A road map for the management of a pregnancy complicated by maternal bladder exstrophy.

Bladder exstrophy (BE) is a congenital genito-urinary malformation where there is a defect in the abdominal wall resulting in a protruding open bladder with exposed mucosa (Resnik R.P. et al. Creasy and Resnik's maternal-fetal medicine: principles and practice. Elsevier, 2019). Several reconstructive procedures are required to correct the anomalies, resulting in an ileal conduit which is an alternate urinary reservoir reconstructed from the terminal ileum (Madersbacher S, et al. J Urol 169(3):985-90, 2003). We describe the care of a pregnant woman with BE and outline the principles of management of her pregnancy with a multidisciplinary team. Timely pre-operative planning is advised to minimise intraoperative complications in the event of a caesarean section. The woman went on to have an uncomplicated classical caesarean section at term by midline laparotomy with a good outcome for both mother and baby.

Late first-trimester ultrasound findings can alter management after high-risk NIPT result.

OBJECTIVE: To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result for various chromosomal abnormalities. METHODS: This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first-line screening test. Data were collected from pre-NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome-wide analysis for the last 2 years. RESULTS: Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high-risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high-risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. CONCLUSIONS: LFTU after a high-risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at-risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high-risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Influence of fibroids on cell-free DNA screening accuracy.

OBJECTIVE: Cell-free DNA (cfDNA) screening assesses both maternal and placental cfDNA. Fibroids are common and release cfDNA into maternal serum. Genetic abnormality is seen in 50% of fibroids. We aimed to assess the impact of fibroids on the accuracy of genome-wide cfDNA screening. METHODS: This was a prospective cohort study of singleton pregnancies examined at one of two centers in Melbourne and Sydney, Australia, between 1 November 2019 and 31 December 2020. All cases underwent pretest ultrasound examination to confirm an ongoing pregnancy of at least 10 weeks' gestation, and, at this stage, the number and volume of any uterine fibroid were documented. Genome-wide cfDNA screening was performed to detect all copy-number variants (CNV) > 7 megabases. The incidence of a false-positive result was compared between cases with and those without fibroids. RESULTS: Over the 14-month study period, 13 184 patients underwent cfDNA screening, of whom 1017 (7.7%) had fibroids. Fibroids were not identified in any of the 17 participants who had a false-positive result for chromosomes 13, 18, 21, X or Y. Ninety-five (0.7%) cases were screen-positive for subchromosomal aberration (SA), rare autosomal trisomy (RAT) or multiple abnormalities (MA), with 10 of these cases having a fetal genetic abnormality. The incidence of a false-positive RAT, MA or SA result was significantly higher in participants with fibroids (20/1017 (2.0%)) than in those without fibroids (64/12 167 (0.5%)). Women with fibroids were approximately six times as likely to have a false-positive result for SA, and this was associated positively with both fibroid number and volume. CONCLUSIONS: Most women with fibroids do not have an abnormal result on genome-wide cfDNA screening. However, CNVs due to fibroids are associated with false-positive SA findings, although fibroids do not appear to influence cfDNA screening accuracy for the common autosomal trisomies or sex-chromosomal abnormalities. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study.

OBJECTIVE: To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT). DESIGN: Historical cohort study. SETTING: A multicentre private practice in Sydney, Australia. POPULATION: Women who failed to obtain a result from NIPT (n = 131). METHODS: The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population. MAIN OUTCOME MEASURES: Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotrophin (ß-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery. RESULTS: Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free ß-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02). CONCLUSION: Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia. FUNDING: None received. TWEETABLE ABSTRACT: Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes.

Are serum HE4 or ROMA scores useful to experienced examiners for improving characterization of adnexal masses after transvaginal ultrasonography?

OBJECTIVE: To determine whether serum human-epididymis protein-4 (HE4) levels or Risk of Ovarian Malignancy Algorithm (ROMA) scores are useful second-stage tests for tumors thought to be difficult to characterize as benign or malignant on the basis of ultrasound findings by experienced examiners, and to investigate whether adding information on serum HE4 levels or ROMA scores to ultrasound findings improves diagnostic performance. METHODS: This was a prospective cross-sectional diagnostic accuracy study conducted in a tertiary referral center that enrolled consecutive women with a known adnexal mass scheduled for surgery. Experienced level III examiners classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant after preoperative ultrasound examination. Serum HE4 and CA 125 levels were measured before surgery. RESULTS: The final database comprised 360 women, of whom 216 (60%) had benign and 144 (40%) had malignant disease. Examiners were highly confident in 196 cases (54%), moderately confident in 135 (38%) and completely uncertain about their diagnosis in 29 (8%) cases. With a sensitivity of 67% and specificity of 70%, subjective assessment outperformed HE4 and ROMA in the subgroup of difficult tumors. Both tests had low discriminatory capacity with poor areas under the receiver-operating characteristics curve of 0.536 (95% CI, 0.302-0.771) and 0.565 (95% CI, 0.294-0.836), respectively. A strategy that incorporates sequential testing of serum HE4 or ROMA scores after transvaginal ultrasonography resulted in a deterioration in overall test performance. CONCLUSION: Measurement of serum HE4 or calculating scores using the ROMA as secondary tests does not seem useful for classifying adnexal tumors after subjective assessment with transvaginal ultrasonography.