The WHO 2013 oral glucose tolerance test: The utility of isolated glucose measurements - A retrospective cohort study.

OBJECTIVE: The WHO 2013 guidelines recommend screening for gestational diabetes mellitus (GDM) by 3-point oral glucose tolerance test (OGTT). The objective of this retrospective cohort study was to evaluate GDM diagnosed by an isolated high glucose. STUDY DESIGN: We included pregnant women deemed at risk for GDM were offered GDM screening. We examined the records of 1939 consecutively screened pregnancies at two teaching hospitals in Amsterdam during 2016-2020. Using the WHO 2013 diagnostic criteria, we calculated the proportion of GDM cases diagnosed by isolated abnormal glucose values. RESULTS: Among those screened in our high risk cohort, GDM incidence was 31.5%. Of the GDM diagnoses, 57.0% were based on an isolated fasting glucose value, 30.9% based on multiple raised glucose measurements, 7.4% on an isolated raised 2-hour glucose and 4.7% on an isolated raised 1-hour glucose. For 1-hour glucose, the number needed to screen was 67 persons for one additional GDM case. CONCLUSION: The 1-hour glucose in the 3 point OGTT, as suggested by the WHO 2013 guidelines for GDM, contributes only small numbers of GDM cases and a high number needed to screen (67 for 1 additional case in a selective high risk GDM screening strategy), and is likely even less effective in universally screened populations.

Impact of suspected late-onset fetal growth restriction on obstetrical interventions and perinatal outcomes at term; a retrospective cohort study.

OBJECTIVES: First, assess accuracy of late third trimester universal fetal growth screening in high risk nulliparous women with a singleton in vertex presentation at term. Second, assess instrumental delivery rates and perinatal outcomes in this population. STUDY DESIGN: Single centre retrospective cohort study in a teaching hospital, The Netherlands. RESULTS: In a cohort of 1902 pregnancies, growth ultrasound after 33 weeks was moderately accurate in detecting children with a birthweight below the 10th centile with a sensitivity of 46.2% and a false positive rate of 4.7%. Induction of labour followed an antenatal suspicion of FGR more often than in the group with normal expected fetal weight (73.4% vs 52.6% OR 2.49 (1.88-3.3)) as could be expected from application of guidelines. The caesarean section rates was lowest in the group with suspected FGR compared to the group with expected normal fetal weight (15.2% vs 22.1% OR 0.63 (0.45-0.9)). There were no differences between both groups in rates of composite severe adverse perinatal outcome (0.7% vs 0.8% OR 0.87 (0.2-3.93)). CONCLUSIONS: The detection of growth restriction using universal screening in term high risk nulliparous women with a singleton in vertex position is moderate. Despite this, caesarean section rates were not increased and perinatal outcomes were similar when compared to that found in the randomized controlled trial on which the recommendation for induction of labour for suspected term FGR is based. This supports universal late third trimester fetal growth screening in pregnancies under consultant-led care in the two tiers Dutch obstetrical system.

New possibilities for ST analysis - A post-hoc analysis on the Dutch STAN RCT.

BACKGROUND: The diagnostic value of ST analysis of the fetal electrocardiogram (fECG) during labor is uncertain. False alarms (ST events) may be explained by physiological variation of the fetal electrical heart axis. Adjusted ST events, based on a relative rather than an absolute rise from baseline, correct for this variation and may improve the diagnostic accuracy of ST analysis. AIMS: Determine the optimal cut-off for relative ST events in fECG to detect fetal metabolic acidosis. STUDY DESIGN: Post-hoc analysis on fECG tracings from the Dutch STAN trial (STAN+CTG branch). SUBJECTS: 1328 term singleton fetuses with scalp ECG tracing during labor, including 10 cases of metabolic acidosis. OUTCOME MEASURES: Cut-off value for relative ST events at the point closest to (0,1) in the receiver operating characteristic (ROC) curve with corresponding sensitivity and specificity. RESULTS: Relative baseline ST events had an optimal cut-off at an increment of 85% from baseline. Relative ST events had a sensitivity of 90% and specificity of 80%. CONCLUSIONS: Adjusting the current definition of ST events may improve ST analysis, making it independent of CTG interpretation.

Fetal and Neonatal Alloimmune Thrombocytopenia: Management and Outcome of a Large International Retrospective Cohort.

OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome. RESULTS: A total of 615 pregnancies complicated by FNAIT from 10 countries were included. Anti-HPA-1a was the most commonly implicated antibody. Antenatal treatment was administered in 273 pregnancies (44%), varying from intrauterine platelet transfusion to maternal administration of immunoglobulins, steroids, or a combination of those. Intracranial haemorrhage was diagnosed in 23 fetuses or neonates (3.7%). Overall perinatal mortality was 1.14% (n = 7). CONCLUSION: This study presents the largest cohort of cases of FNAIT published. Our data show that antenatal treatment for FNAIT results in favourable perinatal outcome. Over time, in most centres, treatment for FNAIT changed from an invasive to a complete non-invasive procedure.

Prediction of neonatal outcome in women with gestational hypertension or mild preeclampsia after 36 weeks of gestation.

BACKGROUND: There is little knowledge about neonatal complications in GH and PE and induction at term, we aim to assess whether they can be predicted from clinical data. METHODS: We used data of the HYPITAT trial and evaluated whether adverse neonatal outcome (Apgar score < 7, pH < 7.05, NICU admission) could be predicted from clinical data. Logistic regression, ROC analysis and calibration were used to identify predictors and evaluate the predictive capacity in an antepartum and intrapartum model. RESULTS: We included 1153 pregnancies, of whom 76 (6.6%) had adverse neonatal outcome. Parity (primipara OR 2.75), BMI (OR 1.06), proteinuria (dipstick +++ OR 2.5), uric acid (OR 1.4) and creatinine (OR 1.02) were independent antepartum predictors; In the intrapartum model, meconium stained amniotic fluid (OR 2.2), temperature (OR 1.8), duration of first stage of labour (OR 1.15), proteinuria (dipstick +++ OR 2.7), creatinine (OR 1.02) and uric acid (OR 1.5) were predictors of adverse neonatal outcome. Both models showed good discrimination (AUC 0.75 and 0.78), but calibration was limited (Hosmer-Lemeshow p = 0.41, and p = 0.20). CONCLUSIONS: In women with GH or PE at term, it is difficult to predict neonatal complications, possibly since they are rare in the term pregnancy. However, the identified individual predictors may guide physicians to anticipate requirements for neonatal care.

Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study.

OBJECTIVE: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. DESIGN: Retrospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines. MAIN OUTCOME MEASURES: Number and type of ST-events. RESULTS: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. CONCLUSIONS: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

Fetal blood sampling in addition to intrapartum ST-analysis of the fetal electrocardiogram: evaluation of the recommendations in the Dutch STAN® trial.

OBJECTIVES: To evaluate the recommendations for additional fetal blood sampling (FBS) when using ST-analysis of the fetal electrocardiogram. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: In labouring women allocated to the STAN® arm of a previously published randomised controlled trial who underwent one or more FBS during delivery, we assessed whether FBS was performed according to the trial protocol and how fetal acidosis, defined as an FBS pH < 7.20, was related to ST-waveform analysis. MAIN OUTCOME MEASURES: The number of FBS showing fetal acidosis, related to the different STAN® criteria where additional FBS is recommended. RESULTS: Among 2827 women monitored with STAN®, 297 underwent FBS, of whom 171 (57.6%) were performed according to the predefined criteria and 126 were performed in absence of these criteria. In the first group, rates of fetal acidosis (pH < 7.20) were two of 18, none of nine, 12 of 111 and three of 33 when FBS was taken for abnormal cardiotocogram (CTG) at the start, intermediary CTG at the start, abnormal CTG >60 minutes, and poor electrocardiogram quality, respectively. When the predefined criteria were not met and ST-analysis showed no ST-events, only two incidents of fetal acidosis were seen. CONCLUSIONS: The performance of FBS is valuable in the advised STAN® criteria. When these criteria are not met, performance of FBS does not seem helpful in the detection of fetal acidosis.

Fetal thrombocytopenia.

Fetal thrombocytopenia is most often caused by maternal alloantibodies against fetal platelets crossing the placenta and resulting in platelet destruction. This condition, known as fetal and neonatal alloimmune thrombocytopenia, is usually detected after the birth of a symptomatic child who shows signs of bleeding in the skin or in the brain. In the most severe cases, intracranial hemorrhage leads to severe handicap or death. The challenge for the clinician is to provide preventive treatment in the next pregnancy. The current cornerstone of this treatment is maternal intravenous administration of immunoglobulins during the second half of pregnancy.

Kell alloimmunization in pregnancy: associated with fetal thrombocytopenia?

BACKGROUND AND OBJECTIVES: Kell haemolytic disease in pregnancies has been suggested to be associated with decreased fetal platelet counts. The aim of this study was to evaluate the incidence and clinical significance of fetal thrombocytopenia in pregnancies complicated by Kell alloimmunization. MATERIALS AND METHODS: In this retrospective cohort study, fetal platelet counts were performed in 42 pregnancies with severe Kell alloimmunization prior to the first intrauterine blood transfusion. Platelet counts from 318 first intrauterine transfusions in RhD alloimmunized pregnancies were used as controls. RESULTS: Fetal thrombocytopenia (platelet count < 150 x 10(9)/l) was found in 4/42 (10%) in the Kell group and in 84/318 (26%) in the RhD group. None of the fetuses in the Kell alloimmunized pregnancies, including 15 with severe hydrops, had a clinically significant thrombocytopenia defined as a platelet count < 50 x 10(9)/l. In the RhD alloimmunized pregnancies, 2/230 (1%) of the non-hydropic fetuses and 7/30 (23%) of the severely hydropic fetuses had a clinically significant thrombocytopenia. CONCLUSION: In contrast to fetuses with severe anaemia and hydrops due to RhD alloimmunization, fetuses with severe anaemia due to Kell alloimmunization are generally not at risk for substantial thrombocytopenia.

Thrombocytopenia in hydropic fetuses with parvovirus B19 infection: incidence, treatment and correlation with fetal B19 viral load.

OBJECTIVE: To examine (1) the incidence of fetal thrombocytopenia in hydropic fetuses with congenital B19 virus infection, (2) the effect of intrauterine platelet transfusions and (3) the correlation between fetal B19 viral load and severity of thrombocytopenia. DESIGN: Retrospective analysis of data from prospectively collected fetal blood samples. SETTING: Leiden University Medical Centre, the national centre for management of intrauterine fetal disease in the Netherlands. POPULATION: Thirty hydropic fetuses treated with intrauterine red blood cell and platelet transfusions for human B19 virus-induced severe fetal anaemia and thrombocytopenia over a 10-year period. METHODS: Fetal blood samples (n= 30) taken before and after intrauterine transfusion were investigated. No cases were excluded, and there was no loss to follow up. MAIN OUTCOME MEASURES: Parameters recorded were gestational age, experienced fetal movements, gravidity and parity, severity of fetal hydrops, severity of fetal anaemia and thrombocytopenia and megakaryocyte and reticulocyte counts. Survival and procedure-associated complications were documented. Quantitative B19 viral load measurements were performed on all fetal samples. RESULTS: Forty-six percent of all hydropic fetuses showed severe thrombocytopenia. No antenatal intracerebral haemorrhage or procedure-associated bleeding occurred. Overall, survival was 77%. Platelet counts increased following platelet transfusion and decreased significantly following red blood cell transfusion alone. No correlation was found between fetal viral loads and platelet counts. CONCLUSION: Thrombocytopenia was frequently encountered in fetal B19V infection, but fetal bleeding complications were not noted. Absence of a direct relationship between fetal B19 viral load and platelet counts suggests a temporal dissociation between these findings. Dilutional thrombocytopenia is frequently seen in the fetus following red blood cell transfusion alone. The clinical significance of this phenomenon is unclear. The risk of fluid overload by fetal platelet transfusion in a severely hydropic fetus should be weighed against the low incidence of fetal bleeding complications.

Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective.

OBJECTIVE: To describe the outcome of pregnancies with fetal and neonatal alloimmune thrombocytopenia (FNAIT) in relation to the invasiveness of the management protocol. DESIGN: Retrospective analysis of prospectively collected data from a national cohort. SETTING: Leiden University Medical Centre, the national centre for management of severe red cell and platelet alloimmunisation in pregnancy. POPULATION: Ninety-eight pregnancies in 85 women with FNAIT having a previous child with thrombocytopenia with (n= 16) or without (n= 82) an intracranial haemorrhage (ICH). METHODS: Our management protocol evolved over time from (1) serial fetal blood samplings (FBS) and platelet transfusion (n= 13) via (2) combined FBS with maternal intravenous immunoglobulins (n= 33) to (3) completely noninvasive treatment with immunoglobulins only (n= 52 pregnancies, resulting in 53 neonates). Perinatal outcome was assessed according to the three types of management. MAIN OUTCOME MEASURES: Occurrence of ICH, perinatal survival, gestational age at birth and complications of FBS. RESULTS: All but one of 98 pregnancies ended in a live birth; none of the neonates had an ICH. The median gestational age at birth was 37 weeks (range 32-40). In groups 1 and 2, three emergency caesarean sections were performed after complicated FBS, resulting in two healthy babies and one neonatal death. CONCLUSION: Noninvasive antenatal management of pregnancies complicated by FNAIT appears to be both effective and safe.

[Successful treatment and pregnancy in a women with the non-classic form of congenital adrenal hyperplasia]. / Succesvolle behandeling en zwangerschap bij een vrouw met de niet-klassieke vorm van het adrenogenitaal syndroom.

In an 18-year-old woman non-classic 21-hydroxylase deficiency was diagnosed and dexamethasone treatment was instituted. Ten years later, she became pregnant for the first time; at 37 weeks unexpected intrauterine foetal death was found to have occurred. A second pregnancy ended with a spontaneous abortion following a 12-week period of amenorrhoea. At the third pregnancy, the medication was replaced with hydrocortisone as it was suspected that the use of dexamethasone may have played a role in the intrauterine foetal death and the spontaneous abortion. The patient gave birth to a healthy, but dysmature, daughter. Female patients with non-classic congenital adrenal hyperplasia present with signs of androgen excess. Treatment with glucocorticoids reduces the symptoms and restores the menstrual cycle and fertility. Preconceptional advice by a clinical geneticist is recommended, because of the risk of an affected child. If there is no risk of having a child with congenital adrenal hyperplasia, hydrocortisone or prednisone is the treatment of choice during pregnancy as neither cross the placenta.