Pregnancy-induced severe hypertriglyceridemia effectively treated with therapeutic plasmapheresis.

INTRODUCTION: Hypertriglyceridemia is associated with significant morbidity during pregnancy. Hypertriglyceridemia-induced pancreatitis (HTGP) is associated with genetically determined dyslipidemia or a secondary condition such as diabetes, alcohol, pregnancy, or medication use. The lack of data on the safety of drugs to be used to decrease triglyceride levels during pregnancy dictates that other strategies must be chosen. PATIENT AND METHODS: We describe a case of a pregnant woman with severe hypertriglyceridemia treated with two different techniques of plasmapheresis (Dual Filtration apheresis and Centrifugal Plasma Separation). RESULTS: The patient could be treated throughout the pregnancy, with good control of the triglycerides, and a healthy baby was born. CONCLUSION: Hypertriglyceridemia is a major issue during pregnancy. The use of plasmapheresis is a safe and efficient tool in that clinical scenario.

The predictive value of the sFlt-1/PlGF ratio in suspected preeclampsia in a New Zealand population: A prospective cohort study.

BACKGROUND: Internationally, placental growth factor (PlGF)-based tests are used as prognostic markers in suspected preeclampsia. However, Ministry of Health guidelines do not currently endorse PlGF-based tests in New Zealand (NZ). AIMS: To investigate the predictive value of soluble fms-like tyrosine kinase 1 (sFlt-1)/PlGF ratio in suspected preeclampsia in a NZ population. MATERIALS AND METHODS: A prospective cohort study of singleton pregnancies at 20+0 -36+6 weeks gestation with suspected preeclampsia as defined by Society of Obstetric Medicine Australia and NZ (SOMANZ) criteria. PRIMARY OBJECTIVE: to evaluate a sFlt-1/PlGF ratio >38 at ≤35+0 weeks gestation to predict birth ≤14 days. SECONDARY OBJECTIVES: to assess a sFlt-1/PlGF ratio cut-off of 38 at ≤37+0 weeks gestation, to rule out preeclampsia ≤1 week, rule in preeclampsia ≤4 weeks, and to predict perinatal outcome. Clinicians were blinded to sFlt-1/PlGF ratio results. RESULTS: Included were 222 participants, 19.4% Maori and 10.4% Pasifika. A sFlt-1/PlGF >38 predicted birth ≤14 days, positive predictive value (PPV) 51.4% (95% CI, 39.6-63.0) and negative predictive value (NPV) 95.9% (95% CI, 91.4-98.1), median (interquartile range) days to birth 14 (2-27) vs 49 (33-70), P < 0.000. A sFlt-1/PlGF cut-off of 38 ruled out preeclampsia ≤1 week (NPV 96.2% (95% CI, 92.3-98.2)) and ruled in preeclampsia ≤4 weeks (PPV 75.0% (95% CI, 65.0-82.9)). A sFlt-1/PlGF >38 was associated with greater perinatal morbidity. CONCLUSIONS: The predictive value of the sFlt-1/PlGF ratio in NZ is comparable to that reported in international trials. Used in clinical practice the sFlt-1/PlGF ratio may aid risk stratification in suspected preeclampsia, directing limited resources to those pregnancies at highest risk.

Prediabetes in pregnancy, can early intervention improve outcomes? A feasibility study for a parallel randomised clinical trial.

OBJECTIVE: Measurement of glycated haemoglobin (HbA1c) in early pregnancy is routine in New Zealand to identify women with diabetes and prediabetes. However, the benefit of early intervention in women with prediabetes is inconclusive. Our aim was to test the feasibility of a two-arm parallel randomised controlled trial of standard care versus early intervention in pregnancies complicated by prediabetes. SETTING: Two tertiary referral centres in New Zealand. PARTICIPANTS: Women <14 weeks' gestation and HbA1c ≥5.9%-6.4% (41-46 mmol/mol) measured at booking, without pre-existing diabetes. INTERVENTIONS: Randomisation was done by remote web-based allocation into one of two groups. Women in the early intervention group attended an antenatal diabetes clinic, commenced daily home blood glucose monitoring, and medication was prescribed if lifestyle measures failed to maintain target blood glucose levels. Controls received lifestyle education, continued standard care with their midwife and/or obstetrician, and were asked to perform a 75 g oral glucose tolerance test at 24 weeks' gestation with a referral to clinic if this test was positive. Both groups received lifestyle questionnaires at recruitment and in late pregnancy. OUTCOME MEASURES: Recruitment rate, adherence to protocol and validation of potential primary outcomes. RESULTS: Recruitment rates were lower than expected, especially in Maori and Pacific women. Non-adherence to allocated treatment protocol was significant, 42% (95% CI 24% to 61%) in the early intervention group and 30% (95% CI 16% to 51%) in controls. Caesarean section and pre-eclampsia were signalled as potential primary outcomes, due to both the high observed incidence in the control group and ease of measurement. CONCLUSIONS: For a future definitive trial, extending the gestation of eligibility and stepped-wedge cluster randomisation may overcome the identified feasibility issues. Consistent with published observational data, pre-eclampsia and emergency caesarean section could be included as primary outcome measures, both of which have a significant impact on maternal and neonatal morbidity and healthcare costs. TRIAL REGISTRATION NUMBER: ACTRN12615000904572; Pre-results.

Evaluation of the NZ guidelines for screening for persistent postpartum hyperglycaemia following gestational diabetes.

BACKGROUND: Recent New Zealand guidelines recommend annual glycated haemoglobin (HbA1c) measurements from three months postpartum, replacing the glucose tolerance test (GTT) at six weeks, to screen for persistent hyperglycaemia following gestational diabetes. Data suggest that this screening approach may miss cases of type 2 diabetes, but are they detected at subsequent screening and will screening rates improve? AIMS: Our aim was to evaluate the effectiveness of HbA1c monitoring in improving screening rates following gestational diabetes and in detecting postpartum hyperglycaemia. MATERIALS AND METHODS: During 2015 in Christchurch, all women with gestational diabetes were offered HbA1c and GTT measurements at three months postpartum and subsequent annual HbA1c measurements were recommended. Data from electronic hospital records were collected for a minimum 18 months postpartum. RESULTS: Of the cohort of 333 women, 218 (65%) completed both HbA1c and GTT at three months postpartum, 74 (22%) HbA1c only, 16 (5%) GTT only, 25 (8%) no screening; 184 (55%) had subsequent HbA1c tests. Diabetes was detected by GTT in five (2%) women and by HbA1c in only one out of five (20%); the disagreement between tests resolved in three out of four (75%) women with subsequent testing. Prediabetes was detected by GTT in 30 (14%) women; however, HbA1c only detected five out of 30 (17%) and subsequent HbA1c testing identified a further two out of 30 with prediabetes. CONCLUSIONS: HbA1c measurement at three months postpartum had a good uptake. However, most cases of diabetes were identified by subsequent HbA1c testing, the uptake of which was suboptimal. The importance of annual HbA1c monitoring following gestational diabetes needs greater emphasis.

Antenatal haemoglobin A1c centiles: does one size fit all?

BACKGROUND: In New Zealand, haemoglobin A1c measurements are routinely offered at booking, preferably before 20 weeks gestation, to detect pre-existing hyperglycaemia. A haemoglobin A1c <5.9% (41 mmol/mol) is considered normal based on the reference range for the non-pregnant population. AIMS: To determine pregnancy-specific haemoglobin A1c centiles by gestation and ethnicity. MATERIALS AND METHODS: This is a population-based observational study of pregnancies uncomplicated by diabetes (pre-existing or gestational) with ≥1 haemoglobin A1c measurement. Haemoglobin A1c centiles were calculated from data extracted from electronic laboratory and clinical records for pregnancies during 2008-2010. RESULTS: Included were 6800 pregnancies, European 80% (5462), Maori 6% (415), Pacific Islander 3% (196) and 11% (727) 'Others' (mostly Asian). Haemoglobin A1c levels fell with increasing gestation, reaching a nadir at 24 weeks, a trend verified by longitudinal data from 112 women. The 97.5th centile for haemoglobin A1c in European women was 5.76% (39.5 mmol/mol) at 8+0  weeks, 5.70% (38.8 mmol/mol) at 16+0  weeks, and 5.65% (38.3 mmol/mol) at 24+0  weeks. Non-European women had both higher plasma glucose levels (although within the range considered normal) and higher mean haemoglobin A1c levels compared with Europeans; mean (SD) difference in haemoglobin A1c in Maori +0.13% (0.05) (+1.4 mmol/mol (0.5)), Pacific +0.20% (0.03) (+2.2 mmol/mol (0.3)), 'Others' +0.10% (0.03) (+1.1 mmol/mol (0.3)). CONCLUSIONS: The New Zealand haemoglobin A1c cut-point ≥5.9% (41 mmol/mol) for identifying hyperglycaemia in early pregnancy is greater than the 97.5th centile in European and 'Other' women. Utilising population haemoglobin A1c centiles adjusted by gestation may thus better guide management decisions.

Is There a Role for HbA1c in Pregnancy?

Outside pregnancy, HbA1c analysis is used for monitoring, screening for and diagnosing diabetes and prediabetes. During pregnancy, the role for HbA1c analysis is not yet established. Physiological changes lower HbA1c levels, and pregnancy-specific reference ranges may need to be recognised. Other factors that influence HbA1c are also important to consider, particularly since emerging data suggest that, in early pregnancy, HbA1c elevations close to the reference range may both identify women with underlying hyperglycaemia and be associated with adverse pregnancy outcomes. In later pregnancy, HbA1c analysis is less useful than an oral glucose tolerance test (OGTT) at detecting gestational diabetes. Postpartum, HbA1c analysis detects fewer women with abnormal glucose tolerance than an OGTT, but the ease of testing may improve follow-up rates and combining HbA1c analysis with fasting plasma glucose or waist circumference may improve detection rates. This article discusses the relevance of HbA1c testing at different stages of pregnancy.

An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes.

OBJECTIVE: Pregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA1c ≥6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at <20 weeks' gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODS: During 2008-2010 in Christchurch, New Zealand, women were offered an HbA1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA1c performance was assessed using World Health Organization criteria. RESULTS: HbA1c was measured at a median 47 days' gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA1c ≥5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA1c <6.5% (<48 mmol/mol). This HbA1c threshold was also 98.4% (95% CI 97-99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA1c of 5.9-6.4% (41-46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA1c <5.9% (<41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28-5.53), preeclampsia was 2.42 (1.34-4.38), shoulder dystocia was 2.47 (1.05-5.85), and perinatal death was 3.96 (1.54-10.16). CONCLUSIONS: HbA1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA1c ≥5.9% (≥41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.

Customised birthweight centiles are useful for identifying small-for-gestational-age babies in women with type 2 diabetes.

BACKGROUND: Customised birthweight centiles identify small-for-gestational-age (SGA) babies at increased risk of morbidity more accurately than population centiles, but they have not been validated in obese populations. AIMS: To compare the rates of SGA by population and customised birthweight centiles in babies of women with type 2 diabetes and examine perinatal outcomes in customised SGA infants. METHODS: Data were from a previous retrospective cohort study detailing pregnancy outcomes in 212 women with type 2 diabetes. Customised and population birthweight centiles were calculated; pregnancy details and neonatal outcomes were compared between groups that delivered infants who were SGA (birthweight < 10th customised centile) and appropriate weight for gestational age (AGA) (birthweight 10-90th customised centile). RESULTS: Fifteen (7%) babies were SGA by population centiles and 32 (15%) by customised centiles. Two babies of Indian women were reclassified from SGA to AGA by customised centiles. Nineteen babies were reclassified from AGA to SGA by customised centiles; of these, 15 (79%) were born to Polynesian women, five (26%) were born less than 32 weeks and two (11%) were stillborn. Customised SGA infants, compared with AGA infants, were more likely to be born preterm (19 (59%) vs 20 (16%), P < 0.001) and more likely to be stillborn (4 (13%) vs 0 P = 0.001). After excluding still births, admission to the neonatal unit was also more common (19 of 28 (68%) vs 43 of 127 (34%), P < 0.001). CONCLUSIONS: In our population more babies were classified as SGA by customised compared with population centiles. These customised SGA babies have high rates of morbidity.

Transfer of rofecoxib into human milk.

OBJECTIVE: To determine the milk-to-plasma (M/P) concentration ratio of rofecoxib in lactating mothers and estimate likely infant exposure. METHODS: Rofecoxib 25 mg was given to six lactating women at weaning. Blood and milk were sampled up to 72 h post-dose for determination of rofecoxib concentrations. M/P ratios were derived from the respective area under the concentration-time curves. The infant 'dose' in milk was estimated and expressed as a percentage of the maternal dose, corrected for weight. RESULTS: The median (range) M/P ratio and infant 'dose' were 0.25 (0.16-0.32) and 2.1% (1.8-3.2%), respectively. CONCLUSIONS: The use of rofecoxib during breastfeeding is unlikely to pose harm to the suckling infant on the basis of low transfer into human milk.