The importance of collaboration in maternal medicine: A retrospective descriptive study of a maternal multidisciplinary team meeting.

OBJECTIVE: In the present study we aimed to review the evolution and function of the maternal medicine multidisciplinary team (MMMDT) meeting of a maternal medicine service of a tertiary level stand-alone maternity hospital. METHODS: We conducted a retrospective descriptive study of all minutes of MMMDT meetings from 2014 to 2020, with the aim of evaluating meeting characteristics and patient demographics. RESULTS: There were 575 multidisciplinary team (MDT) discussions of 486 women during 43 meetings in the 7 year period. On average, 13 (range 3-23; SD = 5.28) women were discussed at each meeting, attended by 17 (range: 11-27; SD = 4.26) attendees. There were 18 women discussed during successive pregnancies. When analyzing the 2017-2020 data, preconceptual discussions made up 7.3% (n = 42) of patients discussed, with 5.7% (n = 33) being postnatal. The mean maternal age was 32.5 years (range 15-48 years) and women were most likely to be discussed in the mid-trimester period (21-24 weeks gestation). The top five primary specialities involved were hematology, neurology, rheumatology, neurosurgery and gastroenterology; however, 22 specialities were represented overall when classified by the primary medical condition. When examining the MDT input, hematology input was required in 144 patients (25.0%), radiology in 161 (28.0%) patients, and 117 in anesthesiology (20.3%). When examining the number of teams required to manage the patient, 80 women required the input of three specialities, with 16 women requiring the input of four specialities. CONCLUSION: We demonstrate the value and role of the MDT in the management of complex patients, providing a forum to discuss care in all phases of the obstetric journey.

Management of pregnancy in a patient with long-chain 3-hydroxyacyl CoA dehydrogenase deficiency.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare mitochondrial defect of ß-oxidation of long-chain fatty acids. Patients may present with muscle pain, hypotonia, peripheral neuropathy, cardiomyopathy, recurrent rhabdomyolysis and sudden death. Dietary management of LCHADD aims at preventing prolonged fasting and decreasing energy production from long-chain fatty acids compensated by an increase in medium-chain triglyceride fat. Herein, we present medical and dietetic management of a successful pregnancy in a LCHADD female patient and the delivery of a healthy baby boy.

Haematological parameters and coagulation in umbilical cord blood following COVID-19 infection in pregnancy.

OBJECTIVE: The aim of this study was to evaluate infants, born to women with SARS-CoV-2 detected during pregnancy, for evidence of haematological abnormalities or hypercoagulability in umbilical cord blood. STUDY DESIGN: This was a prospective observational case-control study of infants born to women who had SARS-CoV-2 RNA detected by PCR at any time during their pregnancy (n = 15). The study was carried out in a Tertiary University Maternity Hospital (8,500 deliveries/year) in Ireland. This study was approved by the Hospital Research Ethics Committee and written consent was obtained. Umbilical cord blood samples were collected at delivery, full blood count and Calibrated Automated Thrombography were performed. Demographics and clinical outcomes were recorded. Healthy term infants, previously recruited as controls to a larger study prior to the outbreak of COVID-19, were the historical control population (n = 10). RESULTS: Infants born to women with SARS-CoV-2 had similar growth parameters (birth weight 3600 g v 3680 g, p = 0.83) and clinical outcomes to healthy controls, such as need for resuscitation at birth (2 (13.3%) v 1 (10%), p = 1.0) and NICU admission (1 (6.7%) v 2 (20%), p = 0.54). Haematological parameters (Haemoglobin, platelet, white cell and lymphocyte counts) in the COVID-19 group were all within normal neonatal reference ranges. Calibrated Automated Thrombography revealed no differences in any thrombin generation parameters (lag time (p = 0.92), endogenous thrombin potential (p = 0.24), peak thrombin (p = 0.44), time to peak thrombin (p = 0.94)) between the two groups. CONCLUSION: In this prospective study including eligible cases in a very large population of approximately 1500 women, there was no evidence of derangement of the haematological parameters or hypercoagulability in umbilical cord blood due to COVID-19. Further research is required to investigate the pathological placental changes, particularly COVID-19 placentitis and the impact of different strains of SARS-CoV-2 (particularly the B.1.1.7 and the emerging Delta variant) and the severity and timing of infection on the developing fetus.

The Effect of COVID-19 Infection During Pregnancy; Evaluating Neonatal Outcomes and the Impact of the B.1.1.7. Variant.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection during pregnancy has been associated with adverse perinatal outcomes. We aim to evaluate the neonatal outcomes including the incidence of preterm birth, admission to the neonatal unit and incidence of congenital anomalies in this cohort. We will also describe these outcomes in the context of the B.1.1.7. variant outbreak, the dominant variant in Ireland since January 2021, which has had a greater impact on pregnant patients. METHODS: This was a retrospective study of liveborn infants, delivered between 1st March 2020 and 1st March 2021, to women with a severe acute respiratory syndrome coronavirus 2 diagnosis during pregnancy, in a tertiary maternity hospital (8,500 deliveries/year). Clinical data were collected, and analyses were performed to evaluate the impact of maternal symptom status, time from diagnosis to delivery and the B.1.1.7. variant on neonatal outcome. RESULTS: In total 133 infants (1.6%) were born to women with severe acute respiratory syndrome coronavirus 2 identified during pregnancy. The median birth weight was 3.45 kg and gestational age at birth was 39.3 weeks. 14 infants (10.5%) were preterm. 22 infants (16.5%) required admission to the neonatal unit and 7 (5.3%) were small for gestational age. There was no difference in growth, preterm birth or neonatal unit admission based on maternal symptom status or infection after the outbreak of B.1.1.7. as the dominant strain. CONCLUSIONS: Following a COVID-19 infection in pregnancy, there was no increase in the incidence of preterm birth or neonatal intensive care unit admission compared with 5-year hospital data. Maternal symptom status did not influence neonatal outcomes. Further studies to evaluate the impact of COVID-19 in early pregnancy, the variants of concern, particularly the emerging Delta variant and COVID-19 placentitis are required.

Medication use in pregnancy and lactation: A gap to be filled in postgraduate medical education.

OBJECTIVE: Medication use is a common therapeutic intervention during pregnancy, in the postpartum period and during lactation. Women routinely consult a variety of medical practitioners to request advice and prescription of medication. However, it is noted internationally that healthcare providers have insufficient knowledge to support women through their therapeutic journeys, and continual education is not provided as routine during postgraduate training and practice. STUDY DESIGN: There are five colleges in Ireland responsible for postgraduate medical training in Ireland for medicine, surgery, general practice, anaesthesiology and psychiatry. These are responsible for the curriculum design and implementation of 45 training programs, with the Royal College of Physicians responsible for 26 training programs and the Royal College of Surgeons of Ireland responsible for 15 training programs. We reviewed the national postgraduate training curricula of all speciality in the Republic of Ireland, excluding care of the elderly and pathology (given these practitioners would not be actively prescribing and treating pregnant or lactating women). RESULTS: We demonstrate that less than 50 % of the 43 post-graduate training programs mention medications in pregnancy and lactation. Pregnancy is not mentioned by 12 programs in any degree, and 18 programs do not mention lactation or breastfeeding in any form. CONCLUSION: It is imperative that consistent knowledge is provided and accessible to healthcare providers in order to support women and their families through healthy pregnancies, and support breastfeeding for as long as possible. Therefore, we call on postgraduate training bodies to include comprehensive education on medications in pregnancy and lactation in their syllabi going forward.

Alterations in fibrin formation and fibrinolysis in early onset-preeclampsia: Association with disease severity.

OBJECTIVE: ; Early-onset preeclampsia is a rare pregnancy-specific disorder associated with significantly increased maternal and fetal morbidity and mortality. Whilst it is known that even normotensive pregnancies are associated with changes in clot formation and dissolution, the nature of how these changes differ in those with early onset preeclampsia has not been well established. We sought to evaluate parameters of fibrin formation and fibrinolysis in individuals with early onset preeclampsia in comparison to both pregnant and non-pregnant controls. Furthermore, such parameters were correlated with markers of disease severity in this patient cohort, including the presence of multiorgan involvement, the rate of disease progression and the extent of the anti-angiogenic state in this condition. STUDY DESIGN: ; Patients with early onset preeclampsia (N = 20) and both pregnant (N = 16) and non -pregnant (N = 16) controls were recruited from the cohort at a large urban maternity hospital which saw over 15,000 deliveries during the study period. Platelet poor plasma was prepared from collected whole blood and analysed for parameters of fibrin formation and fibrinolysis (lagtime to and rate of fibrin formation; PAI-1; PAI-2; D-dimer; plasmin-antiplasmin; tPA) in addition to markers of angiogenesis (sFLT-1; Endoglin) using commercially available specific immunoassays. RESULTS: ; The maximum rate of fibrin formation as well as PAI-1, PAI-2 and D-dimer levels were all significantly increased in those with early onset preeclampsia and pregnant controls when compared to non-pregnant controls without significant differences between the 2 former groups. Plasmin-antiplasmin levels were significantly reduced in a similar manner. tPA levels were significantly elevated in EOP compared to both pregnant and non-pregnant controls. EOP was associated with significantly increased anti-angiogenic factors (sFLT-1; Endoglin) when compared to both pregnant and non-pregnant controls. CONCLUSION: ; Markers of fibrin formation and fibrinolysis are significantly alerted in early onset preeclampsia; furthermore, certain markers correlate with disease severity in this patient cohort.

Prevalence of postpartum venous thromboembolism risk factors in an Irish urban obstetric population.

BACKGROUND: Obstetric venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality. A clear understanding of the burden of VTE risk at a population level is a prerequisite to effective prevention; however, existing data are limited. OBJECTIVES: Describe the prevalence and patterns of VTE risk factors among postpartum women and consider the implications for VTE prevention practices. METHOD: We undertook a cross-sectional study of prospectively collected data from sequential postpartum VTE risk assessments completed between January 2015 and December 2017 in the Rotunda Hospital, Dublin. RESULTS: We analyzed postpartum VTE risk factors in a large unselected Irish urban obstetric cohort of 21 019 consecutively sampled women. This represents more than 90% of all women giving birth in a single institution over a 3-year period. The most common VTE risk factors related to maternal characteristics and delivery characteristics, including overweight and obesity (36%), age ≥35 (35%) and cesarean delivery (32%). More than three-quarters of women had at least 1 VTE risk factor (78%) and more than 40% had multiple (2 or more) VTE risk factors. One-fifth of women had no VTE risk factors before delivery, yet went on to develop VTE risk factors during delivery or in the postpartum period. Reflecting the differences in thromboprophylaxis thresholds internationally, the proportion of women who would have received a recommendation for postpartum thromboprophylaxis ranged from 7% to 37% under various clinical guidelines. CONCLUSION: This study demonstrates the high prevalence of VTE risk factors among postpartum women. Postpartum VTE risk is highly individualized and complex.

Thrombocalc: implementation and uptake of personalized postpartum venous thromboembolism risk assessment in a high-throughput obstetric environment.

INTRODUCTION: Venous thromboembolism risk assessment (VTERA) is recommended in all pregnant and postpartum women. Our objective was to develop, pilot and implement a user-friendly electronic VTERA tool. MATERIAL AND METHODS: We developed "Thrombocalc", an electronic VTERA tool using Microsoft EXCEL™ . Thrombocalc was designed as a score-based tool to facilitate rapid assessment of all women after childbirth. Calculation of a total score estimated risk of venous thromboembolism in line with consensus guidelines. Recommendations for thromboprophylaxis were included in the VTERA output. Implementation was phased. Uptake of the VTERA tool was assessed prospectively by monitoring the proportion of women who gave birth in our institution and had a completed risk assessment. Factors affecting completion and accuracy of risk assessments were also assessed. RESULTS: Thrombocalc was used prospectively to risk-assess 8380 women between September 2014 and December 2015. Compliance with this tool increased dramatically throughout the study period; over 92% of women were risk-assessed in the last quarter of data collection. Compliance was not adversely affected if delivery took place out of working hours [adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 0.93-1.14]. Risk assessment was less likely in the case of cesarean deliveries (aOR 0.66, 95% CI 0.60-0.73) and stillborn infants (aOR 0.48, 95% CI 0.29-0.79). Misclassification of risk factors led to approximately 207 (2.5%) inaccurate thromboprophylaxis recommendations. CONCLUSIONS: Our electronic, score-based VTERA tool provides a highly effective mechanism for rapid assessment of individual postpartum venous thromboembolism risk in a high-throughput environment.

Adjustment of therapeutic LMWH to achieve specific target anti-FXa activity does not affect outcomes in pregnant patients with venous thromboembolism.

Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality in the developed world. Low molecular weight heparins (LMWH) are routinely used to provide therapeutic anticoagulation during pregnancy for women with VTE, with measurement of plasma anti-FXa activity used to guide dosing in certain patient groups. There is limited evidence to support the use of anti-FXa monitoring in pregnant patients. This study seeks to ascertain whether anti-FXa monitoring of pregnant patients with VTE influences patient outcomes. We performed a single-centre case series including two consecutive groups of pregnant patients treated with LMWH for VTE sustained in the index pregnancy with and without monitoring of anti-FXa levels. 35,394 patients delivered during the study period in a large urban stand-alone maternity hospital, with 26 cases of VTE eligible for inclusion. There was no significant difference between the two groups in any clinical outcome; including maternal blood loss at delivery, recurrent thromboembolic events or rates of planned delivery. These data provide clinical evidence to support current international guideline recommendations that measurement of plasma anti-FXa activity in the majority of patients receiving therapeutic-intensity antenatal LMWH is not warranted.

The effect of maternal subclinical hypothyroidism on IQ in 7- to 8-year-old children: A case-control review.

BACKGROUND: In Ireland, pregnant women are not routinely screened for subclinical hypothyroidism (SCH). AIM: Our objective was to compare the intelligence quotient (IQ) of children whose mothers had been diagnosed with SCH prenatally with matched controls using a case-control retrospective study. MATERIALS AND METHODS: In a previous study from our group, 1000 healthy nulliparous women were screened anonymously for SCH. This was a laboratory diagnosis involving elevated TSH with normal fT4 or normal TSH with hypothyroxinaemia. We identified 23 cases who agreed to participate. These were matched with 47 controls. All children underwent neurodevelopmental assessment at age 7-8. Wechsler Intelligence Scale for Children IV assessment scores were used to compare the groups. Our main outcome measure was to identify whether there was a difference in IQ between the groups. RESULTS: From the cohort of cases, 23 mothers agreed to the assessment of their children as well as 47 controls. The children in the control group had higher mean scores than those in the case group across Verbal Comprehension Intelligence, Perceptual Reasoning Intelligence, Working Memory Intelligence, Processing Speed Intelligence and Full Scale IQ. Mann-Whitney U-test confirmed a significant difference in IQ between the cases (composite score 103.87) and the controls (composite score 109.11) with a 95% confidence interval (0.144, 10.330). CONCLUSIONS: Our results highlight significant differences in IQ of children of mothers who had unrecognised SCH during pregnancy. While our study size and design prevents us from making statements on causation, our data suggest significant potential public health implications for routine prenatal screening.

Haemorrhagic and thrombotic complications in pregnant women with acquired and congenital cardiac disease.

BACKGROUND: Pregnant patients with cardiac disease have significantly higher predicted maternal morbidity and mortality compared to the general obstetric population. Published guidelines on optimal management of these patients recommend multidisciplinary care provision. There are few published data on the incidence of haematological complications in pregnant women with cardiac disease, although the data that does exist suggests a relatively high rate of bleeding and thrombotic events. AIMS: To determine the outcomes in terms of haematological morbidity occurring within a cohort of pregnant women with cardiac disease in the setting of multidisciplinary care provision. METHODS: Patients were identified from a database compiled by the obstetric cardiology service listing all cardiac patients managed in the Rotunda maternity hospital during the period from 2004 to 2011. Data were obtained from the medical and obstetric case notes relating to details of perinatal care and the occurrence of antenatal and postnatal complications. RESULTS: During the 8-year review period, 451 women with cardiac disease were assessed. Fifty-nine were determined to have moderate to high-risk disease. Each received consultant-delivered multidisciplinary care, where written management strategies were agreed by collaborating senior colleagues either preconceptually or in early pregnancy. No venous thromboembolic events occurred and a modest rate of post-partum haemorrhage (approximately 5%) was recorded. There were no maternal deaths. CONCLUSION: The relatively favourable outcomes observed within our institution highlight the importance of a multidisciplinary approach to the management of pregnant women with cardiac disease, particularly in scenarios where limited published evidence exists to guide management.

Association of copy number variants with specific ultrasonographically detected fetal anomalies.

OBJECTIVE: To evaluate the association of other-than-common benign copy number variants with specific fetal abnormalities detected by ultrasonogram. METHODS: Fetuses with structural anomalies were compared with fetuses without detected abnormalities for the frequency of other-than-common benign copy number variants. This is a secondary analysis from the previously published National Institute of Child Health and Human Development microarray trial. Ultrasound reports were reviewed and details of structural anomalies were entered into a nonhierarchical web-based database. The frequency of other-than-common benign copy number variants (ie, either pathogenic or variants of uncertain significance) not detected by karyotype was calculated for each anomaly in isolation and in the presence of other anomalies and compared with the frequency in fetuses without detected abnormalities. RESULTS: Of 1,082 fetuses with anomalies detected on ultrasound scan, 752 had a normal karyotype. Other-than-common benign copy number variants were present in 61 (8.1%) of these euploid fetuses. Fetuses with anomalies in more than one system had a 13.0% frequency of other-than-common benign copy number variants, which was significantly higher (P<.001) than the frequency (3.6%) in fetuses without anomalies (n=1,966). Specific organ systems in which isolated anomalies were nominally significantly associated with other-than-common benign copy number variants were the renal (P=.036) and cardiac systems (P=.012) but did not meet significance after the adjustment. CONCLUSIONS: When a fetal anomaly is detected on ultrasonogram, chromosomal microarray offers additional information over karyotype, the degree of which depends on the organ system involved. LEVEL OF EVIDENCE: : II.

The prevalence of maternal F cells in a pregnant population and potential overestimation of foeto-maternal haemorrhage as a consequence.

BACKGROUND: Acid elution (AE) is used to estimate foeto-maternal haemorrhage (FMH). However AE cannot differentiate between cells containing foetal or adult haemoglobin F (F cells), potentially leading to false positive results or an overestimate of the amount of FMH. The prevalence of F cells in pregnant populations remains poorly characterised. The purpose of this study was to ascertain the incidence of HbF-containing red cells in our pregnant population using anti-HbF-fluorescein isothiocyanate flow cytometry (anti-HbF FC) and to assess whether its presence leads to a significant overestimate of FMH. MATERIAL AND METHODS: Eighty-eight pregnant patients were assessed for the presence of F cells and foetal red cells by AE and anti-HbF FC. The "FMH equivalent", estimated by AE and anti-HbF FC, was calculated. RESULTS: Thirty-six percent of the pregnant population had F-cell populations detectable by anti-HbF FC while AE detected F cells in 48% of the population. The mean estimated FMH equivalent determined by AE and anti-HbF FC was 0.59 mL (0-23.93 mL) and 0.41 (0 to 2.19 mL), respectively (p=0.012). In 3% of our population, AE overestimated the FMH by >3 mL due to the presence of an F-cell population of at least 16%. DISCUSSION: Thirty-six percent of a prospectively evaluated group of consecutive pregnant women were found to have F-cell populations. In some patients, these findings were clinically significant as AE overestimated the degree of FMH as a consequence.

Practice patterns and preferences of obstetricians and gynecologists regarding thromboprophylaxis at the time of Cesarean section.

OBJECTIVE: Our survey aimed to identify knowledge and application of guidelines in the United States by assessing practicing obstetricians and gynecologists (OBGYN) use of thromboprophylaxis, preferred methods and whether their type of practice influenced their choices. STUDY DESIGN: A cross-sectional survey of fellows of the American College of Obstetricians and Gynecologists (ACOG) was performed. A 21-item paper and electronic questionnaire was sent to each participant. A total of three mailings were carried out. RESULTS: In total, 400 OBGYN were invited to participate. Questionnaires were returned by 209 (52.3%), 157 (75.1%) of whom provided prenatal care within the last year. All respondents used at least one method of thromboprophylaxis routinely. About 92.4% used pneumatic compression devices. An equal proportion used unfractionated heparin and low molecular weight heparin routinely (17.8%). About 19.1% routinely used combination prophylaxis. In total, 77.1% (n = 121) used the ACOG guidelines. Local hospital guidelines were referenced by 38.2% (n = 60). Other guidelines referenced were the ACCP guideline (n = 34, 21.7%) and several international guidelines (n = 5, 3.3%). CONCLUSION: Awareness of the risk of thromboembolism around delivery by cesarean section is high among OBGYN practitioners. Broadening guidelines to encompass all deliveries, not only cesareans, with a focus on identifying the patient at risk, would likely be successful.

Pulmonary embolus in pregnancy.

Venous thromboembolism remains in the top three leading causes of maternal death in the US, representing 10.2% of pregnancy-related deaths. Risk of developing a pulmonary embolus appears to increase throughout pregnancy, with a peak in incidence in the early postpartum period. Overall the incidence of VTE is 0.6-1.8 VTEs per 1000 deliveries. Diagnosis and management of pulmonary embolus can prove challenging, but the aim should be to optimize maternal outcome while minimizing hemorrhagic complications. Low-molecular-weight heparin is a safe and effective treatment for the majority of cases of pregnancy-related pulmonary embolus.

The correlation of ultrasonographic placental architecture with placental histology in the low-risk primigravid population.

AIM: To determine the association, if any, between placental architecture findings assessed ultrasonographically at 22 and 36 weeks and placental histology. METHODS: There was prospective recruitment of 1011 low-risk primigravids from the antenatal clinic at the Rotunda Hospital, Dublin, Ireland. Ultrasound of the placenta was performed at 22 and 36 weeks and histological assessment was made of the placenta of all participants. RESULTS: Complete data pertaining to ultrasound and placental histology was available for 810 women (80%). Placental calcification on ultrasound in the third trimester was associated with a higher incidence of placental infarction identified following placental histology (80.0% vs. 21.5%; P=0.009: r=0.115). The placental thickness on ultrasound in the second trimester was less in cases complicated by chorioamnionitis (2.62 cm vs. 3.07 cm; P=0.039: r=-0.176). Chronic villitis was associated with a statistically significant increased incidence of antenatal placental infarction identified on ultrasound in the third trimester (10.7% vs. 1.9%; P=0.020: r=0.113). Intervillous thrombi occurred more frequently in cases with reduced placental thickness on ultrasound in the second trimester (3.0 cm vs. 3.3 cm; P=0.035: r=-0.171). CONCLUSIONS: Antenatal ultrasound of the placenta may aid detection of placental disease, particularly in the identification of placental infarction.

Early fetal anatomical sonography.

Over the past decade, prenatal screening and diagnosis has moved from the second into the first trimester, with aneuploidy screening becoming both feasible and effective. With vast improvements in ultrasound technology, sonologists can now image the fetus in greater detail at all gestational ages. In the hands of experienced sonographers, anatomic surveys between 11 and 14 weeks can be carried out with good visualisation rates of many structures. It is important to be familiar with the normal development of the embryo and fetus, and to be aware of the major anatomical landmarks whose absence or presence may be deemed normal or abnormal depending on the gestational age. Some structural abnormalities will nearly always be detected, some will never be and some are potentially detectable depending on a number of factors.

The impact of positive acquired thrombophilia serology on ultrasound, obstetric outcome and the placenta in a low-risk primigravid population.

Our aim was to determine the prevalence and sequelae of positive acquired thrombophilia serology in the asymptomatic low-risk primigravid population. We undertook a prospective blinded study of 1011 primigravid patients screening for lupus anticoagulant, anticardiolipin antibody, anti-ß 2 glycoprotein-1 and antinuclear antibody assessment at booking and 36 weeks gestation. Serial ultrasounds of the fetus with uterine and umbilical Dopplers and placental evaluation were performed at 24 and 36 weeks gestation. Antenatal course, labour and delivery outcome and placental histology were reviewed. The incidence of positive acquired thrombophilia serology was 27.4%. Overall, there was no difference in rates of fetal loss or maternal disease between women with positive acquired thrombophilia serology and the control population. Routine testing for acquired thrombophilic traits is therefore not warranted.