Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block.

OBJECTIVE: Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations. METHODS: In total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma. RESULTS: Similar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hi NK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+ and CD4+ T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma. CONCLUSION: Our study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.

The presence of lupus nephritis additionally increases the risk of preeclampsia among pregnant women with systemic lupus erythematosus.

INTRODUCTION: Pregnant women with systematic lupus erythematosus (SLE) have an increased risk of obstetric complications, such as preeclampsia and premature births. Previous studies have suggested that renal involvement could further increase the risk for adverse obstetric outcomes. Aims: The aim of this study was to compare the obstetric outcomes in a Swedish cohort of patients with SLE with and without lupus nephritis (LN). PATIENTS AND METHODS: The study was conducted as a retrospective observational study on 103 women with SLE, who gave birth at the Karolinska University Hospital between the years 2000-2017. Thirty-five women had previous or active LN and 68 women had non-renal lupus. Data was collected from digital medical records. The outcomes that were analysed included infants born small for gestational age (SGA), premature birth, preeclampsia, SLE- or nephritis flare and caesarean section. RESULTS: Women with LN, both with previous and with renal flare during pregnancy suffered from pre-eclampsia more often compared to women with non-renal lupus (25.7% vs 2.9%, p = 0.001) and this complication was associated with premature birth (p = 0.021) and caesarean section (p = 0.035). CONCLUSIONS: Lupus nephritis is a significant risk factor for adverse obstetric outcomes in women with SLE, including preeclampsia. Those patients could benefit from more frequent antenatal controls and more vigorous follow-up.

The impact of cardiovascular diseases on maternal deaths in the Nordic countries.

INTRODUCTION: Cardiovascular diseases have become increasingly important as a cause of maternal death in the Nordic countries. This is likely to be associated with a rising incidence of pregnant women with congenital and acquired cardiac diseases. Through audits, we aim to prevent future maternal deaths by identifying causes of death and suboptimal factors in the clinical management. MATERIAL AND METHODS: Maternal deaths in the Nordic countries from 2005 to 2017 were identified through linked registers. The national audit groups performed case assessments based on hospital records, classified the cause of death, and evaluated the standards of clinical care provided. Key messages were prepared to improve treatment. RESULTS: We identified 227 maternal deaths, giving a maternal mortality rate of 5.98 deaths per 100 000 live births. The most common cause of death was cardiovascular disease (n = 36 deaths). Aortic dissection/rupture, myocardial disease, and ischemic heart disease were the most common diagnoses. In nearly 60% of the cases, the disease was not recognized before death. In more than half of the deaths, substandard care was identified (59%). In 11 deaths (31%), improvements to care that may have made a difference to the outcome were identified. CONCLUSIONS: Between 2005 and 2017, cardiovascular diseases were the most common causes of maternal deaths in the Nordic countries. There appears to be a clear potential for a further reduction in these maternal deaths. Increased awareness of cardiac symptoms in pregnant women seems warranted.

Inflammatory and endothelial markers during the menstrual cycle.

BACKGROUND: The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle. METHODS: The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle. RESULTS: Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p < 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase. CONCLUSIONS: Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.

The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage: a pilot study.

BACKGROUND: Histidine-rich glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage. METHODS: The study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. RESULTS: The results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p<0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p<0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p<0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p<0.05). CONCLUSIONS: Women who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.

Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion.

Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.

Histidine-rich glycoprotein gene polymorphism in patients with recurrent miscarriage.

Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.

Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: a retrospective case control study.

BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p=0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01-2.64, p=0.045) and G/G (AOR 1.52, 95% CI 1.02-2.27, p=0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.

Impaired endothelial function and elevated levels of pentraxin 3 in early-onset preeclampsia.

OBJECTIVE: To study endothelial function in relation to anti-angiogenic biomarkers and the inflammatory process in preeclampsia. DESIGN: Observational study. SETTING: Data were obtained from pregnant women who were admitted to the obstetrical ward at the Karolinska University Hospital, Solna, Stockholm, Sweden. POPULATION: Thirty-five women with newly developed and untreated preeclampsia and 30 healthy controls. METHODS: Flow-mediated dilation of the brachial artery, levels of anti-angiogenic and inflammatory markers were measured in plasma during pregnancy and 3-6 months after delivery. Main outcome measures. Flow-mediated dilation of the brachial artery, anti-angiogenic and inflammatory markers. RESULTS: Flow-mediated dilation was decreased in the preeclamptic group at inclusion and at follow-up (p<0.05). Pentraxin 3 (PTX3) and ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) were elevated in women with preeclampsia during pregnancy (p<0.001). Furthermore flow-mediated dilation was lower and the ratio sFlt-1/PlGF and PTX3 were higher in early-onset preeclampsia than late preeclampsia (p=0.018, 0.002 and 0.039). Levels of PTX3 at inclusion correlated inversely with flow-mediated dilation at follow-up both in the preeclampsia and control groups (Spearman, r(s) =-0.47, p=0.02 and r(s) =-0.46, p=0.02 respectively). CONCLUSION: Impaired endothelial function and increased ratio sFlt/PlGF, elevated PTX3 is present in women with preeclampsia and is especially pronounced in women with early-onset preeclampsia.

Cord blood monocyte subsets are similar to adult and show potent peptidoglycan-stimulated cytokine responses.

Human monocytes can be divided into two major subpopulations, CD14(++) CD16(-) and CD14(+) CD16(+) cells, which are suggested to play different roles in antimicrobial responses. In neonates, characteristics and functional responses of monocyte subsets have not previously been explored, and might contribute to the qualitative difference between neonatal and adult cytokine profiles. We report that at baseline, monocyte subsets in cord blood and adult peripheral blood are present in similar frequencies, and show similar expression of CD11c, CD80/CD86, CD163 and HLA-DR. In response to the bacterial ligand peptidoglycan, cord blood monocytes had high inherent capacity for production of the early-response cytokines with levels of tumour necrosis factor and interleukin-12p70 exceeding adult levels, and also a higher phosphorylation of p38-mitogen-activated protein kinase. The CD14(+) CD16(+) cells expressed more interleukin-12p70 than CD14(++) CD16(-) cells and were present in a higher frequency in peptidoglycan-stimulated cord blood mononuclear cell cultures. Together, the behaviour of cord blood CD14(+) CD16(+) cells following peptidoglycan stimulation might indicate a qualitative difference between the neonatal antimicrobial response and that of the adult. In addition we found that serum factors in cord blood and adult sera affected cytokine production similarly, with the exception of tumour necrosis factor, regardless of the source of serum or cells. Overall, our data provide new insights into monocyte heterogeneity in cord blood and monocyte subset responses to a bacterial ligand at birth.

Efficacy of obstetric thromboprophylaxis and long-term risk of recurrence of venous thromboembolism.

OBJECTIVE: To study the efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) in pregnant women with one previous venous thromboembolic event (VTE). Secondary aims were to study the long-term risk of secondary recurrence, bleeding and obstetric complications. DESIGN: A prospective national study of long-term LMWH thromboprophylaxis in Sweden. SETTINGS: All hospitals in Sweden during January 1998-December 2002, PARTICIPANTS: Pregnant women with one previous VTE and controls drawn from the Swedish Medical Birth Registry. The women were cross-matched with the Swedish Hospital Discharge Register to identify all recurrences and to ascertain the annual risk of recurrence. MAIN OUTCOME MEASURES: Recurrence of VTE, bleeding complications at delivery and obstetric complications. RESULTS: 326 of 393 registered women could be evaluated. The relative risk reduction in VTE was 88%. There was an absolute increased risk of VTE during the thromboprophylaxis period: 1.2% compared to 0.2% among controls (p<0.001). The risk during the immediate post-treatment period (43-100 days post-partum) was increased 28-fold. The annual incidence of VTE after delivery was 1%. The risk of hematoma and major blood loss at delivery was increased during thromboprophylaxis (p<0.001). There were no differences in the incidences of preeclampsia, intrauterine growth restriction or placental abruption. CONCLUSIONS: The relative risk reduction in VTE during thromboprophylaxis was 88%. After pregnancy, the annual long-term risk of recurrence was 1%. The risk was most pronounced in the post-treatment period. There was an increased risk of bleeding complications among women given LMWH, but there was no effect on obstetric complications.

Obstetric and neonatal outcomes in pregnant women treated with high-dose thromboprophylaxis: a retrospective, single-center study.

INTRODUCTION: It is well established that women with very high risk of developing antenatal thrombosis benefit from high-dose thromboprophylaxis, however data on outcomes and the safety and efficacy of thromboprophylaxis are scarce. The aim of the study was to evaluate the safety and effectiveness of the Swedish guidelines for high-dose thromboprophylaxis and the obstetric outcomes in a single-center patient cohort. PATIENTS AND METHODS: Forty-seven women treated at the Department of Obstetrics and Gynecology, Karolinska University Hospital, Solna, Sweden, between 2004 and 2017 were included in this retrospective study. Data on treatment, obstetric, and neonatal outcomes and medical history were collected. Data derived from the Swedish Medical Birth Registry on women giving birth in Stockholm County 2004-2016 were used as controls. The protocol of the study was approved by the Regional Ethics Committee in Stockholm, Sweden. RESULTS: The initial thromboprophylaxis dose was 5000 IU dalteparin twice daily. No patient developed ablatio placentae or preeclampsia. One patient suffered antenatal muscle vein thrombosis. Six patients (12.7%) suffered postpartum hemorrhage (PPH); however only one patient had severe PPH. Forty-eight children were born. Three children (6%) were diagnosed with intrauterine growth retardation, five (10%) were born small for gestational age and seven (15%) were born premature, the majority of which (except for two premature) to women with thrombophilia. DISCUSSION: High-dose thromboprophylaxis was effective and safe. The incidence of preeclampsia and ablatio was lower than in controls; however, neonatal outcomes were worse, especially among mothers with thrombophilia. Due to the diversity of the thrombophilic traits, no thrombophilia-specific conclusion could be drawn. Stricter adherence to the guidelines could further decrease the risk for bleeding, whereas more frequent antenatal controls could possible improve neonatal outcomes.

Factor V Leiden mutation and pregnancy-related complications.

OBJECTIVE: The objective of the study was to determine the prevalence of the factor V Leiden (FVL) mutation and its association with obstetric complications, blood loss during delivery, and venous thromboembolism (VTE). STUDY DESIGN: This was a prospective, observational, case-cohort study of 491 FVL carriers and 1055 controls derived from 6003 screened women. Data were analyzed with a Student t test and cross-tabulation. RESULTS: FVL carriership prevalence was 8.3%. Gestational age at delivery, birthweight deviation, gestational hypertension, and preeclampsia incidences did not differ between groups. The incidences of placental abruption, neonatal asphyxia, eclampsia, intrauterine fetal death, intrapartum death, and unexplained late miscarriage were low. The incidence of major blood loss at delivery was lower in carriers. There were 3 VTEs among carriers and none among controls. CONCLUSION: FVL carriership did not influence pregnancy-induced hypertension, birthweight, or prematurity but raised the risk of venous thromboembolism and lowered the risk of major blood loss.

Management and outcomes of newborns at risk for inherited antithrombin deficiency.

BACKGROUND: As levels of antithrombin (AT) are low at birth, diagnosing inherited AT deficiency in newborns is challenging. In Stockholm, Sweden, pregnant women with known AT deficiency are referred to the Karolinska University Hospital, where local guidelines for management of newborns at risk of inherited AT deficiency have been established. Data on pregnancy, obstetric, and neonatal outcomes are recorded in a registry. OBJECTIVES: We aimed to evaluate the current practice at the Karolinska University Hospital for managing delivery of newborns at risk for AT deficiency, the predictive value of AT levels at birth, and the neonatal outcomes of newborns with AT deficiency. PATIENTS/METHODS: This was an observational, retrospective study. All children born to mothers with AT deficiency at the Karolinska University Hospital 2003-2018 were identified from the registry and included in the study. Data were collected from the medical records and the registry. AT activity was measured postnatally and after 6 months of age. RESULTS: The total study cohort included 41 newborns. There was a significant association between low AT values postnatally and after 6 months of age (P = .001). Half (21/41) of the children were diagnosed with AT deficiency; two suffered from sinus thrombosis, which presented at 10 days of age. Both children with sinus thrombosis were delivered using vacuum extraction. CONCLUSIONS: The current practice of testing newborns can in most cases predict inherited AT deficiency. The risk for thrombosis during the neonatal period is enhanced by the use of instrumental delivery.

[Program for clinical care of immune thrombocytopenic purpura in pregnancy]. / Immunologisk trombocytopen purpura ­ vård under graviditet - Vårdprogram utvärderat i en svensk studie.

A program for care of women with immune thrombocytopenic purpura (ITP) with the recommendation to avoid treatment if platelets were >20 × 109/l during pregnancy, with the target level 100 × 109/l at delivery, was introduced. Treatment should be given with intravenous immunoglobulin (IVIG) or corticosteroids. Out of 75 pregnancies with ITP, 39 percent were treated and the treatment period was shorter with IVIG. Blood loss at delivery was similar as the reference population. Epidural analgesia was given in only 17 percent of the vaginal deliveries. Twenty-three percent of the infants had platelet counts less than 50 × 109/l during the first days after birth. If the women had prior neonatal trombocytopenia 63 percent got a child with thrombocytopenia and 40 percent of those with platelets <20 × 109/l during pregnancy had a child with thrombocytopenia. Multidisciplinary care of pregnant women with ITP including obstetricians, hematologists and neonatologists is recommended.

Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology.

The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. We now explored the proteome of these MVs. Thirty-one women undergoing ART were blood sampled at down-regulation (DR) of oestrogen and at high level stimulation (HLS) with its 10-100-fold increased oestrogen level. Samples were analysed by liquid chromatography and tandem mass spectrometry to identify and quantify the proteome. We identified 306 proteins in the MVs and 72 had changed significantly at HLS compared to DR and more than 20% of them were associated with haemostasis. Thus, proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context.

Blood inflammatory and endothelial markers in women with von Willebrand disease.

INTRODUCTION: VWD-affected females often experience menorrhagia. Periodical fluctuations of the sex steroids during the menstrual cycle cause changes both in the coagulation and immune system. The aim of the current study was to assess the changes in selected inflammatory and endothelial markers in women with VWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with corresponding data from healthy controls. MATERIALS AND METHODS: The study group included 12 VWD-affected females with regular menstrual cycle, with none of them being prescribed hormone treatment. They were not pregnant or breastfeeding. The control group consisted of 102 healthy females, matched for age and BMI. RESULTS: Within the VWD group, endostatin was higher during the follicular phase, compared to the luteal phase, although the difference was not significant (p = 0.062). sICAM-1 and IL-6 were higher in VWD-affected females, compared to the controls, sVCAM-1, cathepsin S and sP-selectin were lower (p<0.003 for all cases). The pattern was constant throughout the menstrual cycle. CONCLUSIONS: Higher levels of endostatin during early follicular phase could potentially predispose women with VWD to the development of heavy menstrual bleeding, due to antiangiogenic properties and ability to suppress several coagulation factors. Lower p-selectin levels in VWD group, compared to controls, may also contribute to the bleeding tendency. Changes in other proteins, involved in angiogenesis are hypothetically related to the formation of angiodysplasia-common complication of VWF deficiency. The latter statement requires confirmation in larger studies.

The Stockholm classification of stillbirth.

OBJECTIVE: To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death. DESIGN: Descriptive. SETTING: All delivery wards in Stockholm. POPULATION: Stillbirths from 22 completed weeks in Stockholm, Sweden. METHODS: Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated. MAIN OUTCOME MEASURE: The classification and the results of the validation are presented. RESULT: The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa=0.70). CONCLUSIONS: The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death.

Group B streptococcal carriage in Sweden: a national study on risk factors for mother and infant colonisation.

BACKGROUND: To study group B streptococcus (GBS) colonisation in parturients and infants in relation to obstetric outcome and to define serotypes and antibiotic resistance in GBS isolates acquired. METHODS: A population-based, national cohort of parturients and their infants was investigated. During 1 calendar week in 2005 all women giving birth (n=1,754) were requested to participate in the study. RESULTS: A total of 1,569 mother/infant pairs with obstetric and bacteriological data were obtained. Maternal carriage rate was 25.4% (95% confidence interval (CI): 23.3-27.6). In GBS-positive mothers with vaginal delivery and no intrapartum antibiotics, the infant colonisation rate was 68%. Some 30% of infants were colonised after acute caesarean section, and 0% were colonised after an elective procedure. Duration of transport of maternal recto/vaginal swabs of more than 1 day impeded culture sensitivity. Infant mMales were more frequently colonised than females (76.9 versus 59.8%, odds ratio (OR): 2.16; 95% CI: 1.27-3.70), as were infants born after rupture of membranes > or =24 h (p =0.039). Gestational age, birth weight and duration of labor did not significantly influence infant colonisation. Some 30% of parturients with at least one risk factor for neonatal disease received intrapartum antibiotics. The most common GBS serotypes were type III and V. Some 5% of the isolates were resistant to clindamycin and erythromycin, respectively. CONCLUSIONS: Maternal GBS prevalence and infant transfer rate were high in Sweden. Males were more frequently colonised than females. The sensitivity of maternal cultures decreased with the duration of sample transport. Clindamycin resistance was scarce. The use of intrapartum antibiotics was limited in parturients with obstetric risk factors for early onset group B streptococcal disease.

Efficacy of treatment immune thrombocytopenic purpura in pregnancy with corticosteroids and intravenous immunoglobulin: a prospective follow-up of suggested practice.

: The current study is performed to assess a routine for treatment of immune thrombocytopenic purpura in pregnancy. A prospective programme for monitoring and treatment with intravenous immunoglobulin or cortisone in pregnancies with immune thrombocytopenic purpura was suggested to all delivery units in Sweden. Treatment should be avoided if platelet counts were more than 20 × 10/l during pregnancy with no bleeding complications and with a target of 100 × 10/l at delivery. Descriptive statistics and logistic regression analysis were used. Seventy-five pregnancies were followed; treatment was given in 29 (39%) of the pregnancies; in 13 intravenous immunoglobulin, in six cortisone, in nine a combination of both immunoglobulin and cortisone and in one platelets was given. The mean platelet increase before delivery after immunoglobulin was 46 × 10/l approximately 3 days later. At delivery, 34 (45%) of all pregnancies reached target platelet level more than 100 × 10/l, whereas five (7%) had platelets less than 50 × 10/l. Mode of delivery and blood loss were similar to a reference group. Of the neonates, 23% had platelets less than 50 × 10/l with a nadir reached on day 2-4; 9% required treatment. Women with platelets less than 20 × 10/l in pregnancy or with prior neonatal thrombocytopenia were at a, respectively, five-fold and eight-fold increased risk of neonatal thrombocytopenia. A routine to avoid treatment when platelets are at least 20 × 10/l during pregnancy and to aim for 100 × 10/l at delivery seem safe. Severe maternal thrombocytopenia and prior neonatal thrombocytopenia were predictors of neonatal thrombocytopenia.