The effect of HPV vaccination on the rate of high-grade cytology in 25-year-old women attending cervical screening in Ireland.

INTRODUCTION: Women vaccinated through the initial catch-up HPV vaccination programme (2011/12 to 2013/14) first became eligible for cervical screening in 2019 at age 25. This study aims to examine the changes in detection of HG cytology outcomes in 25-year-olds screened from 2010 to 2022 compared to population data on HPV vaccination in this group. METHODS: This was an ecological-type study. Cytology results from the CervicalCheck database from 2010 to 2022 (High Grade, Low Grade, and No Abnormality Detected) were plotted against data from the National Immunisation Office on the uptake of HPV vaccinations in females from 2010 to 2022. RESULTS: Vaccination rates in the catch-up programme were lower (44-70%) than for routine HPV immunisation at age 12/13 in 2010/11 (81%). The rate of high-grade cytology in 25-year-olds in 2015-2018 was 3.7% of all cytology tests taken in this age group. For the corresponding period from 2019 to 2022 (when vaccinated women were attending screening), the average percentage of HG cytology in 25-year-olds was 1.5%, representing a significant reduction in HG cytology proportions (p < 0.001). CONCLUSION: This study provides early evidence of the potential impact of HPV vaccination on cervical disease in the Republic of Ireland. Despite lower vaccination uptake in the initial catch-up group, we are seeing early signs of the positive protective effect of HPV vaccination in women at the time of their first cervical screening test. Plans to incorporate individual-level HPV vaccination status for women on the cervical screening register will allow more detailed assessment of the impact of HPV vaccination.

Rare case of steroid cell tumour presenting as resistant hypertension in early pregnancy.

A woman 12 weeks and 3 days pregnant was referred to the emergency department with significant hypertension which, despite aggressive medical management, remained uncontrolled. Markedly elevated levels of renin and aldosterone beyond what is typical in early pregnancy were present, which together with the finding of a right ovarian cyst pointed to the possible diagnosis of an extrarenal reninoma.and the decision was made to perform a right-sided oophorectomy at 16 weeks gestation. Histology demonstrated a staining pattern most consistent with a steroid cell tumour leading to the diagnosis of refractory hypertension secondary to an ovarian steroid cell tumour. Post oophorectomy blood biochemistry rapidly returned to normal, and our patient's hypertension slowly resolved allowing for a large reduction in antihypertensive agent requirements and a successful pregnancy outcome.

Follow-up and outcomes of patients with a pregnancy of unknown location: A comparison of two prediction models.

BACKGROUND: The time period while delineating the final diagnosis following presentation with a pregnancy of unknown location (PUL) can be an anxious time, as well as being time and resource intensive. Prediction models have been utilised in order to tailor counselling, frame expectations and plan care. OBJECTIVES: We aimed to review diagnoses of PUL in our population and assess the value of two prediction models. STUDY DESIGN: We reviewed all 394 PUL diagnoses over a three year period in a tertiary level maternity hospital. We then retrospectively applied the M1 and M6NP models to assess their accuracy when compared to the final diagnosis. RESULTS: PUL comprises of 2.9% (394/13401) of attendances in our unit, requiring 752 scans and 1613 separate blood tests. Just under one in ten women (9.9%, n = 39) presenting with a PUL had a viable pregnancy at discharge, however of the remainder, only 18.0% (n = 83) required medical or surgical treatment for a PUL. The M1 model was more successful at predicting an ectopic pregnancy than the M6NP, with the latter over-predicting viable pregnancies (33.4%, n = 77). CONCLUSIONS: We demonstrate that the management of women with a PUL could be stratified through the application of outcome prediction models, having positive results for framing expectations and potentially reducing this resource-intensive diagnosis.

Induction of labor: reviewing the past to improve the future.

BACKGROUND: Women undergoing induction of labor should be empowered with accurate information. OBJECTIVE: This study aimed to examine the characteristics of and indications for induction of labor and delivery outcomes to help inform practice and counseling. STUDY DESIGN: We conducted a retrospective cohort study of all singleton pregnancies undergoing induction of labor over a 3-month period in a tertiary-level hospital in the Republic of Ireland. Data were obtained from paper and electronic registries. Descriptive and inferential statistics were performed on data collected. RESULTS: There were 1084 women delivered, with an induction rate of 46.0% (n=499). Primiparous women were more likely to be induced compared with multiparous women (51.4%; n=254/494 vs 41.5%; n=245/590; P<.001), and were more likely to be induced for postmaturity (30.7%; n=78/254 vs 23.6%; 58/245; P≤.001). More than half (50.3%; 251/399) were induced before 40 weeks' gestation, irrespective of parity. Multiparous women and those induced for maternal medical indications had a shorter overall time to delivery interval (21.7 hours [standard deviation, 13.0] vs 13.8 hours [standard deviation, 11.2]; P<.001 and 18.3 hours [standard deviation, 12.7] vs 14.7 hours [standard deviation, 12.4]; P<.01). CONCLUSION: Information on induction of labor can aid in the guidance and education of women undergoing the process, educate clinicians for appropriate counseling, and facilitate shared decision-making.

Corrigendum to "Trust and cancer screening: Effects of a screening controversy on women's perceptions of cervical cancer screening" [Prev. Med. Rep. 25 (2022) 101684].

[This corrects the article DOI: 10.1016/j.pmedr.2021.101684.].

Trust and cancer screening: Effects of a screening controversy on women's perceptions of cervical cancer screening.

There is a paucity of data on trust of service users in cervical screening. A significant controversy in Ireland's national cervical cancer screening programme emerged in 2018. The Health Service Executive (HSE) confirmed that a clinical audit had revealed that more than 200 women who developed cancer had not been told of earlier misdiagnosed smear tests. During this high profile controversy we conducted qualitative interviews exploring factors that influence cervical screening participation. Women who had been invited for routine screening tests were recruited from the national screening register. Telephone interviews were conducted with 48 women aged 25-65 years; with a range of screening histories - 34 were adequately screened (attended all routine screening tests) and 14 were inadequately screened (attended some/no screening tests). Thematic analysis was conducted and all interviewees spontaneously raised the screening controversy revealing that the crisis had resulted in serious loss of trust, faith and confidence in the screening programme. Publicity surrounding the controversy had some beneficial effects, including increased awareness of the value of screening and beliefs that intense focus on the programme will improve the service long-term. Strategies which incorporate these findings could help rebuild trust in screening.

Interval cancer audit and disclosure in cervical screening programmes: An international survey.

BACKGROUND: Legal cases involving the National Cervical Screening Programme in Ireland following non-disclosure of an interval cervical cancer audit prompted this first international comparative survey of interval cervical cancer audit. METHODS: A survey of 22 international population-based cervical screening programmes was conducted, to determine if they undertook audit of invasive cervical cancers. Those countries/regions that perform reviews were asked (i) how the audit was undertaken, including how the reviews were performed and how they controlled for retrospective bias, (ii) how women are informed of the audit process and how their consent is obtained, and (iii) how audit results were disclosed to patients. RESULTS: Seventeen countries/regions invited completed the survey (77%); 65% (11/17) have an audit process for interval cervical cancers. Five perform individual patient reviews; three perform programme-wide review, with calculation of interval cancer detection rates; one routinely performs programme-wide review with calculation of interval cancer detection rates and offers individual reviews, and one routinely performs local hospital-level reviews. In the remaining country/region, hospital laboratories audit cancers, with a national audit process for all cervical cancers. Varying methodologies for retrospective cytology review were employed; four include control samples, with a ratio varying from 1:1 to 1:2. Three conduct a blinded review. Most countries/regions do not discuss interval cancer audit with participants and 3/11 (27.3%) inform women when a cervical cancer audit takes place. Disclosure is limited and variable. CONCLUSION: The responses suggest that there is no consistent approach to audit of interval cervical cancers or to disclosure of audit results.

Attitudes and experiences with termination of pregnancy among Irish obstetrics & gynaecology trainees in the context of recent legal change: A survey study.

OBJECTIVE: This study examines Irish obstetrics and gynaecology trainees' experiences with and opinions of termination of pregnancy (ToP) after legal change. STUDY DESIGN: We invited obstetrics & gynaecology non-consultant hospital doctors (NCHDs) to participate in a web-based survey through a professional e-mail listserv. We conducted descriptive statistical analyses of responses using Stata SE Version 16. RESULTS: A total of 102/202 (50.5%) trainees responded to the survey. Of these, 61.8% believed that ToP should be allowed on request up to 12 weeks and in limited circumstances thereafter (in line with current law), and 19.6% believe ToP should be allowed on request even after 12 weeks. Knowledge about the abortion law was high (70.6% achieved a perfect knowledge score). Since the new law came into effect, 61.8% of trainees reported participation in abortion care, though only 25.5% had performed surgical procedures. More than 75% of respondents would like to receive more training in all clinical skills related to ToP. In the future, 67.6% of respondents would be willing to provide TOP in all circumstances allowed by law. CONCLUSION: Irish obstetrics & gynaecology NCHDs are generally supportive of the legislation. Few trainees have performed surgical abortions, and most would like to receive additional clinical training related to ToP.

Management of monochorionic twins discordant for structural fetal anomalies.

OBJECTIVE: To review the perinatal management and outcomes of monochorionic twin pregnancies (MC) discordant for congenital anomalies (DCA). METHODS: Retrospective, study of all MC DCA cases referred to our tertiary referral center from 1997 to 2018. We excluded cases complicated with twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence, twin reversed arterial perfusion sequence or selective intra-uterine growth restriction. Patients were counseled about the possibility of expectant (EM) or interventional management (selective feticide [SF] or termination of the entire pregnancy [TOP]). RESULTS: One hundred eight of 4157 (2.6%) MC pregnancies were discordant for anomaly. Fifty two of 108 n(48.1%) underwent SF at a mean gestational age of 31.4 ± 5.9 weeks while 52/108(48.1%) opted for EM. Livebirth rate of the healthy co-twin was similar between the two groups (SF: 88.5% vs EM: 82.7%, P = .87). In the SF group, six healthy co-twins (6/52, 11.5%) died 5.3 ± 3.1 days after SF of the abnormal co-twin. In the EM group, in-utero demise of the abnormal twin occurred in 9 of 52 (17.3%) of the cases and was followed by the spontaneous demise of the healthy co-twin in 4 of 9 (44.4%) of these cases. CONCLUSION: Selective feticide does not seem to significantly alter survival of the healthy co-twin compared to EM.

A double dilemma: treatment of stage IV fetal twin-twin transfusion syndrome in the setting of maternal recurrent venous thromoembolism: a case report.

BACKGROUND: Fetal conditions can pose significant challenges in the management of pregnancies complicated by pre-existing maternal medical conditions. CASE PRESENTATION: We report a case of a 34-year-old woman with Stage IV Twin Twin Transfusion syndrome in the presence of maternal recurrent complex venous thromboembolic disease. Following a previous pregnancy loss, complicated by a third episode of thromboembolic disease, an inferior vena cava filter was placed. One month later, a pregnancy was confirmed and subsequently identified as a monochorionic twin pregnancy. Twin-Twin Transfusion syndrome was identified at 18 weeks' gestation and progressed rapidly to Quintero Stage IV. In consultation with a multi-disciplinary international team, fetoscopic laser photocoagulation was performed. The pregnancy progressed to delivery of female infants at 33 weeks gestation, who have achieved all developmental milestones at 2 years of age. CONCLUSIONS: We describe the multi-disciplinary effort to optimise the maternal condition to allow fetoscopic laser photocoagulation and continued management of the maternal and fetal conditions to a successful pregnancy outcome.

Rounded intraplacental hematoma - A high risk placental lesion as illustrated by a prospective study of 26 consecutive cases.

BACKGROUND: A rounded intraplacental hematoma (RIH) is a recently delineated placental lesion. Following the observation of two cases of RIH in placentas associated with stillbirth in 2012, we postulated that RIHs were associated with a higher risk obstetric phenotype when compared to other lesions characteristic of maternal vascular malperfusion (MVM). We aimed to investigate this further by reviewing the associated maternal and fetal characteristics in a series of prospectively identified cases. METHODS: Pregnancies where a RIH was identified on placental examination were prospectively collected from February 2014-July 2016. Comparison was made with pregnancies with placental evidence of MVM but without RIH. RESULTS: 26 placentas with a RIH were identified and 26 placentas with MVM were selected for comparison. There was a statistically significantly increased incidence of stillbirth in the RIH group as compared with the MVM-only group (p = 0.022). Also, pregnancies with RIHs had a lower maternal age (p = 0.041), decreased incidence of antenatally diagnosed growth restriction (p = 0.023), a trend to increased incidence of clinical abruption (p = 0.051) and heavier mean infant birthweight (p = 0.034). Both groups had a high incidence of pre-eclampsia, Caesarean section and preterm delivery when compared with the general population. DISCUSSION: This is the first study to prospectively identify and collect RIHs using standardised pathological criteria and more than doubles the number of reported cases to date. We present 2 comparable, high-risk cohorts but with a significantly increased incidence of stillbirth in those in which RIHs were seen. Further study of these lesions is justified with an emphasis on the potential for antenatal detection using ultrasound evaluation of placental texture.

Neonatal and maternal outcomes following midtrimester preterm premature rupture of the membranes: a retrospective cohort study.

BACKGROUND: Preterm premature rupture of membranes (PPROM) complicates 1% of all pregnancies and occurs in one third of all preterm deliveries. Midtrimester PPROM is often followed by spontaneous miscarriage and elective termination of ongoing pregnancies is offered in many countries. The aim of this retrospective descriptive cohort study was to investigate the natural history of midtrimester PPROM in a jurisdiction where termination of pregnancy in the absence of maternal compromise is unavailable. METHODS: Cases of midtrimester PPROM diagnosed between 14 and 23 + 6 weeks' gestation during April 2007 to June 2012 were identified following a manual search of all birth registers, pregnancy loss registers, annual reports, ultrasound reports, emergency room registers and neonatal death certificates at Cork University Maternity Hospital - a large (circa 8500 births per annum) tertiary referral maternity hospital in southwest Ireland. Cases where delivery occurred within 24 h of PPROM were excluded. RESULTS: The prevalence of midtrimester PPROM was 0.1% (42 cases/44,667 births). The mean gestation at PPROM was 18 weeks. The mean gestation at delivery was 20 + 5 weeks, with an average latency period of 13 days. Ten infants were born alive (23%; 10/42). The remainder (77%; 32/42) died in utero or intrapartum. Nine infants were resuscitated. Two infants survived to discharge. The overall mortality rate was 95% (40/42). Five women had clinical chorioamnionitis (12%; 5/42) but 69% demonstrated histological chorioamnionitis. One woman developed sepsis (2.4%; 1/42). Other maternal complications included requirement of intravenous antibiotic treatment (38%; 17/42), retained placenta (21%, 9/42) and post-partum haemorrhage (12%; 5/42). CONCLUSIONS: This study provides useful and contemporary data on midtrimester PPROM. Whilst fetal and neonatal mortality is high, long-term survival is not impossible. The increased risk of maternal morbidity necessitates close surveillance.

Heart rate variability in neonates of type 1 diabetic pregnancy.

BACKGROUND: Cardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. AIMS: Our aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. STUDY DESIGN AND SUBJECTS: This was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). OUTCOME MEASURES: Heart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. RESULTS: Neonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (p<0.05). This altered HRV was significantly related to fetal acidaemia, cord blood glucose values and maternal glycaemic control during pregnancy (p<0.05). CONCLUSION: Neonates of pregestational diabetic pregnancy have altered HRV which is related to maternal hyperglycaemia, fetal acidaemia and fetal glycaemia. Exposure of the developing heart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life.

Relationship between maternal antibody type and antenatal course following intrauterine transfusion for red cell alloimmunisation.

OBJECTIVE: To determine the antenatal course of severe red cell alloimmunisation in pregnancies requiring intrauterine fetal transfusion. STUDY DESIGN: A retrospective cohort study over 16 years in a single national quaternary fetal medicine centre. From 1996 to 2011, 242 red cell intrauterine transfusions (IUT) were performed in 102 alloimmunised pregnancies. Antibody type was categorized into Rh(D) and non-Rh(D) (including Rh(c), Kell and Rh(E)). Women with Rh(D) antibodies were further stratified into those with and without additional red cell antibodies. Data were compared using the Mann-Whitney U and Fisher's exact tests. Two-tailed P values at the 5% level were considered significant. RESULTS: Comparing Rh(D) and non-Rh(D) pregnancies, there were no differences in either gestational age or fetal haemoglobin at first IUT, number of transfusions required, gestation at delivery, caesarean delivery rates or perinatal losses. In women sensitized to Rh(D), the presence of additional antibodies did not influence the degree of fetal anaemia or the first transfusion-delivery interval, although rates of fetal hydrops were higher in the presence of multiple antibodies. The "procedure-related" loss rate was 1.7% per procedure in our institution. CONCLUSION: Antibody status does not appear to influence clinical outcomes following fetal transfusion for alloimmunisation.

Selective serotonin reuptake inhibitors and pregnancy: A review of maternal, fetal and neonatal risks and benefits.

Depression is common in women of childbearing age. Whereas non-pharmacological interventions are recommended as first line interventions, pharmacological treatment may be required. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants in pregnancy. Ideally, discussion of the risks and benefits of SSRI use in pregnancy should occur prior to pregnancy. The potential risks of psychotropic medications need to be balanced against the risks associated with untreated psychiatric conditions and the discontinuation of necessary medications.

Fetal and maternal leptin in pre-gestational diabetic pregnancy.

OBJECTIVE: To compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. METHODS: In a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. RESULTS: No difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36-1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5-1108.2 pg/mL; type 2 diabetes: 202.2 pg/mL, 35.1-1553.3 pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7-810 pg/mL) and type 2 (447.2 pg/mL, 136.3-679 pg/mL) diabetes than among women without diabetes (80.3 pg/mL, 27.3-623.1 pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=0.39, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=0.28, P=0.04). CONCLUSION: Fetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life.

Clinical and ultrasound features of placental maturation in pre-gestational diabetic pregnancy.

BACKGROUND: Pre-gestational diabetes (PGDM) is a significant cause of neonatal morbidity and mortality. Delayed villous maturation (DVM) is a placental diagnosis with increased risk of perinatal mortality. AIMS: This study aimed to prospectively look at the incidence of DVM in a PGDM population compared to non-diabetic controls. Additionally, we analysed antenatal ultrasound and clinical markers for DVM in the diabetic population. STUDY DESIGN: This is a prospective study. SUBJECTS: Placentae of women with non-diabetic and PGDM pregnancies underwent detailed blinded histo-pathological examination. OUTCOME MEASURES: Clinical data, including birth weight, peri-natal outcome, and, in PGDM group, glycaemic control and ultrasound findings, were obtained. RESULTS: 77 non-diabetic women and 74 PGDM women consented to the study. The incidence of DVM in the PGDM group was higher than in the non-diabetic group (21/74 (28.4%) vs. 11/77 (14.3%) p=0.02; RR 1.98). In the PGDM group clinical and ultrasound markers were compared between the DVM group (n=21) and the non-DVM group (n=53). There was no difference in perinatal outcome nor glycaemic control between these two groups. CONCLUSION: DVM, a placental finding with an increased risk of perinatal mortality, is increased in PGDM population compared to non-diabetic controls. No association was found with maternal glycaemic control. The presence of placental DVM was not associated with antenatal ultrasound parameters nor clinical perinatal outcome.

Maternal and fetal placental growth hormone and IGF axis in type 1 diabetic pregnancy.

AIM: Placental growth hormone (PGH) is a major growth hormone in pregnancy and acts with Insulin Like Growth Factor I (IGF-I) and Insulin Like Growth Hormone Binding Protein 3 (IGFBP3). The aim of this study was to investigate PGH, IGF-I and IGFBP3 in non-diabetic (ND) compared to Type 1 Diabetic (T1DM) pregnancies. METHODS: This is a prospective study. Maternal samples were obtained from 25 ND and 25 T1DM mothers at 36 weeks gestation. Cord blood was obtained after delivery. PGH, IGF-I and IGFBP3 were measured using ELISA. RESULTS: There was no difference in delivery type, gender of infants or birth weight between groups. In T1DM, maternal PGH significantly correlated with ultrasound estimated fetal weight (r = 0.4, p = 0.02), birth weight (r = 0.51, p<0.05) and birth weight centile (r = 0.41, p = 0.03) PGH did not correlate with HbA1c. Maternal IGF-I was lower in T1DM (p = 0.03). Maternal and fetal serum IGFBP3 was higher in T1DM. Maternal third trimester T1DM serum had a significant band at 16 kD on western blot, which was not present in ND. CONCLUSION: Maternal T1DM PGH correlated with both antenatal fetal weight and birth weight, suggesting a significant role for PGH in growth in diabetic pregnancy. IGFBP3 is significantly increased in maternal and fetal serum in T1DM pregnancies compared to ND controls, which was explained by increased proteolysis in maternal but not fetal serum. These results suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in T1DM pregnancies, which are at higher risk of macrosomia.

Secondary recurrent miscarriage is associated with previous male birth.

Secondary recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses after delivery of a viable infant. Previous reports suggest that a firstborn male child is associated with less favourable subsequent reproductive potential, possibly due to maternal immunisation against male-specific minor histocompatibility antigens. In a retrospective cohort study of 85 cases of secondary RM we aimed to determine if secondary RM was associated with (i) gender of previous child, maternal age, or duration of miscarriage history, and (ii) increased risk of pregnancy complications. Fifty-three women (62.0%; 53/85) gave birth to a male child prior to RM compared to 32 (38.0%; 32/85) who gave birth to a female child (p=0.002). The majority (91.7%; 78/85) had uncomplicated, term deliveries and normal birth weight neonates, with one quarter of the women previously delivered by Caesarean section. All had routine RM investigations and 19.0% (16/85) had an abnormal result. Fifty-seven women conceived again and 33.3% (19/57) miscarried, but there was no significant difference in failure rates between those with a previous male or female child (13/32 vs. 6/25, p=0.2). When patients with abnormal results were excluded, or when women with only one previous child were considered, there was still no difference in these rates. A previous male birth may be associated with an increased risk of secondary RM but numbers preclude concluding whether this increases recurrence risk. The suggested association with previous male birth provides a basis for further investigations at a molecular level.