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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cytokines in implantation.

The process of implantation in the human involves 'invasion' of the maternal endometrium by the trophoblast surrounding the developing blastocyst, in response to which there is a cellular reaction in the endometrium. The overall situation has some features analogous to invasion by a tumour and some which are more characteristic of an inflammatory response. In addition, and also in common with cancer and inflammation, there is a release of biologically active molecules, including cytokines, at and around the implantation site. It is believed that these cytokines may play an important role in the successful establishment of the pregnancy; the evidence for this belief is examined in this review.

Colony-Stimulating Factors↗
PubMed1995

Relationships between the uterine environment and maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in early pregnancy.

Blood was obtained from 218 women between 6 and 13 weeks of gestation. Measurements of serum insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14) concentrations were compared with maternal weight and height, maternal smoking habit, indices of maternal haematological status and two placental hormones [human chorionic gonadotrophin (HCG) and human placental lactogen (HPL)]. IGFBP-1 concentration was negatively correlated with maternal weight (P < 0.001) and body mass index (P < 0.001); PP14 concentration was not correlated with these measurements. PP14 concentration was negatively correlated with maternal haemoglobin concentration (P = 0.010), mean corpuscular volume (P = 0.003) and serum ferritin concentration (P = 0.016). The concentrations of PP14 were significantly less among smokers (P < 0.001); IGFBP-1 concentrations were uninfluenced by smoking. IGFBP-1 concentration was positively correlated with maternal serum HCG (P = 0.003) and maternal serum HPL (P = 0.002). PP14 concentration was positively correlated with maternal serum HCG (P < 0.0001) but not with HPL. These findings demonstrate that the maternal environment has an early influence on both endometrial and placental function.

Body Mass Index↗
PubMed1995

Variations in concentrations of the major endometrial secretory proteins (placental protein 14 and insulin-like growth factor binding protein-1) in assisted conception regimes.

We have previously shown that placental protein 14 (PP14) concentrations were depressed in two pregnancies that followed down-regulation of the anterior pituitary and exogenous hormone support prior to a frozen-thawed embryo transfer. We now report on a more comprehensive series of pregnancies following this form of treatment, in-vitro fertilization (IVF) and natural cycle frozen-thawed embryo transfer. Serum specimens were analysed for PP14 and insulin-like growth factor binding protein-1 12 days after embryo transfer and at 7 weeks gestation. At 12 days after embryo transfer, the mean serum PP14 concentrations in the IVF and natural cycle were significantly higher in those who conceived than those who did not (82 versus 23 and 107 versus 39 micrograms/l respectively, P < 0.001). Although the mean PP14 concentration in the hormone-supported pregnant patients was higher than in the non-pregnant patients, this had not reached statistical significance 12 days after embryo transfer (49 versus 31 micrograms/l). By 7 weeks gestation the PP14 concentrations in the hormone-supported pregnant patients were significantly higher than in the non-pregnant patients (152 versus 31 micrograms/l, P < 0.001). However, the PP14 concentrations for hormone-supported pregnant patients were significantly lower (P < 0.001) than those for pregnant IVF or natural cycle patients at 7 weeks gestation (152, 777 and 660 micrograms/l respectively). The PP14 concentrations in the pregnant patients, although lower than those in IVF and natural cycle pregnancies, were higher than those previously reported in ovarian failure and Turner's syndrome ovum donation cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1995

Selective miscarriage of Down's syndrome fetuses in women aged 35 years and older.

OBJECTIVE: To estimate the fetal loss of Down's syndrome fetuses between the time of chorionic villus sampling (10 weeks gestation) and the time of amniocentesis (16 weeks gestation) and term in women aged 35 years and older. DESIGN: The age specific prevalence rates in the first trimester of Down's syndrome were estimated using the Danish cytogenetic register in combination with results from four published studies. These were compared with the reported prevalence at the time of amniocentesis and at birth. SUBJECTS: 5927 singleton pregnancies undergoing chorionic villus sampling (71 cases of Down's syndrome and 5856 unaffected cases). This was combined with published data on a further 231 cases of Down's syndrome and 16,620 unaffected cases. MAIN OUTCOME MEASURES: Age specific prevalences at the time of chorionic villus sampling. Proportion of pregnancies lost between the time of chorionic villus sampling and the time of amniocentesis and term. RESULTS: Thirty-two percent of Down's syndrome pregnancies are lost between the time of chorionic villus sampling (10 weeks) and the time of amniocentesis (16 weeks) and 54% are lost by term. CONCLUSIONS: The high fetal loss rates of Down's syndrome between the time of chorionic villus sampling and term introduce problems when evaluating first trimester screening tests with respect to their effective detection rates at term. A recommendation for quoting term risks is made.

Abortion, Spontaneous↗
PubMed1995

Lack of evidence for a circadian rhythm of IGFBP-1 in the mother and fetus during labour.

OBJECTIVE: To determine whether the circadian rhythm of circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) is evident at the time of delivery. DESIGN: Prospective observational study in six pregnant women and cross-sectional study in 65 women at the time of delivery. SUBJECTS: Six pregnant women sampled over a period of 24 hours, 23 women sampled at the time of elective caesarean section, and 42 women sampled at the time of vaginal delivery. RESULTS: In the women sampled serially over a 24 hour period there was an obvious circadian rhythm of IGFBP-1 with a peak between 01.00 and 09.00 hours. In the women sampled at the time of delivery there was no evidence for any relationship between the time of delivery and maternal or fetal levels of IGFBP-1. CONCLUSIONS: The circadian rhythm of IGFBP-1 is not observed in women in labour. Therefore, the time of day is not an important confounding variable in studies on IGFBP-1 levels at the time of normal delivery.

Cesarean Section↗
PubMed1995

Elevated levels of insulin-like growth factor binding protein-1 in fetal distress.

OBJECTIVE: To investigate the association between fetal distress (abnormal cardiotocograph tracing and/or a low fetal pH) and the levels of fetal IGFBP-1. DESIGN: Prospective comparative study. SUBJECTS AND METHODS: Twenty-two women in labour with evidence of fetal distress defined by FIGO criteria and 19 women in uncomplicated labour. The gestation range was 37 to 42 weeks and birthweight range was 2500 to 4240 g. IGFBP-1 was determined by radioimmunoassay. RESULTS: The umbilical levels of IGFBP-1 were significantly higher in the study group compared with the control group (median 282.5 micrograms/l versus 128 micrograms/l, P = 0.0046; Mann-Whitney U test). There was a significant inverse correlation between fetal IGFBP-1 and cord pH (r = 0.58, P < or = 0.0001). There was no difference between the maternal serum levels of IGFBP-1 in the two groups. CONCLUSION: Umbilical IGFBP-1 is elevated in association with fetal distress.

Adolescent↗
PubMed1995

Risk factors for HIV infection overlooked in routine antenatal care.

We have ascertained the extent to which risk factors for HIV infection may escape detection by standard history-taking procedures in an antenatal clinic. This study was based on 1264 women from a multi-ethnic population in an inner London health district (City and Hackney). All had agreed to undergo attributable HIV testing and a detailed personal interview. Thirty-nine per cent (494 of 1264 women) reported risk factors contributed personally or by a partner. Most of these risk factors had not been earlier disclosed by routine history taking. In most cases the risk was residence and risk activity in a World Health Organization (WHO) Pattern 2 country. [HIV spread WHO categories: Pattern 1--principally homosexual/bisexual males and i.v. drug use (areas = North America, Western Europe, Australasia, parts of South America) with male to female ratio 10/1; Pattern 2--Heterosexual (areas = Sub Saharan Africa, Caribbean and part South America) with male to female 1/1.] Thirty-one subjects (2.4%) were aware that their partners had participated in bisexual activity. Only six subjects perceived themselves at risk through their own or partner's drug injecting activity. The frequency of risk factors was substantially greater than that ascertained by the routine history. The findings highlight the potential risk of heterosexual spread resulting from travel to or residence in high prevalence territories. The contribution by male partners is significant and is particularly difficult to detect during a routine interview. These data support the recommendation that voluntary HIV serum testing should be universal rather than a selective offer based on risk factors determined at a routine history.

Female↗
PubMed1995

Screening for Down's syndrome.

Down's syndrome (DS) is the commonest cause of severe mental retardation in children. It is the result of trisomy of chromosome 21 which is usually a random event though it is commoner in older mothers. DS can be diagnosed by chorionic villus sampling (CVS) and amniocentesis followed by karyotyping. Because of the risks associated with these invasive procedures, they can only be offered to a high-risk group. At one time the sole basis for identifying this increased risk was maternal age, but within the past ten years a series of biochemical and ultrasound abnormalities have been shown in DS pregnancies. The biochemical abnormalities include changes in the levels of most fetal and placental products in the maternal circulation. The best-known of these changes are the reduced levels of alphafetoprotein (AFP) and oestriol (E3) and increased levels of human chorionic gonadotrophin (hCG). The mechanism underlying these biochemical phenomena is unknown. Screening programmes involving the measurement of hCG and AFP, with or without additional parameters such as E3, at 15-18 weeks of pregnancy can typically identify 60% or more of cases of DS with a screen-positive rate of 5%. The combined risk derived from the various biochemical parameters, together with maternal age, is calculated by one of a number of computer programmes which have been developed for this purpose. There has been considerable discussion as to the exact biochemical tests which should be used for DS screening. This had led to controversy as to whether measurement of E3 has a place, and whether or not measurement of the free beta-subunit of hCG should replace measurement of the intact molecule. A notable recent development is the suggestion that measurement of the urinary beta-core of the hCG could be a highly discriminatory marker. A number of factors can affect the results of biochemical screening for DS. These include maternal weight, gestational age, ethnic origin, smoking, and diabetes. In addition, abnormal levels of the biochemical products may be found in other chromosome abnormalities.

Biomarkers↗
PubMed1994

Risk identification for HIV infection in an inner London antenatal population.

This study was carried out to ascertain whether routine antenatal history taking is an effective means of identifying risk factors for HIV infection. Information about risk obtained at routine booking was compared with answers to selected questions obtained at a research interview. The study was conducted at St. Bartholomew's Hospital Homerton, and ran from February 1991 to March 1992. Of the 3729 women interviewed, 1671 had been hand booked (unstructured questionnaire) and 2058 had been computer booked (structured questionnaire). Hand booking failed to identify 77% of risk factors compared with 7% for computer booking. The findings highlight the underdetection of risk activity and confirm the need for intermittent, anonymous sampling to obtain background information against which a decision to implement universal testing may be made.

Female↗
PubMed1994

Second trimester amniotic fluid placental alkaline phosphatase levels are low in Down's syndrome but not in other fetal abnormalities.

Second trimester amniotic fluid placental alkaline phosphatase (PLAP) immunoreactivity was measured in 756 normal pregnancies, 63 Down's syndrome pregnancies and 42 pregnancies associated with other chromosomal abnormalities. PLAP levels were significantly reduced in cases of Down's syndrome (MoM = 0.72, U = 17,565, P = 0.0002, 95% Cl = 0.63-0.88). However, there was no significant difference between other aneuploid conditions and the normals (MoM = 0.88, U = 13,289, P = 0.35, 95% CI = 0.77-1.08). PLAP is the carrier protein for immunoglobulin G. Neonates with Downs syndrome but not other chromosomal abnormalities are associated with a deficiency of IgG. These data therefore support the theory that the low IgG levels in Downs syndrome are a result of a defect in PLAP transport.

Alkaline Phosphatase↗
PubMed1994

Use of anthropometric indicators and maternal risk factors to evaluate intrauterine growth retardation in infants weighing more than 2500 grams at birth.

The overall objectives of this study were to characterize the patterns of IUGR of infants weighing more than 2500 g at birth and to identify pregnancy-related risk factors associated with IUGR. A total of 195 term newborns were studied from a Pediatric Hospital in the city of Hermosillo, Sonora, Mexico. The experimental group consisted of 140 newborns whose birth weights ranged between 2500 and 3200 g. A total of 55 non-IUGR infants were included in the control group whose birth weights were between 3200 and 4000 g. IUGR was evaluated based on the fetal growth ratio method defined as the observed birth weight at a given gestational age to the mean birth weight using a sex-specific reference growth standard. Overall, 35% of infants weighing between 2500-3200 g showed patterns of IUGR. These patterns of underweight were associated with lower values in several of the anthropometric indicators and proportionality ratios used. Of all the maternal risk factors evaluated only previous history of low birth weight was found to be statistically significant between IUGR and non-IUGR groups, after adjustment of several control variables. Further analysis of IUGR infants with maternal history of low birth weight demonstrated significantly lower mean values for a variety of anthropometric indicators in comparison to non-IUGR infants without maternal history of low birth weight.

Anthropometry↗
PubMed1994

Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A, markers for fetal Down syndrome at 8-14 weeks.

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.

Biomarkers↗
PubMed1994

Human maternal uniparental disomy for chromosome 16 and fetal development.

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.

Adult↗
PubMed1994

Urinary beta-core human chorionic gonadotrophin: a new approach to Down's syndrome screening.

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary beta-core-hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome. beta-Core-hCG levels were corrected for creatinine and expressed as multiples of the normal gestation-specific median (MOM) level derived from 67 singleton controls. There was a highly statistically significant elevation in level among the singleton Down's syndrome cases (P < 0.0005; Wilcoxon rank sum test). All had levels exceeding 2 MOM with a median of 6.11 MOM (95 per cent confidence interval 3.7-10.0). The levels were extremely low in Edwards' syndrome (0.08 MOM) and triploidy (0.02 MOM), but the twin pregnancy discordant for Down's syndrome did not have a raised beta-core-hCG level (0.64 MOM). The findings are sufficiently encouraging to investigate the possibility of urinalysis as a routine modality in the prenatal screening for Down's syndrome and other common serious aneuploidies.

Adolescent↗