The IRELAnD study-investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial.

BACKGROUND: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. OBJECTIVE: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. STUDY DESIGN: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. RESULTS: From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. CONCLUSION: In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

Single-use negative pressure wound therapy to prevent surgical site complications in high-risk patients undergoing caesarean sections: a real-world study.

Surgical site complications (SSCs), including surgical site infection (SSI), are common following C-sections. Management of the post-operative incision with single-use negative pressure wound therapy (sNPWT) has been shown to reduce the risk of SSC in high-risk individuals. This study explored the outcomes of routine, real-world use of sNPWT in high-risk patients undergoing C-sections. An observational, retrospective in-service evaluation was conducted across eight obstetric centres in the Republic and Northern Ireland. Patients undergoing C-sections were stratified for their risk of developing SSC using commonly known risk factors, including BMI ≥30, smoking, diabetes, and whether the patients had undergone previous C-sections or had a previous history of wound dehiscence. Those at high-risk were treated with sNPWT post-operatively. Data relating to any SSC that developed post-operatively, for up to 30 days, were captured. Data were compared with original research previously published by Wloch et al. (2012). Of 1111 women considered high-risk, 106 (9.5%) went on to develop SSCs, predominantly superficial SSIs. SSCs were associated with extra visits with their general practitioner (GP), outpatient visits, or inpatient hospital stays in 5.7%, 2.4%, and 1.7% of the entire cohort, representing 59.4%, 25.5%, and 17.9% of the 106 patients with SSC. Patients needed on average 1.8 extra GP visits and 0.7 extra outpatient visits. Patients who needed to be readmitted to hospital had an average length of stay of 4 days. In comparison with a previously published cohort, in which sNPWT was not used, we observed a significant reduction in the incidence of SSCs across BMI groups 18.5-24.9 (P = 0.02), 25-29.9 (P = 0.003), and ≥35 kg/m2 (P = 0.04). In those patients who had undergone at least one previous C-section, the rates of complications also reduced (P = 0.006). This analysis provides further justification for using sNPWT to manage surgical incisions in patients considered at high risk of developing post-procedural SSCs, particularly those with a BMI ≥30 or a history of more than one C-section.

Cross-sectional observational study protocol: missing microbes in infants born by caesarean section (MiMIC): antenatal antibiotics and mode of delivery.

INTRODUCTION: The intestinal microbiome in early life plays a major role in infant health and development. Factors like antibiotic exposure, breast/formula feeding and mode of delivery are known to affect the microbiome. The increasing occurrence of caesarean section (C-section) deliveries and antibiotic exposure warrants further insight into the potential missing microbes in those infants. The study objective is to study the effect of maternal antibiotic administration during pregnancy and/or C-section mode of delivery on the development of the infant's intestinal microbiome until the age of 2 years. METHODS AND ANALYSIS: A single site, cross-sectional observational study of C-section and vaginally delivered infants being either exposed to maternal antibiotic treatment or not during the third trimester of pregnancy. Throughout the nine visits, stool, urine, saliva, hair, breast milk and vaginal swabs will be collected from either mother and/or infant for microbiome and metabolomic analysis. ETHICS AND DISSEMINATION: The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The trial has been registered at ClinicalTrials.gov.The findings from this study will be disseminated in peer-reviewed journals, during scientific conferences, and directly to the study participants. Sequencing data will be deposited in public databases. TRIAL REGISTRATION NUMBER: NCT04134819.

Dietary behaviours and weight management: A thematic analysis of pregnant women's perceptions.

Maternal obesity is associated with increased risk of gestational diabetes and other complications. Although antenatal interventions to help prevent these complications are ongoing, an understanding of overweight and obese pregnant women's opinions and attitudes is lacking. Therefore, this study aims to explore these women's experiences and perceptions of dietary behaviours and weight management during pregnancy. Secondary analysis of qualitative data originally collected to examine lifestyle behaviours in pregnant women was conducted. The data were from a purposive sample of overweight and obese pregnant women attending a public antenatal clinic in Cork, Ireland. The data were explored using thematic analysis. Interviews with 30 overweight and obese pregnant women were analysed. Three themes were developed relating to overweight and obese women's dietary behaviours and weight management perceptions including 'pregnancy's influence on dietary behaviours', 'external influences on dietary behaviours' and 'perception of and preferences for weight related advice and resources'. Together these themes reveal women's experiences of diet and how pregnancy factors (physiological changes) and external factors (family and friends) can influence dietary behaviours. Furthermore, perceptions of weight management advice and lack thereof were highlighted with women drawing attention to potential resources for future use during pregnancy. This study provides important insights into overweight and obese pregnant women's dietary behaviours and perceptions of weight management. According to these findings, there is a need for clear and unambiguous information about weight management, acceptable weight gain, food safety and how to achieve a balanced diet.

Exploring obstetricians', midwives' and general practitioners' approach to weight management in pregnant women with a BMI ≥25 kg/m2: a qualitative study.

OBJECTIVE: The aim of this study was to explore healthcare professionals' (HCPs) beliefs and attitudes towards weight management for pregnant women with a body mass index (BMI) ≥25 kg/m2. DESIGN: Qualitative study. SETTING: A public antenatal clinic in a large academic maternity hospital in Cork, Ireland, and general practice clinics in the same region. PARTICIPANTS: HCPs such as hospital-based midwives and consultant obstetricians and general practitioners (GPs). METHOD: Semistructured interviews were conducted with a purposive sample of hospital-based HCPs and a sample of GPs working in the same region. Interviews were recorded, transcribed and thematically analysed using NVivo software. RESULTS: Seventeen HCPs were interviewed (hospital based=10; GPs=7). Four themes identified the complexity of weight management in pregnancy and the challenges HCPs faced when trying to balance the medical and psychosocial needs of the women. HCPs acknowledged weight as a sensitive conversation topic, leading to a 'softly-softly approach' to weight management. HCPs tried to strike a balance between being woman centred and empathetic and medicalising the conversation. HCPs described 'doing what you can with what you have' and shifting the focus to managing obstetric complications. Furthermore, there were unclear roles and responsibilities in terms of weight management. CONCLUSION: HCPs need to have standardised approaches and evidence-based guidelines that support the consistent monitoring and management of weight during pregnancy.

Risk factors for surgical site infection after cesarean delivery: A case-control study.

BACKGROUND: The cesarean delivery (CD) rate is increasing worldwide. Surgical site infection (SSI) incidence is likely to follow an upward trajectory. We examined the incidence and risk factors for SSI after CD. METHODS: A case-control study of women who had a lower-segment CD during the study period was performed at Ireland's Cork University Maternity Hospital. Cases were patients who presented to the hospital with SSI and who met the criteria of the U.S. Centers for Disease Control and Prevention. Controls were randomly selected from the discharge register of CDs at a ratio of 2:1. Data were extracted from the medical records. A multivariable stepwise logistic regression model approach was used, and the results were expressed as adjusted odds ratios (aORs). RESULTS: The SSI rate was 2%. The greatest contribution to risk of SSI was associated with maternal obesity (aOR, 4.76; 95% confidence interval [CI], 2.00-11.32) and hypertensive disorders (aOR, 6.67; 95% CI, 1.54-28.99]. There was also an increased risk for women who underwent an emergency CD (aOR, 3.50; 95% CI, 1.09-11.30), for women who had ≥5 vaginal examinations (aOR, 3.24; 95% CI, 0.92-11.41), and for women without hypertensive disorders who delivered a baby weighing <3,500 g (aOR, 2.18; 95% CI, 1.08-4.37). CONCLUSIONS: Obesity, hypertensive disorders, emergency CD, and multiple vaginal examinations were independent risk factors for SSI after CD.

Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To assess the vitamin D status of men and women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to investigate associations between vitamin D status and fertility variables. METHODS: A cross-sectional prospective study was undertaken of men and women attending a fertility clinic in Ireland for IVF/ICSI between January and March 2014. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25(OH)D). Questionnaires examined knowledge and practices concerning vitamin D. Fertility variables and pregnancy outcomes were assessed in relation to vitamin D status. RESULTS: Overall, 73 men and 64 women provided blood samples. Among men, no correlation was found between 25(OH)D and total motility (ρ=0.069, P=0.562), progressive motility (ρ=0.066, P=0.576), count (ρ=0.001, P=0.996), or morphology (ρ=-0.034, P=0.774) of sperm. Additionally, there was no association between 25(OH)D and ongoing pregnancy rates (P=0.158). There was no difference in 25(OH)D between men with and without male factor subfertility issues (P=0.856). Among women, there was no significant correlation between 25(OH)D and anti-Müllerian hormone (P=0.629) or number of collected (P=0.198) and fertilized oocytes (P=0.136). There was no difference in 25(OH)D between women with and without ongoing pregnancy (P=0.222). CONCLUSION: No correlation was found between fertility variables or pregnancy outcomes and male or female vitamin D status.

Fetal heart rate patterns in neonatal hypoxic-ischemic encephalopathy: relationship with early cerebral activity and neurodevelopmental outcome.

Despite widespread use of fetal heart rate monitoring, the timing of injury in hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine fetal heart rate patterns during labor in infants with clinical and electroencephalographic (EEG) evidence of HIE and to relate these findings to neurodevelopmental outcome. Timing of onset of pathological cardiotocographs (CTGs) was determined in each case by two blinded reviewers and related to EEG grade at birth and neurological outcome at 24 months. CTGs were available in 35 infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were normal in 24/35 (69%), suspicious in 8/35 (23%), and pathological in 3/35 (8%). All CTGs developed nonreassuring features prior to delivery. Three patterns of fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in 11/35 (31%); group 2, normal CTGs on admission with gradual deterioration to pathological in 20/35 cases (57%); and group 3, normal CTGs on admission with acute sentinel events in 4/35 (11.5%). The median (interquartile range) duration between the development of pathological CTGs and delivery was 145 (81, 221) minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation between duration of pathological CTG trace and grade of encephalopathy (R = 0.09, P = 0.63) or neurological outcome (P = 0.75). However, the grade of encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to worse outcomes. The majority of infants with HIE have normal CTG traces on admission but develop pathological CTG patterns within hours of delivery. More severe encephalopathy was associated with normal admission CTG and acute sentinel events shortly before delivery.

Haemostasis in normal and abnormal pregnancy.

Haemostasis is a complex and dynamic equilibrium involving pro-coagulants, the natural anticoagulation system and fibrinolysis. Normal human pregnancy is associated with profound alterations to the process of haemostasis such that the pro-coagulant effect becomes dominant. There are very few studies which have attempted to elucidate the adaptations that take place in the uteroplacental circulation where the haemostatic system faces the conflicting tasks of maintaining blood fluidity during pregnancy while preparing for the haemostatic challenge of delivery. It is hypothesised that excessive thrombosis within the uteroplacental circulation provides the mechanistic basis for the reported associations between the inherited thrombophilias and major pregnancy complications. The evidence underpinning this widely quoted hypothesis is weak.