Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial).

OBJECTIVE: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy. METHODS: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated. RESULTS: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%. CONCLUSION: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective.

The challenge of multidisciplinary research: improving diabetic pregnancy together.

Improving diabetic pregnancy outcome is a goal shared by many involved specialists. Despite proper glucose control, the incidence of maternal and perinatal complications is very high, including a high risk for pre-eclampsia, congenital malformations, perinatal mortality and macrosomia. To improve outcome, not only collaborating in the doctor's office is required but also participation in critical evaluation of our treatment strategies by means of randomised clinical trials.

[Diabetes and pregnancy; the prevention of hypoglycaemia]. / Diabetes en zwangerschap; het voorkómen van hypoglykemie.

In women with type-1 diabetes, the prevalence of maternal and fetal complications is high despite the overall adequate blood glucose control (HbA1c < 7%). Further improvements are hampered by the high incidence of maternal hypoglycaemia, including coma, especially during the first trimester of pregnancy. The reasons for this include the intensified insulin treatment, the decrease in hypoglycaemia awareness and the increase in glucose fluctuations. A further improvement of glucose control would provisionally seem possible only by using short-acting insulin analogues. These agents are currently under investigation. Continuous subcutaneous glucose measurements early in pregnancy show considerable glucose fluctuations despite almost normal HbA1c values. Moreover, they often reveal a hypoglycaemic event that the pregnant woman has not recognised. It is possible that these glucose fluctuations, rather than the too high average blood glucose levels, are responsible for congenital malformations and fetal macrosomia. Neonatal hypoglycaemia is associated with poor psychoneurological development. This relationship has not been established for maternal hypoglycaemia during pregnancy.

Effect of breast milk of diabetic mothers on bodyweight of the offspring in the first year of life.

OBJECTIVE: There is increasing evidence that in healthy populations, breast-fed infants are leaner than formula-fed infants. It is of interest to know the effects of breast-feeding on infant weight in case of maternal diabetes, given the high incidence of fetal macrosomia and risk of childhood obesity in this population. DESIGN AND SUBJECTS: As part of a nation-wide study in the Netherlands on diabetes and pregnancy, 229 women with Type 1 diabetes were sent a questionnaire on weight and height of their infant, the type of nutrition given during the first 6 weeks of life, the duration of lactation and intercurrent diseases during the first year of life. RESULTS AND CONCLUSION: Our data show no significant difference between breast-,formula-, and mixed-fed infants in weight and body mass index (BMI) at 1 y of age, which is not in accordance with the findings in nondiabetic populations.

Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants.

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.

Poor glucose control in women with type 1 diabetes mellitus and 'safe' hemoglobin A1c values in the first trimester of pregnancy.

OBJECTIVE: To observe glycemic excursions, measured continuously over 24 h, in relation to hemoglobin A1c values in the first trimester of pregnancy of women with type 1 diabetes mellitus. METHODS: The MiniMed Continuous Glucose Monitoring System (CGMS) was used to obtain glucose values every 5 min during 24 h. Hemoglobin A1c was determined at the end of the continuous glucose recording and 6-12 weeks after the continuous glucose recording. RESULTS: Continuous glucose recordings were obtained in 13 women between 7 and 15 weeks of gestation. Nine patients had hemoglobin A1c levels of < or = 7.0% (< 1% above the upper limit of normal range) while up to 41.3% of the readings had values of < 3.9 mmol/l (70 mg/dl) and up to 52.8% of the readings had values of > 7.8 mmol/l (140 mg/dl). CONCLUSIONS: Hemoglobin A1c does not reflect the complexities of glycemic control in women with type 1 diabetes who are considered to have accomplished tight glycemic control in the first trimester of pregnancy.

Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in The Netherlands.

AIMS/HYPOTHESIS: To investigate the incidence of foetal macrosomia (i.e. birth weight >90th percentile) in a non-selected nationwide cohort of women with Type I (insulin-dependent) diabetes mellitus in The Netherlands and to identify risk indicators predictive for macrosomia. METHODS: We conducted a prospective nationwide cohort based survey regarding the outcome of Type I diabetic pregnancy in The Netherlands. Data of 289 women who gave birth to a live singleton infant without major congenital malformations at more than or equal to 28 weeks of gestation are shown. RESULTS: The incidence of foetal macrosomia was very high (48.8%), with 26.6% of infants weighing more than 97.7th percentile. Glycaemic control during pregnancy was good (i.e. mean HbA(1c)

[Pregnancy in women with diabetes mellitus type I: maternal and perinatal complications, in spite of good blood glucose control]. / Zwangerschap bij vrouwen met diabetes mellitus type I: nog steeds maternale en perinatale complicaties, ondanks goede bloedglucoseregulatie.

OBJECTIVE: To examine the maternal and neonatal outcome of pregnancies of women with type I diabetes mellitus. DESIGN: Retrospective. METHODS: The medical records of pregnancies (> or = 16 weeks) in women with type I diabetes mellitus between 1986/'97 were studied in University Medical Center Utrecht, Academic Hospital Groningen and Isala Clinics, location 'De Weezenlanden', Zwolle, the Netherlands. RESULTS: During the study period, 172 women had 220 pregnancies: 212 single and 8 twin pregnancies. The mean age was 29.1 years (SD: 4.1), the mean duration of standing of the diabetes was 12 years (range: 1-32) and the mean concentration of glycosylated haemoglobin (HbA1c) was 6.3% at 10 weeks of pregnancy. The incidence of children with congenital malformations was 4 times higher (n = 19; 9.0%) than that in the Dutch population (2%). Macrosomia occurred in 92 children (43.4%) and perinatal mortality in 7 (3.3%). Maternal hypertensive complications occurred in 39 single pregnancies (18.4%), which is 2-3 times more often than in the Dutch population. CONCLUSION: In type I diabetic women maternal complications, perinatal morbidity and mortality are increased, despite near optimal glycaemic control.

The fourth sound of Korotkoff in pregnancy: a myth.

OBJECTIVE: To determine the detection rate and the reproducibility of the first (K1), the fourth (K4) and the fifth (K5) phases of the Korotkoff sounds in pregnant women. STUDY DESIGN: In 77 pregnant women receiving antenatal care in a tertiary referral centre, two observers took 231 simultaneous blood pressure measurements with a shared mercury sphygmomanometer and a multi-aural stethoscope. Detection rates, percentages of observer agreement within 5 mmHg and kappa values were calculated for K1, K4 and K5. RESULTS: Both observers were able to detect K1, K4 and K5 in 98, 24 and 98% of all 231 measurements, respectively. In 46% of measurements, and in 23% of women, neither observer was able to detect K4. The observers agreed within 5 mmHg in 98 (kappa = 0.99), 69 (kappa = 0.42), and 96% (kappa = 0.99) of measurements for K1, K4 and K5, respectively. CONCLUSION: K4 cannot be detected and reproduced accurately in a significant proportion of pregnant women, and therefore should be abandoned as diastolic endpoint in pregnancy.