Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

Detection and clinical outcome of small-for-gestational-age fetuses in the third trimester-A comparison between routine ultrasound examination and examination on indication.

INTRODUCTION: Fetal growth restriction is a major risk factor for adverse perinatal outcome. As most of the growth-restricted fetuses are small for gestational age (SGA), an efficient antenatal screening method for SGA fetuses would have a major impact on perinatal health. The aim of this study was to compare the SGA prediction rate achieved with third-trimester routine ultrasound estimation of fetal weight (EFW) with that obtained using ultrasound examination on indication. The secondary aim was to evaluate the clinical outcome in relation to the SGA screening method. MATERIAL AND METHODS: During 1995-2009, two perinatal centers in southern Sweden offered routine ultrasound examination at 32-34 gestational weeks to 99 265 women with singleton pregnancies. Of these, 59 452 (60%) underwent the ultrasound examination. The other population, comprising 24 868 pregnancies, was cared for in another three centers that used a risk-based method with ultrasound examinations on indication only. Of them, 5792 (23%) underwent ultrasound examination at 32-36 gestational weeks. The deviation in the EFW from the expected one was expressed as the EFW z-score, SGA EFW being defined as the EFW z-score less than -2. SGA prediction ability was assessed by receiver operating characteristic (ROC) curves. Crude and adjusted risk ratios were calculated for selected variables of perinatal outcome when comparing the populations. RESULTS: The SGA prediction ability for routine ultrasound was high, area under the ROC curve was 0.90 (95% CI 0.89-0.91). For an EFW z-score of -1, the sensitivity was 67.3% and specificity was 90.5% among routinely screened pregnancies; corresponding numbers in the ultrasound on indication population were 34.3% and 96.6%. The screened population had a lower risk of preterm birth, birthweight z-score less than -3, and Apgar score less than 7 at 5 min with adjusted risk ratios 0.87 (95% CI 0.82-0.92), 0.75 (95% CI 0.61-0.92), and 0.77 (95% CI 0.68-0.87), respectively. No difference in perinatal mortality was detected. There were no differences in perinatal outcome between the two subcohorts of infants born SGA. CONCLUSIONS: Third-trimester routine ultrasound improves the detection of SGA antenatally compared with ultrasound performed on indication, but no convincing improvement in perinatal outcome was identified.

Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France.

AIM: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). METHODS: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

Cerebroplacental ratio as predictor of adverse perinatal outcome in the third trimester.

INTRODUCTION: Fetal growth restriction is associated with adverse perinatal outcome and the clinical management of these pregnancies is a challenge. The aim of this study was to investigate the potential of cerebroplacental ratio (CPR) to predict adverse perinatal outcome in high-risk pregnancies in the third trimester. Another aim was to study whether the CPR has better predictive value than its components, middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA) PI. MATERIAL AND METHODS: The study was a retrospective cohort study including 1573 singleton high-risk pregnancies with Doppler examinations performed at 32+0 to 40+6 gestational weeks at Lund University Hospital and the University Hospital of Malmö between 29 December 1994 and 31 December 2017. Receiver operating characteristics (ROC) curves were used to investigate the predictive value of the gestational age-specific z-scores for CPR, UA PI and MCA PI, respectively, for the primary outcome "perinatal asphyxia/mortality" and the secondary outcomes "birthweight small for gestational age (SGA)" and two composite outcomes: "appropriate for gestational age/large for gestational age liveborn infants with neonatal morbidity" and "SGA liveborn infants with neonatal morbidity." RESULTS: The performance in predicting perinatal asphyxia/mortality was poor for all three variables and did not differ significantly. The ROC area under curve (AUC) was 0.56, 0.55 and 0.53 for CPR, UA PI and MCA PI z-scores, respectively. The ROC AUC for CPR z-scores to predict SGA was 0.73, significantly higher than that for either UA PI or MCA PI (P < .001). The ability of CPR and the MCA PI to predict appropriate for gestational age/large for gestational age infant morbidity and SGA infant morbidity was similar and significantly better than UA PI (P < .001). CONCLUSIONS: In the present study, none of the three Doppler measures proved to be useful in predicting perinatal asphyxia and mortality. CPR and MCA PI were equally good in predicting neonatal morbidity, especially in SGA pregnancies, and both were significantly better predictors than the UA PI. CPR had a high predictive value for SGA at birth, better than that of its two components, UA PI and MCA PI.

Safety Aspects of Perinatal Ultrasound.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety.

Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5 years.

AIM: It is not clear whether perinatal acidosis can predict poor outcomes in extremely preterm infants and we investigated associations between intrapartum hypoxia and mortality and neurodevelopmental outcomes. METHODS: We used nationwide data on 705 infants from the Extremely Preterm Infants in Sweden Study, delivered at 22-26 weeks of gestation during 2004-2007. Comprehensive neurodevelopmental assessments were performed on survivors at 2.5 (n = 456) and 6.5 (n = 441) years of corrected age. Gestational age-related changes in umbilical cord arterial pH were compared with reference values for term newborn infants, and base excess was also calculated. Associations between low blood gas values (<10th percentile) and mortality and neurodevelopmental outcome were estimated. RESULTS: Cord blood determination was more common in surviving infants (P < .001), with pH determined in 322/705 (46%) and base excess in 311/705 (44%). Extremely preterm infants had higher pH values than term infants (P < .0001), with no change from 22 to 26 weeks of gestation (P = .61, r2  = .001). Multiple logistic regression showed no association between low blood gas values and risk of death or neurodevelopmental impairment at 6.5 years (P ≥ .17). CONCLUSION: Hypoxia with acidosis at birth was not associated with an increased risk of death or impaired neurodevelopmental in extremely preterm born children at 6.5 years.

Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016.

Importance: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective: To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants: All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures: Delivery at 22-26 weeks' gestational age. Main Outcomes and Measures: The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results: During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008). Conclusions and Relevance: Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

Antenatal corticosteroids: a retrospective cohort study on timing, indications and neonatal outcome.

INTRODUCTION: An antenatal corticosteroid (ACS) delivery interval of 24 h to seven days is commonly referred to as optimal timing. We aimed to investigate whether the ACS delivery interval was associated with the obstetric indication for treatment and with neonatal complications. MATERIAL AND METHODS: The study was a retrospective chart review of clinical data from preterm neonates delivered at the Skåne University Hospital, Lund University, Sweden, from 1 January 2013 to 31 December 2016. The ACS delivery intervals were compared between groups of women with various clinical scenarios and related to neonatal outcomes. RESULTS: The study included 498 preterm neonates from 431 women. One to seven days before delivery, 41% of the women received ACS. Women with preterm prelabor rupture of membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight days, respectively, compared with women with maternal/fetal indications or preterm labor (three and two days, respectively) (p < 0.001). Neonates with an ACS delivery interval of more than seven days were at a higher risk of respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.05-3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI 1.45-5.33) than were neonates with an ACS delivery interval of one to seven days. CONCLUSION: Optimal timing of ACS treatment varied significantly based on the clinical indication. Women with preterm prelabor rupture of membranes or vaginal bleeding were more likely to have an ACS delivery interval of more than seven days. A prolonged ACS delivery interval was associated with an increased risk of neonatal respiratory morbidity and a prolonged stay in the neonatal care unit, but not with neonatal mortality.

Outcome of extremely preterm infants after iatrogenic or spontaneous birth.

INTRODUCTION: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. MATERIAL AND METHODS: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. RESULTS: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. CONCLUSIONS: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.

EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. METHODS: This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. DISCUSSION: The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. TRIAL REGISTRATION: NCT02097667 registered 31st October 2013.

Doppler Audio Signal Analysis as an Additional Tool in Evaluation of Umbilical Artery Circulation.

Purpose To investigate the predictive capacity of a new method for sound spectrum analysis of Doppler signals recorded from the umbilical artery in high-risk pregnancies. Material and Methods The retrospective study comprised 127 pregnant women with various pregnancy complications between 23 and 39 gestational weeks. Umbilical artery blood flow velocity waveforms were recorded with Doppler ultrasound and characterized by pulsatility index (PI) and blood flow class (BFC). Doppler audio signals were stored on a digital video recorder and the sound frequency at the energy level 15 dB below its peak (MAXpeak-15 dB) was estimated off-line. The prediction of probability for composite adverse pregnancy outcome (operative delivery for fetal distress, admission to neonatal intensive care unit, perinatal death) was evaluated using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results With increasing umbilical artery BFC, the MAXpeak-15 dB frequencies decreased (p < 0.0001) and the PI increased (p < 0.0001). The ROC AUCs for adverse outcome for MAXpeak-15 dB and for PI were 0.842 and 0.836 (p = 0.88), respectively. For the combination of MAXpeak-15 dB and PI, the corresponding AUC was 0.894, significantly higher than that of PI (p < 0.03) and of MAXpeak-15 dB (p < 0.05). Conclusion Umbilical artery Doppler sound spectrum analysis might be a useful supplement to PI in the clinical evaluation of fetoplacental circulation.

Impact of obstetric factors on outcome of extremely preterm births in Sweden: prospective population-based observational study (EXPRESS).

INTRODUCTION: A population-based observational study investigated the contribution of obstetric factors to the survival and postnatal development of extremely preterm infants. MATERIAL AND METHODS: Mortality up to 1 year and neurodevelopment at 2.5 years (Bayley-III test, cerebral palsy, vision, hearing) were evaluated in infants born before 27 weeks of gestation in Sweden 2004-2007 (n = 1011), using logistic regression analyses of risk factors. RESULTS: Of 844 fetuses alive at admission, 8.4% died in utero before labor, 7.8% died intrapartum. Of 707 live-born infants, 15% died within 24 h, 70% survived ≥365 days, 64% were assessed at 2.5 years. The risk of death within 24 h after birth decreased with gestational age [odds ratio (OR) 0.3; 95% CI 0.2-0.4], antenatal corticosteroids (OR 0.3; 95% CI 0.1-0.6), and cesarean section (OR 0.4; 95% CI 0.2-0.9); it increased with multiple birth (OR 3.0; 95% CI 1.5-6.0), vaginal breech delivery (OR 2.3; 95% CI 1.0-5.1), 5-min Apgar score <4 (OR 50.4; 95% CI 28.2-90.2), and birth at a level II hospital (OR 2.6; 95% CI 1.2-5.3). The risk of death between 1 and 365 days remained significantly decreased for gestational age and corticosteroids. The risk of mental developmental delay at 2.5 years decreased with gestational age, birthweight and fetal growth; it increased with vaginal breech delivery (OR 2.0; 95% CI 1.2-7.4), male gender, low Apgar score and high Clinical Risk Index for Babies score. CONCLUSION: Several obstetric factors, including abdominal delivery, influenced the risk of death within the first day of life, but not later. Antenatal corticosteroids and gestational age decreased the mortality up to 1 year. Mental developmental delay was related to vaginal breech delivery.

The added predictive value of biphasic events in ST analysis of the fetal electrocardiogram for intrapartum fetal monitoring.

OBJECTIVE: To study the predictive value of biphasic ST-events for interventions for suspected fetal distress and adverse neonatal outcome, when using ST-analysis of the fetal electrocardiogram (FECG) for intrapartum fetal monitoring. DESIGN: Prospective cohort study. SETTING: Three academic hospitals in Sweden. POPULATION: Women in labor with a high-risk singleton fetus in cephalic position beyond 36 weeks of gestation. METHODS: In women in labor who were monitored with conventional cardiotocography, ST-waveform analysis was recorded and concealed. Traces with biphasic ST-events of the FECG (index) were compared with traces without biphasic events of the FECG. The ability of biphasic events to predict interventions for suspected fetal distress and adverse outcome was assessed using univariable and multivariable logistic regression analyses. MAIN OUTCOME MEASURES: Interventions for suspected fetal distress and adverse outcome (defined as presence of metabolic acidosis (i.e. umbilical cord pH <7.05 and base deficit in extracellular fluid >12 mmol), umbilical cord pH <7.00, 5-min Apgar score <7, admittance to neonatal intensive care unit or perinatal death). RESULTS: Although the presence of biphasic events of the FECG was associated with more interventions for fetal distress and an increased risk of adverse outcome compared with cases with no biphasic events, the presence of significant (i.e. intervention advised according to cardiotocography interpretation) biphasic events showed no independent association with interventions for fetal distress [odds ratio (OR) 1.71, 95% confidence interval (CI) 0.65-4.50] or adverse outcome (OR 1.96, 95% CI 0.74-5.24). CONCLUSION: The presence of significant biphasic events did not discriminate in the prediction of interventions for fetal distress or adverse outcome. Therefore, biphasic events in relation to ST-analysis monitoring during birth should be omitted if future studies confirm our findings.

Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material.

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high-risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in an animal model. In the present pilot study, the method was for the first time applied to human pregnancies. Doppler umbilical artery velocimetry was performed in 13 preterm fetuses before and after two doses of 12 mg betamethasone. The auditory measure defined by the frequency band where the spectral energy had dropped 15 dB from its maximum level (MAXpeak-15 dB ), increased two days after betamethasone administration (p = 0.001) parallel with a less pronounced decrease in PI (p = 0.04). The new auditory parameter MAXpeak-15 dB reflected the changes more sensitively than the PI did.

EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden.

AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions. METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

Survival and neonatal morbidity among extremely preterm born infants in relation to gestational age based on the last menstrual period or ultrasonographic examination.

OBJECTIVES: The aim of this study was to investigate the potential impact of gestational age (GA) estimation on the basis of the last menstrual period (LMP) in comparison with GA based on ultrasound examination on rates of survival and neonatal morbidity among extremely preterm infants. METHODS: The Swedish national registry of infants born extremely preterm (Extremely Preterm Infants in Sweden Study), including infants born before 27 weeks of gestation, was used to identify 645 infants with available information. Incidences of stillbirth, survival, small for GA (SGA), and major neonatal morbidity were calculated in relationship to the GA estimated by each of the approaches. RESULTS: Pregnancies, in general, appeared to be longer when GA was estimated by LMP than by ultrasound (17.2% of the pregnancies were longer than 27 weeks). The incidences of stillbirth, neonatal death, and major neonatal morbidity in relationship to GA were similar for both groups. The risks for SGA were elevated when GA according to ultrasound examination was at least 7 days shorter than GA based on the LMP. CONCLUSIONS: In our cohort of infants born extremely preterm, estimation of GA on the basis of LMP indicated a longer pregnancy than estimated by ultrasound but did not influence the incidences of neonatal survival and morbidity.

Impact of sex on perinatal mortality and morbidity in twins.

OBJECTIVE: Twin studies offer opportunities to investigate mechanisms underlying sex-associated differences in perinatal outcomes. The objective of the study was to investigate sex-related differences in perinatal complications. STUDY DESIGN: A cohort of 16,045 twin pregnancies - 32,090 twins - was explored for obstetric complications, perinatal and infant mortality, and neonatal morbidities. RESULTS: Twin pregnancies with a female fetus had an increased risk for preeclampsia, but otherwise there were no pregnancy complications associated with fetal sex. After birth, female-female twins had lower early neonatal and infant mortality, and lower risk for respiratory morbidities than male-male twins at all gestational ages. In unlike-sexed twin pairs, very preterm males had higher respiratory morbidity than females and, females were at higher risk for being growth restricted. CONCLUSION: Male-male twins have higher respiratory morbidity and neonatal mortality than female-female twins. In unliked-sexed twin pairs, the males seem to be protected by having a female co-twin.

Effectiveness of electronic fetal monitoring with additional ST analysis in vertex singleton pregnancies at >36 weeks of gestation: an individual participant data metaanalysis.

OBJECTIVE: The purpose of this study was to assess the effectiveness of electronic fetal monitoring (EFM) alone and with additional ST analysis (EFM + ST) in laboring women with a singleton term pregnancy that is in cephalic presentation in the prevention of metabolic acidosis by the application of individual patient data metaanalysis. STUDY DESIGN: We conducted an individual patient data metaanalysis using data from 4 randomized trials, which enabled us to account for missing data and investigate relevant subgroups. The primary outcome was metabolic acidosis, which was defined as an umbilical cord-artery pH <7.05 and a base deficit that had been calculated in the extra cellular fluid compartment >12 mmol/L. We performed 8 explanatory subgroup analyses for 8 different endpoints. RESULTS: We analyzed data from 12,987 women and their newborn infants. Metabolic acidosis was present in 57 women (0.9%) in the EFM + ST group and 73 women (1.1%) in the EFM alone group (relative risk [RR], 0.76; 95% CI, 0.53-1.10). Compared with EFM alone, the use of EFM + ST resulted in a reduction in the frequency of instrumental vaginal deliveries (RR, 0.90; 95% CI, 0.83-0.99) and fetal blood samples (RR, 0.49; 95% CI, 0.44-0.55). Cesarean delivery rates were comparable between both groups (RR, 0.99; 95% CI, 0.91-1.09). Subgroup analyses showed that EFM + ST resulted in fewer admissions to a neonatal intensive care unit for women with a duration of pregnancy of >41 weeks (RR, 0.61; 95% CI, 0.39-0.95). CONCLUSION: EFM + ST does not reduce the risk of metabolic acidosis, but it does reduce the need for instrumental vaginal deliveries and fetal blood sampling.