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.

First-trimester and combined first- and second-trimester prediction of small-for-gestational age and late fetal growth restriction.

OBJECTIVE: To develop a first-trimester or combined first- and second-trimester screening algorithm for the prediction of small-for-gestational age (SGA) and late fetal growth restriction (FGR). METHODS: This was a retrospective study of women with singleton pregnancy, who underwent routine first-, second- and third-trimester ultrasound assessment. Late FGR was defined, at ≥ 32 weeks' gestation in the absence of congenital anomalies, as either (i) estimated fetal weight (EFW) or birth weight (BW) < 3rd centile, or (ii) EFW < 10th centile and either uterine artery mean pulsatility index (UtA-PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile. Neonates with BW < 10th centile, regardless of prenatal parameters, were defined as SGA. The predictive effectiveness of maternal and first- and second-trimester factors was tested using logistic regression and receiver-operating characteristics curve analyses. RESULTS: A total of 3520 fetuses were included (late FGR, n = 109 (3.1%); SGA, n = 292 (8.3%)). Of the late FGR cases, 56 (1.6%) fulfilled the antenatal criteria (EFW < 3rd centile or EFW < 10th centile plus abnormal UtA-PI or CPR) and were defined as prenatally detected late FGR. A first-trimester screening model (comprising conception method, smoking status, maternal height, pregnancy-associated plasma protein-A (PAPP-A) and UtA-PI) could predict 50.0% of the prenatally diagnosed and 36.7% of the overall late FGR fetuses for a 10% false-positive rate (FPR). A model combining first- and second-trimester screening parameters (conception method, smoking status, PAPP-A, second- trimester EFW, head circumference/abdominal circumference ratio and UtA-PI) could predict 78.6% of the prenatally detected, and 59.6% of the overall late FGR fetuses, for a 10% FPR (area under the curve 0.901 (95% CI, 0.856-0.947) and 0.855 (95% CI, 0.818-0.891), respectively). The prediction of SGA was suboptimal for both first-trimester and combined screening. CONCLUSIONS: A simple model combining maternal and first- and second-trimester predictors can detect 60% of fetuses that will develop late FGR, and 79% of those fetuses that will be classified prenatally as late FGR, for a 10% FPR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model.

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

Ovarian cancer diagnosed during pregnancy: clinicopathological characteristics and management.

The aim of this study was to discuss the diagnostic and therapeutic dilemmas in cases of pregnant women with adnexal masses, reporting an interesting case with synchronous literature review. The patient, a gravida 2, para 1, 37 year-old woman was diagnosed with a large unilateral adnexal lesion during a scheduled third trimester ultrasound assessment. A large papillary papule with a network of blood vessels showing decreased resistance in blood flow was noticed as well. Surgical intervention revealed ascitic fluid and a large cystic mass arising from the right ovary. Cesarean section and right salpingooophorectomy, including the mass, were performed. Frozen section biopsy was positive for malignancy. Total hysterectomy and left salpingo-oophorectomy, total omentectomy, biopsies from the pelvic peritoneum, pelvic/para-aortic lymphadenectomy and appendicectomy followed. Histology showed mucinous ovarian adenocarcinoma Grade I Stage Ic according to FIGO classification. Surgical intervention, in cases of persisting adnexal lesions, is often necessary, even during pregnancy.

Nuchal translucency and major congenital heart defects in fetuses with normal karyotype: a meta-analysis.

OBJECTIVE: To pool published data regarding the sensitivity and specificity of nuchal translucency (NT) in the diagnosis of major congenital heart defects (CHDs) in fetuses with normal karyotype. METHODS: MEDLINE and Scopus searches using combinations of the terms 'nuchal' and 'cardiac*' were complemented by perusal of references of the retrieved articles and an additional automated search using the 'search for related articles' function on PubMed. Only fetuses with normal karyotype and major CHDs were analyzed. Weighted estimates were made and summary receiver-operating characteristics curves were constructed. RESULTS: The analysis included 20 studies (205 232 fetuses; 537 cases with major CHDs). The pooled sensitivity and specificity of NT > 95(th) centile for diagnosis of major CHDs was 44.4% (95% CI, 39.5-49.5) and 94.5% (95% CI, 94.4-94.6), respectively. The pooled sensitivity and specificity of NT > 99(th) centile was 19.5% (95% CI, 15.9-23.5) and 99.1% (95% CI, 99.1-99.2), respectively. For the subgroup of studies in which NT was measured by Fetal Medicine Foundation-certified operators, the pooled sensitivity and specificity of NT > 95(th) centile was 45.6% (95% CI, 39.6-51.7) and 94.7% (95% CI, 94.6-94.9), respectively. The corresponding estimates for NT > 99(th) centile were 21.0% (95%CI, 16.5-26.1) and 99.2% (95% CI, 99.2-99.3). The pooled positive likelihood ratio for NT > 99(th) centile was 30.5 (95% CI, 24.3-38.6). There was high across-studies heterogeneity for most estimates. CONCLUSION: Approximately 44% of chromosomally normal fetuses with CHDs have NT > 95(th) centile and 20% have NT > 99(th) centile. However, there is high heterogeneity across studies, which largely remains even in subgroup analyses of studies of apparently similar design, potentially indicating the presence of some residual unidentified bias.

Recurrent short rib polydactyly syndrome.

We present three consecutive cases of skeletal dysplasias of a non-consanguineous couple with five pregnancies. The diagnosis of short-rib polydactyly syndrome (SRPS) was feasible by ultrasound during the 1st trimester of pregnancy. SRPS represents a heterogeneous group of lethal skeletal dysplasias. It is characterised by short limb dwarfism complicated by thoracic hypoplasia, polydactyly and different anomalies of major organs such as congenital heart defects and renal dysplasia. Four major types of the SRPS have been described: type I (Saldino-Noonan); type II (Majewski); type III (Verma-Naumoff) and type IV (Beemar-Langer). However, there is phenotypic overlapping between four types and with those of non-lethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). Our cases show the importance of the nuchal translucency (NT) scan that offers the opportunity to examine fetal anatomy in the 1st trimester and diagnose rare skeletal abnormalities early in pregnancy.

First trimester diagnosis of 13q-syndrome associated with increased fetal nuchal translucency thickness. Clinical findings and systematic review.

13q-syndrome is a rare chromosomal disorder caused by partial deletion of the long arm of chromosome 13 with variable phenotypic presentation. Further sonographic features involve fetal growth restriction, bradycardia, encephalocele, facial dysmorphism and upper extremity deformity. We report a case of 13q-syndrome presenting as increased nuchal translucency diagnosed by chromosome studies and confirmed by array comparative genomic hybridization (CGH) analysis in the first trimester of pregnancy. Pregnancy was terminated at 14 weeks' gestation. The parents did not give consent for a postmortem examination. Furthermore we performed a systematic review of the international literature on previous cases of 13q-syndrome diagnosed prenatally. Our case emphasizes the importance of a detailed 11-14 week ultrasound assessment in diagnosing fetal chromosomal aberrations in combination with the modern aspects of array CGH, thus providing more precise and rapid prenatal diagnosis.

Congenital cystic adenomatoid malformation: is there a need for pregnancy termination?

Aim. Congenital cystic adenomatoid lung malformation is a rare unilateral dysplasia of the lung. Three pathologic types are described in the literature: type I with cysts >2 cm, type II with cysts <1 cm, and type III with microcysts. The aim of this paper is to present a case of a fetus with congenital cystic adenomatoid lung malformation and discuss the necessity for pregnancy termination according to its prognosis and future mortality. Case. A 36-year-old pregnant woman (para: 1, gravida: 1) presented in our department for anatomy ultrasound screening at 20 + 1 weeks of gestation. The ultrasound detected a cystic adenomatoid right lung malformation measuring 1.45 × 1.67 cm which caused mediastinal shift of the heart and the lung to the left side. Other findings were cysts of the choroid plexus and echogenic intracardiac foci. The parents after genetic counseling decided pregnancy termination. The pregnant received cabergoline for ablactation. Conclusion. Congenital cystic adenomatoid lung malformation has different prognosis according to the type (69% in type I, 0% in types II and III). Fetal hydrops, cardiac and skeletal anomalies, Potter's syndrome, and gastrointestinal atresia are common cofindings. Genetic counseling is necessary, and pregnancy termination is proposed to the cases with poor prognosis.

Prenatal diagnosis of fetal left ventricular non-compaction cardiomyopathy.

Isolated left ventricular non-compaction (LVNC) is a rare disorder, classified as a primary genetic cardiomyopathy by the American Heart Association or as an unclassified cardiomyopathy by the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. The key features are the prominent trabeculae and deep intratrabecular recesses resulting in thickened myocardium with the two layers consisting of compacted and non-compacted myocardium. These recesses are in continuity with the left ventricular cavity and are filled with blood without evidence of communication to the epicardial coronary artery system. We present a case of LVNC detected prenatally at 25 + 4 weeks of gestation.

Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization.

Small supernumerary marker chromosomes (sSMCs) cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques. Until recently, the large variety of marker chromosomes, as well as the limitations in their identification, have presented a diagnostic problem. In order to determine the origin of sSMCs, we used a variety of fluorescence in situ hybridization (FISH) methods, including centromere-specific multicolor FISH, acrocentric specific multicolor FISH, subcentromere-specific multicolor FISH and multicolor FISH with whole chromosome paint probes. Moreover, uniparental disomy testing was in all cases attempted. From a total of 28,000 pre-natal samples from four diagnostic genetics laboratories in Greece, 23 (0.082%) supernumerary marker chromosomes were detected. The mean maternal age was 36.2 years (range 27-43) and the mean gestational age at which amniocentesis was performed was 18.5 weeks (range 16-23). Eighteen markers were de novo and 5 markers were inherited. Molecular cytogenetic methods were applied to determine the chromosomal origin and composition of the sSMC. In total, 17 markers were derived from acrocentric chromosomes (14, 15, 21 and 22) and 6 markers were non-acrocentric, derived from chromosomes 9, 16, 18, 20 and Y. Uniparental disomy was not detected in any of the cases studied. With regard to pregnancy outcome, 13 pregnancies resulted in normal healthy neonates, while 10 pregnancies were terminated due to ultrasound abnormalities. A total of 23 marker chromosomes from 28,000 pre-natal samples (0.082%) were identified. Molecular cytogenetic techniques provided valuable information on the chromosomal origin and composition of all the sSMCs. Especially in cases with normal ultrasound, the FISH results rendered genetic counseling possible in a category of cases previously considered a diagnostic problem. Abnormal outcome was observed in 10 cases (43,5%), 7 of which showed abnormal ultrasound findings. New technologies, such as array-comparative genomic hybridization, should be used in future genotype-phenotype correlation studies, although the high mosaicism rate poses a problem.

Ovarian masses during adolescence: clinical, ultrasonographic and pathologic findings, serum tumor markers and endocrinological profile.

This retrospective study was undertaken to assess the epidemiological and clinical features, laboratory findings, preoperative work-up, surgical treatment and pathologic findings in adolescents with ovarian cysts. All adolescents who were referred to our institution and had been operated on because of a diagnosed ovarian mass, from January 1997 to June 2003, were included in this study. Forty-four cases of women with an ovarian mass were retrospectively analyzed. These patients, aged between 12 and 21 years, had 47 ovarian masses (three patients had bilateral lesions), of which 49% were non-neoplastic and 51% were neoplastic. Of the neoplastic lesions, 62.5% were germ cell tumors, 20.8% were epithelial and 16.7% were sex cord-stromal tumors. Of the neoplastic tumors, 95.8% were benign while 4.2% were malignant. Procedures included 30 operative laparoscopies (68.20%) and 14 exploratory laparotomies (31.8%). Simple excision of the ovarian cyst was performed in 39 cases (88.6%). According to our study, most of the adolescents with an ovarian cyst underwent an operation because of a neoplastic lesion. The majority of ovarian tumors occurring in adolescents are non-epithelial in origin, and germ cell tumors are the most common histological type. Ultrasound examination is one of the most important diagnostic tools. Preoperative diagnostic approach of these patients should always include careful history taking, physical examination, imaging and evaluation of serum assays. Gynecologists who care for young girls must be familiar with the differential diagnosis of ovarian masses whose surgical treatment should be conservative when appropriate, so that hormonal status and future fertility are not compromised in this group of patients.