Preeclampsia in kidney transplanted women; Outcomes and a simple prognostic risk score system.

Women pregnant following kidney transplantation are at high risk of preeclampsia. Identifying the effects of preeclampsia on pregnancy outcome and allograft function in kidney transplanted women, and predicting which women will require more targeted follow-up and possible therapeutic intervention, could improve both maternal and neonatal outcome. In this retrospective cohort study of all pregnancies following kidney transplantation in Norway between 1969 and 2013, we used medical records to identify clinical characteristics predictive of preeclampsia. 175 pregnancies were included, in which preeclampsia was diagnosed in 65. Pregnancies with preeclampsia had significantly higher postpartum serum creatinine levels, higher risks of preterm delivery, caesarean delivery, and small for gestational age infants. In the final multivariate model chronic hypertension (aOR = 5.02 [95% CI, 2.47-10.18]), previous preeclampsia (aOR = 3.26 [95% CI, 1.43-7.43]), and elevated serum creatinine (≥125 µmol/L) at the start of pregnancy (aOR = 5.79 [95% CI, 1.91-17.59]) were prognostic factors for preeclampsia. Based on this model the risk was 19% when none of these factors were present, 45-59% risk when one was present, 80-87% risk when two were present, and 96% risk when all three were present. We suggest that the risk of preeclampsia in pregnancies in kidney transplanted women can be predicted with these variables, which are easily available at the start of pregnancy.

Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome: A case report.

RATIONALE: Antiphospholipid syndrome (APS) in pregnancy may trigger the life-threatening catastrophic antiphospholipid syndrome (CAPS). Complement activation is implicated in the pathogenesis, and inhibition of complement factor C5 is suggested as an additional treatment option. PATIENT CONCERNS, DIAGNOSIS AND INTERVENTIONS: We present a pregnant patient treated with the C5-inhibitor eculizumab due to high risk of developing devastating APS-related complications. The complement inhibitory effects of the treatment were examined both in the patient and the premature infant. OUTCOMES: Complement activity in the mother recovered considerably faster than anticipated; however, no new thrombosis or CAPS developed during the last week of pregnancy or postpartum. Blood sampling from the umbilical vein and artery, and from the infant after delivery showed low complement activity; however, only 0.3% of the eculizumab concentration detected in the mother, consistent with low placental passage of eculizumab. LESSONS: The data underscore the importance of close monitoring of complement inhibition and individualizing dosage regimens in pregnant patients receiving eculizumab. We document how traditional functional complement activity tests cannot assess the effect of eculizumab in premature infants due to the very low levels of complement factors detected in this infant born in gestational week 33. Only trace amounts of eculizumab passed the placenta. In conclusion, complement C5 inhibition might be a safe candidate treatment option for APS during pregnancy and delivery, and additionally, enables prolongation of pregnancy with important weeks.

Pregnancy outcomes following maternal kidney transplantation: a national cohort study.

INTRODUCTION: Internal design flaws in previous reports of pregnancies following kidney transplantation have been outlined, and the need for a validation has been stated. The aim of this study was to collect information about obstetrical and neonatal outcomes in all Norwegian pregnancies following maternal kidney transplantation, and to compare these data with the general Norwegian population. MATERIAL AND METHODS: A retrospective cohort study based on 1 272 000 deliveries in Norway between 1969 and 2013. All data were collected from medical records. From the source population, we compared 119 first deliveries in kidney transplanted women with 238 first deliveries in nontransplanted women. An explanatory strategy was used in the analysis. RESULTS: The risk of preeclampsia was significantly increased in kidney-transplanted women compared with nontransplanted women (adjusted incidence rate ratio: 6.06, 95% confidence interval 3.18-11.55). Additionally, preeclampsia in kidney-transplanted women was early onset (diagnosed <34 gestational weeks) in half of the cases. There were also persistent risks of cesarean delivery (adjusted incidence rate ratio 4.14, 95% confidence interval 2.56-6.66), preterm delivery (adjusted incidence rate ratio 4.45, 95% confidence interval 2.13-9.30) and a birthweight below the 10th centile (22.7% vs. 9.7%) in the kidney-transplanted group. A high proportion (63%) of the kidney-transplanted women with chronic hypertension developed preeclampsia. CONCLUSIONS: Using consistent diagnostic criteria, this study shows high rates of maternal and neonatal complications in pregnancies following kidney transplantation. In particular, we reveal a high rate of early-onset preeclampsia requiring operative preterm delivery, conferring long-term risks on both the mother and child.

Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy.

Preeclampsia (PE) affects approximately 5% of all pregnancies, but is increased several-fold in women with pre-gestational type 1 diabetes mellitus (T1DM). Increased oxidative stress and altered maternal plasma trace elements that modulate the antioxidant system have been implicated in PE. In non-diabetic women, increased plasma copper and iron and decreased manganese, selenium, and zinc have been associated with PE in cross-sectional studies. In a longitudinal study, we hypothesized that plasma levels of trace elements differ between T1DM women with vs. without subsequent PE. Samples were collected during the first (gestation 12.2 ± 1.9 weeks, [mean ± SD]), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy, all before the onset of PE. We compared 23 T1DM women who subsequently developed PE with 24 T1DM women who remained normotensive; and we included 19 non-diabetic (non-DM) normotensive pregnant women as reference controls. Trace elements were measured using inductively coupled plasma mass spectroscopy. In T1DM women with subsequent PE vs normotensive, only plasma zinc was significantly higher at the first trimester, while copper:zinc and copper:high-density lipoprotein cholesterol ratios were higher throughout gestation (all P < .05). These findings persisted after adjustment for covariates. Higher copper:zinc ratios may contribute to oxidative stress in T1DM women who develop PE. Ratios of pro- to anti-oxidant factors may predict risk for PE in diabetic pregnancies more effectively than individual trace element levels.

Placental glucose transfer: a human in vivo study.

OBJECTIVES: The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption). METHODS: Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery). RESULTS: There were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values. CONCLUSIONS: We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta.

Maternal deaths in Norway 2005-2009.

BACKGROUND: Norway has low maternal mortality, but such deaths are underreported even in high-income countries. Our goal was to identify the exact number of maternal deaths, the causes of death and the potential for improvement through medical care in Norway. MATERIAL AND METHOD: We traced maternal deaths in the period from 1 January 2005 to 31 December 2009 by linking the Medical Birth Registry and the Cause of Death Registry, supplemented with data from maternity clinics. We identified the cause of death and the lessons that could be learned by a meticulous review of each case. RESULTS: We found 26 maternal deaths during the period, 14 of which were due to direct causes and 12 to indirect causes. The maternal mortality ratio was 8.7/100,000 live births. Fourteen of the deaths were registered in official statistics. Of the 12 deaths that were not included in the statistics, 11 were found through matching the registers and one had been reported directly by the hospital. The most common causes of death were hypertensive disorders during pregnancy (n = 6), thromboembolism (n = 4) and mental illness (n = 4). None of the deaths due to thromboembolism appeared in official statistics. The same applied to nine of the 12 indirect maternal deaths. We found a potential for improved medical care in 14 of 26 cases. Half of these were deaths due to hypertensive disorders during pregnancy or thromboembolism. INTERPRETATION: Maternal death was considerably underreported in Norwegian official statistics during the period studied. Greater attention should be given to better blood-pressure treatment, stabilisation and timely delivery in the case of hypertension during pregnancy, and to screening for possible pulmonary embolism. The same applies to mental illness and internal medical disorders in pregnant women.

PP076. Gender differences in fetal growth and fetal-placental ratio in preeclamptic and normal pregnancies.

INTRODUCTION: Boys have higher morbidity and mortality than girls,particularly when born prematurely, despite higher birthweight. Adaptation to poor intrauterine environment by reducing fetal growth is more prevalent in female than male fetuses. Differences in reponses between the genders might be mediated by placental functions, as illustrated by the fetal-placental ratio. OBJECTIVES: To study the fetal-placental ratio in normal and preeclamptic pregnancies and compare this ratio in boys and girls. METHODS: The STORK study (n=1031) is a prospective, longitudinal study of fetal growth. We calculated fetal-placental ratio for boys and girls in normal and preeclamptic pregnancies. Differences between groups were analysed by independent t-tests. RESULTS: Boys had a higher fetal-placental ratio than girls (5.26 vs 5.1 g, p=0.015) in normal pregnancies. 39 women (3.8%) developed preeclampsia. Boys had the same ratio in both groups. Girls in preeclamptic pregnancies had a lower ratio than in normal pregnancies (4.5 vs 5.1 g, p=0.05). CONCLUSION: Boys appear to invest more in their own growth than in placental growth. In preeclampsia they maintain the same fetal-placental ratio. In girls, birthweight is lower whereas placental weight is maintained, giving a reduced fetal-placental ratio. This pattern is more pronounced in preeclampsia. #Birthweight according to gestational age * corrected for gestational age.

Plasma lipoproteins and preeclampsia in women with type 1 diabetes: a prospective study.

CONTEXT: In nondiabetic pregnancy, cross-sectional studies have shown associations between maternal dyslipidemia and preeclampsia (PE). In type 1 diabetes mellitus (T1DM), the prevalence of PE is increased 4-fold, but prospective associations with plasma lipoproteins are unknown. OBJECTIVES: The aim of this study was to define lipoprotein-related markers and potential mechanisms for PE in T1DM. DESIGN AND SETTINGS: We conducted a multicenter prospective study in T1DM pregnancy. PATIENTS: We studied 118 T1DM women (26 developed PE, 92 remained normotensive). Subjects were studied at three visits before PE onset [12.2 ± 1.9, 21.6 ± 1.5, and 31.5 ± 1.7 wk gestation (means ± SD)] and at term (37.6 ± 2.0 wk). Nondiabetic normotensive pregnant women (n = 21) were included for reference. MAIN OUTCOME MEASURES: Conventional lipid profiles, lipoprotein subclasses [defined by size (nuclear magnetic resonance) and by apolipoprotein content], serum apolipoproteins (ApoAI, ApoB, and ApoCIII), and lipolysis (ApoCIII ratio) were measured in T1DM women with and without subsequent PE. RESULTS: In women with vs. without subsequent PE, at the first and/or second study visits: low-density lipoprotein (LDL)-cholesterol, particle concentrations of total LDL and large (but not small) LDL, serum ApoB, and ApoB:ApoAI ratio were all increased (P < 0.05); peripheral lipoprotein lipolysis was decreased (P < 0.01). These early differences remained significant in covariate analysis (glycated hemoglobin, actual prandial status, gravidity, body mass index, and diabetes duration) but were not present at the third study visit. High-density lipoprotein and very low-density lipoprotein subclasses did not differ between groups before PE onset. CONCLUSIONS: Early in pregnancy, increased cholesterol-rich lipoproteins and an index suggesting decreased peripheral lipolysis were associated with subsequent PE in T1DM women. Background maternal lipoprotein characteristics, perhaps masked by effects of late pregnancy, may influence PE risk.

[A 33-year old pregnant woman with nausea, itching and fatigue]. / En 33 år gammel gravid kvinne med kvalme, kløe og slapphet.

Acute fatty liver of pregnancy (AFLP) is a serious, but rare condition with substantial maternal and perinatal mortality and morbidity. It occurs in the third trimester or early postpartum period. The medical history, physical examination and laboratory tests are often sufficient to make the diagnosis, and liver biopsy is rarely indicated. We present a 33-year-old woman with the diagnosis AFLP. Her case is presented to draw attention to AFLP as a differential diagnosis to liver diseases in pregnancy, especially the HELLP syndrome (haemolysis, elevated liver enzymes and low platelets). Appropriate diagnosis and prompt delivery is essential to optimal maternal and fetal outcome in both the AFLP and HELLP syndromes, and this should be followed by intensive care treatment of the dysfunctional maternal multiorgan system.

[Female circumcision--complications and treatment]. / Omskjaering av kvinner--komplikasjoner og behandling.

The majority of women with extensive forms of genital cutting develop one or more chronic complications such as dysmenorrhea, dyspareunia, pain and cysts in the perineum, vaginal obstruction with haematocolpos, relative urine retention and recurrent urinary tract infections. Extensive forms of circumcision also influence childbirths. The severity of the cutting is associated with the probability of developing later complications. The women's clinics at the regional hospital in Norway have established outpatient clinics to receive women with complications after genital cutting. The aim was to develop an adequate health service to the affected. In order to improve the access to care and to ensure anonymity the women may refer themselves. During 2004, a total of 60 women were treated. The majority suffered from poor urinary flow, pain at micturition, dysmenorrhea and dyspareunia. Reconstruction of the vaginal orifice was performed to relieve some of the discomforts. The numbers of women who visit the clinics are increasing. The surgical procedure itself is not technically difficult, but the consultation before and after the surgery require cultural sensitivity. As health care personnel we can influence the affected to realise that genital cutting is an assault against a small girl. Norwegian health care workers need to learn more about how to communicate well about the medical as well as the cultural and mental aspects of genital cutting.

[Postpartum dyspnea, edema and fever]. / Dyspné, ødem og feber i barseltiden.

BACKGROUND: Cardiomyopathy is a condition with heart failure caused by a reduction in the contractility of the heart. Peripartum cardiomyopathy is a rare, but serious condition, characterised by development of heart failure during the last month of pregnancy or the first five months after delivery. MATERIAL AND METHODS: We present a case in which a woman pregnant with twins developed heart failure a few days after giving birth. We give a short report of symptoms, clinical signs, diagnosis, treatment and prognosis for subsequent pregnancies. RESULTS AND INTERPRETATION: The condition was initially diagnosed and treated as pneumonia, but despite treatment and improvement in her laboratory tests, her condition worsened. The symptoms were dyspnoea, peripheral oedemas and pulmonary oedema. Peripartum cardiomyopathy was diagnosed after echocardiography. Treatment of heart failure with diuretics, nitroglycerine, angiotensin-converting enzyme inhibitor and beta blocker was given with good results. This case is presented in order to draw attention to a rare, but serious condition in pregnancy or the postnatal period which easily can be misjudged or mistreated.

Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.

BACKGROUND: To investigate the effect of dietary intake of the NO-donor L-arginine on the diastolic blood pressure in women with pre-eclampsia. METHODS: A randomized double-blind study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women with gestational length ranging from 28+0 to 36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up to 5 days. The primary end-point was to identify a difference in diastolic blood pressure alteration between the two groups after 2 days of intervention. Secondary end-points included the interval from study start to delivery, the proportion of women delivered after 2, 5 or 10 days from treatment start and mean birth weight. RESULTS: There was no statistically significant alteration in diastolic blood pressure in the L-arginine group compared with the placebo group after 2 days of treatment (p = 0.4). No differences in the proportions of women delivered by day 2, 5 or 10 after study start, in the mean interval from study start to delivery, or in mean birth weight percentile were observed between the two groups. CONCLUSIONS: Oral L-arginine supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L-arginine treatment could be clinically beneficial for the mother or the fetus if started earlier in the disease process than for the women in our study remains to be seen.