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Background and Objective: Pregnancy alters the severity of asthma unpredictably. Uncertainty still exists about longitudinal changes in pulmonary function during pregnancy in both healthy and asthmatic women. This study aimed to compare pulmonary function changes during pregnancy in healthy and asthmatic women and to determine the relationship between pulmonary function and asthma-related quality of life during pregnancy. A secondary aim was to investigate the application of forced expiratory volume in 6 s (FEV6) for monitoring asthma during pregnancy., Methods: Pregnant women with (n = 20) and without asthma (n = 20) had pulmonary function tests at 8-20, 21-28 and 29-40 weeks gestation. Those with asthma also completed the Asthma Control Questionnaire (ACQ) and mini Asthma Quality of Life Questionnaire (mAQLQ) at each visit., Results: Pulmonary function declined in both groups at follow-up #1 (more markedly in those with asthma) but then improved at follow-up #2 (more markedly in those with asthma). In those with asthma, ACQ scores increased, while mAQLQ scores declined at follow-up #1; whilst at follow-up #2 these changes were in the opposite direction. FEV6 and forced vital capacity (FVC) were highly correlated (r = 0.88, p < 0.01) in asthmatics., Conclusions: Pulmonary function changes during second and third trimesters were more pronounced in asthmatics than in healthy women. FEV6 monitoring may assist pregnant women and their health professionals in optimizing asthma management. The changes in pulmonary function in women with asthma were not significantly associated with changes in asthma control or asthma-related quality of life.

Objective: To examine whether mRNA circulating in maternal blood coding genes regulating fetal growth are differentially expressed in (1) severe preterm fetal growth restriction (FGR) and (2) at 28 weeks' gestation in pregnancies destined to develop FGR at term., Study Design: mRNA coding growth genes were measured in 2 independent cohorts. The first was women diagnosed with severe preterm FGR (<34 weeks' gestation; n = 20) and gestation matched controls (n = 15), where the mRNA was measured in both maternal blood and placenta. The second cohort was a prospective longitudinal study (n = 52) of women whom had serial ultrasound assessments of fetal growth. mRNA coding growth genes in maternal blood were measured at 28 and 36 weeks in pregnancies with declining growth trajectories (ending up with term FGR; n = 10 among the 52 recruited) and controls who maintained normal growth trajectory (n = 15)., Results: In women with severe preterm FGR, there was increased expression of placental growth hormone (6.3-fold), insulin-like growth factors (IGF1, 3.4-fold; IGF2, 5.0-fold), IGF receptors (2.1-fold) and IGF binding proteins (3.0-fold), and reduced expression of ADAM12 (0.5-fold) in maternal blood (and similar trends in placenta) compared with controls (P < .05). Notably, at 28 weeks' gestation there was increased IGF2 (3.9-fold), placental growth hormone (2.7-fold), and IGF BP2 (2.1-fold) expression in maternal blood in women destined to develop FGR at term (P < .05)., Conclusion: Measuring mRNA coding growth genes in maternal blood may detect unsuspected severe preterm FGR already present in utero, and predict term FGR when measured at 28 weeks' gestation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

This study compared self-reported sleep latency (SL) and total sleep time (TST) to objective measures on polysomnography (PSG) during pregnancy. Thirty-three women in the third trimester (T3) of pregnancy, 16 women in the first trimester (T1) of pregnancy, and 15 non-pregnant women underwent overnight PSG, and shortly after awakening reported their perceived SL and TST. Results showed that, on average, the T3 group slightly overestimated their TSTs, whereas the T1 and non-pregnant groups underestimated TSTs when compared with objective measurement. All groups overestimated SL, and perceived SL was closest to the first epoch of 10 min of uninterrupted sleep or the first epoch of slow-wave sleep, rather than the first epoch of sleep (the current definition used for diagnostic sleep studies). The wide variation in discrepancies between estimation and PSG measurement for both TST and SL shows that self-reports made by both pregnant and non-pregnant women tend to be unreliable, which has important implications both clinically and for the many studies based on self-reported sleep patterns in pregnancy.

Aim: Cervico-vaginal fluid (CVF) may provide insight into the biochemical pathways of human reproduction and parturition. The aim of this study was to establish a 2-D electrophoretic map of human CVF in healthy, pregnant women at term., Methods: CVF was collected, concentrated and processed by routine 2-D polyacrylamide gel electrophoresis using pH 4-7-immobilised pH gradient strips and 8-16% gradient polyacrylamide gels. Imaged gels were analysed, yielding more than 400 proteins. A total of 157 proteins were common to all gels with a subgroup of the most abundant proteins being excised and characterised either by MALDI or by electrospray ion-trap mass spectrometry., Results: Twenty-one proteins were successfully identified, yielding 15 different proteins. These included blood transport proteins (albumin and transthyretin); a structural protein (beta-actin); proteins involved in fatty acid metabolism (fatty acid-binding protein and acetyl-CoA-binding protein); a calcium-binding protein (annexin III); an anti-inflammatory cytokine (interleukin-1 receptor antagonist); proteinase inhibitors (alpha-1-antitrypsin, monocyte/neutrophil elastase inhibitor, squamous cell carcinoma antigen-1 and cystatin A); and enzymes involved in oxidative stress defence (thioredoxin, peroxiredoxin 2, glutathione S-transferase P and copper,zinc superoxide dismutase)., Conclusion: CVF is a complex body fluid consisting of both endogenous and environmental proteins. The putative role of some of these proteins in the human reproductive tract is discussed.

Methods: A questionnaire was administered to 958 women attending the antenatal clinic at Mercy Hospital for Women, Melbourne, to ascertain their choice of title during pregnancy Midwifery, nursing and medical staff (376 in total) were also invited to respond to a similar questionnaire., Results: The response rate was 73.6% from the survey of all women who were overwhelmingly in favour of being called 'patient' as their first choice (34%), followed by 'other' (20%) and then 'mother' (19%). Virtually all women requesting 'other' wished to be called by their name. Women wishing to be called 'patient' for first choice did not significantly differ from the remainder of the study group in age, gestation, number of previous pregnancies, or number of children. When women from the Family Birth Centre (FBC) were analysed as a separate group, they had a clear preference to be called 'other' (unanimously, by their name) than the general antenatal population (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.1, 8.3; p < 0.0001). The staff survey, with a response rate of 84%, also demonstrated that 'patient' was the most popular first choice for patient title. Medical staff were significantly more likely to choose 'patient' (OR 4.2, 95% CI 2.3, 7.7; p < 0.0001), though the term 'patient' was the preferred choice of all staff.

Australian women make decisions about returning to paid work and care for their child within a policy environment that presents mixed messages about maternal employment and childcare standards. Against this background, an investigation of first-time mothers' decision-making about workforce participation and childcare was undertaken. Four women were studied from pregnancy through the first postnatal year using interview and diary methods. Inductive analyses identified three themes, all focused on dimensions of family security: financial security relating to family income, emotional security relating to childcare quality, and pragmatic security relating to childcare access. The current policy changes that establish improved childcare quality standards in Australia present a positive step toward alleviating family insecurities, but are insufficient to alleviate the evidently high levels of tension between workforce participation and family life experienced by these four women transitioning back into the workforce in Australia. (Contains 1 table.)

Objectives: To evaluate fetal heart rate (FHR) patterns during sleep in pregnancies complicated by preterm fetal growth restriction (FGR). To determine whether co‐existing sleep‐disordered breathing (SDB) impacts on acute FHR events or perinatal outcome. Design: Observational case control study. Setting and population: Women with preterm FGR and gestation‐matched well grown controls (estimated fetal weight above the 10th percentile with normal Doppler studies); tertiary maternity hospital, Australia. Methods: A polysomnogram, a test used to measure sleep patterns and diagnose sleep disorders, and concurrent cardiotocography (CTG), were analysed for respiratory events and FHR changes. Main outcome measures: Frequency of FHR events overnight in FGR cases versus controls and in those with or without SDB. Results: Twenty‐nine patients with preterm FGR and 29 controls (median estimated fetal weight 1st versus 60th percentile, P < 0.001) underwent polysomnography with concurrent CTG at a mean gestation of 30.2 weeks. The median number of FHR events per night was higher among FGR cases than among controls (3.0 events, interquartile range [IQR] 1.0–4.0, versus 1.0 [IQR 0–1.0]; P < 0.001). Women with pregnancies complicated by preterm FGR were more likely than controls to be nulliparous, receive antihypertensive medications, be supine at sleep onset, and to sleep supine (32.9% of total sleep time versus 18.3%, P = 0.03). SDB was common in both FGR and control pregnancies (48% versus 38%, respectively, P = 0.55) but was generally mild and not associated with an increase in overnight FHR events or adverse perinatal outcome. Conclusions: Acute FHR events overnight are more common in pregnancies complicated by preterm FGR than in pregnancies with normal fetal growth. Mild SDB was common in late pregnancy and well tolerated, even by fetuses with preterm FGR. Mild sleep‐disordered breathing seems well tolerated even by highly vulnerable fetuses. Mild sleep‐disordered breathing seems well tolerated even by highly vulnerable fetuses. This article includes Author Insights, a video abstract available at https://vimeo.com/bjogabstracts/authorinsights17192. [ABSTRACT FROM AUTHOR]

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease. [ABSTRACT FROM AUTHOR]

In Australia, a significant proportion of stillbirths remain unexplained. Recent research has highlighted nocturnal maternal behaviours as potentially modifiable contributors. This study determined whether sleep‐related behaviours including sleep position and sleep‐disordered breathing adversely affect fetuses overnight, in both uncomplicated pregnancies and those at increased risk due to hypertensive disorders or fetal growth restriction (FGR). All participants underwent polysomnography with time‐synchronized fetal heart rate (FHR) monitoring (cardiotocography – CTG) in late pregnancy. CTGs were analysed for abnormal FHR events, including decelerations and reduced variability, by two blinded observers and exported into the sleep study to temporally align FHR events with sleep behaviours. For each FHR event, 10 control epochs with normal FHR were randomly selected for the same participant. Conditional logistic regression assessed the relationships between FHR events and sleep behaviours. From 116 participants, 52 had a total of 129 FHR events overnight; namely prolonged decelerations and prolonged periods of reduced variability. Significantly more FHR events were observed in women with FGR and/or a hypertensive disorder compared with uncomplicated pregnancies (P = 0.006). FHR events were twice as likely to be preceded by a change in body position within the previous 5 min, compared with control epochs (P = 0.007), particularly in hypertensive pregnancies both with and without FGR. Overall, FHR events were not temporally related to supine body position, respiratory events or snoring. Our results indicate that most fetuses tolerate sleep‐related stressors, but further research is needed to identify the interplay of maternal and fetal conditions putting the fetus at risk overnight. Key points: Maternal sleep behaviours including supine position and sleep‐disordered breathing are potential contributors to stillbirth but much of this work is based on self‐reported data.Using time‐synchronized polysomnography and cardiotocography, we found that nocturnal fetal heart rate decelerations were more likely to be preceded by a change in body position compared with epochs containing normal fetal heart rate, particularly in hypertensive pregnancies with or without fetal growth restriction.There was no temporal relationship between maternal sleeping position, snoring or apnoeic events and an abnormal fetal heart rate overnight.We conclude that most fetuses can tolerate sleep‐related stressors with no evidence of fetal heart rate changes indicating compromised wellbeing.Further work needs to identify how sleep behaviours contribute to stillbirth risk and how these intersect with underlying maternal and fetal conditions. [ABSTRACT FROM AUTHOR]

Introduction: Placental dysfunction and inefficiency, is important in understanding fetal growth restriction and low birth weight. Two recent studies have examined the relationship between antidepressant use in pregnancy and placental weight ratios; one found lower placental weight ratio associated with antidepressant use and the other found a higher ratio.Methods: This study examined 342 women recruited in early pregnancy, including 75 taking antidepressants, 29 with current depression and 238 controls. Antidepressant use was measured through self-report in early and late pregnancy, hospital records at delivery and drug concentrations in umbilical cord and maternal blood obtained at delivery. Maternal depression was measured using the Structured Clinical Interview for the DSM IV (SCID) at recruitment. Placentas were collected at delivery and weighed, and infant birth weight recorded. Placental efficiency was measured using standardised placental weight residuals and included as the outcome in general linear models (ANOVA/ANCOVA) to test hypotheses.Results: While placental weight was higher for those on antidepressants compared to controls (z=.30 c.f. Z=-0.08, p=.012), there were no significant differences between the three groups after adjusting for maternal body mass index at recruitment. When comparing antidepressant groups separately there were small-to-moderate positive associations between (SSRI) concentrations and placental weight (rho's > 0.20, p's > 0.05), which did not reach significance.Conclusion: Antidepressant use in pregnancy was not associated with significant changes in placental efficiency after adjustment for confounding variables. Future research should expand on this to examine other aspects of placental function and include a wide range of potential confounding variables to draw clinically meaningful conclusions. [ABSTRACT FROM AUTHOR]

Abstract Background Uncontrolled asthma during pregnancy is associated with the maternal hazards of disease exacerbation, and perinatal hazards including intrauterine growth restriction and preterm birth. Interventions directed at achieving better asthma control during pregnancy should be considered a high priority in order to optimise both maternal and perinatal outcomes. Poor compliance with prescribed asthma medications during pregnancy and suboptimal prescribing patterns to pregnant women have both been shown to be contributing factors that jeopardise asthma control. The aim is to design and evaluate an intervention involving multidisciplinary care for women experiencing asthma in pregnancy. Methods/design A pilot single-blinded parallel-group randomized controlled trial testing a Multidisciplinary Approach to Management of Maternal Asthma (MAMMA©) which involves education and regular monitoring. Pregnant women with asthma will be recruited from antenatal clinics in Victoria, Australia. Recruited participants, stratified by disease severity, will be allocated to the intervention or the usual care group in a 1:1 ratio. Both groups will be followed prospectively throughout pregnancy and outcomes will be compared between groups at three and six months after recruitment to evaluate the effectiveness of this intervention. Outcome measures include Asthma Control Questionnaire (ACQ) scores, oral corticosteroid use, asthma exacerbations and asthma related hospital admissions, and days off work, preventer to reliever ratio, along with pregnancy and neonatal adverse events at delivery. The use of FEV1/FEV6 will be also investigated during this trial as a marker for asthma control. Discussion If successful, this model of care could be widely implemented in clinical practice and justify more funding for support services and resources for these women. This intervention will also promote awareness of the risks of poorly controlled asthma and the need for a collaborative, multidisciplinary approach to asthma management during pregnancy. This is also the first study to investigate the use of FEV1/FEV6 as a marker for asthma control during pregnancy. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12612000681853)

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks' gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth. There are no reliable tests for placental insufficiency, which can lead to fetal growth restriction and stillbirth. Here the authors demonstrate that low levels of circulating SPINT1 are associated to low birthweight, and several ultrasound and neonatal anthropomorphic indicators of placental insufficiency. [ABSTRACT FROM AUTHOR]

Objective: Sleep-disordered breathing (SDB) is characterised by intermittent hypoxemia, sympathetic activation and widespread endothelial dysfunction, sharing pathophysiologic features with the hypertensive disorders of pregnancy. We sought to determine whether coexisting SDB would adversely impact the outcomes of women with gestational hypertension (GH) and preeclampsia (PE), and healthy matched controls. Study design: Women diagnosed with GH or PE along with BMI- and gestation-matched normotensive controls underwent polysomnography in late pregnancy to establish the presence or absence of SDB (RDI ≥ 5). Clinical outcomes of hypertensive disease severity were compared between groups, and venous blood samples were taken in the third trimester and at delivery to examine for any impact of SDB on the anti-angiogenic markers of PE. Results: Data was available for 17 women with PE, 24 women with GH and 44 controls. SDB was diagnosed in 41% of the PE group, 63% of the GH group and 39% of the control group. Women with PE and co-existing SDB did not have worse outcomes in terms of gestation at diagnosis of PE (SDB = 29.1 (25.9, 32.1) weeks vs. no SDB = 32.0 (29.0, 33.9), p = n.s.) and days between diagnosis of PE and delivery (SDB = 20.0 (4.0, 35.0) days vs. no SDB = 10.5 (9.0, 14.0), p = n.s.). There were also no differences in severity of hypertension, antihypertensive treatment and biochemical, haematological and anti-angiogenic markers of PE between SDB and no SDB groups. Similar results were observed among women with GH. Healthy control women with SDB were no more likely to develop a hypertensive disorder of pregnancy in the later stages of pregnancy (SDB = 5.9% vs. no SDB = 7.4%, p = n.s.). Increasing the threshold for diagnosis of SDB to RDI ≥ 15 did not unmask a worse prognosis. Conclusion: The presence of SDB during pregnancy did not worsen the disease course of GH or PE, and was not associated with high blood pressure or anti-angiogenic markers of hypertensive disease amongst healthy pregnant women. Given the numerous reports of the relationship between SDB and diagnosis of hypertensive disorders of pregnancy, it appears more work is required to distinguish causal, versus confounding, pathways. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. Study design: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. Results: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p =.19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group—SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group—SDB = 41.7% vs. No SDB = 25.0%, p =.44), nor did SDB affect the total number of decelerations overnight (HDP group—SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p =.94; control group—SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26–22.26), p =.02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p =.015) and fewer growth restricted babies at birth (30% vs. 68.4%, p =.026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. Conclusion: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease. [ABSTRACT FROM AUTHOR]

Study Question: Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)?Summary Answer: IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR.What Is Known Already: It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner-the concept of 'primipaternity'. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR.Study Design, Size, Duration: Theories about the development of preeclampsia and the relative contribution of spermatic factors were explored by comparing the risk of hypertensive disorders of pregnancy and FGR among IVF pregnancies conceived with autologous gametes (own eggs and partner sperm) and those conceived with donor sperm, donor egg (and partner sperm) and donor embryo. To do this, we performed a retrospective cohort analysis of pregnancy outcomes among singleton pregnancies (n = 15 443) conceived through fertility clinics within Australia between 2009 and 2017.Participants/materials, Setting, Methods: All pregnancies resulting in a singleton pregnancy delivering after 20 weeks' gestation were included. The cohort was divided into donor sperm, donor egg and donor embryo (where both gametes came from a donor to create an embryo, or in a surrogate pregnancy) groups. We also compared the data with a control group, defined as IVF-conceived pregnancies from autologous cycles. A multivariable regression model was used to calculate an adjusted odds ratio (aOR).Main Results and the Role Of Chance: The final cohort contained 1435, 578 and 239 pregnancies conceived by donor sperm, donor egg and donor embryo, respectively, and 13 191 controls. There were a very small number of women lost to follow-up (31 women; 0.2% of total cohort). Compared to control pregnancies, there was no increase in the risk of hypertensive disorders among pregnancies conceived via donor sperm (aOR 0.94; 95% CI 0.73-1.21). Subgroup analysis was performed for a cohort where parity was known (n = 4551), and of these, 305 multigravida pregnancies were conceived via donor sperm. Among this cohort, no increased risk of preeclampsia or pregnancy-induced hypertension was found (aOR 1.18; 95% CI: 0.69-2.04) as a result of primipaternity (new sperm donor).A significantly increased risk for hypertensive disorders of pregnancy was associated with the use of donor eggs (but partner sperm; aOR 2.34; 95% CI 1.69-3.21). However, the association was no greater among pregnancies conceived with donor embryos (i.e. donated egg and sperm; aOR 2.0; 95% CI 1.25-3.17) than among the donor oocyte group. The overall incidence of FGR (defined as birthweight <10th centile) was 18%. There were no significant differences observed between donor sperm, or donor embryo pregnancies; however, egg donation was associated with a 1.5-fold increase in FGR.Limitations, Reasons For Caution: This study was limited by a lower than expected rate of hypertensive disorders of pregnancy (n = 862, 5.6%), which is contrary to the well-established increased risk among women using IVF. However, this is likely to be evenly distributed across the study groups and, therefore, unlikely to have introduced significant bias.Wider Implications Of the Findings: These findings suggest that exposure to new sperm may not be implicated in the pathogenesis of preeclampsia. The mechanism of increased risk seen in conceptions arising from egg or embryo donation remains unclear. Further investigation is required to elucidate these mechanisms and, ultimately, improve pregnancy outcomes following IVF.Study Funding/competing Interest(s): This study was supported by the Australian Commonwealth Government-Graduate Research Scheme (A.K.). Salary support was provided by the National Health and Medical Research Council of Australia (S.T.), Mercy Foundation (A.L.), and the Department of Obstetrics and Gynaecology at the University of Melbourne (R.H.). There are no competing interests. [ABSTRACT FROM AUTHOR]

Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia. The aim of this study was to determine the association between PPI use during pregnancy and preeclampsia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preeclampsia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preeclampsia (aOR of 1.17; 95% CI, 1.04-1.32) and preeclampsia at term (aOR of 1.20; 95% CI, 1.04-1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery <37 weeks) preeclampsia (aOR of 0.63; 95% CI, 0.41-0.96) and early (delivery <34 weeks) preeclampsia (aOR of 0.41; 95% CI, 0.20-0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preeclampsia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preeclampsia may help prevent this severe form of disease. [ABSTRACT FROM AUTHOR]

Summary: Sleep‐disordered breathing is more common in hypertensive disorders during pregnancy; however, most studies have not adequately accounted for the potential confounding impact of obesity. This study evaluated the frequency of sleep‐disordered breathing in women with gestational hypertension and pre‐eclampsia compared with body mass index‐ and gestation‐matched normotensive pregnant women. Women diagnosed with gestational hypertension or pre‐eclampsia underwent polysomnography shortly after diagnosis. Normotensive controls body mass index‐matched within ±4 kg m−2 underwent polysomnography within ±4 weeks of gestational age of their matched case. The mean body mass index and gestational age at polysomnography were successfully matched for 40 women with gestational hypertension/pre‐eclampsia and 40 controls. The frequency of sleep‐disordered breathing in the cases was 52.5% compared with 37.5% in the control group (P = 0.18), and the respiratory disturbance index overall did not differ (P = 0.20). However, more severe sleep‐disordered breathing was more than twice as common in women with gestational hypertension or pre‐eclampsia (35% versus 15%, P = 0.039). While more than half of women with a hypertensive disorder of pregnancy meet the clinical criteria for sleep‐disordered breathing, it is also very common in normotensive women of similar body mass index. This underscores the importance of adjusting for obesity when exploring the relationship between sleep‐disordered breathing and hypertension in pregnancy. More severe degrees of sleep‐disordered breathing are significantly associated with gestational hypertension and pre‐eclampsia, and sleep‐disordered breathing may plausibly play a role in the pathophysiology of pregnancy hypertension in these women. This suggests that more severe sleep‐disordered breathing is a potential therapeutic target for reducing the prevalence or severity of hypertensive disorders in pregnancy. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls. uEVs were isolated by centrifugation and analyzed by Western blot. Expression, proteolytic cleavage and phosphorylation was determined by densitometric analysis normalized to the exosome marker CD9. Results showed a significant increase in phosphorylation of the activating S130 site in NKCC2, the drug target for frusemide, in women with pre-eclampsia compared with normal pregnant women. Phosphorylation of the activating sites T101/105 in NKCC2 was similar but the activating T60 site in NCC, the drug target for thiazide diuretics, showed significantly less phosphorylation in pre-eclampsia compared with normal pregnancy. Expression of the larger forms of the α subunit of ENaC, the drug target for amiloride, was significantly greater in pre-eclampsia, with more fragmentation of theγ subunit. The differences observed are predicted to increase the activity of NKCC2 and ENaC while reducing that of NCC. This will increase sodium reabsorption, and so contribute to hypertension in pre-eclampsia. [ABSTRACT FROM AUTHOR]

Objective To evaluate the implementation of the 2013 Royal Australian and New Zealand College of Obstetricians and Gynaecologists ‘Management of Hepatitis B in Pregnancy’ guideline. Methods Retrospective cohort study of the clinical management and obstetric outcomes among hepatitis B virus-positive women in a single tertiary maternity hospital. Women with viral load >200,000 IU/ml were referred to a specialised clinic for consideration of tenofovir disoproxil fumarate therapy to reduce mother to child transmission. Results A total of 11,496 women gave birth during the study period, of which 101 (0.9%) women were hepatitis B virus positive. Viral load was measured in 99 (98%) of 101 hepatitis B virus-positive women; 30 (30%) had a viral load >200,000 IU/ml. Twenty-six women accepted tenofovir disoproxil fumarate; of these, 23 had a successful virological response (viral load <200,000 IU/ml before delivery). Conclusions Adherence to updated management guidelines and patient acceptance of tenofovir disoproxil fumarate in our Australian population were high when provided in the context of a dedicated perinatal service. [ABSTRACT FROM AUTHOR]

Pregnant women have a two- to threefold increased prevalence of restless legs syndrome (RLS) compared to the general population, and the majority of RLS patients also experience periodic limb movements in sleep (PLMS). PLMS have been associated with sleep disturbance as well as autonomic heart rate and blood pressure responses; however, the prevalence, cause and significance of PLMS during pregnancy remain unknown. This study evaluated the presence of PLMS in late pregnancy and its relationship to hypertensive disorders of pregnancy. Ninety-one women in the third trimester of pregnancy underwent overnight polysomnography. An RLS questionnaire and the Multivariate Apnea Risk Index were administered and venous blood was sampled within 2 weeks of the sleep study. After exclusions due to obstructive sleep apnoea and signal loss, PLMS data were available for 73 women, 36 hypertensive women and 37 BMI- and gestation-matched controls. PLMS were found to be very common during pregnancy; 45% of women had a PLMS index > 5 and 25% had a PLMS index > 15. The number of PLMS per hour did not differ by hypertensive status. Sleep quality was mostly unaffected by PLMS, as was change in blood pressure overnight. While RLS was reported by 18.3% of the sample, this did not reliably predict the presence of PLMS. Despite iron deficiency being common in this population, it was not associated with PLMS. This novel study investigating the frequency and impact of PLMS during pregnancy revealed that PLMS are very common in the third trimester; however, this disorder appears to be benign in terms of objective sleep quality and relationship with pregnancy-related hypertension. [ABSTRACT FROM AUTHOR]

The health services participating in the CoMaND and CHOPAN projects include: Mercy Health (Mercy Hospital for Women, Werribee Mercy Hospital); the Royal Women's Hospital, the Women's at Sandringham; Monash Health (Monash Medical Centre, Casey Hospital, Dandenong Hospital); Northern Health (the Northern Hospital); Western Health (Joan Kirner Women's and Children's Hospital); Eastern Health (Box Hill Hospital, the Angliss Hospital); Peninsula Health (Frankston Hospital). Keywords: COVID-19; Maternal health; Perinatal; Obstetrics; Pregnancy; Neonatology; Clinical trials as topic EN COVID-19 Maternal health Perinatal Obstetrics Pregnancy Neonatology Clinical trials as topic 433 434 2 11/02/21 20211101 NES 211101 Acknowledgements The CoMaND project is funded by a philanthropic grant from the Norman Beischer Medical Research Foundation and a University of Melbourne Department of Obstetrics and Gynaecology Innovation grant. Neonatology, COVID-19, Maternal health, Perinatal, Obstetrics, Pregnancy, Clinical trials as topic. [Extracted from the article]

Preeclampsia is a major pregnancy complication where excess placental release of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin causes maternal endothelial and multisystem organ injury. Clinical trials have commenced examining whether pravastatin can be used to treat preeclampsia. However, the preclinical evidence supporting pravastatin as a treatment is limited to animal models, with almost no studies in human tissues. Therefore, we examined whether pravastatin reduced sFlt-1 and soluble endoglin secretion and decreased endothelial dysfunction in primary human tissues. Pravastatin reduced sFlt-1 secretion from primary endothelial cells, purified cytotrophoblast cells, and placental explants obtained from women with preterm preeclampsia. It increased soluble endoglin secretion from endothelial cells but did not change secretion from placental explants. The regulation of sFlt-1 by pravastatin seemed to be mediated via the 3-hydroxy-3-methylglutaryl-coenzyme A reductase cholesterol synthesis pathway. Pravastatin also reduced markers of endothelial dysfunction, including vascular cell adhesion molecule-1 expression and leukocyte adhesion on endothelial cells and increased endothelial cell migration and invasion. We also treated 4 patients with preterm preeclampsia presenting at <30 weeks of gestation with daily pravastatin. Pravastatin seemed to stabilize blood pressure, proteinuria, and serum uric acid levels. Furthermore, serum sFlt-1 levels decreased. We collected the placentas at delivery and found that pravastatin reduced sFlt-1 secretion. These results indicate that pravastatin reduced sFlt-1 and soluble endoglin production and decreased endothelial dysfunction in primary human tissues. We also present pilot data, suggesting that pravastatin can stabilize clinical and biochemical features of preterm preeclampsia. Our data obtained in human tissues support the concept that pravastatin is a candidate therapeutic for preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Telehealth has the potential to improve asthma management through regular monitoring of lung function and/or asthma symptoms by health professionals in conjunction with feedback to patients. Although the benefits of telehealth for improving asthma management have been extensively studied, the feasibility of telehealth for supporting asthma management in pregnant women has not been investigated. This study aims to evaluate the use of telehealth for remotely monitoring lung function and optimising asthma control during pregnancy. Methods: A randomised controlled trial comparing usual care with a telehealth program (MASTERY©) has been conducted. The intervention comprised a mobile application - Breathe-easy© supported by a Bluetooth-enabled handheld device (COPD-6®), which was used for self-monitoring of lung function (FEV1, FEV6) twice daily, and recording asthma symptoms and medication usage weekly; and a written asthma action plan (WAAP). The primary outcome measure is change in asthma control measured using the Asthma Control Questionnaire (ACQ). Secondary outcomes include changes in mini-Asthma Quality of Life Questionnaire (mAQLQ) score, lung function, asthma-related health visits, days off work/study, and oral corticosteroid use. Outcome data were collected at baseline, 3 months and 6 months by a research assistant masked to group allocation. Maternal and neonatal outcomes were also collected post-partum. Discussion: This is the first study to evaluate the application of telehealth to optimize asthma management in pregnant women. If effective, this telehealth program could improve asthma self-management by pregnant women which may reduce the maternal and fetal risks of poorly controlled asthma during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled asthma during pregnancy is associated with maternal and perinatal hazards. A pharmacist-led intervention directed at improving maternal asthma control, involving multidisciplinary care, education, and regular monitoring to help reduce these risks, was developed and evaluated.Methods: A randomized controlled trial was carried out in the antenatal clinics of two major Australian maternity hospitals. Sixty pregnant women < 20 weeks gestation who had used asthma medications in the previous year were recruited. Participants were randomized to either an intervention or a usual care group and followed prospectively throughout pregnancy. The primary outcome was Asthma Control Questionnaire (ACQ) score. Mean changes in ACQ scores from baseline were compared between groups at 3 and 6 months to evaluate intervention efficacy.Results: The ACQ score in the intervention group (n = 29) decreased by a mean ± SD of 0.46 ± 1.05 at 3 months and 0.89 ± 0.98 at 6 months. The control group (n = 29) had a mean decrease of 0.15 ± 0.63 at 3 months and 0.18 ± 0.73 at 6 months. The difference between groups, adjusting for baseline, was -0.22 (95% CI, -0.54 to 0.10) at 3 months and -0.60 (95% CI, -0.85 to -0.36) at 6 months. The difference at 6 months was statistically significant (P < .001) and clinically significant (> 0.5). No asthma-related oral corticosteroid use, hospital admissions, emergency visits, or days off from work were reported during the trial.Conclusions: A multidisciplinary model of care for asthma management involving education and regular monitoring could potentially improve maternal asthma outcomes and be widely implemented in clinical practice.Trial Registry: Australian and New Zealand Clinical Trials Registry; No.: ACTRN12612000681853; URL: www.anzctr.org.au. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes. Study Design: We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth. Results: Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1–13.8) for cases and 2.2 (1.3–3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25–5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2–29.7, p = 0.03) and body mass index (OR 2.52; 1.09–5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93–30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different. Conclusion: OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth. [ABSTRACT FROM AUTHOR]

Background Mother-to-child transmission ( MTCT) of hepatitis B virus continues to occur despite the interventions of hepatitis B vaccination and immunoglobulin. The most significant risk factor in transmission is high maternal viral load. Being aware of viral replicative activity permits risk stratification and allows the opportunity for additional preventative measures such as antiviral therapy. Methods Retrospective audit of investigations and clinical management among hepatitis B surface antigen-positive pregnant women from three maternity services across Victoria over a five-year period from 2006 to 2011. Results Over the study period at the three institutions, there were 46,855 births, and 398 hepatitis B-positive pregnant women. 87% of the women were non-Australian-born. Viral load testing was performed in <20% of all pregnancies, and hepatitis B e antigen status assessed in 33%. Only 18% of the women with hepatitis B were referred for specialist care, but if referred, they were more likely to have an assessment of viral replicative status performed. Compliance with administration of neonatal hepatitis B immunoglobulin and birth-dose vaccination was high (>90%). Conclusion There is scope for considerable improvement in referral and assessment of pregnant women with hepatitis B infection. Guidelines addressing the issue of maternal viral replicative status and the need for antiviral therapy may assist in guiding clinical management. [ABSTRACT FROM AUTHOR]

Background: Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses that are hypoxic, none can determine the severity of hypoxia/acidemia. We hypothesized a hypoxic/ acidemic fetus would up-regulate and release hypoxia-induced mRNA from the fetoplacental unit into the maternal circulation, where they can be sampled and quantified. Furthermore, we hypothesized the abundance of hypoxia induced mRNA in the maternal circulation would correlate with severity of fetal hypoxia/acidemia in utero. We therefore examined whether abundance of hypoxia-induced mRNA in the maternal circulation correlates with the degree of fetal hypoxia in utero. Methods: We performed a prospective study of two cohorts: 1) longitudinal study of pregnant women undergoing an induction of labor (labor induces acute fetal hypoxia) and 2) pregnancies complicated by severe preterm growth restriction (chronic fetal hypoxia). For each cohort, we correlated hypoxia induced mRNA in the maternal blood with degree of fetal hypoxia during its final moments in utero, evidenced by umbilical artery pH or lactate levels obtained at birth. Gestational tissues and maternal bloods were sampled and mRNAs quantified by microarray and RT-PCR. Results: Hypoxia-induced mRNAs in maternal blood rose across labor, an event that induces acute fetal hypoxia. They exhibited a precipitous increase across the second stage of labor, a particularly hypoxic event. Importantly, a hypoxia gene score (sum of the relative expression of four hypoxia-induced genes) strongly correlated with fetal acidemia at birth. Hypoxia-induced mRNAs were also increased in the blood of women carrying severely growth restricted preterm fetuses, a condition of chronic fetal hypoxia. The hypoxia gene score correlated with the severity of ultrasound Doppler velocimetry abnormalities in fetal vessels. Importantly, the hypoxia gene score (derived from mRNA abundance in maternal blood) was significantly correlated with the degree of fetal acidemia at birth in this growth restriction cohort. Conclusions: Abundance of mRNAs coding hypoxia-induced genes circulating in maternal blood strongly correlates with degree of fetal hypoxia/acidemia. Measuring hypoxia-induced mRNA in maternal blood may form the basis of a novel non-invasive test to clinically determine the degree of fetal hypoxia/acidemia while in utero. [ABSTRACT FROM AUTHOR]

Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios. [ABSTRACT FROM AUTHOR]

Aim: Inherited thrombophilic polymorphisms have been linked to pregnancy-related thromboembolism and other adverse pregnancy outcomes. As there are limited data on the prevalence of these polymorphisms in Australian populations, we aimed to assess this in an antenatal population. Methods: Healthy nulliparous women ( n = 2031) were recruited to this study. The women had no past or family history of venous thromboembolism. Women were excluded if they or a family member was known to be a carrier of any thrombophilic marker. Genotyping from venous blood for the factor V Leiden, prothrombin 20210A, MTHFR 677 and 1298 and thrombomodulin C1418T polymorphisms was undertaken. Results: Key findings were that 107 of 2019 (5.30, 95% confidence interval 4.36–6.37%) women tested were heterozygous carriers of factor V Leiden and one was homozygous (0.05, 0–0.27%); 2.43% of women were heterozygous carriers of the prothrombin gene mutation (1.80–3.20%) while no women were homozygous for this mutation; 11.62% (10.22–13.02%) and 9.98% (8.67–11.29%) were homozygous for the MTHFR 677 and 1298 polymorphisms, respectively, and 3.43% (2.63–4.22%) of women were homozygous for the thrombomodulin polymorphism. Conclusions: The prevalence of these polymorphisms is consistent with previously published data in Caucasian populations. These data will provide the basis for further assessment of the relationship between poor pregnancy outcome and these inherited thrombophilic polymorphisms in an asymptomatic antenatal population. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We sought to determine the long-term risk of type 2 diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM) and assess what maternal antepartum, postpartum, and neonatal factors are predictive of later development of type 2 diabetes. RESEARCH DESIGN AND METHODS--This was a retrospective cohort study using survival analysis on 5,470 GDM patients and 783 control subjects who presented for postnatal follow-up at the Mercy Hospital for Women between 1971 and 2003. RESULTS--Risk of developing diabetes increased with time of follow-up for both groups and was 9.6 times greater for patients with GDM. The cumulative risk of developing type 2 diabetes for the GDM patients was 25.8% at 15 years postdiagnosis. Predictive factors for the development of type 2 diabetes were use of insulin (hazard ratio 3.5), Asian origin compared with Caucasian (2.1), and 1-h blood glucose (1.3 for every 1 mmol increase above 10.1 mmol). BMI was associated with an increased risk of developing type 2 diabetes but did not meet the assumption of proportional hazards required for valid inference when using Cox proportional hazards. CONCLUSIONS--While specific predictive factors for the later development of type 2 diabetes can be identified in the index pregnancy, women with a history of GDM, as a group, are worthy of long-term follow-up to ameliorate their excess cardiovascular risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to evaluate the acceptability of the SpaceLabs 90207 ambulatory blood pressure monitor among pregnant women. METHODS: Patients participating in research projects involving ambulatory blood pressure monitoring(ABPM) in pregnancy(N = 110) were asked to complete a questionnaire relating to patient satisfaction on completion of the monitoring period. The first part of the questionnaire involved rating on a visual Likert scale(0–10) whether they found the monitor heavy, noisy, cumbersome, disturbing, or embarrassing to wear. The second part of the questionnaire addressed whether cuff inflation caused significant sleep disturbance or physical discomfort. Outcome MEASURES: The mean(SD) and range of the Likert scores are reported. The number of patients reporting sleep disturbance or physical discomfort was calculated. Logistic regression was used to examine which factors were significant predictors of discontinuing monitoring. RESULTS: The mean(SD) responses measured by the Liken scores were: finding the monitor heavy 3.2(2.3); comfortable 4.8(2.3); straightforward to use 8.8(1.8); cumbersome 3.8(2.3); disturbing 4.5(2.7); noisy 1.6(2.2); and embarrassing to wear 1.7(2.1). Difficulty initiating sleep was reported by 28.8% of patients, and a further 56.3% reported difficulty maintaining sleep due to the monitor. Sleep disturbance was found to be the strongest predictor[r = 0.52; OR 1.68(1.23, 2.27), p = 0.0009] for the 15% of patients discontinuing the monitoring. CONCLUSIONS: While pregnant women tolerate the noise, weight, inconvenience, and disturbance associated with ambulatory blood pressure monitoring(ABPM) well, sleep disturbance is a major cause of dissatisfaction and noncompliance. Future studies should evaluate critically the number of nocturnal blood pressure assessments required, and should allow for a withdrawal rate of approximately 15% when performing sample size calculations for ABPM studies in pregnancy. [ABSTRACT FROM AUTHOR]

Lists brief medical reports for various studies and findings. Occupational fatigue and preterm premature rupture of membranes; Blood pressure in late pregnancy and work outside the home; Cesarean delivery rates; Appendectomy and protection against ulcerative colitis; Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women; Preoperative depression and mortality in coronary artery bypass surgery; Others.

Objective: The objective of the study was to determine the frequency of microbial invasion of the amniotic cavity in the midtrimester of pregnancy in patients undergoing amniocentesis for clinical indications.Study Design: This was a prospective investigation of the amniotic fluid of 344 asymptomatic women recruited in midpregnancy for the presence of microbial DNA. Amniotic samples obtained at the time of amniocentesis for genetic testing on women between 15 and 22 weeks of gestation were tested specifically for the presence of Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, and Mycoplasma genitalium as well as for other bacteria and fungi using broad-range polymerase chain reaction only. Pregnancy outcomes were reviewed independent of all molecular test results.Results: Using broad-range polymerase chain reaction, the prevalence of microbial invasion of the amniotic cavity in women between 15 and 22 weeks of gestation was 0% (0 vs 344). Early preterm delivery occurred in only 4 women (1%); 1 delivered electively and 3 spontaneously. None were associated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, or Mycoplasma genitalium. In addition, broad range polymerase chain reaction did not reveal the presence of other bacterial or fungal microbes.Conclusion: Microbial invasion of the amniotic cavity in midtrimester gestations of low-risk pregnant women was not detected using molecular methods in 344 patients. [ABSTRACT FROM AUTHOR]

Background: Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk of adverse perinatal outcomes including stillbirth.Objective: Measuring RNA circulating in the maternal blood may provide a noninvasive insight into placental function. We examined whether measuring RNA in the maternal blood at 26-30 weeks' gestation can identify pregnancies at risk of late-onset FGR. We focused on RNA highly expressed in placenta, which we termed "placental-specific genes."Study Design: This was a case-control study nested within a prospective cohort of 600 women recruited at 26-30 weeks' gestation. The circulating placental transcriptome in maternal blood was compared between women with late-onset FGR (<5th centile at >36+6 weeks) and gestation-matched well-grown controls (20-95th centile) using microarray (n = 12). TaqMan low-density arrays, reverse transcription-polymerase chain reaction (PCR), and digital PCR were used to validate the microarray findings (FGR n = 40, controls n = 80).Results: Forty women developed late-onset FGR (birthweight 2574 ± 338 g, 2nd centile) and were matched to 80 well-grown controls (birthweight 3415 ± 339 g, 53rd centile, P < .05). Operative delivery and neonatal admission were higher in the FGR cohort (45% vs 23%, P < .05). Messenger RNA coding 137 placental-specific genes was detected in the maternal blood and 37 were differentially expressed in late-onset FGR. Seven were significantly dysregulated with PCR validation (P < .05). Activating transcription factor-3 messenger RNA transcripts were the most promising single biomarker at 26-30 weeks: they were increased in fetuses destined to be born FGR at term (2.1-fold vs well grown at term, P < .001) and correlated with the severity of FGR. Combining biomarkers improved prediction of severe late-onset FGR (area under the curve, 0.88; 95% CI 0.80-0.97). A multimarker gene expression score had a sensitivity of 79%, a specificity of 88%, and a positive likelihood ratio of 6.2 for subsequent delivery of a baby <3rd centile at term.Conclusion: A unique placental transcriptome is detectable in maternal blood at 26-30 weeks' gestation in pregnancies destined to develop late-onset FGR. Circulating placental RNA may therefore be a promising noninvasive test to identify pregnancies at risk of developing FGR at term. [ABSTRACT FROM AUTHOR]

Objective: To estimate whether low-dose aspirin use is associated with an altered risk of delivering a small-for-gestational age (SGA) neonate among women with a history of having an SGA neonate in a prior pregnancy.Methods: We performed a Swedish register-based cohort study including women in their second pregnancy who had a history of having an SGA neonate (birth weight less than the 10th percentile). The association between use of low-dose aspirin in subsequent pregnancy and birth of an SGA neonate or a severely SGA neonate (birth weight less than the third percentile) were estimated using inverse propensity-weighted estimation, accounting for potential confounders.Results: Among 8,416 women who gave birth to an SGA neonate in their first pregnancy, 801 (9.5%) used low-dose aspirin during their second pregnancy. The incidence of SGA neonates was similar among women using low-dose aspirin (21.7%) and those who did not use aspirin (20.7%). Low-dose aspirin use in pregnancy was not associated with an altered risk of having an SGA neonate (adjusted relative risk [aRR] 0.86, 95% CI 0.67-1.10) or a severely SGA neonate (aRR 0.98, 95% CI 0.71-1.34). Given the strong association between preeclampsia and SGA, we performed subgroup analyses based on preeclampsia status. Among women who had an SGA neonate and co-existing preeclampsia in their first pregnancy, low-dose aspirin was not associated with an altered risk of having an SGA (aRR 0.83, 95% CI 0.63-1.10) or severely SGA (aRR 1.02, 95% CI 0.73-1.44) neonate. Additionally, no association was seen among women who developed preeclampsia in their second pregnancy.Conclusion: Among women with a history of having an SGA neonate, low-dose aspirin was not associated with a decreased risk of having an SGA or severely SGA neonate in subsequent pregnancy. These findings suggest that low-dose aspirin should not be used to prevent recurrent SGA. [ABSTRACT FROM AUTHOR]

Background: Betel nut is the fourth most commonly abused substance worldwide and has been associated with significant adverse health outcomes. Little is known about its effects on the fetus.Objective: To perform a systematic review of studies investigating prenatal betel nut use and adverse perinatal outcomes.Search Strategy: Pubmed, Embase, and Cochrane databases were searched from inception until July 2018 using the terms areca, betel nut, pregnancy, pregnancy complications, and infection.Selection Criteria: Eligible studies included case-control, cohort, and randomized control studies involving pregnant women.Data Collection and Analysis: Where appropriate, bivariate meta-analysis was performed, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Main Results: In total, 28 studies were screened and eight studies (including 15 270 women) were included in the review and meta-analysis. Preterm birth, low birthweight, and anemia were most commonly investigated. Meta-analysis revealed a significant association between betel nut use and low birthweight, with a pooled OR of 1.75 (95% CI, 1.35-2.27).Conclusions: The review identified only eight eligible studies, all based in the Asia-Pacific region. There was a significant association between low birthweight and betel nut exposure in pregnancy. Further prospective studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Inherited Thrombophilia Polymorphisms and Pregnancy Outcomes in Nulliparous Women," which appeared in the January 2010 issue of the magazine.