Biparietal diameter and crown-rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome.

OBJECTIVES: 1. To compare the ultrasound biparietal diameter and crown-rump length of fetuses with and without Down's syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Down's syndrome. DESIGN: Matched case-control study. Cases were singleton Down's syndrome pregnancies with a biparietal diameter or a crown-rump length recorded. Five controls were matched to each case on: medical centre; the date of the ultrasound scan examination (within two years); gestational age measured as the number of days since the first day of the last menstrual period; and the ultrasound measure used (ie the biparietal diameter (the measure of choice), or the crown-rump length otherwise). If a woman had a serum screening test for Down's syndrome, the biparietal diameter or crown-rump length measurement had to be taken prior to the screening test so that the result of the test could not influence whether a scan was performed. SETTING: Ten antenatal screening centres in seven countries in Europe and North America. SUBJECTS: Two hundred and one women with singleton Down's syndrome pregnancies and 1005 women with unaffected singleton pregnancies. RESULTS: The median biparietal diameter of fetuses with Down's syndrome was identical to that among the controls (median difference 0.0 mm, 95% confidence intervals (CI) -0.5 to 0.5 mm). The estimates of gestational age based on biparietal diameter yielded a median gestational age less than that based on the women's last menstrual period: three days less for cases and two days less for controls; small but statistically significant differences probably reflected a minor systematic difference in the conversion of a biparietal diameter to a gestational age estimate. The median crown-rump length of fetuses with Down's syndrome was also identical to that among controls (median difference 0.0 mm, 95% CI-1.5 to 2.0 mm). There was no significant difference between the median gestational age estimate based on crown-rump length and that based on the women's last menstrual period. CONCLUSION: In antenatal screening for Down's syndrome the routine use of an ultrasound biparietal diameter or crown-rump length measurement to estimate gestational age will not adversely affect the detection rate. To avoid differences in gestational age estimates using the last menstrual period and the biparietal diameter influencing screening performance, separate medians should be derived for each serum marker using the two methods of estimating gestational age. The appropriate set of medians can then be used to calculate the multiple of the median value for each woman screened depending on the method used to estimate her gestational age.

[Correlation between elevated maternal serum alpha-fetoprotein, certain pregnancy complications and fetal death]. / Emelkedett anyai szérum alfa-fötoprotein szint összefüggése bizonyos terhességi szövödményekkel és a magzati halálozással.

In a prospective epidemiological study of 23,792 singleton pregnancies the authors investigated the relationship between elevated maternal serum alfa-fetoprotein level and the risk of pathological pregnancy outcome. It has been found that elevated level of maternal alfa-fetoprotein (above 2.5 MoM) is associated with a higher risk of pathological pregnancies and an increased risk of subsequent fetal death. Physicians should be aware of the benefits of the maternal alpha-fetoprotein screening not only in the context of prenatal detection of congenital defects, but also in early identification of increased risk of certain obstetric complications.

[Relationship between congenital heart disease and various factors affecting pregnancy]. / A veleszületett szívhibák és a terhesség alatt ható különbözö tényezök közötti kapcsolat vizsgálata.

In a prospective epidemiological study data of 24,732 pregnancies were analysed by computer programmes for the incidence of congenital heart disease (CHD) and its relationship to various factors affecting pregnancy (age and weight of mother, smoking, alcohol-, and coffee-consumption, usage of oral contraception). Frequency of CHD was 0.9%. Data showed that CHD could be associated with alcohol consumption, smoking, maternal age. Other factors like coffee consumption or taking oral contraceptive tablets did not influence the frequency of CHD. Authors conclude that in the prevention of CHD, reduction or even omission of both alcohol consumption and smoking are highly justified.

PIP: The frequency of congenital heart disease in a neonatal population and the possible correlation between congenital heart disease and factors exerting an influence during pregnancy such as smoking, alcohol consumption, coffee drinking, maternal age and contraceptive use before and during pregnancy were studied. The data of 24,732 children born in the country of Baranya, Hungary between January 1, 1985 and June 30, 1990 were analyzed utilizing the computer-assisted System of Pregnancy Control and Registration. The frequency of congenital anomalies was .9% in this population, higher than the rate found in the research literature. The odds ratio was twice as high as the average value for pregnant women under 16 and 3 times as high for those over 41. There was not eve a weak stochastical connection between the weight of the mother and congenital defects. On the other hand, the number of cigarettes smokes had a significant effect on risk: the odds were almost 3 times higher among those smoking 11-20 cigarettes. This fact necessitates increased efforts at education. The chi-square test (p=0) indicated a close correlation between alcohol consumption and congenital heart disease. The Yule measurement number (.54) indicated a medium stochastical link. A total of 938 women (3.4%) were regular alcohol users, and the odds ratio in their children was 3.5 indicating a 3 1/2 times higher risk of giving birth to children with congenital heart disease. The confidence interval ranged between 2.3 and 5.3. The weak stochastical connection regarding the effect of oral contraceptives suggests that children of women taking oral contraceptives before pregnancy face a lower risk of congenital heart disease. There was no significant connection between coffee drinkers (119/13,739 = .87%) and nondrinkers (104/10.995 = .94). The moderation or complete cessation of smoking and alcohol consumption during pregnancy could reduce the risk of congenital anomalies.

[Screening for diabetes in obese pregnant women]. / A gestatiós diabetes szürése elhízott terheseknél.

Oral glucose tolerance testing (oGTT) was performed according to WHO criteria among obese pregnant women (body mass index greater than 28) who were recruited with the help of computerized pregnancy counselling data base. oGTT was carried out for the first time between gestational ages of 16-20 weeks, and it was repeated monthly as far as possible. Gestational diabetes was diagnosed in 4 cases out of 50 obese patients. Two gestational diabetic patients needed insulin treatment. According to computerized data obese patients have significantly higher risk of having macrosomic infants and/or intrauterine death. Fasting blood glucose values of obese pregnant women were significantly higher in all the gestational ages. It is emphasized that obesity means a risk factor for gestational diabetes, but the onset of carbohydrate intolerance may be prevented or diagnosed as early as possible with the help of repeated oGTT during pregnancy and dietary counselling. In this way fetal complications, especially macrosomia will not develop.

[Effect of oral contraceptives on developmental anomalies and on the sex ratio of newborn infants]. / Az orális kontraceptivumok hatása a fejlödési rendellenességek és az újszülöttek nemi arányának alakulására.

Several studies have suggested that maternal use of oral contraceptives before and early pregnancy may be associated with various congenital malformations. It had been found according to the computer-analysis of epidemiologic data of 17,031 single pregnancies--the use of oral contraceptives taken prior to conception or during early pregnancy has not been proved to increase the frequencies of the malformation of the offspring. On the other hand it was found, that oral contraception used before and in the early pregnancy increases the chance that infants delivered subsequently will be female.

Passive smoking in utero: no objective morphogenetic changes in the neonate.

The relationship between smoking during pregnancy and minor morphogenetic and anthropometric variants of the fetus was investigated in a case-control study. Sixty infants of mothers admitting to have smoken more than 20 cigarettes a day during pregnancy were matched to 120 infants of non-smoking mothers. No differences in the prevalence of 54 informative morphogenetic variants and in the values of 31 anthropometric measurements and indices were found.

Screening for gestational diabetes among women who have previously had a large baby or a stillborn infant.

In Baranya county, Hungary oral glucose tolerance tests were done according to WHO recommendations in pregnant women with a history of a previous baby weighing greater than or equal to 4000 g and/or a previous unexplained intrauterine fetal death. The first oral glucose tolerance test was done at 16-20 weeks gestation, and it was repeated monthly if it was normal. Patients with impaired glucose tolerance or gestational diabetes were treated by diet and/or insulin. 152 patients were involved in the screening program. Twenty-six of 81 patients had a "lag" curve blood glucose still above 5.5 mmol/ at 180 min.

[The value of determination of human chorionic gonadotropin beta subunit in extrauterine pregnancies]. / A human chorion gonadotropin béta-subunit meghatározás értéke méhen kívüli terhességekben.

The authors deal with the value of the avidin-biotin enzyme immunoassay (A-B-Elisa) which was introduced by them for the demonstration of human chorion gonadotropin beta subunit (HCG-b). It is pointed out that the possibility of the diagnosis of extrauterine pregnancy improved significantly by measuring the HCG-b level with A-B-ELISA method. The HCG-b hormone level over 5 mIU/ml refers to trophoblast activity and it is absolutely necessary to observe the patients in this case. In cases where the HCG-b level is low and the clinical symptoms are uncertain the patient must be kept under close observation and serial serum samples must be examined. Significant rise of HCG-b level refers to normal intrauterine pregnancy whereas a slightly rising, or unchanging or even decreasing hormone level suggest the possibility of extrauterine gravidity.

ELISA test for the detection of an immunological blocking factor in human pregnancy serum.

We have previously shown that progesterone-treated lymphocytes of healthy pregnant women can produce a 34 kDa protein, progesterone-induced blocking factor (PIBF) capable of blocking lymphocyte function in vitro. Lymphocytes of women with idiopathic threatened pre-term delivery failed to produce this factor. On the assumption that the PIBF appears in the serum of healthy pregnant women but not in that of women at risk for immunologically based abortion of pre-term delivery, an ELISA has been designed for detecting the blocking factor in serum samples. Sera obtained at the time of delivery, as well as those from women with pre-term deliveries or miscarriages, contained significantly less PIBF than sera of 209 healthy pregnant women. Data obtained by testing sera of women at 16 weeks gestation whose pregnancies ended in spontaneous abortion showed that the predictive value of the test depended on the time interval between blood sampling and the onset of abortion. In 11 of 13 women with uterine contractions the outcome of pregnancy was predictable by normal or lower than normal levels of PIBF in the sera taken at the time the symptoms were presented. The data suggest that determination of PIBF in pregnancy serum might contribute to the diagnosis of immunologically bases pre-term disruption of pregnancy.

[Early screening of gestational diabetes in high risk pregnancy cases]. / A gestatios diabetes korai szürése "high risk" terhesek körében.

Oral glucose tolerance testing was performed according to WHO criteria among pregnant women with historical risk factors for gestational diabetes (a previous baby weighing 4000 g or more, a previous unexplained intrauterine death) in Baranya county. Oral glucose tolerance test was carried out for the first time between gestational ages of 16-20 weeks, and it was repeated monthly in cases of normal curve. Patients with impaired glucose tolerance or diabetes were cared, dietary of prophylactic insulin treatment was introduced. 152 patients were involved in the screening program. 26 patients had gestational diabetes or impaired glucose tolerance. The glucose tolerance test curve was "stretched" in 81 patients. Early screening and management of pregnant women with maternal historical risk factors is emphasised from the view of diminishing complications, especially the frequency of macrosomia.

Amniotic fluid beta-2 microglobulin in normal and complicated pregnancies.

Beta-2 microglobulin concentrations were measured in amniotic fluid samples obtained from normal pregnant women at various stages of gestation and complicated pregnancies during weeks 32-42 of gestation by the ELISA method. The concentration of beta-2 microglobulin in amniotic fluid increases markedly up to the 20-24th weeks of pregnancy and reaches a peak during the second trimester, occasionally reaching an eightfold value compared to the maternal serum concentration, while at term the values are similar. The decrease of amniotic fluid beta-2 microglobulin level in the third trimester reflects the maturation of foetal renal tubular function and suggests that this test may be of significance in determining foetal age. Our results revealing elevated concentrations of beta-2 microglobulin in patients with diabetes, toxaemia and placental insufficiency may indicate slower renal maturation of the foetus.