BACKGROUND Severe, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth.METHODS Women with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data.RESULTS The most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86–0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83–0.94).CONCLUSION Ultrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians.TRIAL REGISTRATION ClinicalTrials.gov NCT02097667.FUNDING The European Union, Rosetrees Trust, Mitchell Charitable Trust.

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). 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. 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. 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.

IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18–32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children’s Abilities-Revised questionnaire.Ethics and disseminationThe Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.Trial registration numberMain sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Introduction and aims: Fetal growth restriction is associated with increased risk of adverse perinatal outcome. The aim 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 if CPR has better predictive value than its components, middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA) PI. Methods: A register-based study including 1573 singleton high-risk pregnancies with Doppler examinations at 32+0 to 40+6 gestational weeks at two perinatal centers between 1994 and 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 outcome "perinatal asphyxia/mortality", "birthweight small for gestational age (SGA)" and two composite outcomes: "non-SGA liveborn infants with neonatal morbidity" and "SGA liveborn infants with neonatal morbidity." Sub-analyses were made for pregnancies with spontaneous onset of labor and trial of labor. 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, respectively. CPR performed significantly better than its components in predicting SGA, ROC AUC 0.73. The ability of CPR and the MCA PI to predict the two composite outcomes were similar and significantly better than UA PI. In the sub-analyses the results were similar, but CPR performed significantly better in predicting "perinatal asphyxia/mortality" than its components, although the predicting ability was poor. Conclusions: All three Doppler measures were poor 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 than the UA PI. CPR had high predictive value for SGA at birth.

Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.

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.

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. 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. 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. 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.

The Ian Donald Gold Medal is awarded once a year to an individual who has made a significant scientific contribution to the advancement of diagnostic ultrasound in obstetrics and gynecology and who has changed the way in which ultrasound is practiced, through research or innovation. It is a great honor for me to introduce the 2022 winner of this prestigious award, Professor Eduard Gratacós, from the University of Barcelona, Spain. Some 30 years ago, Eduard was resident in obstetrics and gynecology at Hospital Clinic in Barcelona. In the late 1990s, he spent 4 years in Leuven, Belgium, focusing on fetal surgery. In 2000, he returned to Barcelona, where he became Professor in obstetrics and gynecology. In 2013, when two hospitals merged, he was appointed as Director of the Barcelona Center for Fetal, Maternal and Neonatal Medicine (BCNatal) and of the associated Fetal Medicine Research Center. Eduard Gratacós is head of a large referral center for fetomaternal medicine and fetal surgery, that employs 82 clinicians and takes care of 4500 high-risk pregnancies and performs 80 fetal surgeries annually. The Research Center combines clinical research with advanced laboratory and animal experimental research. Eduard’s main line of research in fetal surgery concerns congenital diaphragmatic hernia. He is one of the pioneers of fetal endoscopic tracheal occlusion (FETO)

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.

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.

ABSTRACT Objective To describe the short‐ and long‐term outcomes of infants with early‐onset fetal growth restriction (FGR) and umbilical artery absent or reversed end‐diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively. Methods This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early‐onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level‐3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small‐for‐gestational‐age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non‐FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery. Results There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non‐FGR group. The FGR infants had a median birth weight of 630 g (range, 340–1165 g) and gestational age at birth of 187 days (range, 164–209 days), as compared with 950 g (range, 470–2194 g) and 185 days (range, 154–209 days), respectively, in the non‐FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non‐FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non‐FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent ( P = 0.008, P < 0.001 and P = 0.017, respectively). In the FGR group, the survival rate at 2 years (83% of liveborn infants) and the rate of cerebral palsy (7%) did not differ significantly from those in the non‐FGR group (82% and 8%, respectively). The rate of survival without neurodevelopmental impairment was higher in the non‐FGR group (83%) than in the FGR group (62%) ( P < 0.001), as well as in infants in the FGR group delivered at or after 26 weeks (72%) compared with those delivered before 26 weeks (40%) ( P = 0.003). Within the FGR group, outcomes were similar between twins and singletons and, in those who survived beyond 2 years, outcomes were similar between fetuses with absent and those with reversed end‐diastolic flow in the umbilical artery. Conclusions Infants delivered very preterm after severe FGR with AREDF in the umbilical artery had a similar rate of survival as did non‐FGR infants of corresponding gestational age; however, they were at higher risk of neurodevelopmental impairment, the risk being most pronounced following birth before 26 weeks. Gestational age remains an important factor associated with the prognosis of early‐onset FGR; nevertheless, the present results support the hypothesis, which should be tested prospectively, that fetuses with early‐onset FGR and umbilical artery AREDF may benefit from early intervention rather than expectant management, and that umbilical artery Doppler findings could be incorporated into clinical protocols for cases very early in gestation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

ABSTRACT Objective To investigate if the extent of absent end‐diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome. Methods This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (T a /T tot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the T a /T tot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed. Results A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163–279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320–3326 g) and deviation from expected birth weight (standard deviation score) was –2.975 (range, –6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the T a /T tot ratio in the total study group. Mean T a /T tot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively ( P = 0.002). For fetuses examined before 30 weeks' gestation, a T a /T tot ratio cut‐off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver‐operating‐characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66). Conclusions In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth‐restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision‐making in very preterm growth‐restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

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. 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.” 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). 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.

In recent years, ultrasound clinics whose primary purpose is to provide souvenir two-dimensional or three-dimensional (3D) images or video recordings of the developing baby have become commonplace. In light of well-publicized concerns about ultrasound safety and the potential for anxiety to be caused by incorrect diagnosis and, in certain cases, for false reassurance to be given, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) does not endorse ultrasound scans undertaken solely for non-diagnostic purposes in these settings. In this context, the distinction between clinics offering diagnostic obstetric or gynecological ultrasound performed by practitioners who are trained, certified and recognized by national and/or professional bodies and those settings undertaking ultrasound scans without these safeguards, whose primary intent is ‘souvenir ultrasound’, is important.

The embryonic period of gestation extends from conception until 9 weeks post-conception. For the purposes of this guidance, it is assumed that the embryonic period is completed at 10 + 6 weeks (based on last menstrual period dating or crown–rump length). This period is characterized by rapid cell division and development of the embryonic organs. At this stage, the fetal–placental circulation is not yet established. Spectral Doppler, color flow imaging, power imaging and other Doppler ultrasound modalities should not be used routinely in the embryonic period. If use of Doppler is clinically indicated, then the exposure time should be kept to a minimum. The fetal period commences at 11 weeks (after the last menstrual period; corresponding to a crown–rump length ≥ 45 mm). By this stage, organogenesis is complete and the fetal–placental circulation is established. From 11 + 0 to 13 + 6 weeks, spectral Doppler, color flow imaging, power imaging and other Doppler ultrasound modalities may be used routinely for certain clinical indications, such as screening for trisomy and cardiac anomalies. When performing Doppler ultrasound, the displayed thermal index (TI) should be ≤ 1.0 and exposure time should be kept as short as possible (usually no longer than 5–10 min). When scanning maternal uterine arteries at any point in the first trimester, there are unlikely to be any fetal safety implications as long as the embryo/fetus lies outside the Doppler ultrasound beam.

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.

On March 11, 2020, the World Health Organization formally declared the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known as COVID-19) a pandemic. This has impacted the way health care facilities operate globally to ensure patient and practitioner safety and to minimize all risks associated with infection transmission.

care obstetric units in Ghana between April and July 2015. All 3 hospitals are located in Southern Ghana. The Korlebu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi each oversee ∼11,000 annual deliveries and Cape Coast Teaching Hospital (CCTH) in Kumasi oversees ∼2800 deliveries annually. Data were collected regarding each hospital’s total deliveries, live births, and maternal deaths during the study period. Research assistants reviewed daily admission and delivery records for pregnant women between the ages of 18 and 49 years who either delivered at a study site or were referred to a study site within 42 days after completion of pregnancy with pregnancy-related or delivery-related complications. A version of the World Health Organization (WHO) Maternal Near Miss Screening Tool, modified for use in settings without all the intervention procedures or laboratory tests of the full WHO tool, was used. Patients were assessed for symptom-based, intervention-based, or organ dysfunction-based criteria, and were labeled “nearmiss” if there was a positive response to any of the 3. Patients who did not meet near-miss criteria qualified for the control group, and 2 uncomplicated, vaginal deliveries were included as controls for each near-miss case. Analysis did not include women who died during childbirth or did not provide consent. The primary cause and contributing factors for each near-miss case were determined by a physician and were based on the WHO International Classification of Diseases, and then further reviewed for confirmation by a study investigator. Of 8433 live births during the study period, 288 were identified to be cases of maternal near-miss [3.42%, or 34.2 maternal near-misses per 1000 live births [95% confidence interval (CI): 30.2-38.1]. By study site, there were 79 (27.5%) near-misses at CCTH, 120 (41.7%) at KATH, and 89 (30.8%) at KBTH. Across the 3 study sites, there were 62 maternal deaths per 1000 live births [maternal mortality incidence ratio of 7.35 (95% CI: 5.5-9.2)] during the study period; the near-miss to maternal mortality ratio was 4.6:1 (95% CI: 3.4-6.0)]. Severe preeclampsia/eclampsia was the most common primary cause of near-miss cases (n= 110; 38.2%), followed by severe hemorrhage (n= 35, 12.1%), ruptured uterus (n= 12, 4.2%), and maternal sepsis (n= 10, 3.6%). The most common contributing causes of maternal near-miss were anemia (n= 81, 28.1%), hypertensive disorder (n= 78, 27.1%), infection during pregnancy (n= 49, 17.0%), obstructed labor (n= 39, 13.5%), and other obstetric complications (n= 41, 14.2%). The proportion of contributing causes varied by site. KATH had lower rates of preeclampsia and eclampsia compared to the other sites, CCTH had a higher proportion of pregnancy-related infection and anemia, and KBTH had more cases of hypertensive disorders, preeclampsia and eclampsia. In a multivariate model, maternal fever within 7 days before birth was associated with maternal near-miss (odds ratio= 5.95, 95% CI: 3.754-9.424). Deliveries beginning in spontaneous labor were significantly less likely to have a maternal near-miss (odds ratio= 0.09, 95% CI: 0.057-0.141). In conclusion, maternal near-miss cases outnumbered maternal mortality at a ratio of 4.6 to 1. The maternal nearmiss incidence in this study was ∼34 per 1000 live births. The leading cause of near-miss was determined to be preeclampsia/eclampsia, and the single biggest factor associated with maternal-near miss was maternal fever in the 7 days leading up to delivery. Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016