Congenital anomalies: Impact of prenatal diagnosis on mode of delivery.

An important aspect of prenatal diagnosis is the avoidance of emergency caesarean delivery (CD) where the abnormality is considered lethal and the infant will not survive. A consecutive cohort of 211,163 women delivered of infants weighing 500 grams or more in three tertiary referral centers from 01/95 to 12/04, was analyzed for perinatal death attributed to congenital malformations. In the group that died in the neonatal period, the emergency CD rate was significantly lower where anomaly was detected versus undetected (17.5% versus 31%). Further, in contrast to undiagnosed anomalies, the indication for emergency CD was more often maternal in the diagnosed group (42% versus 19%, p=0.019). When a diagnosis of lethal congenital anomaly has been made in the prenatal period, the reduction in the emergency CD rate by almost half in this study supports a pivotal role for prenatal diagnosis in optimizing maternal care

Vaccination of children and teenagers to prevent cervical cancer

In Europe, 15,000 women die from cervical cancer each year. In Ireland, it results in around 180 new cases and 80 deaths every year. Human papillomaviruses (HPVs) play a key role in this cancer’s aetiology. Recently, effective vaccines have been developed against HPV, which raises the possibility of preventing cervical cancer. This review examines the evidence both for and against the vaccination of children and teenagers for HPV to protect against cervical cancer. Randomised controlled trials of HPV vaccines have demonstrated their immunogenicity, and ability to prevent incident and persistent type-specific HPV infection, and the associated cytological abnormalities of the cervix. Vaccination of children and teenagers remains controversial, as the long-term impact of these vaccines remains unknown. Important ethical issues have also emerged around the prospect of mandatory vaccination programmes. However, most gynaecologic oncologists have embraced this step as a proven preventive strategy. Further well-designed studies of vaccines are needed to guide clinicians’ decision-making.</p

Performance of prenatal cfDNA screening for sex chromosomes

Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.</p

Rare chromosomal abnormalities: can they be identified using conventional first trimester combined screening methods?

Objective: To evaluate the performance of first trimester combined screening for the detection of rare chromosomal abnormalities, other than Trisomies 21, 18 or 13 or 45 × . Study design: A database containing 36,254 pregnancies was analyzed. These patients were recruited at 15 US centers and included singleton pregnancies from 10 3/7-13 6/7 weeks. All patients had a nuchal translucency (NT) scan and those without a cystic hygroma (N = 36,120) underwent a combined first trimester screening test ('FTS' - NT, PAPP-A and fbHCG). A risk cut-off of 1:300, which was used for defining high risk for Trisomy 21, was also used to evaluate the detection rate for rare chromosomal abnormalities using the combined FTS test. Results: 36,120 patients underwent combined FTS. Of these, 123 were found to have one of the following chromosomal abnormalities: Trisomy 21, Trisomy 18, Trisomy 13 or Turner syndrome. This study focuses on 40 additional patients who were found to have 'other' rare chromosomal abnormalities such as triploidy, structural chromosomal abnormalities, sex chromosome abnormalities or unusual chromosomal abnormalities (e.g. 47XX + 16), giving an incidence of 1.1 in 1000 for these rare chromosomal abnormalities. Of these 40 pregnancies, only 2 (5%) had an NT measurement of ≥3 mm. The detection rate for combined FTS, using a risk cut-off of ≥1:300, was 35 % (14 of 40 cases). Therefore, 65 % of cases of rarer fetal chromosomal abnormalities had a 'normal' combined FTS risk ( Conclusion: Traditional FTS methods are unable to identify the vast majority of rare chromosomal abnormalities. Our data do not support the potential detection of rare fetal chromosomal abnormalities as a reason to favour nuchal translucency-based first trimester screening over NIPT.</p

Rare chromosomal abnormalities: can they be identified using conventional first trimester combined screening methods?

Objective: To evaluate the performance of first trimester combined screening for the detection of rare chromosomal abnormalities, other than Trisomies 21, 18 or 13 or 45 × . Study design: A database containing 36,254 pregnancies was analyzed. These patients were recruited at 15 US centers and included singleton pregnancies from 10 3/7-13 6/7 weeks. All patients had a nuchal translucency (NT) scan and those without a cystic hygroma (N = 36,120) underwent a combined first trimester screening test ('FTS' - NT, PAPP-A and fbHCG). A risk cut-off of 1:300, which was used for defining high risk for Trisomy 21, was also used to evaluate the detection rate for rare chromosomal abnormalities using the combined FTS test. Results: 36,120 patients underwent combined FTS. Of these, 123 were found to have one of the following chromosomal abnormalities: Trisomy 21, Trisomy 18, Trisomy 13 or Turner syndrome. This study focuses on 40 additional patients who were found to have 'other' rare chromosomal abnormalities such as triploidy, structural chromosomal abnormalities, sex chromosome abnormalities or unusual chromosomal abnormalities (e.g. 47XX + 16), giving an incidence of 1.1 in 1000 for these rare chromosomal abnormalities. Of these 40 pregnancies, only 2 (5%) had an NT measurement of ≥3 mm. The detection rate for combined FTS, using a risk cut-off of ≥1:300, was 35 % (14 of 40 cases). Therefore, 65 % of cases of rarer fetal chromosomal abnormalities had a 'normal' combined FTS risk ( Conclusion: Traditional FTS methods are unable to identify the vast majority of rare chromosomal abnormalities. Our data do not support the potential detection of rare fetal chromosomal abnormalities as a reason to favour nuchal translucency-based first trimester screening over NIPT.</p

Performance of prenatal cfDNA screening for sex chromosomes

Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.</p

Maternal outcomes and risk factors for COVID-19 severity among pregnant women

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease

Born into direct provision: outcomes of infants born to asylum seekers

Aim  Asylum seekers in Ireland have free access to antenatal care. Our aim was to review the outcomes of liveborn infants to mothers living in direct provision centres and the antenatal care their mothers accessed.  Methods  This was a retrospective review of infants born to asylum seekers, between November 2017 and February 2020, in a tertiary neonatal unit. The results were compared to the 2018 general hospital outcomes.  Results  During this period, 81 neonates were born to 78 asylum seekers. The median booking gestation was 30+4 weeks and only 9 (12%) had an early dating scan and 30 (42%) had a complete anatomy scan. Fifteen (20%) mothers had positive serology. Ten (12%) neonates were born prematurely, 20 (25%) were admitted to NICU and there were two (2%) neonatal deaths. At discharge, only 19 (23%) were exclusively breast fed. Fifty-six (71%) infants were followed in clinic and 10 (18%) had at least one “non-attendance”. Sixteen (20%) patients used an interpreter and language barriers lead to several miscommunications.  Conclusion  Infants born to asylum seekers had significantly higher rates of NICU admission (25% v 13%), maternal blood borne infections (20% v 1.5%) and lower rates of exclusive breastfeeding (23% v 45%) compared with the general hospital population.</p

Screening for foetal abnormalities in a contemporary Irish practice

Background: A number of non-invasive screening tests for foetal chromosomal aneuploidy are available for both the first and second trimester of pregnancy. The RCOG and ACOG advocate national screening; however, there are no national guidelines for chromosomal screening in Ireland. Methods: The RCSI Foetal Medicine Unit (FMU) at the Rotunda Hospital is a recently opened private clinic that offers these screening tests electively. A retrospective population study was carried out to assess the age distribution of patients presenting for the ‘combined’ first trimester screening test, and the number of women who chose to go on for further invasive testing, as a reflection of Irish interest in prenatal screening. Results: Of 520 women assessed in a six-month period, 66 women (13%) had at least one abnormal parameter. A total of 320 women (62%) were older than 35 years, a significant risk factor for foetal Down syndrome, and 20 women (30%) opted for diagnostic testing. Based on karyotyping and pregnancy outcomes, the FMU has a detection rate of 100%, with three aneuploid cases detected from three documented. Conclusions: Low numbers of at-risk women seeking diagnostic testing may indicate that many women are screening to simply assuage anxiety. High numbers of at-risk women presenting suggest a public awareness of the link between maternal age and increased risk for chromosomal aneuploidy, while overall high screening numbers demonstrate a significant interest of Irish women in the accessibility of prenatal screening.</p

Outcomes after laser ablation in twin-to-twin transfusion syndrome

Aim: Twin-to-Twin Transfusion Syndrome (TTTS) is associated with high perinatal morbidity and mortality in monochorionic twins. Ultrasound Doppler studies of the umbilical arteries (UAD) have a vital role in fetal assessment in multiple pregnancies complicated by TTTS. The Quintero staging is used to grade the severity of the condition.  Methods: The aim of the study was to describe UAD findings and outcomes in a cohort of 78 twin pregnancies treated with laser ablation.  Results: Of the 78 twin pregnancies, 39 women had two surviving babies (50%) and 17 (22%) had a single survivor. The most frequent Quintero stage at diagnosis was Stage three (38%, 30/78), followed by Stage two (32%, 25/78), Stage one (24%, 19/78) and Stage four (5%, 4/78). The Quintero stage was not significantly associated with survival (chi sq 5.31 p=0.151). While 50% of pregnancies had normal UAD at the time of TTTS diagnosis, 50% had at least one abnormal UAD. A normal UAD was not associated with higher survival (68% v 53%, chi sq 3.26 p=0.071).  Conclusion: Laser ablation for TTTS was associated with 50% double survival and 22% single survival. UAD abnormalities or the Quintero stage was not associated with survival after laser ablation.</p