Two-Dimensional Echocardiography Estimates of Fetal Ventricular Mass throughout Gestation.

BACKGROUND: Two-dimensional (2D) ultrasound quality has improved in recent years. Quantification of cardiac dimensions is important to screen and monitor certain fetal conditions. We assessed the feasibility and reproducibility of fetal ventricular measures using 2D echocardiography, reported normal ranges in our cohort, and compared estimates to other modalities. METHODS: Mass and end-diastolic volume were estimated by manual contouring in the four-chamber view using TomTec Image Arena 4.6 in end diastole. Nomograms were created from smoothed centiles of measures, constructed using fractional polynomials after log transformation. The results were compared to those of previous studies using other modalities. RESULTS: A total of 294 scans from 146 fetuses from 15+0 to 41+6 weeks of gestation were included. Seven percent of scans were unanalysable and intraobserver variability was good (intraclass correlation coefficients for left and right ventricular mass 0.97 [0.87-0.99] and 0.99 [0.95-1.0], respectively). Mass and volume increased exponentially, showing good agreement with 3D mass estimates up to 28 weeks of gestation, after which our measurements were in better agreement with neonatal cardiac magnetic resonance imaging. There was good agreement with 4D volume estimates for the left ventricle. CONCLUSION: Current state-of-the-art 2D echocardiography platforms provide accurate, feasible, and reproducible fetal ventricular measures across gestation, and in certain circumstances may be the modality of choice.

Successful integration of newborn genetic testing into UK routine screening using prospective consent to determine eligibility for clinical trials.

OBJECTIVE: INGR1D (INvestigating Genetic Risk for type 1 Diabetes) was a type 1 diabetes (T1D) genetic screening study established to identify participants for a primary prevention trial (POInT, Primary Oral Insulin Trial). METHODS: The majority of participants were recruited by research midwives in antenatal clinics from 18 weeks' gestation. Using the NHS Newborn Bloodspot Screening Programme (NBSP) infrastructure, participants enrolled in INGR1D had an extra sample taken from their day 5 bloodspot card sent for T1D genetic screening. Those at an increased risk of T1D were informed of the result, given education about T1D and the opportunity to take part in POInT. RESULTS: Between April 2018 and November 2020, 66% of women approached about INGR1D chose to participate. 15 660 babies were enrolled into INGR1D and 14 731 blood samples were processed. Of the processed samples, 157 (1%) had confirmed positive results, indicating an increased risk of T1D, of whom a third (n=49) enrolled into POInT (20 families were unable to participate in POInT due to COVID-19 lockdown restrictions). CONCLUSION: The use of prospective consent to perform personalised genetic testing on samples obtained through the routine NBSP represents a novel mechanism for clinical genetic research in the UK and provides a model for further population-based genetic studies in the newborn.

Failure and regret after laparoscopic filshie clip sterilization under local anesthetic.

OBJECTIVE: To estimate the failure, regret, and reversal rates 5 or more years after laparoscopic Filshie clip sterilization using local anesthesia. METHODS: A total of 1,101 women underwent Filshie clip sterilization between 1983 and 2002. They completed follow-up questionnaires that were analyzed for the following outcomes: failed sterilization, regret after the operation, and sterilization reversal. RESULTS: Two hundred thirty-three of 968 (24%) eligible women sent the questionnaire had moved from their last known address. Of the remaining 735 women, 573 (78%) completed the questionnaire: 223 (39%) 5-6 years after the operation, 175 (30%) after 7-9 years, and 175 (30%) after 10-15 years. One pregnancy occurred 10 months after surgery, and one woman had the procedure repeated when unilateral tubal patency was identified by hysterosalpingography 3 weeks after surgery. Twenty-four (4%) women regretted having the operation; 7 (1.2%) women had a reversal operation, and all subsequently conceived. CONCLUSION: Failure after tubal sterilization using Filshie clips is less than 1:500 operations. Patient selection and surgeons' experience may have influenced these results. Regret occurred in a small proportion. LEVEL OF EVIDENCE: III.

Clinical validation of routine antenatal anti-D prophylaxis questions the modelling predictions adopted by NICE for Rhesus D sensitisation rates: results of a longitudinal study.

OBJECTIVE: To compare the rates of Rh(D) sensitisations with a policy of restricted routine antenatal anti-D prophylaxis (first pregnancy only) with the rates predicted with universal routine antenatal anti-D prophylaxis (all pregnancies). STUDY DESIGN: A retrospective longitudinal observational study involving 15,500 confinements in Rhesus D negative (Rh(D)-ve) women between 1990 and 2003 in a single health district was conducted. All Rh(D) sensitised pregnancies were identified and evidence for routine antenatal anti-D prophylaxis administration during the first pregnancy was investigated. The rate of Rh(D) sensitisations following a policy of restricted prophylaxis was compared with that predicted with mathematical modelling following universal prophylaxis. RESULTS: There were 50 newly sensitised and 37 previously sensitised pregnancies among 15,596 Rh(D)-ve women. For the calculated 13,575 Rh(D)-ve women whose first confinement was in Oxford and who were eligible for restricted prophylaxis, there were 30 new and 26 previously sensitised pregnancies. Of these 30 new sensitisations, 10 were nulliparae, 12 parity 1, and eight parity 2 or greater (third or later continuing pregnancy); only one of these latter eight women had received routine prophylaxis, four had delivered their first baby before the programme was introduced, and in three documentary evidence could not be confirmed that prophylaxis had been given. There was no difference between a policy of restricted and universal routine antenatal anti-D prophylaxis in the sensitisation rates for women during their third or subsequent pregnancy. CONCLUSIONS: This study has shown that restricted routine antenatal prophylaxis provides continuing protection for subsequent pregnancies although the mechanism for this is unclear. These results challenge the wisdom and expense of a policy of universal prophylaxis and prompt a need for further similar analyses to test the appropriateness of the NICE guideline.

Evidence to support the single-dose over the two-dose protocol for routine antenatal anti-D Rhesus prophylaxis: a prospective observational study.

OBJECTIVE: To assess the potential benefit of the single-dose compared with two-dose protocol for routine antenatal anti-D prophylaxis (RAADP). STUDY DESIGN: Prospective observational study during February to October 2009 in a district teaching hospital delivering 6000 women annually. Obstetric notes of eligible RhD negative women were reviewed following delivery to identify gestation and dose for RAADP injections, with laboratory confirmation when necessary. The primary outcome was compliance administering RAADP at the appropriate gestation with the secondary analysis of compliance for nulliparae and multiparae. RESULTS: For 644 eligible women, there was no statistically significant difference in administering the 28 week injection between the two-dose (95%) and single-dose (98%) protocols (P=0.17, OR 2.47: 95%CI (0.73, 8.34)). Compliance giving the injection at the correct gestation at 28 ± 1 weeks was achieved in 78% and 77% respectively (P=0.72, OR 1.10: 95%CI (0.69, 1.74)). For the two-dose protocol the second injection was given to 96% of those who had received the first injection, but at the correct time point in only 67%. By eliminating the variability of the 34 week injection, the single-dose protocol resulted in significantly greater overall success in giving RAADP at the appropriate times compared with the two-dose protocol (P=0.021, OR 1.68: 95%CI (1.08, 2.64)). There were no differences between nulliparae and multiparae for both protocols. CONCLUSION: The single-dose protocol provides enhanced compliance over the two-dose protocol with the potential for reduced sensitisation combining economic and manpower benefits. There remains room for improvement in administering RAADP at the correct gestation.

Urinary peptide profiling identifies a panel of putative biomarkers for diagnosing and staging endometriosis.

OBJECTIVE: To identify a potential diagnostic endometriosis marker using matrix-enhanced laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based urinary proteomics. DESIGN: Prospective randomized pilot study. SETTING: University hospital, tertiary referral center for endometriosis. PATIENT(S): 53 women undergoing laparoscopic surgery for pain and/or infertility comprising 30 women without endometriosis and 23 with endometriosis. INTERVENTION(S): Laparoscopy and urine specimens. MAIN OUTCOME MEASURE(S): Urinary peptide profiles. RESULT(S): We observed distinct patterns of peptide profiles in the urine samples of women presenting with typical clinical symptoms of endometriosis. Six statistically significant putative peptide markers were identified (four during the periovulatory phase and two during the luteal phase) by comparing controls with moderate/severe endometriosis patients. The periovulatory peptide mass of 1,767.1 Da and the luteal peptide mass of 1,824.3 Da both showed a sensitivity of 75% and a specificity of 85% and 71%, respectively. Also detected were seven peptide markers (two during the periovulatory phase and five during the luteal phase) by comparing the urinary peptide profiles of patients with minimal/mild to moderate/severe endometriosis. The periovulatory peptide mass of 3,280.9 Da and the luteal peptide mass of 1,933.8 Da showed a sensitivity of 82% and 75% and a specificity of 88% and 75%, respectively. CONCLUSION(S): Urinary proteomic analysis may provide a novel method of diagnosing and staging endometriosis.

Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.

Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10⁻7, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10⁻9, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10⁻³, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10⁻9 (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.

A prospective cohort study of menstrual symptoms and morbidity over 15 years following laparoscopic Filshie clip sterilisation.

OBJECTIVE: To observe the incidence of menstrual symptoms and relevant surgery after sterilisation. STUDY DESIGN: 1101 women sterilised with Filshie clips between 1983 and 2002 were assessed prospectively comparing menstrual symptomatology documented immediately before surgery and 5-14 years later by questionnaire. MAIN OUTCOME MEASURES: Prevalence of menstrual dysfunction and subsequent surgery related to pre-operative menstrual symptoms and contraception. RESULTS: After excluding 232 (24%) of the 968 eligible women sent questionnaires whose address had changed, 573 of the remaining 735 women (78%) completed the questionnaire, 223 5-6 years after sterilisation, 175 after 7-9 years and 175 after 10-15 years; the respondents were demographically representative of the total population. Heavy periods increased from 9% before to 35% (P<0.0001) after sterilisation, painful periods from 2% to 21% (P<0.0001) and 6% had undergone hysterectomy or endometrial ablation. These findings were not influenced by the pre-sterilisation method of contraception but were inversely related to advancing age (P<0.0002). The lowest rates of menstrual symptoms were reported 10-15 years after sterilisation. CONCLUSION: Menstrual symptoms increased following Filshie clip sterilisation irrespective of pre-sterilisation symptoms and contraception. Whatever the causative mechanism, the progestogen-loaded intrauterine system (IUS), with similar efficacy but with improved menstrual symptoms, should be considered before sterilisation.

The kinetics of routine antenatal prophylactic intramuscular injections of polyclonal anti-D immunoglobulin.

OBJECTIVE: To observe the pharmacokinetics of intramuscular anti-D immunoglobulin (IgG) given for routine antenatal prophylaxis. DESIGN: Prospective observational study. SETTING: Maternity unit and antenatal serology laboratory in a district teaching hospital. POPULATION: Forty-five rhesus-D-negative pregnant women not sensitised to RhD. METHODS: Serial serum quantitations of anti-D IgG following the intramuscular injections of anti-D IgG 100 microg (500 IU) at 28 and 34 weeks of gestation. Anti-D IgG concentrations were assayed with the RFA-300 continuous flow analyser. MAIN OUTCOME MEASURES: The kinetic profile and duration of detectable anti-D IgG in maternal serum following the first and second injections of anti-D IgG. RESULTS: For the 43 women in whom serial data were collected, there were no detectable differences between pregnancies with an RhD-positive (26) or -negative (17) fetus. Maximum IgG concentrations were detected two to five days following the first anti-D IgG injection and ranged between 0 and 28 ng/mL. Only 30% of women still undelivered at 40 weeks of gestation had detectable IgG at 2 ng/mL or greater. There was a significant relationship between higher maximum values and low maternal surface body area (R2 = 0.204, P = 0.002), but this did not influence duration of persistent IgG. CONCLUSION: Using previously published data, 70% women are not adequately protected with anti-D IgG 12 weeks after the first prophylactic injection. Despite this, previous clinical results suggest that the antenatal prophylaxis schedule used provides adequate protection and that the recommendation for the lowest concentration of protective anti-D IgG antibody levels currently in use is probably overestimated.