Mixed Bacterial Growth in Prenatal Urine Cultures; An Investigation into Prevalence, Contributory Factors and the Impact of education-based Interventions.

PURPOSE: Undiagnosed urinary tract infections (UTIs) in pregnancy are associated with adverse perinatal outcome. Urine microbiology cultures reported as 'mixed bacterial growth' (MBG) frequently present a diagnostic dilemma for healthcare providers. We investigated external factors contributing to elevated rates of (MBG) within a large tertiary maternity centre in London, UK, and assessed the efficacy of health service interventions to mitigate these. DESCRIPTION: This prospective, observational study of asymptomatic pregnant women attending their first prenatal clinic appointment aimed to establish (i) the prevalence of MBG in routine prenatal urine microbiology cultures, (ii) the association between urine cultures and the duration to laboratory processing and (iii) ways in which MBG may be reduced in pregnancy. Specifically we assessed the impact of patient-clinician interaction and that of an education package on optimal urine sampling technique. ASSESSMENT: Among 212 women observed over 6 weeks, the negative, positive and MBG urine culture rates were 66%, 10% and 2% respectively. Shorter duration from urine sample collection to laboratory arrival correlated with higher rates of negative cultures. Urine samples arriving in the laboratory within 3 hours of collection were most likely to be reported as culture negative (74%), and were least likely to be reported as MBG (21%) or culture positive (6%), compared to samples arriving > 6 hours (71%, 14% and 14% respectively; P < 0.001). A midwifery education package effectively reduced rates of MBG (37% pre-intervention vs 19% post-intervention, RR 0.70, 95% CI 0.55 to 0.89). Women who did not receive verbal instructions prior to providing their sample had 5-fold higher rates of MBG (P < 0.001). CONCLUSION: As many as 24% of prenatal urine screening cultures are reported as MBG. Patient-midwife interaction before urine sample collection and rapid transfer of urine samples to the laboratory within 3 hours reduces the rate of MBG in prenatal urine cultures. Reinforcing this message through education may improve accuracy of test results.

Factors associated with preterm birth in women undergoing cervical cerclage.

OBJECTIVES: Cervical cerclage is used to manage women at high risk of late miscarriage (LM) and spontaneous preterm birth (PTB) due to factors such as history of cervical insufficiency (CI), uterine anomaly, cervical surgery and ultrasound (US) diagnosed cervical shortening. Urinary tract infection (UTI) and subsequent pyelonephritis, and bacterial infection are associated with PTB, but their role in PTB after cervical cerclage is unknown. We examined the relationship between UTI and bacterial vaginosis (BV), fetal fibronectin (fFN) test and PTB in women undergoing elective- or US-indicated cervical cerclage. We also investigated whether fetal fibronectin (fFN) test were useful to predict PTB. STUDY DESIGN: This is a single center, retrospective study of singleton pregnant women at PTB clinic, University College London Hospital (UCLH, 2005-2015) who underwent elective or US-indicated cervical cerclage. Women were tested for UTI and BV before cerclage placement and received mid-gestation fFN testing. Patient data were extracted from the PTB clinic database and electronic records. Statistical analyses used Pearson's chi-square and Mann-Whitney U tests. P values were corrected by Bonferroni method as required. RESULTS: 267 singleton pregnant women attended our clinic with completed birth outcome. Of those, 32.2% (86/267) delivered prematurely. All women with UTI or BV received antibiotic treatment. Women with a UTI before cerclage placement were more likely to deliver preterm when compared to those with negative MSU culture (OR 3.39, 95%CI 1.24-9.27, p = 0.04). Their gestational age at delivery were also lower than those with negative MSU result (36+6, IQR 31+4-38+2week vs 38+1, IQR 36+1-39+5-week, p = 0.05). However, UTI after cerclage placement or BV either before or after cerclage placement were not associated with PTB. Women who had a positive fFN result were more likely to deliver preterm (OR 3.85, 95% CI 1.81-8.41, p = 0.0007). CONCLUSIONS: The presence of a UTI before cervical cerclage is associated with a higher rate of PTB in women who receive a cervical cerclage, even when treated. We did not find an association between pre or post-cerclage BV or post-cerclage UTI and PTB. Further research is needed to elucidate the link between UTI and PTB in women undergoing cervical cerclage.

Antenatal corticosteroids and outcomes in gastroschisis: A multicenter retrospective cohort study.

OBJECTIVE: In gastroschisis, there is evidence to suggest that gut dysfunction develops secondary to bowel inflammation; we aimed to evaluate the effect of maternal antenatal corticosteroids administered for obstetric reasons on time to full enteral feeds in a multicenter cohort study of gastroschisis infants. METHODS: A three center, retrospective cohort study (1992-2013) with linked fetal/neonatal gastroschisis data was conducted. The primary outcome measure was time to full enteral feeds (a surrogate measure for bowel function) and secondary outcome measure was length of hospital stay. Analysis included Mann-Whitney and Cox regression. RESULTS: Of 500 patients included in the study, 69 (GA at birth 34 [25-38] weeks) received antenatal corticosteroids and 431 (GA at birth 37 [31-41] weeks) did not. Antenatal corticosteroids had no effect on the rate of reaching full feeds (Hazard ratio HR 1.0 [95% CI: 0.8-1.4]). However, complex gastroschisis (HR 0.3 [95% CI: 0.2-0.4]) was associated with an increased time to reach full feeds and later GA at birth (HR 1.1 per week increase in GA [95% CI: 1.1-1.2]) was associated with a decreased time to reach full feeds. CONCLUSION: Maternal antenatal corticosteroids use, under current antenatal steroid protocols, in gastroschisis is not associated with an improvement in neonatal outcomes such as time to full enteral feeds or length of hospital stay.

Predictive value of cervical cytokine, antimicrobial and microflora levels for pre-term birth in high-risk women.

Spontaneous preterm birth (sPTB, delivery <37 weeks gestation), accounts for approximately 10% of births worldwide; the aetiology is multifactorial with intra-amniotic infection being one contributing factor. This study aimed to determine whether asymptomatic women with a history of sPTB or cervical surgery have altered levels of inflammatory/antimicrobial mediators and/or microflora within cervical fluid at 22-24 weeks gestation. External cervical fluid was collected from women with history of previous sPTB and/or cervical surgery at 22-24 weeks gestation (n = 135). Cytokine and antimicrobial peptides were measured on a multiplex platform or by ELISA. qPCR was performed for detection of 7 potentially pathogenic bacterial species. IL-8 and IL-1ß levels were lower in women who delivered preterm compared to those who delivered at term (IL-8 P = 0.02; IL-1ß P = 0.04). There were no differences in elafin or human beta defensin-1 protein levels between the two groups. Multiple bacterial species were detected in a higher proportion of women who delivered preterm than in those who delivered at term (P = 0.005). Cervical fluid IL-8 and IL-1ß and microflora have the potential to be used as biomarkers to predict sPTB in high risk women.

Top research priorities for preterm birth: results of a prioritisation partnership between people affected by preterm birth and healthcare professionals.

BACKGROUND: We report a process to identify and prioritise research questions in preterm birth that are most important to people affected by preterm birth and healthcare practitioners in the United Kingdom and Republic of Ireland. METHODS: Using consensus development methods established by the James Lind Alliance, unanswered research questions were identified using an online survey, a paper survey distributed in NHS preterm birth clinics and neonatal units, and through searching published systematic reviews and guidelines. Prioritisation of these questions was by online voting, with paper copies at the same NHS clinics and units, followed by a decision-making workshop of people affected by preterm birth and healthcare professionals. RESULTS: Overall 26 organisations participated. Three hundred and eighty six people responded to the survey, and 636 systematic reviews and 12 clinical guidelines were inspected for research recommendations. From this, a list of 122 uncertainties about the effects of treatment was collated: 70 from the survey, 28 from systematic reviews, and 24 from guidelines. After removing 18 duplicates, the 104 remaining questions went to a public online vote on the top 10. Five hundred and seven people voted; 231 (45%) people affected by preterm birth, 216 (43%) health professionals, and 55 (11%) affected by preterm birth who were also a health professional. Although the top priority was the same for all types of voter, there was variation in how other questions were ranked. Following review by the Steering Group, the top 30 questions were then taken to the prioritisation workshop. A list of top 15 questions was agreed, but with some clear differences in priorities between people affected by preterm birth and healthcare professionals. CONCLUSIONS: These research questions prioritised by a partnership process between service users and healthcare professionals should inform the decisions of those who plan to fund research. Priorities of people affected by preterm birth were sometimes different from those of healthcare professionals, and future priority setting partnerships should consider reporting these separately, as well as in total.

Human beta defensin (HBD) gene copy number affects HBD2 protein levels: impact on cervical bactericidal immunity in pregnancy.

Human beta defensin 2 (HBD2) is an endogenous mucosal antimicrobial peptide (AMP) upregulated during infection and inflammation. HBD2 is encoded by the DEFB4 gene, which exhibits extensive copy number variation. Previous studies have demonstrated a relationship between HBD copy number and serum HBD2 protein levels; however, our current understanding of the influence of copy number on mucosal AMP function remains limited. This study explores the relationship between HBD copy number, cervicovaginal HBD2 protein levels and antimicrobial activity in 203 women with risk factors for preterm birth. We provide evidence that suggests HBD copy number modulates cervical antimicrobial immunity.

Hospital admission for hyperemesis gravidarum in women at increased risk of spontaneous preterm birth.

BACKGROUND: Progesterone administration prevents spontaneous preterm birth (sPTB) in women at increased risk. Progesterone concentration is lower in women with subsequent sPTB. Conversely, high concentrations of progesterone are implicated in the pathogenesis of hyperemesis gravidarum (HG). We hypothesized that women at increased risk of sPTB or spontaneous late miscarriage would be less likely to have a diagnosis of HG. To explore this hypothesis, we compared the incidence of HG in women at increased risk of sPTB and women with no identifiable risk factors. METHODS: Women at increased risk of sPTB were identified from a specialist Preterm Birth Clinic (PTBC) database where criteria for PTBC attendance are previous cervical surgery, previous sPTB <34 weeks, previous spontaneous late miscarriage, incidental sonographic cervical shortening, and uterine anomaly. Hospital antenatal booking and coding records for the same time period were examined to identify HG admissions. Women with multiple gestations, trophoblastic disease, or pre-existing abnormal thyroid function were excluded. The incidence of HG among PTBC (n=394) and non-PTBC attendees (n=4762) was calculated. RESULTS: The incidence of HG was lower in women at increased risk of sPTB (1.52%, n=6) compared with women with no identifiable risk factor for sPTB (3.33%, n=159; P=.049). CONCLUSION: Hospital admission for HG is reduced in women with risk factors for sPTB compared with those without risk factors. Exploration of the pathogenesis of HG may improve understanding of the mechanisms underlying sPTB.

Is early delivery beneficial in gastroschisis?

PURPOSE: Gastroschisis neonates have delayed time to full enteral feeds (ENT), possibly due to bowel exposure to amniotic fluid. We investigated whether delivery at <37weeks improves neonatal outcomes of gastroschisis and impact of intra/extra-abdominal bowel dilatation (IABD/EABD). METHODS: A retrospective review of gastroschisis (1992-2012) linked fetal/neonatal data at 2 tertiary referral centers was performed. Primary outcomes were ENT and length of hospital stay (LOS). Data (median [range]) were analyzed using parametric/non-parametric tests, positive/negative predictive values, and regression analysis. RESULTS: Two hundred forty-six patients were included. Thirty-two were complex (atresia/necrosis/perforation/stenosis). ENT (p<0.0001) and LOS (p<0.0001) were reduced with increasing gestational age. IABD persisted to last scan in 92 patients, 68 (74%) simple (intact/uncompromised bowel), 24 (26%) complex. IABD or EABD diameter in complex patients was not significantly greater than simple gastroschisis. Combined IABD/EABD was present in 22 patients (14 simple, 8 complex). When present at <30weeks, the positive predictive value for complex gastroschisis was 75%. Two patients with necrosis and one atresia had IABD and collapsed extra-abdominal bowel from <30weeks. CONCLUSION: Early delivery is associated with prolonged ENT/LOS, suggesting elective delivery at <37weeks is not beneficial. Combined IABD/EABD or IABD/collapsed extra-abdominal bowel is suggestive of complex gastroschisis.

Gastroschisis with intestinal atresia--predictive value of antenatal diagnosis and outcome of postnatal treatment.

PURPOSE: The purpose of this study is to evaluate (1) the predictive value of fetal bowel dilatation (FBD) for intestinal atresia in gastroschisis and (2) the postnatal management and outcome of this condition. METHODS: A retrospective review of all gastroschisis cases diagnosed in our fetal medicine unit between 1992 and 2010 and treated postnatally in our center was performed. RESULTS: One hundred thirty cases had full postnatal data available. Intestinal atresia was found at surgery in 14 neonates (jejunum, n = 6; ileum, n = 3; ascending colon, n = 3; multiple, n = 2). Polyhydramnios and FBD were more likely in the atresia group compared with infants with no atresia (P = .0003 and P = .005, respectively). Fetal bowel dilatation had 99% negative predictive value (95% confidence interval, 0.9-0.99) and 17% positive predictive value (95% confidence interval, 0.1-0.3) for atresia. Treatment of intestinal atresia included primary anastomosis (n = 5), delayed anastomosis (n = 2), and stoma formation followed by anastomosis (n = 7). Infants with atresia had longer duration of parenteral nutrition, higher incidence of sepsis, and cholestasis compared with infants with no atresia (P = .0003). However, the presence of atresia did not increase mortality. CONCLUSIONS: Polyhydramnios and FBD are associated with atresia. Absence of FBD in gastroschisis excludes intestinal atresia. In our experience, atresia is associated with a longer duration of parenteral nutrition but does not influence mortality. These findings may be relevant for antenatal counseling.