Publications by authors named "K H Nicolaides"

1,512 Publications

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Reference Ranges for the Pulsed wave Doppler of the Fetal Cardiac Inflow and Outflow Tracts from 13 to 36 Weeks Gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores.

J Am Soc Echocardiogr 2021 May 3. Epub 2021 May 3.

Medway Fetal and Maternal Medicine Centre, Medway Maritime Hospital, Gillingham, Kent, United Kingdom; Institute of Medical Sciences, Canterbury Christ Church University, Rowan William's Court, Chatham, Kent ME4 4UF.

Objective: Doppler assessment ventricular filling and outflow tract velocities are an integral part of the fetal echocardiogram, to assess diastolic function, systolic function and outflow tract obstruction. There is a paucity of prospective data from a large sample of normal fetuses in the published literature. We report reference ranges for pulsed wave Doppler flow of the mitral valve, tricuspid valve, aortic valve and pulmonary valve as well as heart rate, in a large number of fetuses prospectively examined at a single tertiary fetal cardiology centre.

Methods: The study population comprised 7885 fetuses at 13 to 36 weeks' gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective pulsed wave Doppler blood flow measurements were taken of the mitral, tricuspid, aortic and pulmonary valves. The fetal heart rate was recorded at the time of each assessment. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age.

Results: The measurement for each cardiac Doppler measurement was expressed as a z score (difference between observed and expected value divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac inflow and outflow tracts.

Conclusions: The study establishes reference ranges for fetal cardiac Doppler measurements and heart rate between 13 to 36 weeks' gestation that may be useful in clinical practice.
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http://dx.doi.org/10.1016/j.echo.2021.04.017DOI Listing
May 2021

Three-dimensional echocardiography and strain cardiac imaging in women with gestational diabetes mellitus.

Ultrasound Obstet Gynecol 2021 May 5. Epub 2021 May 5.

Hospital Clínico Universitario Virgen de la Arrixaca Murcia, Spain. Institute for Biomedical Research of Murcia, IMIB-Arrixaca, Murcia, Spain.

Objective: Gestational diabetes mellitus (GDM) is associated with premature cardiovascular disease and adverse cardiovascular outcomes in the mother. Subclinical cardiac functional changes in the left ventricle have been reported during pregnancy using conventional echocardiography but results are inconsistent. The aims of the current study are to assess whether GDM is associated with biventricular systolic dysfunction in the mothers and whether these cardiac changes can be detected using the novel echocardiographic modalities of strain imaging and three-dimensional (3D) echocardiography.

Methods: This was a cross sectional study in 123 women with GDM and 246 controls examined at 26-40 weeks of gestation. All women underwent echocardiography using the X5-1 transducer EPIC 7G Philips and 3D volumes of the left and right ventricle and left atrium were collected. Ejection fraction and left ventricular mass were measured by 3D echocardiography. Left ventricular mass was indexed to body surface area. Speckle tracking echocardiography was used to assess global longitudinal strain of the left and right ventricle and strain of the left atrium.

Results: Women with GDM, compared to controls, were older (35.1, SD 5.2 vs 32.4, SD 5.5 years; p<0.001), had higher body mass index (30.6, IQR 26.2 to 35.2 vs 27.5, IQR 24.7 to 30.7 kg/m ; p<0.001) and higher systolic blood pressure (119.9, SD 11.2 vs 116.4 SD 12.0 mmHg; p=0.007). In all women with GDM there was good glycemic control. In women with GDM, compared to controls, there was lower global longitudinal strain of the left ventricle (-19.3, IQR -21.4 to -17.6 vs -20.1, IQR -22.1 to -18.7%; p=0.002) and right ventricle (-22.2, IQR -26.1 to -19.8 vs -24.1, -27.0 to -21.9%; p<0.001). There was no significant difference between the groups in ejection fraction and left ventricular mass, diastolic function, assessed by left atrial strain and 3D functional indices.

Conclusion: Women with GDM, compared to women with uncomplicated pregnancy, have lower left and right ventricular myocardial deformation. Volumetric assessment using 3D echocardiography does not provide incremental information about maternal cardiac function. Strain imaging is a sensitive echocardiographic modality to detect early cardiac functional changes in women with GDM. Further studies are needed to assess the pattern of deterioration of cardiac function with advancing age in women with history of GDM. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23666DOI Listing
May 2021

Competing risks model for prediction of small for gestational age neonates from biophysical markers at 19-24 weeks' gestation.

Am J Obstet Gynecol 2021 Apr 23. Epub 2021 Apr 23.

Fetal Medicine Research Institute, King's College Hospital, London, UK. Electronic address:

Background: Antenatal identification of women at high-risk to deliver small for gestational age (SGA) neonates, may improve the management of the condition. The traditional but ineffective methods for SGA screening are the use of risk scoring systems based on maternal demographic characteristics and medical history and the measurement of the symphysial-fundal height. Another approach is to use logistic regression models that have higher performance and provide patient-specific risks for different pre-specified cut-offs of birth weight percentile and gestational age at delivery. However, such models have led to an arbitrary dichotomization of the condition; different models for different SGA definitions are required and adding new biomarkers or examining other cut-offs requires re-fitting of the whole model. An alternative approach for prediction of SGA neonates is to consider SGA as a spectrum disorder whose severity is continuously reflected in both the gestational age at delivery and z-score in birth weight for gestational age.

Objective: To develop a new competing risks model for prediction of SGA neonates based on a combination of maternal demographic characteristics and medical history with sonographic estimated fetal weight (EFW), uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP) at 19-24 weeks of gestation.

Study Design: This was a prospective observational study in 96,678 women with singleton pregnancies undergoing routine ultrasound examination at 19-24 weeks of gestation, which included recording of EFW, UtA-PI and MAP. The competing risks model for SGA is based on a prior joint distribution of gestational age at delivery (GA) and birth weight Z score (Z), according to maternal demographic characteristics and medical history. The likelihoods of the EFW, UtA-PI and MAP were fitted conditionally to both GA and Z and modified the prior distribution, according to Bayes theorem, to obtain an individualized posterior distribution for GA and Z and therefore patient specific risks for any desired cut-offs for Z and GA. The model was internally validated by randomly dividing the data into a training dataset, to obtain the parameters of the model, and a test dataset to evaluate the model. The discrimination and calibration of the model were also examined.

Results: The EFW was described by a regression model with an interaction term between GA and Z. Folded plane regression models were fitted for UtA-PI and MAP. The prediction of SGA by maternal factors improved by adding biomarkers and for increasing degree of prematurity, higher severity of smallness and for co-existence of preeclampsia. Screening by maternal factors EFW, UtA-PI and MAP, predicted 41%, 56% and 70% of SGA neonates with birth weight <10 percentile delivered at ≥37, <37 and <32 weeks' gestation, at 10% false positive rate. The respective rates for birth weight <3 percentile were 47%, 65% and 77%. The rates in the presence of preeclampsia were 41%, 72% and 91% for SGA neonates with birth weight <10th percentile and 50%, 75% and 92% for SGA neonates with birth weight <3rd percentile. Overall the model was well calibrated. The detection rates and the calibration indices were similar in the training and test datasets, demonstrating the internal validity of the model.

Conclusion: The performance of screening for SGA neonates by a competing risks model that combines maternal factors with EFW, UtA-PI and MAP is superior to that of screening by maternal characteristics and medical history alone.
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http://dx.doi.org/10.1016/j.ajog.2021.04.247DOI Listing
April 2021

Competing risks model for prediction of preeclampsia.

Am J Obstet Gynecol 2021 Apr 21. Epub 2021 Apr 21.

Fetal Medicine Research Institute, King's College Hospital, 16-20 Windsor Walk, Denmark Hill, London SE5 8BB, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2021.04.239DOI Listing
April 2021

Percutaneous fetoscopic spina bifida repair: effect on need for postnatal cerebrospinal fluid diversion, ambulation and bladder catheterization.

Ultrasound Obstet Gynecol 2021 Apr 20. Epub 2021 Apr 20.

Fetal Medicine Research Institute, King's College Hospital, London, UK.

Background: A trial comparing prenatal with postnatal open spina bifida (OSB) repair established that prenatal surgery was associated with better postnatal outcome. However, in the trial the fetal surgery was carried out through hysterotomy. Minimally invasive approaches are being developed to mitigate the risks of open maternal fetal surgery.

Objective: To investigate the impact of a novel neurosurgical technique for repair of feta; OSB, the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) via percutaneous fetoscopy, on long-term postnatal outcomes.

Study Design: Descriptive data for all patients undergoing fetoscopic OSB repair and available 12- and 30-month follow-up for assessment of need for cerebrospinal fluid (CSF) diversion and bladder catheterization and ambulation, respectively. A total of 170 consecutive patients were treated prenatally at eight centers via percutaneous fetoscopic OSB repair using a biocellulose patch between the neural placode and skin/myofascial flap, without suture of the duramater. A total of 103 babies had follow-up at 12 months of age and 59 had follow-up at 30 months of age. Univariate and multivariate logistic regression analysis was used to examine the effect on CSF diversion at 12 months, and ambulation and bladder catheterization at 30 months. Potential co-factors were gestational age at fetal surgery and delivery, preoperative ultrasound findings of anatomical level of the lesion, cerebral lateral ventricle diameter, lesion type and presence of bilateral talipes, as well as postnatal findings of CSF leak at birth, motor level, bilateral talipes and reversal of hindbrain herniation. Significance was set at p<0.05.

Results: At 12-months of age 53.4% (55/103) of babies did not require ventriculoperitoneal shunt or third ventriculostomy. At 30-months of age, 54.2% (32/59) of the children were ambulating independently and 61% (36/59) did not require chronic intermittent catheterization of the bladder. Multiple logistic regression analysis demonstrated that significant prediction for CSF diversion was provided by anatomical and functional motor level of the lesion, lateral ventricle size and type of lesion (myeloschisis). Significant predictors of ambulatory status were prenatal bilateral talipes and anatomical and functional motor level of the lesion. There were no significant predictors for the need of bladder catheterization.

Conclusion: Children that underwent prenatal OSB repair via the percutaneous fetoscopic SAFER technique achieved long-term neurological outcomes similar to those reported in the literature after hysterotomy-assisted OSB repair. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23658DOI Listing
April 2021