The Experience of Anaemia and Ingesting Oral Iron Supplementation in Pregnancy: A Qualitative Study.

INTRODUCTION: The objective of this study was to understand the experience of iron deficiency anaemia requiring oral iron in pregnancy and the factors affecting compliance with oral iron supplementation. Participants' understanding regarding the possible consequences of anaemia in pregnancy was also explored. Feedback on a proposed randomised controlled trial of daily versus alternate day oral iron in pregnancy was sought. MATERIALS & METHODS: Following ethical approval, fourteen semi-structured one-to-one interviews were carried out using an interview tool with open-ended questions. Recruitment was carried out through social media and from an antenatal out-patient setting. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Fatigue emerged as a predominant and troubling symptom. Awareness was often highlighted through friends/family and from healthcare professionals, particularly in first pregnancies. Knowledge surrounding the potential short-term and long-term adverse consequences of untreated anaemia however was limited. Gastro-intestinal side-effects, a previous experience of poor tolerance and forgetfulness all negatively impacted compliance with oral iron supplementation in pregnancy. Routine, a perceived improvement in fatigue with supplementation and reduced dose frequency recurred as themes which positively affected compliance. Pregnancy as a motivating factor recurred as a theme in analysis. The role of diet was felt to be important. Knowledge of iron-rich foods and absorption aids and inhibitors was good, but practice on optimal ingestion of oral iron supplementation varied. Feedback on trial acceptability was positive with the benefit of extra supportive care noted. Incorporating study visits with routine care was advised in view of time constraints. This area of research was perceived as important. CONCLUSION: In order to successfully reduce the rates of iron deficiency anaemia in pregnancy, it is crucial that all factors affecting compliance with oral iron are considered. Providing women with the important information on the possible consequences of sub optimally treated anaemia may help to improve this public health issue.

Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive treatment.

STUDY QUESTION: Which transcriptomic alterations in mid-luteal endometrial scratch biopsies, taken prior to the assisted reproductive treatment (ART) treatment cycle are associated with unsuccessful pregnancy? SUMMARY ANSWER: Dysregulated interleukin-17 (IL-17) pathway components are demonstrated in women who fail to become pregnant after ART. WHAT IS KNOWN ALREADY: Implantation failure is now recognised as a critical factor in unexplained infertility and may be an important component of failed ART. STUDY DESIGN, SIZE, DURATION: Using a prospective longitudinal study design, 29 nulliparous women with unexplained infertility undergoing ART were recruited between October 2016 and February 2018. Mid-luteal stage endometrium and matched serum samples were collected, and patients underwent a single embryo transfer in the subsequent cycle. RNA-seq analysis of endometrial biopsies was performed on the discovery cohort (n = 20). PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene set enrichment analysis of the differentially expressed genes (DEGs) was performed. Endometrium and serum were then prepared for IL-17A analysis by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: There were 204 differentially expressed protein-coding genes identified in tissue from women who became pregnant (n = 9) compared with tissue from women who failed to become pregnant (n = 11) (false discovery rate; P < 0.05). Of the 204 DEGs, 166 were decreased while 38 were increased in the pregnant compared to the non-pregnant groups. Gene set enrichment analysis of the DEGs identified an over-representation of IL-17 and Pl3K-Akt signalling pathways. All the DEGs within the IL-17 signalling pathway (MMP3, MMP1, IL1ß, LCN2, S100A9 and FOSL1) demonstrated decreased expression in the pregnant group. Serum IL-17 protein levels were increased in the non-pregnant discovery cohort (n = 11) and these findings were confirmed a validation cohort (n = 9). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study include the cohort size and the lack of aneuploidy data for the embryos; however, all embryos transferred were single good or top-quality blastocysts. WIDER IMPLICATIONS OF THE FINDINGS: These findings demonstrate dysregulated IL-17 pathway components in women who fail to become pregnant after ART. Elevated serum levels of the pro-inflammatory cytokine IL-17 may predict failure of ART in women with unexplained infertility. Future trials of anti-IL-17 therapies in this cohort warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S): Funding from the UCD Wellcome Institutional Strategic Support Fund, which was financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership (ref 204844/Z/16/Z), is acknowledged. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NA.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

The role of the cervix in fertility: is it time for a reappraisal?

Knowledge regarding the role of the cervix in fertility has expanded considerably over the past 20 years and in this article, we propose that it is now time for its function to be reappraised. First, we review the anatomy of the cervix and the vaginal ecosystem that it inhabits. Then, we examine the physiology and the role of the cervical mucus. The ongoing mystery of the exact mechanism of the sperm-cervical mucus interaction is reviewed and the key players that may unlock this mystery in the future are discussed. The soluble and cellular biomarkers of the lower female genital tract which are slowly being defined by contemporary research are reviewed. Attempts to standardize these markers, in this milieu, are hindered by the changes that may be attributed to endogenous or exogenous factors such as: age, hormonal changes during the menstrual cycle, ectropion, infection, smoking and exposure to semen during sexual intercourse. We review what is known about the immunology of the cervix. With the widespread use of large loop excision of the transformation zone (LLETZ) for treatment of cervical intraepithelial neoplasia, the anatomy of the cervix is changing for many women. While LLETZ surgery has had very positive effects in the fight against cervical cancer, we debate the impact it could have on a woman's fertility.

Novel placental ultrasound assessment: potential role in pre-gestational diabetic pregnancy.

OBJECTIVES: Management of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics. METHODS: This was a prospective cohort study of 50 women with diabetes and 250 controls (12-40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology. RESULTS: Placental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found. CONCLUSIONS: This study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

Technology-supported dietary and lifestyle interventions in healthy pregnant women: a systematic review.

Overweight and obesity are associated with increased risk of adverse maternal and fetal outcomes. However, the actuality of delivering effective lifestyle interventions in clinical practice is hampered by a high demand for resources. The use of technology to assist lifestyle interventions needs to be explored as a valid method of reducing strain on resources, and enhancing the effectiveness and population reach of interventions. The aim was to systematically review the literature on the use of technology-supported lifestyle interventions for healthy pregnant women and their impact on maternal outcomes. Online databases and registries were searched in March 2013. Primary outcomes of selected English language studies were fasting maternal glucose, incidence of gestational diabetes mellitus (GDM) and maternal gestational weight gain. Secondary outcomes were intervention uptake and acceptance, and dietary or physical activity modification. Studies whose subjects were diagnosed with GDM prior to intervention were excluded. The minimal number of eligible studies and varying outcomes precluded formal meta-analysis of the data. Initially, 203 articles were identified and screened. Seven articles, including five randomised controlled trials, met inclusion criteria for the current review. Results demonstrate several potential benefits associated with technology-supported interventions in pregnancy, despite minimal search results. Although communication technology holds potential as a safe therapeutic tool for the support of lifestyle interventions in pregnancy, there is a paucity of data on its effectiveness. Further RCTs examining the effectiveness of communication technology are required, particularly among those most likely to benefit from lifestyle interventions, such as overweight and obese pregnant women.

Well-being in pregnancy: an examination of the effect of socioeconomic, dietary and lifestyle factors including impact of a low glycaemic index dietary intervention.

BACKGROUND/OBJECTIVE: Well-being has been linked to the quality of diet and lifestyle in adults; however, there is a paucity of data in pregnancy. The aim of this study was to examine the relationship between well-being and socioeconomic status, diet and lifestyle during pregnancy and to consider the effect of intervention with low glycaemic index (GI) diet on well-being. SUBJECTS/METHODS: This was a cohort analysis of 619 participants of the ROLO study (Randomised cOntrol trial of LOw GI diet versus no dietary intervention to prevent recurrence of fetal macrosomia). The following data were collected: educational attainment, dietary intakes (food frequency questionnaire), physical activity (self-reported) and well-being (WHO-5-Item Wellbeing Index--expressed as a percentage). RESULTS: Well-being was positively associated with education and physical activity. Third-level education was associated with a 3.07-point higher well-being percentage score, and each day that an individual achieved >30 min walking per week was associated with a 1.10-point increase in percentage well-being score, Radj(2) 2.4% (F=7.260, P=0.001). The intervention low GI group had a significantly lower percentage well-being score than the usual diet group (56.3% vs 59.9%, P=0.015). No correlation was noted between well-being and GI status calculated from food diaries (P=0.469). Well-being was not associated with micronutrient intake. CONCLUSIONS: Well-being in pregnancy was independently and positively associated with education and physical activity and negatively associated with low GI dietary intervention. These findings have significance not only for women at risk of low mood but also for healthcare professionals when counselling women about the importance of healthy lifestyle in pregnancy.

Computerized assessment of placental calcification post-ultrasound: a novel software tool.

OBJECTIVES: Placental calcification is associated with an increased risk of perinatal morbidity and mortality. The subjectivity of current ultrasound methods of assessment of placental calcification indicates that a more objective method is required. The aim of this study was to correlate the percentage of calcification defined by the clinician using a new software tool for calculating the extent of placental calcification with traditional ultrasound methods and with pregnancy outcome. METHODS: Ninety placental images were individually assessed. An upper threshold was defined, based on high intensity, to quantify calcification within the placenta. Output metrics were then produced including the overall percentage of calcification with respect to the total number of pixels within the region of interest. The results were correlated with traditional ultrasound methods of assessment of placental calcification and with pregnancy outcome. RESULTS: The results demonstrate a significant correlation between placental calcification, as defined using the software, and traditional methods of Grannum grading of placental calcification. Whilst correlation with perinatal outcome and cord pH was not significant as a result of small numbers, patients with placental calcification assessed using the computerized software at the upper quartile had higher rates of poor perinatal outcome when compared with those at the lower quartile (8/22 (36%) vs 3/23 (13%); P = 0.069). CONCLUSION: These results suggest that this computerized software tool has the potential to become an alternative method of assessing placental calcification.

Recurrent twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation: a systematic review of the literature.

OBJECTIVES: Selective fetoscopic laser photocoagulation (SFLP) is now the treatment of choice for twin-twin transfusion syndrome (TTTS). The incidence of recurrent TTTS following SFLP has been inconsistently reported across different studies. We performed a systematic review of TTTS recurrence following SFLP. METHODS: PubMed and MEDLINE online databases were searched for articles published between 2000 and August 2011, using combinations of the terms 'twin-twin transfusion', 'TTTS', 'laser', 'recur' and 'outcome'. Citations identified in the primary search were screened for eligibility. Studies reporting outcomes from selective SFLP for TTTS in twin pregnancies, which addressed specifically the issue of TTTS recurrence, were included. The primary outcome was rate of TTTS recurrence. Secondary outcomes were therapeutic preference and fetal outcomes in cases of recurrent TTTS. RESULTS: The primary search identified 22 eligible studies that are included in this review (n = 2447 twin pregnancies). Two studies included a minority of non-selective procedures. The published incidence of recurrent TTTS ranged from 0 to 16%. Clinical management was reported in 65.7% (71/108) cases, with repeat SFLP the most commonly performed secondary intervention. Only three studies provided comprehensive outcome data for cases of recurrent TTTS. The overall rate of neurologically-intact survival was 44% (23/52). The data were inadequate to determine the effects of secondary therapeutic approach, placental location or gestational age on perinatal outcome in cases of recurrent TTTS. CONCLUSIONS: The published rate of TTTS recurrence following SFLP in monochorionic twin pregnancies ranges from 0 to 16%. Although limited follow-up data suggest that recurrence is associated with significant perinatal mortality and morbidity, further study is needed. Currently, there are insufficient data available to guide recommendations for clinical management of TTTS recurrence. Future studies on SFLP for TTTS must include details on recurrence rates and provide outcome data specific to the recurrent subset.