Labor induction at 41+0 gestational weeks or expectant management for the nulliparous woman: The Finnish randomized controlled multicenter trial.

INTRODUCTION: Neonatal and maternal risks increase in term pregnancy as gestational age advances and become increasingly evident post-term. Management practices of late- and post-term pregnancies vary, and the optimal time point for intervention by labor induction is yet to be determined. MATERIAL AND METHODS: This randomized controlled trial of 381 nulliparous women with unripe cervices compared labor induction at 41+0 gestational weeks (early induction) with expectant management and labor induction at 41+5 to 42+1 gestational weeks (expectant management). This multicenter study included all five university hospitals and the largest central hospital in Finland. The study period was 2018-2022. Participants were randomized to either early induction (48.8%, n = 186) or expectant management (51.2%, n = 195) with equal randomization ratios of 1:1. This was a superiority trial, and the primary outcomes were rates of cesarean section (CS) and composite of adverse neonatal outcomes. The trial was registered at the ISRCTN registry (ISRCTN83219789, https://doi.org/10.1186/ISRCTN83219789). RESULTS: The rates of CS (16.7% [n = 31] vs. 24.1% [n = 47], RR 0.7 [95% CI: 0.5-1.0], p = 0.07) and a composite of adverse neonatal outcomes (9.7% [n = 18] vs. 14.4% [n = 28], RR 0.7 [95% CI: 0.4-1.2] p = 0.16) did not significantly differ between the groups, but the operative delivery rate was lower in the early induction group than in the expectant management group (30.6% [n = 57] vs. 45.6% [n = 89], p = 0.003). The rates of hemorrhage ≥1000 mL and neonatal weight ≥4000 g were also lower in the early induction group, as was the vacuum extraction rate in women with vaginal delivery. Of the women with expectant management, 45.6% (n = 89) had spontaneous onset of labor. No perinatal deaths occurred, but one case of eclampsia appeared in the expectant management group. CONCLUSIONS: Offering labor induction to nulliparous women at 41+0 gestational weeks may decrease the probability of operative delivery, postpartum hemorrhage, and neonatal weight ≥4000 g. However, this study was underpowered to affirm the trends of rising rates of CS and adverse neonatal outcomes in the expectant management group. Thus, expectant management could remain an option for some, as one in two women with expectant management had a spontaneous onset of labor.

Gestational anemia and maternal antenatal and postpartum psychological distress in a prospective FinnBrain Birth Cohort Study.

BACKGROUND: Gestational anemia, most commonly caused by iron deficiency, may increase the risk of maternal anxiety and depression and have a potentially far-reaching impact on mother's and newborn's health. Several mechanisms, such as effects of iron deficiency on cerebral neurotransmitter metabolism, have been suggested. None of the earlier studies have assessed the association between gestational anemia and depression, anxiety and pregnancy-related anxiety simultaneously. METHODS: Women, participating in the FinnBrain Birth Cohort Study and attending maternity welfare clinics in Turku, whose hemoglobin (Hb) values during pregnancy were available were included in this study (n = 1273). The study group consisted of 301 women with Hb levels < 11.0 g/dL at any time during pregnancy, and 972 women with Hb ≥ 11.0 g/dL were included in the control group. Symptoms of depression, anxiety, and pregnancy-related anxiety were assessed using the Edinburgh Postnatal Depression Scale (EPDS), Symptom Checklist-90 (SCL), and Pregnancy-Related Anxiety Questionnaire (PRAQ) questionnaires at 14, 24, and 34 gestational weeks, and EPDS and SCL were also performed 3 and 6 months postpartum. RESULTS: Gestational anemia was not associated with an increased risk of depression either prenatally or postpartum when the analyses were adjusted for maternal age at birth, parity, smoking during pregnancy, maternal education, and gestational age. However, a weak connection was found between gestational anemia and prenatal anxiety in the early pregnancy. Furthermore, the analysis between women with Hb < 10.0 g/dL and those with Hb ≥ 10.0 g/dL showed an association between gestational anemia and anxiety in the late pregnancy, but otherwise no difference in psychological distress was found. CONCLUSIONS: No evidence supporting the association between gestational anemia and antenatal or postpartum depression was found. However, a weak connection between gestational anemia and antenatal anxiety was observed. This finding needs further investigation to establish timing and investigate causality.

Brain volumes and white matter microstructure in 8- to 10-year-old children born with fetal growth restriction.

BACKGROUND: Fetal growth restriction caused by placental insufficiency is associated with increased risk of poor neurodevelopment, even in the absence of specific perinatal brain injury. Placental insufficiency leads to chronic hypoxaemia that may alter cerebral tissue organisation and maturation. OBJECTIVE: The aim of this study was to assess the effects fetal growth restriction and fetal haemodynamic abnormalities have on brain volumes and white matter microstructure at early school age. MATERIALS AND METHODS: This study examined 32 children born with fetal growth restriction at 24 to 40 gestational weeks, and 27 gestational age-matched children, who were appropriate for gestational age. All children underwent magnetic resonance imaging (MRI) at the age of 8-10 years. Cerebral volumes were analysed, and tract-based spatial statistics and atlas-based analysis of white matter were performed on 17 children born with fetal growth restriction and 14 children with birth weight appropriate for gestational age. RESULTS: Children born with fetal growth restriction demonstrated smaller total intracranial volumes compared to children with normal fetal growth, whereas no significant differences in grey or white matter volumes were detected. On atlas-based analysis of white matter, children born with fetal growth restriction demonstrated higher mean and radial diffusivity values in large white matter tracts when compared to children with normal fetal growth. CONCLUSION: Children ages 8-10 years old born with fetal growth restriction demonstrated significant changes in white matter microstructure compared to children who were appropriate for gestational age, even though no differences in grey and white matter volumes were detected. Poor fetal growth may impact white matter maturation and lead to neurodevelopmental impairment later in life.

Means of reaching successful antenatal transfers to level 3 hospitals in cases of threatened very preterm deliveries: a national survey.

INTRODUCTION: Centralization of very preterm deliveries to level 3 hospitals is recommended to improve infant survival and prevent brain injury. We studied the clinical practices of centralization from level 2 to level 3 hospitals in cases of threatening very preterm delivery in Finland. MATERIALS AND METHODS: Obstetricians in all 16 level 2 hospitals in Finland were invited to participate in an online survey regarding antenatal transfer to level 3 hospitals among women with threatened delivery below 32 gestational weeks. We report clinical thresholds used as indications and contraindications for antenatal transfers, and logistical factors related to transfers. RESULTS: Twelve out of 16 (75%) hospitals completed the survey. The lower gestational age threshold for antenatal transfer ranged from 22 + 0 to 23 + 0 weeks. All hospitals regarded preterm premature rupture of membranes, chorioamnionitis, and severe pre-eclampsia as indications for antenatal transfer to a level 3 hospital. Most hospitals reported transferring women in spite of regular contractions (interval over 5 min) or cervical dilatation up to 4 cm. Suspicion of placental abruption, abnormal cardiotocography tracing and poor maternal condition were the most frequently reported contraindications for antenatal transfer. The time to arrange antenatal transfer was less than 2 h in all hospitals, and overcrowding of level 3 hospitals rarely hindered antenatal transfer. CONCLUSIONS: Successful centralization of very preterm deliveries is reached in Finland by rapid and active antenatal transfers. This study identified clinical thresholds used by obstetricians in a setting of long distances and high centralization rate.

Gestational iron deficiency anemia is associated with preterm birth, fetal growth restriction, and postpartum infections.

OBJECTIVES: Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. METHODS: We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. RESULTS: Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. CONCLUSIONS: Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system.

Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction.

BACKGROUND: According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. OBJECTIVE: We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. STUDY DESIGN: A prospectively collected cohort of children born with FGR (birth weight <10th percentile and/or abnormal umbilical artery flow, n = 28) underwent a 24-hour Holter monitoring at the mean age of 9 years and gestational age matched children with birth weight appropriate for gestational age (AGA, n = 19) served as controls. Time- and frequency domain HRV indices were measured and their associations with antenatal hemodynamic changes were analyzed. RESULTS: Time- and frequency domain HRV parameters (standard deviation of R-R intervals, SDNN; low frequency, LF; high frequency, HF; LF/HF; very low frequency, VLF) did not differ significantly between FGR and AGA groups born between 24 and 40 weeks. Neither did they differ between children born with FGR and normal umbilical artery pulsatility or increased umbilical artery pulsatility. In total, 56% of the FGR children demonstrated blood flow redistribution (cerebroplacental ratio, CPR < -2 SD) during fetal life and their SDNN (p = .01), HF (p = .03) and VLF (p = .03) values were significantly lower than in FGR children with CPR ≥ -2SD. CONCLUSIONS: Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR.

Foetal growth restriction has negative influence on narrative skills in 8-10-year-old children.

AIM: The risk for neurocognitive difficulties is increased in children born with foetal growth restriction (FGR), but no data exist yet on their narrative skills. The narrative skills of 8- to 10-year-old children born with FGR between 24 and 40 weeks were compared with those of children born with appropriate growth for gestational age (AGA). METHODS: A prospectively collected cohort of 36 children with FGR was recruited prenatally at a Finnish tertiary hospital from 1998-2001, and 31 children with AGA served as controls. Narrative skills were assessed using a standardised test, and correlations between narrative, communication, reading and spelling skills were studied. RESULTS: Children born with FGR produced significantly less information and shorter utterances in their narratives than the AGA group. Children born preterm with FGR performed significantly more poorly in their narratives than the preterm AGA group. Poor narrative skills correlated with poor communication, reading and spelling skills. CONCLUSION: Children born with FGR had poorer narrative skills compared with their AGA peers at the age of 8-10 years, and narrative skills were linked to other language-based skills, which underlines the importance of early detection and preventive measures to optimise the educational outcome of children born with FGR.

Fetal hemodynamics and language skills in primary school-aged children with fetal growth restriction: A longitudinal study.

AIM: Long-term follow-up studies on children born with fetal growth restriction (FGR) have revealed a specific profile of neurocognitive difficulties, including problems with speech, language and literacy skills. We hypothesized that problems with communication skills, including language use and literacy skills of FGR children at primary school age are associated with prenatal circulatory changes. METHODS: Ultrasonographic assessment of fetoplacental hemodynamics was performed prenatally in 77 fetuses. After a follow-up period of 8-10 years, assessment of reading and spelling skills using standardized tests and the Children's Communication Questionnaire (CCC-2) was performed to measure different language skills in 37 FGR children and 31 appropriately grown (AGA) controls, matched for gestational age. RESULTS: Increased blood flow resistance in the umbilical artery (UA PI >2 SD) during fetal life showed odds ratios of 3.5-19.1 for poor literacy and communication skills and need for speech and language therapy. Furthermore, FGR children with prenatal cerebral vasodilatation (cerebroplacental ratio (CPR) < -2 SD) had significantly poorer literacy and communication skills, at primary school age compared to the AGA controls. Abnormal CPR demonstrated odds ratios of 4.2-28.1 for poor literacy and communication skills and need for speech and language therapy. CONCLUSION: Increased blood flow resistance in the umbilical artery and cerebral vasodilatation are associated with poor communication, language, and literacy skills at early school age in children born with FGR. These findings indicate the need for continuous follow-up of this group and timely targeted support to ensure optimal academic outcomes.

Foetal growth restriction is associated with poor reading and spelling skills at eight years to 10 years of age.

AIM: Foetal growth restriction (FGR) is associated with communication problems, which might lead to poor literacy skills. The reading and spelling skills of eight- to 10-year-old FGR children born at 24-40 gestational weeks were compared with those of their gestational age-matched, appropriately grown (AGA) peers. METHODS: A prospectively collected cohort of 37 FGR and 31 AGA children was recruited prenatally at a Finnish tertiary care centre during 1998-2001. The children's reading and spelling skills were assessed using standardised tests for Finnish-speaking second and third graders. RESULTS: Significantly more children performed below the 10th percentile normal values for reading and spelling skills in the FGR group than in the AGA group. At nine years of age, the FGR children had significantly poorer performance in word reading skills and reading fluency, reading accuracy and reading comprehension than the AGA controls. No between-group differences were detected at eight years of age. CONCLUSION: FGR is associated with poor performance in reading and spelling skills. A third of the FGR children performed below the 10th percentile normal values at nine years of age. These results indicate a need to continuously evaluate linguistic and literacy skills as FGR children age to ensure optimal support.

Expression of CPPED1 in human trophoblasts is associated with timing of term birth.

Understanding of timing of human parturition is incomplete. Therefore, we carried out proteomic analyses of full-term placentas from uncomplicated pregnancies to identify protein signatures associated with the onset of spontaneous delivery. We found quantitative associations of 10 proteins with spontaneous term birth, evident either in the basal or in the chorionic plates or in both. Additional 18 proteins were associated according to the location within placenta indicating local variations in protein amounts. Calcineurin-like phosphoesterase domain-containing 1 (CPPED1), a phosphatase previously suggested dephosphorylating AKT1/PKB, was one of the identified proteins. qRT-PCR revealed the mRNA level of CPPED1 was higher in elective caesarean deliveries than in spontaneous births, while immunohistochemistry showed CPPED1 in cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts. Noteworthy, phosphorylation status of AKT1 did not differ between placentas from elective caesarean and spontaneous deliveries. Additionally, analyses of samples from infants indicated that single-nucleotide polymorphisms rs11643593 and rs8048866 of CPPED1 were associated with duration of term pregnancy. Finally, post-transcriptional silencing of CPPED1 in cultured HTR8/SVneo cells by siRNAs affected gene expression in pathways associated with inflammation and blood vessel development. We postulate that functions regulated by CPPED1 in trophoblasts at choriodecidual interphase have a role in the induction of term labour, but it may be independent of AKT1.

Fetal hemodynamics and adverse outcome in primary school-aged children with fetal growth restriction: a prospective longitudinal study.

INTRODUCTION: Fetal growth restriction is associated with short-term and long-term mortality and morbidity. We hypothesized that adverse outcome in children with fetal growth restriction at primary school age is associated with fetoplacental circulatory abnormalities. MATERIAL AND METHODS: Comprehensive ultrasonographic assessment of fetoplacental hemodynamics was performed in 72 growth-restricted fetuses prenatally, and short-term outcome data were collected. At the median age of 9 years, mortality and morbidity were determined using medical charts and questionnaires. The impact of abnormal fetoplacental hemodynamics on mortality and morbidity with significant developmental disorders or delay were studied. RESULTS: Fetal growth restriction children with adverse long-term outcome were delivered earlier and with lower birthweights than were those with non-compromised outcome. Seventy percent of the fetal growth restriction group showed non-compromised long-term outcomes and participated in mainstream education at the appropriate age level. Absent/retrograde diastolic flow in the umbilical artery (p < 0.001), negative A-wave in the ductus venosus (p = 0.006), cardiomegaly (p = 0.02), hydrops (p = 0.006) and cardiovascular profile score <6 (p = 0.002) were associated with increased risk of adverse outcome. After adjustment for gestational age, these parameters demonstrated hazard ratios of 5.0-16.5 for adverse long-term outcome; increased systemic venous pulsatility and low cardiovascular profile score had the highest predictive power. CONCLUSIONS: Absent or reversed end-diastolic flow in the umbilical artery, reversed A-wave in the ductus venosus, cardiomegaly, hydrops, and low cardiovascular profile score are associated with adverse outcomes at primary school age in fetal growth restriction children. These fetal parameters play a significant role in the prediction of long-term outcomes for fetal growth restriction children.

Placental and fetal hemodynamics in prolonged pregnancies.

OBJECTIVE: We hypothesized that Doppler measurements of the placental and fetal central and peripheral hemodynamics would predict adverse outcomes in prolonged uncomplicated singleton pregnancies. METHOD: A total of 160 participants were recruited to this study. Doppler measurements of placental and fetal hemodynamics as well as cardiotocography (CTG) were assessed prior to induction of labor at >41+ weeks. CTG during delivery, umbilical artery (UA) pH and base excess at birth and neonatal data were evaluated. RESULTS: In 16% of cases the outcome was unfavorable, defined as UA pH <7.10, 5-min Apgar score <7, cesarean delivery for fetal distress and/or need for admission to neonatal intensive care. There were no differences in the pulsatility indices of the uterine and umbilical arteries, middle cerebral artery, descending aorta, ductus venosus and inferior vena cava between the groups with favorable and unfavorable outcome. In addition, the ventricular inflow patterns, outflow velocities of the great arteries, cardiac outputs and myocardial performance indices were similar between the groups. CONCLUSION: Doppler parameters of the placental and fetal central and peripheral hemodynamics do not differ prior to the induction of labor in prolonged pregnancies with favorable and unfavorable outcomes. This suggests that their value is limited and that other clinical tools are needed for intermittent fetal surveillance in prolonged pregnancies. © 2016 John Wiley & Sons, Ltd.

Fetal growth restriction and cardiovascular outcome in early human infancy: a prospective longitudinal study.

The association between low birth weight and premature cardiovascular disease has led to the "prenatal origin of adult disease-hypothesis". We postulated that fetal growth restriction is associated with cardiovascular changes detectable at birth and in early infancy. Fifty-two appropriately grown fetuses (AGA) and 60 growth-restricted fetuses (FGR) with (n = 20) or without (n = 40) absent or reversed end-diastolic umbilical artery blood flow were prospectively examined by echocardiography before birth, at 1 week and 6 months of life. The impact of growth restriction on postnatal blood pressure, heart rate, cardiovascular dimensions, and function, as well as on vascular morphology of umbilical cord vessels was studied. FGR fetuses displayed significant blood flow redistribution and were delivered earlier with lower birth weights than AGA fetuses. After adjustment for gender, gestational age, and weight at birth, there were no intergroup differences in blood pressure, heart rate, left ventricular morphology, mass, and performance, and in cord vessel morphology. During the first 6 months of life brachioradial pulse wave velocity increased more in FGR fetuses, while other parameters describing vascular stiffness remained comparable between the groups. Fetal growth restriction had no detectable adverse impact on cardiovascular dimensions and function at birth. Cardiovascular findings also remained comparable during the first 6 months of life between the groups except a higher increase in brachioradial pulse wave velocity in the FGR group. Our observations suggest that abnormalities that link reduced intrauterine growth with premature cardiovascular diseases may commence later in childhood, indicating a potential window for screening and prevention.

[Evidence-based cesarean section]. / Tutkimusnäyttöön perustuva keisarileikkaus.

Cesarean delivery is the most frequent major surgery in Finland: in 2013 over 16% of the deliveries were via cesarean route. 27% of the mothers are estimated to face complications. Optimal surgical techniques and other operation-related measures aim to reduce the incidence of complications. Recommendations favor preoperative antibiotics, vaginal preparation, transversal skin incision, non-development of bladder flap, blunt cephalo-caudad uterine extension, spontaneous placental removal, late cord clamping, continuous sutures for uterine closure and subcutaneous skin sutures. Optimal measures will not only reduce complications in cesarean deliveries but bring cost savings and unify the clinical routines and training in specialization programs.

Combination of PAPPA, fhCGß, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia.

OBJECTIVE: To evaluate the efficacy of first-trimester markers-pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin ß (fhCGß), alpha-fetoprotein (AFP), placental growth factor (PlGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). METHODS: During 2005-2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. RESULTS: PAPPA, fhCGß, and PlGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). CONCLUSIONS: First-trimester maternal serum levels of PAPPA, fhCGß, AFP, PlGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE.

Cyclosporine treatment in severe gestational pemphigoid.

Gestational pemphigoid, a rare autoimmune skin disease typically occurring during pregnancy, is caused by autoantibodies against collagen XVII. Clinically it is characterised by severe itching followed by erythematous and bullous lesions of the skin. Topical or oral glucocorticoids usually relieve symptoms, but in more severe cases systemic immunosuppressive treatments are needed. Data on immunosuppressive medication controlling gestational pemphigoid are sparse. We report 3 intractable cases of gestational pemphigoid treated with cyclosporine.

Gestational pemphigoid.

Gestational pemphigoid (pemphigoid gestationis, PG) is a rare autoimmune skin disorder occurring characteristically during pregnancy. Autoantibodies against placental BP180 (also known as BPAG2 or collagen XVII) cause damage to the skin basement membrane, resulting in severe itching and blistering rash over the body and the extremities. The diagnosis of PG is confirmed by immunofluorescence analysis of a skin biopsy, while serum levels of pemphigoid antigen BP180 antibody can be used to assess disease activity. PG with mild symptoms can be treated with topical corticosteroids, while oral corticosteroids are the mainstay in treatment of severe PG. PG usually flares up at the time of delivery, and resolves spontaneously shortly after. However, relapses in subsequent pregnancies are common. As PG has been linked to the risk of prematurity and fetal growth restriction, prenatal monitoring jointly by a dermatologist and an obstetrician is recommended. Mothers should also be informed of the potential risk of re-activation of the disease in subsequent pregnancies and during hormonal contraception.

Controlled ovarian hyperstimulation leads to high progesterone and estradiol levels during early pregnancy.

STUDY QUESTION: Are there differences in estrogen and progesterone secretion in singleton pregnancies, up to Week 11, between spontaneous pregnancies, after controlled ovarian hyperstimulation and fresh embryo transfer (COH + ET) and after frozen embryo transfer in a spontaneous cycle (FET)? SUMMARY ANSWER: Serum progesterone and estradiol (E2) concentrations after COH + ET were higher in early pregnancy, lasting up to Week 7-8, than FET and spontaneous pregnancies, while hormone levels after FET did not differ from spontaneous pregnancies. WHAT IS ALREADY KNOWN: The risk of adverse perinatal outcomes after COH + ET seems to be increased when compared with spontaneous pregnancies. One of the reasons suggested for this is related to ovarian hyperstimulation. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study consisting of three different groups of pregnant women which were followed-up weekly until Week 11 of their pregnancies. The spontaneous pregnancy group consisted of 41 women, the COH + ET group consisted of 39 and the FET group consisted of 30 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women in the control group with spontaneous conception were recruited from local prenatal clinics. Women in the COH + ET and FET groups were recruited from the Reproductive Unit of Oulu University Hospital. At each visit, a three-dimensional ultrasonography was performed to examine the ovarian volumes and vascularization. A blood sample was drawn to analyse progesterone and E2 levels. The pregnancy outcome was included in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE: At pregnancy Week 5, the serum progesterone levels were higher after the COH + ET (median 312, inter-quartile range 183-480 nmol/l), when compared with the spontaneous (63, 52-80 nmol/l; P < 0.001) and FET (74, 48-96 nmol/l; P < 0.001) pregnancies. At Week 11, the P (189, 124-260 nmol/l) was still higher in the COH + ET group (FET 101, 78-120 nmol/l, P < 0.001; spontaneous 115, 80-139 nmol/l, P < 0.01) than the other two groups. The E2 levels at Week 5 were also significantly higher after COH + ET (4.1, 2.2-6.6 nmol/l) than in the spontaneous pregnancies (1.1, 0.7-1.6 nmol/l, P < 0.001) or after FET (0.7, 0.6-0.9 nmol/l, P < 0.001). The volume of the ovaries and the intraovarian vasculature in the COH + ET group were significantly higher when compared with the other two groups (P < 0.001). The birthweight was negatively correlated with the serum P (R -0.340, P < 0.01) and E2 (R= -0.275, P < 0.05) in pregnancy Weeks 5-8. In the multivariate analysis evaluating the factors affecting birthweight of the newborn, the significant factors were the length of gestation, maternal height and progesterone or E2 secretion during Weeks 5-8. LIMITATIONS, REASONS FOR CAUTION: Because of the low number of patients in this study, larger cohort studies are required to confirm the findings. WIDER IMPLICATIONS OF THE FINDINGS: The findings here indicate that COH-induced increased luteal activity should be evaluated by measuring steroid levels or the ovarian size or vascularity, rather than number of oocytes retrieved. If unphysiologically high steroid activity during pregnancy after COH contributes to the risk of adverse perinatal outcomes after fresh embryo transfer, milder stimulation protocols or even freezing of all of the embryos should be considered. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a research grant from the Academy of Finland. The authors declare no conflicts of interest.

[Gestational pemphigoid]. / Raskauspemfigoidi--ihotautilääkärin ja synnytyslääkärin yhteinen haaste.

Gestational pemphigoid is a rare pruritic bullous pregnancy associated dermatosis caused by autoantibodies against placental and dermal collagen XVII. Clinically, it is characterized by severe pruritus and blisters on abdominal skin and extremities. Immunofluorescence analysis of perilesional skin is used in the diagnostics and maternal serum BP180-levels reflect the disease activity. Topical steroids and antihistamins usually relieve mild symptoms, but in severe cases oral corticosteroid is the drug-of-choice. Spontaneous recovery is common after parturition but this disease typically recurs in the following pregnancies. Due to the associated risk of prematurity and fetal growth restriction, prenatal monitoring jointly by a dermatologist and an obstetrician is recommended.

Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease.

Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case-control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case-control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors.