Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-ß2 glycoprotein I domain 1 antibodies.

OBJECTIVE: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti-ß2 glycoprotein I (anti-ß2GPI) in healthy pregnant and non-pregnant women of different ethnicities. METHODS: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-ß2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-ß2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide 2 (anti-CCP2) and anti-thyroid peroxidase (anti-TPO) were investigated in Sudanese females. RESULTS: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-ß2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-ß2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-ß2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-ß2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. CONCLUSIONS: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study.

OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population. DESIGN: Cohort study. SETTING: Sweden. POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion. METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking. MAIN OUTCOME MEASURES: Dementia, CVD, stroke. RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81). CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.

Gene Expression in Placentas From Nondiabetic Women Giving Birth to Large for Gestational Age Infants.

Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate δ synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII α 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.

Placental STAT3 signaling is activated in women with polycystic ovary syndrome.

STUDY QUESTION: Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling? SUMMARY ANSWER: Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS. WHAT IS KNOWN ALREADY: Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth. STUDY DESIGN, SIZE, DURATION: In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P < 0.05) versus controls. Placental mTOR signaling was not affected in PCOS women when compared with controls. Circulating levels of androstenedione, androst-5-ene-3ß, 17ß-diol, testosterone, 5α-dihydrotestosterone and etiocholanolone glucuronide were higher and estradiol lower in women with PCOS than in controls (all P < 0.05). No correlation between sex steroid levels in serum and P-STAT3 was observed. LIMITATIONS, REASONS FOR CAUTION: Women with PCOS and pregnancy complications were excluded to avoid the confounding effects of placental pathologies, which could modify STAT3 and mTOR signaling. Moreover, 97.4% of women with PCOS in the study displayed oligoamenorrhea at diagnosis. Thus, the current findings could be restricted to PCOS women with the oligo-anovulatory phenotype without pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS: Phosphorylation of STAT3 is increased in the placenta from women with PCOS and uncomplicated pregnancies, indicating that specific metabolic placental pathways are activated in the absence of obstetric and perinatal complications. STUDY FUNDING/COMPETING INTERESTS: The work was supported by the Swedish Medical Research Council (Project No. 2011-2732 and 2014-2775); Jane and Dan Olsson Foundation, Wilhelm and Martina Lundgrens's Science Fund; Hjalmar Svensson Foundation (E.S.-V and M.M.); Adlerbert Research Foundation; Swedish federal government under the LUA/ALF agreement ALFFGBG-136481 and 429501 and the Regional Research and Development agreement (VGFOUREG-5171, -11296 and -7861). MM thanks the Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests.

Sexual orientation of women does not affect outcome of fertility treatment with donated sperm.

STUDY QUESTION: Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? SUMMARY ANSWER: Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. WHAT IS KNOWN ALREADY: Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. STUDY DESIGN, SIZE, DURATION: This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n = 438, heterosexual n = 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n = 225, heterosexuals n = 230) during 2005-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: All clinics in Sweden offering sperm donation recruited patients. Differences in patients' medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearson's χ(2) test or Fisher's exact probability test. MAIN RESULTS AND THE ROLE OF CHANCE: 71.8% of heterosexuals and 69.0% of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7% for heterosexuals and 19.5% for lesbians. For D-IUI, the live birth rate was 12.8% for heterosexuals and 16.0% for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7% for heterosexuals and 26.2% for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%), uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, P = 0.03; polyps 1.8%, P = 0.03; child 2.5%, P = 0.003). LIMITATIONS, REASONS FOR CAUTION: This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. WIDER IMPLICATIONS OF THE FINDINGS: These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest.

The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring.

It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.

Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study.

OBJECTIVE: To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12 weeks) or second (12-21 weeks) trimester are associated with placental dysfunction disorders. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All pregnancies in the Swedish Medical Birth Register estimated to have started on 1 January 1997 or later and ended in a single birth on 31 December 2009 or earlier (n = 1 156 050). METHODS: Odds ratios with 95% confidence intervals were estimated for placental dysfunction disorders in women with an inpatient diagnosis of hyperemesis gravidarum, using women without inpatient diagnosis of hyperemesis gravidarum as reference. Risks were adjusted for maternal age, parity, body mass index, height, smoking, cohabitation with the infant's father, infant's sex, mother's country of birth, education, presence of hyperthyreosis, pregestational diabetes mellitus, chronic hypertension and year of infant birth. MAIN OUTCOME MEASURES: Placental dysfunction disorders, i.e. pre-eclampsia, placental abruption, stillbirth and small for gestational age (SGA). RESULTS: Women with hyperemesis gravidarum in the first trimester had only a slightly increased risk of pre-eclampsia. Women with hyperemesis gravidarum with first admission in the second trimester had a more than doubled risk of preterm (<37 weeks) pre-eclampsia, a threefold increased risk of placental abruption and a 39% increased risk of an SGA birth (adjusted odds ratios [95% confidence intervals] were: 2.09 [1.38-3.16], 3.07 [1.88-5.00] and 1.39 [1.06-1.83], respectively). CONCLUSIONS: There is an association between hyperemesis gravidarum and placental dysfunction disorders, which is especially strong for women with hyperemesis gravidarum in the second trimester.