A proposal for standardized magnetic resonance imaging (MRI) descriptors of abnormally invasive placenta (AIP) - From the International Society for AIP.

Abnormally invasive placenta (AIP) is used to describe a placenta that does not separate naturally after delivery and cannot be extirpated without causing abnormally high blood loss. Recently, the use of a standardized terminology for descriptors of AIP signs seen on ultrasound has been prosed but to date no such unified descriptors have been developed for magnetic resonance imaging (MRI). The purpose of this paper is to propose a unified terminology based on a consensus opinion from the members of the International Society for AIP (IS-AIP) that include obstetricians, gynecologists, radiologists, pathologists, anesthesiologists and basic science researchers. We assume that using these standardized MRI descriptors for AIP will be useful for clinical use, education, teaching and future research projects, thus assumably improving care of patients with this condition. In addition, using a uniform terminology for AIP should become the first step of a standardized MRI report.

The International Network of Obstetric Survey Systems study of uterine rupture: a descriptive multi-country population-based study.

OBJECTIVE: International comparison of complete uterine rupture. DESIGN: Descriptive multi-country population-based study. SETTING: International. POPULATION: International Network of Obstetric Survey Systems (INOSS). METHODS: We merged individual data, collected prospectively in nine population-based studies, of women with complete uterine rupture, defined as complete disruption of the uterine muscle and the uterine serosa, regardless of symptoms and rupture of fetal membranes. MAIN OUTCOME MEASURES: Prevalence of complete uterine rupture, regional variation and correlation with rates of caesarean section (CS) and trial of labour after CS (TOLAC). Severe maternal and perinatal morbidity and mortality. RESULTS: We identified 864 complete uterine ruptures in 2 625 017 deliveries. Overall prevalence was 3.3 (95% CI 3.1-3.5) per 10 000 deliveries, 22 (95% CI 21-24) in women with and 0.6 (95% CI 0.5-0.7) in women without previous CS. Prevalence in women with previous CS was negatively correlated with previous CS rate (ρ = -0.917) and positively correlated with TOLAC rate of the background population (ρ = 0.600). Uterine rupture resulted in peripartum hysterectomy in 87 of 864 women (10%, 95% CI 8-12%) and in a perinatal death in 116 of 874 infants (13.3%, 95% CI 11.2-15.7) whose mother had uterine rupture. Overall rate of neonatal asphyxia was 28% in neonates who survived. CONCLUSIONS: Higher prevalence of complete uterine ruptures per TOLAC was observed in countries with low previous CS and high TOLAC rates. Rates of hysterectomy and perinatal death are about 10% following complete uterine rupture, but in women undergoing TOLAC the rates are extremely low (only 2.2 and 3.2 per 10 000 TOLACs, respectively.) TWEETABLE ABSTRACT: Prevalence of complete uterine rupture is higher in countries with low previous CS and high TOLAC rates.

Defining definitions: a Delphi study to develop a core outcome set for conditions of severe maternal morbidity.

OBJECTIVE: Develop a core outcome set of international consensus definitions for severe maternal morbidities. DESIGN: Electronic Delphi study. SETTING: International. POPULATION: Eight expert panels. METHODS: All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions. MAIN OUTCOME MEASURES: Definitions with a rate of agreement of more than 70%. RESULTS: The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions. CONCLUSION: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative. TWEETABLE ABSTRACT: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth.

BACKGROUND: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. METHODS: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. FINDINGS: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). INTERPRETATION: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical fatigue score from baseline to 12 weeks postpartum. RESULTS: The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue and depression scores, as well as in haematological and iron parameters, all in favour of intravenous iron. There were no serious adverse reactions. CONCLUSION: A single dose of intravenous iron was associated with a statistically significant reduction in aggregated physical fatigue within 12 weeks after postpartum haemorrhage compared to standard medical care with oral iron below the prespecified criteria of clinical superiority. As patient-reported outcomes improved significantly and intravenous iron resulted in a fast hematopoietic response without serious adverse reactions, intravenous iron may be a useful alternative after postpartum haemorrhage if oral iron is not absorbed or tolerated.

Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia: a randomized controlled pilot study.

BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8%). There was no significant difference between groups in fatigue or depression scores. RBC transfusion was associated with a higher Hb on day 1, inhibition of reticulocytosis during the first week and low iron levels. Intravenous iron was associated with increased reticulocytosis during the first week, repleted iron stores and a higher Hb in weeks 3-12. CONCLUSION: This pilot study shows that intravenous iron could be an attractive alternative to RBC transfusion in severe postpartum anaemia, and that a larger trial is needed and feasible.

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries.

OBJECTIVE: The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries. DESIGN: Population-based cohort study. SETTING AND POPULATION: A 3-year Nordic collaboration among obstetricians to identify and report on uterine rupture, peripartum hysterectomy, excessive blood loss, and AIP from 2009 to 2012 The Nordic Obstetric Surveillance Study (NOSS). METHODS: In the NOSS study, clinicians reported AIP cases from maternity wards and the data were validated against National health registries. MAIN OUTCOME MEASURES: Prevalence, risk factors, antenatal suspicion, birth complications, and risk estimations using aggregated national data. RESULTS: A total of 205 cases of AIP in association with laparotomy were identified, representing 3.4 per 10 000 deliveries. The single most important risk factor, which was reported in 49% of all cases of AIP, was placenta praevia. The risk of AIP increased seven-fold after one prior caesarean section (CS) to 56-fold after three or more CS. Prior postpartum haemorrhage was associated with six-fold increased risk of AIP (95% confidence interval 3.7-10.9). Approximately 70% of all cases were not diagnosed antepartum. Of these, 39% had prior CS and 33% had placenta praevia. CONCLUSION: Our findings indicate that a lower CS rate in the population may be the most effective way to lower the incidence of AIP. Focused ultrasound assessment of women at high risk will likely strengthen antenatal suspicion. Prior PPH is a novel risk factor associated with an increased prevalence of AIP. TWEETABLE ABSTRACT: An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Expectant management of PPROM and major complications before planned delivery: a retrospective cohort study.

Women with pre-term pre-labour rupture of membranes (PPROM) 22-33 weeks' gestation were included in a retrospective cohort study with a structured audit to identify risk factors of major complications following PPROM and to assess whether these complications are predictable. Of the 234 women analysed, 106 (45%) delivered within three days. Eighty-four women (36%) had at least one major complication and 45% of these complications occurred within three days. The complication rate was 64% in early PPROM before 28 weeks' gestation and 11% in late PPROM at 28 weeks' gestation or later. Nulliparous women had an increased risk of major complications (adjusted hazards ratio: 3.07 (95% confidence interval: 1.28-7.37)). The complication rates were highest in early PPROM and during the first three days after PPROM. Multiparous women with late PPROM, who do not deliver within the first three days, have the lowest risk of major complications and are suitable for home care.

Risk factors of recurrent anal sphincter ruptures: a population-based cohort study.

OBJECTIVE: To determine the incidence and risk factors of recurrent anal sphincter rupture (ASR). DESIGN: Population-based retrospective cohort study. SETTING: Data were taken from the National Medical Birth Registry, Denmark. POPULATION: Patients with a first and a second vaginal delivery in the time period 1997-2010. METHODS: Univariate analysis and multivariate logistic regression were used to determine risk factors of recurrent ASR. MAIN OUTCOME MEASURES: The incidence of recurrent ASR and odds ratios for possible risk factors of recurrent ASR: age, body mass index, grade of ASR, birthweight, head circumference, gestational age, presentation, induction of labour, oxytocin augmentation, epidural, episiotomy, vacuum extraction, forceps, shoulder dystocia, delivery interval and year of second delivery. RESULTS: Out of 159 446 women, 7336 (4.6%) experienced an ASR at first delivery, and 521 (7.1%) had a recurrent ASR (OR 5.91). The risk factors of recurrent ASR in the multivariate analysis were: birthweight (adjusted OR, aOR, 2.94 per increasing kg, 95% CI 2.31-3.75); vacuum extraction (aOR 2.96, 95% CI 2.03-4.31); shoulder dystocia (aOR 1.98, 95% CI 1.11-3.54); delivery interval (aOR 1.08 by year, 95% CI 1.02-1.15); year of second delivery (aOR 1.06, 95% CI 1.03-1.09); and prior fourth-degree ASR (aOR 1.72, 95% CI 1.28-2.29). Head circumference was a protective factor (aOR 0.91 per increasing cm, 95% CI 0.85-0.98). CONCLUSIONS: The incidence of recurrent ASR was 7.1%. Risk factors of recurrent ASR were excessive birthweight, vacuum extraction, shoulder dystocia, delivery interval, year of second delivery and prior fourth-degree ASR. A larger head circumference reduced the risk of recurrent ASR.

Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort.

BACKGROUND: Inherited thrombophilias have inconsistently been linked to adverse pregnancy outcomes. Differences in study design, size and population could explain this heterogeneity. OBJECTIVE: The aim of the present study was to evaluate if factor (F)V Leiden G1691A, prothrombin mutation G20210A (PTM) and methylenetetrahydrofolate reductase C677T (MTHFR) increased the risk of severe preeclampsia, fetal growth restriction, very preterm delivery, placental abruption and a composite of these outcomes also including stillbirth. PATIENTS AND METHODS: In a nested case-cohort study of pregnant women in Denmark, we genotyped 2032 cases and 1851 random controls. Each of the medical records of the cases was validated. We calculated both genomic and allelic models, and present both models. We also performed sensitivity analyses adjusting for parity, age, smoking, body mass index and socioeconomic status. RESULTS: In the allelic models, FV Leiden increased the risk of the composite outcome (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.8), severe preeclampsia (OR 1.6, 95% CI 1.1-2.4), fetal growth restriction (OR 1.4, 95% CI 1.1-1.8) and placental abruption (OR = 1.7 (95% CI 1.2-2.4). In the sensitivity analyses, adjustment diminished these estimates slightly. PTM was not significantly associated with any of the outcomes, and MTHFR was only significantly associated with severe preeclampsia (OR 1.3, 95% CI 1.1-1.6). CONCLUSION: FV Leiden predisposes to adverse pregnancy outcomes in a setting of Scandinavian women.

Severe postpartum haemorrhage and mode of delivery: a retrospective cohort study.

OBJECTIVE: To examine the association between intended mode of delivery and severe postpartum haemorrhage. DESIGN: A retrospective cohort study. SETTING: Material from a nationwide study in Denmark. POPULATION: Danish women giving birth in 2001-08. METHODS: We compared use of red blood cell transfusion by intended mode of delivery in the total population (n = 382 266), in low-risk nulliparous women (n = 147 132) and in women with a previous caesarean delivery (n = 25 156). MAIN OUTCOME MEASURE: Red blood cell transfusion within 7 days of delivery. RESULTS: In the total population the crude transfusion rates for women with planned caesarean delivery and intended vaginal delivery were 2.24 and 1.75%. After adjustment for maternal age, body mass index, birthweight, smoking, parity, number of infants and previous caesarean delivery, the risk of red blood cell transfusion was significantly lower in women with planned caesarean delivery compared with intended vaginal delivery (odds ratio 0.82; 95% CI 0.73-0.92; P < 0.01). In low-risk nulliparous women and in women with a previous caesarean delivery the transfusion rates were lower for planned caesarean delivery compared with intended vaginal delivery before and after adjustment. CONCLUSION: Compared with intended vaginal delivery, planned caesarean delivery was associated with a reduced risk of severe postpartum haemorrhage indicated by use of red blood cell transfusion.

Preterm delivery and risk of subsequent cardiovascular morbidity and type-II diabetes in the mother.

OBJECTIVE: Preterm delivery has been shown to be associated with subsequent maternal cardiovascular morbidity. However, the impact of the severity and recurrence of preterm delivery on the risk of specific cardiovascular events and the metabolic syndrome in the mother, have not been investigated. DESIGN: National registry-based retrospective cohort study. SETTING: Women delivering in Denmark from 1978 to 2007. POPULATION: Women with a first singleton delivery (n = 782 287), and with a first and second singleton delivery (n = 536 419). METHODS: Cox proportional hazard models, with the gestational age stratified into four groups as primary exposure. We made adjustments for maternal age, year of delivery, hypertensive pregnancy disorders, fetal growth deviation, placental abruption and stillbirth. MAIN OUTCOME MEASURES: Subsequent maternal hypertension, ischaemic heart diseases, thromboembolism and type-II diabetes. RESULTS: After a first delivery at 32-36 completed weeks of gestation, the adjusted risk of subsequent type-II diabetes increased 1.89-fold (1.69-2.10) and the risk of thromboembolism increased 1.42-fold (1.24-1.62). Women having a preterm delivery in the first pregnancy and a term delivery in the second had a 1.58-fold (1.34-1.86) increased risk of type-II diabetes and a 1.18-fold (0.96-1.44) increased risk of thromboembolism. Women having two preterm deliveries had a 2.30-fold (1.71-3.10) increased risk of type-II diabetes and a 1.80-fold (1.29-2.50) increased risk of thromboembolism. CONCLUSIONS: Preterm delivery is independent of other pregnancy complications associated with subsequent maternal overt type-II diabetes and thromboembolism. The recurrence of preterm delivery will augment these risks.

Interleukin-18 and interleukin-12 in maternal serum and spontaneous preterm delivery.

INTRODUCTION: Mice disrupted for the interleukin (IL)-18 gene appear more disposed to preterm delivery (PTD) induced by inflammation. A synergy between IL-18 and IL-12 has been suggested. The objective of this study was to investigate a possible relation between human maternal serum levels of IL-18, IL-12 and spontaneous PTD. MATERIALS AND METHODS: A cohort of 93 consecutive women with symptoms of threatening PTD on admission was enrolled at the delivery ward, Aarhus University Hospital, Denmark. MEASURES: Serum IL-18 and IL-12 measured using Luminex xMAP technology. Endpoint: PTD before 34 weeks gestation. RESULTS: Pregnant women admitted with symptoms of threatening PTD and delivering before 34 weeks of gestation had significantly lower levels of IL-18 compared to women delivering at or after 34 weeks of gestation (medians: 14.5 versus 26.6 pg/ml; p=0.035). IL-12 levels were not different in women delivering before or after 34 weeks of gestation. Patients having low IL-18 (below the 25-percentile) and high IL-12 (above the 75-percentile) had a twofold increase in risk of delivering before 34 weeks of gestation (RR 2.1 [1.7-2.6]). CONCLUSION: Results from this study indicate, that low serum IL-18 level could be associated with PTD in women with symptoms of PTD. A possible interaction between IL-18 and IL-12 was found, as the risk of delivering before 34 weeks is increased with the combination of low IL-18 and high IL-12, but further studies are warranted to investigate these interleukins and their possible role in PTD.

Variations in policies for management of the third stage of labour and the immediate management of postpartum haemorrhage in Europe.

BACKGROUND: The EUropean Project on obstetric Haemorrhage Reduction: Attitudes, Trial, and Early warning System (EUPHRATES) is a set of five linked projects, the first component of which was a survey of policies for management of the third stage of labour and immediate management of postpartum haemorrhage following vaginal birth in Europe. OBJECTIVES: The objectives were to ascertain and compare policies for management of the third stage of labour and immediate management of postpartum haemorrhage in maternity units in Europe following vaginal birth. DESIGN: Survey of policies. SETTING: The project was a European collaboration, with participants in 14 European countries. SAMPLE: All maternity units in 12 countries and in selected regions of two countries in Europe. METHODS: A postal questionnaire was sent to all or a defined sample of maternity units in each participating country. MAIN OUTCOME MEASURES: Stated policies for management of the third stage of labour and the immediate management of postpartum haemorrhage. RESULTS: Policies of using uterotonics for the management of the third stage were widespread, but policies about agents, timing, clamping and cutting the umbilical cord and the use of controlled cord traction differed widely. For immediate management of postpartum haemorrhage, policies of massaging the uterus were widespread. Policies of catheterising the bladder, bimanual compression and in the choice of drugs administered were much more variable. CONCLUSIONS: Considerable variations were observed between and within countries in policies for management of the third stage of labour. Variations were observed, but to a lesser extent, in policies for the immediate management of postpartum haemorrhage after vaginal birth. In both cases, policies about the pharmacological agents to be used varied widely.