Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study.

OBJECTIVE: Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac malformations. DESIGN: Register-based study. SETTING: Denmark. POPULATION: 364 012 singleton pregnancies from 2007 to 2014. METHODS: We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions. MAIN OUTCOME MEASURES: Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1 year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated. RESULTS: SCM were reported in 972 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89-5.13), 1.73 (95% CI 1.08-2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41-47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52-2.30) and 1.38 (95% CI 1.00-1.92) for SCM and other cardiac malformations, respectively. CONCLUSIONS: Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered. TWEETABLE ABSTRACT: Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.

The importance of non-technical performance for teams managing postpartum haemorrhage: video review of 99 obstetric teams.

OBJECTIVE: Little is known about how teams' non-technical performance influences clinical performance in obstetric emergencies such as postpartum haemorrhage. DESIGN: Video review - observational study. SETTING: A university hospital (5000 deliveries) and a regional hospital (2000 deliveries) in Denmark. POPULATION: Obstetric teams managing real-life postpartum haemorrhage. METHODS: We systematically assessed 99 video recordings of obstetric teams managing real-life major postpartum haemorrhage. Exposure was the non-technical score (AOTP); outcomes were the clinical performance score (TeamOBS) and the delayed transfer to the operating theatre (defined as blood loss >1500 ml in the delivery room). RESULTS: Teams with an excellent non-technical score performed significantly better than teams with a poor non-technical score: 83.7 versus 0.3% chance of a high clinical performance score (P < 0.001), 0.2 versus 80% risk of a low clinical performance score (P < 0.001), and 3.5 versus 31.7% risk of delayed transfer to the operating theatre (P = 0.008). The results remained robust when adjusting for potential confounders such as bleeding velocity, aetiology, time of day, team size, and hospital. The specific non-technical skills associated with high clinical performance were vigilance, role assignment, problem-solving, management of disruptive behavior, and leadership. Communication with the patient and closing the loop were of minor importance. All performance assessments showed good reliability: the intraclass correlation was 0.97 (95% CI 0.96-0.98) for the non-technical score and 0.84 (95% CI 0.76-0.89) for the clinical performance score. CONCLUSION: Video review offers a new method and new perspectives for research in obstetric teams to identify how teams become effective and safe; the skills identified in this study can be included in future obstetric training programmes. TWEETABLE ABSTRACT: Non-technical performance is important for teams managing postpartum haemorrhage; video review of 99 obstetric teams.

Prediction of severe pre-eclampsia/HELLP syndrome by combination of sFlt-1, CT-pro-ET-1 and blood pressure: exploratory study.

OBJECTIVES: To evaluate the performance of a combination of angiogenic and vasoactive biomarkers to predict the development of severe pre-eclampsia (PE)/HELLP syndrome in the third trimester. METHODS: Included were 215 women referred in the third trimester to an obstetric outpatient clinic with suspected PE (mean gestational age, 35 + 4 weeks), and 94 with normal pregnancy attending a midwife clinic. Cases were categorized as having subclinical PE, essential hypertension, gestational hypertension, moderate PE, and severe PE/HELLP syndrome. Blood samples were analyzed by immunoassay and groups were compared with respect to potential clinical and biochemical biomarkers, with the primary outcome being development of severe PE/HELLP syndrome within 1 week and within 2 weeks of analysis. The most promising markers were also assessed in combination. RESULTS: In the patients presenting with mild to moderate symptoms of PE, the individual markers which performed best for the prediction of progression to severe PE/HELLP syndrome within 1 week and within 2 weeks of biomarker evaluation were C-terminal pro-endothelin-1 (CT-pro-ET-1) (area under the receiver-operating characteristics curve (AUC), 0.82 and 0.78, respectively), soluble fms-like tyrosine kinase-1 (sFlt-1) (AUC, 0.81 and 0.76), systolic blood pressure (AUC, 0.80 and 0.68) and midregional pro-atrial natriuretic peptide (AUC, 0.79 and 0.77). The combination of biomarkers with the best performance was CT-pro-ET-1, sFlt-1 and systolic blood pressure, achieving an AUC of 0.94 for prediction of development of severe PE/HELLP syndrome within 1 week and an AUC of 0.83 for prediction of their development within 2 weeks of biomarker evaluation. CONCLUSIONS: The performance of CT-pro-ET-1 for prediction of the development of PE/HELLP syndrome in the third trimester was promising, especially in combination with sFlt-1 and systolic blood pressure. This was an exploratory study and our findings should be confirmed in further studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Placental magnetic resonance imaging T2* measurements in normal pregnancies and in those complicated by fetal growth restriction.

OBJECTIVES: The magnetic resonance imaging (MRI) variable transverse relaxation time (T2*) depends on multiple factors, one important one being the presence of deoxyhemoglobin. We aimed to describe placental T2* measurements in normal pregnancies and in those with fetal growth restriction (FGR). METHODS: We included 24 normal pregnancies at 24-40 weeks' gestation and four FGR cases with an estimated fetal weight below the 1(st) centile. Prior to MRI, an ultrasound examination, including Doppler flow measurements, was performed. The T2* value was calculated using a gradient echo MRI sequence with readout at 16 different echo times. In normal pregnancies, repeat T2* measurements were performed and interobserver reproducibility was assessed in order to estimate the reproducibility of the method. Placental histological examination was performed in the FGR cases. RESULTS: The method was robust regarding the technical and interobserver reproducibility. However, some slice-to-slice variation existed owing to the heterogeneous nature of the normal placenta. We therefore based T2* estimations on the average of two slices from each placenta. In normal pregnancies, the placental T2* value decreased significantly with increasing gestational age, with mean ± SD values of 120 ± 17 ms at 24 weeks' gestation, 84 ± 16 ms at 32 weeks and 47 ± 17 ms at 40 weeks. Three FGR cases had abnormal Doppler flow, histological signs of maternal hypoperfusion and a reduced T2* value (Z-score < -3.5). In the fourth FGR case, Doppler flow, placental histology and T2* value (Z-score, -0.34) were normal. CONCLUSIONS: The established reference values for placental T2* may be clinically useful, as T2* values were significantly lower in FGR cases with histological signs of maternal hypoperfusion. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age.

OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months of age in children exposed prenatally to progesterone compared with a placebo and evaluate their medical histories up to 8 years of age. METHODS: In this study, Danish participants of the PREDICT study, including 989 surviving children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development was evaluated by the parent-completed Ages and Stages Questionnaire (ASQ) at either 48 or 60 months after the estimated date of delivery. We used the method of generalized estimating equation to account for the correlation within twins. RESULTS: A total of 492 children had been exposed prenatally to progesterone and 497 to placebo. There was no difference in the number of admissions to or length of stay in hospital between the treatment groups, and we found no overall difference in the rates of diagnoses made. However, the odds ratios (ORs) for a diagnosis concerning the heart was 1.66 (95% CI, 0.81-3.37), favoring placebo, among all children, 2.38 (95% CI, 1.07-5.30) in dichorionic twins and 8.19 (95% CI, 1.02-65.6) in all children when excluding diagnoses made at outpatient clinic visits. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared with the placebo group (P = 0.03). In dichorionic twins, the risk of having a low ASQ score (< 10(th) centile) was decreased in the progesterone group (OR, 0.34 (95% CI, 0.14-0.86)). CONCLUSION: Second- and third-trimester exposure of the fetus to progesterone does not seem to have long-term harmful effects during childhood, but future studies should focus on cardiac disease in the child. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Time to subsequent live birth according to mode of delivery in the first birth.

OBJECTIVE: To estimate the rate and time to next live birth by mode of delivery. DESIGN: Hospital-based cohort. SETTING: Aarhus University Hospital (AUH), Denmark. POPULATION: All pregnant women attending AUH were invited to enroll in the Aarhus Birth Cohort (ABC) study between 1989 and 2010 (n = 91,625). METHODS: Women were followed from their first live birth until the subsequent live birth or until censoring due to study end using Cox regression models. MAIN OUTCOME MEASURES: Rate and time to subsequent live birth according to mode of delivery. RESULTS: 46,162 index live births were identified, of which 22,462 (49%) had a subsequent live birth. Women with any type of caesarean had a 6% reduction in the rate of subsequent live birth (HR 0.94, 95% CI 0.89, 0.98), which remained unchanged in the analysis by type (emergency, HR 0.95, 95% CI 0.89, 1.02; elective, HR 0.91, 95% CI 0.85, 0.98) compared with women who had a spontaneous vaginal delivery (SVD). Operative vaginal delivery was associated with an 8% reduction in subsequent live birth rates (HR 0.92, 95% CI 0.86, 0.98) and vaginal delivery complicated by shoulder dystocia with a 19% reduction compared with SVD. Median time to next birth in days was shortest in women with a first caesarean (994 days, 95% CI 973, 1026) and longest in women with a vaginal delivery complicated by shoulder dystocia (1065 days, 95% CI 994, 1191). In women with planned pregnancies, the shortest median time to second birth was in women with breech vaginal deliveries (859 days, 95% CI 737, 1089) and the longest in women with vaginal deliveries complicated by shoulder dystocia (1193 days, 95% CI 1028, 1430). CONCLUSION: The impact of mode of delivery on subsequent rate and time to next birth was minimal in this study. The greatest reduction was among women with assisted vaginal delivery complicated by shoulder dystocia. This study is strengthened by data on pregnancy planning as well as information on complications of pregnancy, delivery and neonatal morbidities, all of which may influence a woman's decision on subsequent birth.

Longer time-to-pregnancy in spontaneously conceived pregnancies is associated with lower PAPP-A and free ß-hCG in first trimester screening for Down syndrome.

OBJECTIVE: The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (ß-hCG) and hence the risk estimates in Down syndrome screening. METHODS: The study included a cohort of 10 469 singleton pregnant women who underwent first trimester combined screening and responded to a questionnaire regarding TTP. PAPP-A and free ß-hCG levels were measured between gestational week 8 + 0 and 13 + 6 and were related to TTP. RESULTS: The median PAPP-A and free ß-hCG MoMs were significantly lower in women with a TTP ≥24 months compared with the reference group with a TTP <6 months (PAPP-A: 0.96 vs 1.06 MoM, p = 0.003; free ß-hCG: 1.04 vs 1.12 MoM, p = 0.03). This led to an increased odds for trisomy 21 risk ≥1 : 300 for TTP ≥24 months compared with TTP <6 months, but when adjusting for potential confounders, the odds ratio (OR) lost significance (OR 1.4, 95% confidence interval; 0.8-2.4). CONCLUSION: Time-to-pregnancy ≥24 months in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free ß-hCG.

Team performance during vacuum-assisted vaginal delivery: video review of obstetric multidisciplinary teams.

Introduction: Vacuum extraction is generally considered an operator-dependent task, with most attention directed toward the obstetrician's technical abilities (1-3). Little is known about the effect of the team and non-technical skills on clinical outcomes in vacuum-assisted delivery. This study aimed to investigate whether the non-technical skills of obstetricians were correlated with their level of clinical performance via the analysis of video recordings of teams conducting actual vacuum extractions. Methods: We installed between two or three video cameras in each delivery room at Aarhus University Hospital and Horsens Regional Hospital and obtained 60 videos of teams managing vacuum extraction. Appropriate consent was obtained. Two raters carefully reviewed the videos and assessed the teams' non-technical skills using the Assessment of Obstetric Team Performance (AOTP) checklist, rating all items on a Likert scale score from 1 to 5 (1 = poor; 3 = average; and 5 = excellent). This resulted in a total score ranging from 18 to 90. Two different raters independently assessed the teams' clinical performance (adherence to clinical guidelines) using the TeamOBS-Vacuum-Assisted Delivery (VAD) checklist, rating each item (0 = not done, 1 = done incorrectly; and 2 = done correctly). This resulted in a total score with the following ranges (low clinical performance: 0-59; average: 60-84; and high: 85-100). Interrater agreement was analyzed using intraclass correlation (ICC), and the risk of high or low clinical performance was analyzed on a logit scale to meet the assumption of normality. Results: Teams that received excellent non-technical scores had an 81% probability of achieving high clinical performance, whereas this probability was only 12% among teams with average non-technical scores (p < 0.001). Teams with a high clinical performance often had excellent behavior in the non-technical items of "team interaction," "anticipation," "avoidance fixation," and "focused communication." Teams with a low or average clinical performance often neglected to consider analgesia, had delayed abandonment of the attempted vaginal delivery and insufficient use of appropriate fetal monitoring. Interrater reliability was high for both rater-teams, with an ICC for the non-technical skills of 0.83 (95% confidence interval [CI]: 0.71-0.88) and 0.84 for the clinical performance (95% CI: 0.74-0.90). Conclusion: Although assisted vaginal delivery by vacuum extraction is generally considered to be an operator-dependent task, our findings suggest that teamwork and effective team interaction play crucial roles in achieving high clinical performance. Teamwork helped the consultant anticipate the next step, avoid fixation, ensure adequate analgesia, and maintain thorough fetal monitoring during delivery.

Self-hypnosis for coping with labour pain: a randomised controlled trial.

OBJECTIVE: To estimate the use of epidural analgesia and experienced pain during childbirth after a short antenatal training course in self-hypnosis to ease childbirth. DESIGN: Randomised, controlled, single-blinded trial using a three-arm design. SETTING: Aarhus University Hospital Skejby in Denmark during the period July 2009 until August 2011. POPULATION: A total of 1222 healthy nulliparous women. METHOD: Use of epidural analgesia and self-reported pain during delivery was compared in three groups: a hypnosis group receiving three 1-hour lessons in self-hypnosis with additional audiorecordings to ease childbirth, a relaxation group receiving three 1-hour lessons in various relaxation methods and mindfulness with audiorecordings for additional training, and a usual care group receiving ordinary antenatal care only. PRIMARY OUTCOME: Use of epidural analgesia. Secondary outcomes included self-reported pain. RESULTS: There were no between-group differences in use of epidural analgesia-31.2% (95% confidence interval [95% CI] 27.1-35.3) in the hypnosis group, 29.8% (95% CI 25.7-33.8) in the relaxation group and 30.0% (95% CI 24.0-36.0) in the control group. No statistically significant differences between the three groups were observed for any of the self-reported pain measures. CONCLUSION: In this large randomised controlled trial of a brief course in self-hypnosis to ease childbirth, no differences in use of epidural analgesia or pain experience were found across study groups. Before turning down self-hypnosis as a method for pain relief, further studies are warranted with focus on specific subgroups.

Elective caesarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial.

OBJECTIVES: To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes. DESIGN: Randomised controlled multicentre open-label trial. SETTING: Seven Danish tertiary hospitals from March 2009 to June 2011. POPULATION: Women with uncomplicated pregnancies, a single fetus, and a date of delivery estimated by ultrasound scheduled for delivery by elective caesarean section. METHODS: Perinatal outcomes after elective caesarean section scheduled at a gestational age of 38 weeks and 3 days versus 39 weeks and 3 days (in both groups ±2 days). MAIN OUTCOME MEASURES: The primary outcome was neonatal intensive care unit (NICU) admission within 48 hours of birth. Secondary outcomes were neonatal depression, NICU admission within 7 days, NICU length of stay, neonatal treatment, and maternal surgical or postpartum adverse events. RESULTS: Among women scheduled for elective caesarean section at 38⁺³ weeks 88/635 neonates (13.9%) were admitted to the NICU, whereas in the 39⁺³ weeks group 76/637 neonates (11.9%) were admitted (relative risk [RR] 0.86, 95% confidence interval [95% CI] 0.65-1.15). Neonatal treatment with continuous oxygen for more than 1 day (RR 0.31; 95% CI 0.10-0.94) and maternal bleeding of more than 500 ml (RR 0.79; 95% CI 0.63-0.99) were less frequent in the 39 weeks group, but these findings were insignificant after adjustment for multiple comparisons. The risk of adverse neonatal or maternal outcomes, or a maternal composite outcome (RR 1.1; 95% CI 0.79-1.53) was similar in the two intervention groups. CONCLUSIONS: This study found no significant reduction in neonatal admission rate after ECS scheduled at 39 weeks compared with 38 weeks of gestation.

Ultrasound evaluation of Cesarean scar after single- and double-layer uterotomy closure: a cohort study.

OBJECTIVES: To compare residual myometrial thickness (RMT) and size of the Cesarean scar defect after single- and double-layer uterotomy closure following first elective Cesarean section. METHODS: A retrospective cohort study was conducted in 149 women at least 6 months after an uncomplicated, elective Cesarean delivery. Two-dimensional transvaginal ultrasonographic measures of RMT, scar defect depth, width and length and myometrial thickness adjacent to the scar were compared in 68 women with single-layer and 81 women with double-layer closure delivered before and after, respectively, a change in the surgical procedure. Outcomes between the two groups were compared. RESULTS: Median RMT was 5.8 (interquartile range (IQR), 4.1-7.8) mm in women with double-layer closure vs 4.6 (IQR, 3.4-6.5) mm in those with single-layer closure (P = 0.04). Scar defect length was greater in women with single-layer closure (median, 6.8 (IQR, 4.4-8.5) mm) than in those with double-layer closure (median, 5.6 (IQR, 3.9-6.8) mm) (P = 0.01). Measurements of defect depth and width, and the proportion of scars with RMT < 2.3 mm were similar in the two groups. CONCLUSIONS: RMT was greater and defect length, but not defect depth and width, was smaller following double-layer compared with single-layer closure, which may indicate some limited benefit of double-layer closure following first elective Cesarean section.

Changes in human placental oxygenation during maternal hyperoxia estimated by blood oxygen level-dependent magnetic resonance imaging (BOLD MRI).

OBJECTIVES: To investigate changes in human placental oxygenation during maternal hyperoxia using non-invasive blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS: Eight healthy pregnant women with uncomplicated singleton pregnancies at gestational weeks 28-36 were examined with BOLD MRI, over two consecutive 5-min periods of different oxygenation: first normoxia (21% O2 ) and then hyperoxia (12 L O2 /min), achieved by controlling the maternal oxygen supply with a non-rebreather facial mask. Selecting three slices showing cross-sections of the central part of the placenta, we investigated total placental oxygenation by drawing regions of interest (ROIs) covering the entire placenta, and regional placental oxygenation by drawing smaller ROIs in the darker and brighter areas of the placenta. For each ROI, the difference in BOLD signal between the two episodes was determined and the percentage increase in BOLD signal during hyperoxia (ΔBOLD) was calculated. RESULTS: In the BOLD image, the normoxic placenta appeared heterogeneous, with darker areas located to the fetal side and brighter areas to the maternal side. During hyperoxia, the placenta became brighter and the structure more homogeneous, and the BOLD signal of the total placenta increased (ΔBOLDtot , 15.2 ± 3.2% (mean ± SD), P < 0.0001). The increase was seen predominantly in the dark areas in the fetal part of the placenta (ΔBOLDfet , 32.1 ± 9.3%) compared with in the bright areas in the maternal part of the placenta (ΔBOLDmat , 5.4 ± 3.5%). CONCLUSION: During hyperoxia, placental oxygenation was increased predominantly in the darker placental areas, which, given their anatomical location, represent the fetal circulation of the placenta. To our knowledge, this is the first study to successfully visualize changes in placental oxygenation using BOLD MRI.

Parvovirus B19 infection in human pregnancy.

Human parvovirus B19 infection is widespread. Approximately 30-50% of pregnant women are nonimmune, and vertical transmission is common following maternal infection in pregnancy. Fetal infection may be associated with a normal outcome, but fetal death may also occur without ultrasound evidence of infectious sequelae. B19 infection should be considered in any case of nonimmune hydrops. Diagnosis is mainly through serology and polymerase chain reaction. Surveillance requires sequential ultrasound and Doppler screening for signs of fetal anaemia, heart failure and hydrops. Immunoglobulins, antiviral and vaccination are not yet available, but intrauterine transfusion in selected cases can be life saving.

Current debate on the use of antibiotic prophylaxis for caesarean section.

Caesarean delivery is frequently complicated by surgical site infections, endometritis and urinary tract infection. Most surgical site infections occur after discharge from the hospital, and are increasingly being used as performance indicators. Worldwide, the rate of caesarean delivery is increasing. Evidence-based guidelines recommended the use of prophylactic antibiotics before surgical incision. An exception is made for caesarean delivery, where narrow-range antibiotics are administered after umbilical cord clamping because of putative neonatal benefit. However, recent evidence supports the use of pre-incision, broad-spectrum antibiotics, which result in a lower rate of maternal morbidity with no disadvantage to the neonate.

Early fetal growth, PAPP-A and free ß-hCG in relation to risk of delivering a small-for-gestational age infant.

OBJECTIVES: To examine early fetal growth, pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG) in relation to the risk of delivering a small-for-gestational age (SGA) infant. METHODS: Included in the study were 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital, Denmark, between January 2005 and December 2007. Maternal serum levels of PAPP-A and free ß-hCG were measured between gestational weeks 8 and 13. Two ultrasound examinations were performed, the first at 11-13 weeks and the second at 18-22 weeks, from which gestational age was estimated based on crown-rump length and biparietal diameter, respectively. Early fetal growth was expressed as an index: the ratio between the estimated number of days from the first to the second scan and the actual calendar time elapsed in days. SGA was defined as birth weight < 5(th) centile for gestational age, and the risk of SGA was evaluated according to different cut-offs of the early fetal growth index and the serum markers. RESULTS: PAPP-A < 0.4 MoM combined with an early fetal growth index < 10(th) centile resulted in an increased risk of SGA (odds ratio (OR), 5.8; 95% CI, 2.7-12.7). Low PAPP-A, low free ß-hCG and slow early fetal growth were statistically, independently associated with SGA, and the association between free ß-hCG < 0.3 MoM and SGA was as strong as that between PAPP-A < 0.3 MoM and SGA (OR, 3.1 and 3.0, respectively). CONCLUSION: The combination of slow early fetal growth and low PAPP-A resulted in a nearly six-fold increased risk of delivery of an SGA infant. These findings might improve our chances of early identification of fetuses at increased risk of growth restriction.

Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model.

OBJECTIVE: The purpose of this study was to measure differences in oxygenation between the left and right sides of the fetal liver during varying oxygenation levels. METHODS: Eight ewes carrying singleton fetuses at gestational age 125 days (term, 145 days) were included in the study. Under anesthesia the ewes were ventilated with gas containing different levels of oxygen, thereby subjecting the fetuses to hyperoxia (mean ± SD maternal arterial partial pressure of oxygen (pO2), 23.2 ± 8.2 kPa) and hypoxia (mean maternal arterial pO2, 7.1 ± 0.5 kPa). Changes in oxygenation within the fetal liver were assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). RESULTS: During hyperoxia there was no difference between the BOLD signal in the left and right sides of the fetal liver; mean change in BOLD (ΔBOLD)(hyperox), -0.9 ± 3.7%. During hypoxia, however, the decrease in the BOLD signal was more pronounced in the right side as compared with the left side, thereby creating a significant increase in the left-right difference in the BOLD signal; mean ΔBOLD(hypox), 5.2 ± 2.2% (P = 0.002, paired t-test). The left-right difference was directly proportional to the degree of hypoxia (R2 = 0.86, P = 0.007). CONCLUSIONS: To our knowledge, this is the first study demonstrating differences in oxygenation between the left and right sides of the fetal liver during hypoxia, a difference that can be explained by increased ductus venosus shunting. Thus, the BOLD MRI technique is a promising non-invasive tool that might be useful for the future monitoring of the human fetus.

Acupuncture for the induction of labour: a double-blind randomised controlled study.

OBJECTIVE: To investigate whether acupuncture is effective for the induction of labour in post-term pregnancies. DESIGN: A double-blind multicentre randomised controlled study. SETTINGS: Aarhus University Hospital and Herning Regional Hospital, Denmark. POPULATION: One hundred and twenty-five healthy women with uneventful pregnancies at gestational week 41(+6) were randomised into two groups. METHODS: The intervention group was given acupuncture twice on the same day at acupuncture point GV20 and bilaterally at points BL67, LI4 and SP6. The control group received sham acupuncture at the same points. MAIN OUTCOME MEASURES: At effect evaluation, which was carried out 24 hours after randomisation, the primary endpoint was labour or delivery. RESULTS: The primary endpoint was achieved in seven women (12%) in the acupuncture group and eight women (14%) in the control group (P = 0.79). Stratification for parity and fetal gender did not alter the results. CONCLUSION: Under the treatment regimen investigated in this study, acupuncture for the induction of labour in post-term women at gestational age 41(+6) weeks may not be effective.

Low PAPP-A in the first trimester is associated with reduced fetal growth rate prior to gestational week 20.

OBJECTIVE: To evaluate the association between maternal pregnancy-associated plasma protein-A (PAPP-A) and fetal growth from the first to the second trimester. METHODS: A prospective cohort study including 8347 pregnant women attending prenatal care at Aarhus University Hospital were conducted. PAPP-A was measured during 8 to 14 gestational weeks. Fetal growth between the two scans in the first and second trimesters was estimated by (GA(20)- GA(12))/Days(calendar), where GA(12) reflects gestational age in days calculated from crown-rump length at a 12-week scan, GA(20) reflects gestational age in days calculated from biparietal diameter at a 20-week scan, and Days(calendar) reflects the number of calendar days between the two scans. RESULTS: Fetal growth rate from the first to the second trimester was correlated with PAPP-A, with a regression coefficient of 0.009 (95% CI, 0.007-0.012, P < 0.001). PAPP-A below 0.30 MoM was associated with a fetal growth rate below the tenth centile, with an adjusted OR of 2.05 (95% CI, 1.24-3.38). CONCLUSION: Low levels of PAPP-A are associated not only with low birth weight at term but also with slower fetal growth prior to 20 weeks of gestation.