Dynamic growth changes in fetal growth restriction using serial ultrasonographic biometry and umbilical artery doppler: The multicenter PORTO study.

OBJECTIVE: To describe the growth dynamics of fetuses with initial fetal growth restriction (FGR) later outgrowing the 10th centile for estimated fetal weight with respect to perinatal outcomes and maternal factors. METHODS: A multicenter prospective study recruited 1116 patients for ultrasound surveillance between 2010 and 2012. All pregnancies were growth-restricted singleton gestations between 24 + 0 and 36 + 0 weeks. Biometry and Doppler analysis were carried out, and delivery and adverse perinatal outcomes were recorded. RESULTS: A total of 193 (17%) fetuses outgrew their diagnosis of initial FGR (surpassed the 10th centile) on their last sonogram before delivery. These fetuses were termed "growers," to compare with the true FGR group. The mothers of "growers" were less likely to be smokers (14% vs 25%, P = 0.0001) or affected by hypertensive pregnancy complications (5.2% vs 15%, P = 0.001). Of the growers, 49 (25%) had an abnormal umbilical artery Doppler; however, in most cases (33/49, 67%), this was a single episode of raised umbilical artery pulsatility index, which subsequently normalized. CONCLUSION: There were dynamic growth changes in FGR fetuses, with 17% outgrowing their original diagnosis. Positive growth spurts more commonly occurred in healthy mothers. Once a fetus had outgrown the 10th centile, antenatal surveillance could be decreased.

Thyroglobulin levels among iodine deficient pregnant women living in Northern Ireland.

BACKGROUND: Iodine deficiency has re-emerged among pregnant cohorts in the UK. Thyroglobulin (Tg) is a protein produced uniquely by the thyroid gland which appears to mount a U-shaped response to extremes of iodine status. Tg has been suggested as an alternative marker for chronic iodine deficiency but the value of Tg in pregnancy has not been fully elucidated. A recent non-European study suggested a median Tg ≤10 µg/L with <3% of values >44 µg/L was indicative of sufficiency in the second trimester of pregnancy. METHODS: We measured serum Tg levels in each trimester in 241 pregnant women living in Northern Ireland, a population with mild iodine deficiency at all stages of pregnancy as defined by urinary iodine concentration (UIC) and iodine: creatinine ratio (ICR). Women with Tg antibodies (6% in 1st trimester) were excluded. RESULTS: The median UIC in this cohort was in the deficient range at 73, 94 and 117 µg/L in sequential trimesters (adequacy ≥ 150 µg/L). Corresponding median Tg levels were 19, 16 and 16 µg/L respectively. Median Tg for all samples was 17 µg/L (IQR 11-31) suggestive of iodine deficiency. Tg was >44 µg/L in 14.3%, 9.4% and 12.4% of women in sequential trimesters respectively. Women with either UIC/ICR below the cut-offs 150 µg/L and 150 µg/g creatinine had higher Tg concentrations in 1st and 2nd trimester (p < 0.01; p < 0.001) but not in 3rd trimester. CONCLUSION: This study adds to the evolving evidence that Tg measurement is of value in reflecting iodine status in pregnancy.

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis.

Correlation of maternal body mass index with umbilical artery Doppler in pregnancies complicated by fetal growth restriction and associated outcomes.

OBJECTIVE: To evaluate the correlation between umbilical artery (UA) Doppler and its feasibility across categories of maternal body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) in the presence of fetal growth restriction (FGR). METHODS: A total of 1074 singleton pregnancies with suspected FGR on ultrasound examination between 24+0 and 36+0 weeks of pregnancy were reviewed. Evaluation of the UA Doppler was performed at 1- to 2-weekly intervals. Abnormal UA Doppler findings and delivery outcomes were compared between the different maternal BMI categories. RESULTS: Increased UA pulsatility index (PI >95th centile) was reported in 81% of obese class II patients (BMI 35-39.9) compared with a 46% incidence in the remaining categories, normal (BMI <24.9), overweight (BMI 25-29.9), and obese class I (BMI 30-34.9) (P = 0.001). In absent or reversed end diastolic flow (AEDF/REDF) we found an increasing incidence across the BMI categories (4%-25%) (P < 0.001). Higher maternal BMI was associated with lower birthweights and higher cesarean section rates. Increasing maternal BMI did not affect successful assessment of UA Doppler. CONCLUSION: There is a positive correlation between increasing maternal BMI and abnormal UA Doppler findings in FGR. Maternal BMI may be considered as an additional risk factor when evaluating UA Doppler for placental insufficiency.

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

CONTEXT: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. OBJECTIVE: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. DESIGN AND INTERVENTION: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling. SETTINGS AND PARTICIPANTS: Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. MAIN OUTCOME MEASURES: Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed. RESULTS: The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis. CONCLUSIONS: The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

Iodine deficiency among pregnant women living in Northern Ireland.

OBJECTIVE: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). DESIGN AND METHODS: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. RESULTS: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. CONCLUSIONS: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

PARROT Ireland: Placental growth factor in Assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol.

INTRODUCTION: Women presenting with suspected pre-eclampsia are currently triaged on the basis of hypertension and dipstick proteinuria. This may result in significant false positive and negative diagnoses resulting in increased morbidity or unnecessary intervention. Recent data suggest that placental growth factor testing may be a useful adjunct in the management of women presenting with preterm pre-eclampsia. The primary objective of this trial is to determine if the addition of placental growth factor testing to the current clinical assessment of women with suspected preterm pre-eclampsia, is beneficial for both mothers and babies. METHODS AND ANALYSIS: This is a multicentre, stepped wedge cluster, randomised trial aiming to recruit 4000 women presenting with symptoms suggestive of preterm pre-eclampsia between 20 and 36+6 weeks' gestation. The intervention of an unblinded point of care test, performed at enrolment, will quantify maternal levels of circulating plasma placental growth factor. The intervention will be rolled out sequentially, based on randomisation, in the seven largest maternity units on the island of Ireland. Primary outcome is a composite outcome of maternal morbidity (derived from the modified fullPIERS model). To ensure we are not reducing maternal morbidity at the expense of earlier delivery and worse neonatal outcomes, we have established a co-primary outcome which will examine the effect of the intervention on neonatal morbidity, assessed using a composite neonatal score. Secondary analyses will examine further clinical outcomes (such as mode of delivery, antenatal detection of growth restriction and use of antihypertensive agents) as well as a health economic analysis, of incorporation of placental growth factor testing into routine care. ETHICS AND DISSEMINATION: Ethical approval has been granted from each of the seven maternity hospitals involved in the trial. The results of the trial will be presented both nationally and internationally at conference and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02881073.

Knowledge about iodine requirements during pregnancy and breastfeeding among pregnant women living in Northern Ireland.

BACKGROUND: Iodine is an essential micronutrient important for foetal nerve and brain development, especially in the early stages of pregnancy. The re-emergence of mild to moderate iodine deficiency has recently been reported in the United Kingdom (UK). The level of knowledge amongst pregnant women regarding iodine nutrition is poorly understood. The aim of this study was to determine the level of knowledge about iodine nutrition during pregnancy among pregnant women living in Northern Ireland (NI). METHODS: A cross-sectional study in pregnant women was carried out in Royal Jubilee Maternity Hospital Belfast, from March to June 2015. Two hundred pregnant women were provided with a short questionnaire on iodine knowledge during routine clinic visits and comparisons were made across trimester and parity. RESULTS: Only 20% of women were aware of the potentially increased iodine requirements during pregnancy and breast feeding; 45% were unable to identify any foods they thought would be iodine rich. The three main sources of dietary iodine in the UK are fish, dairy and eggs and 30, 9 and 15% correctly identified these as good sources respectively. When asked about whether they felt they had been given sufficient advice about folic acid and iodine in pregnancy, 90% felt this was so for folic acid, but only 5% for iodine. CONCLUSIONS: This study suggests that iodine knowledge among pregnant women living in NI is poor. In the absence of any iodine fortification programme, women in the UK may be vulnerable to iodine deficiency in pregnancy. At present they are poorly equipped to make positive dietary changes to meet their increasing iodine requirements during pregnancy and breastfeeding. Public health strategies should be considered to target this population group.

Preeclampsia Prevention Using Routine Versus Screening Test-Indicated Aspirin in Low-Risk Women.

The objective was to evaluate whether routine aspirin 75 mg is more cost-effective than the Fetal Medicine Foundation screen-and-treat approach for preeclampsia prevention in low-risk nulliparous women. A health economic decision analytical model was devised to estimate the discounted net health and cost outcomes of routine aspirin versus Fetal Medicine Foundation screening test-indicated aspirin for a cohort of 100 000 low-risk nulliparous women. Both strategies were compared with no intervention. A subanalysis also compared disaggregated components of the algorithm. The analysis used data from hospital administration, literature, and a randomized controlled trial. Sensitivity analyses assessed the impact of aspirin adherence, test cost, and accuracy on study results. Presumed rates of preeclampsia were 3.75% with no intervention versus 0.45% with aspirin use. Results found that routine aspirin was the preferred strategy, in terms of greater health gains and larger cost savings. It provided 163 quality-adjusted life-years relative to no intervention, whereas the screen-and-treat policy achieved 108 quality-adjusted life-years. Routine aspirin would result in an estimated cost saving of €14.9 million annually relative to no intervention, whereas screen-and-treat approach would result in a smaller cost saving of €3.1 million. When the analysis was extended to consider alternative screen-and-treat strategies, routine aspirin remained the optimally cost-effective approach. In conclusion, routine aspirin use in low-risk nulliparous women has a greater health gain and cost saving compared with both the Fetal Medicine Foundation and other screen-and-treat approaches.

Placental vascularization indices and prediction of pre-eclampsia in high-risk women.

OBJECTIVE: To assess ability of first and second trimester Placental Vascularization Indices (PVIs) to predict pre-eclampsia (PE) in high-risk pregnancies. METHOD: PVIs derived from 3-Dimensional power Doppler imaging were measured at 11+0-13 + 6 (n = 194) and 19+0-21 + 6 weeks (n = 195). Logistic regression (LR) models used PE as the outcome. To quantify added value of PVIs to baseline characteristics in predicting PE, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices were calculated. RESULTS: Overall rate of PE was 12% (n = 26). Lower first trimester PVIs were seen in women with PE (mean, SD); Vascularization Index (VI,%): 10.0 (6.2) v 14.7 (7.6), P = 0.005, Flow Index (FI): 37.7 (9.1) v 42.9 (10.4), P = 0.03, Vascularization Flow Index (VFI): 3.8 (2.5) v 6.6 (4.0), P < 0.001). All first trimester PVIs predicted PE in LR models adjusted for covariates. IDI and NRI analyses confirmed added clinical utility of VI (IDI 0.05, P = 0.004; NRI 0.66, P < 0.001) and VFI (IDI 0.06, P = 0.004; NRI 0.53, P = 0.91). In the second trimester, FI was lower in women with PE (39.6 (9.1) v 44.4 (8.6), P = 0.01) and predicted PE in adjusted LR models (standardised OR 0.53, 95% CI 0.29-0.97, P = 0.04). FI discriminated between cases and non-cases of PE (IDI 0.04, P = 0.04). CONCLUSION: First trimester placental vascularization indices (VI, FI and VFI) have the potential to predict PE in high-risk pregnancies, with FI remaining predictive in the second trimester.

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial.

BACKGROUND: 2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth. METHODS: This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022. FINDINGS: 37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio [aOR] 0·90, 95% CI 0·75-1·07; p=0·23). INTERPRETATION: The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven. FUNDING: Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.

Trial of feasibility and acceptability of routine low-dose aspirin versus Early Screening Test indicated aspirin for pre-eclampsia prevention (TEST study): a multicentre randomised controlled trial.

OBJECTIVE: Evaluate the feasibility and acceptability of routine aspirin in low-risk women, compared with screening-test indicated aspirin for the prevention of pre-eclampsia and fetal growth restriction. DESIGN: Multicentre open-label feasibility randomised controlled trial. SETTING: Two tertiary maternity hospitals in Dublin, Ireland. PARTICIPANTS: 546 low-risk nulliparous women completed the study. INTERVENTIONS: Women underwent computerised randomisation to: Group 1-routine aspirin 75 mg from 11 until 36 weeks; Group 2-no aspirin and; Group 3-aspirin based on the Fetal Medicine Foundation screening test. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Proportion agreeing to participate; (2) compliance with protocol; (3) proportion where first trimester uterine artery Doppler was obtainable and; (4) time taken to issue a screening result. Secondary outcomes included rates of pre-eclampsia and small-for-gestational-age fetuses. RESULTS: 546 were included in the routine aspirin (n=179), no aspirin (n=183) and screen and treat (n=184) groups. 546 of 1054 were approached (51.8%) and enrolled. Average aspirin adherence was 90%. The uterine artery Doppler was obtained in 98.4% (181/184) and the average time to obtain a screening result was 7.6 (0-26) days. Of those taking aspirin, vaginal spotting was greater; n=29 (15.1%), non-aspirin n=28 (7.9%), OR 2.1 (95% CI 1.2 to 3.6). Postpartum haemorrhage >500 mL was also greater; aspirin n=26 (13.5%), no aspirin n=20 (5.6%), OR 2.6 (95% CI 1.4 to 4.8). CONCLUSION: Low-risk nulliparous women are open to taking aspirin in pregnancy and had high levels of adherence. Aspirin use was associated with greater rates of vaginal bleeding. An appropriately powered randomised controlled trial is now required to address the efficacy and safety of universal low-dose aspirin in low-risk pregnancy compared with a screening approach. TRIAL REGISTRATION NUMBER: ISRCTN (15191778); Post-results.

Intravaginal rings for continuous low-dose administration of cervical ripening agents.

Intravaginal rings (VRs) have been widely reported for administration of pharmaceutical drugs - most notably estrogens, progestogens and antiretrovirals - to the vagina for clinical benefit. Here, for the first time, we describe the design, manufacture and preclinical testing of VRs for sustained/controlled release of the cervical ripening agents isosorbide mononitrate (ISMN) and misoprostol (MP), either singly or in combination. Matrix-type silicone elastomer VRs containing ISMN showed declining daily release rates, ranging from 31 to 168 mg (Day 1) to 3-25 mg (Day 11). Novel orifice-type rings, in which a MP-containing silicone elastomer core is partially exposed to the external environment by overmolding with a non-medicated silicone elastomer sheath containing orifices, provided relatively constant daily MP release rates over 14 days (∼20 or 60 µg/day depending on the formulation type). Combination VRs offered simultaneous release of both ISMN and MP over 14 days, with an almost constant MP release rate (60 µg/day) and steadily declining daily ISMN release (295 mg on Day 1 and 24 mg on Day 11). The VR design can be readily tailored to provide sustained or controlled release of ISMN and MP at rates potentially useful for cervical ripening.

Prenatal surgery for spina bifida: a therapeutic dilemma. Proceedings of the SHINE conference, Belfast.

This is a transcript of a scientific conference on the subject of prenatal surgery for spina bifida. It represents the views of three patients, an obstetrician, a postnatal neurosurgeon, a neonatologist, a paediatric neurologist, two surgeons who practice open spina bifida foetal surgery, a fetoscopic surgeon and an obstetrician experienced in randomised trials and systematic reviews. Implications for current practice and recommendations for future research are also discussed in detail.

Can promoting awareness of fetal movements and focusing interventions reduce fetal mortality? A stepped-wedge cluster randomised trial (AFFIRM).

BACKGROUND: In 2013, the stillbirth rate in the UK was 4.2 per 1000 live births, ranking 24th out of 49 high-income countries, with an annual rate of reduction of only 1.4% per year. The majority of stillbirths occur in normally formed infants, with (retrospective) evidence of placental insufficiency the most common clinical finding. Maternal perception of reduced fetal movements (RFM) is associated with placental insufficiency and increased risk of subsequent stillbirth.This study will test the hypothesis that the introduction of a package of care to increase women's awareness of the need for prompt reporting of RFM and standardised management to identify fetal compromise with timely delivery in confirmed cases, will reduce the rate of stillbirth. Following the introduction of a similar intervention in Norway the odds of stillbirth fell by 30%, but the efficacy of this intervention (and possible adverse effects and implications for service delivery) has not been tested in a randomised trial. METHODS: We describe a stepped-wedge cluster trial design, in which participating hospitals in the UK and Ireland will be randomised to the timing of introduction of the care package. Outcomes (including the primary outcome of stillbirth) will be derived from detailed routinely collected maternity data, allowing us to robustly test our hypothesis. The degree of implementation of the intervention will be assessed in each site. A nested qualitative study will examine the acceptability of the intervention to women and healthcare providers and identify process issues including barriers to implementation. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Scotland A Research Ethics Committee (Ref 13/SS/0001) and from Research and Development offices in participating maternity units. The study started in February 2014 and delivery of the intervention completed in December 2016. Results of the study will be submitted for publication in peer-reviewed journals and disseminated to local investigating sites to inform education and care of women presenting with RFM. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov NCT01777022. VERSION: Protocol Version 4.2, 3 February 2017.

Pregnancy-specific stress, fetoplacental haemodynamics, and neonatal outcomes in women with small for gestational age pregnancies: a secondary analysis of the multicentre Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction.

OBJECTIVES: To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal intensive care unit admission and adverse obstetric outcomes in women with small for gestational age pregnancies. It was hypothesised that maternal pregnancy-specific stress would be associated with fetoplacental haemodynamics and neonatal outcomes. DESIGN: This is a secondary analysis of data collected for a large-scale prospective observational study. SETTING: This study was conducted in the seven major obstetric hospitals in Ireland and Northern Ireland. PARTICIPANTS: Participants included 331 women who participated in the Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction. Women with singleton pregnancies between 24 and 36 weeks gestation, estimated fetal weight <10th percentile and no major structural or chromosomal abnormalities were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Serial Doppler ultrasound examinations of the umbilical and middle cerebral arteries between 20 and 42 weeks gestation, Pregnancy Distress Questionnaire (PDQ) scores between 23 and 40 weeks gestation and neonatal outcomes. RESULTS: Concerns about physical symptoms and body image at 35-40 weeks were associated with lower odds of abnormal UAPI (OR 0.826, 95% CI 0.696 to 0.979, p=0.028). PDQ score (OR 1.073, 95% CI 1.012 to 1.137, p=0.017), concerns about birth and the baby (OR 1.143, 95% CI 1.037 to 1.260, p=0.007) and concerns about physical symptoms and body image (OR 1.283, 95% CI 1.070 to 1.538, p=0.007) at 29-34 weeks were associated with higher odds of abnormal MCA PI. Concerns about birth and the baby at 29-34 weeks (OR 1.202, 95% CI 1.018 to 1.421, p=0.030) were associated with higher odds of AEDF. Concerns about physical symptoms and body image at 35-40 weeks were associated with decreased odds of neonatal intensive care unit admission (OR 0.635, 95% CI 0.435 to 0.927, p=0.019). CONCLUSIONS: These findings suggest that fetoplacental haemodynamics may be a mechanistic link between maternal prenatal stress and fetal and neonatal well-being, but additional research is required.

The impact of maternal obesity on completion of fetal anomaly screening.

OBJECTIVE: To examine the impact of maternal obesity on completion of fetal anomaly screening. METHODS: A retrospective analysis of 500 anomaly scans (19+0-21+6 weeks) was included. Women were categorised according to the World Health Organisation (WHO) body mass index (BMI) classification: normal weight (18.50-24.99 kg/m2), overweight (25.00-29.99 kg/m2), obese class I (30-34.99 kg/m2), obese class II (35.00-39.99 kg/m2) and obese class III (≥40.00 kg/m2). A fetal anomaly imaging scoring system was developed from the National Health Service (NHS) Fetal Anomaly Screening Programme standard to evaluate scans. RESULTS: Image quality deteriorated as BMI increased and was significantly different across the BMI categories (P<0.001). Performance was poorest in imaging of the fetal chest and was significantly different across BMI categories (P<0.001). In obese class III, 33% of four-chamber cardiac views and 38% of outflow tract views were not obtained. In total, 119 women (23.6%) had an incomplete scan. In obese class III, 44.1% of scans were incomplete compared with 10.2% in the normal BMI category (P<0.001). Of 117 women attending for repeat scans, 78.6% were complete, 11.1% were incomplete, 6.8% were advised to re-attend and 3.4% were referred to Fetal Medicine. CONCLUSION: Maternal obesity has a significant impact on completion of fetal anomaly screening.

Prenatal prediction of significant intertwin birthweight discordance using standard second and third trimester sonographic parameters.

INTRODUCTION: Our study aim was to evaluate standard ultrasound-derived fetal biometric parameters in the prediction of clinically significant intertwin birthweight discordance defined as ≥18%. MATERIAL AND METHODS: This was a secondary analysis of a prospective cohort study of 1028 unselected twin pairs recruited over a two-year period. Dichorionic twins underwent two-weekly ultrasonographic surveillance from 24 weeks' gestation, with surveillance of monochorionic twins two-weekly from 16 weeks. Ultrasonographic biometric data from 24 to 36 weeks were evaluated for the prediction of an intertwin birthweight discordance threshold ≥18%. Umbilical artery Doppler waveform data was also analyzed to evaluate whether it was predictive of birthweight discordance. RESULTS: Of the 956 twin pairs analyzed for discordance, 208 pairs were found to have a clinically significant birthweight discordance ≥18%. All biometric parameters were predictive of significant inter-twin birthweight discordance at low cut-offs, with low discriminatory powers when ROC curves were analyzed. Discordance in estimated fetal weight was predictive of a significant birthweight discordance at all gestational categories with cut-offs between 8 and 11%. A low-discriminatory power and poor sensitivity and specificity were also observed. An abnormal umbilical artery Doppler was predictive of birthweight discordance ≥18% between 28 and 32 weeks' gestation, although with poor sensitivity and specificity. CONCLUSIONS: Calculation of estimated fetal weight and birthweight discordance between twins allows minimal margin for error. These margins make it difficult to accurately predict those who are at or above the discordance threshold of 18%. These findings highlight that small intertwin discrepancies in weight and biometry should not be overlooked and merit further investigation.

Gestational hypertensive disease in twin pregnancy: Influence on outcomes in a large national prospective cohort.

OBJECTIVE: Gestational hypertensive disease (GHD) is associated with pregnancy-related complications and poor maternal and fetal outcomes in singleton pregnancies. We sought to examine the influence of GHD in a large prospective cohort of twin pregnancies. STUDY DESIGN: The ESPRIT study was a national multicenter observational cohort study of 1028 structurally normal twin pregnancies. Each pregnancy underwent sonographic surveillance with two-week ultrasound from 24 weeks for dichorionic and from 16 weeks for monochorionic gestations. Characteristics and demographics as well as labour and delivery outcome data were prospectively recorded. Perinatal mortality, admission to the neonatal intensive care unit (NICU) and a composite of morbidity of respiratory distress syndrome, hypoxic ischaemic encephalopathy, periventricular leukomalacia, necrotising enterocolitis and sepsis were documented for all cases. Outcomes for patients with documented GHD (pre-eclampsia and gestational hypertension) were compared with those without GHD. RESULTS: Perinatal outcome data were recorded for 977 patients. Women with GHD had a higher body mass index (27.1 ± 6.4 vs 25.2 ± 4.5, P < 0.0001) than those without and were more likely to be nulliparous (65% (59/92) vs 46% (407/885), P = 0.001). Both groups had similar mean birthweights, but those with GHD were more likely to have a birthweight discordance ≥18% (35% (32/92) vs 20% (179/885), P = 0.001). Rates of caesarean delivery were higher in those twin pregnancies affected by GHD, and while the rate of composite morbidity was similar in both groups, twins in the GHD group had higher rates of NICU admission. CONCLUSION: In twin gestations, gestational hypertension independently confers an increased risk for emergency caesarean delivery, birthweight discordance and NICU admission, such that intensive maternal-fetal monitoring is justified when hypertension develops in a twin pregnancy.