Nov. 30, 2000 -- For nearly 25 years, doctors have routinely recommended that pregnant women age 35 and older undergo amniocentesis, a test used to detect Down's syndrome and other serious genetic disorders that are more common among babies born to older moms. But new research suggests that many could forgo having an "amnio" if a simple blood test performed first shows that the developing baby is likely to be normal.
Amniocentesis, in which fluid is withdrawn from the uterus and cells in it analyzed for abnormalities, is the most accurate method for determining the health of a fetus.
In 1978, a government panel recommended that all expectant moms over age 35 be offered an amnio because their risk of having a Down's syndrome baby was, at the time, felt to be higher. Up to 80% of these women currently choose to have one.
Women who undergo an amnio may miscarry, although this is rare. Many more moms suffer through the gut-wrenching, two-week wait for results. Expectant women younger than age 35, in contrast, are frequently offered a different procedure that involves drawing blood from their arm and testing it for the presence of three elements that, in abnormal levels, suggest that the fetus could have Down's syndrome. Results of the triple test, as it is called, are available in about a week.
After analyzing CDC statistics from 1974 to 1997 concerning births and mothers' ages, James Egan, MD, and his colleagues at the University of Connecticut concluded that a mother's age alone is not an accurate method for deciding who should have an amnio.
Using 1997 statistics, they found that if all women were to receive the triple test, and amnios were performed only on women whose triple tests were abnormal, 150,000 fewer amnios might have been done nationwide. Also, 1,500 more babies with Down's syndrome might have been detected, and 770 fewer fetal deaths might have occurred as a result of an amnio. The research is published in the December issue of the journal Obsterics and Gynecology.
"Age is clearly a risk factor for Down's syndrome," Egan tells WebMD. "It's just that we have a better test than we used to have, and the woman could have a blood test at 15 or 16 weeks, and 16 or 17 weeks have an amnio after getting more complete information about her risk" of carrying a child with the disease.
"There really isn't a pressing need to reduce amnios," says James Haddow, MD, one of the founders of the Foundation for Blood Research in Scarborough, Maine. Haddow and others conducted similar research in 1994. "The amnio is still the best, most reliable way to get an answer. But it would certainly be a benefit to reduce them in terms of avoiding pregnancy loss and costs. What we would like to do is find ways to reduce amnios but not sacrifice detection [of Down's syndrome]," which Haddow says is achieved with the approach of doing the triple test first.
"For women who are pregnant now, or will be in the next couple of months, this might be fresh in their minds and they might decide to go this route rather than go straight to an amnio," Haddow says.
But this idea is not without controversy. Craig Dickman, MD, an obstetrician-gynecologist in suburban Washington, D.C., says he wouldn't suggest the blood test be done before an amnio to his older moms until more studies are completed. "To say that that the triple test should replace an amnio -- I am not sure I would agree with that. It has too high a false-positive rate. I think most women want [whichever test] is the least risky and that would be blood test. But is it accurate enough?"
Stephen T. Chasen, MD, describes the issue of when to perform an amnio vs. the triple test as one charged with emotion, with fearful parents on the one side and a cost-conscious health care system on the other. Chasen agrees with Haddow that the study does a good job of rehashing this debate, but he says it won't end here.
"It is perfectly reasonable for women 35 and over to have a triple test prior to deciding to undergo amniocentesis" unless they want more assurance that the amnio can provide, says Chasen, an assistant professor of obstetrics-gynecology at Weill Medical College of Cornell University in New York. He was not involved in this study.
"A good argument can be made that too many amniocenteses are performed to identify fetuses with Down's syndrome," he says, but this is an incomplete argument. Sure, more Down's babies would be identified using the triple test and age as a guide. However, many more candidates for amnios would be found as well. More amnios mean more chances of fetal loss. "Is it worth it? Should we be asking that question of individual women?" Chasen asks.
Chasen says that up to one-fourth of the amnios he performs are on women younger than 35. At Cornell, all pregnant women, regardless of their age, are offered the triple test and amnios.
Since almost all fetuses with Down's syndrome or other abnormalities will be diagnosed, "they can then make an informed decision about whether the benefits of the test ... justify the risk [of] miscarriage," Chasen says. Women who want to be as certain as possible that they will not have a child with Down's syndrome "don't really care about the number of extra miscarriages that will be seen annually nationwide with a more liberal policy of amniocentesis. Having a child with Down's syndrome is a devastating, permanently life-altering event. Many women can accept a small individual risk of miscarriage to know that this won't happen to them."
Nov. 21, 2000 -- Doctors have shown they can detect Down's syndrome at an early stage in pregnancy simply by taking a tiny sample of the mother's blood.
The test could give parents an earlier indication of whether their baby has particular chromosomal abnormalities and eventually may do away with existing methods of detecting those abnormalities in the developing baby in the womb -- some of which carry a risk of miscarriage.
It involves looking at the mother's blood to try and find genetic material from the baby that can then be studied for abnormalities using existing laboratory testing techniques.
Researchers from Hong Kong who used the testing method say they hope it will lead to safer and more reliable ways of diagnosing fetal abnormalities.
Reporting their findings in The Lancet this week, they write: "Ultimately, prenatal diagnosis by this technique could reduce our reliance on invasive methods."
The vast majority of Down's syndrome cases are due to an accident of nature, a chromosomal abnormality that can happen to anyone, while a fewer number of cases are due to a genetic problem inherited from either the mother or father.
The most common way of diagnosing it at the moment is amniocentesis -- a test that involves inserting a fine needle through the abdominal wall to the uterus to remove a small quantity of the amniotic fluid. This fluid then undergoes biochemical and chromosomal analysis to spot certain abnormalities in the fetus.
The procedure normally is carried out between the 15th and 20th week of the pregnancy. It is often distressing for the mother because chromosome tests can take several weeks to process. This means that, if the mother opts for a termination because the results show there are defects, it has to be performed when she is well into her pregnancy.
Because of the risk of miscarriage, the test normally is only offered to women aged over 35, when the risk of Down's syndrome exceeds the risk of losing the baby because of the amniocentesis, or if there is a family history of abnormalities.
Some women are offered an alternative test -- known as chorionic villus sampling (CVS) -- which can be performed much earlier than an amniocentesis, from around 12 weeks, where a tiny quantity of tissue can be taken from the placenta. However, this too carries a risk of miscarriage.
The hope is the new technique will be easier and safer. Scientists at the Chinese University of Hong Kong identified three women who were carrying fetuses already known to have the most common form of Down's syndrome, and 10 others who were carrying babies with normal chromosomes.
At 12 weeks gestation, doctors took a tiny sample of each mother's blood. Then they took another sample at 15 weeks, after some of the women had undergone CVS testing. The reason for this was that CVS could introduce fetal cells into the mother's blood during the procedure. The scientists wanted to see if the same cells were already there before the pregnant women underwent any tests.
Using a technique called fluorescence in-situ hybridization (FISH) -- where fluorescent markers are used to paint a picture of the part of the chromosome under investigation -- the researchers were able to pinpoint fragments of fetal DNA.
In all three Down's syndrome cases, they were able to detect the chromosomal abnormalities from the mother's blood early on in the pregnancy. After each woman had CVS testing, they checked the samples again and found the same defects.
"These results indicate that these cells were present in maternal plasma before the invasive procedure," the researchers write. "We have shown that prenatal detection can be accomplished by FISH analysis of fetal cells harvested from maternal plasma. The procedure is simple, and our data suggest future large-scale trials should be initiated to assess the diagnostic accuracy of this method."
Despite the fears of miscarriage, tests like amniocentesis and CVS are relatively safe, says Deborah Driscoll, MD, associate professor of medicine at the University of Pennsylvania's department of obstetrics and gynecology in Philadelphia. But because of the miscarriage fears, doctors are looking to make more options available. That is what's motivating investigators like the ones here to look for tests that are easier to do and come with lower risks than those commonly used today.
As for this research, "this is very preliminary and interesting, but it's still too premature if this will be clinically useful," says Driscoll, a geneticist and obstetrician at Penn.
"Clearly it is easier to do this test, but whether it will be as sensitive [as the standard tests today] remains to be seen," she tells WebMD.
Driscoll says that CVS and amniocentesis give more information than just the signals of Down's syndrome. Doctors get the number of chromosomes present and they can see the chromosomes' structure. Clinicians are not going to stop doing these standard tests and lose all that other important information in order to do a test for just one genetic abnormality. But the study should spark more research into finding more testing options for future patients, she says.
June 9, 2006 -- Bed alarms may be the most effective way to cure bedwetting, according to a new review of available bedwetting treatments.
But researchers Kelly Russell, BSc, and Darcie Kiddoo, MD, FRCSC, from the University of Alberta in Canada, say the device can be difficult to use, and treatment with the drug desmopressin may be an effective alternative.
The results appear in Evidence-Based Child Health: A Cochrane Review Journal.
From 13% to19% of boys, and 9% to 16% of girls over the age of 5 wet the bed during the night. Bedwetting resolves naturally in about 15% of those children each year, but researchers say 2% to 3% of adolescents continue to wet the bed and may require treatment.
Training First, Drugs Second, to Treat Bedwetting
In the study, researchers reviewed 230 studies on currently available treatments for bedwetting and compared their effectiveness in achieving 14 or more consecutive dry nights.
The results showed that training with a bed alarm was the most successful way to end bedwetting and prevent relapses after treatment ends. The alarm goes off when the child urinates. The goal is to get the child to associate the alarm with inhibiting urination so he will get up to use the toilet.
The alarms don't always wake the child, even though the rest of the house is roused. However, researchers say the treatment can still succeed if the family works together and wakes the child when the alarm goes off.
Similarly, researchers found behavioral treatments, like rewarding a child for a dry night, or taking him or her to the toilet late at night, may also work. But these methods can be very time-consuming and there was no evidence about their effectiveness.
Nonetheless, since there is no medical risk associated with behavioral treatments, researchers say they may be a reasonable first approach for parents before they seek professional help.
Desmopression Best Among Drug Options
Of the available bedwetting drug treatments, desmopression and tricyclic antidepressants were better than placebo at increasing the number of dry nights. But there was no evidence the benefit continues once treatment stops.
Researchers say there are concerns about overdosing with tricyclics. Therefore, desmopression is preferred.
Other available drug treatments, including indomethacin, diclofenac, and diazepam, may also reduce bedwetting, but researchers say they are potent drugs and should be considered only after other treatments have failed.
SOURCES: Russell, K. Evidence Based-Child Health: A Cochrane Review Journal, June 8, 2006; vol 1: pp 5-8. News release, John Wiley & Sons.
|補體B因子Factor B complement BF||S||0.2～0.5g/L||0.01|
|C3裂解產物C3 split product C3SP||S||-||同左|
|白細胞殺菌功能試驗||B 15min |
類風濕因子 RF ＜60IU/ml
|抗核抗體 ANA ＜1:160IFA||雙鏈DNA抗體||抗甲狀腺球蛋白抗體|
|（八）激素及藥物的免疫檢驗 參見第 頁 |
|紅細胞計數 RBC count||初生2周內 |
|白細胞計數 WBC count||4～10×109/L||106||4000～10000/μl|
|白細胞分類計數 WBC-DC||末梢血||3～5%中性帶狀核 |
|血小板計數Blood platelet count Pt,PT||100～300×109/L||1||10萬～30萬/μl|
|網織紅細胞計數Retculocyte count REC||0.5～1.5% |
|點彩紅細胞計數Stipping erythrocyte count||0～0.8%||-||同左|
|變性珠蛋白小體Heinz body MCT||男||41～53%||-||同左|
|紅細胞沉降率Erythrocyte sedimentation ESR||B Westergren |
|血塊收縮時間Clot retraction time CRT||1h后開始，24h后結束||-||同左|
|出血時間Bleeding time BT||Duke||1～3min||-||同左|
|血凝時間Clotting time CT||5～8min||-||同左|
|凝血酶原時間Prothrombin time PTT||一步法Quick||11～15s||-||同左|
|凝血酶原消耗試驗Prothrombin consamption PTCT||＞30s||-||同左|
|凝血酶時間Thrombin time TT||16～18s||-||同左|
|游離肝素時間Free heparin time FHT||P加甲苯胺藍||TT縮短＞5s||- |
|凝血活酶生成試驗Thromboplastin generation test TGT||STGT10～14s||＞15異常||-||同左|
Factor ⅩⅢdeficiency screening test
|P||Ⅷ：C102.96 ±26.97% |
|血漿比重Plasm specific gravity||1.024～1.029||-||同左|
|Erythrocyte osmotic –fragility test||完全溶血||3.0g/L NaCl液||-||0.3%NaCl液|
|自身溶血試驗Autohemolysis test||不加糖24h |
|熱溶血試驗Warm hemolysis test||陰性||-||陰性|
|冷溶血試驗Cold hemolysis test |
冷凝集試驗 Cold agglutinin test
|蔗糖溶血試驗Sucrose hemolysis test||定性 |
|酸化溶血試驗Acidified serum lysis test||溶血率||＜5%||-||陰性|
|血液熱不穩定試驗Heat instability test||＜5%||-||陰性|
|不穩定血紅蛋白檢查Unstable hemoglobin||加熱法||＜5%(異丙醇法 陰性)||-||陰性|
|血紅蛋白溶解度試驗Hemoglobin solubility test||88～100(平均94.4)%||-||陰性|
|高鐵血紅蛋白還原試驗Methemoglobin reduction test||還原率||＞75%(定性陰性)||-||陰性|
|G6PD缺陷篩選試驗G6PD deficiency screening test||陰性||-||陰性|
|紅細胞G6PD測定Erythrocyte G6PD assay||520～1040U/nmolHb||64.5||7.9～16.3U/gHb|
|HbF酸洗脫試驗HbF acid elution test||Rbc 新生兒 |
|還原型谷胱甘肽測定Reduced gluta-thione test||0.29～0.56mol/molHb||0.0645||4.49～8.65μmol/gHb|
|谷胱甘肽穩定試驗Glutathione stability test||GSH||減少不>20%||-||同左|
阿司匹林耐量試驗Aspirin tolerance test ATT
|血小板壽命測定Platelet life span assay||B 同位素法 |
|血小板表面相關抗體 PA||BLT PAIgG |
|Platelet adhesiveness test PAdT||女||（39±5）%|
|血小板第3因子有效性試驗 PF3QT||BLT 白陶土法||第一組比第二組延長≤5s||-||同左|
|血小板第4因子試驗Platelet factor 4 test||P||＜10μg/L||-||同左|
|活化凝血時間測定Activated clotting time ACT||B||70～100s||-||同左|
|活化凝血時間測定Activated clotting time ACT||B||70～100s||-||同左|
|復鈣交叉試驗Cross Pecalcification test||P||延長的復鈣時間不能被等量正常血漿糾正者提示有抗敏物質|
|簡易凝血活酶生成試驗 STGT||P火箭電泳法 |
|蝰蛇蛇毒時間測定Russell’s Viper venon time test||P||12～17s||-||同左|
|蝰蛇毒磷脂凝固時間Venon Phaspholipid Coag.test||P||7～12.5s||-||同左|
|蝰蛇毒復鈣時間Venon recalcificatione time test||P||19.2±2.8s||-||同左|
|血漿因子Ⅴ活動度測定Foctor Ⅴactivity test||P 一期法||102.4±37.9||同左|
|血漿因子Ⅶ活動度測定Foctor Ⅶastivity test||P 一期法||104±19.2||同左|
|血漿因子ⅩⅢ活性測定FoctorⅩⅢastiviity test||P 半定量法||24h內凝塊不溶解||同左|
|血漿因子ⅩⅢα與β亞基抗原測定Factor ⅩⅢsubunit α&βantigen test||P ⅩⅢαAg |
|優球蛋白溶解時間Euglobulin clot lysis time||PP 加酶法 |
|纖溶活性測定Fibrinolytic activity test||P||同左|
|纖溶酶原測定 Plasminogen test||P免疫擴散法 |
|魚精蛋白副凝時間Protamine paracoagutation time||陰性|
|連續凝血酶時間Serial thrombin time||18～38s|
|葡萄球菌猬集試驗Staph.clumping test SCT||陰性|
|纖維蛋白原降解產物Fibrinogen degrad prod FDP||＜10mg/L||＜10μg/ml|
|抗凝血酶Ⅲ抗原測定Antithrombin ⅢAg AT-Ⅲ.Ag||0.029±0.006g/L|
|血液紅細胞容量測定Red cell volume||男 |
|全血容量Total blood volume||60～80ml/kg||-||同左|
|紅細胞壽命測定Red cell life span assay||凝集反應法 |
|比粘度測定Viscosity assay||B毛細玻管法 |
|analysis of data||分析資料|
|analysis of variance(ANOVA)||方差分析|
|arithmetic weighted mean||加權算術均數|
|bivariate normal population||雙變量正態總體|
|case fatality rate(or case mortality)||病死率|
|coefficient of correlation||相關系數|
|coefficient of regression||回歸系數|
|coefficient of variability(or coefficieut of variation)||變異系數|
|collection of data||收集資料|
|combined standard deviation||合并標準差|
|combined variance(or poolled variance)||合并方差|
|completely random design||完全隨機設計|
|correction for continuity||連續性校正|
|correction for grouping||歸組校正|
|degree of confidence||可信度，置信度|
|degree of dispersion||離散程度|
|degree of freedom||自由度|
|degree of variation||變異度|
|design of experiment||實驗設計|
|deviation from the mean||離均差|
|diagnose accordance rate||診斷符合率|
|difference with significance||差別不顯著|
|difference with significance||差別顯著|
|equation of linear regression||線性回歸方程|
|error of replication||重復誤差|
|error of type II||Ⅱ型錯誤，第二類誤差|
|error of type I||Ⅰ型錯誤，第一類誤差|
|homogeneity of variance||方差齊性|
|homogeneity test of variances||方差齊性檢驗|
|inspection of data||檢查資料|
|latin sguare design||拉丁方設計|
|least significant difference||最小顯著差數|
|least square method||最小平方法，最小乘法|
|linear regression eguation||直線回歸方程|
|logarithmic normal distribution||對數正態分布|
|matched pair design||配對設計|
|mean of population||總體均數|
|method of least squares||最小平方法，最小乘法|
|method of grouping||分組法|
|method of percentiles||百分位數法|
|mid-value of class||組中值|
|normal probability curve||正態概率曲線|
|percentage bar chart||百分條圖|
|planning of survey||調查計劃|
|power of a test||把握度，檢驗效能|
|public health statistics||衛生統計學|
|random numbers table||隨機數目表|
|randomized blocks analysis of variance||隨機單位組方差分析|
|randomized blocks design||隨機單位組設計|
|range of normal values||正常值范圍|
|rank correlation coefficent||等級相關系數|
|relative ratio with fixed base||定基比|
|schedule of survey||調查表|
|simple random sampling||單純隨機抽樣|
|size of sample||樣本含量|
|sources of variation||變異來源|
|standard error (SE)||標準誤|
|standard error of estimate||標準估計誤差|
|standard error of the mean||均數的標準誤|
|standardized normal distribution||標準正態分布|
|sum of cross products of||隨機變量|
|deviation from mean||離均差積和|
|sum of ranks||秩和|
|sum of sguares of deviation from mean||離均差平方和|
|test of normality||正態性檢驗|
|test of one-sided||單側檢驗|
|test of one-tailed||單尾檢驗|
|test of significance||顯著性檢驗|
|test of two-sided||雙側檢驗|
|test of two-tailed||雙尾檢驗|
|treatment of date||數據處理|
|two-factor analysis of variance||雙因素方差分析|
|type I error||第一類誤差|
|type II error||第二類誤差|
|velocity of development||發展速度|
|velocity of increase||增長速度|