Diagnosis and management of late-onset fetal growth restriction

This thesis describes the impact and the complexity of the diagnosis and management of late-onset fetal growth restriction. Fetal growth restriction is a condition in which the fetus is unable to reach its intrinsic growth potential due to reduced placental function. The lack of oxygen and nutrients hampers the fetus from optimal growth and development. Late-onset fetal growth restriction affects a high number of pregnancies and has a large societal impact in terms of adverse outcomes and an increased risk for the development of cardiovascular disease later in life. This thesis emphasizes that the detection of these fetuses at risk is challenging because symptoms may be subtle at term gestation. Small size as stand-alone modality is only moderately predictive and unreliable. The condition affects both small fetuses and fetuses who are within ‘normal’ birth weight ranges. Small- or large fetal size does not necessarily reflect pathology but puts the fetus at a higher risk and an appropriate size is not a guarantee of normal outcomes. The observed large heterogeneity in Dutch hospital protocols underlines the complexity of the condition. To overcome some of the inconsistencies, a consensus definition and core outcome set were developed. Furthermore, two research protocols to investigate the role of Doppler ultrasound as a marker of placental function in the management of late-onset fetal growth restriction are outlined. The challenge for the coming decade is to implement the consensus definitions and to evaluate (new) placental markers to improve identification of the compromised fetuses at (near) term gestation

Abnormal Fetal Growth:Small for Gestational Age, Fetal Growth Restriction, Large for Gestational Age: Definitions and Epidemiology

Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth, "small for gestational age" and "large for gestational age" are commonly used terms. However, both are statistical definitions of fetal size below or above a certain threshold related to a reference population, rather than referring to an abnormal condition. Fetuses can be constitutionally small or large and thus healthy, whereas fetuses with seemingly normal size can be growth restricted or overgrown. Although golden standards to detect abnormal growth are lacking, understanding of both pathologic conditions has improved significantly.</p

Evaluation and Management of Suspected Fetal Growth Restriction

Impaired fetal growth owing to placental insufficiency is a major contributor to adverse perinatal outcomes. No intervention is available that improves outcomes by changing the pathophysiologic process. Monitoring in early-onset fetal growth restriction (FGR) focuses on optimizing the timing of iatrogenic preterm delivery using cardiotocography and Doppler ultrasound. In late-onset FGR, identifying the fetus at risk for immediate hypoxia and who benefits from expedited delivery is challenging. It is likely that studies in the next decade will provide evidence how to best integrate different monitoring variables and other prognosticators in risk models that are aimed to optimize individual treatment strategies

Diagnosis and Monitoring of White Coat Hypertension in Pregnancy:an ISSHP Consensus Delphi Procedure

BACKGROUND: There is no accepted definition or standardized monitoring for white coat hypertension in pregnancy. This Delphi procedure aimed to reach consensus on out-of-office blood pressure (BP) monitoring, and white coat hypertension diagnostic criteria and monitoring. METHOD: Relevant international experts completed three rounds of a modified Delphi questionnaire. For each item, the predefined cutoff for group consensus was ≥70% agreement, with 60% to 70% considered to warrant reconsideration at the subsequent round, and <60% considered insufficient to warrant consideration. RESULTS: Of 230 experts, 137 completed the first round and 114 (114/137, 83.2%) completed all three. For out-of-office BP monitoring, there was consensus that home BP monitoring (HBPM) should be chosen; instructions given, pairs of BP values taken, opportunity given for women to qualify values they do not regard as valid, and BP considered evaluated when ≥25% of values are above a cutoff. For HBPM, BP should be taken at least 2 to 3 d/wk, at minimum in the morning; however, many factors may affect frequency and timing. Experts endorsed a clinic BP <140/90 mm Hg as normal. While not reaching consensus, most agreed that HBPM values should be lower than clinic BP. Among those, HBPM <135/85 mm Hg was considered normal. There was consensus that white coat hypertension warrants: HBPM at least 1 d/wk before 20 weeks, 2 to 3 d/wk after 20 weeks or if persistent hypertension develops, and symptom monitoring (ie, headache, visual symptoms, and right upper quadrant/epigastric pain). CONCLUSIONS: Consensus-based diagnostic criteria and monitoring strategies should inform clinical care and research, to facilitate evaluation of out-of-office BP monitoring on pregnancy outcomes

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable ‘over treatment’ of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes. Methods: International multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score < 7 at 5 min, cord pH < 7.10, emergency delivery for fetal distress, and severe neonatal morbidity. Discussion: The CEPRA trial will identify whether the CPR is a good indicator for delivery in women with perceived reduced fetal movements. Trial registration: Dutch trial registry (NTR), trial NL7557. Registered 25 February 2019

Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis A multicentre retrospective cohort study

OBJECTIVE: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension. DESIGN AND SETTING: Multicentre retrospective cohort study between 2008-2021. POPULATION: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis. METHODS AND MAIN OUTCOME MEASURES: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications. RESULTS: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 at term age (79% of live births and 60% of pregnancies). No maternal deaths were observed, one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention. CONCLUSIONS: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contra-indication for pregnancy. Individualized, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population

Development of a Core Outcome Set and Minimum Reporting Set for intervention studies in growth restriction in the NEwbOrN (COSNEON): study protocol for a Delphi study.

BACKGROUND: Growth restriction in the newborn (GRN) can predispose to severe complications including hypoglycemia, sepsis, and necrotizing enterocolitis. Different interventions and treatments, such as feeding strategies, for GRN have specific benefits and risks. Comparing results from studies investigating intervention studies in GRN is challenging due to the use of different baseline and study characteristics and differences in reported study outcomes. In order to be able to compare study results and to allow pooling of data, uniform reporting of study characteristics (minimum reporting set [MRS]) and outcomes (core outcome set [COS]) are needed. We aim to develop both an MRS and a COS for interventional and treatment studies in GRN. METHODS/DESIGN: The MRS and COS will be developed according to Delphi methodology. First, a scoping literature search will be performed to identify study characteristics and outcomes in research focused on interventions/treatments in the GRN. An international group of stakeholders, including experts (clinicians working with GRN, and researchers who focus on GRN) and lay experts ([future] parents of babies with GRN), will be questioned to rate the importance of the study characteristics and outcomes in three rounds. After three rounds there will be two consensus meetings: a face-to-face meeting and an electronic meeting. During the consensus meetings multiple representatives of stakeholder groups will reach agreement upon which study characteristics and outcomes will be included into the COS and MRS. The second electronic consensus meeting will be used to test if an electronic meeting is as effective as a face-to-face meeting. DISCUSSION: In our opinion a COS alone is not sufficient to compare and aggregate trial data. Hence, to ensure optimum comparison we also will develop an MRS. Interventions in GRN infants are often complicated by coexisting preterm birth. A COS already has been developed for preterm birth. The majority of GRN infants are born at term, however, and we therefore chose to develop a separate COS for interventions in GRN, which can be combined (with expected overlap) in intervention studies enrolling preterm GRN babies. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness ( COMET ) database. Registered on 30 June 2017