Volume 49, Issue 7 - Highlight: Cesarean Section – New Insights; Guest Editor: Michael Stark

In the age of hospital births, it is commonplace to contrast the vaginal route and the abdominal route as the basic classification. From the “point of view” of the foetus/neonate, we provide reasons to contrast “birth without labour” (that is birth by pre-labour caesarean section) and all the other vaginal and abdominal modes of birth. From a great diversity of theoretical reasons, one can anticipate that babies born by pre-labour caesarean sections are different from the others. We also provide reasons to popularize the concepts of “in labour non-emergency caesarean sections” and “planned in-labour caesarean sections”.

Objectives To examine the impact of early term caesarean section (CS) on respiratory morbidity and early neonatal outcomes when elective caesarean section was carried out before 39 completed weeks gestation in our population. Methods A one-year population-based retrospective cohort analysis using routinely collected hospital data. Livebirths from women who had elective lower segment cesarean section (ELSCS) for uncomplicated singleton pregnancies at early term (ET) 37+0 to 38+6 weeks were compared to full term (FT)≥39+0 weeks gestation. Exclusion criteria included diabetes, antenatal corticosteroid use, stillbirths, immediate neonatal deaths, normal vaginal deliveries and emergency caesareans sections. The outcomes were combined respiratory morbidity (tachypnea [TTN] and respiratory distress syndrome [RDS]), Apgar <7 at 5 min of age, respiratory support, duration of respiratory support and NICU admission. Results Out of a total of 1,466 elective CS with term livebirths, the timing of CS was early term (ET) n=758 (52%) and full term (FT) n=708 (48%). There was a higher incidence of respiratory morbidities and neonatal outcomes in the ET in comparison to FT newborns. In the univariable analysis, significant risks for outcomes were: the need for oxygen support OR 2.42 (95% C.I. 1.38–4.22), respiratory distress syndrome and/or transient tachypnea of newborn (RDSF/TTN) OR 2.44 (95% C.I. 1.33–4.47) and neonatal intensive care unit (NICU) admission OR 1.91 (95% C.I. 1.22–2.98). Only the need for oxygen support remained (OR 1.81, 95% C.I. 1.0–3.26) in the multivariable analysis. These results were observed within the context of a significantly higher proportion of older, multiparous, and higher number of previous caesarean sections in the early term CS group. Conclusions There is a significant risk of respiratory morbidities in infants born by elective cesarean section prior to full term gestation. Obstetricians should aim towards reducing the high rate of women with previous multiple cesarean sections including balancing the obstetric indication of early delivery among such women with the evident risk of neonatal respiratory morbidity.

Objectives The consultation of women aspiring a vaginal birth after caesarean may be improved by integrating the individual evaluation of factors that predict their chance of success. Retrospective analysis of correlating factors for all trials of labor after caesarean that were conducted at the Department of Obstetrics of Charité-Universitätsmedizin Berlin, Campus Virchow Clinic from 2014 to October 2017. Methods Of 2,151 pregnant women with previous caesarean, 408 (19%) attempted a vaginal birth after cesarean. A total of 348 women could be included in the evaluation of factors, 60 pregnant women were excluded because they had obstetric factors (for example preterm birth, intrauterine fetal death) that required a different management. Results Spontaneous delivery occurred in 180 (51.7%) women and 64 (18.4%) had a vacuum extraction. 104 (29.9%) of the women had a repeated caesarean delivery. The three groups showed significant differences in body mass index, the number of prior vaginal deliveries and the child’s birth weight at cesarean section. The indication for the previous cesarean section also represents a significant influencing factor. Other factors such as maternal age, gestational age, sex, birth weight and the head circumference of the child at trial of labor after caesarean showed no significant influence. Conclusions The clear majority (70.1%) of trials of labor after caesarean resulted in vaginal delivery. High body mass index, no previous spontaneous delivery, and fetal distress as a cesarean indication correlated negatively with a successful vaginal birth after cesarean. These factors should be used for the consultation of pregnant women.

Objectives Woman with a history of a previous cesarean section (CS) can choose between an elective repeat CS (ERCS) and a trial of labor (TOL), which can end in a vaginal birth after cesarean (VBAC) or an unplanned CS. Guidelines describe women’s rights to make an informed decision between an ERCS or a TOL. However, the rates of TOL and vaginal birth after CS varies greatly between and within countries. The objective of this study is to asses nation-wide implementation of counselling with a decision aid (DA) including a prediction model, on intended delivery compared to care as usual. We hypothesize that this may result in a reduction in practice variation without an increase in cesarean rates or complications. Methods In a multicenter controlled before and after cohort study we evaluate the effect of nation-wide implementation of a DA. Practice variation was defined as the standard deviation (SD) of TOL percentages. Results A total of 27 hospitals and 1,364 women were included. A significant decrease was found in practice variation (SD TOL rates: 0.17 control group vs. 0.10 intervention group following decision aid implementation, p=0.011). There was no significant difference in the ERCS rate or overall CS rates. A 21% reduction in the combined maternal and perinatal adverse outcomes was seen. Conclusions Nationwide implementation of the DA showed a significant reduction in practice variation without an increase in the rate of cesarean section or complications, suggesting an improvement in equality of care.

Objectives To evaluate if induction of labor (IOL) in obese women at 39 weeks of gestation decreases the risk of cesarean delivery (CD). Methods We conducted a retrospective propensity score matched study using the Center for Disease Control’s (CDC’s) Period Linked Birth-Infant Death data. The study population consisted of cephalic singleton births to women with BMI greater or equal to 30.0 kg/m 2 who delivered at or beyond 39 weeks between 2013 and 2017. Women with prior CD were excluded. Women who underwent IOL at 39 weeks were propensity score matched 1:5 on the basis of CD risk factors to women who did not undergo IOL at 39 weeks but may have had an IOL at a later gestational age. Conditional logistic regression compared CD rates and maternal outcomes between obese women induced at 39 weeks with those not induced at 39 weeks. Results Our cohort consisted of 197,343 obese women induced at 39 weeks and 986,715 obese women not induced at 39 weeks. Overall, the risk of CD among women who had an IOL at 39 weeks was lower than those without an IOL at 39 weeks, 0.59 (0.58–0.60). The decrease in CD risk was more pronounced in multiparas, 0.47 (0.46–0.49) than nulliparas, 0.81 (0.79–0.83). When stratified by BMI, the effect of IOL on lowering CD risk was similar across all obesity classes. Aside from an increased risk of instrumental deliveries, morbidities were comparable in both groups. Conclusions IOL at 39 weeks among obese women appears to lower the risk of CD, without compromising maternal outcomes.

Objectives Worldwide, the overall cesarean section is rising. Trial of labor after cesarean (TOLAC) is an overall safe option with an immediate impact on neonatal and maternal short- and long-term health. Since the use of prostaglandins in cervical ripening is associated with an increased risk of uterine rupture, mechanical methods as balloon catheters or osmotic dilators have been suggested for cervical ripening prior to induction of labour. Here we are analyzing and comparing the VBAC rate, as well as maternal and fetal outcome in cervical ripening prior to TOLAC. Methods This prospective dual center study analyses maternal and neonatal outcomes of TOLAC in women with an unfavorable cervix requiring cervical ripening agent. The prospective application of an osmotic dilator (Dilapan-S, n=104) was analysed in comparison to the retrospective application of off-label dinoprostone (n=102). Results The overall fetal and neonatal outcome revealed no significant differences in both groups. Patients receiving cervical ripening with the osmotic dilator delivered vaginally/by ventouse in 52% of cases, compared to 53% when using dinoprostone (p=0.603). The interval between application to onset of labor was significantly higher in the osmotic dilator group (37.9 vs.20.7 h, p=<0.001). However, time from onset of labor to delivery was similar in both groups (7.93 vs. 7.44 h, p=0.758). There was one case of uterine rupture in the dinoprostone group. Conclusions Our data shows that the application of the osmotic dilator leads to similar outcomes in VBAC rate and time from onset of labor to delivery as well as safety in both groups compared to off-label use dinoprostone. Cervical ripening using the mechanical dilator is a viable and effective option, without the risk of uterine hyperstimulation.

Objectives This article suggests a unified way to perform Cesarean sections. Even in the same departments, different modifications are in use. Therefore, one cannot rely on the early or late outcome of the procedure as long as all the surgical steps are not standardized. Methods The Misgav Ladach (Stark) Cesarean Section presented here is an evidence-based operation. Its basic principles are a modified Joel-Cohen abdominal incision, one-layer continuous suturing of the uterus using a big needle, leaving peritoneum open, closing fascia continuously and a few Donati skin sutures. Results This method has been subjected to scores of comparative studies with other methods in use, proving its advantages over them concerning duration, blood loss, febrile morbidity, need for analgesics, and costs. Conclusions It is suggested that this method should be used as the standardized universal method which will enable comparison between obstetricians and institutions, and offer the parturient the best possible outcome.

Objectives Uterine closure technique in caesarean section (CS) influences the rate of late complications in subsequent pregnancies. As no common recommendation on suture techniques exists, we developed a questionnaire to determine the techniques currently used and the frequencies of late complications. Methods The online questionnaire consisted of 13 questions and was sent to 648 obstetric hospitals (level I–IV) in Germany. Number of CS, rate of vaginal birth after caesarean section (VBAC), the type of uterus suturing technique and the frequency of uterine dehiscences, ruptures and placenta accreta spectrum (PAS) were queried. The answers were anonymous, and results were evaluated descriptively. Results The response rate was 24.7%. The mean CS rate was 27.3% (±6.2), the repeat CS rate 33.2% (±18.1). After CS, 46.2% (±20.2) women delivered vaginally. To close the uterotomy, 74.4% of hospitals used single layer continuous sutures, 16.3% single layer locked sutures, 3.8% interrupted sutures, 3.1% double layer continuous sutures and 2.5% used other suture techniques. The percentages of observed uterine dehiscences did not differ significantly between the different levels of care nor did the uterotomy suture techniques. Conclusions There is no uniform suturing technique in Germany. A detailed description of suture technique in surgery reports is required to evaluate complications in subsequent pregnancies. National online surveys on obstetric topics are feasible and facilitate the discussion on the need to define a standardized uterine closure technique for CS.

Objectives In Germany, cesarean section (CS) rates more than doubled within the past two decades. For analysis, auditing and inter-hospital comparison, the 10-Group Classification System (TGCS) is recommended. We used the TGCS to analyze CS rates in two German hospitals of different levels of care. Methods From October 2017 to September 2018, data were prospectively collected. Unit A is a level three university hospital, unit B a level one district hospital. The German birth registry was used for comparison with national data. We performed two-sample Z tests and bootstrapping to compare aggregated (unit A + B) with national data and unit A with unit B. Results In both datasets (national data and aggregated data unit A + B), Robson group (RG) 5 was the largest contributor to the overall CS rate. Compared to national data, group sizes in RG 1 and 3 were significantly smaller in the units under investigation, RG 8 and 10 significantly larger. Total CS rates between the two units differed (40.7 vs. 28.4%, p<0.001). The CS rate in RG 5 and RG 10 was different (p<0.01 for both). The most relative frequent RG in both units consisted of group 5, followed by group 10 and 2a. Conclusions The analysis allowed us to explain different CS rates with differences in the study population and with differences in the clinical practice. These results serve as a starting point for audits, inter-hospital comparisons and for interventions aiming to reduce CS rates.

Objectives This review examined prenatal care provided to incarcerated women to identify areas where improvement is needed, and examined current legislative gaps such that they can be addressed to ensure uniform templates of care be instituted at women’s prisons. Methods Data were compiled from 2000-2021 citations in PubMed and Google Scholar using the keywords: prison AND prenatal care AND pregnancy. Results Although the right to health care of inmates is protected under the Eight Amendment to the United States Constitution, the literature suggests that prenatal care of incarcerated individuals is variable and would benefit from uniform federal standards. Inconsistency in reporting requirements has created a scarcity of data for this population, making standardization of care difficult. Although incarceration may result in improved access to care that women may not have had in their community, issues of shackling, inadequate prenatal diet, lack of access to comprehensive mental health management, and poor availability of opioid use disorder (OUD) management such as Medication Assisted Therapy (MAT) amd Opioid Treatment Programs (OTP), history of post-traumatic stress disorder (PTSD) are just a few areas that must be focused on in prenatal care. After birth, mother-baby units (MBU) to enhance maternal-fetal bonding also should be a prison standard. Conclusions In addition to implementing templates of care specifically directed to this subgroup of women, standardized state and federal legislation are recommended to ensure that uniform standards of prenatal care are enforced and also to encourage the reporting of data regarding pregnancy and neonatal outcomes in correctional facilities.

Brain injury of the surviving twin from monochorionic pregnancies following intrauterine fetal demise during the second and third trimesters is a rare but severe complication. Monochorionicity and gestational age at the time of stillbirth seem to be decisive factors in terms of long-term neurologic outcome prediction for the survivor. Magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) in particular, seem to bring the earliest and most accurate diagnosis. Ultrasound detection of brain damage is possible in later stages of fetal brain injury. It is essential to provide early diagnosis and multidisciplinary counsel to the parents to ensure informed decision making. For couples who choose to terminate pregnancy legislation related to late abortion might lead to further distress. Our paper aims to stress the importance of MRI DWI in the evaluation of surviving twins following single intrauterine fetal demise in monochorionic pregnancies and the delicate context of the medical professionals and parents facing this clinical situation, sometimes complicated by legal constraints.

Thalassemias are among the most frequent genetic disorders worldwide. They are an important social and economic strain in high-risk populations. The benefit of β-thalassemia screening programs is growing evident but the capacity to diagnose fetal β-thalassemia exceeds the treatment possibilities and even when treatment before birth becomes feasible, difficult decisions about the relative risks will remain. This paper can be of practical and ethically justified aid when counseling women about screening, diagnosis, and treatment of β-thalassemia. It takes in consideration various social challenges, medical issues such as antenatal screening, preimplantation genetic diagnosis, prenatal diagnosis, non-invasive prenatal testing and prenatal therapy. We also describe the Sardinian experience in applying and promoting high-risk population screening and diagnosis programs and future trends in the management of β-thalassemia.

Skin-over-biocellulose for Antenatal Fetoscopic Repair (SAFER) is a recently developed technique for fully percutaneous fetoscopic repair of myelomeningocele. The formation of a neo-dura mater triggered by the use of a biocellulose patch over the placode obviates the need of primary repair of fetal dura mater, and seems to further improve neurodevelopmental outcome. Insufflation of humidified carbon dioxide into the amniotic cavity requires proper training and a different equipment set from those used in the classic “under-water” fetoscopy. To shorten the learning curve of novice teams, we have developed a structured training course encompassing three critical steps: (1) visiting the proctor center, (2) selection of the first case, and (3) on-site training of the surgical team. Upon the site arrival, there will be: (1) theoretical lecture for all specialists involved in the fetal care, (2) simulation training, and (3) surgical proctoring. Proctor team can take over the surgery if the local team cannot complete. This training course has been successfully used in five different countries: Israel, Chile, Italy, USA and England and all local teams are already performing surgeries solo without any failures or maternal morbidity. Teaching new procedures in fetal medicine is challenging, because of the small number of candidate cases, and the direct relation of good outcomes and the number of cases operated. This proposed training modules may be adopted by other teams that want to embark on this type of novel minimally invasive treatment.

Chronic hypertension in pregnancy accounts for a substantial proportion of maternal morbidity and mortality and is associated with adverse perinatal outcomes, most of which can be mitigated by appropriate surveillance and management protocols. The aim of this study was to review and compare recommendations of published guidelines on this condition. Thus, a descriptive review of influential guidelines from the National Institute for Health and Care Excellence, the Society of Obstetric Medicine of Australia and New Zealand, the International Society of Hypertension, the International Society for the Study of Hypertension in Pregnancy, the European Society of Cardiology, the International Federation of Gynecology and Obstetrics, the Society of Obstetricians and Gynaecologists of Canada and the American College of Obstetricians and Gynecologists on chronic hypertension in pregnancy was conducted. All guidelines agree on the definition and medical management, the need for more frequent antenatal care and fetal surveillance and the re-evaluation at 6–8 weeks postpartum. There is also a consensus that the administration of low-dose aspirin is required to prevent preeclampsia, although the optimal dosage remains controversial. No universal agreement has been spotted regarding optimal treatment blood pressure (BP) targets, need for treating mild-to-moderate hypertension and postnatal BP measurements. Additionally, while the necessity of antenatal corticosteroids and magnesium sulfate for preterm delivery is universally recommended, the appropriate timing of delivery is not clearly outlined. Hence, there is a need to adopt consistent practice protocols to optimally manage these pregnancies; i.e. timely detect and treat any potential complications and subsequently reduce the associated morbidity and mortality.

Objectives Pregnancy is associated with physiological alterations in insulin sensitivity and lipid metabolism. This study investigates the associations between pregestational body mass index (pBMI) and the rate of gestational weight gain (rGWG) in the second trimester with the biomarkers of lipid, fatty acids metabolism and insulin resistance. Methods Sixty nine pregnant women followed. The body weights of the pregnant women were measured and blood samples were obtained at 11–14th and 24–28th weeks of pregnancy. Glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, insulin levels and fatty acids were measured. Rate of GWG (kg/week) and The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were calculated. The pregnant women were stratified according to their pBMI and the 2nd trimester rGWG. Results The rate of GWG was significantly higher for the group with pBMI<25, compared to the group with pBMI≥25 (p=0.024). Triglyceride, total cholesterol, LDL and HDL cholesterol were significantly increased in the second trimester compared with the first trimester. Palmitic acid, oleic acid, linoleic acid, myristic acid, docosahexaenoic acid (DHA), arachidonic acid (AA), total omega-6 (n − 6) and omega-3 (n − 3) fatty acid levels and n − 6/n − 3 ratio were significantly higher in the second trimester. Glucose was significantly decreased and insulin was increased in the second trimester. In the overweight/obese group; HOMA-IR, insulin, AA, palmitoleic acid and stearic acid were found to be high in comparison to the group with low/normal pBMI. No parameters were associated with rGWG. Conclusions The changes in lipid parameters, free fatty acids, insulin and HOMA-IR in the second trimester were compatible with the changes in lipid metabolism and the development of insulin resistance. Pregestational BMI was shown to have a stronger influence on lipid profile, insulin resistance, and fatty acids than rGWG.

Objectives Antenatal exposure to organic pollutants is a leading public health problem. Meconium is a unique matrix to perform prenatal studies because it enables us to retrospectively evaluate fetal exposure accumulated during the second and third trimester. The aim of the present study was to evaluate associations between organic pollutant levels in meconium and birth weight in NW Spain. Methods In this study, we quantify the concentrations of 50 organic pollutants together with the total values of the most important chemical groups in meconium using gas chromatography coupled to tandem mass spectrometry. Results Organochlorine pesticides, polychlorinated biphenyls and polybrominated diphenyl ethers were detected with the highest levels in meconium from small for gestational age newborns. It was estimated that several congeners were statistically significant (p<0.05). However, organophosphorus pesticides attained higher concentrations in newborns with an appropriate weight. Conclusions The occurrence of transplacental transfer can be confirmed. Prenatal exposure to organic pollutants was associated with a decrease in birth weight and, therefore, organic pollutants could have an impact on fetal growth. Nevertheless, these results need validation in larger sample sized studies.

Objectives Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmin-induced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic inflammation in mice. Methods Under ultrasound guidance, the first cohort of dams received an intra-amniotic injection of the alarmin high-mobility group box-1 (HMGB1, n=10) or phosphate-buffered saline (PBS, n=9) as controls. A second cohort of dams received HMGB1 intra-amniotically and were subcutaneously treated with betamethasone (n=15) or vehicle (n=15). Dams were observed until delivery, and perinatal outcomes were observed. Results Intra-amniotic HMGB1 reduced gestational length (p=0.04), inducing preterm birth in 40% (4/10) of cases, of which 100% (4/4) were categorized as late preterm births. Importantly, treatment with betamethasone extended the gestational length (p=0.02), thereby reducing the rate of preterm birth by 26.6% (from 33.3% [5/15] to 6.7% [1/15]). Treatment with betamethasone did not worsen the rate of neonatal mortality induced by HMGB1 or alter weight gain in the first three weeks of life. Conclusions Treatment with betamethasone prevents preterm birth induced by the alarmin HMGB1. This study supports the potential utility of betamethasone for treating women with sterile intra-amniotic inflammation.

Objectives Women with gestational diabetes (GDM) and weight gain during pregnancy above recommended more often give birth to macrosomic children. The goal of this study was to evaluate the diagnostic accuracy of the modified formula for ultrasound assessment of fetal weight created in a pilot study using a similar specimen in comparison to the Hadlock-2 formula. Methods This is a prospective, cohort, applicative, observational, quantitative, and analytical study, which included 213 pregnant women with a singleton pregnancy, GDM, and pregnancy weight gain above recommended. Participants were consecutively followed in the time period between July 1st, 2016, and August 31st, 2020. Ultrasound estimations were made within three days before the delivery. Fetal weights estimated using both formulas were compared to the newborns’ weights. Results A total of 133 fetal weight estimations were made. In comparison to the newborns’ weight modified formula had significantly smaller deviation in weight estimation compared to the Hadlock-2 formula, higher frequency of deviation within 5% of newborns weights (78.2% [95% CI=0.74–0.83] vs. 60.2%), smaller frequency of deviations from 5 to 10% (19.5 vs. 33.8%) and above 10%, which was even more significant among macrosomic children. There were 36/50 (72%) correctly diagnosed cases of macrosomia by modified and 33/50 (66%) by Hadlock-2 formula. Area under the curve (AUC) for the modified formula was 0.854 (95% CI=0.776–0.932), and for the Hadlock-2 formula 0.824 (95% CI=0.740–0.908). The positive predictive value of the modified formula was 81.81%, the negative 97.91%. Conclusions In cases of greater fetal weights, the modified formula showed greater precision.

Objectives Evaluate ultrasound diagnostic accuracy, maternal−fetal characteristics and outcomes in case of vasa previa diagnosed antenatally, postnatally or with spontaneous resolution before delivery. Methods Monocentric retrospective study enrolling women with antenatal or postnatal diagnosis of vasa previa at Sant’Anna Hospital in Turin from 2007 to 2018. Vasa previa were defined as fetal vessels that lay 2 cm within the uterine internal os using 2D and Color Doppler transvaginal ultrasound. Diagnosis was confirmed at delivery and on histopathological exam. Vasa previa with spontaneous resolutions were defined as fetal vessels that migrate >2 cm from uterine internal os during scheduled ultrasound follow-ups in pregnancy. Results We enrolled 29 patients (incidence of 0.03%). Ultrasound antenatally diagnosed 25 vasa previa (five had a spontaneous resolution) while four were diagnosed postnatally, with an overall sensitivity of 96.2%, specificity of 100%, positive predictive value of 96.2%, and negative predictive value of 100%. Early gestational age at diagnosis is significally associate with spontaneously resolution (p 0.023; aOR 1.63; 95% IC 1.18–2.89). Nearly 93% of our patient had a risk factor for vasa previa: placenta previa at second trimester or low-lying placenta, bilobated placenta, succenturiate cotyledon, velametous cord insertion or assisted reproduction technologies. Conclusions Maternal and fetal outcomes in case of vasa previa antenatally diagnosed are significally improved. Our data support the evaluation of umbilical cord insertion during routine second trimester ultrasound and a targeted screening for vasa previa in women with risk factor: it allows identification of fetus at high risk, reducing fetal mortality in otherwise healthy newborns.

Objectives To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). Methods The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit’s policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. Results Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0–52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65–1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59–1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66–2.01) or unit policies (aOR 1.04; 95% CI 0.63–1.70). Conclusions Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

Objectives Sphingosine-1-phosphate (S1P) is a signalling lipid involved in embryonic development, physiological homeostasis, and pathogenic processes in multiple organ systems. Disturbance of S1P homeostasis has been associated with various human diseases in which the immune response and vascular integrity are severely compromised. Up-to-date, no study has analyzed S1P levels in neonates. The objective of this study was to determine S1P serum concentrations in neonates and establish S1P reference ranges. Methods S1P levels in the umbilical cord blood of 460 term and preterm neonates were compared to a previously described cohort of healthy adult blood donors. S1P levels were further correlated with demographic characteristics, cellular sources of S1P, and inflammatory markers. Results The median S1P serum level in neonates was 1.70 μmol/L (IQR 1.41–1.97 μmol/L) and significantly higher than normal values reported in adults. S1P levels correlated positively with the number of red blood cells (p<0.001) and negatively with neutrophil precursors (p=0.028). Conclusions Elevated S1P levels in neonates compared to adults possibly result from higher S1P content in its cellular sources due to the essential role of S1P during embryogenesis. Generated S1P ranges may be used as reference ranges for future studies in neonates.