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.

Effects of oophorectomy on functional properties of resistance arteries isolated from the cancellous bone of the rabbit femur.

Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen diameter, maximal response to high potassium, or maximal response to high potassium and 10(-5) M noradrenaline. However, OOX significantly increased the maximal response to noradrenaline (OOX 2.14 +/- 0.36 N/m, Sham 1.25 +/- 0.14 N/m) and endothelin-1 (OOX 1.76 +/- 0.32, Sham 0.95 +/- 0.15) in metaphyseal arteries. Moreover, the corresponding maximal active pressure for the agonists was significantly increased. OOX did not influence endothelial function assessed by the effects of acetylcholine or substance P. The functional responses of diaphyseal arteries were unaffected by OOX. The study demonstrates regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis.

Food-search strategy in ling (Molva molva L.): crepuscular activity and use of space.

The activity rhythm and use of space in the food-searching behaviour of ling (Molva molva L.) were studied by means of a stationary positioning system. The system consisted of a fixed array of three hydrophones, which monitored the position of each individual being tracked once every three minutes. Five ling were tagged in situ by allowing them to ingest a transmitter wrapped in bait and were tracked continuously for 6 to 11 days. Ling showed a crepuscular activity rhythm with higher levels of swimming activity at dawn and dusk. The fish occupied a home range throughout the study, and during inactive periods (about 65% of the time) they remained within a small core area. Most of the time spent outside the core area was during the period of high activity at dawn. Food-search behaviour was studied by setting mackerel-baited fishing gear in the experimental area. When baits were present, ling moved more slowly and within a more limited area, indicating area-restricted searching in the presence of a food odour. Ling responded to and located baits in both their active and inactive periods during the day, but were not observed to react at night. Comparing these findings with those from similar tracking experiments on cod (Gadus morhua L.) suggested that ling are less active at night and show a more restricted use of space by occupying a core area. This may reflect different feeding strategies between these gadoid species with ling taking a higher proportion of mobile prey and being more dependent on visual stimuli.

Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation.

Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance.

The effect of oophorectomy on mechanical properties of rabbit cerebral and coronary isolated small arteries.

OBJECTIVE: Our purpose was to study the effect of oophorectomy on the passive and active mechanical characteristics of rabbit small cerebral and small coronary arteries. STUDY DESIGN: Ring preparations of small cerebral and small coronary arteries from rabbits that had undergone oophorectomy and sham operation were mounted on myographs 6 weeks after operation. Experiments were performed as follows. (1) concentration-response relations for vasopressin (10(-11) to 10(-7) mol/L), U46619 (10(-10) to 10(-6) mol/L), 5-hydroxytryptamine (10(-7) to 10(-5) mol/L), and endothelin (10(-13) to 10(-7) mol/L); (2) relaxing effects of acetylcholine (10(-8) to 10(-4) mol/L); (3) length-tension relations after addition of high potassium (124 mmol/L), vasopressin (10(-7) mol/L), and a mixture composed of potassium (124 mmol/L), vasopressin (10(-7) mol/L), and prostaglandin F 2 alpha (10(-5) mol/L); (4) calculation of vessel morphologic features and determination of hydroxyproline as a measure of collagen content. RESULTS: Oophorectomy did not influence basal tone, relaxant effects of acetylcholine, vessel morphologic features, elastic characteristics, or hydroxyproline content of the vessels. However, in cerebral arteries at a normalized lumen diameter, oophorectomy induced a marked increase in the force development after stimulation with agonists but not after depolarization with high potassium. The reason for this was a leftward shift in the active length-tension curves (vasopressin activation). In coronary arteries none of these changes were seen after oophorectomy. CONCLUSION: These data demonstrate that withdrawal of ovarian hormones changes the position of the active length-tension curve for pharmacomechanical but not electromechanical coupling of small cerebral arteries without interference with the elastic characteristics of these vessels.

[The use of Doppler-ultrasound in obstetrics]. / Anvendelsen af Doppler-ultralyd i obstetrikken.

Several investigations have suggested an association between intrauterine growth retardation or an adverse neonatal outcome and increased vascular resistance in the fetal and maternal uteroplacental circulation assessed by Doppler-ultrasound. Meta-analysis of nine randomized controlled trials showed that the use of Doppler-ultrasound in the surveillance of high-risk pregnancies reduced the perinatal mortality considerably. Taken together, there is evidence to suggest that Doppler-ultrasound is a valuable tool for discriminating between normal small and "sick" small fetuses. Screening in unselected populations of low-risk pregnancies, however, seems to be without any benefit.

Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo-controlled study.

OBJECTIVE: Our purpose was to study the effects of isradipine, a dihydropyridine calcium channel blocker, on mother and fetus in the treatment of hypertensive disorders of pregnancy. STUDY DESIGN: The investigation was performed as a two-group, parallel, double-blind multicenter study of isradipine versus placebo. Fifty-four women were randomized to treatment with isradipine slow-release capsules given orally 5 mg twice a day and 57 to a placebo group. RESULTS: Isradipine lowered the maternal mean arterial blood pressure effectively in women with nonproteinuric hypertension but did not do so in women with proteinuria at recruitment or appearing during treatment. Blood flow in the umbilical artery and maternal renal and liver function were not influenced by treatment. Isradipine had few side effects and was well tolerated. CONCLUSION: Calcium channel blockade with isradipine is effective for treatment of nonproteinuric hypertension but not in preeclampsia.

Changes in amino acids, ammonium, and coagulation factors after transcervical resection of the endometrium with a glycine solution used for uterine irrigation.

OBJECTIVE: Transcervical resection of the endometrium with the use of 1.5% glycine for irrigation is associated with postoperative nausea in some patients. This could be because of hyponatremia or toxic effects of glycine and its metabolites. Moreover, 1.5% glycine is hypoosmolar, and hemolysis and fibrinolysis are possible. Changes in plasma factors related to these potential complications of transcervical resection of the endometrium were measured. STUDY DESIGN: In 101 patients undergoing transcervical resection of the endometrium sodium, ammonium, and coagulation factors were measured preoperatively and postoperatively at intervals. In the initial 30 patients glycine and 28 other amino acids were measured at the same intervals. The results were correlated with the patients' clinical status and operative parameters. RESULTS: Glycine and nine other amino acids and ammonia showed increased postoperative plasma levels; these changes were correlated with the absorption of the irrigating glycine solution and the development of hyponatremia. Minor activation of fibrinolysis and hemolysis was also seen. CONCLUSION: Nausea after transcervical resection of the endometrium with 1.5% glycine for irrigation may be partly explained by toxic effects of glycine and its secondary metabolites in addition to the effects of water intoxication and hyponatremia. Minor, clinically insignificant changes in the coagulation system may also occur. Studies on alternatives to glycine for creation of near-isotonic irrigating solutions are encouraged.

[Levonorgestrel IUD]. / Levonorgestrelspirale.

PIP: Levonorgestrel (LNG) has been recently introduced on the Danish market. In addition to being a contraceptive method, the LNG-releasing IUD also constitutes a therapeutic principle for idiopathic menorrhagia. The LNG-releasing IUD consists of a T-shaped plastic rod in which the vertical leg is surrounded by a cylinder that functions as a hormone reservoir and allows the release of LNG at a rate of 20 mcg/24 hours. The released hormone exerts in part a local atrophying effect on the endometrium and in part a slightly suppressing effect on the ovarian function. The preventive effect of this IUD is greater than that of the well-known copper IUD, and the risk of infection in connection with its use is significantly less. In contrast to the copper IUD, the LNG-releasing IUD reduces the amount and length of bleeding during menstruation, and only 20% of users experience amenorrhea. In Sweden and Finland LNG-releasing IUDs were compared in randomized studies to copper-T IUDs. LNG-releasing IUDs had a significantly lower Pearl index (0.1-0.6 vs. 3.3-6.7). In a multicenter study 937 women were randomized to Nova-T IUDs and 1821 women to LNG IUDs. Among LNG-releasing IUD users unwanted pregnancy occurred in 5 cases, equivalent to 0.5 per 100, and among Nova-T users 35 pregnancies occurred, corresponding to 5.9 per 100. In a Danish study with 1697 Nova-T IUD users the rate of pregnancy was even greater than 3.7/100 after 6 years of observation. In a 1994 Swedish study the rate (per 100 women) of expulsion during 5 years was 5.8 LNG and 6.7 Nova; bleeding problems 13.7 and 20.9 (p = 0.01), respectively; amenorrhea 6.0 and 0 (p = 0.001), respectively; hormonal side effects 12.1 and 2.0 (p = 0.001), respectively; and infection 0.8 and 2.2 (p = 0.01), respectively. The LNG-releasing IUD seems to be a new therapeutic method for menorrhagia. It is not yet clear whether this treatment principle can also be used for women with metrorrhagia.^ieng

The effects of dihydralazine, labetalol and magnesium sulphate on the isolated, perfused human placental cotyledon.

OBJECTIVE: To assess the effects of dihydralazine, labetalol and magnesium sulphate on the vascular tone in the isolated, perfused human placental cotyledon. METHODS: In vitro perfusion of the fetal compartment of isolated, human placental cotyledons. RESULTS: None of the drugs affected basal vascular tone. The thromboxane A2-mimic U46619 and endothelin-1 induced a concentration-dependent increment in perfusion pressure, while 5-hydroxytryptamine induced a variable increase, and norepinephrine induced a small, transient increase in perfusion pressure. After preconstriction with U46619, magnesium sulphate (1.5 x 10(-3) to 6 x 10(-3) mol/l) induced a decrease in perfusion pressure, while dihydralazine (10(-6) to 10(-4) mol/l) or labetalol (10(-7) to 10(-4) mol/l) enhanced the perfusion pressure. These effects of dihydralazine and labetalol were unaffected by treatment with indomethacin 10(-6) mol/l, but could be reversed by addition of magnesium sulphate 6 x 10(-3) mol/l. Labetalol 10(-6) to 10(-4) mol/l also caused an increase in the perfusion pressure induced by endothelin-1, but showed no effects after preconstriction with 5-hydroxytryptamine. Pretreatment with labetalol 10(-4) mol/l inhibited the transient increase in perfusion pressure induced by norepinephrine 3 x 10(-5) mol/l. CONCLUSIONS: The present data demonstrated that the commonly used vasodilating agents labetalol and dihydralazine do not produce vasodilatation in the human perfused cotyledon after vasoconstriction induced by agents of suggested importance for maintenance of fetal placental vascular tone, and that high concentrations of these drugs may even enhance vasoconstriction induced by thromboxane and endothelin-1 in this area. Magnesium sulphate may show the potential to reverse such unwanted effects of dihydralazine and labetalol.