Biomedical subjects

Sean F Daly

Publications and source records attributed to Sean F Daly.

5 recordsLinked to original sources

PubMed2005

Neural tube defects: is a decreasing prevalence associated with a decrease in severity?

OBJECTIVE: Severe neural tube defects (NTDs) tend to occur with disproportionate frequency in areas of high prevalence. The objective of our study was to determine the birth prevalence of NTDs during a 25-year period at a single institution based in an area of high prevalence for NTDs and to investigate if a decreasing prevalence resulted in a change in the type of NTDs. STUDY DESIGN: All cases of NTD affected births born at the Coombe Women's Hospital during the interval 1975-1999 were reviewed. There were 171,260 births at the Coombe Women's Hospital between 1975 and 1999. During this interval, there were 522 NTD affected births. RESULTS: From 1975 until 1999 the prevalence of NTDs significantly decreased (P < 0.0001). This transition from high to low prevalence was associated with a significant decrease in severe forms of NTDs (P < 0.0001). This decreasing trend in rate and severity of NTD affected births was most dramatic prior to either food fortification or periconceptual folic acid supplementation. CONCLUSIONS: Our transition from high to low prevalence for NTDs has been associated with a significant decrease in severe forms of NTDs.

Anencephaly↗

PubMed2005

Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery.

BACKGROUND: Little is known about the interactions between choline and folate and homocysteine metabolism during pregnancy despite the facts that pregnancy places considerable stress on maternal folate and choline stores and that choline is a critical nutrient for the fetus. Choline, via betaine, is an important folate-independent source of methyl groups for remethylating homocysteine in liver. OBJECTIVES: Our aims were to examine the intermediates of choline oxidation in maternal and umbilical cord plasma and to determine the relations between this pathway and folate-dependent homocysteine remethylation. DESIGN: Blood samples were taken from 201 pregnant women and, at delivery, from the umbilical cord veins of their healthy, full-term infants. The blood samples were analyzed for plasma free choline, betaine, dimethylglycine, folate, vitamin B-12, total homocysteine (tHcy), and creatinine concentrations. RESULTS: Choline concentrations in umbilical cord plasma were approximately 3 times those in maternal plasma (geometric x: 36.6 and 12.3 micromol/L, respectively; P < 0.0001). Betaine and dimethylglycine concentrations were also significantly higher in umbilical cord than in maternal plasma. Choline was positively associated with tHcy (r = 0.34, P < 0.0001), betaine (r = 0.58, P < 0.0001), and dimethylglycine (r = 0.30, P < 0.0001) in maternal blood. Much weaker relations were seen in the fetal circulation. In a multiple regression model, choline was a positive predictor of maternal tHcy, whereas vitamin B-12 and betaine were negative predictors. CONCLUSIONS: The positive association between maternal choline and tHcy during pregnancy suggests that the high fetal demand for choline stimulates de novo synthesis of choline in maternal liver, with a resultant increase in tHcy concentrations. If this is confirmed, it may be appropriate to provide choline supplements during pregnancy to prevent elevated tHcy concentrations.

Betaine↗

PubMed2005

Increased fetal RhD gene in the maternal circulation in early pregnancy is associated with an increased risk of pre-eclampsia.

OBJECTIVE: To determine whether the fetal RhD gene is present in the maternal circulation in early pregnancy prior to the clinical manifestation of pre-eclampsia. DESIGN: This is a nested case-control study. SETTING: Blood samples were obtained from patients attending for a first antenatal visit. SAMPLE: Cases were asymptomatic RhD negative women (n= 23) who subsequently developed pre-eclampsia matched to RhD negative controls (n= 23) for parity and gestational age. METHODS: Real time PCR using TaqMan primers and probes directed against the RhD gene quantified fetal DNA in the maternal circulation. MAIN OUTCOME MEASURES: Quantity of RhD gene detected. RESULTS: As the copy number of RhD gene per millilitre of whole blood at 15 weeks of gestation increased, there was a significantly increased risk of developing pre-eclampsia. There was a graded association between copy number of RhD gene in early pregnancy and severity of disease with controls having 6942, mild pre-eclamptics 83,273 and severe pre-eclamptics 285,793 copies/mL (logscale 3.6, 4.0 and 4.5, respectively). CONCLUSION: Increased fetal RhD gene is present in the maternal circulation in early pregnancy in women who subsequently develop pre-eclampsia and there appears to be a graded response between the quantity of fetal DNA and severity of pre-eclampsia.

Adult↗

PubMed2004

Increased fetal DNA in the maternal circulation in early pregnancy is associated with an increased risk of preeclampsia.

OBJECTIVE: The aim of our study was to determine if fetal DNA is present in the maternal circulation in early pregnancy before the clinical manifestation of preeclampsia, and if this could be predictive of the development of preeclampsia. STUDY DESIGN: Blood were obtained from patients attending for a first antenatal visit. Cases were asymptomatic women who subsequently developed preeclampsia matched to control women for parity and gestational age. Real-time polymerase chain reaction (PCR) using TaqMan primers and probes directed against SRY gene sequences quantified fetal DNA in the maternal circulation. RESULTS: There were 88 cases of women with preeclampsia and 176 control women, both sampled at a mean gestation (+/-SD) of 15.7 +/- 3.6 weeks. The presence of fetal DNA in the maternal circulation in early pregnancy is associated with an 8-fold increased risk of developing preeclampsia. CONCLUSION: Increased fetal DNA is present in the maternal circulation in early pregnancy in women who subsequently develop pre-eclampsia and there appears to be a graded response between the quantity of fetal DNA and the risk of developing pre-eclampsia.

Adult↗

PubMed2003

Elevated plasma homocysteine in early pregnancy: a risk factor for the development of nonsevere preeclampsia.

OBJECTIVE: We have recently demonstrated that an elevated plasma homocysteine in early pregnancy is associated with the development of severe preeclampsia. The aim of this study was to determine whether an elevated plasma homocysteine in early pregnancy is also associated with the development of nonsevere preeclampsia. STUDY DESIGN: Blood was obtained from patients attending for a first antenatal visit. Subjects were asymptomatic women who subsequently developed nonsevere preeclampsia. Controls were matched for parity, gestational age, and date of sample collection. Plasma homocysteine was measured using fluorescence polarization immunoassay. RESULTS: There were 71 cases of nonsevere preeclampsia sampled at a mean gestational age (+/-SD) of 15.9+/-3.6 weeks and 142 controls at 15.6+/-3.4 weeks. The preeclampsia cases had a mean (+/-SD) homocysteine level of 8.4+/-2.4 micromol/L, whereas controls had a mean homocysteine of 7.07+/-1.5 micromol/L (P</=.0001). CONCLUSION: Women who develop nonsevere preeclampsia have higher plasma homocysteine levels in early pregnancy compared with women who remain normotensive throughout pregnancy. An elevated plasma homocysteine value in early pregnancy may be associated with a 4-fold increased risk for development of nonsevere preeclampsia.

Adult↗