G. H. A. Visser

Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study

Objectiveu2002 To evaluate mortality and morbidity in a large cohort of twin pregnancies according to chorionicity. We aimed to estimate the optimal time of delivery.

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

Abstractn 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.n 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.n 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 HbA1c ≤7.0%), in almost all (84%) women. Multiple logistic regression analysis resulted in a predictive model for macrosomia that incorporated five variables: third trimester HbA1c (Odds Ratio [95% Confidence Interval]: (1.6[1.1–2.4]), absence of third trimester severe hypoglycaemia (3.0[1.2–7.3]), the use of insulin lispro (3.1[0.9–10.4]), weight gain during pregnancy (1.1[1.0–1.2]) and non-smoking (2.8[0.9–9.3]). Third trimester HbA1c was the most powerful predictor for the occurrence of macrosomia, but its predictive capacity was weak (explained variance <5%).n Conclusion/interpretation. Despite apparent good glycaemic control, the incidence of foetal macrosomia in this non-selected prospective nationwide cohort of 289 Type I diabetic women was very high. Third trimester HbA1c was the most powerful predictor, but its predictive capacity was weak. Thus, future research should focus on new more detailed glucose monitoring techniques (such as a continuous glucose monitoring system) as well as to alternative factors to reduce macrosomia.

Emergence of behavioural states in fetuses of type-1-diabetic women.

The aim of this study was to investigate the effects of tightly controlled maternal (type-1-)diabetes mellitus on the development of fetal behavioural states. Seventeen diabetic women, who required insulin (Whites class C predominantly) and were treated with continuous subcutaneous insulin infusion (CSII) therapy, participated in the study. Adjustment to an insulin-pump occurred before conception or during early pregnancy. In all diabetic women (near-)normoglycemia was achieved during pregnancy, with glycosylated hemoglobin-values within the normal range (6-8.5%). Fifty-three 2-h recordings of fetal heart rate, uterine contractions and of real-time ultrasound scanning for fetal body movements, breathing and eye movements were obtained from the 17 fetuses. The fetuses were longitudinally studied between 32 and 40 weeks post menstrual age, at intervals of 2 weeks. The 3 state variables, fetal heart rate, body movements and eye movements, were analyzed for the presence of combinations meeting the definitions of the four fetal behavioural states. Findings in the fetuses of diabetic women were compared with those obtained from 28 low risk fetuses. The criteria of states were met in only 3 of 8 fetuses studied at 38 weeks and in one of two studied at 40 weeks. For comparison: in low risk fetuses studied at 38 and 40 weeks, states were present in 70% and 90% of the cases, respectively. This poorly developed state organization exhibited by the near term fetuses of the diabetic group, was related to maternal parity, but not to pre- or postconceptional onset of CSII-treatment. Fetuses of nulliparous diabetic women showed more often asynchrony of transitions (greater than 3 min) and interruption of periods of concordant association. This resulted in significantly higher percentages of no-coincidence and in low incidence of behavioural states as compared with control fetuses of nulliparous women. In the few multiparous diabetic cases studied near term the development of fetal behavioural states was normal. We conclude therefore that, despite tight control of maternal diabetes, the development of behavioural states is disturbed in fetuses of nulliparous diabetic women.

Vibro-acoustic stimulation of the human fetus: effect on behavioural state organization

Vibro-acoustic stimulation of the human fetus in being increasingly performed both antenatally and during labour, to differentiate between poor and good fetal health in cases of flat or otherwise suspect fetal heart rate patterns. In a controlled study we investigated the effect of the electronic artificial larynx (EAL) on fetal behavioural state organization. In 10 healthy women with normal pregnancies of 38-40 weeks of gestation, recordings of fetal heart rate, body movements and eye movements, with a duration of 120-210 min, were carried out during two consecutive days. In each fetus, 3-4 episodes of state 1F and consecutive state 2F were studied, one of which served as a control observation. EAL stimulation during state 1F was associated with excessive fetal movements and with a state change in 7 out of 9 observations (four times into 2F; three times into 4F). Stimulation during state 2F was associated with a change into 4F in four of the nine observations. On days with EAL stimulation the fetuses spent more time in state 4F or in an episode not classifiable (because of an atypical FHR pattern with tachycardia and small accelerations) than control fetuses (21% vs. 3% of time). Disorganized states or periods of state 4F sometimes lasted for more than 1 h following the stimulation. It is concluded that stimulation with the EAL induces excessive fetal movements, a prolonged tachycardia, non-physiological state changes and a disorganisation and change in the distribution of fetal behavioural states. Until more is known regarding the safety and risks of vibro-acoustic stimulation, it should not be used in a routine clinical setting.

Do HbA1c levels and the self-monitoring of blood glucose levels adequately reflect glycaemic control during pregnancy in women with type 1 diabetes mellitus?

Aims/hypothesisPregnancies of women with type 1 diabetes mellitus are associated with maternal and perinatal complications. These complication rates remain elevated despite achievement of the treatment goals described in the widely used guidelines of the American Diabetes Association (i.e. HbA1c level ≤7.0%). Against this background, we sought to answer two questions: (1) are HbA1c levels within 1% above normal appropriate in pregnant women with type 1 diabetes or should treatment be aimed at normal HbA1c levels; and (2) how many self-monitored blood glucose (SMBG) levels are needed per day to obtain an adequate image of glycaemic control in pregnant women with type 1 diabetes?Materials and methodsWe asked 43 pregnant women with type 1 diabetes to use the Continuous Glucose Monitoring System (CGMS) once in each trimester of pregnancy, while continuing their SMBG measurements. Glucose levels measured with the CGMS were compared between patients with HbA1c levels of 4.0–6.0%, 6.0–7.0% and >7.0%. Self-monitored glucose levels and those measured with CGMS were compared between patients with four or five, six to nine and ten or more SMBG determinations daily.ResultsIn patients with HbA1c levels ≤6.0%, the glucose levels obtained by CGMS were significantly better than in patients with HbA1c levels >6.0%. In women with HbA1c levels 6.0–7.0% and >7.0%, these levels did not differ. The detection rate of hyper- and hypoglycaemic episodes was significantly higher in patients with ten or more SMBG determinations daily than in patients with fewer than ten.Conclusions/interpretationTreatment of diabetes in pregnant women should be aimed at achieving HbA1c levels within the normal range, i.e. ≤6.0%. A minimum of ten SMBG determinations daily is necessary to obtain adequate information of all daily glucose fluctuations.

MORPHOLOGICAL FINDINGS IN PLACENTAE OF INSULIN-DEPENDENT DIABETIC-PATIENTS TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII)

Twenty-one placentae from type I (insulin-dependent) pregnant diabetic patients, treated with continuous subcutaneous insulin infusion (CSII), were studied morphologically. Despite a near-optimal blood glucose control the placental changes were identical to those previously reported in diabetic pregnancy. The most frequently observed lesion was that of relative placental immaturity; this, when extensive, was related to antenatal fetal asphyxia. These data indicate that near normoglycaemia, achieved with CSII, does not modify the morphological expression of the disease in the placenta. Furthermore, it highlights the importance of placental development in the context of diabetic pregnancy.

Inter- and intra-observer agreement of intrapartum ST analysis of the fetal electrocardiogram in women monitored by STAN.

Objectiveu2002 The objective of this study was to quantify inter‐ and intra‐observer agreement on classification of the intrapartum cardiotocogram (CTG) and decision to intervene following STAN guidelines.

THE EFFECTS OF MATERNAL HYPEROXIA ON FETAL BREATHING MOVEMENTS, BODY MOVEMENTS AND HEART-RATE VARIATION IN GROWTH RETARDED FETUSES

In hypoxemic intrauterine growth-retarded fetuses (IUGR) there is a reduction in the incidence of fetal movements and in fetal heart rate variation. A causal relationship with the impairment of fetal oxygenation has been suggested. In 16 IUGR fetuses and in 13 normally grown fetuses maternal hyperoxygenation was applied for 40 min to increase fetal PO2 levels. All IUGR fetuses had abnormal Doppler blood velocity waveforms of the umbilical artery suggesting an impaired uteroplacental exchange. The effect of hyperoxygenation on fetal breathing and body movements and on fetal heart rate was evaluated. In the IUGR fetuses there was a significant increase in fetal breathing and body movements and in heart rate variation during hyperoxygenation as compared to the preceding control period of 40 min. No significant changes in fetal breathing and body movements were found in the normally grown control fetuses. A surprising observation was the increase of the number of heart rate decelerations after discontinuation of the maternal hyperoxygenation. It is concluded that in IUGR fetuses the increase in fetal heart rate variation and the increase in the incidence of breathing and body movements during maternal hyperoxygenation substantiates the relationship between these variables and the oxygenation status of the fetus.

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 ≤ 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.

Pregnancy Outcome in Type 2 Diabetes Mellitus: A Retrospective Analysis from the Netherlands

MAIN OBJECTIVESnThe objective was to describe pre-gestational history and the maternal, fetal and neonatal outcome in pregnancies in women with pre-gestational type 2 diabetes during the period between 1992 and 2006 from one center in the Netherlands.nnnMETHODSnPatients attending the obstetric-diabetology outpatient clinic of a tertiary referral center were studied. This center also has a regular diabetes clinic and a community midwifery service. Patients were identified from the database. Maternal outcome (pre-eclampsia, pre-term delivery, Caesarean section) and fetal and neonatal outcome (macrosomia, congenital malformations, perinatal mortality, neonatal hypoglycemia) were analyzed as well HbA1c levels, planning of pregnancy, gestational age at first antenatal visit and ethnic background.nnnRESULTSnSixty-six singleton pregnancies from 48 women were analyzed. Their age was 34 +/- 5 yr, the BMI 31.7 +/- 7.4 and the median duration of diabetes was 3 yr. 52% were Caucasian and 35% were of Moroccan descent. 49% did not complete secondary school. Moroccan descent was associated with a lower educational level and a BMI comparable with the whole study group. The proportion of planned pregnancies was approximately 70%. The mean HbA1c in the first trimester was 6.4 +/- 1.1% and the gestational age at first visit was 10 +/- 5 wk, in one-quarter before 6 wk. The prevalences of variables related to maternal and neonatal outcome were as follows: spontaneous abortion 13.6%, pre-eclampsia 8.9%, pre-term delivery 21.4%, spontaneous labor 25.0%, induced labor 48.2%, Caesarean section 42.9%, macrosomia (>/=90th percentile) 41.1%, severe hypoglycemia 41.5% and major congenital malformations 5.1%.nnnCONCLUSIONSnPre-gestational type 2 diabetes is associated with an increased incidence of adverse pregnancy outcome despite reasonable mean HbA1c level and despite a high frequency of planned pregnancies. Many women report relatively late. Improvement in the outcome requires more active peri-gestational specialist care and a tailored approach is required towards migrant communities.