Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1/creatinine ratio improves the prediction value.

OBJECTIVES: To evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. STUDY DESIGN: This case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. RESULTS: Urine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). CONCLUSIONS: Urinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.

Which type of forceps is better for nonrotational operative births? A simulation study comparing Thierry spatulas and Simpson-Braun and Kielland forceps.

OBJECTIVE: Obstetric forceps play an important role in safe childbirth, yet there is a lack of distinction between various forceps types in clinical practice. This study aimed to evaluate and compare perineal pressure and forces on the baby during nonrotational forceps-assisted births using Simpson-Braun forceps, Kielland forceps, and Thierry spatulas on a simulation model. METHODS: This experimental study involved six obstetricians conducting 108 forceps-assisted births on a simulation model. Instruments were assessed for their impact on perineal pressure, traction force, and operator-assessed difficulty. RESULTS: Thierry's spatulas exerted the lowest force on the baby, while Kielland forceps exhibited the lowest perineal pressure, though not statistically significant. An experienced obstetrician demonstrated less perineal pressure with Simpson forceps. Notably, no significant differences in difficulty were observed between instruments. CONCLUSION: This study highlights distinctions in forceps performance, with Thierry spatulas applying the least force on the fetal head, while an experienced obstetrician fared better with Simpson forceps in terms of perineal pressure. Kielland forceps remain a viable alternative for nonrotational forceps births, showing comparable outcomes.

Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. MATERIALS AND METHODS: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). RESULTS: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). CONCLUSION: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

(New) antenatal ultrasound signs of fetal junctional epidermolysis bullosa: A case report and systematic review of literature.

Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible.

The PREDG study: A randomised controlled trial testing whether an educational intervention can prevent gestational weight gain in women with obesity.

OBJECTIVE: The PREDG trial was designed to study the influence of an educative program on gestational weight gain in women with pregestational obesity. METHODS: Randomized controlled clinical trial (https://www.isrctn.com/ISRCTN61793947) in 169 women with pregestational obesity (BMI ≥30 kg/m2). Women were randomized to participate in a group education program in nutrition and physical activity or conventional follow-up in a specialized Unit of Obesity and Pregnancy. The nutritional intervention was adjusted to prepregnancy BMI and to the physical activity intensity. Quality was based on the Mediterranean diet. Macronutrients were distributed as follows: 50% carbohydrates, 20% protein and 30% fat. Adequate gestational weight gain was defined between 5 and 9 kg (IOM 2009). Mean gestational weight gain was compared between groups by using the T Student test and frequencies of adequate gestational weight gain were compared by using ꓫ2. RESULTS: Gestational weight gain was lower in the intervention group: 8 (4-11) vs 9.2 (6-13) kg, p 0.026. Gestational weight gain was below 9 kg in 24 of 39 (61.5%) women of the intervention vs 10 of 41 (24.4%) of the control group (p 0.001). Regarding obstetric complications, there were 15 (8.3%) cases of gestational diabetes with no differences between the groups. There were 14 of 85 (18.2%) cases of gestational hypertension or preeclampsia in the intervention group compared with 26 of 84 (32.5%) in the control group (p 0.040). With reference to neonatal weight, there were 7 of 82 (8.5%) large for gestational age neonates in the intervention group compared with 15 of 79 (19.2%) in the control group (p 0.050). CONCLUSIONS: A group-based educative and structured intervention results in an adequate weight gain and lower rates of gestational hypertension, preeclampsia and large for gestational age neonates in pregnant women with obesity.

Vacuum-assisted birth in maternal lateral posture versus lithotomy. A simulation study.

OBJECTIVE: Maternal lateral postures provide advantages during childbirth. This study aims to investigate the feasibility of assisting vacuum births in maternal lateral postures in a simulation model. STUDY DESIGN: In a simulation model, four obstetricians and four medical students were randomly allocated to perform vacuum-assisted births first in maternal lateral posture or lithotomy. A modification of Aldo Vacca's 5-step technique was developed to assist vacuum-assisted births in lateral posture. The lateral distance, vertical distance, and distance from the cup center to the flexion point were measured for every placement of the cup. RESULTS AND CONCLUSIONS: A total of 128 vacuum-assisted births were performed. The mean distance to the flexion point was 1.15 ± 0.71 cm for the lithotomy posture and 1.31 ± 0.82 cm for the lateral posture (P = 0.127). There were no statistically significant differences in vacuum extractor cup placement accuracy based on maternal posture. Performing vacuum-assisted births in maternal lateral posture is feasible in a simulation model. The technique is easy to learn, and the differences in cup placement between the lateral and lithotomy postures are small.

The influence of air pollution on gestational age at delivery and birthweight in patients with or without respiratory allergy: A nested case-control study.

INTRODUCTION: Air pollution is a current major health issue. The burden of airborne pollutants and aeroallergen levels varies throughout the year, as well as their interaction and consequences. Prenatal exposure during pregnancy has been associated with adverse perinatal outcomes. The aim of this study was to evaluate the impact of air pollutants on perinatal outcomes in patients with or without respiratory allergy. MATERIAL AND METHODS: Nested case-control retrospective study on 3006 pregnant women. Correlations between concentrations of common pollutants in each trimester of pregnancy and on average during the whole pregnancy and both gestational age at delivery and birthweight were studied. Pearson's correlation coefficient and binary logistic regression were used. RESULTS: In general, pollutants correlated more strongly with birthweight than with gestational age at delivery. Nine-month NO2 , SO2 , CO, and benzene, and second-trimester CO negatively correlated with birthweight, whereas only first-trimester NO2 showed a very mild correlation with gestational age at delivery. Negative correlations between pollutants and birthweight were much stronger in the respiratory allergy group (n = 43; 1.4%) than in the non-allergic group. After adjustments, the most significant predictive pollutant of birthweight was SO2 in both groups. The best predictive model was much stronger in the allergic group for third-trimester SO2 (R2 = 0.12, p = 0.02) than in the non-allergic group for total SO2 (R2 = 0.002, p = 0.02). For each unit that SO2 increased, birthweight reduced by 3.22% vs. 1.28% in each group, respectively. CONCLUSIONS: Air pollutant concentrations, especially SO2 , negatively influenced birthweight. The impact of this association was much stronger and more relevant in the group of women with respiratory allergies.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

INTRODUCTION: The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. MATERIAL AND METHODS: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. RESULTS: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. CONCLUSIONS: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

The effect of maternal obesity and lipid profile on first-trimester serum progesterone levels.

BACKGROUND: Prepregnancy overweight increases the risk of adverse perinatal outcomes. Maternal lipid profile plays a key role in the production of pregnancy hormones. The influence that obesity has on the specific mechanisms that may be involved and the potential associations with abnormal conditions in pregnancy are still poorly understood. OBJECTIVE: This study aimed to evaluate the effect of maternal body mass index and lipid profile on first-trimester serum progesterone levels. STUDY DESIGN: This was a prospective cohort study including 734 pregnant people. First-trimester maternal serum progesterone, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured between 9 and 11 weeks' gestation. Free ß-hCG, PAPP-A, age, body mass index, smoking status, gestational age at delivery, fetal sex, and birthweight were also recorded. Pregnant people were classified according to their body mass index into underweight (n=21), normal weight (n=395), overweight (n=221), obesity class I (n=64), and obesity class II/III (n=33) groups. RESULTS: Gestational age at sampling was 10.0 4±1.12 weeks. Serum progesterone levels decreased as maternal body mass index increased (35.84±12.00 ng/mL, 33.08±11.27 ng/mL, 28.04±8.91 ng/mL, 24.37±8.56 ng/mL, and 19.87±11.00 mL for underweight, normal weight, overweight, obesity class I, and obesity class II/III groups, respectively; P<.000001). There were statistically significant negative correlations between maternal progesterone and body mass index, triglycerides, and cholesterol/high-density lipoprotein cholesterol ratio, and positive correlations with gestational age at sampling, maternal age, cholesterol, high-density lipoprotein cholesterol, crown-rump length, free ß-hCG, and PAPP-A. Linear regression showed that the only independent predictor variables for progesterone levels were body mass index (P<.0001), PAPP-A (P<.0001), high-density lipoprotein cholesterol (P<.0001), and free ß-hCG (P<.0001) (R2=0.33; P<.0000001). CONCLUSION: First-trimester serum progesterone levels were lower in overweight pregnant people and markedly decreased in those with obesity, especially obesity class II/III. Maternal high-density lipoprotein cholesterol was independently related to progesterone levels as a protective factor. Benefits of progesterone supplementation in pregnant people with obesity need further evaluation.

Intrapartum ultrasound in maternal lateral versus semi-recumbent posture. A repeated measures study.

OBJECTIVE: This study aimed to assess whether intrapartum ultrasound (ITU) measurements in maternal lateral posture are superimposable to ITU measurements in semi-recumbent position. STUDY DESIGN: A single-center, repeated measures design was used. Women in the second stage of labor were randomized to ITU first in semi-recumbent followed by ITU in side-lying posture without and with contraction, or inversely. The angle of progression (AOP) and the head-perineum distance (HPD) between contractions (AOP1 and HPD1) and with contraction (AOP2 and HPD2) were measured in each maternal posture. The differences between AOP1 and AOP2 (dAOP), and between HPD1 and HPD2 (dHPD) were calculated. RESULTS AND CONCLUSIONS: Forty-two women participated in the study. A generalized estimating equation model showed that AOP1 (-3.00°; 95 % CI -5.77 to -0.23; p = 0.03) and AOP2 (-4.14°; 95 % CI -7.20 to -1.08; p = 0.008) were lower in semi-recumbent compared to maternal lateral posture. HPD1 (+1.43 mm; 95 % CI 0.05-2.81; p = 0.042) and HPD2 (+1.53 mm; 95 % CI 0.17-2.89; p = 0.03) were higher in semi-recumbent position. Differences in the ITU measurements in maternal lateral posture compared to semi-recumbent position are small. Monitoring the second stage of labor with ITU in lateral maternal posture is possible.

Influence on operative time of immediate skin-to-skin care in low-risk primary cesarean births for breech presentation: Retrospective cohort study.

BACKGROUND: Multiple benefits for both, mother and baby have been reported from immediate skin-to-skin care (SSC). The aim of this study was to analyze the influence of SSC on operative time and blood loss in primary cesarean births for breech presentation. METHODS: A SSC protocol for cesarean birth was implemented in our institution on February 25, 2019. In this single-center retrospective cohort study, we compared the outcomes of planned primary cesarean births for breech presentation at term before and after its implementation. RESULTS: Data from 110 women who had a cesarean birth for breech presentation at term were analyzed, 55 in each group. Group 1 were women who had immediate SSC and Group 2 were women without immediate SSC. Maternal and surgical characteristics, and neonatal outcomes were similar in both groups. The mean operative time was 3.22 minutes shorter in the immediate SSC group compared with the not immediate SSC group (37.13 ± 12.27 vs 40.35 ± 12.23 minutes; P = 0.171). CONCLUSIONS: In conclusion, immediate SSC following a low-risk cesarean birth for breech presentation neither prolongs the operative time nor increases blood loss during the procedure. Although we were unable to demonstrate a significant reduction in the operative time with the immediate SSC protocol, a decrease of 3 minutes was noted.

The influence of maternal respiratory allergy on obstetrics and perinatal outcomes: A nested case-control study.

OBJECTIVE: To evaluate the influence of respiratory allergy on obstetrics and perinatal outcomes. METHODS: A nested case-control retrospective study on 41 035 pregnant women. Obstetrics and perinatal outcomes of women with or without respiratory allergy were compared. Rates of preterm delivery (<37 weeks of gestation), low birth weight (<2500 g), neonatal acidosis (pH < 7.20), low 5-min APGAR score (<7), cesarean section rate and indications, and perinatal morbidity and mortality were analyzed. Results are expressed as number and percentages. χ2 and Fisher exact tests were used for comparisons. Logistic regression was used. Statistical significance was set at 95% level (P < 0.05). RESULTS: A total of 724 (1.8%) patients had respiratory allergy, and their rates of preterm delivery and low birth weight were significantly higher than those of control women (both P < 0.001). Nevertheless, analyzing the causes, multiple gestation rate was significantly higher in this group, and adjusting by this, no statistical difference was found in any of the perinatal outcomes studied. In addition, in vitro fertilization and sterility were also significantly higher in the respiratory allergy group (both P < 0.001). CONCLUSION: Women with respiratory allergy are at higher risks of prematurity and low birth weight but these results are mediated by sterility, in vitro fertilization, and multiple gestation rate. Nonetheless, participation of inflammatory mechanisms should be further studied.

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study.

OBJECTIVES: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. METHODS: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. RESULTS: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. CONCLUSIONS: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.

Influence of Diet and Lifestyle on the Development of Gestational Diabetes Mellitus and on Perinatal Results.

GDM is a multifactorial disease, so there is controversy regarding the mechanisms involved in its pathogenesis. We speculate whether lifestyle and eating habits influenced the appearance and pathogenesis of GDM. To explore this issue, the aim of the present study was to analyze maternal diet and lifestyle characteristics in early pregnancy and their influence on the development of GDM. The study included 103 pregnant women who completed a questionnaire on nutritional knowledge, lifestyle and eating habits. Perinatal and biochemical outcomes as well as pregestational lifestyle and eating habits were compared between normoglycemic women and those who developed GDM. The results obtained showed that women who developed GDM had erroneous knowledge regarding nutrition. Consumption of white bread (p = 0.018), added sugars (p = 0.037), legumes (p = 0.025), fish (p = 0.014), butter (p = 0.010) and the performance of less physical activity (p = 0.024) correlated with glucose intolerance in pregnant women. In conclusion, we found a relationship between dietary and lifestyle habits at the beginning of pregnancy and the later diagnosis of GDM.

Longitudinal changes in fetal head biometry and fetoplacental circulation in fetuses with congenital heart defects.

INTRODUCTION: Objectives were to analyze changes in fetal cephalic biometry and fetoplacental circulation throughout pregnancy in fetuses with congenital heart defects. MATERIAL AND METHODS: Prospective study conducted on three university tertiary referral hospitals. Fetuses with the diagnosis of isolated congenital heart defects attending between 2014 and 2018 were included. Congenital heart defects were divided into two groups according to the oxygen supply to the central nervous system: group I (expected low placental blood content and low oxygen delivery to the brain) and group II (expected intermediate and high placental blood content). Fetal biometry and Doppler parameters were collected between 25-30 weeks of gestation and 34-40 weeks of gestation and transformed into Z scores. The results were compared with healthy controls. Finally, general linear modeling was performed to analyze repeated measurements. RESULTS: In all, 71 fetuses met the inclusion criteria. Fetuses with congenital heart defects had significantly smaller head (biparietal diameter [p < 0.001], head circumference [p = 0.001]) and abdominal circumference (p < 0.001), and lower estimated fetal weight (p < 0.001) than controls. When analyzing according to congenital heart defects type, head size was significantly smaller in group I compared with group II (p = 0.04). Regarding Doppler parameters, fetuses with congenital heart defects showed higher umbilical artery pulsatility index (p < 0.001) and lower cerebroplacental ratio (p = 0.044) than controls. In group I, umbilical artery pulsatility index was above the 95th centile in 15.4% of fetuses compared with 6.7% in group II and 1.9% in controls (p < 0.001); moreover, middle cerebral artery pulsatility index was below the 5th centile in 5.4% of group I fetuses compared with 0% in group II and 1.2% in controls (p = 0.011). General linear model for two measurements showed significant longitudinal changes in biometric parameters. Growth rate of fetal head through pregnancy (head circumference Z score) was lower in fetuses with congenital heart defects compared with controls (p = 0.043). In group I, the head circumference Z score longitudinal decrease was significantly higher than in group II (p < 0.001). CONCLUSIONS: Fetuses with congenital heart defects are at risk of smaller head size and Doppler changes. Growth rate of fetal head throughout pregnancy is also affected. These findings are mainly associated with cardiac defects with expected low oxygen supply to the central nervous system.

Ligilactobacillus salivarius PS11610 exerts an effect on the microbial and immunological profile of couples suffering unknown infertility.

PROBLEM: Unknown or idiopathic infertility has been associated with urogenital tract dysbiosis, reducing pregnancy and delivery ratios during assisted reproductive treatments (ART). The Ligilactobacillus salivarius PS11610 strain has shown extraordinary antimicrobial activity in vitro against urogenital pathogens as well as other probiotic characteristics. Therefore, an intervention study was performed to evaluate the effect of L. salivarius PS11610 on the microbial composition of urogenital tract in infertile couples with bacterial dysbiosis. METHOD OF STUDY: Seventeen couples undergoing ART diagnosed with unknown infertility were selected. After confirming urogenital dysbiosis, they started a 6-month treatment with L. salivarius PS11610 (1 dose/12 h for female and 1 dose/24 h for male). Vaginal, seminal, glans, uterine and plasma samples were collected for determination of the microbiome and immune profile at the beginning and the end of the treatment. RESULTS: Supplementation with L. salivarius PS11610 significantly modified the urogenital microbiome composition in male and female samples, solving dysbiosis of 67% of the couples. Pathogens disappeared from the vaginal samples whereas Lactobacilli percentage increased after 3 and 6 months of treatment. Moreover, L. salivarius PS11610 changed the uterine microbiome that could be associated with a change of the uterine immune profile. Additionally, the probiotic intake could be associated with the observed change in the systemic immunological profile of couples. Finally, the pregnant and delivery ratio were improved. CONCLUSIONS: Probiotic supplementation with L. salivarius PS11610 improved the male and female urogenital tract microbiome, modulating the immune system and increasing pregnancy success in couples undergoing ART.

Prenatal prediction of very late onset small-for-gestational age newborns in low-risk pregnancies.

OBJECTIVE: To find a multivariate model for predicting small-for-gestational age newborns at 36 weeks' gestation by using clinical, biochemical and ultrasound measurements. MATERIALS AND METHODS: We evaluated 564 low-risk pregnant women and recorded maternal age, maternal body mass index, maternal mean blood pressure, soluble fms-like tyrosine kinase-1 (multiples of the median), placental growth factor (multiples of the median), soluble fms-like tyrosine kinase-1/placental growth factor ratio, estimated fetal weight centile and mean uterine artery pulsatility index at 36 weeks. Binary logistic regression was used. Statistical significance was set at 95% level (p < 0.05). RESULTS: We found three multivariate models showing relatively small differences in predictive capability. Model 1 only included estimated fetal weight centiles (area under the curve [AUC] 0.86; R2 = 0.42; p < 0.0001), Model 2 estimated fetal weight centiles and placental growth factor (multiples of the median) (AUC 0.87; R2 = 0.44; p < 0.0001) and Model 3 estimated fetal weight centiles, placental growth factor (multiples of the median) and mean uterine artery pulsatility index (AUC 0.88; R2 = 0.45; p < 0.0001). CONCLUSION: Small-for-gestational age at delivery may be predicted by using a multivariate formula. The inclusion of parameters other than estimated fetal weight centile at 36 weeks' gestation modestly improves the predictive capability of the model. Clinical decisions should consider whether or not these slight differences deserve a change in current strategies.

Quantitative proteomic analysis of serum-purified exosomes identifies putative pre-eclampsia-associated biomarkers.

BACKGROUND: The high incidence of pre-eclampsia, which affects 2-7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions. METHODS: We compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics. RESULTS: We developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model. CONCLUSIONS: We have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.