Guideline No. 439: Diagnosis and Management of Vasa Previa

ObjectiveTo summarize the current evidence and to make recommendations for diagnosis and classification of vasa previa and for management of women with this diagnosis.Target populationPregnant women with vasa previa or low-lying fetal vessels.OptionsTo manage vasa previa in hospital or at home, and to perform a cesarean delivery preterm or at term, or to allow a trial of labour when a diagnosis of vasa previa or low-lying fetal vessels is suspected or confirmed.OutcomesProlonged hospitalization, preterm birth, rate of cesarean delivery, and neonatal morbidity and mortality.Benefits, harms, and costsWomen with vasa previa or low-lying fetal vessels are at an increased risk of maternal and fetal or postnatal adverse outcomes. These outcomes include a potentially incorrect diagnosis, need for hospitalization, unnecessary restriction of activities, an early delivery, and an unnecessary cesarean delivery. Optimization of diagnostic and management protocols can improve maternal and fetal or postnatal outcomes.EvidenceMedline, Pubmed, Embase, and the Cochrane Library were searched from inception to March 2022, using medical subject headings (MeSH) and keywords related to pregnancy, vasa previa, low-lying fetal vessels, antepartum hemorrhage, short cervix, preterm labour, and cesarean delivery. This document presents an abstraction of the evidence rather than a methodological review.Validation methodsThe authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).Intended audienceObstetric care providers, including obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, and radiologists.Tweetable AbstractUnprotected fetal vessels in placental membranes and cord that are close to the cervix, including vasa previa, need careful characterization by sonographic examination and evidence-based management to reduce risks to the baby and the mother during pregnancy and delivery.SUMMARY STATEMENTS

• 1.A marginal sinus or a loop of cord above the cervix are frequent causes of an incorrect diagnosis of vasa previa (low).
• 2.Depending on gestational age when vasa previa or low-lying fetal vessels are diagnosed, these conditions will resolve closer to the time of delivery in a large proportion of women (moderate).
• 3.Most women with vasa previa have an associated risk factor (moderate).
• 4.Depending on individual patient factors, vasa previa can be safely managed on an outpatient basis in many women (moderate).
• 5.Bed rest or reduced activity does not improve outcomes in women with vasa previa and can be harmful. However, sexual intercourse/insertion of foreign bodies in vagina or rectum have potential for harm, particularly in the third trimester (low).

RECOMMENDATIONS

• 1.The physician interpreting an obstetric sonographic examination should classify fetal vessels <2 cm from the cervical os as vasa previa (strong, moderate).
• 2.The physician interpreting an obstetric sonographic examination should classify vessels between 2 and 5 cm from the cervical os as low-lying fetal vessels (conditional, low).
• 3.The obstetric sonographic provider should use transvaginal sonography with colour mapping and pulsed-wave Doppler to diagnose vasa previa or other related variants (strong, moderate).
• 4.When a diagnosis of vasa previa or low-lying fetal vessels is made remote from delivery, the obstetric care provider should confirm the diagnosis closer to the time of delivery (strong, moderate).
• 5.The obstetric sonographic provider should assess the placental cord insertion site in all women at the routine second trimester fetal anatomical scan (conditional, moderate).
• 6.The physician interpreting an obstetric sonographic examination should not diagnose an abnormality of placental morphology, location, placental cord insertion, or vasa previa before the routine second trimester obstetrical sonographic scan (conditional, moderate).
• 7.The obstetric sonographic provider should perform targeted screening for vasa previa in all women with a risk factor (strong, moderate).
• 8.The obstetric care provider should consider hospitalization in women with vasa previa at 32 weeks of gestation, and in women with additional risk factors for early delivery, such as multiple gestation or a short cervix, before 32 weeks (conditional, moderate).
• 9.In women with vasa previa and a singleton pregnancy, the obstetric care provider should perform a cesarean delivery at 35⁰ to 35⁶ weeks. They should consider an earlier delivery if there are additional risk factors for preterm delivery (strong, moderate).
• 10.In women with vasa previa and a twin pregnancy, the obstetric care provider should consider a cesarean delivery at 33⁰ to 34⁶ weeks for dichorionic twins and at 32⁰ to 33⁶ weeks for monochorionic twins. They should consider an earlier delivery if there are additional risk factors for preterm delivery, such as higher-order multiple pregnancy or a short cervix (conditional, low).
• 11.In women with low-lying fetal vessels, the obstetric care provider should consider a cesarean delivery at 37⁰ to 38⁶ weeks for a singleton pregnancy and at 36⁰ to 37⁶ weeks for dichorionic twins (conditional, low).
• 12.In women with vasa previa, the obstetric care provider should consider timely access to an operating room, an obstetrician, an anesthetist, and an appropriate neonatal intensive care unit when deciding location of admission for observation or delivery (conditional, low).

     

Guideline No. 441: Antenatal Fetal Health Surveillance

ObjectiveTo summarize the current evidence and to make recommendations for antenatal fetal health surveillance (FHS) to detect perinatal risk factors and potential fetal decompensation in the antenatal period and to allow for timely intervention to prevent perinatal morbidity and/or mortality.Target populationPregnant individuals with or without maternal, fetal, or pregnancy-associated perinatal risk factors for antenatal fetal decompensation.OptionsTo use basic and/or advanced antenatal testing modalities, based on risk factors for potential fetal decompensation.OutcomesEarly identification of potential fetal decompensation allows for interventions that may support fetal adaptation to maintain well-being or expedite delivery.Benefits, harms, and costsAntenatal FHS in pregnant individuals with identified perinatal risk factors may reduce the chance of adverse outcomes. Given the high false-positive rate, FHS may increase unnecessary interventions, which may result in harm, including parental anxiety, premature or operative birth, and increased use of health care resources. Optimization of surveillance protocols based on evidence-informed practice may improve perinatal outcomes and reduce harm.EvidenceMedline, PubMed, Embase, and the Cochrane Library were searched from inception to January 2022, using medical subject headings (MeSH) and key words related to pregnancy, fetal monitoring, fetal movement, stillbirth, pregnancy complications, and fetal sonography. This document represents an abstraction of the evidence rather than a methodological review.Validation methodsThe authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).Intended audienceAll health care team members who provide care for or education to obstetrical patients, including maternal fetal medicine specialists, obstetricians, family physicians, midwives, nurses, nurse practitioners, and radiologists.SUMMARY STATEMENTS

• 1.Accurate and ongoing early identification of risk factors for potential fetal decompensation allows care providers to develop an individualized care plan to optimize fetal well-being (moderate).
• 2.The nonstress test (NST) may be used in conjunction with a review of the total clinical picture to assess fetal well-being. An NST should be used only in the presence of a clear indication or finding associated with increased risk of fetal hypoxemia (moderate).
• 3.Sonography can evaluate amniotic fluid, estimated fetal weight, biophysical profile/modified biophysical profile, and Doppler blood flows to provide information regarding fetal well-being in pregnancies at risk of fetal morbidity (moderate).
• 4.Interprofessional team communication and documentation should be clear, using accepted and defined terminology (high).

RECOMMENDATIONS

• 1.Care providers should review and document perinatal risk factors (prior pregnancy, fetal, maternal, familial) at the initial visit and update factors throughout pregnancy (strong, moderate).
• 2.Pregnant individuals should be advised of local resources and/or the need for transfer of care based on pregnancy risk factors (strong, moderate).
• 3.Regular prenatal visits should include assessment and documentation of the presence of fetal heart tones, uterine size, pregnancy concerns or risk factors, the plan of care, and the discussion with the pregnant individual (strong, moderate).
• 4.All pregnant individuals should be advised to regularly monitor fetal movements starting at 26 weeks gestation (conditional, low).
• 5.If a reduction of fetal movements is identified, regardless of the technique used to assess fetal movements, pregnant individuals should be advised to present to their care provider or local obstetrical unit immediately for further evaluation (strong, low).
• 6.The nonstress test (NST) should be administered and interpreted by appropriately trained health professionals (strong, high).
• 7.A ≥2 cm × 1 cm pocket of fluid by transabdominal sonography should be used as the criterion for the amniotic fluid component of the biophysical profile (strong, moderate).
• 8.To ensure patient safety, care providers should develop clear protocols locally to communicate and document changes in fetal status identified during antenatal fetal surveillance and escalation of care (strong, moderate).
• 9.Care providers should use non-routine antenatal fetal health surveillance modalities, such as an NST, biophysical profile, or fetal Doppler sonography, only in the presence of a clear indication or finding associated with increased risk of fetal hypoxemia (strong, moderate).

     

Guideline No. 440: Management of Monochorionic Twin Pregnancies

ObjectiveThis guideline reviews the evidence-based management of normal and complicated monochorionic twin pregnancies.Target PopulationWomen with monochorionic twin or higher order multiple pregnancies.Benefits, Harms, and CostsImplementation of these recommendations should improve the management of both complicated and uncomplicated monochorionic (and higher order multiple) twin pregnancies. They will help users monitor monochorionic twin pregnancies appropriately and identify and manage monochorionic twin complications optimally in a timely manner, thereby reducing perinatal morbidity and mortality.These recommendations entail more frequent ultrasound monitoring of monochorionic twins compared to dichorionic twins.EvidencePublished literature was retrieved through searches of PubMed and the Cochrane Library using appropriate MeSH headings (Twins, Monozygotic; Ultrasonography, Prenatal; Placenta; Fetofetal Transfusion; Fetal Death; Fetal Growth Retardation). Results were restricted to systematic reviews, randomized controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials.Validation MethodsThe content and recommendations were drafted and agreed upon by the principal authors. The Board of the SOGC approved the final draft for publication. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).Intended AudienceMaternal-fetal medicine specialists, obstetricians, radiologists, sonographers, family physicians, nurses, midwives, residents, and other health care providers who care for women with monochorionic twin or higher order multiple pregnancies.Tweetable AbstractCanadian (SOGC) guidelines for the diagnosis, ultrasound surveillance and management of monochorionic twin pregnancy complications, including TTTS, TAPS, sFGR (sIUGR), acardiac (TRAP), monoamniotic twins and intrauterine death of one MC twin.SUMMARY STATEMENTS

• 1.Morbidity and mortality in twin pregnancies are most commonly related to: (1) chorionicity, (2) prematurity, (3) fetal growth restriction, and (4) congenital anomalies (high).
• 2.Virtually all monochorionic placentas have vascular anastomoses between the two placental cord insertions (high).
• 3.Besides prematurity and growth discordance, the vast majority of twin complications arise in monochorionic twin pregnancies (high).
• 4.Twin–twin transfusion syndrome affects approximately 10%–15% of monochorionic twin pregnancies (high).
• 5.The diagnosis of twin–twin transfusion syndrome is based on ultrasound findings of significant discordance in both amniotic fluid volume and bladder size (high). Cardiac dysfunction in the recipient twin or growth discordance often co-exist, but are not essential criteria for the diagnosis (high).
• 6.Fetoscopic laser ablation of the placental vascular anastomoses is the best treatment for twin-twin transfusion syndrome presenting before 28-30 weeks gestation, rather than amnioreduction or septostomy (high).
• 7.The Solomon laser technique decreases the risk of twin–twin transfusion syndrome recurrence and twin anaemia-polycythaemia sequence (high).
• 8.Twin anaemia-polycythaemia sequence occurs spontaneously in 4%–5% of monochorionic twin pregnancies (moderate). It typically develops later in pregnancy than twin–twin transfusion syndrome (usually >24–26 weeks gestation) (moderate). Twin anaemia-polycythaemia sequence may co-exist with twin–twin transfusion syndrome and has been reported in up to 13% of cases of TTTS in which the fetoscopic laser ablation procedure was incomplete (high).
• 9.Ultrasound features of twin anaemia-polycythaemia sequence are increasingly discordant middle cerebral artery peak systolic velocities, suggestive of anaemia in one fetus and polycythaemia in the other, often without significant amniotic fluid discordance (high). Other signs may include differential placental echogenicities and a “starry sky” liver in the recipient twin (moderate).
• 10.Selective fetal growth restriction in monochorionic twin pregnancies has been defined as an estimated fetal weight (EFW) of one twin below the 3^rd percentile, or at least 2 of the following four variables: (1) EFW <10^th percentile, (2) abdominal circumference <10^th percentile, (3) EFW discordance ≥25%, or (4) umbilical artery pulsatility index of the smaller twin >95^th percentile (high).
• 11.In monochorionic twins, estimated fetal weight discordance >25% and abnormal umbilical artery Doppler waveforms are independent risk factors for an adverse perinatal outcome. (high).
• 12.The ultrasonographic features of twin reversed arterial sequence are an amorphous, usually edematous, acardiac twin, which is retrogradely perfused via a placental artery-to-artery anastomosis by its healthy “pump” co-twin (high).
• 13.A large acardiac twin (e.g., an acardiac:“pump” twin abdominal circumference ratio ≥50%) may put its “pump” co-twin at risk of high-output cardiac failure (high). The overall risk of intrauterine death of the “pump” twin is approximately 30% before 18 weeks gestation (high).
• 14.If one of a monochorionic twin pair dies, the surviving co-twin may be at risk of neurological morbidity and intrauterine death (high). Imaging may not detect changes in the co-twin’s brain for several weeks after the death of its sibling (moderate).
• 15.Ultrasound features of monoamniotic twins include the absence of a dividing amniotic membrane, a single placenta, close proximity of placental cord roots, concordant sex and, commonly, cord entanglement (high).
• 16.Only 2%–4% of monoamniotic twins will develop twin–twin transfusion syndrome (high).
• 17.Structural anomalies, particularly cardiac, are more common in monochorionic twins than in dichorionic twins or singletons (high).
• 18.Conjoined twins are extremely rare and the organs/structures that are shared will determine the potential for surgical intervention and survival (high).

RECOMMENDATIONS

• 1.In spontaneously conceived pregnancies, we recommend using the larger of the two crown–rump lengths to estimate gestational age (conditional, moderate).
• 2.Viability, gestational age, chorionicity and amnionicity should be assessed between 11⁰ and 13⁶ weeks gestation in all multiple pregnancies (strong, high).
• 3.If chorionicity cannot be confidently established sonographically, pregnancies should be monitored as if they were monochorionic (conditional, moderate).
• 4.Twins should be labelled on antenatal ultrasound according to their lateral (right/left) or vertical (top/bottom) orientation, rather than their proximity to the cervix, and, ideally, that labelling should be maintained across all subsequent ultrasound examinations (strong, moderate).
• 5.A detailed anatomy scan should be performed at approximately 18–20 weeks gestation for all monochorionic twins (strong, high). Where the expertise is available, an early anatomy ultrasound can be performed at 12–14 weeks gestation (conditional, moderate).
• 6.In all twin pregnancies, cervical length should be assessed, either transabdominally or transvaginally, at the time of the anatomical ultrasound scan and, ideally, once more at around 23–24 weeks gestation (strong, moderate).
• 7.All monochorionic pregnancies should undergo ultrasound surveillance every 2 weeks from 16 weeks gestation until delivery to detect twin–twin transfusion syndrome, twin anaemia-polycythaemia sequence and selective fetal growth restriction (strong, high).
• 8.Ultrasound assessment of all monochorionic twins from 16 weeks onwards should include measurement of growth (fetal biometry), fetal bladder filling, and the single deepest pocket of amniotic fluid on both sides of the membrane, as well as umbilical and middle cerebral artery peak systolic velocity Doppler studies for each fetus (strong, high).
• 9.Monochorionic twins without complications should be delivered between 36 and 37 weeks gestation. Unless there are other obstetric contraindications, vaginal delivery is appropriate (strong, high).
• 10.If twin–twin transfusion syndrome or significant selective fetal growth restriction is suspected, the ductus venosus should be assessed (strong, high). Cardiac structure and function should be assessed in the recipient twin whenever twin–twin transfusion syndrome is suspected (strong, high).
• 11.For cases of twin–twin transfusion syndrome, urgent consultation with or referral to one of the fetal therapy laser centres in Canada is recommended, as fetoscopic laser ablation of placental vascular anastomoses is the best therapy for twin–twin transfusion syndrome (strong, high).
• 12.Ultrasonography should be performed weekly for 4 weeks after fetoscopic placental laser and then every 2 weeks following clinical resolution, with ongoing antenatal care shared or co-ordinated with the regional maternal–fetal medicine centre (strong, high). Assessment should include amniotic fluid volume in both sacs, bladder sizes, Doppler waveforms (middle cerebral artery peak systolic velocity, umbilical artery pulsatility index and ductus venosus), and intra-cranial anatomies, as well as measurement of cervical length and documentation of any chorio-amnion separation (strong, high).
• 13.Fetal intracranial anatomy should be carefully re-evaluated after an interval of at least 4 weeks following a laser procedure (strong, moderate).
• 14.Whenever monochorionic twin complications are encountered, including twin anaemia-polycythaemia sequence, selective fetal growth restriction, twin reversed arterial perfusion sequence, monoamnioticity, discordance for an anomaly, or a single intrauterine death, referral to, or at least consultation with, the regional maternal–fetal medicine program or fetal therapy centre is recommended (strong, high), so that all management options can be explored. The optimal management of twin anaemia-polycythaemia sequence has yet to be determined. (conditional, moderate).
• 15.When selective fetal growth restriction is suspected, fetal surveillance should be intensified and the pregnancy managed by referral to, or at very least with input from, a regional maternal–fetal medicine centre with expertise in this condition (strong, moderate).
• 16.In selective fetal growth restriction, timing of delivery should take into account gestational age, evidence of haemodynamic compromise as assessed by umbilical and middle cerebral artery and ductus venosus Doppler studies, and biophysical wellbeing (strong, moderate).
• 17.Whenever the death of one monochorionic twin is diagnosed early in pregnancy, colour Doppler ultrasonography should be used to exclude twin reversed arterial perfusion sequence, by confirming the absence of blood flow in the suspected demised twin (strong, high).
• 18.In twin reversed arterial perfusion sequence, especially with a large acardiac twin, occlusion of the circulation to the acardiac twin, either by laser, radio frequency ablation of the intra-fetal vessels or bipolar cautery should be considered (conditional, moderate).
• 19.After the spontaneous death of one monochorionic twin, surveillance for fetal anaemia by middle cerebral artery peak systolic velocity measurement should be instituted rapidly, as anaemia correlates with the risk of a hypotensive neurological injury (strong, high). The surviving twin may benefit from intrauterine transfusion (conditional, moderate). Fetal neurosonography and, ideally, MRI should be used to identify any potential cerebral injury; however, ultrasonographic evidence of injury may take 3-4 weeks to develop after the death of the co-twin (strong, high).
• 20.Care should be taken not to misdiagnose monochorionic-diamniotic pregnancies as monoamniotic, when one twin has anhydramnios (e.g., the donor in twin–twin transfusion syndrome) (conditional, moderate).
• 21.Monoamniotic twins are at high risk of cardiac abnormalities and should undergo a detailed anatomical ultrasound with particular emphasis on fetal cardiac evaluation (strong, high).
• 22.Monoamniotic twins should be monitored closely from viability onwards (either as out-patients or in-patients) and should undergo an elective caesarean delivery at approximately 33 weeks gestation (conditional, moderate).
• 23.Aneuploidy screening can be offered in monochorionic pregnancies as either combined prenatal serum screening (i.e., first-trimester screening or integrated prenatal screening, as available provincially) or cell-free fetal DNA analysis of maternal blood (conditional, moderate).
• 24.Invasive prenatal testing (chorionic villus sampling or amniocentesis) should be offered in the presence of a structural anomaly or abnormal genetic screening (strong, high). Amniocentesis from both sacs should be considered for discordant anomalies because of the rare possibility of heterokaryotypic anomalies in monochorionic twins (strong, high).
• 25.If indicated for discordance for an anomaly, selective termination of pregnancy in monochorionic twins must always be performed by a vascular occlusion method and never by intravascular fetal injection (strong, high).

     

Induction of labour in patients with prior caesarean births or uterine surgery

The current evidence favours trial of labour after one caesarean in the absence of any other contraindications, recognizing that risks with both trial of labour after caesarean (TOLAC) and elective repeat caesarean section (ERCS) birth are relatively uncommon. When the need for induction of labour (IOL) following a previous caesarean arises, shared decision-making should be based on the current available evidence. This approach, however, needs to be tailored, taking into account the individual's history, initial examination and response to the ongoing process of induction to optimize the maternal and foetal outcomes. This paper aims to review the evidence and provide guidance on decision making surrounding labour induction in a pregnancy following a prior caesarean or uterine surgery.     

No. 381-Assisted Vaginal Birth

ObjectivesTo provide evidence-based guidelines for safe and effective assisted vaginal birth.OutcomesPrerequisites, indications, contraindications, along with maternal and neonatal morbidity associated with assisted vaginal birth.EvidenceMedline database was searched for articles published from January 1, 1985, to February 28, 2018 using the key words “assisted vaginal birth,” “instrumental vaginal birth,” “operative vaginal delivery,” “forceps delivery,” “vacuum delivery,” “ventouse delivery.” The quality of evidence is described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on Preventive Health Care.ValidationThese guidelines were approved by the Clinical Practice Obstetrics Committee and the Board of the Society of Obstetricians and Gynaecologists of Canada.Recommendations

• 1The need for assisted vaginal birth can be reduced by: dedicated and continuous support during labour (I-A), oxytocin augmentation of inadequate labour (I-A), delayed pushing in women with an epidural (I-A), increased time pushing in nulliparous women with an epidural (I-B), as well as optimization of fetal head position through manual rotation (I-A).
• 2Encouraging safe and effective assisted vaginal birth by experienced and skilled care providers may be a useful strategy to reduce the rate of primary Caesarean delivery (II-2B).
• 3Safe and effective assisted vaginal birth requires expertise in the chosen method, comprehensive assessment of the clinical situation alongside clear communication with the patient, support people, and health care personnel (III-B).
• 4Practitioners performing assisted vaginal birth should have the knowledge, skills, and experience necessary to assess the clinical situation, use the selected instrument, and manage complications that may arise from assisted vaginal birth (II-2B).
• 5Obstetrical trainees should receive comprehensive training in assisted vaginal birth and be deemed competent prior to independent practice (III-B).
• 6When assisted vaginal birth is deemed to have a higher risk of not being successful, it should be considered a trial of assisted vaginal birth and be conducted in a location where immediate recourse to Caesarean delivery is available (III-B).
• 7The physician should determine the instrument most suitable to the clinical circumstances and their level of skill. Vacuum and forceps are associated with different short- and long-term benefits and risks. Unsuccessful delivery is more likely with vacuum than forceps (I-A).
• 8Planned sequential use of instruments is not recommended as it may be associated with an increased risk of perinatal trauma. If an attempted vacuum is unsuccessful, the physician should consider the risks of proceeding to an attempted forceps delivery versus Caesarean section (II-2B).
• 9Restrictive use of mediolateral episiotomy is supported in assisted vaginal birth (II-2B).
• 10A debrief should be done with the patient and support people immediately following an attempted or successful assisted vaginal birth. If this is not possible, ideally this should be done prior to hospital discharge and include the indication for assisted vaginal birth, management of any complications, and the prognosis for future deliveries (III-B).
• 11In a subsequent pregnancy, patients should be encouraged to consider spontaneous vaginal birth. However, care planning should be individualized and patient preference respected (II-3B).

     

Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1

IntroductionStatins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.MethodsAt E14.5, untreated pregnant wild-type (WT, n=13–18), untreated HO-1^+/− (Het, n=6–9), and Het mice treated with pravastatin (Het+Pravastatin, n=12–14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.ResultsCompared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0–73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2–5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.DiscussionPravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.     

Acute chorioamnionitis and intra-amniotic inflammation are more severe according to outside-in neutrophil migration within the same chorio-decidua

ObjectiveNo information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue.Materials and methodsWe included 106 singleton preterm-births (gestational age at delivery: 20–34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: ‘inflammation restricted to the decidua’ (n = 22); 2) group-2: ‘inflammation restricted to the MT of chorion and the decidua’ (n = 31); 3) group-3: ‘inflammation in the CT of chorion’ (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1–8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm³), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm³) were examined in 50 amniotic fluid samples within 7 days of birth.ResultsAmnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3).ConclusionAcute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.     

First trimester genetic sonogram for screening fetal Down syndrome: A population-based study

ObjectiveTo evaluate the performance of first trimester sonomarkers in the detection of fetal Down syndrome among Thai pregnant women.Materials and methodsPregnant women at 11–13⁺⁶ weeks’ gestation underwent ultrasound examination for assessment of nuchal translucency (NT), nasal bone (NB), tricuspid regurgitation (TR), and abnormal ductus venosus (aDV) Doppler waveforms. The women were followed up for final outcomes. Fetal abnormalities other than trisomy 21 were excluded. The performances of each sonomarker and their combinations in predicting fetal Down syndrome were calculated.ResultsA total of 7820 pregnant women meeting the inclusion criteria were available for analysis, including 20 cases with fetal Down syndrome and 7800 unaffected cases. Of the four sonomarkers, NT, as a single sonomarker, had the highest detection rate (55.0% at a false positive rate of about 5%), whereas the remaining single sonomarkers had low detection rate (15–20%). The combination of all sonomarkers had the highest detection rate of 70% but the false positive rate was as high as 10.8%. The combination of NT and NB had a detection rate of 60% with an acceptable false positive rate of 6.9%, whereas the other combinations yielded relatively high false positive rates.ConclusionThe first trimester genetic sonogram in screening for Down syndrome among Asian women is acceptably effective and may be offered to some selected groups of the population. NT is the best sonomarker with a detection rate of 55% at 5% false positive rate and its combination with NB can improve performance with minimal increase in false positive rate.     

SLC11A1 is expressed in the human placenta across multiple gestational ages

The human placenta functions as an innate immune barrier to prevent fetal infection. However, the molecular mechanisms accounting for placental resistance to pathogens are currently poorly understood. The solute carrier family 11 member 1 (SLC11A1) is a divalent cation transporter expressed primarily by macrophages and neutrophils that is essential for controlling infections by intracellular pathogens such as Salmonella, Leishmania and Mycobacteria. This report demonstrates that SLC11A1 is expressed in the syncytiotrophoblast of the human placenta at multiple gestational ages. These results suggest that SLC11A1 may play a role in blocking productive placental infections by certain intracellular pathogens.     

Effects of ketone supplements on blood β-hydroxybutyrate,glucose and insulin: A systematic review and three-level meta-analysis

BackgroundEffects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial.ObjectiveThis study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects.MethodsMedline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression.ResultsThe meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = −0.3796, 95% CI [-0.4550, −0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30–60 min; >120 min) and insulin (30–60 min; 90–120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450–550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350–550 mg/kg).ConclusionDose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication.Registry and registry numberPROSPERO (CRD42022360620).     

Effects of topical sesame (Sesamum indicum) oil on the pain severity of chemotherapy-induced phlebitis in patients with colorectal cancer: A randomized controlled trial

Background and purposeChemotherapy-induced phlebitis (CIP) is one of the most important and common complications in patients with cancer. Currently, the use of complementary methods to prevent or alleviate phlebitis symptoms has attracted great attention. In this study, we aimed to assess the effects of topical sesame oil in reducing the pain severity of CIP.Materials and methodsThis randomized clinical trial was conducted on 60 patients with colorectal cancer afflicted with CIP. Patients received, twice a day for seven consecutive days, a 5-min massage solely (as the control group) or with 10 drops of sesame oil (as the experimental group) within the 10 cm radius of the affected site. The pain severity was evaluated by the visual analog scale on the first, third, fifth, and seventh days of the intervention.ResultsMean changes of the pain severity compared to the baseline were significant on the third (P = 0.009), fifth (P < 0.001), and seventh (P < 0.001) days of the intervention in favor of the experimental group. Also, a significant reduction in the pain severity both in the experimental and control groups was observed during the seven days (F = 720.66, P_time < 0.001); however, the decrease was more significant in the experimental group (F = 21.46, P_group < 0.001).ConclusionApplication of massage with sesame oil as a complementary method is effective in reducing the pain severity of patients with CIP.