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.

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.

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.