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.

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.

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.

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.

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.

Troponin T and pro-B-type natriuretic Peptide in fetuses of type 1 diabetic mothers.

OBJECTIVE: Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro-B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester. RESULTS: Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05). CONCLUSIONS: Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

Effect of pregestational diabetes mellitus on fetal cardiac function and structure.

OBJECTIVE: Fetuses of diabetic pregnancy experience cardiomyopathy, the intracardiac cause of which is understood poorly. The aim of this study was to assess the interrelation between cardiac functional and structural changes in fetuses of mothers with pregestational diabetes mellitus. STUDY DESIGN: Twenty-six mothers with pregestational diabetes mellitus were recruited prospectively to have a fetal echocardiogram at 13, 20, and 36 weeks of gestation to assess cardiac function and structure. For comparison, 30 healthy control subjects were recruited at each gestational age. RESULTS: In the first trimester, there was evidence of poorer fetal cardiac diastolic function among the diabetic cohort (lower left early/atrial ratio, longer isovolumetric relaxation time and higher left myocardial performance index; P < .05). In the third trimester, the fetal interventricular septum and the right ventricular free wall were thicker in the diabetic cohort (P < .05). CONCLUSION: In fetuses of pregestational diabetic pregnancy, sonographic evidence of altered cardiac function is evident before ultrasound evidence of cardiac structural changes. This suggests that altered cardiac function may precede cardiac structural changes in fetuses of pregestational diabetic pregnancy.

First-trimester fetal cardiac function.

OBJECTIVE: The purpose of this study was to establish normal values for fetal heart function in the first trimester. METHODS: This was a prospective observational study with institutional ethics approval and written maternal consent. Thirty-two healthy pregnant women were recruited, and transabdominal fetal echocardiography was performed between 12 and 14 completed weeks' gestation. Myocardial function was assessed with the myocardial performance index to assess combined systolic and diastolic function, isovolumetric contraction time to assess systolic function, and isovolumetric relaxation time to assess diastolic function. Mitral and tricuspid inflows were also assessed by determining the ratio between passive and active ventricular filling. The ventricular outflows were also assessed by peak systolic velocities (PSVs) and time velocity integrals (TVIs). RESULTS: The mean gestational age at the time of echocardiography was 13 weeks, and the mean crown-rump length was 79 mm. All fetuses had a normal nuchal translucency measurement (mean, 1.5 mm). The myocardial performance index was the same in the left and right sides of the heart, 0.5. The mean isovolumetric relaxation time and isovolumetric contraction time on the left side of the heart were 41 and 36 milliseconds, respectively. The mean passive/active ventricular filling ratio was 0.6 at both the mitral and tricuspid valves. The mean aortic PSV was 26 cm/s, and mean pulmonary artery PSV was 32 cm/s. The mean aortic outflow TVI was 3.6 cm, and the mean pulmonary outflow TVI was 4.1 cm. CONCLUSIONS: This study establishes normal values for cardiac function at 12 to 14 weeks' gestation. These values may assist in assessment of fetal health in early pregnancy.

Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers.

To report the incidence of cardiomegaly in stillborn normally formed infants of mothers with diabetes mellitus. This is a retrospective study with institutional ethics approval. The presence of cardiomegaly was recorded in stillborn infants of diabetic mothers (N = 27) and compared with that recorded in stillborn large-for-gestational age (LGA > 90th percentile, n = 18) and stillborn appropriately grown (10th to 90th percentiles, n = 107) nondiabetic infants. Blinded to the clinical details, the histology slides were reviewed to measure cardiac wall thickness and to record the presence or absence of myocardial fiber disarray. Stillborn infants of mothers with diabetes mellitus, when compared with appropriately grown stillborn nondiabetic infants and when adjusted for birth weight, had heavier hearts, thicker ventricular free wall measurements, and lighter brains. While cardiomegaly was reported in 22% of stillborn LGA infants, comparison with stillborn appropriately grown infants revealed no difference in heart weights corrected for birth weight. Comparison of LGA nondiabetic infants with stillborn diabetes mellitus infants revealed greater actual heart weight/expected for birth weight (P < 0.05) and lighter brains (actual brain weight/expected for birth weight, P < 0.05) in the diabetes mellitus group. Cardiomegaly is a common finding in stillborn infants of mothers with diabetes mellitus and may contribute to the risk of fetal death in these pregnancies.