Magnetic resonance imaging-estimated placental perfusion in fetal growth assessment.

OBJECTIVE: To evaluate in-vivo placental perfusion fraction, estimated by magnetic resonance imaging (MRI), as a marker of placental function. METHODS: A study population of 35 pregnant women, of whom 13 had pre-eclampsia (PE), were examined at 22-40 weeks' gestation. Within a 24-h period, each woman underwent an MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction), venous blood sampling and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. The perfusion fractions in pregnancies with and without fetal growth restriction were compared and correlations between the perfusion fraction and ultrasound estimates and plasma markers were estimated using linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of PE (P < 0.05) and therefore we included an interaction term between PE and covariates in the models. RESULTS: The median placental perfusion fractions in pregnancies with and without fetal growth restriction were 21% and 32%, respectively (P = 0.005). The correlations between placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (P = 0.002 and P = 0.0001, respectively). The highest coefficient of determination (R(2) = 0.56) for placental perfusion fraction was found for a model that included pulsatility index in the ductus venosus, plasma level of soluble fms-like tyrosine kinase-1, estimated fetal weight and presence of PE. CONCLUSION: The placental perfusion fraction has the potential to contribute to the clinical assessment of cases with placental insufficiency.

In vivo ³¹P-MR spectroscopy in normal pregnancy, early and late preeclampsia: a study of placental metabolism.

INTRODUCTION: Preeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥ 34 weeks) onset. (31)P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia. METHODS: The study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a (31)P-MRS examination of the placenta. RESULTS: The phosphodiester (PDE) spectral intensity fraction of the total (31)P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001). DISCUSSION: Since PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy. CONCLUSIONS: Our findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.

Risk of retained placenta in women previously delivered by caesarean section: a population-based cohort study.

OBJECTIVE: To evaluate whether women with a caesarean section at their first delivery have an increased risk of retained placenta at their second delivery. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All women with their first and second singleton deliveries in Sweden during the years 1994-2006 (n = 258,608). Women with caesarean section or placental abruption in their second pregnancy were not included in the study population. METHODS: The risk of retained placenta at second delivery was estimated for women with a first delivery by caesarean section (n = 19,458), using women with a first vaginal delivery as reference (n = 239,150). Risks were calculated as odds ratios by unconditional logistic regression analysis with 95% confidence intervals (95%) after adjustments for maternal, delivery, and infant characteristics. MAIN OUTCOME MEASURES: Retained placenta with normal (≤1000 ml) and heavy (>1000 ml) bleeding. RESULTS: The overall rate of retained placenta was 2.07%. In women with a previous caesarean section and in women with previous vaginal delivery, the corresponding rates were 3.44% and 1.96%, respectively. Compared with women with a previous vaginal delivery, women with a previous caesarean section had an increased risk of retained placenta (adjusted OR 1.45; 95% CI 1.32-1.59), and the association was more pronounced for retained placenta with heavy bleeding (adjusted OR 1.61; 95% CI 1.44-1.79). CONCLUSIONS: Our report shows an increased risk for retained placenta in women previously delivered by caesarean section, a finding that should be considered in discussions of mode of delivery.

Invasive procedures for fetal karyotyping: no cause of subsequent gestational hypertension or pre-eclampsia.

The aim was to estimate the risk of maternal hypertensive complications following first- or second-trimester invasive diagnostic procedures, i.e. chorionic villus sampling (CVS) and amniocentesis (AC). Odds ratios (ORs) for gestational hypertension, mild pre-eclampsia or severe pre-eclampsia were calculated for women who underwent CVS (n = 1,984) or AC (n = 21,748) compared with non-exposed women (n = 47,854). No increase in the development of gestational hypertension, mild pre-eclampsia or severe pre-eclampsia was observed. The results do not support an association between invasive procedures for fetal karyotyping and subsequent gestational hypertension or pre-eclampsia.

Prenatal ultrasound exposure and children's school performance at age 15-16: follow-up of a randomized controlled trial.

OBJECTIVE: To evaluate the association between prenatal ultrasound exposure and school performance at 15-16 years of age. METHODS: The study population consisted of children born to women who participated in a randomized controlled trial on the second-trimester ultrasound examination in Sweden from 1985 to 1987. Information about the children's grades when graduating from primary school and information on socioeconomic factors was obtained from Swedish nationwide registers. Comparisons were made using linear and logistic regression analyses according to randomization to ultrasound, ultrasound exposure in the second trimester and ultrasound exposure at any time during pregnancy. Boys and girls were analyzed separately. RESULTS: Of the 4756 singleton children from the randomized trial, we identified 4458 (94%) in the National School Register. There were no statistically significant differences in school performance for boys or girls according to randomization or exposure to ultrasound in the second trimester. Compared to those who were unexposed, boys exposed to ultrasound at least once at any time during fetal life had a tendency towards lower mean school grades in general (-4.39 points; 95% CI, -9.59 to 0.81 (max possible, 320) points) and in physical education (-0.45 points; 95% CI, -0.91 to 0.01 (max possible, 20) points), but the differences did not reach significance. CONCLUSION: In general, routine ultrasound examination in the second trimester had no effect on overall school performance in teenagers.

Reference values for clinical chemistry tests during normal pregnancy.

OBJECTIVE: Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. DESIGN: Longitudinal study of laboratory markers in normal pregnancies. SETTING: Uppsala University Hospital, Sweden. POPULATION: Healthy pregnant females. METHODS: We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. RESULTS: Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. CONCLUSIONS: Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

Prenatal ultrasound and the risk of childhood brain tumour and its subtypes.

We carried out a nationwide case-control study of childhood brain tumours in Sweden (n=512) by histological subtype in relation to prenatal ultrasound, extracting data from antenatal records and the Medical Birth Register. We found no increased risk for brain tumour after ultrasound exposure, either for all tumours or for any subgroup.

Prenatal X-ray exposure and childhood brain tumours: a population-based case-control study on tumour subtypes.

We investigated childhood brain tumours by histological subtype in relation to prenatal X-ray among all children, less than 15 years of age, born in Sweden between 1975 and 1984. For each case, one control was randomly selected from the Medical Birth Register, and exposure data on prenatal X-ray were extracted blindly from antenatal medical records. Additional information on maternal reproductive history was obtained from the Medical Birth Register. We found no overall increased risk for childhood brain tumour after prenatal abdominal X-ray exposure (adjusted odds ratio (OR): 1.02, 95% confidence interval (CI): 0.64-1.62); primitive neuroectodermal tumours had the highest risk estimate (OR: 1.88, 95% CI: 0.92-3.83).

Ultrasound finding of an echogenic mass in women with secondary postpartum hemorrhage is associated with retained placental tissue.

OBJECTIVES: To describe sonographic findings associated with retained placental tissue in patients with secondary postpartum hemorrhage, and to compare these findings with those of women with a normal puerperium. METHODS: This was a prospective observational study of 79 women with secondary postpartum hemorrhage. Ultrasound examinations were performed on the day the patients presented with clinical symptoms and were scheduled for postpartum days 1, 3, 7, 14, 28 and 56, continuing until uterine surgical evacuation was performed or until the bleeding stopped. The maximum anteroposterior (AP) diameters of the uterus and uterine cavity were measured and morphological findings in the cavity were recorded. The findings were compared with previously published results from a normal population. RESULTS: The patients were divided into two groups. Group 1 (n = 18) underwent surgery and Group 2 (n = 61) was treated conservatively. Sonography revealed an echogenic mass in the uterine cavity in 17 patients from Group 1, and in 14 of these patients histology confirmed placental tissue. The AP diameter of the uterine cavity was above the 90(th) percentile in all but two of the 18 Group 1 patients. In 18 patients from Group 2 the cavity was empty and in 43 a mixed-echo pattern was found. The uterine cavity was wider compared with the controls, but the values largely overlapped. CONCLUSION: This report supports the opinion that the sonographic finding of an echogenic mass in the uterine cavity in women with secondary postpartum hemorrhage is associated with retained placental tissue.

Molecular imaging using hyperpolarized 13C.

MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity of this modality has limited the clinical use to imaging of water protons. With hyperpolarization techniques, the signal from a given number of nuclear spins can be raised more than 100 000 times. The strong signal enhancement enables imaging of nuclei other than protons, e.g. (13)C and (15)N, and their molecular distribution in vivo can be visualized in a clinically relevant time window. This article reviews different hyperpolarization techniques and some of the many application areas. As an example, experiments are presented where hyperpolarized (13)C nuclei have been injected into rabbits, followed by rapid (13)C MRI with high spatial resolution (scan time <1 s and 1.0 mm in-plane resolution). The high degree of polarization thus enabled mapping of the molecular distribution within various organs, a few seconds after injection. The hyperpolarized (13)C MRI technique allows a selective identification of the molecules that give rise to the MR signal, offering direct molecular imaging.

Sinistrality--a side-effect of prenatal sonography: a comparative study of young men.

Although ultrasound during pregnancy is used extensively, there is little published on adverse fetal effects. We undertook a cohort study including men born in Sweden from 1973 to 1978 who enrolled for military service. We estimated relative risks for being born left-handed according to ultrasound exposure in fetal life using logistic regression analysis. Eligible for the study were 6,858 men born at a hospital that included ultrasound scanning in standard antenatal care (exposed) and 172,537 men born in hospitals without ultrasound scanning programs (unexposed). During the introduction phase (1973 to 1975) there was no difference in left-handedness between ultrasound exposed and unexposed (odds ratio = 1.03, 95% confidence interval (CI) = 0.91 to 1.17). When ultrasonography was offered more widely (1976 to 1978), the risk of left-handedness was higher among those exposed to ultrasound compared with those unexposed (odds ratio = 1.32, 95% CI = 1.16 to 1.51). We conclude that ultrasound exposure in fetal life increases the risk of left-handedness in men, suggesting that prenatal ultrasound affects the fetal brain.

Parahydrogen-induced polarization in imaging: subsecond (13)C angiography.

High nuclear spin polarization of (13)C was reached in organic molecules. Enhancements of up to 10(4), compared to thermal polarization at 1.5 T, were achieved using the parahydrogen-induced polarization technique in combination with a field cycling method. While parahydrogen has no net polarization, it has a high spin order, which is retained when hydrogen is incorporated into another molecule by a chemical reaction. By subjecting this molecule to a sudden change of the external magnetic field, the spin order is transferred into net polarization. A (13)C angiogram of an animal was generated in less than a second. Magn Reson Med 46:1-5, 2001.

Psychological distress before and after prenatal invasive karyotyping.

BACKGROUND: The aim was to evaluate the psychological and physical impact on women submitting to early amniocentesis or chorionic villus sampling and their preferences concerning fetal invasive procedures in a forthcoming pregnancy. METHOD: Fifty-one women undergoing early amniocentesis or chorionic villus sampling at 10-13 weeks gestation participated. The women completed questionnaires including the Hospital Anxiety and Depression Scale on three occasions: before, immediately after, and one week after the invasive procedure. RESULTS: The women were more concerned about a spontaneous abortion and waiting for the result than about a possible unreliable result. A majority of the women did not worry about the risk of fetal injury induced by the procedure. More women in the chorionic villus sampling group found the invasive procedure to be physically straining. Two-thirds of the women experienced no or minor psychological strain but one-third experienced major strain. Approximately 20% were classified as doubtful cases and cases of clinical anxiety. Nearly all women would choose to have an invasive procedure of the same kind in a forthcoming pregnancy. CONCLUSIONS: The psychological and physical impact on women undergoing invasive procedures for fetal karyotyping does not constitute a major clinical problem. However, a certain number of women report distress and anxiety which should be attended to by professionals involved in fetal invasive procedures. These women may benefit from more support.

Ultrasonic evaluation of the uterus and uterine cavity after normal, vaginal delivery.

OBJECTIVE: To describe uterine and uterine cavity changes throughout the puerperium, as revealed by ultrasound. METHODS: This was a prospective, longitudinal study in which 42 women with uncomplicated vaginal term deliveries were examined serially by ultrasound on postpartum days 1, 3, 7, 14, 28 and 56. The first four examinations were performed transabdominally and the last two transvaginally. The involution process of the uterus was assessed by measuring the anteroposterior diameter of the uterus and uterine cavity. Morphological findings were recorded. The influence on the involution process of parity, breast-feeding, maternal smoking and infant's birth weight were also evaluated. RESULTS: The maximum anteroposterior diameter of the uterus diminished substantially and progressively from 92.0 mm on day 1 postpartum to 38.9 mm on day 56. The maximum anteroposterior diameter of the uterine cavity diminished from 15.8 mm on day 1 to 4.0 mm on day 56. However, the anteroposterior diameter of the uterine cavity, 5 cm from the fundus, typically increased on days 7 and 14 postpartum. The position of the uterus and the shape and the appearance of the cavity change in a unique way during the normal puerperium. The uterus was most often retroverted and empty in the early puerperium. Fluid and debris in the whole cavity were seen in the middle part of the puerperium. In late puerperium the cavity was empty and appeared as a thin white line. Endometrial gas was occasionally visualized. No correlation was found between the involution of the uterus and parity, breast-feeding and the infant's birth weight. CONCLUSION: Transabdominal sonography is suitable for examination of the uterus during the first 14 days postpartum but from day 28 the transvaginal route is preferable. The uterine body and position, as well as the cavity, are easy to examine by ultrasound. Accumulation of fluid and debris in the uterine cavity is a common and insignificant finding of the involuting uterus. It is located in the cervical area in the early puerperium and in the whole uterine cavity in the middle part of the puerperium. Findings from uncomplicated vaginal deliveries are needed as a reference when the diagnostic efficacy of ultrasound for pathological conditions is to be tested.

Women's knowledge, concerns and psychological reactions before undergoing an invasive procedure for prenatal karyotyping.

OBJECTIVES: To evaluate women's reasons for having an invasive procedure, their knowledge, how information was obtained, their satisfaction with this information, their concerns about complications and psychological reactions and distress evoked by the procedure. METHODS: Ninety-four pregnant women undergoing early amniocentesis or chorionic villus sampling (CVS) at 10-13 weeks' gestation participated in a questionnaire study. The women could choose between early amniocentesis (n = 38) and CVS (n = 31), or to be randomized to either of them (n = 25). RESULTS: Apart from two items, no differences were found between the groups. Age was the main reason for testing, and anxiety was stated as a reason by 38.3%. The women knew more about methods for fetal karyotyping, what the tests can reveal and how they are performed, than about the risks and reliability of the tests. The main source of information had been doctors and midwives at the antenatal care center. For a majority of women (64.9%) the decision to have the test was made together with their partner. The women's concerns were focused on worry about fetal injury, miscarriage and waiting for the result. The test did not have a major psychological impact on the women in general, but a substantial minority reacted with anxiety and distress. CONCLUSIONS: Knowledge of factors important to women and their concerns is essential for professionals working with genetic counselling and performance of invasive procedures.

Outcomes of post-term births: the role of fetal growth restriction and malformations.

OBJECTIVE: To evaluate the risks of adverse pregnancy outcomes among term and post-term small for gestational age (SGA) and appropriate for gestational age (AGA) births, before and after excluding infants with congenital malformations. METHODS: We did a population-based study of 510,029 singleton term (37-41 completed weeks) and post-term (at or after 42 weeks) births recorded in the Swedish Birth Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risks of stillbirth, infant death, convulsions, meconium aspiration, and Apgar score less than 4 at 5 minutes. RESULTS: Among term births, 2.2% were SGA; among post-term births, 3.8% were SGA. Compared with term AGA births, term SGA births were at increased risk of stillbirth (OR 8.02; 95% CI 6.57, 9.80) and infant death (OR 7.57; 95% CI 6.39, 8.96). Among post-term SGA births, the ORs were 10.56 (95% CI 6.95, 16.05) for stillbirth and 5.00 (95% CI 3.04, 8.22) for infant death. When births with congenital malformations were excluded, the risk of infant death decreased considerably. Risks of convulsions and Apgar score less than 4 were higher in SGA than AGA infants. Post-term AGA infants had no significant increase in the risks of stillbirth or infant death but did have increased risks of convulsions, meconium aspiration, and Apgar score less than 4. CONCLUSION: The increased risk of stillbirth in post-term pregnancies is partly explained by an increased rate of SGA infants. The increased risk of death among SGA infants is caused to a large extent by congenital malformations.

Water-gymnastics reduced the intensity of back/low back pain in pregnant women.

OBJECTIVE: To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave. METHODS: A prospective, randomized study. One hundred and twenty-nine women were randomized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were randomized to a control group. The women in both groups filled in questionnaires in gestational weeks 18, 34 and within the first postpartum week. Every day from week 18 to labor they assessed the intensity of back/low back pain. RESULTS: Back pain intensity increased during pregnancy. No excess risk for the pregnancy associated with water-gymnastics was observed. The women participating in water-gymnastics recorded a lower intensity of back/low back pain. The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group (124 women) compared with 1484 in the control group (120 women). After weeks 32 33, seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain (p=0.031). CONCLUSIONS: Intensity of back/low back pain increased with advancing pregnancy. There was no excess risk for urinary or vaginal infections associated with water-gymnastics. Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain. Water-gymnastics decreased the number of women on sick-leave because of back/low back pain. Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave.