constituents of the metabolic syndrome, may predispose to RPL and offer new insights to its pathophysiology.

Composition of the vaginal microbiota during pregnancy in women living in sub-Saharan Africa: a PRISMA-compliant review.

BACKGROUND: The vaginal microbiota (VMB) are the set of microorganisms residing in the human vagina. During pregnancy, their composition is Lactobacillus-dominant in most Caucasian women. Previous studies suggest that the VMB of women with African ancestry is more likely to be non-Lactobacillus dominant (dysbiotic) compared to other populations, and possibly relate to the high incidence of pregnancy complications, such as preterm birth. This work reviewed the literature on VMB composition in pregnant women from sub-Saharan Africa. METHODS: A search was conducted in PubMed and Embase databases following PRISMA guidelines. Observational and intervention studies analysing VMB communities from sub-Saharan African pregnant women using molecular techniques were included. RESULTS: Ten studies performed in seven sub-Saharan African countries were identified. They independently showed that Lactobacillus-dominant VMB (particularly L. iners or L. crispatus) or VMB containing Lactobacilli are the most prevalent, followed by a more diverse anaerobe-dominant VMB, in the studied populations. The majority of pregnant women with a sexually-transmitted infection had a Lactobacillus-dominant VMB, but with a significantly higher presence of anaerobic species. CONCLUSION: In agreement with studies performed in other populations, Lactobacillus species are the most prevalent VMB species during pregnancy in sub-Saharan African women. The frequency of diverse anaerobe-dominant VMB is high in these populations. In Africa, studies on VMB in pregnancy are scant, heterogeneous in methodology, and knowledge remains limited. More insights on VMB composition and their possible sequalae among these populations is needed.

Spiral artery blood flow during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed. METHODS: A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. RESULTS: In healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70-0.89) and 0.50 (95% CI: 0.47-0.54) in the first trimester to 0.50 (95% CI: 0.45-0.55, p < 0.001) and 0.39 (95% CI: 0.37-0.42, p < 0.001) in the second trimester and to 0.49 (95% CI: 0.44-0.53, p = 0.752) and 0.36 (95% CI: 0.35-0.38, p = 0.037) in the third trimester, respectively. In parallel, PSV altered from 0.22 m/s (95% CI: 0.13-0.30 m/s) to 0.28 m/s (95% CI: 0.17-0.40 m/s, p = 0.377) and to 0.25 m/s (95% CI: 0.20-0.30 m/s, p = 0.560) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.80, p < 0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p = 0.349). CONCLUSIONS: This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI was found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita.

Pathogenic variants in the X-linked gene ZC4H2, which encodes a zinc-finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo-/akinesia and/or (neurogenic) AMC.

Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.

Can Fetal Growth Velocity and First Trimester Maternal Biomarkers Improve the Prediction of Small-for-Gestational Age and Adverse Neonatal Outcome?

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the value of adding fetal growth velocity and first trimester maternal biomarkers to baseline screening, for the prediction of small-for-gestational age (SGA) and adverse neonatal outcomes. METHOD: A retrospective cohort study was conducted of singleton pregnancies in the Maastricht University Medical Centre between 2012 and 2016. The biomarkers PAPP-A, ß-hCG, PlGF, and sFlt-1 were measured at 11-13 weeks of gestational age (GA) and two fetal growth scans were performed (18-22 and 30-34 weeks of GA). Differences in biomarkers and growth velocities were compared between appropriate-for-gestational age (AGA; birth weight percentile 10-90) and SGA (birth weight percentile <10). Combinations of the biomarkers and fetal growth velocity were added to baseline screening for the prediction of SGA and adverse neonatal outcome. RESULTS: We included 296 singleton pregnancies. Compared to AGA (n = 251), SGA neonates (n = 45) had significantly lower growth velocities in the abdominal circumference (mm/week): 10.1 ± 0.98 versus 10.8 ± 0.98, p = 0.001. Compared with AGA, the SGA neonates had higher sFlt-1 multiples of the median (MoM): 0.89 (0.55) versus 0.76 (0.44), p = 0.023, and a higher sFlt-1/PlGF MoM ratio: 1.09 (1.03) versus 0.90 (0.64), p = 0.027. For a 15% false-positive rate, the prediction of SGA neonates increased from 44.8% for the baseline screening model to 56.5% after the addition of fetal growth velocities, and to 73.9% after the further addition of maternal biomarkers (PPV 9.6%, NPV 82.4%). The corresponding AUC for the three models were 0.722, 0.804, and 0.839, respectively. In addition, AGA neonates with reduced fetal growth velocity had more adverse neonatal outcomes compared to the AGA reference group (12.4 vs. 3.9%, p = 0.013). CONCLUSIONS: Combining fetal growth velocity with first trimester biomarkers resulted in a better prediction of SGA compared to baseline screening parameters alone. This approach could possibly result in reduced adverse neonatal outcomes in neonates, who are at a potential risk due to late mild placental dysfunction.

Circulating Fibronectin and Plasminogen Activator Inhibitor-2 Levels as Possible Predictors of Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIM: Placental syndromes (PS) are characterized by endothelial dysfunction complicating placental dysfunction. Possible markers for endothelial dysfunction and amount of trophoblast are fibronectin and plasminogen activator inhibitor-2 (PAI-2), respectively. We aimed (1) to determine whether in women with recurrent PS (rPS), this complication is preceded by deviating fibronectin- and PAI-2-levels, and (2) whether this is dependent on pre-pregnant plasma volume (PV). METHODS: In 36 former patients, we determined fibronectin- and PAI-2-levels in blood-samples collected preconceptionally and at 12-16 weeks in their next pregnancy. Differences were analyzed between pregnancies with rPS (n = 12) and without rPS (non-rPS, n = 24) using linear mixed models, with subanalyses based on pre-pregnant normal or subnormal PV. RESULTS: We observed higher fibronectin-levels at 12-16 weeks (p < 0.05 and p < 0.01, respectively) and lower PAI-2-levels at 16 weeks (p < 0.01) in the rPS subgroup, the intergroup differences being larger in women with subnormal PV. CONCLUSION: We showed that former PS patients who developed rPS have raised fibronectin- and reduced PAI-2-levels already in early/mid pregnancy. These deviations are even more prominent in women with subnormal pre-pregnant PV, supporting development of a 2-step screening program for former patients to identify the high-risk subgroup of women who may benefit from closer surveillance.

Maternal metabolic syndrome, preeclampsia, and small for gestational age infancy.

OBJECTIVE: We sought to explore to what extent the presence of cardiometabolic and cardiovascular risk constitutions differ between pregnancies complicated by small-for-gestational-age (SGA) infancy, preeclampsia (PE), or a combination of both. STUDY DESIGN: We conducted a cohort study in women after pregnancies complicated by placental syndrome with fetal manifestations (SGA infancy [n = 113]), maternal manifestations (PE [n = 729]), or both (n = 461). Independent sample t test was used to compare cardiometabolic and cardiovascular risk factors between groups. Logistic regression was used to calculate odds ratios and adjusted odds ratios of the prevalence of the metabolic syndrome and its constituents between groups. Adjustments were made for maternal age, parity, smoking, interval between delivery and measurements, and intrauterine fetal demise. RESULTS: The metabolic syndrome was present in 7.5% of women who delivered SGA infants, 15.6% of former PE women, and 19.8% of women after pregnancy complicated by both SGA and PE. Hypertension was observed in 25% of former PE women and 15% of women with solely SGA. Women who delivered a SGA infant had lower global vascular compliance compared to former PE women without SGA. CONCLUSION: Cardiometabolic risk factors consistent with metabolic syndrome relate to the maternal rather than to the fetal presentation of placental syndrome. Nonetheless, highest incidence of metabolic syndrome was observed in women with both PE and SGA. PE relates to chronic hypertension, whereas increased arterial stiffness seems to be associated with women who deliver a SGA infant.

Cardiovascular and thrombogenic risk of decidual vasculopathy in preeclampsia.

OBJECTIVE: Women with a history of preeclampsia (PE) have an increased prevalence of cardiometabolic, cardiovascular, and prothrombotic risk factors. Remotely, these women are at increased risk of developing cardiovascular and thrombotic disease. Decidual vasculopathy (DV) describes vascular lesions in the maternal spiral arteries of the uterus, which are found in approximately 40-60% of women with PE. DV is thought to be related to atherosclerosis because of their morphological similarity. The aim of this study was to investigate the association of cardiovascular and thrombogenic risk factors with DV in women with a history of PE. STUDY DESIGN: We retrospectively analyzed the cardiovascular and thrombogenic risk of women with a history of PE, comparing cases with DV (n = 95) with cases without the lesions (n = 81) 7 months after the index pregnancy. Data from a cohort of patients with a history of PE were matched with records from our pathology database. RESULTS: The DV group showed higher diastolic blood pressure (73 vs 70 mm Hg, P = .031), lower left ventricular stroke volume (71 vs 76 mL, P = .032), higher total peripheral vascular resistance (1546 vs 1385, P = .009), and a higher percentage of low plasma volume (34% vs 19%, P = .030). DV did not relate to other cardiovascular parameters, urinary protein, body mass index, lipid or glucose metabolism parameters, or thrombophilia. CONCLUSION: In this study, in women with a history of PE, cases with DV had increased cardiovascular risk, exhibiting circulatory alterations, suggesting reduced venous reserves and elevated arterial tone, without metabolic or thrombophilic disturbances.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial).

BACKGROUND: Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. METHODS/DESIGN: Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. INTERVENTION: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, ß-error 0.2 and α-error 0.05). DISCUSSION: This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. TRIAL REGISTRATION: NTR3492 Dutch Trial Register (http://www.trialregister.nl).

The association between non-viral sexually transmitted infections and pregnancy outcome in Latin America and the Caribbean: A systematic review.

Introduction: Non-viral sexually transmitted infections are known to be associated with adverse pregnancy outcomes. For these pathogens, standard antenatal screening is not broadly performed in Latin America and the Caribbean. The aim of this study was to comprehensively review the association of non-viral sexually transmitted infections and neonatal outcomes among pregnant women in the region. Methods: Four databases (PubMed, Embase, SciELO and LILACS) were examined to identify eligible studies published up to September 2022. English or Spanish cross-sectional, case-control and cohort studies assessing the association of non-viral sexually transmitted infections and adverse pregnancy outcomes were evaluated. Articles were firstly screened by means of title and abstract. Potential articles were fully read and assessed for inclusion according to the eligibility criteria. Snowballing search was performed by screening of bibliographies of the chosen potentially relevant papers. Risk of bias within studies was assessed using the Joanna Briggs Institute reviewer's manual. Results: A selection of 10 out of 9772 search records from five Latin America and the Caribbean countries were included. Six studies associated Treponema pallidum infection with preterm birth (1/6), history of previous spontaneous abortion (2/6), fetal and infant death (1/6), low birth weight (1/6) and funisitis of the umbilical cord (1/6). Three studies associated Chlamydia trachomatis infection with preterm birth (2/3), ectopic pregnancy (1/3) and respiratory symptoms on the newborn (1/3). One study associated Mycoplasma genitalium infection with preterm birth. Conclusion: This review provides evidence on the association of non-viral sexually transmitted infections with adverse pregnancy outcomes. Further investigation is needed to establish more associations between non-viral sexually transmitted infections and pregnancy outcome, especially for Mycoplasma genitalium, Trichomonas vaginalis and Neisseria gonorrhoeae. Overall, this review calls for more research for public health interventions to promote screening of non-viral sexually transmitted infections during pregnancy, among high-risk population groups of pregnant women living in the region.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (-12%) and hypoxia-exposed placentas (-16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (-26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia.

Study protocol for two randomised controlled trials evaluating the effects of Cerclage in the reduction of extreme preterm birth and perinatal mortality in twin pregnancies with a short cervix or dilatation: the TWIN Cerclage studies.

INTRODUCTION: Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage. METHODS AND ANALYSIS: We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05968794.

Antibiotic Use in Pregnancy: A Global Survey on Antibiotic Prescription Practices in Antenatal Care.

Antibiotic prescription and use practices in the antenatal care setting varies across countries and populations and has the potential to significantly contribute to the global spread of antibiotic resistance. This study aims to explore how healthcare practitioners make decisions about antibiotic prescriptions for pregnant women and what factors play a role in this process. A cross-sectional exploratory survey consisting of 23 questions, including 4 free-text and 19 multiple-choice questions, was distributed online. Quantitative data were collected through multiple-choice questions and was used to identify the most common infections diagnosed and the type of antibiotics prescribed. Qualitative data were gathered through free-text answers to identify gaps, challenges, and suggestions, and the data were analyzed using thematic analysis. A total of 137 complete surveys mostly from gynecologists/obstetricians from 22 different countries were included in the analysis. Overall, national and international clinical guidelines and hospital guidelines/protocols were the most frequently used sources of information. This study highlights the crucial role of laboratory results and guidelines at different levels and emphasizes region-specific challenges and recommendations. These findings underscore the pressing need for tailored interventions to support antibiotic prescribers in their decision-making practice and to address emerging resistance.