Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial.

BACKGROUND: The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. METHODS: RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed. FINDINGS: Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected. INTERPRETATION: Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone. FUNDING: La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III.

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases.

Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3-11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

Ultrasound cesarean scar assessment one year postpartum in relation to one- or two-layer uterine suture closure.

INTRODUCTION: This study compared healing of the scars after cesarean section during the first postpartum year using a single- or double-layer suturing technique. Scarring was assessed by a transvaginal ultrasound. We explored the appearance and localization of uterine scars with regard to the obstetric history. Our aim was to compare the position of the scar or defect, if present, its dimensions, and any residual myometrium with respect to the suturing technique during the cesarean section. MATERIAL AND METHODS: Women with uncomplicated singleton pregnancies indicated for elective or acute cesarean section were randomly allocated to the uterine closure technique group. During the first postpartum year, their lower uterine segment was examined with a transvaginal ultrasound in three consecutive visits at 6 weeks, 6 months and 12 months. RESULTS: 324 women attended the 12-month visit; of these, 149 underwent single-layer closure of the uterine incision and 175 double-layer technique. A higher proportion of the defects is seen in the single-layer closure technique of suturing. Defects in the single-layer group were wider (0.002) and the residual myometrial thickness in the single-layer group were thinner (0.019). Women who underwent cesarean section at the stage of full cervical dilation had scars that were closer to the external cervical os (0.000). The position of the uterus varies greatly between controls (0.000). The combination of uterine position and scar defect presence changed significantly between controls (0.001), and was significantly dependent on the suturing method (0.003). Defects with or without contact with the uterine cavity changed statistically between controls (0.017). Both types of defects were more common in the single-layer closure technique group. CONCLUSIONS: The findings of this study demonstrate that double-layer technique with the first continuous nonlocking suture followed by a second continuous nonlocking suture is associated with better suture healing and greater residual myometrial thickness. No difference was observed between single- and double-layer closure for the presence of maternal infectious morbidity, wound infection or blood transfusion.

Maternal Cardiovascular Risk Assessment 3-to-11 Years Postpartum in Relation to Previous Occurrence of Pregnancy-Related Complications.

The aim of the present study was to assess the long-term outcomes of women 3-to-11 years postpartum in relation to the previous occurrence of pregnancy-related complications such as gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR). Body mass index (BMI), waist circumference values, the average values of systolic (SBP) and diastolic (DBP) blood pressures and heart rate, total serum cholesterol levels, serum HDL (high-density lipoprotein) cholesterol levels, serum LDL (low-density lipoprotein) cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum CRP (C-reactive protein) levels, plasma homocysteine levels, serum uric acid levels, individual and relative risks of having a heart attack or stroke over the next ten years were compared between groups (50 GH, 102 PE, 34 FGR and 90 normal pregnancies) and correlated with the severity of the disease with regard to clinical signs (25 PE without severe features, 77 PE with severe features), and delivery date (36 early PE, 66 late PE). The adjustment for potential covariates was made, where appropriate. At 3-11 years follow-up women with a history of GH, PE regardless of the severity of the disease and the delivery date, PE without severe features, PE with severe features, early PE, and late PE had higher BMI, waist circumferences, SBP, DBP, and predicted 10-year cardiovascular event risk when compared with women with a history of normotensive term pregnancy. In addition, increased serum levels of uric acid were found in patients previously affected with GH, PE regardless of the severity of the disease and the delivery date, PE with severe features, early PE, and late PE. Higher serum levels of lipoprotein A were found in patients previously affected with early PE. The receiver operating characteristic (ROC) curve analyses were able to identify a substantial proportion of women previously affected with GH or PE with a predisposition to later onset of cardiovascular diseases. Women with a history of GH and PE represent a risky group of patients that may benefit from implementation of early primary prevention strategies.

Antenatal assessment of liver position, rather than lung-to-head ratio (LHR) or observed/expected LHR, is predictive of outcome in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVES: Respiratory morbidity in congenital diaphragmatic hernia (CDH) is associated with high mortality and adverse outcome. Accurate prenatal diagnosis is essential for prognosis and potential treatment in utero. The aim was to evaluate the prenatal ultrasound findings in assessing the respiratory prognosis in fetuses with isolated left-sided CDH. METHODS: We retrospectively analyzed the medical records of 59 prenatally diagnosed left-sided CDH cases managed at a tertiary perinatal center. RESULTS: Survival rate in the study group was 73% (43/59). We found no statistically significant relationship between survival and the presence of polyhydramnios, gestational age at diagnosis, lung-to-head ratio (LHR) and observed/expected LHR (O/E LHR) values, gestational age at birth and birth weight. Intrathoracic liver herniation was a statistically significant parameter adversely affecting survival (37.2% in survivors, 68.8% in non-survivors, p = 0.031) and logistic regression confirmed this relationship. The presence of pneumothorax and severe pulmonary hypertension were significantly associated with mortality (82% non-survivors versus 15% in survivors, p = 0.0001). CONCLUSION: Intrathoracic liver herniation seems to be a reliable parameter in the prediction of survival and neonatal respiratory morbidity in fetuses with isolated left-sided CDH. In contrast, we found no significant correlation between perinatal outcome and LHR, O/E LHR values, birth weight and gestational age.

Assessment of placental and maternal stress responses in patients with pregnancy related complications via monitoring of heat shock protein mRNA levels.

The study describes the stress response in the central cotyledon zone of placental tissue and in maternal whole peripheral blood to pregnancy related complications including gestational hypertension (n = 31), preeclampsia w or w/o fetal growth restriction (n = 95), and fetal growth restriction (n = 39) using real-time RT-PCR and genes encoding Hsp27, Hsp60, Hsp70, Hsp90 and HspBP1 proteins. The placental tissue does not respond to pregnancy induced hypertension, fetal growth restriction and short-term severe preeclampsia that requires immediate termination of gestation. Upregulation of Hsp27, Hsp90 and HspBP1 appears just in case of long-term deteriorated conditions (usually in mild preeclampsia, that enable further continuation of gestation, when properly treated). On the other hand, maternal circulation is able to reflect both maternal and fetal pathologic conditions. While pregnancy related complications always induce upregulation of Hsp70 and downregulation of Hsp90 in maternal whole peripheral blood, the increase of Hsp60 mRNA levels occurs entirely in patients with preeclampsia and/or fetal growth restriction. Hsp60, Hsp70 and Hsp90 are dysregulated in maternal circulation irrespective of the severity of the disease (in both mild and severe preeclampsia) and the requirements for the delivery (before and after 34th week of gestation). Nevertheless, the highest Hsp60 mRNA levels may be observed in pregnancies with signs of the centralization of the fetal circulation associated with fetal hypoxia.