Search PubMed⌕ Search

Biomedical subjects

M D Kilby

Publications and source records attributed to M D Kilby.

At least 37 records · Page 2Linked to original sources

Thyroid hormone responsiveness in N-Tera-2 cells.

N-TERA-2 cl/D1 (NT2) cells, a human embryonal cell line with characteristics of central nervous system precursor cells, were utilised to study thyroid hormone action during early neuronal growth and differentiation. Undifferentiated NT2 cells expressed mRNAs encoding thyroid hormone receptors (TRs) alpha1, alpha2 and beta1, iodothyronine deiodinases types 2 (D2) and 3 (D3) (which act as the pre-receptor regulators), and the thyroid hormone-responsive genes myelin basic protein (MBP) and neuroendocrine specific protein A (NSP-A). When terminally differentiated into post-mitotic neurons (hNT), TRalpha1 and TRbeta1 mRNA expression was decreased by 74% (P=0.05) and 95% (P<0.0001) respectively, while NSP-A mRNA increased 7-fold (P<0.05). However, mRNAs encoding TRalpha2, D2, D3 and MBP did not alter significantly upon neuronal differentiation and neither did activities of D2 and D3. With increasing 3,5,3'-triiodothyronine (T(3)) concentrations, TRbeta1 mRNA expression in cultured NT2 cells increased 2-fold at 10 nM T(3) and 1.3-fold at 100 nM T(3) (P<0.05) compared with that in T(3)-free media but no change was seen with T(3) treatment of hNT cells. D3 mRNA expression in NT2 cells also increased 3-fold at 10 nM T(3) (P=0.01) and 2.4-fold at 100 nM T(3) (P<0.05) compared with control, but there was no change in D3 enzyme activity. In contrast there was a 20% reduction in D3 mRNA expression in hNT cells at 10 nM T(3) (P<0.05) compared with control, with accompanying reductions in D3 activity with increasing T(3) concentrations (P<0.05). There was no significant change in the expression of the TRalpha isoforms, D2, MBP and NSP-A with increasing T(3) concentrations in either NT2 or hNT cells. Undifferentiated NT2 and differentiated hNT cells show differing patterns of T(3)-responsiveness, suggesting that there are different regulatory factors operating within these cell types.

Cell Differentiation↗

The 'Severe Hypertensive Illness in Pregnancy' (SHIP) audit: promoting quality care using a high risk monitoring chart and eclampsia treatment pack.

We set out to measure the standards of care in a regional cohort of women with severe hypertensive illness of pregnancy and to subsequently improve the quality of care using a series of interventions. This was a multi centre cyclical criterion audit involving 21 maternity units in the West Midlands Region. Prospective data collection involved named co-ordinators in each unit using customised proformas. Intervention comprised feedback of baseline results to each hospital, a monitoring chart and eclampsia treatment pack. The first audit period (n = 183) was for a 4-month period between 1/9/96 and 31/12/96 and the second audit period (n = 111) was during the same 4-month period 1 year later. Although compliance with the audit standards set increased in all but one standard, there is clearly a need to make further improvements in the quality of care administered.

Adult↗

Fetal magnetic resonance imaging in prenatal diagnosis of central nervous system abnormalities: 3-year experience.

OBJECTIVE: To evaluate the comparative merits of ultrasound and fetal magnetic resonance imaging (MRI) in the correct antenatal diagnosis of suspected central nervous system abnormalities. METHODS: A retrospective review of 27 consecutive pregnancies referred for fetal MRI for suspected central nervous system abnormalities between July 1998 and July 2001. Women were referred for the MRI examination when further anatomical and/or pathological clarification of the ultrasound scan findings was needed. Antenatal ultrasound scan and MRI were reviewed in relation to the findings on postpartum investigations. RESULTS: Data were complete for 26 pregnancies. The median gestational age at the time of the ultrasound examination was 26 weeks (95% CI 24 weeks 2 days to 28 weeks 1 day). The median gestational age at the time of magnetic resonance imaging was 27 weeks' gestation (95% Cl 26 weeks 1 day to 29 weeks 2 days). Eight fetuses had associated skeletal, renal and/or cardiac abnormalities previously noted on ultrasound examination. MRI confirmed the ultrasound diagnosis in 15/26 cases (58%). It changed the diagnosis to the correct one in 7/26 (27%) and misdiagnosed four cases (15%). Three of the four cases that were misdiagnosed on MRI occurred in the first 18 months of our 36-month experience. CONCLUSION: Ultrasound remains the primary imaging modality for prenatal diagnosis. Fetal MRI appears to be a useful adjunct to ultrasound to confirm or exclude certain abnormalities; this will consequently help in the counselling of parents and assist in planning further management. However, like any imaging technique, the sensitivity and specificity of the test are likely to improve with experience.

Adult↗

Management of pregnancy in women with pulmonary hypertension secondary to SLE and anti-phospholipid syndrome.

Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE). Pulmonary hypertension may be present at the time of diagnosis or may develop after the diagnosis of SLE or anti-phospholipid syndrome (APS). It often presents in the reproductive years and has a significant impact on pregnancy outcome, being a significant cause of indirect maternal deaths. In our observational case series of three patients there were two deaths (66%). In cases 1 and 2 the pulmonary hypertension developed during pregnancy and deteriorated rapidly with markedly abnormal mean pulmonary artery pressures of 80 and 70 mmHg respectively prior to death. Both patients died within 48 hours of delivery. In case 3 the pulmonary hypertension was milder and was diagnosed very early in pregnancy. The patient received multidisciplinary care from the first trimester and the management of the pregnancy, delivery and the early puerperium was planned. Careful epidural anaesthesia was used and the patient had invasive monitoring on the intensive therapy unit (ITU) for 72 hours. Women with pulmonary hypertension need to be aware of the high risk of maternal mortality associated with pregnancy but we believe that an improvement in outcome can be achieved by careful assessment and the use of a multidisciplinary approach from early in pregnancy.

Adult↗

Duplication of chromosome 2 in association with ventriculomegaly - a case report.

This is a case report of the prenatal diagnosis of a de novo interstitial duplication of chromosome 2 (46,XX,dup(2)(p13p21) de novo) with an associated phenotypic abnormality. This chromosomal duplication is rare, only one has previously been described prenatally. Postnatal reports of similar duplications in this region have described associated dysmorphic features and significant neurodevelopmental delay. In our case, the only ultrasound finding was moderately severe ventriculomegaly. At post-mortem, ventriculomegaly was confirmed and there was associated macrocephaly (head circumference above the 97th centile) with no dysmorphic features seen.

Adult↗

Klippel-Trenaunay-Weber (KTW) syndrome: the use of in utero magnetic resonance imaging (MRI) in a prospective diagnosis.

The diagnosis of the Klippel-Trenaunay-Weber (KTW) syndrome is rarely made antenatally. We report the use of both ultrasound and in utero magnetic resonance imaging (MRI) in the prenatal diagnosis of this syndrome. This is the first report of the use of prenatal MRI in the diagnosis of this condition. There was concordance in the findings of both modalities, with limb hypertrophy, and multiple haemangiomata - both subcutaneous and internally - demonstrated with ultrasound and MRI. The patient elected to terminate the pregnancy because of associated oligohydramnios and a small fetal chest noted at 20 weeks. The postmortem examination confirmed the antenatal diagnosis.

Abortion, Induced↗

Noninvasive techniques to detect fetal anemia due to red blood cell alloimmunization: a systematic review.

OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia. METHODS: Literature from 1970 to 2000 was identified using general bibliographic databases (MEDLINE and EMBASE), the Cochrane Library and relevant specialist register of the Cochrane Collaboration, and by checking reference lists of known primary and review articles. Studies were selected if the accuracy of the fetal ultrasound parameters or Doppler studies of blood flow in the fetal vessels was estimated compared with a reference standard (fetal hemoglobin). The diagnostic tests evaluated were ultrasound measurement of the fetal spleen perimeter and Doppler studies of blood velocity estimates in the umbilical vein, ductus venosus, middle cerebral artery, thoracic aorta, and umbilical vessel combined with the thoracic aorta. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. Data from the selected studies were abstracted as 2 x 2 tables comparing the diagnostic test result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios. RESULTS: The review included eight primary studies with 362 pregnancies affected by red cell alloimmunization. Prospective patient recruitment and complete population details were reported in half of the selected studies (four of eight). Only one study reported masking the diagnostic test results to clinicians. The diagnostic test performance varied widely according to the type of the test evaluated and the cutoff level used to define fetal anemia, which varied from study to study. The diagnostic test study of highest methodological quality reported a positive likelihood ratio of 8.45 (95% confidence interval 4.69, 15.56) and negative likelihood ratio of 0.02 (95% confidence interval 0.001, 0.25) for maximum middle cerebral artery Doppler velocity. CONCLUSION: The literature reporting noninvasive techniques to predict fetal anemia is methodologically poor and a standard approach to the evaluation of these techniques is lacking. A recommendation for practice cannot be generated without further rigorous research.

Blood Flow Velocity↗

First-trimester prenatal diagnosis of a familial subtelomeric translocation.

A new fluorescent in situ hybridization (FISH) technique utilizes a complete set of telomeric probes to screen for deletions or rearrangements within the subtelomeric regions of all chromosomes on a single slide. Such cryptic chromosome rearrangements would otherwise remain undetected by standard cytogenetic analysis. In this case report, we describe the first-trimester prenatal diagnosis of an unbalanced rearrangement in a family where such a cryptic subtelomeric rearrangement is segregating. Interestingly the fetus was also noted to have an increased nuchal translucency at the time first-trimester chorionic villus sampling was performed and a FISH diagnosis made. The result was subsequently confirmed on fetal material obtained after elective termination of the pregnancy. We believe this to be the first report in the literature (as by Medline, December 1999) of a first-trimester prenatal diagnosis using such subtelomeric probes where confirmation by conventional cytogenetic analysis was not possible.

Abnormalities, Multiple↗

Etiology and outcome of hydrops fetalis.

OBJECTIVES: To identify the etiology and pregnancy outcome of hydrops fetalis in a cohort of pregnancies referred to a tertiary maternal fetal medicine center in the UK. These data allow the review of a large series of pregnancies affected by hydrops fetalis and emphasize the importance of investigation and then treatment of individual cases. This provides parents with improved information and especially specific prognostic information. METHODS: A retrospective review of 63 consecutive cases of hydrops fetalis managed between September 1996 and March 1999. RESULTS: Of the pregnancies, 12.7% (n = 8) were associated with an 'immune' etiology. Of these, 62.5% (n = 5) had fetal anemia due to anti-D, 25% (n = 2) anti-Kell and 12.5% (n = 1) anti-c antibodies. The remaining 55 cases (87.3%) had a non-immune cause. Eight (14.5%) were due to human parvovirus B19 infection. Fourteen cases (25.5%) were associated with aneuploidy and, in four (7.3%), a primary hydrothorax was the cause of the non-immune hydrops fetalis. A cardiac cause was found in five (9.1%) cases. Three of these had supraventricular tachycardia and one had congenital complete heart block. Cystic hygroma was associated with hydrops fetalis in six cases. Twin-twin transfusion syndrome was the cause for hydrops in two cases. Massive transplacental hemorrhage was identified in one case. Fetal akinesia and muscular dystrophy caused hydrops in one case each. In 14.5% (8/55) of cases no obvious cause was identified and these were classified as 'idiopathic'. Three other cases could not be classified because parents declined investigations (unclassified). In the pregnancies with non-immune hydrops fetalis, the outcome was favorable in 27.3% (15/55) of cases. CONCLUSION: The prognosis of hydrops fetalis differs markedly between different etiological groups. Etiologies range from treatable causes with a good outcome and probably no long-term side-effects (as in case of parvovirus B19), to others which are incompatible with life or are associated with considerable perinatal morbidity and mortality.

Cohort Studies↗

The West Midlands "Severe Hypertensive Illness in Pregnancy" (SHIP) audit.

OBJECTIVE: To study the management of a series of women presenting with acute-onset hypertension in the 21 maternity units in the West Midlands region, in order to measure the standard of care and the outcomes of these patients and their babies. DESIGN: Multicenter audit. SETTING: Twenty-one Maternity Units in the West Midlands region with 85,658 births during the audit period. METHODS: Prospective data collection by named coordinators (multidisciplinary) in each unit using customized proformas. The proformas were then forwarded to the Research Coordinator for input onto a database and observational analyses. RESULTS: The total number of cases was 516. Eighty-one percent were diagnosed as having severe preeclampsia, 14% HELLP syndrome, and 5% eclampsia. Seven percent were admitted to the intensive therapy unit. Seventy percent of births were preterm, 62% of babies were low birth weight (< 2.5 kg), 57% of babies were admitted to the neonatal unit, and the perinatal mortality rate was 5%. The commonest antihypertensive agents were hydralazine and nifedipine. In terms of compliance with audit standards, 61% had both oxygen saturation and noninvasive blood pressure monitoring, 47% had good fluid balance documentation, and 79% had no fluid mismanagement. Seventy-four percent were seen by a consultant obstetrician, 62% were seen by a member of an "expert team," 83% adhered to local guidelines, and 71% of eclamptics received magnesium sulfate (MgSO4). CONCLUSION: Our study shows that severe hypertensive illness of pregnancy remains an important cause of maternal mortality and perinatal mortality. This audit highlights areas in which standards of care can be improved.

Adult↗

Expression of 11 beta-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies.

Interconversion of active and inactive glucocorticoids, e.g. cortisol (F) and cortisone (E) is catalysed by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) which exists as two isoforms. We have used human placental bed biopsies and an in-vitro cytotrophoblast cell culture system to examine the expression and activity of the 11 beta-HSD isoforms along with that of the glucocorticoid and mineralocorticoid receptors (GR and MR). Immunohistochemistry localized 11 beta-HSD1 to decidualized stromal cells and 11 beta-HSD2 to villous cytotrophoblast, syncytiotrophoblasts and trophoblast cells invading the placental bed and maternal vasculature. In primary cultures of human cytotrophoblast, 11 beta-HSD2, GR and MR mRNA were expressed. Low levels of 11 beta-HSD1 mRNA were noted in these cultured cells, but could be explained on the basis of contaminating, vimentin-positive decidual stromal cells (< or =5%). Enzyme activity studies confirmed the presence of a high-affinity, NAD-dependent dehydrogenase activity (K(m) 137 nmol/l and V(max) 128 pmol E/h/mg protein), indicative of the 11 beta-HSD2 isoform. No reductase activity was observed. The presence of functional MR and GR was determined using Scatchard analyses of dexamethasone and aldosterone binding (MR K(d) 1.4 nmol/l B(max) 3.0; GR K(d) 6.6 nmol/l B(max) 16.2 fmol/ng protein). The expression of 11 beta-HSD1 in maternal decidua and 11 beta-HSD2 in adjacent trophoblast suggests an important role for glucocorticoids in determining trophoblast invasion. The presence of the MR within trophoblast indicates that some of the effects of cortisol could be MR- rather than GR-mediated.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms.

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) inactivates cortisol to cortisone. In the placenta 11beta-HSD2 activity is thought to protect the fetus from the deleterious effects of maternal glucocorticoids. Patients with apparent mineralocorticoid excess owing to mutations in the 11beta-HSD2 gene invariably have reduced birth weight, and we have recently shown reduced placental 11beta-HSD2 activity in pregnancies complicated by intrauterine growth restriction. This is reflected in the literature by evidence of hypercortisolemia in the fetal circulation of small babies. In this study we have determined the levels of placental 11beta-HSD2 mRNA expression across normal gestation (n = 86 placentae) and in pregnancies complicated by intrauterine growth restriction (n = 19) and evaluated the underlying mechanism for any aberrant 11beta-HSD2 mRNA expression in intrauterine growth restriction. 11beta-HSD2 mRNA expression increased more than 50-fold across gestation, peaking at term. Placental 11beta-HSD2 mRNA levels were significantly decreased in intrauterine growth restriction pregnancies when compared with gestationally matched, appropriately grown placentae [e.g. at term DeltaCt (11beta-hydroxysteroid dehydrogenase type 2/18S) 12.8 +/- 0.8 (mean +/- SE) vs. 10.2 +/- 0.2, respectively, P < 0.001]. These differences were not attributable to changes in trophoblast mass in intrauterine growth restriction placentae, as assessed by parallel analyses of cytokeratin-8 mRNA expression. No mutations were found in the 11beta-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11beta-HSD2 gene was not imprinted. Although the underlying cause is unknown, 11beta-HSD2 gene expression is reduced in intrauterine growth restriction pregnancies. These data highlight the important role of 11beta-HSD2 in regulating fetal growth, a known factor in determining fetal morbidity but also the subsequent development of cardiovascular disease in adulthood.

11-beta-Hydroxysteroid Dehydrogenases↗

Outcome after prenatal diagnosis of hypoplastic left-heart syndrome: a case series.

BACKGROUND: Traditionally, after prenatal diagnosis of hypoplastic left-heart syndrome (HLHS) couples have been offered termination of pregnancy or comfort care. Success of postnatal surgical options such as the Norwood procedure have been associated with survival of up to 60%. Whether survival is affected by the congenital anomaly being identified prenatally or postnatally remains uncertain. METHODS: We reviewed all cases of prenatally diagnosed HLHS referred to the Fetal Medicine Unit at Birmingham Women's Hospital over 6 years between 1994 and 1999. FINDINGS: 87 cases of HLHS were referred at a median gestational age (95% CI) of 23 (19-37) weeks. Of these, 53 (61%) chose prenatal karyotyping. The overall frequency of abnormal karyotype was found in seven of 59 cases (12%) and associated structural anomalies in 18 of 87 (21%). After counselling, 38 of 87 couples (44%) chose termination of pregnancy. Of the remaining 49 fetuses, 11 (23%) were not considered for postnatal surgery because of parental choice and they died after compassionate care. Of the 36 babies who had surgery postnatally, 12 survived (33%). We recorded a survival rate of 38% for the stage-1 Norwood procedure in the prenatally diagnosed HLHS in our centre. These data suggest that at the point of prenatal detection, the overall survival rate for fetuses with HLHS is 25% (if terminated pregnancies are excluded). INTERPRETATION: Fetal echocardiography allows early diagnosis of HLHS and gives clinicians the opportunity to triage this group dependent on prenatal findings, including karyotyping and the exclusion of other structural anomalies. These prospective data provide up-to-date information on the basis of which parents can make decisions.

Abortion, Induced↗

Expression of thyroid receptor isoforms in the human fetal central nervous system and the effects of intrauterine growth restriction.

BACKGROUND: Congenital hypothyroidism is known to be associated with mental retardation which, if recognized promptly, is largely prevented by thyroid hormone replacement. Intrauterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity, and is also associated with neurodevelopmental delay. Fetuses with IUGR have reduced circulating concentrations of free thyroxine (T4) and free triiodothyronine (T3), leading to the hypothesis that a reduction in the tissue effects of thyroid hormones in the central nervous system (CNS) may contribute to neurodevelopmental morbidity. Since thyroid hormone effects are mediated through binding to specific nuclear thyroid hormone receptors (TRs), we have defined the pattern of TR isoform expression in the CNS throughout normal human development and have compared TR expression in the CNS of normal fetuses with those affected by IUGR. METHODS: Samples of normal human fetal brain from first and second trimesters were obtained at surgical termination of pregnancy. Appropriately grown and third trimester fetuses affected by Intrauterine growth restriction (IUGR) were also investigated after unexplained stillbirth at post mortem examination. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to examine the expression of TR isoform mRNAs in frozen cerebral cortex from 10 to 16 weeks gestation. TR protein expression in human fetal brains (both cerebral hemispheres and cerebellum) was also examined in formalin fixed sections and expression of TR alpha1, alpha2, beta1 and beta2 isoforms being defined using semiquantitative immunocytochemistry. RESULTS: RT-PCR revealed the presence of mRNAs encoding TR alpha1, beta1 and beta2 isoforms and the nonfunctional TRalpha2 variant in the fetal cerebral cortex from week 10 of human pregnancy. Immunostaining of the fetal brain revealed TR alpha1 and alpha2 protein from week 11 of human gestation. Expression of all TR isoform proteins was largely confined to the pyramidal neurones of the cerebral cortex and the Purkinje cells of the cerebellum with increasing receptor expression evident with gestational age. Semiquantitative observer scoring showed that by the second trimester, there was a marked increase in the proportion of pyramidal and Purkinje cells expressing TR isoforms, while by the third trimester, all these cells immunostained. Comparison of TR immunostaining in the cerebral cortex and cerebellum from IUGR fetuses (n = 18) matched for gestational age to normal fetuses revealed a lower intensity of expression of all the TR isoforms confirmed by observer scoring and quantification using TR protein immunofluoresence (P<0.01). CONCLUSIONS: Our findings indicate both pre- and post-translational expression of TR alpha and beta isoforms in the cerebral cortex of first trimester fetuses. These findings support the view that the transplacental passage of thyroid hormone in early gestation may be critical to neurological development. Our finding that in severe IUGR the expression of TR isoforms in the human fetal cerebral cortex and cerebellum was significantly reduced, in association with reduced circulating thyroid hormone concentrations indicate that changes in free ligand and receptors may affect CNS development. These findings should prompt further investigation of the potential therapeutic role of peripartum thyroid hormone treatment.

Case-Control Studies↗

Hepatocyte growth factor activator (HGF-A) and its zymogen in human placenta.

HGF-activator (HGF-A) is a circulating serine protease known to be responsible for activation of hepatocyte growth factor (HGF). Active HGF is thought to be an important regulator of trophoblast growth. In vitro, HGF-A is produced via proteolytic cleavage of its zymogen by thrombin. Immunocytochemistry and Western immunoblotting were performed using human placental tissue from all three trimesters with an antibody that recognizes both HGF-A and its zymogen. Western immunoblotting revealed a 97 kDa band equivalent to the zymogen in placenta from all three trimesters. A smaller 34 kDa band equivalent to HGF-A was only seen in first and second trimester placenta. The anti-HGF-A/zymogen antibody demonstrated immunostaining in placental villi and membranes throughout gestation. Within first trimester villi immunostaining was strongest within the syncytio- and cytotrophoblast layers, but was also seen within stromal and endothelial cells. Likewise, in third trimester placenta the syncytio-cytotrophoblast layer showed the strongest immunoreactivity. In vitro, HGF can induce trophoblast DNA synthesis and the localization of HGF-A to the peri-villous trophoblast layer (which expresses c-met, the HGF receptor) suggests that it may be responsible for activation of pro-HGF at this site. This adds further weight to the hypothesis that HGF in vivo is an important regulator of trophoblast growth.

Blotting, Western↗

Unexpected rapid rise of maternal serum anti-D levels during pregnancy.

Two cases are described where hydrops faetalis developed as a result of very sudden and unexpected rises in serum anti-D levels. In both cases intravascular intrauterine transfusion was employed and a favourable outcome obtained. These cases show that continued vigilance is required even when anti-D levels are low. Weak antibody titres may be detected using enzyme-treated red cells, and failure to use this more sensitive technique meant that in one of the cases the initial weak antibody was not detected. There is currently a debate about the use of this more sensitive test in view of the increased work involved.

Journal Article↗

The outcome of pregnancy in Kell alloimmunisation.

OBJECTIVE: To assess management and outcome of pregnancies with anti-Kell in the West Midlands in the UK over 13 years. DESIGN: A retrospective review of casenotes. SETTING: A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital. POPULATION: Sixty-five pregnancies were identified in 52 Kell-sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre. METHODS: Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package. MAIN OUTCOME MEASURES: Mode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome. RESULTS: Alloimmunisation was transfusion-related in 29 pregnancies and pregnancy-induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy-related in 12 cases and transfusion-related in five. Antibody titres and amniotic fluid OD450 were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation. CONCLUSIONS: Anti-Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.

Adolescent↗