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Biomedical subjects

N J Sebire

Publications and source records attributed to N J Sebire.

At least 73 records · Page 4Linked to original sources
PubMed2002

Trichorionic triplet pregnancies at 10-14 weeks: outcome after embryo reduction compared to expectant management.

OBJECTIVE: To compare the outcome of trichorionic triplet pregnancies managed expectantly with those reduced to twins or singletons. METHODS: This was a retrospective study of trichorionic triplet pregnancies with three live fetuses at 10-14 (median 12) weeks' gestation referred to our unit for consideration of embryo reduction. Women were counselled as to the available options of either expectant management or embryo reduction. In those choosing reduction, a needle was inserted into the uterus transabdominally and potassium chloride was injected into the fetal heart. Using data derived from this study and from a review of studies reporting on survival and handicap by gestational age in singletons, the effects of embryo reduction on survival and handicap rates were estimated. Main outcome measures were miscarriage before 24 weeks of gestation, preterm delivery before 32 weeks, perinatal death and handicap rates. RESULTS: In total, there were 280 trichorionic triplet pregnancies and 125 of these were managed expectantly, 133 were reduced to two fetuses and 22 were reduced to one fetus. The rates of miscarriage were 3.2% for those managed expectantly, 8.3% for those reduced to twins and 13.6% for those reduced to singletons. The rates of early preterm delivery in those pregnancies that did not miscarry were 23.1%, 9.8% and 5.3%, respectively. The percentages for pregnancies with at least one survivor were 95.2%, 91.0% and 81.8%, respectively, and the median gestation at delivery was 34 weeks for the non-reduced, 36 weeks for those reduced to twins and 38 weeks for those reduced to singletons. From the published series on early preterm delivery, it was estimated that survival increases from about 27% at 24 weeks to about 98% at 32 weeks, and handicap decreases from 28% at 24 weeks to less than 5% at 32 weeks. From these estimates and the data on triplet pregnancies, it was calculated that, in triplets reduced to twins, compared to those managed expectantly, the chance of survival is similar (90.3% compared to 93.3%), but the risk of handicap may be lower (0.6% compared to 1.5% per fetus). CONCLUSIONS: In trichorionic triplet pregnancies, embryo reduction to twins does not improve the chance of survival but may reduce the rate of handicap. Reduction from triplets to singletons may reduce both the survival rate and the handicap rate among survivors.

Adult↗
PubMed2002

Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure.

BACKGROUND: Primary antiphospholipid antibody syndrome (PAPS) is an established cause of recurrent pregnancy loss, traditionally presumed to be due to 'intraplacental thromboses'. This study examines products of conception (POC) from early pregnancy failures to investigate the mechanism of pregnancy loss. METHODS: POC from patients attending a recurrent miscarriage clinic and from terminations of pregnancy for non-medical reasons were examined histologically with particular regard to the presence or absence of vascular or intervillous thromboses and decidual endovascular trophoblast invasion. RESULTS: There were 31 PAPS-positive, 50 PAPS-negative, 34 aneuploid and 20 control cases at 6-14 weeks gestation. Villous morphology and frequency of intervillous thrombosis were not different among groups. Normal intradecidual endovascular trophoblast invasion was identified significantly less frequently in PAPS+ cases (24%), compared with controls (75%), aneuploid (53%), or PAPS- cases (61%; Z = -3.0, P < 0.01). In all cases there was apparently normal interstitial extravillous trophoblast invasion. CONCLUSIONS: Defective decidual endovascular trophoblast invasion, rather than excessive intervillous thrombosis, is the most frequent histological abnormality in PAPS+ associated early pregnancy loss. Furthermore, endovascular trophoblast invasion is not significantly reduced in the majority of fetal aneuploidy-associated pregnancy failures.

Abortion, Habitual↗
PubMed2002

Complete hydatidiform mole and normal live birth: a novel case of confined placental mosaicism: case report.

Hydatidiform molar change, characterized by abnormal fetoplacental development and placental villous trophoblast hyperplasia, results from genetically abnormal conception, in which there is an excess of paternally derived genetic material. The majority of pregnancies in which molar change has been reported in association with a live fetus represent dizygotic twin pregnancies in which one fertilization results in a complete hydatidiform mole (CM) and the other a normal co-twin. In such cases, there is usually a clear distinction, both sonographically and pathologically, between the molar and non-molar regions of the placenta. We present a singleton pregnancy, with diffuse placental molar change detected prenatally, which resulted in a chromosomally and phenotypically normal female infant at term. Pathological examination revealed the presence of intermixed populations of morphologically normal chorionic villi and villi with the characteristics of CM. Studies of genetic polymorphisms demonstrated that the CM, normal villi and fetus were all derived from the same sperm; the fetus was diploid and biparental whereas the areas of pathological CM were androgenetic and monospermic. We believe this represents the first well-documented case of apparent confined placental mosaicism involving CM and a coexisting normal fetus, which has presumably arisen following mitotic abnormalities in the early post-fertilization period.

Adult↗
PubMed2002

Placental massive perivillous fibrin deposition associated with antiphospholipid antibody syndrome.

We present three pregnancies in which massive perivillous fibrous deposition (MPVFD) and maternal floor infarction (MFI) occurred in patients with primary antiphospholipid antibody syndrome (PAPS) attending a recurrent miscarriage clinic, and who were treated with low dose aspirin and heparin. We hypothesise that PAPS may be a predisposing factor to the development of this condition. The increased prevalence of late pregnancy complications in PAPS patients with a history of early miscarriage suggests that aspirin and heparin therapy does not eradicate the underlying pathological process but merely reduces the severity. Therefore, untreated early pregnancy losses may be converted into treated pregnancies with late antenatal complications. Some patients with PAPS may therefore be prone to suffer either the previously reported complications of the uteroplacental vasculature, such as pre-eclampsia, and/or specific complications related to the environment of the intervillus space, such as MPVFD/MFI.

Abortion, Habitual↗
PubMed2002

Risk of partial and complete hydatidiform molar pregnancy in relation to maternal age.

All cases of first histologically confirmed complete and partial moles registered between 1985 and 1999 were identified from the database of a Trophoblastic Disease Registration Centre. The maternal age distribution at diagnosis was calculated for the 7916 molar pregnancies and compared with the maternal age distribution of an unselected population of women from a routine obstetric database. Likelihood ratios were calculated for complete and partial molar pregnancies by maternal age. A positive relationship was found between the risk of molar pregnancy and both upper and lower extremes of maternal age (> or = 45 years and < or = 15 years, respectively). This association, although present for both complete and partial moles, is much greater for complete mole at all maternal ages, and the degree of risk is much greater with older (> or = 45 years) rather than younger (< or = 15 years) maternal age. This study provides, for the first time, data regarding specific risk of partial versus complete hydatidiform mole with maternal age.

Adolescent↗
PubMed2002

Biology and pathology of the placenta in relation to antiphospholipid antibody-associated pregnancy failure.

The placenta is a complex organ composed of maternal and foetal components whose anatomy and function is often greatly simplified in order to explain a range of presumed placenta-related pregnancy complications. Since one of the major roles of the placenta is its materno-foetal transfer function, abnormalities at the materno-foetal interface may be responsible for a range of pregnancy complications manifesting from the first through third trimesters according to the severity of the pathological process in each case. This article reviews some aspects of abnormal early placental development and its consequences, with particular regard to recurrent pregnancy failure and obstetric complications in association with primary antiphospholipid antibody syndrome.

Abortion, Spontaneous↗
PubMed2001

Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London.

OBJECTIVE: To examine the maternal and foetal risks of adverse pregnancy outcome in relation to maternal obesity, expressed as body mass index (BMI, kg/m(2)) in a large unselected geographical population. DESIGN: Retrospective analysis of data from a validated maternity database system which includes all but one of the maternity units in the North West Thames Region. A comparison of pregnancy outcomes was made on the basis of maternal BMI at booking. SUBJECTS: A total of 287,213 completed singleton pregnancies were studied including 176,923 (61.6%) normal weight (BMI 20--24.9), 79 014 (27.5%) moderately obese (BMI 25--29.9) and 31,276 (10.9%) very obese (BMI> or =30) women. MEASUREMENTS: Ante-natal complications, intervention in labour, maternal morbidity and neonatal outcome were examined and data presented as raw frequencies and adjusted odds ratios with 99% confidence intervals following logistic regression analysis to account for confounding variables. RESULTS: Compared to women with normal BMI, the following outcomes were significantly more common in obese pregnant women (odds ratio (99% confidence interval) for BMI 25--30 and BMI> or =30 respectively): gestational diabetes mellitus (1.68 (1.53--1.84), 3.6 (3.25--3.98)); proteinuric pre-eclampsia (1.44 (1.28--1.62), 2.14 (1.85--2.47)); induction of labour (2.14 (1.85--2.47), 1.70 (1.64--1.76)); delivery by emergency caesarian section (1.30 (1.25--1.34), 1.83 (1.74--1.93)); postpartum haemorrhage (1.16 (1.12--1.21), 1.39 (1.32--1.46)); genital tract infection (1.24 (1.09--1.41), 1.30 (1.07--1.56)); urinary tract infection (1.17 (1.04-1.33), 1.39 (1.18--1.63)); wound infection (1.27 (1.09--1.48), 2.24 (1.91--2.64)); birthweight above the 90th centile (1.57 (1.50--1.64), 2.36 (2.23--2.50)), and intrauterine death (1.10 (0.94--1.28), 1.40 (1.14--1.71)). However, delivery before 32 weeks' gestation (0.73 (0.65--0.82), 0.81 (0.69--0.95)) and breastfeeding at discharge (0.86 (0.84--0.88), 0.58 (0.56--0.60)) were significantly less likely in the overweight groups. In all cases, increasing maternal BMI was associated with increased magnitude of risk. CONCLUSION: Maternal obesity carries significant risks for the mother and foetus. The risk increases with the degree of obesity and persists after accounting for other confounding demographic factors. The basis of many of the complications is likely to be related to the altered metabolic state associated with morbid obesity.

Adult↗
PubMed2001

The diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies.

OBJECTIVE: Early ultrasound examination is being used increasingly in the diagnosis of molar pregnancy. The aim of this study was to examine the diagnostic implications of routine ultrasound examination for histologically confirmed molar pregnancies. METHODS: This was a retrospective review of sonographic and histological findings in a series of consecutive cases referred to the National Trophoblastic Disease Surveillance Centre with suspected molar pregnancies. In 194 cases referred to the center over a 6-month period in whom results of a preceding ultrasound examination were documented, review of ultrasound findings and final histological diagnosis was carried out. RESULTS: There were 155 cases with a reviewed histological diagnosis of complete or partial hydatidiform mole. In 131 (67%) cases, the sonographic diagnosis was that of a missed miscarriage/anembryonic pregnancy with no documented suspicion of molar pregnancy, referral being on the basis of histological examination of products of conception. In 63 cases, ultrasound examination suggested molar pregnancy; in 53 (84%) of these, the diagnosis of molar pregnancy was correct. Overall, 37 of 64 (58%) complete moles had sonographic evidence of molar pregnancy compared to 16 of 91 (17%) partial moles. Of 155 histologically confirmed complete or partial hydatidiform moles, only 53 (34%) were suspected as molar sonographically. CONCLUSION: The majority of cases of molar pregnancy now present as missed miscarriage/anembryonic pregnancy sonographically, highlighting the importance of histological examination to diagnose gestational trophoblastic disease.

Abortion, Missed↗
PubMed2001

Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles.

AIMS: To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann syndrome. METHODS AND RESULTS: We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as 'large'. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified. CONCLUSIONS: This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.

Adolescent↗
PubMed2001

Twin-to-twin transfusion syndrome results from dynamic asymmetrical reduction in placental anastomoses: a hypothesis.

Although placental vascular anastomoses between the fetoplacental circulations are ubiquitous in monochorionic twin pregnancies, the factors regulating their formation and maintenance are not understood. Increasing evidence implicates asymmetric anastomotic patterns in the aetiology of severe twin-to-twin transfusion syndrome (TTTS). The authors propose that anastomoses between placental circulations in monochorionic twins occur in a random manner at the embryological stage of connection of embryonic and extra-embryonic circulations. Placental expansion is then associated with random disruption of anastomoses and regression of their associated villus districts. TTTS develops as discordant loss of anastomoses results in asymmetrical flow resistance. Pregnancies with fetal growth concordance but discordant nuchal translucency at 10-14 weeks are at increased risk of developing subsequent severe TTTS because these clinical features indicate significant pressure differentials in the presence of a placentoplacental circulation, consistent with the presence of numerous, asymmetric anastomoses. However, since the anastomotic pattern is dynamic in the first half of pregnancy this hypothesis predicts that it will not be possible to devise a clinical test at 12 weeks that will predict with certainty the outcome of monochorionic twin pregnancies in relation to TTTS because this depends on random subsequent events.

Arteriovenous Anastomosis↗
PubMed2001

Placental villus morphology in relation to maternal hypoxia at high altitude.

Pregnancy at high altitude is associated with maternal hypoxaemic hypoxia with resultant intervillus blood hypoxia. Maternal haemoglobin concentration and blood gases were measured in pregnant women in two cities in Peru; Lima at sea level (n=18) and Cerro de Pasco at 4300 metres above sea level (n=12). Following delivery, placental sections from both groups were examined histomorphometrically using an image analysis system. Villus diameter, villus cross-sectional area, capillary diameter, capillary cross-sectional area and the percentage of villus cross-sectional area occupied by villus capillaries were calculated and parameters were compared between the two altitude groups. Maternal haemoglobin concentration and maternal blood pH were significantly higher, and maternal pO(2), pCO(2)and O(2)saturation were significantly lower in the high altitude group compared to those at sea level. The villus vessel area as a percentage of villus cross-sectional area and capillary diameter were significantly greater in the cases from the high altitude group and villus vessel area as a percentage of the villus cross-sectional area was significantly related to maternal pO(2)(r=-0.7, P=0.01), and maternal pCO(2)(r=0.7, P=0.02), but multiple regression analysis demonstrated that only pO(2)remained significantly independently associated with these villus histological findings (P=0.03). Placental terminal villi from term pregnancies at high altitude show different morphological features from pregnancies at sea level, and these changes are primarily related to maternal pO(2). The predominant morphological alteration is an increase in villus capillary diameter and therefore of the proportion of villus cross-sectional area occupied by capillary lumens.

Altitude↗
PubMed2001

Choriodecidual inflammatory syndrome (CoDIS) is the leading, and under recognised, cause of early preterm delivery and second trimester miscarriage.

Severe preterm birth (delivery before 32 completed weeks of gestation), with or without preterm premature rupture of the membranes (PPROM), remains the leading cause of perinatal mortality. It is proposed that localized inflammation of the chorion and decidua in the membranes immediately above the internal cervical os, with or without amniotic cavity infection and inflammation, is the leading, but under recognised, cause of second trimester miscarriage and severe preterm delivery. The term 'CoDIS' (choriodecidual inflammatory syndrome), may provide a better understanding of the underlying pathophysiology than currently used terminology which over emphasizes the importance of overt intra-amniotic infection as opposed to localized extra-amniotic inflammation which stimulates uterine evacuation.

Abortion, Spontaneous↗
PubMed2001

'Cor placentale': placental intervillus/intravillus blood flow mismatch is the pathophysiological mechanism in severe intrauterine growth restriction due to uteroplacental disease.

The underlying pathophysiology in most cases of severe intrauterine growth restriction and pre-eclampsia is thought to be abnormal and inadequate conversion of the branches of the uterine arteries into low resistance uteroplacental vessels, due to poor extravillous trophoblastic invasion, leading to reduced intervillous blood flow. Since, in most vascular beds the main site of flow resistance is at the level of the small arteries/arterioles rather than the capillary bed itself it is likely that in cases of intrauterine growth restriction due to uteroplacental dysfunction with abnormal fetal umbilical artery flow velocity waveforms, the underlying pathological mechanism is primarily an initial reduction in intervillus flow leading to relative local hypoxia of some villus territories. This results initially in autocrine/paracrine mediated localized stem artery vasoconstriction to minimize intervillus/intravillus flow mismatch which, when widespread, will result in abnormal umbilical artery Doppler waveforms due to the globally increased resistance to fetoplacental flow. Since, a small reduction in vessel radius will result in an exponential increase in flow resistance and reduction in flow, the magnitude of stem vessel constriction need only be small to result in large changes in fetoplacental vascular haemodynamics. Thus, the underlying progressive pathology in this condition may be cardiac failure, secondary to chronic stem vessel vasoconstriction caused by abnormalities in oxygenation of the fetal respiratory system hence the term 'cor placentale' is proposed.

Female↗
PubMed2001

Histological chorioamnionitis in relation to clinical presentation at 14-40 weeks of gestation.

This study examines the prevalence of histological inflammation of the fetal membranes according to gestational age and mode of clinical presentation in a series of 179 consecutive placentas evaluated in a single centre. The frequency of histological inflammation between clinical groups was compared and relation between the prevalence of inflammation and gestational age examined using regression analysis. One hundred and seventy-nine placentas were examined. Histological inflammation was present in 65 (38%) cases including 37/52 (71%) pregnancies presenting with spontaneous preterm labour and delivery (PTL), 23/36 (64%) with preterm prelabour rupture of membranes (PPROM), 1/20 (5%) with vaginal bleeding but no contractions (PVB), 1/13 (8%) with intrauterine death but no labour (IUD), 1/28 (4%) with iatrogenic delivery, 0/4 with termination of pregnancy and 2/20 (10%) delivering spontaneously at term. The prevalence of histological inflammation was significantly higher in those with PTL or PPROM compared to the other groups (P<0.0001). The frequency of histological inflammation was associated with gestational age (F=57.2, P<0.0001, R=0.91), with a peak prevalence (>90%) at 20-24 weeks' gestation.

Journal Article↗