Validation of the Fetal Medicine Foundation competing risks model for small for gestational age neonates in early third trimester.

OBJECTIVES: To evaluate the new 36 weeks' Fetal Medicine Foundation (FMF) competing risks model for the prediction of small for gestational age (SGA) at an earlier gestation of 30+0 to 34+0 weeks. METHODS: This is a retrospective multi-center cohort study of prospectively collected data on 3,012 women with singleton pregnancies undergoing ultrasound examination at 30+0 - 34+0 weeks' gestation, as part of a universal screening program. We used the default 36 weeks' FMF competing risks model for prediction of SGA, combining maternal factors (age, obstetric and medical history, weight, height, smoking, race, conception), estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI), to calculate risks for different cut-offs of birth weight percentile and gestational age at delivery. We examined the model's accuracy by means of discrimination and calibration. RESULTS: The prediction of SGA<3rd percentile improves with the addition of UtA-PI and with shorter examination-to-delivery interval. For 10% false positive rate, maternal factors, EFW and UtA-PI predicted 88.0%, 74.4% and 72.8% of SGA <3rd percentile delivered <37, <40 and <42 weeks, respectively. The corresponding figures for SGA 10th percentile were 83.9%, 69.3% and 66.2%. In terms of population stratification, if the biomarkers used are EFW and UtA-PI and the aim is to detect 90% of SGA <10th percentile, then 10.8% of the population should be scanned within two weeks after the initial assessment, an additional 7.2% (total screen positive rate, SPR 18%) should be scanned within two and four weeks after the initial assessment and an additional 11.7% (total SPR 29.7%) should be examined within four and six weeks after the initial assessment. The new model was well calibrated. CONCLUSIONS: The 36 weeks' FMF competing risks model for SGA is also applicable and accurate at 30+0 - 34+0 weeks' gestation, providing effective risk stratification, especially for cases leading to birth <37 weeks. This article is protected by copyright. All rights reserved.

Effect of mode of delivery on perinatal outcome in severe preterm birth: systematic review and meta-analysis.

OBJECTIVE: To review the evidence on the effect of mode of delivery on perinatal outcome of fetuses born before 32 weeks' gestation. METHODS: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), the ClinicalTrials.gov registry and gray literature sources were searched, starting from the year 2000 to reflect contemporary practice in perinatal care. Non-randomized or randomized studies that included singleton fetuses without chromosomal abnormality or major congenital defect delivered vaginally or via Cesarean section were eligible for inclusion in the analysis. Primary outcomes were neonatal death, defined as death in the first 28 days of age, and survival to discharge. Secondary outcomes were other adverse perinatal events. The ROBINS-I tool was used to assess the risk of bias. The overall quality of evidence for the outcomes was assessed according to GRADE. Summary odds ratios (ORs) with 95% CIs were calculated, and random-effects models were used for data synthesis. Subgroup analysis was performed for delivery before 28 weeks, delivery between 28 and 32 weeks and according to fetal presentation at delivery. RESULTS: A total of 27 retrospective studies (22 887 neonates) were included in the systematic review and meta-analysis, all of which reported on singleton pregnancies. Among cases born before 28 weeks, vaginal delivery significantly increased the risk of neonatal death of fetuses with any type of presentation (n = 1496) (OR 1.87 (95% CI, 1.05-3.35); I2 = 65%, very low quality of evidence) and of fetuses with breech presentation (n = 733) (OR 3.55 (95% CI, 2.42-5.21); I2 = 21%, moderate quality of evidence). The odds of survival to discharge were significantly decreased among fetuses with breech presentation delivered before 28 weeks (n = 646) (OR 0.36 (95% CI, 0.24-0.54); I2 = 21%, low quality of evidence). Among breech fetuses born between 28 and 32 weeks, vaginal delivery increased the odds of perinatal death (intrapartum and neonatal) (n = 1581) (OR 3.06 (95% CI, 1.47-6.35); I2 = 0%, high quality of evidence). In non-cephalic fetuses born between 24 and 32 weeks, vaginal delivery decreased the odds of survival to discharge (n = 1030) (OR 0.28 (95% CI, 0.19-0.40); I2 = 0%, moderate quality of evidence). No significant effect on mortality of mode of delivery was observed in cephalic fetuses at any gestational age. CONCLUSIONS: This systematic review and meta-analysis suggests that vaginal delivery in severe preterm birth is associated with an increased risk of neonatal and perinatal death in breech fetuses, while no significant association was observed for cephalic fetuses. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neonatal and long-term outcomes of infants with congenital cytomegalovirus infection and negative amniocentesis: systematic review and meta-analysis.

OBJECTIVE: Cytomegalovirus (CMV) DNA is detectable in the amniotic fluid collected by amniocentesis in cases in which the fetus has been infected. However, cases of congenital neonatal CMV infection with a negative amniocentesis result have also been reported in the literature. The aim of the present study was to compare pregnancies with a negative amniocentesis result to those with a positive amniocentesis result in terms of incidence of fetal insult and long-term sequelae. METHODS: Observational studies that included pregnant women with CMV infection who underwent amniocentesis and that reported their results together with neonatal and/or long-term outcomes of the offspring were included. The risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. The rate of severe symptoms at birth, defined as neurological symptoms or multiorgan involvement at birth, and the rate of severe sensorineural hearing loss (SNHL) and/or neurodevelopmental impairment at follow-up were the main outcomes of the study. The secondary outcome was the rate of pregnancy termination due to the presence of CMV-associated central nervous system (CNS) findings or multiorgan involvement on ultrasound/magnetic resonance imaging (MRI). RESULTS: Seven studies were included in the systematic review and meta-analysis. The pooled false-negative rate of amniocentesis was 8.0% (95% CI, 5.0-13.0%). The pooled rate of severe symptoms at birth was 0.0% (95% CI, 0.0-1.0%; I2 = 0%) in fetuses with a negative amniocentesis result and 22.0% (95% CI, 11.0-38.0%; I2 = 75%) in those with a positive amniocentesis result. The pooled odds ratio (OR) was 0.03 (95% CI, 0.01-0.10; I2 = 0%). The pooled rate of severe SNHL and/or neurodevelopmental impairment at follow-up in fetuses with a negative amniocentesis result was 0.0% (95% CI, 0.0-1.0%; I2 = 0%) and, in those with a positive amniocentesis result, it was 14.0% (95% CI, 7.0-26.0%; I2 = 64%). The pooled OR was 0.04 (95% CI, 0.01-0.14; I2 = 0%). The pooled rate of pregnancy termination due to the presence of CMV-associated CNS findings or multiorgan involvement on ultrasound/MRI was 0.0% (95% CI, 0.0-2.0%; I2 = 0%) in fetuses with a negative amniocentesis result and 20.0% (95% CI, 10.0-36.0%; I2 = 82%) in those with a positive amniocentesis result. The pooled OR was 0.03 (95% CI, 0.01-0.08; I2 = 0%). A subgroup analysis including only pregnancies with primary CMV infection and a sensitivity analysis including only prospective studies were carried out, showing very similar results to those of the main analysis. CONCLUSION: A negative amniocentesis result in pregnant women with CMV infection ensures lack of fetal insult and long-term sequelae to the child, even if transmission has occurred. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Stillbirth due to SARS-CoV-2 placentitis without evidence of intrauterine transmission to fetus: association with maternal risk factors.

OBJECTIVES: To describe the placental pathology, fetal autopsy findings and clinical characteristics of pregnancies that resulted in stillbirth owing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, and to identify potential risk factors. METHODS: This was a prospective multicenter study of non-vaccinated pregnant women affected by coronavirus disease 2019 (COVID-19) in Greece from April 2020 to August 2021. A total of 165 placentas were examined histologically and six cases of stillbirth associated with SARS-CoV-2 placentitis were retrieved. Complete fetal autopsy was performed in three of these cases. Gross, histopathological, immunohistochemical, molecular and electron microscopy examinations were carried out in the stillbirth placentas and fetal organs. The histological findings of cases with SARS-CoV-2 placentitis were compared with those in 159 cases with maternal COVID-19 which resulted in a live birth. Regression analysis was used to identify predisposing risk factors for SARS-CoV-2 placentitis. RESULTS: The placentas of all six stillborn cases showed severe and extensive histological changes typical of SARS-CoV-2 placentitis, characterized by a combination of marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage, associated with intensely positive immunostaining for SARS-CoV-2 spike protein, the presence of virions on electron microscopy and positive reverse-transcription polymerase chain reaction test of placental tissues. The histological lesions obliterated over 75% of the maternal intervillous space, accounting for intrauterine fetal death. Similar histological lesions affecting less than 25% of the placenta were observed in seven liveborn neonates, while the remaining 152 placentas of COVID-19-affected pregnancies with a live birth did not show these findings. Complete fetal autopsy showed evidence of an asphyctic mode of death without evidence of viral transmission to the fetus. The mothers had mild clinical symptoms or were asymptomatic, and the interval between maternal COVID-19 diagnosis and fetal death ranged from 3 to 15 days. Statistically significant predisposing factors for SARS-CoV-2 placentitis included thrombophilia and prenatally diagnosed fetal growth restriction (FGR). Multiple sclerosis was seen in one case. CONCLUSIONS: SARS-CoV-2 placentitis occurred uncommonly in COVID-19-affected pregnancies of non-vaccinated mothers and, when extensive, caused fetal demise, with no evidence of transplacental fetal infection. Thrombophilia and prenatally detected FGR emerged as independent predisposing factors for the potentially lethal SARS-CoV-2 placentitis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Influence of the second stage of labor on maternal and neonatal outcomes in vaginal births after caesarean section: a multicenter study in Germany.

BACKGROUND: The American College of Obstetricians and Gynecologists (ACOG) introduced a new standard of care in 2014, extending the duration of the second stage of labor in order to reduce caesarean delivery (CD) rates and its severe complications. The aim of the present study is to evaluate success rates of trial of labor after caesarean section (TOLAC), as well as maternal and neonatal outcomes after the establishment of the recent guidelines. METHODS: A retrospective study was performed at two large departments in Germany from January 2008 to January 2018. Patients undergoing TOLAC were divided into two groups. Group I (958 patients) was constituted before the establishment of the current guidelines, and Group II (588 patients) after the establishment of the guidelines. A subgroup analysis was performed to compare neonatal outcomes after successful TOLAC and operative vaginal delivery with those after failed TOLAC and secondary CD. RESULTS: The success rate of vaginal births after cesarean section (VBAC) fell from 66.4% in Group I to 55.8% in Group II (p < 0.001). The median duration of the second stage of labor was statistically significantly longer in Group II than in Group I (79.3 ± 61.9 vs. 69.3 ± 58.2 min) for patients without previous vaginal birth. The incidence of operative vaginal delivery decreased from Group I to Group II (9.6% vs. 6.8%). The incidence of third- and fourth-degree perineal lacerations, blood loss and emergency CD were similar in the two groups. Concerning the neonatal outcome, our groups did not differ significantly in regard of rates of umbilical artery cord pH < 7.1 (p = 0.108), the 5-min Apgar scores below 7 (p = 0.224) and intubation (p = 0.547). However, the transfer rates to the neonatal care unit were significantly higher in Group II than in Group I (p < 0.001). Neonatal outcomes did not differ significantly in the subgroup analysis. CONCLUSION: Extending the second stage of labor does not necessarily result in more vaginal births after TOLAC. Maternal and neonatal outcomes were similar in both groups. Further studies will be needed to evaluate the role of operative vaginal delivery and the duration of the second stage of labor in TOLAC.

Is nuchal translucency measurement feasible in early pregnancy?

BACKGROUND: To investigate whether early nuchal translucency measurement at 7+0 to 9+0 weeks (NT7-9w) is feasible, obtain normal values for different crown-rump lengths (CRL) in the above weeks and create percentile tables. METHODS: A prospective study was conducted in the Obstetrics and Gynecology Department of the University Hospital of Ioannina, including data from women with singleton pregnancies, examined in the early pregnancy unit between November 2010 and May 2015 at a CRL of 10-27 mm. The early pregnancy scan was performed vaginally, and the NT7-9w, CRL, fetal heart rate, and mean yolk sac diameter were measured. Demographic data, including body mass index and smoking, were recorded. RESULTS: NT7-9w was measured successfully in 192 fetuses out of 210 (91.4 %), with a CRL ranging from 10-27 mm. The median maternal age was 31 (range 18-43) years, and the median CRL was 19.9 (range 10.0-27.0) mm. Considering the above measurements, we created normal values and percentiles tables of NT at 7+0 to 9+0 weeks in relation to the corresponding CRL measurement. CONCLUSION: According to the literature, this is the first attempt to measure NT in such weeks of pregnancy. NT measurement as early as 7+0 to 9+0 is feasible and normal values can be created and correlated with CRL measurements. HIPPOKRATIA 2021, 25 (4):151-155.

Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx).

OBJECTIVE: There are limited, unmatched data reporting low complication rates in pregnant women with coronavirus disease 2019 (COVID-19). The aim of this study was to compare COVID-19-related outcomes between pregnant and non-pregnant women after adjusting for potential risk factors for severe outcomes. METHODS: Data were obtained from the COVID-19 National Data Registry of Mexico, which is an ongoing prospective cohort of people of any age with clinically suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and admitted to 475 monitoring hospitals. This study included pregnant and non-pregnant women of reproductive age (15-45 years) with COVID-19 confirmed by reverse transcription polymerase chain reaction. To adjust for underlying risk factors, propensity score matching was conducted for chronic obstructive pulmonary disease, asthma, smoking, hypertension, cardiovascular disease, obesity, diabetes, chronic renal disease, immunosuppression, age, language, nationality and level of health insurance. The primary outcome was death. Secondary outcomes were pneumonia, intubation and intensive care unit (ICU) admission. RESULTS: The cohort comprised 5183 pregnant and 175 905 non-pregnant women with COVID-19. The crude (unmatched) rates of death, pneumonia, intubation and ICU admission in pregnant compared with non-pregnant women were 1.5% vs 1.5%, 9.9% vs 6.5%, 8.1% vs 9.9% and 13.0% vs 6.9%, respectively. After propensity score matching (5183 pregnant and 5183 non-pregnant matched women), pregnant women had a higher odds of death (odds ratio (OR), 1.84; 95% CI, 1.26-2.69), pneumonia (OR, 1.86; 95% CI, 1.60-2.16) and ICU admission (OR, 1.86; 95% CI, 1.41-2.45) than non-pregnant women, but similar odds of intubation (OR, 0.93; 95% CI, 0.70-1.25). CONCLUSION: After adjusting for background demographic and medical factors, pregnancy is a risk factor for death, pneumonia and ICU admission in SARS-CoV-2-infected women of reproductive age. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Heterogeneity in defining fetal corpus callosal pathology: systematic review.

OBJECTIVE: Fetal anomalies of the corpus callosum (CC) have been reported in the prenatal imaging literature since 1985, and, especially when isolated, pose challenges for both the patient and fetal medicine specialist. The purpose of this study was to review systematically the literature on prenatally diagnosed abnormalities of the CC, focusing on the terminology used to describe abnormalities other than complete agenesis of the CC, and to assess the heterogeneity of the nomenclature and definitions used. METHODS: This study was conducted in accordance with the PRISMA statement for reporting systematic reviews. A literature search was performed to identify prospective or retrospective case series or cohort studies, published in English, French, Italian, German or Spanish, reporting fetal imaging findings and describing anomalies of the CC. Quality and risk of bias of the studies were evaluated using the Newcastle-Ottawa scale and a modification of the scale developed by Conde-Agudelo et al. for other fetal imaging studies. The data extracted included the number of patients, the number of different anomalies identified, the descriptive names of the anomalies, and, where applicable, the definitions of the anomalies, the number of cases of each type of anomaly and the biometric charts used. Secondary tests used to confirm the diagnosis, as well as the postnatal or post-termination tests used to ascertain the diagnosis, were also recorded. RESULTS: The search identified 998 records, and, after review of titles and abstracts and full review of 45 papers, 27 studies were included initially in the review, of which 24 were included in the final analysis. These 24 studies had a broad range of quality and risk of bias and represented 1135 cases of CC anomalies, of which 49% were complete agenesis and the remainder were described using the term partial agenesis or nine other terms, of which five had more than one definition. CONCLUSIONS: In comparison to the postnatal literature, in the prenatal literature there is much greater heterogeneity in the nomenclature and definition of CC anomalies other than complete agenesis. This heterogeneity and lack of standard definitions in the prenatal literature make it difficult to develop large multicenter pooled cohorts of patients who can be followed in order to develop a better understanding of the genetic associations and neurodevelopmental and psychological outcomes of patients with CC anomalies. As this information is important to improve counseling of these patients, a good first step towards this goal would be to develop a simpler categorization of prenatal CC anomalies that matches better the postnatal literature. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome of pregnancies with prenatal diagnosis of vasa previa: systematic review and meta-analysis.

OBJECTIVES: To derive accurate estimates of perinatal survival in pregnancies with and without a prenatal diagnosis of vasa previa based on a systematic review of the literature and meta-analysis. METHODS: A search of MEDLINE, EMBASE and The Cochrane Library was performed to review relevant citations reporting on the perinatal outcomes of pregnancies with vasa previa. We included prospective and retrospective cohort and population studies that provided data on pregnancies with a prenatal diagnosis of vasa previa or cases diagnosed at birth or following postnatal placental examination. Meta-analysis using a random-effects model was performed to derive weighted pooled estimates of perinatal survival (excluding stillbirths and neonatal deaths) and intact perinatal survival (additionally excluding hypoxic morbidity). Incidence rate difference (IRD) meta-analysis was used to estimate the significance of differences in pooled proportions between cases of vasa previa with and those without a prenatal diagnosis. Heterogeneity between studies was estimated using Cochran's Q and the I2 statistic. RESULTS: We included 21 studies reporting on the perinatal outcomes of 683 pregnancies with a prenatal diagnosis of vasa previa. There were three stillbirths (1.01% (95% CI, 0.40-1.87%)), five neonatal deaths (1.19% (95% CI, 0.52-2.12%)) and 675 surviving neonates, resulting in a pooled estimate for perinatal survival of 98.6% (95% CI, 97.6-99.3%). Based on seven studies that included cases of vasa previa with and without a prenatal diagnosis, the pooled perinatal survival in pregnancies without a prenatal diagnosis (61/118) was 72.1% (95% CI, 50.6-89.4%) vs 98.6% (95% CI, 96.7-99.7%) in cases with a prenatal diagnosis (224/226). Therefore, the risk of perinatal death was 25-fold higher when a diagnosis of vasa previa was not made antenatally, compared with when it was (odds ratio (OR), 25.39 (95% CI, 7.93-81.31); P < 0.0001). Similarly, the risk of hypoxic morbidity was increased 50-fold in cases with vasa previa without a prenatal diagnosis compared with those with a prenatal diagnosis (36/61 vs 5/224; OR, 50.09 (95% CI, 17.33-144.79)). The intact perinatal survival rate in cases of vasa previa without a prenatal diagnosis was significantly lower than in those with a prenatal diagnosis (28.1% (95% CI, 14.1-44.7%) vs 96.7% (95% CI, 93.6-98.8%)) (IRD, 73.4% (95% CI, 53.9-92.7%); Z = -7.4066, P < 0.001). CONCLUSIONS: Prenatal diagnosis of vasa previa is associated with a high rate of perinatal survival, whereas lack of an antenatal diagnosis significantly increases the risk of perinatal death and hypoxic morbidity. Further research should be undertaken to investigate strategies for incorporating prenatal screening for vasa previa into routine clinical practice. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Incidence of pre-eclampsia and other perinatal complications among pregnant women with congenital heart disease: systematic review and meta-analysis.

OBJECTIVE: It has been proposed recently that pre-eclampsia (PE) may originate from maternal cardiac maladaptation rather than primary placental insult. As congenital heart disease (CHD) is associated with reduced adaptation to the hemodynamic needs of pregnancy, it is hypothesized that women with CHD have an increased risk of PE. The aim of this systematic review was to investigate the risk of PE in pregnant women with CHD. METHODS: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, Chinese or German, with no time restrictions, using databases such as PubMed, Web of Science and SCOPUS. Randomized controlled trials and observational studies (prospective or retrospective cohorts) of pregnant women with a history of CHD were sought. The main outcome was the incidence of PE (including eclampsia and HELLP syndrome). For quality assessment of the included studies, two reviewers assessed independently the risk of bias. For the meta-analysis, the incidence of PE in pregnancies (those beyond 20 weeks' gestation) was calculated using single-proportion analysis by random-effects modeling (weighted by inverse variance). Heterogeneity between studies was assessed using the χ2 (Cochran's Q), tau2 and I2 statistics. Subgroup analysis was performed, and meta-regression was used to assess the influence of several covariates on the pooled results. RESULTS: A total of 33 studies were included in the meta-analysis, including 40 449 women with CHD and a total of 40 701 pregnancies. The weighted incidence of PE was 3.1% (95% CI, 2.2-4.0%), with true-effect heterogeneity of 93% according to I2 , and no publication bias found. No difference was found in the weighted incidence of PE between studies including cyanotic CHD vs those excluding (or not reporting) cyanotic CHD (2.5% (95% CI, 1.6-3.4%) vs 4.1% (95% CI, 2.4-5.7%); P = 0.0923). Meta-regression analysis showed that the only cofactor that significantly influenced the incidence of PE in each study was the reported incidence of aortic stenosis; studies with a higher incidence of aortic stenosis had a higher incidence of PE (estimate: 0.0005; P = 0.038). CONCLUSIONS: We failed to demonstrate an incidence of PE above the expected baseline risk in women with CHD. This observation contradicts the theory of the cardiac origin of PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Quality assessment of fetal middle cerebral and umbilical artery Doppler images using an objective scale within an international randomized controlled trial.

OBJECTIVES: To determine the quality of Doppler images of the fetal middle cerebral artery (MCA) and umbilical artery (UA) using an objective scale, and to determine the reliability of this scale, within a multicenter randomized controlled trial (Revealed versus concealed criteria for placental insufficiency in unselected obstetric population in late pregnancy (Ratio37)). METHODS: The Ratio37 trial is an ongoing randomized, open-label, multicenter controlled study of women with a low-risk pregnancy recruited at 20 weeks. Doppler measurements of the fetal MCA and UA were performed at 37 weeks. Twenty patients from each of the six participating centers were selected randomly, with two images evaluated per patient (one each for the MCA and UA). The quality of a total of 240 images was evaluated by six experts, scored on an objective scale of six items. Inter- and intrarater reliability was assessed using the Fleiss-modified kappa statistic for ordinal scales. RESULTS: On average, 89.2% of MCA images and 85.0% of UA images were rated as being of perfect (score of 6) or almost perfect (score of 5) quality. Kappa values for intrarater reliability of quality assessment were 0.90 (95% CI, 0.88-0.92) and 0.90 (95% CI, 0.88-0.93) for the MCA and UA, respectively. The corresponding inter-rater reliability values were 0.85 (95% CI, 0.81-0.89) and 0.84 (95% CI, 0.80-0.89), respectively. CONCLUSION: The quality of MCA and UA Doppler ultrasound images can be evaluated reliably using an objective scale. Over 85% of images, which were obtained by operators from a broad range of clinical practices within a multicenter study, were rated as being of perfect or almost perfect quality. Intra- and inter-rater reliability of quality assessment was very good. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Effect on perinatal outcome of prophylactic antibiotics in preterm prelabor rupture of membranes: network meta-analysis of randomized controlled trials.

OBJECTIVES: Prophylactic antibiotics are recommended routinely for preterm prelabor rupture of membranes (PPROM), but there is an abundance of potential treatments and a paucity of comparative information. The aims of this network meta-analysis were to compare the efficiency of different antibiotic regimens on perinatal outcomes and to assess the quality of the current evidence. METHODS: This was a network meta-analysis of randomized controlled trials comparing prophylactic antibiotics, or regimens of antibiotics, with each other or with placebo/no treatment, in women with PPROM. MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, US Registry of Clinical Trials ( www.ClinicalTrials.gov) and gray literature sources were searched. The primary outcomes were neonatal mortality and chorioamnionitis; secondary outcomes included other measures of perinatal morbidity. Relative effect sizes were estimated using risk ratios (RR) and the relative ranking of the interventions was obtained using cumulative ranking curves. The quality of evidence for the primary outcomes was assessed according to GRADE guidelines, adapted for network meta-analysis. RESULTS: The analysis included 20 studies (7169 participants randomized to 15 therapeutic regimens). For the outcome of chorioamnionitis, clindamycin + gentamycin (network RR, 0.19 (95% CI, 0.05-0.83)), penicillin (RR, 0.31 (95% CI, 0.16-0.6)), ampicillin/sulbactam + amoxicillin/clavulanic acid (RR, 0.32 (95% CI, 0.12-0.92)), ampicillin (RR, 0.52 (95% CI, 0.34-0.81)) and erythromycin + ampicillin + amoxicillin (RR, 0.71 (95% CI, 0.55-0.92)) were superior to placebo/no treatment. Erythromycin was the only effective drug for neonatal sepsis (RR, 0.74 (95% CI, 0.56-0.97)). Clindamycin + gentamycin (RR, 0.32 (95% CI, 0.11-0.89)) and erythromycin + ampicillin + amoxicillin (RR, 0.83 (95% CI, 0.69-0.99)) were the only effective regimens for respiratory distress syndrome, whereas ampicillin (RR, 0.42 (95% CI, 0.20-0.92)) and penicillin (RR, 0.49 (95% CI, 0.25-0.96)) were effective in reducing the rates of Grade-3/4 intraventricular hemorrhage. None of the antibiotics appeared significantly more effective than placebo/no treatment in reducing the rates of neonatal death, perinatal death and necrotizing enterocolitis. No network RR could be estimated for neonatal intensive care unit admission. The overall quality of the evidence, according to GRADE guidelines, was moderate to very low, depending on the outcome and comparison. CONCLUSIONS: Several antibiotics appear to be more effective than placebo/no treatment in reducing the rate of chorioamnionitis after PPROM. However, none of them is clearly and consistently superior compared to other antibiotics, and most are not superior to placebo/no treatment for other outcomes. The overall quality of the evidence is low and needs to be updated, as microbial resistance may have emerged for some antibiotics, while others are underrepresented in the existing evidence. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Third-trimester uterine artery Doppler for prediction of adverse outcome in late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the predictive ability for adverse perinatal outcome of abnormal third-trimester uterine artery Doppler in late small-for-gestational-age (SGA) fetuses. METHODS: A systematic search was performed to identify relevant observational studies and randomized controlled trials evaluating the performance of abnormal third-trimester uterine artery Doppler for the prediction of adverse perinatal outcome in suspected SGA fetuses and SGA neonates. Abnormal uterine artery Doppler was defined as uterine artery pulsatility index > 95th percentile or ≥ 2 SD above the mean, or bilateral uterine artery notching. Hierarchical summary receiver-operating-characteristics (ROC) curves were constructed using random-effects modeling. Bayesian analysis was used to calculate the posterior probability of adverse perinatal outcome following an abnormal or normal uterine artery Doppler assessment. RESULTS: Seventeen observational studies (including 7552 fetuses either diagnosed with suspected SGA (n = 3461) or later diagnosed as a SGA neonate (n = 4091)) met the inclusion criteria; no randomized-controlled trials met the inclusion criteria. Summary ROC curves showed that, among suspected SGA fetuses, the best predictive accuracy of abnormal third-trimester uterine artery Doppler was for perinatal mortality and the worst was for composite adverse perinatal outcome, with areas under the summary ROC curves of 0.90 and 0.66, respectively. The corresponding positive and negative likelihood ratios were 16.5 and 0.6 for perinatal mortality and 2.82 and 0.65 for composite adverse perinatal outcome, respectively. Following an abnormal vs normal uterine artery Doppler assessment, the posterior risks for composite adverse perinatal outcome, admission to the neonatal intensive care unit, Cesarean section for intrapartum fetal compromise, 5-min Apgar score < 7, neonatal acidosis and perinatal death were: 52.3% vs 20.2%, 48.6% vs 18.7%, 23.1% vs 15.2%, 3.59% vs 1.32%, 9.15% vs 5.12% and 31.4% vs 1.64%, respectively. CONCLUSION: Abnormal uterine artery Doppler in the third trimester appears to be moderately useful in predicting perinatal death in pregnancies with suspected SGA. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Doppler uterino en el tercer trimestre para la predicción de resultados adversos en fetos pequeños para la edad gestacional: revisión sistemática y metaanálisis OBJETIVO: Investigar la capacidad de predicción de resultados perinatales adversos del Doppler uterino anómalo en el tercer trimestre en fetos pequeños para la edad gestacional (PEG). MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales pertinentes y ensayos controlados aleatorizados que hubieran evaluado el comportamiento del Doppler uterino anómalo en el tercer trimestre para la predicción de resultados perinatales adversos en fetos con sospecha de ser PEG y en neonatos PEG. El Doppler uterino anómalo se definió como el índice de pulsatilidad de la arteria uterina >95 percentil o DE ≥2 por encima de la media, o escotadura bilateral de la arteria uterina. Se elaboraron modelos de efectos aleatorizados para la elaboración de una curva jerárquica resumen de las características operativas del receptor (ROC, por sus siglas en inglés). Se utilizó el análisis bayesiano para calcular la probabilidad a posteriori de un resultado perinatal adverso después de una evaluación de Doppler uterino anómalo o normal. RESULTADOS: Diecisiete estudios observacionales (incluidos 7552 fetos diagnosticados como sospechosos de ser PEG (n=3461) o diagnosticados posteriormente como neonatos PEG (n=4091)) cumplieron los criterios de inclusión; ningún ensayo controlado aleatorizado cumplió los criterios de inclusión. Las curvas resumen ROC mostraron que, entre los fetos sospechosos de ser PEG, la mayor precisión predictiva del Doppler uterino anómalo en el tercer trimestre fue para la muerte perinatal y la peor fue para el resultado perinatal adverso compuesto, con áreas por debajo de las curvas resumen ROC de 0,90 y 0,66, respectivamente. Los cocientes de verosimilitud correspondientes, positivo y negativo, fueron de 16,5 y 0,6 para la mortalidad perinatal y de 2,82 y 0,65 para el resultado perinatal adverso compuesto, respectivamente. Los riesgos posteriores a una evaluación de Doppler uterino anómalo vs normal, para el resultado perinatal adverso compuesto, la admisión en la unidad de cuidados intensivos para neonatos, la cesárea por deterioro fetal durante el parto, el test de Apgar a los 5 minutos <7, la acidosis neonatal y la muerte perinatal, fueron: 52,3% vs 20,2%, 48,6% vs 18,7%, 23,1% vs 15,2%, 3,59% vs 1,32%, 9,15% vs 5,12% y 31,4% vs 1,64%, respectivamente. CONCLUSIÓN: El Doppler uterino anómalo en el tercer trimestre parece ser moderadamente útil para predecir la muerte perinatal en embarazos con sospecha de ser PEG.

ISUOG Practice Guidelines: ultrasound assessment of fetal biometry and growth.

INTRODUCTION These Guidelines aim to describe appropriate assessment of fetal biometry and diagnosis of fetal growth disorders. These disorders consist mainly of fetal growth restriction (FGR), also referred to as intrauterine growth restriction (IUGR) and often associated with small­for­gestational age (SGA), and large­for­gestational age (LGA), which may lead to fetal macrosomia; both have been associated with a variety of adverse maternal and perinatal outcomes. Screening for, and adequate management of, fetal growth abnormalities are essential components of antenatal care, and fetal ultrasound plays a key role in assessment of these conditions. The fetal biometric parameters measured most commonly are biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur diaphysis length (FL). These biometric measurements can be used to estimate fetal weight (EFW) using various different formulae1. It is important to differentiate between the concept of fetal size at a given timepoint and fetal growth, the latter being a dynamic process, the assessment of which requires at least two ultrasound scans separated in time. Maternal history and symptoms, amniotic fluid assessment and Doppler velocimetry can provide additional information that may be used to identify fetuses at risk of adverse pregnancy outcome. Accurate estimation of gestational age is a prerequisite for determining whether fetal size is appropriate­for­gestational age (AGA). Except for pregnancies arising from assisted reproductive technology, the date of conception cannot be determined precisely. Clinically, most pregnancies are dated by the last menstrual period, though this may sometimes be uncertain or unreliable. Therefore, dating pregnancies by early ultrasound examination at 8­14 weeks, based on measurement of the fetal crown­rump length (CRL), appears to be the most reliable method to establish gestational age. Once the CRL exceeds 84 mm, HC should be used for pregnancy dating2­4. HC, with or without FL, can be used for estimation of gestational age from the mid­trimester if a first­trimester scan is not available and the menstrual history is unreliable. When the expected delivery date has been established by an accurate early scan, subsequent scans should not be used to recalculate the gestational age1. Serial scans can be used to determine if interval growth has been normal. In these Guidelines, we assume that the gestational age is known and has been determined as described above, the pregnancy is singleton and the fetal anatomy is normal. Details of the grades of recommendation used in these Guidelines are given in Appendix 1. Reporting of levels of evidence is not applicable to these Guidelines.

Pautas de ISUOG para la práctica: evaluación ecográfica de la biometría y el crecimiento fetal INTRODUCCIÓN: El objetivo de estas Pautas es describir la evaluación adecuada de la biometría fetal y el diagnóstico de los trastornos del crecimiento fetal. Estos trastornos consisten principalmente en la restricción del crecimiento fetal (RCF), también conocida como restricción del crecimiento intrauterino (RCIU), que a menudo está asociada con un tamaño pequeño para la edad gestacional (PEG) o grande para la edad gestacional (GEG), que pueden dar lugar a la macrosomía fetal; ambos se han asociado con una variedad de resultados maternos y perinatales adversos. La detección y el tratamiento adecuado de las anomalías del crecimiento fetal son componentes esenciales de la atención prenatal, y la ecografía fetal desempeña un papel fundamental en la evaluación de estas afecciones. Los parámetros biométricos fetales medidos con mayor frecuencia son (todas las siglas procedentes del inglés) el diámetro biparietal (BPD), el perímetro cefálico (HC), el perímetro abdominal (AC) y la longitud de la diáfisis del fémur (FL). Estas mediciones biométricas se pueden utilizar para estimar el peso del feto (PEF) mediante fórmulas diferentes1 . Es importante diferenciar entre el concepto de tamaño fetal en un momento dado y el crecimiento fetal en sí, siendo este último un proceso dinámico cuya evaluación requiere al menos dos ecografías separadas en el tiempo. La historia y los síntomas de la madre, la evaluación del líquido amniótico y la velocimetría Doppler pueden proporcionar información adicional que se puede utilizar para identificar los fetos bajo riesgo de resultados adversos del embarazo. La estimación precisa de la edad gestacional es un prerrequisito para determinar si el tamaño del feto es apropiado para la edad gestacional (AEG). Excepto en el caso de los embarazos procedentes de tecnologías de reproducción asistida, la fecha de concepción no se puede determinar con precisión. Clínicamente, la fecha de la mayoría de los embarazos se establece en función del último período menstrual, aunque a veces esto puede ser incierto o poco fiable. Por lo tanto, el fechado de los embarazos mediante ecografía temprana a las 8-14 semanas, mediante la medición de la longitud céfalo-caudal (LCC) fetal, parece ser el método más fiable para establecer la edad gestacional. Una vez que la LCC excede los 84 mm, se debe usar el HC2-4 para establecer la fecha del embarazo. El HC, con o sin FL, se puede utilizar para estimar la edad gestacional a partir de la mitad del primer trimestre si no se dispone de una ecografía del primer trimestre y el historial menstrual no es fiable. Cuando se ha establecido la fecha prevista del parto mediante una exploración temprana precisa, no se deben utilizar exploraciones posteriores para recalcular la edad gestacional1 . Las exploraciones en serie se pueden utilizar para determinar si el intervalo del crecimiento ha sido normal. En estas Pautas se asume que la edad gestacional es conocida y ha sido determinada según lo anterior, que el embarazo es de feto único y que la anatomía fetal es normal. En el Apéndice 1 se detallan los grados de recomendación utilizados en estas Pautas. El informe sobre los niveles de evidencia no es aplicable a estas Pautas.