Amniocentesis in pregnancies at or beyond 24 weeks: an international multicenter study.

BACKGROUND: Amniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse. OBJECTIVE: To evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation. STUDY DESIGN: We conducted an international multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved 9 referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and postprocedure complications. RESULTS: Of the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within 2 weeks postprocedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24 and 28 weeks and those between 28 and 32 weeks, reinforcing the procedure's safety across these gestational periods. CONCLUSION: Late amniocentesis, at or after 24 weeks of gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.

Uptake rates and attitudes to influenza and COVID-19 vaccination in pregnancy - a prospective cohort study.

Influenza and COVID-19 are highly prevalent RNA viruses. Pregnancy increases the frequency of severe maternal morbidity and mortality associated with these viruses. Vaccination plays an important role in protecting pregnant women and their infants from adverse outcomes. In this prospective study, we aimed to determine the vaccination uptake rate for influenza and COVID-19 in a pregnant population and to explore reasons why women remained unvaccinated. A prospective cohort study was conducted over a two-week period in December 2022 in the National Maternity Hospital, Dublin. There were 588 women surveyed over the 2-week period. Overall, 377 (57%) were vaccinated that year for seasonal influenza, a significant rise from 39% in a similar study in 2016. The majority (n = 488, 83%) of women reported receiving at least one COVID-19 vaccine. However only 132 (22%) received a COVID-19 vaccine in pregnancy, despite 76% (n = 466) stating they would be happy to receive it. Factors such as age, obesity, co-morbidities, ethnic group, and type of antenatal care received were shown to influence vaccination rates. We recommend that the importance of vaccination be stressed regularly to eligible patients at their antenatal clinic visits and where possible combining influenza/COVID-19 vaccination on the same day to improve uptake.

Mid-luteal uterine artery Doppler indices in the prediction of pregnancy outcome in nulliparous women undergoing assisted reproduction.

Traditionally, the assessment of endometrial receptivity at transvaginal ultrasound scan has been based on the thickness and the morphological appearance of the endometrium. The objective of this study was to prospectively evaluate endometrial thickness (ET), endometrial morphology and uterine artery Doppler parameters prior to assisted reproduction treatment (ART) in the prediction of pregnancy outcome. This was a prospective cohort study. ET, morphology and uterine artery Doppler (UtAD) pulsatility index (PI) and resistance index (RI) were measured in the mid-luteal stage of the menstrual cycle ultrasonographically, timed with urinary luteinizing hormone testing. A total of 50 women were included in the analysis. The clinical pregnancy rate (CPR) per embryo transfer was 42.0% (n = 21/50). Twenty nine women (58.0%) had an unsuccessful outcome. There were no differences in mean ± SD endometrial thickness (ET) (10.0 ± 1.8 mm vs. 10.5 ± 2.4; p = 0.43), or endometrial morphology (100% (n = 21) vs 100% (n = 29); p = 1.00) between the pregnant and not pregnant groups. Similarly, there were no differences in mean ± SD UtAD PI (2.17 ± 0.83 vs. 2.07 ± 0.81; p = 0.67 or mean ± SD UtAD RI (0.84 ± 0.10 vs. 0.81 ± 0.10; p = 0.30). Ultrasonographic endometrial assessment did not differentiate between those who would have a subsequent clinical pregnancy.

The impact of accurately timed mid-luteal endometrial injury in nulligravid women undergoing their first or second embryo transfer.

INTRODUCTION: Endometrial injury or 'scratch' preceding an assisted reproductive therapy (ART) cycle has recently been shown not to improve livebirth rates among women undergoing ART. The objective of this study was to compare pregnancy outcomes in nulliparous women who underwent an accurately timed mid-luteal scratch biopsy prior to ART with those who did not. METHODS: This was a prospective cohort study. Women were recruited between October 2016 and February 2018 inclusive. Women who met the inclusion criteria and who did not undergo an endometrial scratch in the study period were used as a comparison group. Patients underwent a cycle of ART in the menstrual cycle following endometrial scratch. RESULTS: Ninety-eight women were eligible for participation in the study. There were no differences in rates of implantation (35.7% (n = 20/56) vs. 35.4% (n = 17/48); p = 1.00), clinical pregnancy (40.0% (n = 20/50) vs. 39.5% (n = 17/43); p = 1.00) or live birth (34.0% (n = 17/50) vs. 25.6% (n = 11/43); p = 0.50) per embryo transfer between those who underwent a scratch and those who did not. CONCLUSION: Endometrial scratch is a simple, inexpensive and low-risk procedure. However, in this relatively small cohort study, no differences in rates of implantation, clinical pregnancy or live birth in women with primary infertility were determined between those who underwent a scratch and those who did not.

Cesarean delivery rates using Robson classification system in Ireland: What can we learn?

OBJECTIVE: It has been proposed that the Robson Ten-Group Classification System be used as a global standard for assessing, monitoring and comparing cesarean delivery (CD) rates within and between maternity services. Our objective was to compare the change of CD rates within the 10-Group Classification System in our institution over 10 years. STUDY DESIGN: From 2005-2014 inclusive data was collected prospectively and all women were classified using the obstetric concepts and parameters described in the Ten-Group Classification System. Linear regression and weighted Least Squares regression analyses were used to analyze trends over time. RESULTS: During 2005-2014 inclusive, 88,004 mothers delivered 89,649 babies ≥500 g. Over the 10 year period there was an increase in CD rate from 18.3% to 23.5%, with a linear increase in CD rate by 0.6% annually (95% CI:0.52, 0.75;p < 0.001). The main contribution to the increase in the CD rate was Group 2a (induced single cephalic nulliparous women at term), Group 2b (pre-labor single cephalic nulliparous women at term) and Group 5 (single cephalic multiparous women at term with a previous CD). No increase in CD rate was noted in Group 1 (single cephalic nulliparous women presenting in spontaneous labor at term). The percentage of women ≥35 years of age increased from 28.4% to 39.8% over the study period (0.98% per year; 95% CI:0.64, 1.33;p < 0.001). CONCLUSION: The driving force for the increase in CD in the National Maternity Hospital has been induction of labor and pre-labor CD in nulliparous women with a single cephalic pregnancy at term. This inevitably results in a larger population of women with a previous CD and therefore a secondary contribution to the increase in the overall CD rate.

Retrievable Inferior vena cava filters in pregnancy: Risk versus benefit?

OBJECTIVE: Venous thromboembolism remains one of the leading causes of maternal mortality in the developed world. Retrievable inferior vena cava (IVC) filters have a role in the prevention of lethal pulmonary emboli when anticoagulation is contraindicated or has failed [1]. It is unclear whether or not the physiological changes in pregnancy influence efficacy and complications of these devices. The decision to place an IVC filter in pregnancy is complex and there is limited information in terms of benefit and risk to the mother. The objective of this study was to determine the efficacy and safety of these devices in pregnancy and to compare these with rates reported in the general population. STUDY DESIGN: The aim of this study was report three recent cases of retrievable IVC filter use in pregnant women in our department and to perform a systematic review of the literature to identify published cases of filters in pregnancy. The efficacy and complication rates of these devices in pregnancy were estimated and compared to rates reported in the general population in a recent review [2]. Fisher's exact test was used for statistical analysis. RESULTS: In addition to our three cases, 16 publications were identified with retrievable IVC filter use in 40 pregnant women resulting in a total of 43 cases. There was no pulmonary embolus in the pregnant group (0/43) compared to 57/6291 (0.9%) in the general population. Thrombosis of the filter (2.3% vs. 0.9%, p = 0.33) and perforation of the IVC (7.0% vs 4.4%, p = 0.44) were more common in pregnancy compared to the general population but the difference was not statistically significant. Failure to retrieve the filter is more likely to occur in pregnancy (26% vs. 11%, p = 0.006) but this did not correlate with the type of device (p = 0.61), duration of insertion (p = 0.58) or mode of delivery (p = 0.37). CONCLUSION: Data for retrievable IVC filters in pregnancy is limited and there may be a publication bias towards complicated cases. This study shows that the filter appears to protect against PE in pregnancy but the numbers are small. Complications such as filter thrombosis and IVC penetration appear to be higher in pregnancy but this difference is not statistically significant. It is not possible to retrieve the device in one out of every four pregnant women. This has implications in terms of long term risk of lower limb thrombosis and post thrombotic syndrome. The decision to use an IVC filter in pregnancy needs careful consideration by a multidisciplinary team. The benefit and risk assessment should be individualised and clearly outlined to the patient.

A prospective pilot study of Dilapan-S compared with Propess for induction of labour at 41+ weeks in nulliparous pregnancy.

BACKGROUND: The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological. AIMS: The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy. METHODS: This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop's score and caesarean delivery rate. RESULTS: Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop's score. CONCLUSIONS: Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas.

Interpregnancy weight changes and impact on pregnancy outcome in a cohort of women with a macrosomic first delivery: a prospective longitudinal study.

OBJECTIVE: To determine the median interpregnancy maternal weight change between first and second pregnancies, and second and third pregnancies and to assess the impact of this weight change on pregnancy outcome in a cohort of women with a macrosomic first delivery. STUDY DESIGN: Prospective longitudinal study conducted over three pregnancies from 2007 to 2015. SETTING: Tertiary referral maternity hospital, Dublin, Ireland. PARTICIPANTS: Women were recruited if their first baby weighed >4.0 kg. METHODS: The pregnancy outcomes in the second and third pregnancies were analysed separately. Data were also analysed for both interpregnancy intervals comparing outcomes for those who gained any weight, or more weight than the median, with those who did not. MAIN OUTCOME MEASURES: Recurrent fetal macrosomia ≥4.0 kg and gestational diabetes mellitus. RESULTS: There were 280 women who delivered a third baby between 2011 and 2015. There were no differences in pregnancy outcomes for the second pregnancy in women who gained interpregnancy weight compared with those who did not and those who gained more interpregnancy weight than the median compared with those who did not. There was a statistically significant increase in birth weight ≥4.0 kg (54.0% vs 39.6% p=0.03) in those women who gained any weight between the second and third pregnancies. In those women who gained more interpregnancy weight than the median (1.70 kg) between a second and third pregnancy, there was a significant increase in the rate of gestational diabetes (6.5% vs 1.4%, p=0.03). CONCLUSIONS: This longitudinal study demonstrates that within this cohort maternal interpregnancy weight change between a second and third pregnancy is associated with an increase in birth weight ≥4.0 kg. Additionally, a gain of more weight than the median (1.70 kg) is associated with a higher rate of gestational diabetes.

Effects of the KIR7.1 Blocker VU590 on Spontaneous and Agonist-Induced Contractions of Human Pregnant Myometrium.

KIR7.1, an inwardly rectifying K+ channel, plays a critical role in regulating uterine excitability during pregnancy and has been suggested as a potential new target for the treatment of conditions arising from dysfunctional uterine contractility, for example, atonic postpartum hemorrhage. The aim of this study was to investigate the effects of the selective KIR7.1 blocker, VU590, on both spontaneous and agonist-stimulated contractions of human pregnant myometrium in vitro. At a concentration of 20 µmol/L, VU590 significantly increased the mean contractile force and the frequency of spontaneous contractions ( P < 0.05) when compared to vehicle-treated tissues. However, there was a significant ( P < 0.0001) monoexponential decay in amplitude with time of exposure. When VU590 was coadministered with EC50 concentration of the uterotonics oxytocin, ergometrine, or carboprost, the only significant changes were an immediate decrease in the amplitude of oxytocin- and carboprost-induced contractions and a delayed reduction in amplitude and an increase in the frequency of ergometrine-induced contractions. Amplitude to all 3 agents in the presence of VU590 showed a monoexponential decay with time of exposure ( P < 0.0001). We conclude that VU590 modifies the contractility of pregnant human myometrium in support of a role for KIR7.1 in regulating that process. However, VU590 in vitro does not produce the types of contraction, either alone or in combination with other uterine stimulants that would suggest its usefulness as a first- or second-line clinical uterotonic agent.

Obstetric and neonatal characteristics of pregnancy and delivery for infant birthweight ≥5.0 kg.

AIM: Infant birthweight ≥5.0 kg represents a significant risk factor for mother and neonate. The objective of this study was to examine the obstetric and neonatal outcome measures in a large cohort of such deliveries. METHODS: The data used for this study were prospectively entered into an obstetric computerized database during the period 1989-2013. All pregnancies where the delivery resulted in an infant weighing ≥5.0 kg were identified. The results were retrospectively analyzed separately for parity, and a separate analysis was performed comparing the outcome measures observed in the earlier years of the study with those of the later years. RESULTS: There were 73,796 deliveries in the time period of which there were n = 201 (0.3%) infants with birth weight ≥5.0 kg. The mean maternal body mass index (BMI) was in the obese category range (30.9 kg/m2) and the median gestation at delivery was 40.8 weeks. The cesarean delivery rate for nulliparous women was 56.3% and for parous women 30.8%. The overall rate of third degree perineal tears was 3.8%, the rate of shoulder dystocia was 4.6% and the rate of Erb's Palsy was 1.5%. There was a significant increase in cesarean delivery in the latter of the study (26.7% versus 43.0%, p = 0.02), due to an increase in the planned pre-labor cesarean deliveries (30.0 versus 12.9%, p = 0.005). There was no difference in adverse outcomes in both groups. CONCLUSION: These findings describe the features of pregnancy associated with infant birthweight ≥5.0 kg, and outline reliable maternal and neonatal morbidity data for these pregnancies. In this cohort, there was no apparent benefit from increased planned pre-labor cesarean delivery rates.

Is routine transvaginal cervical length measurement cost-effective in a population where the risk of spontaneous preterm birth is low?

INTRODUCTION: A recent meta-analysis has suggested that routine measurement of the cervical length should be performed in conjunction with the anomaly scan to identify a group of women at increased risk of preterm delivery. We decided to investigate whether this recommendation is justifiable in a population where the risk of preterm birth is low. MATERIAL AND METHODS: We reviewed 12 years of obstetric data from the Coombe Women and Infants University Hospital. Relative risks of adverse outcomes from the randomized controlled trial were applied and we extrapolated the possible numbers of women requiring intervention. We then used published neonatal data to estimate the cost of neonatal care and estimated the costs of providing the service. RESULTS: Over 12 years from 2000 until 2011, there were 94 646 singleton deliveries, 1776 happening before 34 weeks. Spontaneous onset occurred in 882 (49.7%) of this group. These 882 births were studied. If we apply the figures from a randomized controlled trial, 1609 women (1.7% from our total population) would be expected to have a cervical length 15 mm. If we gave vaginal progesterone to all women with a sonographically short cervix, we would reduce the delivery rate before 34 weeks by 27.7%. The annual costs of providing the service were estimated to be €109 249 and the cost of immediate neonatal care was estimated to be €380 514. CONCLUSION: Given the implications associated with preterm delivery, routine measurement of cervical length at the time of the anomaly scan may be justifiable from a cost point of view in a population where the risk of preterm birth is low.

In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when P<0.05. There were no significant differences in the peak amplitude of response between agents, except for misoprostol, which was inactive. There was a wide difference in potencies using both measures of contractility, with oxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol.

Maternal Age and Contractility of Human Myometrium in Pregnancy.

There is controversy as to whether maternal age exerts an influence on the contractility of human myometrium in pregnancy. The aim of this study was to examine a series of functional contractile parameters of human myometrium in vitro, over a broad range of maternal ages. Myometrial tissue specimens were obtained at cesarean delivery from 32 women with maternal ages ranging from 28 to 52 years. Using in vitro recordings, a number of contractile parameters including maximal amplitude, mean contractile force, time to maximal amplitude, maximum rate of rise, and occurrence of simple and complex (biphasic and multiphasic) contractions were examined for spontaneous and induced contractile activity. The relationship between maternal age and individual parameters was evaluated using linear regression analysis. For all contractile parameters examined, for both spontaneous and induced contractions, no significant correlation was observed with maternal age between 28 and 52 years. The mean maximum amplitude values for spontaneous and oxytocin-induced contractions were 23 ± 3 and 43 ± 5 mN, respectively. The mean contractile forces for spontaneous and oxytocin-induced contractions were 1.5 ± 0.2 and 6.5 ± 0.9 mN, respectively. There was no variation in the proportion of biphasic or multiphasic contractions with maternal age. These results indicate there is no significant functional impairment of uterine contractility and no lack in responsiveness of myometrium in vitro, in the older mother. These findings do not support the concept that there may be a biological basis for dysfunctional labor or increased cesarean delivery rates in older parturients.

A longitudinal study of unplanned pregnancy in a maternity hospital setting.

OBJECTIVE: To review family planning in a cohort of women who delivered a second child within 3 years of their first. METHODS: A longitudinal, observational study included women aged at least 18 years who had delivered a singleton weighing at least 500 g in 2009 after their first pregnancy at a hospital in Dublin, Ireland, and who returned to the hospital for prenatal care for a second pregnancy before January 2012. Logistic regression analyses were performed to examine the effect of maternal characteristics on pregnancy intention. RESULTS: Of 3284 primigravidas who delivered in 2009, 1220 (37.1%) returned with a second pregnancy. The second pregnancy was unplanned in 248 (20.3%) women, and both pregnancies were unplanned in 124 (10.2%). The second pregnancy was more likely to be unplanned in women whose first pregnancy was also unplanned than in those whose first was planned (adjusted odds ratio 6.5; 95% confidence interval 4.6-8.4; P<0.001). Among the 99 women with recurrent unplanned pregnancy who had not been using contraception before the first pregnancy, 85 (85.9%) were also not using contraception before the second. CONCLUSION: Women whose first pregnancy is unplanned are at increased risk of subsequent unplanned pregnancies. Postnatal contraceptive advice in this high-risk group should be prioritized.

Interpregnancy changes in maternal weight and body mass index.

OBJECTIVE: This longitudinal study compared changes in maternal weight and body mass index (BMI) in early pregnancy in the time interval between when a woman first attended for antenatal care with her first child and when she next attended for antenatal care. STUDY DESIGN: We studied women with a singleton pregnancy who delivered their first baby weighing ≥ 500 g in 2009 and who attended again for antenatal care with an ongoing pregnancy before January 1, 2012. Maternal weight and height were measured before 18 weeks' gestation in both pregnancies and BMI was calculated. RESULTS: Of the 3,284 primigravidas, the mean weight at the first visit in 2009 was 66.4 kg (standard deviation [SD] 12.7). The mean BMI was 24.5 kg/m(2) (SD 4.6), and 11.3% (n = 370) were obese. Of the 3,284 women, 1,220 (37.1%) re-attended for antenatal care before 2012 after sonographic confirmation of an ongoing pregnancy. Of the 1,220 women who re-attended, 788 (64.6%) had gained weight (mean 4.6 kg [SD 3.9]), 402 (33%) had lost weight (mean 3 kg [SD 2.9]), and 30 (2.4%) had maintained their weight. CONCLUSION: The birth of a first baby was associated with an increase in maternal weight in two-thirds of women when they next attended for antenatal care.

Gastric neuroendocrine tumours.

BACKGROUND: Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. METHODS: Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. RESULTS: Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. CONCLUSIONS: Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted.