Blood Flow and Respiratory Gas Exchange in the Human Placenta at Term: A Data Update.

Reliable measurements using modern techniques and consensus in experimental design have enabled the assessment of novel data sets for normal maternal and foetal respiratory physiology at term. These data sets include (a) principal factors affecting placental gas transfer, e.g., maternal blood flow through the intervillous space (IVS) (500 mL/min) and foeto-placental blood flow (480 mL/min), and (b) O2, CO2 and pH levels in the materno-placental and foeto-placental circulation. According to these data, the foetus is adapted to hypoxaemic hypoxia. Despite flat oxygen partial pressure (pO2) gradients between the blood of the IVS and the umbilical arteries of the foetus, adequate O2 delivery to the foetus is maintained by the higher O2 affinity of the foetal blood, high foetal haemoglobin (HbF) concentrations, the Bohr effect, the double-Bohr effect, and high foeto-placental (=umbilical) blood flow. Again, despite flat gradients, adequate CO2 removal from the foetus is maintained by a high diffusion capacity, high foeto-placental blood flow, the Haldane effect, and the double-Haldane effect. Placental respiratory gas exchange is perfusion-limited, rather than diffusion-limited, i.e., O2 uptake depends on O2 delivery.

Identification and validation of DNA methylation changes in pre-eclampsia.

INTRODUCTION: Pre-eclampsia (PE) is a dangerous placental condition that can lead to premature labour, seizures and death of mother and infant. Several studies have identified altered placental DNA methylation in PE; however, there is widespread inconsistency between studies and most findings have not been replicated. This study aimed to identify and validate consistent differences in methylation across multiple PE cohorts. METHODS: Seven publicly available 450K methylation array datasets were analysed to identify consistent differentially methylated positions (DMPs) in PE. DMPs were identified based on methylation difference (≥10%) and significance (p-value ≤ 1 × 10-7). Targeted deep bisulfite sequencing was then performed to validate a subset of DMPs in an additional independent PE cohort. RESULTS: Stringent analysis of the seven 450K datasets identified 25 DMPs (associated with 11 genes) in only one dataset. Using more relaxed criteria confirmed 19 of the stringent 25 DMPs in at least four of the remaining six datasets. Targeted deep bisulfite sequencing of eight DMPs (associated with three genes; CMIP, ST3GAL1 and DAPK3) in an independent PE cohort validated two DMPs in the CMIP gene. Seven additional CpG sites in CMIP were found to be significantly differentially methylated in PE. DISCUSSION: The identification and validation of significant differential methylation in CMIP suggests that the altered DNA methylation of this gene may be associated with the pathogenesis of PE, and may have the potential to serve as diagnostic biomarkers for this dangerous condition of pregnancy.

Maternal Obesity Influences Placental Nutrient Transport, Inflammatory Status, and Morphology in Human Term Placenta.

CONTEXT: Maternal obesity has a significant impact on placental development. However, this impact on the placenta's structure and function (ie, nutrient transport and hormone and cytokine production) is a controversial subject. OBJECTIVE: We hypothesized that maternal obesity is associated with morphologic, secretory, and nutrient-related changes and elevated levels of inflammation in the placenta. DESIGN: We collected samples of placental tissue from 2 well-defined groups of pregnant women from 2017 to 2019. We compared the 2 groups regarding placental cytokine and hormone secretion, immune cell content, morphology, and placental nutrient transporter expressions. SETTING: Placenta were collected after caesarean section performed by experienced clinicians at Centre Hospitalier Intercommunal (CHI) of Poissy-Saint-Germain-en-Laye. PATIENTS: The main inclusion criteria were an age between 27 and 37 years old, no complications of pregnancy, and a first-trimester body mass index of 18-25 kg/m2 for the nonobese (control) group and 30-40 kg/m2 for the obese group. RESULTS: In contrast to our starting hypothesis, we observed that maternal obesity was associated with (1) lower placental IL-6 expression and macrophage/leukocyte infiltration, (2) lower placental expression of GLUT1 and SNAT1-2, (3) a lower placental vessel density, and (4) lower levels of placental leptin and human chorionic gonadotropin production. CONCLUSION: These results suggest that the placenta is a plastic organ and could optimize fetal growth. A better understanding of placental adaptation is required because these changes may partly determine the fetal outcome in cases of maternal obesity.

Fetal head progression and regression on maternal pushing at term and labor outcome.

OBJECTIVES: The aim of our study was two-fold. First, to evaluate the association between the change in the angle of progression (AoP) on maternal pushing and labor outcome. Second, to assess the incidence and clinical significance of the reduction of AoP on maternal pushing. METHODS: This was a prospective cohort study of nulliparous women with singleton pregnancy at term. AoP was measured at rest and on maximum Valsalva maneuver before the onset of labor, and the difference between AoP on maximum Valsalva and that at rest (ΔAoP) was calculated for each woman. Following delivery and data collection, we assessed the association between ΔAoP and various labor outcomes, including Cesarean section (CS), duration of the first, second and active second stages of labor, Apgar score and admission to the neonatal intensive care unit (NICU). The prevalence of women with reduction of AoP on maximum Valsalva maneuver (AoP-regression group) was calculated and its association with the mode of delivery and duration of different stages of labor was assessed. RESULTS: Overall, 469 women were included in the analysis. Among these, 273 (58.2%) had spontaneous vaginal birth, 65 (13.9%) had instrumental delivery and 131 (27.9%) underwent CS. Women in the CS group were older, had narrower AoP at rest and on maximum Valsalva, higher rate of epidural administration and lower 1-min and 5-min Apgar scores in comparison with the vaginal-delivery group. ΔAoP was comparable between the two groups. On Pearson's correlation analysis, AoP at rest and on maximum Valsalva maneuver had a significant negative correlation with the duration of the first stage of labor. ΔAoP showed a significant negative correlation with the duration of the active second stage of labor (Pearson's r, -0.125; P = 0.02). Cox regression model analysis showed that ΔAoP was associated independently with the duration of the active second stage (hazard ratio, 1.014 (95% CI, 1.003-1.025); P = 0.012) after adjusting for maternal age and body mass index. AoP reduction on maximum Valsalva was found in 73 (15.6%) women. In comparison with women who showed no change or an increase in AoP on maximum Valsalva, the AoP-regression group did not demonstrate significant difference in maternal characteristics, mode of delivery, rate of epidural analgesia, duration of the different stages of labor or rate of NICU admission. CONCLUSIONS: In nulliparous women at term before the onset of labor, narrower AoP at rest and on maximum Valsalva, reflecting fetal head engagement, is associated with a higher risk of Cesarean delivery. The increase in AoP from rest to Valsalva, reflecting more efficient maternal pushing, is associated with a shorter active second stage of labor. Fetal head regression on maternal pushing is present in about 16% of women and does not appear to have clinical significance. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Transperineal ultrasound assessment of fetal head elevation by maneuvers used for managing umbilical cord prolapse.

OBJECTIVE: To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. METHODS: This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. RESULTS: Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. CONCLUSIONS: To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Evolución del desarrollo psicomotor en preescolares con antecedentes de prematuridad / Evolution of psychomotor development in pre-school children born prematurely

INTRODUCCIÓN: En las últimas décadas, el nacimiento de niños prematuros se ha incrementado notablemente, siendo importante conocer sus efectos. El objetivo del estudio es determinar el perfil de desarrollo psicomotor de niños con antecedentes de prematuridad, a los 4, 5 y 6 años, y compararlos con un grupo de niños nacidos a término para detectar posibles desajustes. PACIENTES Y MÉTODOS: La muestra estaba constituida por 98 participantes, distribuidos uniformemente en 2 grupos, prematuros y a término. Se realizó un estudio de cohorte prospectivo longitudinal analítico observacional con un diseño de casos y controles. Se ha considerado la división del grupo prematuro en muy prematuros y prematuros moderados y tardíos. Las evaluaciones se realizaron con las Escalas McCarthy de Aptitudes y Psicomotricidad para niños. RESULTADOS: Los datos muestran logros dentro de los intervalos medios. No obstante, se evidencian más dificultades en el desarrollo a los 4 años en el grupo de prematuros. Atendiendo a la edad gestacional, los muy prematuros (edad gestacional menor de 32 semanas) muestran puntuaciones significativamente más bajas con respecto a los prematuros moderados y tardíos, fundamentalmente a los 6 años, y con los nacidos a término, a los 4 y 6 años. CONCLUSIONES: A menor edad gestacional, son mayores las dificultades, pudiendo afectar en la etapa de Educación Primaria. Se considera la necesidad de efectuar un seguimiento a todos los prematuros en la etapa preescolar, así como evaluar habilidades más específicas y continuar con la atención desde equipos especializados

INTRODUCTION: The rate of premature births has significantly increased, and it is important to determine its effects. The objective of this study is to determine the psychomotor development profile of a group of children born prematurely, at the age of 4, 5 and 6, and to compare them with a group of full-term birth children, in order to detect any differences. PATIENTS AND METHODS: The sample consisted of 98 participants, evenly distributed into two groups, premature and full-term born children. A prospective longitudinal observational analytical study, with a design of cases and controls, was carried out. For some analyses, the separation into early pre-term, moderate pre-term, and late pre-term was considered. The evaluations were performed using the McCarthy Scale of Aptitudes and Psychomotor skills for children. RESULTS: The data shows achievements within the middle intervals. However, there are more difficulties in development at 4 years in the group of premature children, according to gestational age. Early pre-term (gestational age less than 32 weeks) showed significantly lower scores compared to moderate and late pre-term, mainly at 6 years, and with those born at term, at 4 and 6 years. CONCLUSIONS: Development difficulties are greater at a lower gestational age, and may affect the Primary Education stage. The need to monitor all premature children in the preschool stage is suggested, as well as to evaluate more specific skills and continue with the care from specialist teams

Flash VEP in clinically stable pre-term and full-term infants.

PURPOSE: Pre-term infants are at risk of abnormal visual development that can range from subtle to severe. The aim of this study was to compare flash VEPs in clinically stable pre-term and full-term infants at 6 months of age. METHODS: Twenty-five pre-term and 25 full-term infants underwent flash VEP testing at the age of 6 months. Monocular VEPs were recorded using flash goggles on a RETIscan system under normal sleeping conditions. Amplitude and peak time responses of the P2 component in the two eyes were averaged and compared between the two groups. Multiple regression analyses were performed to assess the relationship of the P2 responses with birth weight (BW) and gestational age (GA). RESULTS: At 6 months corrected age, pre-term infants had significantly delayed P2 peak times than full-term infants (mean difference: 10.88 [95% CI 4.00-17.76] ms, p = 0.005). Pre-term infants also showed significantly reduced P2 amplitudes as compared to full-term infants (mean difference: 2.36 [0.83-3.89] µV, p = 0.003). Although the regression model with GA and BW as fixed factors explained 20% of the variance in the P2 peak time (F2,47 = 5.98, p = .0045), only GA showed a significant negative relationship (ß = -2.66, p = .003). Neither GA (ß = 0.21, p = .28) nor BW (ß = 0.001, p = .32) showed any relationship with P2 amplitude. CONCLUSIONS: Our results demonstrate that, compared with full-term infants, clinically stable pre-term infants exhibit abnormal flash VEPs, with a delay in P2 peak time and a reduction in P2 amplitude. These findings support a potential dysfunction of the visual pathway in clinically stable pre-term infants as compared to full-term infants.

A randomized controlled trial of restricted versus standard fluid management in late preterm and term infants with transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn(TTNB) is the most common respiratory morbidity in late preterm and term babies and is pathophysiologically related to delayed lung fluid clearance after birth. Mimicking low physiological fluid intake in the initial period of life may accelerate the recovery from TTNB. In a randomized controlled trial, we compared the roles of restricted versus standard fluid management in babies with TTNB requiring respiratory support. METHODS: This parallel group,non-blinded, stratified randomized controlled trial was conducted in a level III neonatal unit of eastern India. Late preterm and term babies with TTNB requiring continuous positive airway pressure (CPAP) were randomly allocated to standard and restricted fluid arms for the first 72 hours (hrs). Primary outcome was CPAP duration. RESULTS: In total, 100 babies were enrolled in this study with 50 babies in each arm. CPAP duration was significantly less in the restricted arm (48[42, 54] hrs vs 54[48,72] hrs, p = 0.002). However, no difference was observed in the incidence of CPAP failure between the two arms. In the subgroup analysis, the benefit of reduced CPAP duration persisted in late preterm but not in term infants. However, the effect was not significant in the late preterm babies exposed to antenatal steroid. CONCLUSION: This trial demonstrated the safety and effectiveness of restrictive fluid strategy in reducing CPAP duration in late preterm and term babies with TTNB. Late preterm babies, especially those not exposed to antenatal steroid were the most benefitted by this strategy.

Perinatal outcomes from preterm and early term births in a multicenter cohort of low risk nulliparous women.

Preterm birth is the major contributor for neonatal and under-five years mortality rates and also accounts for a short- and long-term adverse consequences up to adulthood. Perinatal outcomes may vary according to lots of factors as preterm subtype, late prematurity, which account for the vast majority of cases, country and population characteristics. An under-recognition of the perinatal outcomes and its associated factors might have underpowered strategies to provide adequate care and prevent its occurrence. We aim to estimate the frequency of maternal and perinatal outcomes in women with different categories of preterm and term births, factors associated with poorer perinatal outcomes and related management interventions. A multicentre prospective cohort in five maternities in Brazil between 2015 and 2018. Nulliparous low-risk women with singletons were included. Comprehensive data were collected during three antenatal visits (at 19-21weeks, 27-29 weeks and 37-39 weeks). Maternal and perinatal outcomes were also collected according to maternal and neonatal medical records. Women who had spontaneous (sPTB) and provider-initiated (pi-PTB) preterm birth were compared to those who had term birth. Also, late preterm birth (after 34 weeks), and early term (37-38 weeks) were compared to full term birth (39-40 weeks). Bivariate analysis estimated risk ratios for maternal and adverse outcomes. Finally, a multivariate analysis was conducted to address factors independently associated with any adverse perinatal outcome (APO). In total, 1,165 women had outcome data available, from which 6.7% had sPTB, 4.0% had pi-PTB and 89.3% had a term birth. sPTB and pi-PTb were associated with poorer perinatal outcomes, as well as late sPTB, late pi-PTB and early term neonates. pi-PTB (RRadj 8.12, 95% CI [2.54-25.93], p-value 0.007), maternal weight gain between 20 and 27 weeks

Use of the partograph - Current thinking.

The partograph (sometimes called partogram) is a labour monitoring tool that is used in countries worldwide to enable early detection of complications, so that referral, action or closer observations can ensue. While the partograph has received global support, from health professionals, there are concerns that it has not reached its full potential in improving clinical outcomes. This has resulted in several variations of the tool and a plethora of studies aimed at exploring the barriers and facilitators to its use. In this chapter, we will discuss the history of the partograph, outlining how it has evolved over time. We will also suggest reasons why the tool may not be meeting the needs of all practitioners. In particular, we will explore partograph use as a complex intervention, suggesting that its success is likely to be dependent on multiple contextual factors.

Symptoms of Gastroesophageal Reflux in Healthy, Full-Term Infants Younger Than 7 Months Old.

OBJECTIVE: To describe the range of symptoms of gastroesophageal reflux in healthy, full-term infants in the first 7 months of life. DESIGN: Cross-sectional, descriptive study. Median and percentile scores for the Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) were calculated for each of the following age groups of infants: 0 to 2, 2 to 4, 4 to 6, and 6 to 7 months. Psychometric properties, including internal consistency reliability and concurrent validity of the I-GERQ-R, were also tested. SETTING: Online. PARTICIPANTS: Primary caregivers of 559 healthy, full-term (≥37 weeks gestational age) infants younger than 7 months. MEASUREMENTS: Participants were asked to answer questions about themselves, their family, and their infant and to complete the I-GERQ-R, the Infant Gastrointestinal Symptoms Questionnaire, and the Neonatal Eating Assessment Tool. RESULTS: Symptoms of gastroesophageal reflux decreased over the first 7 months of life. Scores in the 95th percentile decreased from 19 in infants 0 to 2 months old to 16.7 in infants 6 to 7 months old. Internal consistency reliability of the I-GERQ-R was acceptable (Cronbach's α = .71). The I-GERQ-R had evidence of concurrent validity with the Infant Gastrointestinal Symptoms Questionnaire (rs = .69, p < .001) and Neonatal Eating Assessment Tool-Breastfeeding Gastroesophageal Function subscale (rs = .52, p < .001). CONCLUSIONS: Authors of prior studies used a cutoff score of 16 for the diagnosis of gastroesophageal reflux disease in infants younger than 18 months. Our results indicate that symptoms of reflux change with age over the first 7 months of life and that using more age-specific reference values may be more appropriate. Health care providers can use these age-specific percentile scores, together with clinical assessment, to identify significant symptomatology related to gastroesophageal reflux disease.

The effect of obesity on the onset of spontaneous labor and scheduled delivery rates in term pregnancies.

OBJECTIVE: To determine the effect of obesity on the onset of spontaneous labor, scheduled delivery rates and perinatal outcomes in term pregnancies. MATERIAL AND METHODS: 242 obese and 244 non-obese pregnant women ≥37 gestational weeks were compared in terms of the onset of spontaneous labor, scheduled delivery rates and perinatal outcomes. RESULTS: Obese pregnant women had statistically significantly lower onset of spontaneous labor and higher rates of scheduled delivery. No difference was determined in respect of the type of delivery, 1st and 5th minutes APGAR scores and the need for intensive care. Higher values of birth weight, large for gestational age, macrosomia, gestational diabetes mellitus and preeclampsia were determined in obese women. CONCLUSION: The onset of spontaneous labor rates in term obese pregnancies were lower and scheduled delivery rates were higher than in the non-obese pregnancies. However, more extensive studies are needed to better understand this relationship.

Membrane sweeping for induction of labour.

BACKGROUND: Induction of labour involves stimulating uterine contractions artificially to promote the onset of labour. There are several pharmacological, surgical and mechanical methods used to induce labour. Membrane sweeping is a mechanical technique whereby a clinician inserts one or two fingers into the cervix and using a continuous circular sweeping motion detaches the inferior pole of the membranes from the lower uterine segment. This produces hormones that encourage effacement and dilatation potentially promoting labour. This review is an update to a review first published in 2005. OBJECTIVES: To assess the effects and safety of membrane sweeping for induction of labour in women at or near term (≥ 36 weeks' gestation). SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (25 February 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 February 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing membrane sweeping used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed on a predefined list of labour induction methods. Cluster-randomised trials were eligible, but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, risk of bias and extracted data. Data were checked for accuracy. Disagreements were resolved by discussion, or by including a third review author. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included 44 studies (20 new to this update), reporting data for 6940 women and their infants. We used random-effects throughout. Overall, the risk of bias was assessed as low or unclear risk in most domains across studies. Evidence certainty, assessed using GRADE, was found to be generally low, mainly due to study design, inconsistency and imprecision. Six studies (n = 1284) compared membrane sweeping with more than one intervention and were thus included in more than one comparison. No trials reported on the outcomes uterine hyperstimulation with/without fetal heart rate (FHR) change, uterine rupture or neonatal encephalopathy. Forty studies (6548 participants) compared membrane sweeping with no treatment/sham Women randomised to membrane sweeping may be more likely to experience: · spontaneous onset of labour (average risk ratio (aRR) 1.21, 95% confidence interval (CI) 1.08 to 1.34, 17 studies, 3170 participants, low-certainty evidence). but less likely to experience: · induction (aRR 0.73, 95% CI 0.56 to 0.94, 16 studies, 3224 participants, low-certainty evidence); There may be little to no difference between groups for: · caesareans (aRR 0.94, 95% CI 0.85 to 1.04, 32 studies, 5499 participants, moderate-certainty evidence); · spontaneous vaginal birth (aRR 1.03, 95% CI 0.99 to 1.07, 26 studies, 4538 participants, moderate-certainty evidence); · maternal death or serious morbidity (aRR 0.83, 95% CI 0.57 to 1.20, 17 studies, 2749 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.83, 95% CI 0.59 to 1.17, 18 studies, 3696 participants, low-certainty evidence). Four studies reported data for 480 women comparing membrane sweeping with vaginal/intracervical prostaglandins There may be little to no difference between groups for the outcomes: · spontaneous onset of labour (aRR, 1.24, 95% CI 0.98 to 1.57, 3 studies, 339 participants, low-certainty evidence); · induction (aRR 0.90, 95% CI 0.56 to 1.45, 2 studies, 157 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.44 to 1.09, 3 studies, 339 participants, low-certainty evidence); · spontaneous vaginal birth (aRR 1.12, 95% CI 0.95 to 1.32, 2 studies, 252 participants, low-certainty evidence); · maternal death or serious morbidity (aRR 0.93, 95% CI 0.27 to 3.21, 1 study, 87 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.40, 95% CI 0.12 to 1.33, 2 studies, 269 participants, low-certainty evidence). One study, reported data for 104 women, comparing membrane sweeping with intravenous oxytocin +/- amniotomy There may be little to no difference between groups for: · spontaneous onset of labour (aRR 1.32, 95% CI 88 to 1.96, 1 study, 69 participants, low-certainty evidence); · induction (aRR 0.51, 95% CI 0.05 to 5.42, 1 study, 69 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.12 to 3.85, 1 study, 69 participants, low-certainty evidence); · maternal death or serious morbidity was reported on, but there were no events. Two studies providing data for 160 women compared membrane sweeping with vaginal/oral misoprostol There may be little to no difference between groups for: · caesareans (RR 0.82, 95% CI 0.31 to 2.17, 1 study, 96 participants, low-certainty evidence). One study providing data for 355 women which compared once weekly membrane sweep with twice-weekly membrane sweep and a sham procedure There may be little to no difference between groups for: · induction (RR 1.19, 95% CI 0.76 to 1.85, 1 study, 234 participants, low-certainty); · caesareans (RR 0.93, 95% CI 0.60 to 1.46, 1 study, 234 participants, low-certainty evidence); · spontaneous vaginal birth (RR 1.00, 95% CI 0.86 to 1.17, 1 study, 234 participants, moderate-certainty evidence); · maternal death or serious maternal morbidity (RR 0.78, 95% CI 0.30 to 2.02, 1 study, 234 participants, low-certainty evidence); · neonatal death or serious neonatal perinatal morbidity (RR 2.00, 95% CI 0.18 to 21.76, 1 study, 234 participants, low-certainty evidence); We found no studies that compared membrane sweeping with amniotomy only or mechanical methods. Three studies, providing data for 675 women, reported that women indicated favourably on their experience of membrane sweeping with one study reporting that 88% (n = 312) of women questioned in the postnatal period would choose membrane sweeping in the next pregnancy. Two studies reporting data for 290 women reported that membrane sweeping is more cost-effective than using prostaglandins, although more research should be undertaken in this area. AUTHORS' CONCLUSIONS: Membrane sweeping may be effective in achieving a spontaneous onset of labour, but the evidence for this was of low certainty. When compared to expectant management, it potentially reduces the incidence of formal induction of labour. Questions remain as to whether there is an optimal number of membrane sweeps and timings and gestation of these to facilitate induction of labour.

Impact of nuchal cord on antenatal and intrapartum foetal heart rate surveillance and perinatal outcome.

Analysing antepartum and intrapartum computerised cardiotocographic (cCTG) parameters in physiological term pregnancies with nuchal (NC) or body cord (BC), in order to correlate them with labour events and neonatal outcome. We enrolled 808 pregnant women, composed of 264 with 'one NC', 121 with 'multiple NCs', 39 with BC and 384 with 'no NC', were monitored from the 37th week of gestation before labour, while 49 pregnant women with 'one or more NCs' and 47 with 'no NCs' were analysed during labour. No differences in maternal characteristics, foetal pH at birth and 5-min Apgar score were observed. The birth weight was significantly lower in the 'multiple NCs' group, while 1-minute Apgar score was lower in the BC group than the other groups, respectively. No relevant differences in cCTG parameters were observed, except for LTI, Delta and number of variable decelerations in antepartum period and only variable deceleration in intrapartum period.Impact statementWhat is already known on this subject? Ultrasound cannot predict which foetuses with NCs are likely to have problem during labour. The question arose if single or multiple NC could affects FHR monitoring prior and during labour.What do the results of this study add? Computerised cardiotocography (cCTG) is a standardised method developed to reduce inter- and intra-observer variability and the poor reproducibility of visual analysis. Few studies have investigated the influence of NCs on FHR variability and, to our knowledge, no one has evaluated its linear and nonlinear characteristics in antepartum and intrapartum period using a computerised analysis system. No differences in maternal characteristics, foetal pH at birth and 5-min Apgar score were observed. Birth weight was significantly lower in the 'multiple NCs' group, while 1-min Apgar score was lower in the BC group than the other groups, respectively. Foetuses with 'one or more NCs' evidenced a larger number of prolonged second stage and meconium-stained liquor cases, while the operative vaginal delivery and emergency caesarean section rates were unchanged. No relevant differences in cCTG parameters were observed, except for LTI, Delta and number of variable decelerations in antepartum period and only variable deceleration in intrapartum period.What are the implications of these findings for clinical practice and/or further research? cCTG monitoring results confirmed their usefulness for assessing the state of good oxygenation for all foetuses investigated.

Association between the fetal cerebroplacental ratio and biomarkers of hypoxia and angiogenesis in the maternal circulation at term.

OBJECTIVES: A low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses. STUDY DESIGN: We used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR <10th centile vs. CPR >10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (R&D Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers. RESULTS: Of the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor. CONCLUSIONS: A low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.

Glucose withdrawal induces Endothelin 1 release with significant angiogenic effect from first trimester (FTM), but not term human umbilical cord perivascular cells (HUCPVC).

BACKGROUND: Perivascular cells (PVC) and their "progeny," mesenchymal stromal cells (MSC), have high therapeutic potential for ischemic diseases. While hypoxia can increase their angiogenic properties, the other aspect of ischemic conditions-glucose shortage-is deleterious for MSC and limits their therapeutic applicability. Regenerative cells in developing vascular tissues, however, can adapt to varying glucose environment and react in a tissue-protective manner. Placental development and fetal insulin production generate different glucose fluxes in early and late extraembryonic tissues. We hypothesized that FTM HUCPVC, which are isolated from a developing vascular tissue with varying glucose availability react to low-glucose conditions in a pro-angiogenic manner in vitro. METHODS: Xeno-free (Human Platelet Lysate 2.5%) expanded FTM (n = 3) and term (n = 3) HUCPVC lines were cultured in low (2 mM) and regular (4 mM) glucose conditions. After 72 h, the expression (Next Generation Sequencing) and secretion (Proteome Profiler) of angiogenic factors and the functional angiogenic effect (rat aortic ring assay and Matrigel™ plug) of the conditioned media were quantified and statistically compared between all cultures. RESULTS: Low-glucose conditions had a significant post-transcriptional inductive effect on FTM HUCPVC angiogenic factor secretion, resulting in significantly higher VEGFc and Endothelin 1 release in 3 days compared to term counterparts. Conditioned media from low-glucose FTM HUCPVC cultures had a significantly higher endothelial network enhancing effect compared to all other experimental groups both in vitro aortic ring assay and in subcutan Matrigel™ plugs. Endothelin 1 depletion of the low-glucose FTM HUCPVC conditioned media significantly diminished its angiogenic effect CONCLUSIONS: FTM HUCPVC isolated from an early extraembryonic tissue show significant pro-angiogenic paracrine reaction in low-glucose conditions at least in part through the excess release of Endothelin 1. This can be a substantial advantage in cell therapy applications for ischemic injuries.

Impact of gestational diabetes mellitus on maternal cardiac adaptation to pregnancy.

OBJECTIVE: To determine whether maternal cardiac adaptation at term differs between women with, and those without, gestational diabetes mellitus (GDM). METHODS: This was a prospective case-control study of pregnant women at term with or without GDM. For both cases and controls, only women without any comorbidity or form of pre-existing diabetes who had a singleton pregnancy without complication (such as pre-eclampsia or fetal growth restriction) were included. All women underwent conventional and speckle-tracking echocardiography to assess both the left- and right-heart geometry and function. RESULTS: A total of 40 women with GDM and 40 healthy controls were enrolled. Women with GDM, compared with controls, had a significantly higher heart rate (83 ± 10 vs 75 ± 9 beats per min; P < 0.001), left ventricular (LV) relative wall thickness (0.43 ± 0.07 vs 0.37 ± 0.08; P < 0.001), LV early diastolic transmitral valve velocity (E) (0.80 ± 0.15 vs 0.73 ± 0.12 m/s; P = 0.026) and LV late diastolic transmitral valve velocity (A) (0.65 ± 0.13 vs 0.57 ± 0.11 m/s; P = 0.006). In women with GDM compared with controls, speckle-tracking analysis revealed a significant reduction in LV global longitudinal strain (GLS) (-16.29 ± 2.26 vs -17.61 ± 1.89; P = 0.012), LV endocardial GLS (-18.50 ± 2.59 vs -19.84 ± 2.35; P = 0.031) and LV epicardial GLS (-14.40 ± 2.01 vs -15.73 ± 1.66; P = 0.005). Right ventricular (RV) analysis revealed a reduced pulmonary acceleration time (58 ± 10 vs 66 ± 11 ms; P = 0.001) and RV E/A ratio (1.13 ± 0.18 vs 1.29 ± 0.35; P = 0.017), as well as a higher RV myocardial systolic annular velocity (0.16 ± 0.04 vs 0.14 ± 0.02; P = 0.023) and peak late diastolic transtricuspid valve velocity (0.46 ± 0.1 m/s vs 0.39 ± 0.08 m/s; P = 0.001), in women with GDM compared to controls. CONCLUSIONS: Our findings show that even a short period of exposure to hyperglycemia, as occcurs in women with GDM, is associated with significant maternal functional cardiac impairment at term. Given these findings, further study of postnatal maternal cardiovascular recovery after GDM pregnancy is warranted. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Oxygen for respiratory support of moderate and late preterm and term infants at birth: Is air best?

Oxygen has been used for newborn infant resuscitation for more than two centuries. In the last two decades, concerns about oxidative stress and injury have changed this practice. Air (FiO2 0.21) is now preferred as the starting point for respiratory support of infants 34 weeks gestation and above. These recommendations are derived from studies that were conducted on asphyxiated, term infants, recruited more than 10 years ago using strategies that are not commonly used today. The applicability of these recommendations to current practice, is uncertain. In addition, whether initiating respiratory support with air for infants with pulmonary disorders provides sufficient oxygenation is also unclear. This review will address these concerns and provide suggestions for future steps to address knowledge and practice gaps.

Predictores pronósticos de desarrollo neurológico en recién nacidos a término con crisis neonatales / Neurodevelopmental outcome predictors of term newborns with neonatal seizures

Introducción: El peso específico de las crisis neonatales en el pronóstico neurológico de recién nacidos a término no se conoce bien, por lo que el objetivo del estudio era describir predictores pronósticos en crisis neonatales. Sujetos y métodos: Estudio observacional prospectivo de recién nacidos a término con crisis clínicas en un centro terciario (2009-2018). Pronóstico adverso se definió como muerte, retraso global del desarrollo, parálisis cerebral o epilepsia. Se analizaron las características perinatales, la etiología, los hallazgos electroencefalográficos, la neuroimagen y los tratamientos antiepilépticos siguiendo un modelo de regresión logística. Resultados: Se incluyó a un total de 102 recién nacidos (52 de los cuales tenían desarrollo normal). Se registraron 12 fallecimientos. En el grupo de supervivientes, 38 niños tuvieron un pronóstico desfavorable (28 con retraso global del desarrollo, 27 con parálisis cerebral, 21 con epilepsia). De las variables pronósticas identificadas en el análisis univariante, las complicaciones perinatales, el inicio de las crisis en el primer día de vida, la actividad basal anormal moderada a grave, un patrón anormal en el electroencefalograma de amplitud integrada y la respuesta al tratamiento continuaron mostrándose como independientemente asociadas a pronóstico adverso después de aplicar un modelo de regresión logística. Conclusiones: Existen datos contradictorios sobre marcadores subrogados en crisis neonatales. Aparte de confirmar el valor predictivo de variables previamente descritas, se halló que la monitorización con electroencefalograma de amplitud integrada constituye una prometedora herramienta diagnóstica. En el futuro, se debería extender su utilización en el abordaje de estos pacientes, lo que sería de vital importancia para un diagnóstico y un tratamiento precoces

Introduction: The concrete burden of neonatal seizures in neurodevelopmental outcome of term newborns is still unknown in literature. The aim of this study was to describe prognostic predictors in neonatal seizures. Subjects and methods: Observational prospective study of term neonates with clinical seizures from a tertiary center (2009-2018). Adverse outcome was determined as death, global developmental delay, cerebral palsy or epilepsy. Perinatal characteristics, etiology, electrographic features, neuroimaging and antiepileptic treatment were analyzed in a logistic regression model. Results: A total of 102 newborns were included (52 infants with normal outcome). Twelve fatalities were registered. In the survival group, 38 children had an adverse outcome (28 global developmental delay, 27 cerebral palsy, 21 epilepsy). From the prognostic variables identified in univariate analysis, perinatal complications, seizure onset in the first day of life, moderate to severe abnormal background activity, abnormal amplitude-integrated EEG pattern, and treatment response remained independently associated with adverse outcome after a logistic regression model. Conclusions: There is conflicting data about surrogate markers in neonatal seizures. Aside from confirming the predictive value of previously described variables, we observed that amplitude-integrated EEG monitoring is a forthcoming prognostic tool. Future approaches may include a wider use of amplitude-integrated EEG monitoring, being crucial for timely seizure identification and prompt treatment

Orofacial anthropometric measures in full-term newborns. / Medidas antropométricas orofaciais em recém-nascidos a termo.

PURPOSE: To describe and compare the anthropometric measurements and the orofacial proportions of healthy term newborns (NB) according to sex, from a public maternity hospital in the state of Sergipe, northeastern Brazil. METHODS: Descriptive and analytical randomized study was carried out. The participants included were 46 randomly selected healthy and full-term RNs of both sexes. A digital caliper was used to measure measurements (in millimeters) with the NB supine and occluded lips. Twice different, previously trained researchers measured each NB. Data were described using simple and percentage frequencies. The mean differences were assessed using the Mann-Whitney test, with a significance of 5%. Associations evaluated by the Fisher Exact test, and Cohen D size effects were calculated. RESULTS: Differences were found between the groups for the anthropometric measurements: midface third height (glabella-subnasal or sn-g) and bottom (subnasal-gnathion or sn-gn); and filter heights (upper-lip subnasal or sn-ls), the upper lips (subnasal-estomus or sn-sto), and lower (stomatal-gnathion or sto-gn), which was always greater in males. The orofacial proportions studied did not show differences between sexes. CONCLUSION: The study showed the presence of sexual dimorphism for the measures of the face at birth in the population born in Aracaju, Sergipe.

OBJETIVO: Descrever e comparar as medidas antropométricas e as proporções orofaciais de recém-nascidos (RNs) a termo saudáveis, segundo o sexo, de uma maternidade pública do estado de Sergipe, Nordeste do Brasil. MÉTODO: Estudo randomizado descritivo e analítico. Participaram 46 RNs a termo e saudáveis, de ambos os sexos, selecionados aleatoriamente. Foi utilizado paquímetro digital para tomadas das medidas (em milímetros), com os RNs em posição supina e lábios ocluídos. Quatro pesquisadores foram previamente treinados, com cada RN sendo medido duas vezes por uma mesma dupla destes. Os dados foram descritos por meio de frequências simples e percentuais. As diferenças de média foram avaliadas através do Teste de Mann-Whitney, com significância de 5%. Associações foram avaliadas através do teste Exato de Fisher. Foram calculados tamanhos de efeitos D de Cohen. RESULTADOS: Foram obtidas diferenças entre os grupos para as medidas antropométricas: terços da face médio (glabela-subnasal ou g-sn) e inferior (subnasal-gnátio ou sn-gn); e alturas do filtro (subnasal-labial superior ou sn-ls), dos lábios superior (subnasal-estômio ou sn-sto) e inferior (estômio-gnátio ou sto-gn), sempre maiores no sexo masculino. As proporções orofaciais estudadas não apresentaram diferenças entre sexos. CONCLUSÃO: O estudo apontou presença de disformismo sexual para as medidas da face ao nascimento na população nascida em Aracaju, Sergipe.