A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland.

AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

Early gestational diabetes mellitus (GDM) is associated with worse pregnancy outcomes compared with GDM diagnosed at 24-28 weeks gestation despite early treatment.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated+ with adverse pregnancy outcomes compared with women with normal glucose tolerance in pregnancy. The WHO recommends screening at 24-28 weeks gestation for GDM. Women who are diagnosed before 24-28 weeks gestation have a longer intervention period which may impact positively on pregnancy outcomes. AIM: This study aimed to examine pregnancy outcomes of women with GDM diagnosed <24 weeks gestation compared with those diagnosed at 24-28 weeks in a large Irish cohort. METHODS: A retrospective cohort study of 1471 pregnancies in women with GDM diagnosed using IADPSG criteria between September 2012 and April 2016 was conducted. At GDM diagnosis, women were classified as early GDM <24 weeks or standard GDM 24-28 weeks gestation. RESULTS: Women with early GDM had a significantly greater risk of pregnancy-induced hypertension (12.4% vs. 5.3%; P < 0.05), post-partum haemorrhage (8.7% vs. 2.4%; P < 0.05) and post-partum glucose abnormalities (32% vs. 15.6%; P < 0.05). Their offspring had a greater risk of pre-maturity (10.9% vs. 6.6%; P < 0.05), stillbirth (1.4% vs. 0.5%; P < 0.05), large for gestational age (19.1% vs. 13.4% P < 0.05) and need neonatal intensive care (30.7% vs. 22.1%; P < 0.05) compared with offspring of women with standard GDM. Rates of C-section and pre-maturity were still higher in the early GDM group when the two groups where compared based on their post-natal OGTT. CONCLUSION: Early GDM women and their offspring are at greater risk of an adverse pregnancy outcome compared with those diagnosed at 24-28 weeks. In view of the abnormal post-natal glucose findings, early GDM may reflect a more advanced state in diabetes pathogenesis.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

Care of women with diabetes before, during and after pregnancy: time for a new approach?

AIMS: This study assesses the impact of pregnancy and pre-pregnancy care on longer-term treatment goals in women with diabetes. METHODS: This retrospective study included women with Type 1 (n = 247) and Type 2 diabetes (n = 137) who were evaluated before, during and after pregnancy. RESULTS: Among women with Type 1 diabetes, average HbA1c at 12 months post-partum was similar to the preconception level [63 vs. 64 mmol/mol (7.9% vs. 8.0%), P = 0.60]. This was also the case for women with Type 2 diabetes [52 vs. 52 mmol/mol (6.9% vs. 6.9%), P = 0.79]. At 12 months post-partum, there was no improvement in other measures of diabetes control and one in five women are lost to follow-up from clinical care. In total, 44.9% of women with Type 1 diabetes and 27.7% of those with Type 2 diabetes attended pre-pregnancy care. Attendees maintained superior glycaemic control throughout the study and were more likely to be receiving specialist care post-partum. CONCLUSIONS: These findings identify a need to change our approach to the reproductive care of women with diabetes. In particular, efforts should be made to ensure all women have access to and attend pre-pregnancy care, and barriers to engagement with post-partum care should be addressed.

Postpartum glucose testing for women with gestational diabetes mellitus: Improving regional recall rates.

Our aim was to evaluate attendance for postpartum glucose testing among women attending five antenatal centres with a diagnosis of GDM in the preceding pregnancy. A central, regional coordinator who made verbal and written contact with each individual facilitated a favourable recall rate of 75%.

ATLANTIC DIP: simplifying the follow-up of women with previous gestational diabetes.

OBJECTIVE: Previous gestational diabetes (GDM) is associated with a significant lifetime risk of type 2 diabetes. In this study, we assessed the performance of HbA1c and fasting plasma glucose (FPG) measurements against that of 75 g oral glucose tolerance testing (OGTT) for the follow-up screening of women with previous GDM. METHODS: Two hundred and sixty-six women with previous GDM underwent the follow-up testing (mean of 2.6 years (s.d. 1.0) post-index pregnancy) using HbA1c (100%), and 75 g OGTT (89%) or FPG (11%). American Diabetes Association (ADA) criteria for abnormal glucose tolerance were used. DESIGN, COHORT STUDY, AND RESULTS: The ADA HbA1c high-risk cut-off of 39 mmol/mol yielded sensitivity of 45% (95% CI 32, 59), specificity of 84% (95% CI 78, 88), negative predictive value (NPV) of 87% (95% CI 82, 91) and positive predictive value (PPV) of 39% (95% CI 27, 52) for detecting abnormal glucose tolerance. ADA high-risk criterion for FPG of 5.6 mmol/l showed sensitivity of 80% (95% CI 66, 89), specificity of 100% (95% CI 98, 100), NPV of 96% (95% CI 92, 98) and PPV of 100% (95% CI 91, 100). Combining HbA1c ≥39 mmol/mol with FPG ≥5.6 mmol/l yielded sensitivity of 90% (95% CI 78, 96), specificity of 84% (95% CI 78, 88), NPV of 97% (95% CI 94, 99) and PPV of 56% (95% CI 45, 66). CONCLUSIONS: Combining test cut-offs of 5.6 mmol/l and HbA1c 39 mmol/mol identifies 90% of women with abnormal glucose tolerance post-GDM (mean 2.6 years (s.d.1.0) post-index pregnancy). Applying this follow-up strategy will reduce the number of OGTT tests required by 70%, will be more convenient for women and their practitioners, and is likely to lead to increased uptake of long-term retesting by these women whose risk for type 2 diabetes is substantially increased.

Changing clinical practice can improve clinical outcomes for women with pre-gestational diabetes mellitus.

Prospective evaluation of pregnancy outcomes in women with pre-gestational diabetes over 6 years. The ATLANTIC Diabetes in Pregnancy group represents 5 antenatal centres along the Irish Atlantic seaboard, providing care for women with diabetes throughout pregnancy. In 2007 the group published a report that recognised that women were poorly prepared for pregnancy and that outcomes were sub-optimal. A change in practice occurred, offering women specialist-led, evidence-based care, both pre-pregnancy and combined antenatal/diabetes clinics during pregnancy. We now compare outcomes from 2005-2007 with 2008-2010. There was an increase in the numbers attending pre-conception care. Glycemic control before and throughout pregnancy improved. There was an overall increase in live births and decrease in perinata mortality rate. There was a decrease in large-for-gestational-age babies in mothers with Type 1 Diabetes. Elective Caesarean section rates increased while emergency section rates decreased. More women had Type 2 diabetes over time and these women were more likely to be obese. Changing the process of clinical care delivery can improve outcomes in for women with pre-gestational diabetes.

A regional pre-pregnancy care (PPC) programme for women with type 1 and type 2 diabetes.

Unfortunately the risks associated with pregnancy in a woman with Diabetes (Type 1 and Type 2) continue to be high. However these risks can be reduced significantly with pregnancy planning and pre-pregnancy care. We report here the establishment of a regional pre pregnancy service and the interim results of its benefits. Pre pregnancy care is as vital as combined diabetes antenatal care for women with diabetes and must become the norm for this population.

ATLANTIC DIP: pregnancy outcomes for women with type 1 and type 2 diabetes.

ATLANTIC DIP prospectively evaluated the perinatal and maternal outcomes of pregnancies complicated by Type 1 and Type 2 diabetes during 2006/2007 in 5 antenatal centres. All women with established diabetes for at least 6 months prior to the index pregnancy and booking for antenatal care between 1/1/2006 and 31/12/2007 were included in the study. Results were collected electronically via the DIAMOND Diabetes Information System. Pregnancy outcome was compared with that of the background population receiving antenatal care in the region during the same time. There were 104 singleton pregnancies during the period of study. The stillbirth rate (SBR) of 25/1000 was 5 times greater than that reported in the background population at 5/1000 and the perinatal mortality rate (PMR) of 25/1000 was 3.5 times greater than background 7/1000. The congenital malformation rate (CMR) of 24/1000 was twice that observed in the background population. Women were not well prepared for pregnancy with 28% receiving pre pregnancy care (PPC), 43% receiving pre pregnancy folic acid and 51% achieving a HbA1C < = 7% at first antenatal visit. Pregnancy induced hypertension (PIH) and/or pre eclampsia toxaemia (PET) were three times more common than in women in the background population. In conclusion women are not well prepared for pregnancy. Maternal and infant morbidity and infant mortality are greater in women with diabetes. A regional pre pregnancy care (PPC) programme and centralised glucose management are urgently needed.

Trimester-specific reference intervals for IFCC standardised haemoglobin A(1c): new criterion to diagnose gestational diabetes mellitus (GDM)?

We established trimester-specific reference intervals for IFCC standardised HbA(1c) in 311 non-diabetic Caucasian pregnant women (n = 246) and non-pregnant women (n = 65). A selective screening strategy based on risk factors for gestational diabetes was employed. Pregnancy trimester was defined as trimester 1 (T1, n = 40) up to 12 weeks + 6 days, trimester 2 (T2, n = 106) 13 to 27 weeks + 6 days, trimester 3 (T3, n = 100) > 28 weeks to delivery. The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol/mol (DCCT: 4.8-5.5%), T1: 24-36 mmol/mol (DCCT: 4.3-5.4%), T2: 25-35 mmol/mol (DCCT: 4.4-5.4%), and T3: 28-39 mmol/mol (DCCT: 4.7-5.7%). HbA(1c) was significantly decreased in trimesters 1 (P < 0.01) and 2 (P < 0.001) compared to non-pregnant women. Retrospective application of selective screening to Caucasian women of the Atlantic DIP cohort determined that 5,208 met the criteria. 945 of those women (18.1%) were diagnosed with Gestational Diabetes Mellitus (GDM) using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) glucose concentration thresholds. HbA(1c) measurement within 2 weeks of the diagnostic Oral Glucose Tolerance Test (OGTT) was available in 622 of 945 (66%). Applying the decision threshold for T2: HbA(1c) > 35 mmol/mol (DCCT > 5.4%) identified 287 of 622 (46%) of those with GDM. HbA(1c) measurement in T2 (13 to 27 weeks) should be included in the diagnostic armamentarium for GDM. This would reduce the need for diagnostic OGTT in a significant number of women.

Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.

Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48-72 h of deer tick attachment. Persons with tick bites were prospectively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection. Ticks were identified, measured for engorgement, and assayed by polymerase chain reaction (PCR) for B. burgdorferi DNA. Duration of attachment was determined from the scutal index of engorgement. Of 316 submissions, 229 were deer ticks; 14% were positive by PCR. Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects (109 bites). There were 4 human cases (3.7% of bites) of B. burgdorferi infection. The incidence was significantly higher for duration of attachment > or =72 h than for <72 h: 3 (20%) of 15 vs. 1 (1.1%) of 94 (P = .008; odds ratio, 23.3; 95% confidence interval, 2.2-242). PCR was an unreliable predictor of infection. Tick identification and measurement of engorgement can be used to identify a small, high-risk subset of persons who may benefit from antibiotic prophylaxis.

Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease.

OBJECTIVE: To determine the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease. RESEARCH DESIGN: Prospective, nonrandomized, nonblinded study. SETTING: Hospital-based, comprehensive sickle cell center. PATIENTS: Children with sickle cell disease aged 18 months to 18 years who were previously unvaccinated or had an inadequate or waning response to H influenzae type b polysaccharide vaccine. SELECTION PROCEDURES: Consecutive eligible patients. INTERVENTIONS: Vaccination and observation for adverse effects. Blood samples were taken before and 1 to 2 and 6 months after vaccination to measure anticapsular antibody levels. MEASUREMENTS AND RESULTS: Vaccination was well tolerated. One hundred percent and 96% of the 31 immunized children had postvaccination anticapsular antibody concentrations of greater than 0.15 and 1.0 mg/L, respectively. Six months after vaccination, 100% and 89% of children had these antibody concentrations. CONCLUSIONS: H influenzae type b conjugate vaccines are safe and highly immunogenic in children with sickle cell disease. It is likely that these vaccines will be protective against invasive H influenzae type b disease.

Immunization of children with sickle cell disease with Haemophilus influenzae type b polysaccharide vaccine.

There are limited data concerning safety and immunogenicity of Haemophilus influenzae type b polysaccharide vaccine in children with sickle cell disease. Ninety-eight patients with sickle cell disease (65 with SS phenotype, 23 with SC phenotype, and 10 with S beta-thalassemia) 1.5 to 20 years of age were given 25 micrograms of vaccine subcutaneously. The vaccine was well tolerated; mild side effects were observed in 6 of 98 (6.1%) children. In addition, one patient with a recent vasoocclusive crisis was hospitalized because of fever and vasoocclusive crisis 8 hours after vaccination. Prevaccination anticapsular antibody concentrations (by radioimmunoassay) were less than 0.15 microgram/mL in 7 of 11 children 18 to 24 months of age (geometric mean 0.17 microgram/mL), in 10 of 25 children 2 to 5 years of age (geometric mean 0.36 microgram/mL), and in 3 of 50 patients 6 to 20 years of age (geometric mean 1.03 microgram/mL). Inadequate response (1- to 2-month postvaccination antibody level less than 1 microgram/mL) was found in 3 of 5 children 18 to 24 months of age (geometric mean 1.74 microgram/mL), in 8 of 21 children 2 to 5 years of age (geometric mean 2.20 micrograms/mL), and in 2 of 49 patients 6 to 20 years of age (geometric mean 18.03 micrograms/mL). Six months after vaccination, greater than 1 microgram/mL of antibody was present in the 2 children 6 to 20 years of age with inadequate response but not in the 7 children 2 to 5 years of age with inadequate response.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumococcal and Haemophilus influenzae type b antigen detection in children at risk for occult bacteremia.

We prospectively evaluated pneumococcal and Haemophilus influenzae type b antigen detection in serum and urine of young (3 to 30 months of age) febrile (temperature greater than or equal to 39 degrees C) children at risk for occult bacteremia. Patients with septic shock, meningitis, or epiglottitis were excluded. Of 576 patients, 16 had pneumococcal bacteremia (final diagnoses: primary bacteremia, nine; otitis media, four; pneumonia, two; unknown, one), and five had H influenzae b bacteremia (final diagnoses: primary bacteremia, two; cellulitis, two; arthritis, one). Latex agglutination was positive in all five patients with H influenzae b bacteremia (positive in three of three urine specimens, three of four sera tested) but only one of 16 patients with pneumococcal bacteremia (positive in one of seven urine samples, zero of 13 sera tested). Both assays had specificities of greater than 95%. Nonspecific agglutination occurred in 7% of specimens tested. Enzyme immunoassay for pneumococcal antigen, although more sensitive than latex agglutination, failed to detect antigen in ten sera and three urine specimens from patients with pneumococcal bacteremia. Thus, neither latex agglutination nor enzyme immunoassay was sufficiently sensitive for detection of occult pneumococcal bacteremia. Latex agglutination for H influenzae b holds promise as a sensitive and specific test for rapid diagnosis of occult bacteremia due to H influenzae b.