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Biomedical subjects

N M Fisk

Publications and source records attributed to N M Fisk.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal blood flow in shared (arteriovenous anastomoses) and non-shared cotyledons in monochorionic placentae.

OBJECTIVES: In this study we aimed to quantitate monochorionic twin placental blood flow in vivo through arterio-venous anastomoses (AVA) and corresponding vessels within normal cotyledons. METHODS: The topography of chorionic plate vasculature was mapped using colour Doppler in ten monochorionic diamniotic twin (MCDA) pregnancies. Cotyledonary flow was derived by insonation of chorionic veins draining normal (n=10) and paired control shared cotyledons (n=10). Venous volume flow was calculated from five determinations of vessel diameter and three of time average mean velocity (TAMV). Measurements were repeated every 2-4 weeks from 18 until 32 weeks' gestation. RESULTS: Blood flow through non-shared and shared cotyledons increased with gestation (p<0.0001). Median flow at 28 weeks through shared cotyledons was 16 ml/min (15-21) (median, interquartile range), lower than in shared cotyledons (31, 25-35) (p<0.001), as was median volume flow across gestation calculated as area under the curve (shared cotyledons 126 (122-167), control cotyledons 269 (214-274), p=0.01). However, velocity was similar, with the difference due to smaller vein diameters draining shared compared to normal cotyledons (mean 3.6mm (SD 0.8) vs. 4.5mm (0.8), p=0.004). Ex vivo quantitation of insonated cotyledons and of all cotyledons confirmed the difference in vein diameter in the placentae studied. CONCLUSIONS: Blood flow through shared cotyledons was lower across gestation than through paired normal cotyledons in the placenta studied due to the smaller diameter of the AVA vessels. The size of AVAs rather than simply their presence and direction may contribute to determining transfusional imbalance in monochorionic twins.

Arteriovenous Anastomosis↗
PubMed2006

Maternal anxiety at amniocentesis and plasma cortisol.

OBJECTIVES: To assess whether anticipation of amniocentesis is linked with maternal anxiety, and whether this anxiety is associated with increased maternal plasma cortisol. METHODS: Two hundred and fifty-four women awaiting a morning amniocentesis for karyotyping (gestation range 15-37 weeks, median 17 weeks) completed Spielberger state and trait anxiety inventory (STAI) questionnaires, and provided blood samples immediately before the procedure for cortisol assay. Six hundred and five women at mean gestation of 20 weeks, attending the same hospital for routine ultrasound but not for amniocentesis, also completed Spielberger STAI questionnaires and served as a comparison group for the anxiety ratings. RESULTS: Mean state and trait anxiety scores (+/- SD) in the comparison group of 605 women at mean gestation of 20 weeks were 36.1 +/- 10.2 (range 20-70) and 35.6 +/- 8.9 (range 20-73), respectively. The mean state anxiety score (+/-SD) of 49.8 +/- 14.0 (range 20-77) of the amniocentesis group was considerably higher than the comparison group (p < 0.001), although the mean trait anxiety score in the amniocentesis group was similar at 36.4 +/- 8.6 (range 21-60). The state, but not trait, anxiety correlated with plasma cortisol (r = 0.176, p = 0.005). Maternal cortisol in the amniocentesis group increased with gestational age (r = 0.310, p < 0.001), whereas state anxiety scores showed no significant change with increase in gestational age (r = - 0.042, ns). Multivariate analysis demonstrated that maternal state anxiety was positively correlated with plasma cortisol independent of gestation and time of collection. CONCLUSION: Women awaiting amniocentesis experience a high state anxiety associated with modestly increased plasma cortisol.

Adult↗
PubMed2006

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.

OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature.

Amniocentesis↗
PubMed2005

Histomorphometric characterisation of shared and non-shared cotyledonary villus territories of monochorionic placentae in relation to pregnancy complications.

OBJECTIVE: Theoretical estimates and physiological inferences suggest that the structure of a shared cotyledon differs from a non-shared cotyledon. The aim of this study was to characterise the histomorphometry of terminal villi in shared and non-shared cotyledons in monochorionic placentae, both from uncomplicated twins and from those with twin-twin transfusion syndrome (TTTS) or discordant growth restriction (DeltaIUGR). METHODS: Forty-one monochorionic placentae from Caucasian non-smokers were obtained at caesarean section. Their vascular anatomy and placental territories were ascertained by dye injection. After fixation, full thickness histological blocks were obtained by systematic random sampling from each twin's territory and the shared cotyledons. Fifty randomly selected terminal villi were assessed for: (i) median villus diameter (ii) median villus capillary diameter (iii) median fetomaternal diffusion distance (iv) median no. of capillaries/villus (v) degree of vascularization (median percentage cross-sectional area of terminal villi occupied by capillaries) using a stage micrometer and image analysis programme. The histomorphometric findings were then correlated with birthweight discordance, placental territory discordance and DeltaAVAs (no. of AVAs from smaller twin (donor) to larger twin (recipient) minus no. of AVAs from larger to smaller twin). RESULTS: Histomorphometric variables were similar in shared and non-shared cotyledons of uncomplicated MCDA twins. However, the median diameter of terminal villi in shared cotyledons in DeltaIUGR and TTTS placentae was significantly smaller [51.2 microm (48.2-58.3), p<0.001 and 52.6 microm (53.1-50.4), p<0.001], and had a similar number of smaller capillaries, larger fetomaternal diffusion distance and reduced vascularization compared to non-shared IUGR and TTTS placentae. However, Deltadiameter (defined as the difference between median diameters of terminal villi in large minus small twins' territories) rose with increasing birthweight discordance (Pearson correlation coefficient=0.82, p<0.001). Multiple linear regression analysis revealed that Deltadiameter was influenced by placental territory discordance (p<0.001) and birthweight discordance (p<0.01): log10 Deltadiameter=1.38+(0.01 x birthweight discordance)+(0.56 x log10 placental territory discordance) (R2=0.82, p<0.001), but there was no significant relationship with DeltaAVA and AAA. In the TTTS group, Deltadiameter correlated significantly with DeltaAVA only: log10Deltadiameter=1.44+(0.02 x DeltaAVA) (R2=0.3, p<0.001). CONCLUSIONS: This is the first study to characterise the histomorphometry of shared and non-shared cotyledons in MC twins. The findings suggest that abnormal placentation, rather than placental vascular anatomy may be responsible for DeltaIUGR in MC twins, whereas TTTS arises from imbalance in interfetal transfusion with resultant differing terminal villus histomorphometric features in donor, recipient and shared cotyledons.

Chorionic Villi↗
PubMed2005

Increased latency of absent end-diastolic flow in the umbilical artery of monochorionic twin fetuses.

OBJECTIVE: To determine if absent end-diastolic flow (AEDF) in the umbilical artery (UA) has a longer latency in monochorionic (MC) twin fetuses compared to singleton or dichorionic twin (DC) fetuses. METHODS: One hundred and eight pregnancies with a fetus with AEDF were reviewed: 47 MC and 17 DC twin pregnancies and 44 singletons. Because twin-twin transfusion syndrome (TTTS) is a potential confounder when determining latency, subgroup analysis was also performed on the 21 MC affected pregnancies without TTTS. Latency of AEDF (in days) was defined as the difference between the gestational age at diagnosis of AEDF and gestational age at delivery or intrauterine death. RESULTS: Latency was similar in MC twins (median, 39 days) and DC twins (30 days) but longer compared to singletons (11 days; P = 0.0001). After excluding pregnancies with TTTS, latency in non-TTTS MC twins (54 days) was longer than in both singletons and DC twins. This was due to an earlier gestational age at AEDF in non-TTTS MC twins of 20 weeks compared to 27 weeks in both singleton and DC twins because median gestational age at delivery was similar in MC twins, DC twins and singletons. CONCLUSIONS: The latency period of UA AEDF is longer in MC twins than in singletons. Our data suggest that in MC twin fetuses without TTTS, AEDF begins earlier and lasts about twice as long as in DC twin fetuses, which is consistent with placental insufficiency not being the sole factor mediating abnormal UA waveforms in MC placentation. This observation is important in counseling and managing twin pregnancies discordant for AEDF.

Chorion↗
PubMed2005

Standardization of power Doppler quantification of blood flow in the human fetus using the aorta and inferior vena cava.

OBJECTIVE: This study aimed to test the applicability to the fetus of mathematical techniques developed to standardize power Doppler indices of adult regional perfusion. METHOD: Fetal power Doppler imaging was performed on 14 fetuses (25-37 weeks' gestation) using a standardized parasagittal plane, examining renal and aortic blood flow, and additionally inferior vena caval (IVC) flow in one fetus. Images were stored and transferred for off-line computer analysis using purpose-designed software. We first tested the need for techniques to remove the effects of red blood cell clumping on power Doppler amplitude, then performed further analyses to: (1) investigate cardiac cycle effects on aortic amplitude; (2) determine the spatial consistency of, and influence of angle of insonation on, maximal pixel value; (3) quantify temporal consistency; and (4) compare peak pixel values in the fetal aorta and IVC. RESULTS: No rouleaux effect on the vascular profile was detectable, in contrast to that identified in the adult. Within each fetus a consistent value was seen in the center of the aorta corresponding to 100% vascular amplitude, which was unaltered by the phase of the cardiac cycle, with a coefficient of variation of 28.9% at 89 degrees and 6.5% at 73 degrees . This value was constant in the aorta and IVC. CONCLUSION: Fetal blood does not appear to form rouleaux to any significant degree, so there is no artificially elevated maximal value for power Doppler amplitude as seen in the adult. We propose that the value representing 100% amplitude may be consistently measured in the center of large fetal vessels such as the aorta, allowing the direct measurement of fractional moving blood volumes in the human fetus.

Adult↗
PubMed2005

Characterisation of deep arterio-venous anastomoses within monochorionic placentae by vascular casting.

OBJECTIVE: To characterise arterio-venous anastomoses (AVA) in monochorionic (MC) placentae and determine (i) whether shared cotyledons lie beneath the co-termination of an artery from one twin and a vein to the contralateral twin and (ii) whether all AVA can be detected by visual inspection of the chorionic plate. METHODS: Vascular casts were made of 15 MC placentae. The number of typical AVAs suspected visually before digestion was compared with the number of AVAs identified after acid digestion. RESULTS: Thirty-three of 67 (49%) suspected typical AVAs were confirmed as typical after casting. There were five false positives and no false negatives. The remainder were classified as atypical AVAs, found in > or =90% of MC placentae. Type I (small vascular connections between two apparently normal cotyledons not seen before casting) and Type II (shared cotyledons arising within larger apparently normal cotyledons) atypical AVAs were found in 53% and 73% of placentae, respectively. CONCLUSIONS: Only half the shared cotyledons in MC placentae are characterised by co-termination of an artery and vein on the chorionic plate. We report the existence of deep anastomoses beneath the chorionic plate that cannot be visualised by chorionic plate inspection. These findings have implications for laser treatment of twin-twin transfusion syndrome.

Adult↗
PubMed2005

Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy.

OBJECTIVE: To investigate (A) the determinants of infant stress response at delivery and (B) test the hypothesis that stress at birth, as reflected by cord arterial cortisol, influences cortisol response to vaccination at two months. DESIGN: Prospective observational study. SETTING: Tertiary referral maternity hospital. POPULATION: One hundred and seventy-two primiparous women with uncomplicated singleton pregnancies. METHODS: Women were recruited antenatally. At birth, cord arterial blood and obstetric data were collected. Saliva was collected from infants immediately before and after vaccination at two months. Cortisol was analysed from cord blood and saliva by radio-immunoassay. MAIN OUTCOME MEASURES: Stress response at birth, as demonstrated by cord arterial cortisol; association with saliva cortisol response to vaccination at two months. RESULTS: Cord arterial cortisol varied with mode of delivery, combined spinal/epidural use and pH. Salivary cortisol response at two months correlated with cord arterial cortisol (r= 0.24, P < 0.05). Infants with the highest and lowest cord arterial cortisol had markedly different cortisol responses at two months (P= 0.017). These groups had different modes of delivery with caesarean rates of <8% in the high cortisol response group and 83% in the low cortisol response group (P < 0.0001). CONCLUSION: Babies born vaginally mount greater cortisol responses at birth than those delivered by caesarean section. Stress at delivery may influence the infant HPA axis response for up to two months.

Amniotic Fluid↗
PubMed2005

Fetal plasma testosterone correlates positively with cortisol.

BACKGROUND: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. AIMS: To investigate the relation between fetal testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. RESULTS: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two.

Adult↗
PubMed2004

Management of other complications specific to monochorionic twin pregnancies.

Monochorionic (MC) twins have a 3-10-fold higher perinatal mortality and morbidity than dichorionic twins. This is largely attributable to their common vascular architecture and the high rate of discordant fetal growth, growth restriction and congenital abnormalities. In the event of a single intrauterine death (IUD), intertwin agonal transfusion results in up to a 38% risk of death and a 46% risk of neurological injury to the co-twin. This chapter addresses the management of complications unique to MC twins. The primary aim of management is to prevent single IUD or, if inevitable, prevent agonal transfusion occurring by vascular occlusive selective feticide. Older fetoscopic techniques have been replaced by the simpler ultrasound-guided techniques of interstitial laser and bipolar cord occlusion. Their application in twin reversed-arterial perfusion sequence has been associated with a 50% reduction of perinatal mortality in the pump twin. Moreover, prophylactic interstitial laser therapy in early pregnancy might obviate the technical and clinical difficulties in the presence of fetal decompensation in later pregnancy. Recent strategies to reduce the high perinatal mortality due to cord entanglement in antenatally diagnosed monoamniotic twins including medical amnioreduction and elective caesarean delivery at 32 weeks, are also discussed.

Chorion↗
PubMed2004

Derivation of rate of arterio-arterial anastomotic transfusion between monochorionic twin fetuses by Doppler waveform analysis.

We aimed to determine rates of interfetal transfusion along arterio-arterial (AA) anastomoses in monochorionic twins in vivo from analysis of Doppler waveform patterns. Twenty-one monochorionic twin pregnancies in which an AA anastomosis was identified antenatally underwent serial Doppler velocimetry. Unidirectional AA anastomotic flow rates increased with increasing gestational age (log y = 8 x 10(-9)x - 5 x 10(-8); p = 0.0002). The mean net rate of flow through an AA anastomosis at 28 weeks gestation was 7.6 x 10(-8) l/s (SD = 4.9 x 10(-8) l/s). This flow was significantly related to the distribution of arterio-venous (AV) anastomoses (p = 0.009) and birthweight discordancy (p = 0.006). We derived estimates of flow along individual AV anastomoses by assuming that net AA countertransfusion is shared equally among uncompensated AV anastomoses, and speculate that the median AV flow rate at 28 weeks is in the order of 6 x 10(-8) l/s. In conclusion, this study demonstrates that flow rates along AA anastomoses can be quantified antenatally. These are the first estimates of flow rates in vivo along placental anastomoses. Although AA net flows are modest, chronic unbalanced counterflow of this magnitude in the absence of compensatory superficial anastomoses could lead to significant haemodynamic compromise.

Arteries↗
PubMed2004

Infant cortisol response after prolonged antenatal prednisolone treatment.

Prednisolone is widely used to treat medical conditions in pregnancy, despite the lack of long-term safety studies on infants. Animal studies have shown that antenatal glucocorticoid treatment can cause in utero growth restriction and up-regulation of the offsprings' hypathalamic-pituitary-adrenal axis. We recruited women treated antenatally with prednisolone, and followed 12 of the infants up to four months, using routine infant vaccinations as a stressor. Birthweights were similar to controls (n = 289, uncomplicated, singleton term pregnancies), as were infants' baseline and stress-induced cortisol levels. Mothers rated their infants as less difficult and more adaptable than controls. This study provides initial reassurance about the safety of prednisolone in pregnancy.

Adult↗
PubMed2004

Human fetal and maternal corticotrophin releasing hormone responses to acute stress.

OBJECTIVES: To study the effect of acute stress, caused by intrauterine needling at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH concentration to determine the extent of their joint control. DESIGN: Venous blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either the IHV or the placental cord insertion (PCI). SETTING: The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London, UK. PATIENTS: Pregnant women undergoing clinically indicated fetal blood sampling or intrauterine blood/platelet transfusion. RESULTS: Fetal plasma cortisol increased with intrahepatic vein transfusion (mean (SD) cortisol response Delta64.7 (54.5) nmol/l; p < 0.0001, n = 11), and fetal corticotrophin concentrations were higher after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma CRH increased after IHV transfusion. Fetal CRH levels did not rise with gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p < 0.0001). There was a modest correlation between paired maternal and fetal values (r = 0.36; n = 36; p = 0.03). CONCLUSIONS: Acute fetal stress, caused by IHV needling of the fetal abdomen, resulted in hypothalamic-pituitary-adrenal axis activation, as shown by a rise in fetal cortisol and corticotrophin. However, it did not result in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH is not derived from the hypophyseal-portal circulation, but from another source, presumably the placenta.

Acute Disease↗
PubMed2003

Transmitted arterio-arterial anastomosis waveforms causing cyclically intermittent absent/reversed end-diastolic umbilical artery flow in monochorionic twins.

OBJECTIVES: To characterize the phenomenon of retrograde transmission of arterio-arterial anastomosis (AAA) interference patterns on umbilical artery (UA) waveform by (a) documenting the periodicity, (b) correlation with in vivo and in vitro demonstration of AAAs and (c) reproducing these patterns by computer modelling. METHODS: Monochorionic twins (MC) twins underwent placental and umbilical Doppler studies. AAAs were sought by pulse wave Doppler of their bi-directional interference pattern and confirmed by postnatal injection studies. The periodicity of transmitted patterns in the UA was determined. Determinants of the transmitted patterns were ascertained by computer modelling of physiological and fetal variables. RESULTS: Among 83 prospectively studied MC twin pregnancies; a transmitted pattern was observed in 6 (7 per cent) patients for 15-114 days. This was found in 20 per cent (6/30) of smaller MC twins discordant for growth restriction but in no appropriately grown twins. It was only observed in association with AAAs validated both in vivo and in ex vivo. Computer modelling demonstrated that this pattern could be reproduced by summating end diastolic flow with a high pulsatility index in the UA in the presence of a large AAA. Consistent with this, MC twins with a transmitted pattern had larger AAAs (median diameter 4.3 mm interquartile range 4.1-5.2) compared to MC twins discordant for intrauterine growth restriction (2.1 mm interquartile range 1.5 to 2.8) (P<0.05) without a transmitted pattern. Perinatal mortality was similar in the fetuses with and without transmitted patterns (0/12 vs. 2/48 P=0.7).

Adult↗
PubMed2003

Reducing the incidence of twins and triplets.

Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.

Embryo Transfer↗