Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.

OBJECTIVE: To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. METHODS: Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. RESULTS: Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. CONCLUSION: Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies.

Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss.

OBJECTIVE: The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception. METHODS: In a prospective multicenter observational study women with a twin pregnancy had an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin. RESULTS: Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7/64) among naturally conceived MC compared to 3.0% (5/165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth-before 28 weeks' gestation-was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins. CONCLUSION: The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins.

How to identify twins at low risk of spontaneous preterm delivery.

OBJECTIVE: The aim of this study was to evaluate transvaginal sonographic assessment of cervical length at 23 weeks as a screening test for spontaneous preterm delivery in order to define a cut-off value that could be used to select twin pregnancies at low risk of spontaneous preterm delivery. METHODS: In a prospective multicenter study of 383 twin pregnancies included before 14 + 6 weeks a cervical scan with measurement of the cervical length was performed at 23 weeks' gestation. The results were blinded for the clinicians if the cervical length was > or = 15 mm. The rates of spontaneous delivery at different cut-off levels of cervical length were determined. RESULTS: Eighty-nine percent of the twins had dichorionic placentation and 58% were conceived after assisted reproduction. The rate of spontaneous preterm delivery was 2.3% (1.5% for dichorionic (DC) and 9.1% for (MC) monochorionic twins) before 28 weeks and 18.5% (17.1% for DC and 29.5% for MC twins) before 35 weeks. The screen-positive rate was 5% for a cervical length < or = 20, 7-8% at < or = 25, 16-17% at < or = 30 and 34-48% at < or = 35 mm depending on chorionicity. The false-negative rate (1 - negative predictive value) ranged from 1.2% at 28 weeks to 18.6% at 35 weeks for all twins. Receiver-operating characteristics curves showed that the sensitivity increased with declining gestational age with cut-off levels of highest accuracy at 21 mm for 28 weeks and 29 mm for 33 weeks. CONCLUSIONS: Cervical length measurement at 23 weeks of gestation is a good screening test for predicting twins at low risk of preterm and very preterm delivery, especially in DC twins. The present results suggest that a cut-off of 25 mm should be recommended.

Testicular feminization syndrome and associated gonadal tumors in Denmark.

We studied the incidence of testicular feminization syndrome in Denmark over a 7-year period and found it to be about 1:20,400. Twenty-one patients are described in greater detail. Four patients had gonadal tumors, none of these being malignant. Ten patients (47.6%) had inguinal hernias in early childhood. All patients but one were gonadectomized. Eleven patients (52.4%) disclosed signs of partial androgen function. Only 5 of them had their gonads removed immediately.

An evaluation of clinical estimation of fetal weight and symphysis fundal distance for detection of SGA infants.

In 58 small for gestational age (SGA) infants and 141 non-SGA infants, the measuring of symphysis fundal distance (SF) was compared with clinical estimation of fetal weight in order to evaluate the efficacy of the two methods of predicting SGA. By regression analyses, the SF curve deviation explains 22% of the variation of birthweight. The estimated fetal weight (EFW) curve deviation explains 40%. By combining the two values, 42% of the variation in birthweight is explained. When receiver operating characteristic (ROC) curve analyses, Kappa index and relative risk were applied the clinical estimation of fetal weight by abdominal palpation was found to be as reliable a predictor of SGA at birth as the measurement of the SF distance. Statistical analyses of the SF curve and EFW curve do not improve the results compared with the last measurement of SF distance and EFW. Combination of the EFW and SF measurements results in a higher sensitivity (one test positive) or a higher predictive value (both tests positive). Only marginal additional diagnostic information was achieved, however, as the ROC curves, Kappa index and Relative risk were nearly unchanged, regardless of combination of EFW and SF measurements.

Serum pharmacokinetics of orally administered desogestrel and binding of contraceptive progestogens to sex hormone-binding globulin.

Serum levels of 3-ketodesogestrel and ethinyl estradiol were analyzed by radioimmunoassay in a balanced crossover study with two tablet formulations containing desogestrel (0.150 mg) and ethinyl estradiol (0.030 mg) in 25 women under steady-state conditions after 21 days of treatment. The pharmacokinetic properties of desogestrel were characterized by the following parameters: (1) maximum serum concentration, (2) time to maximum serum concentration, (3) total area under the serum concentration versus time curve, and (4) serum half-life of elimination. The interindividual variation in these parameters was comparable with that observed with other contraceptive combinations containing ethinyl estradiol and norethisterone, levonorgestrel, or gestodene. The serum distribution of contraceptive progestogens is known to be determined by their affinity to sex hormone-binding globulin and the concentration of sex hormone-binding globulin. We analyzed the structural features that determine binding to sex hormone-binding globulin. The 18-methyl group increased and the 11-methylene group weakened the binding to sex hormone-binding globulin. The double bond at C-15 reinforced the binding only when combined with an 18-methyl group. Therefore, the binding of levonorgestrel (the 18-methyl derivative of norethisterone) and gestodene (the delta-15,18 methyl derivative of norethisterone) to sex hormone-binding globulin was much stronger than that of 3-keto-desogestrel and norethisterone.

PIP: Serum levels of 3-ketodesogestrel and ethinyl estradiol (EE) were analyzed by radioimmunoassay in a balanced crossover study with 2 tablet formulations containing desogestrel (0.150 mg) and EE (0.030 mg) in 25 women under steady-state conditions after 21 days of treatment. The pharmacokinetic properties of desogestrel were characterized by the following parameters: maximum serum concentration, time to maximum serum concentration, total area under the serum concentration vs time curve, and serum 1/2 life of elimination. The interindividual variation in these parameters was comparable with that observed with other contraceptive combinations containing EE and norethisterone, levonorgestrel, or gestodene. The serum distribution of contraceptive progestogens is known to be determined by their affinity to sex hormone- binding globulin (SHBG) and the concentration of SHBG. The authors analyzed the structural features that determine binding to SHBG; the 18- methyl group increased and the 11-methylene group weakened the binding to SHBG. The double bond at C-15 reinforced the binding only when combined with an 18-methyl group. Therefore, the binding of levonorgestrel (the 18-methyl derivative of norethisterone) and gestodene (the delta-15, 18 methyl derivative of norethisterone) to SHBG was much stronger than that of 3-ketodesogestrel and norethisterone.

C-reactive protein during normal pregnancy.

Serum C-reactive protein (CRP) is determined in a prospective longitudinal study of 60 low-risk pregnant women. CRP is also measured in umbilical-cord blood after delivery. The serum CRP concentrations seem to be independent of pregnancy and gestational age. The 95th percentile is estimated to be 20 mg/l, and this value is considered as the upper limit of normal. A rise in CRP level is considered more predictive of infection than a determination of a single high value. CRP does not cross the placental barrier, and may therefore be useful in diagnosing infections in newborns.

Iron, zinc and folate status during pregnancy and two months after delivery.

Iron, zinc and folate statuses of 45 women were determined during pregnancy around 12, 20, 28, 32 and 36 weeks, and again 2 months after delivery. Analyses of plasma ferritin, Hb, MCV, folate and zinc in plasma and whole blood were performed. Iron supplementation was recommended from mid-pregnancy but 13 of the participants did not use the iron supplements. This group had significantly decreased levels of plasma ferritin and MCV at the end of pregnancy, but none developed anemia. Two months post partum the plasma ferritin of the unsupplemented group had normalized and was in the same range as in the supplemented group. The concentrations of zinc in plasma and whole blood and the calculated levels of red cells were low even at the first examination around 12 weeks of gestation, compared with non-pregnant women. Throughout the course of pregnancy the plasma zinc levels continued to decrease, while the whole blood and red cell levels showed a significant rise. At term of gestation almost half the women had subnormal plasma folate levels (L. casei), which persisted during the post partum follow-up. The corresponding value for red cell folate was 10% below normal values at term and 30% subnormal 2 months after parturition. These findings stress the importance of extending the observation period to include also the lactating period, in order to judge the need for folate supplementation.

Ferritin concentration in cerebrospinal fluid.

15 patients with psychosomatic disease, 26 patients with miscellaneous neurological diseases, and 16 patients with cerebrovascular disease were investigated with regard to concentrations of ferritin in serum and cerebrospinal fluid (CSF). The mean CSF ferritin concentration in the psychosomatic group was 6.2 micrograms/l +/- 2.4 (1 S.D.). Patients with recent cerebral infarction had similar values while 2 patients with intracerebral hematomas had very high CSF ferritin concentrations. There was a positive correlation between serum and CSF ferritin levels and between CSF total protein and ferritin in patients with a damaged blood-CSF barrier only. At present, the practical value of analysing ferritin in the CSF is very small.

Submucous paracervical blockade compared with intramuscular meperidine as analgesia during labor: a double-blind study.

A double-blind study was carried out to compare the effect of submucous paracervical blockade using 12 mL 0.25% bupivacaine (55 women) to the effect of intramuscular injection of 75 mg meperidine (62 women) during the first stage of labor. All 117 were normal primiparous pregnancies. Seventy-eight percent of the women in the paracervical blockade group achieved full or acceptable pain relief against 31% in the meperidine group (P less than .01). Transient fetal bradycardia occurred in two cases in the paracervical blockade group and one in the meperidine group; all infants were born in good condition. Fetal distress, defined as an umbilical artery pH of 7.15 or less and/or a one-minute Apgar score of 7 or less was more frequent in the meperidine group (16 infants) than in the paracervical blockade group (six infants) (P less than .05). Submucous paracervical blockade is superior to intramuscular meperidine as pain relief during labor. Furthermore, meperidine results in more infants with asphyxia as compared with paracervical blockade.

Zinc, copper, magnesium, and calcium in blood and plasma after phlebotomy.

Zinc levels in plasma and whole blood were investigated in 2 groups of blood donors. The first group consisted of 19 men and 11 women who donated blood for the first time and were followed during 3 phlebotomies. The second group comprised 44 men with 9 or more previous blood donations, their blood being analysed on a single occasion. Plasma concentrations of copper, magnesium, calcium and ferritin were also analysed. The zinc levels in whole blood and plasma in the second group were significantly lower as compared to the first group (P less than 0.001). Furthermore, the second group had significantly higher levels of copper and copper:zinc quotient in plasma as compared to those of the new blood donors (P less than 0.001). Our results indicate that besides the earlier known effect of blood donation on iron stores, there are also signs of zinc depletion when judged from the zinc levels in plasma and in erythrocytes. No significant changes in calcium and magnesium concentrations were seen during phlebotomy.

Serum ferritin in the elderly.

A two-site immunoradiometric assay for human ferritin has been developed using antibody-coated polystyrene tubes. Serum ferritin was measured in fifty-four men and women aged 73 years. The geometric mean was 166 micrograms/l for thirty-one men and 161 micrograms/l for twenty-two women. One woman was excluded from the statistical calculations. Twenty-eight of the subjects had earlier participated in a study of food consumption by the duplicate portion technique. There was a significant correlation (r = 0.44, P < 0.01) between the food iron intake and the serum ferritin values. A reference material of men and women aged 18-55 years was also analysed. The geometric mean for males was 170 micrograms/l with a 95% confidence range of 46-637 micrograms/l. The female controls were found to have significantly lower values (geometric mean 51 micrograms/l, 95% confidence range 10-260 micrograms/l) than both the older women (P < 0.001) and the male controls (P < 0.001).