Identification of cases with adverse neonatal outcome monitored by cardiotocography versus ST analysis: secondary analysis of a randomized trial.

OBJECTIVE: To evaluate whether correct adherence to clinical guidelines might have led to prevention of cases with adverse neonatal outcome. DESIGN: Secondary analysis of cases with adverse outcome in a multicenter randomized clinical trial. SETTING: Nine Dutch hospitals. POPULATION: Pregnant women with a term singleton fetus in cephalic position. METHODS: Data were obtained from a randomized trial that compared monitoring by STAN® (index group) with cardiotocography (control group). In both trial arms, three observers independently assessed the fetal surveillance results in all cases with adverse neonatal outcome, to determine whether an indication for intervention was present, based on current clinical guidelines. MAIN OUTCOME MEASURES: Adverse neonatal outcome cases fulfilled one or more of the following criteria: (i) metabolic acidosis in umbilical cord artery (pH < 7.05 and base deficit in extracellular fluid >12 mmol/L); (ii) umbilical cord artery pH < 7.00; (iii) perinatal death; and/or (iv) signs of moderate or severe hypoxic ischemic encephalopathy. RESULTS: We studied 5681 women, of whom 61 (1.1%) had an adverse outcome (26 index; 35 control). In these women, the number of performed operative deliveries for fetal distress was 18 (69.2%) and 16 (45.7%), respectively. Reassessment of all 61 cases showed that there was a fetal indication to intervene in 23 (88.5%) and 19 (57.6%) cases, respectively. In 13 (50.0%) vs. 11 (33.3%) cases, respectively, this indication occurred more than 20 min before the time of delivery, meaning that these adverse outcomes could possibly have been prevented. CONCLUSIONS: In our trial, more strict adherence to clinical guidelines could have led to additional identification and prevention of adverse outcome.

Prediction of neonatal metabolic acidosis in women with a singleton term pregnancy in cephalic presentation.

We sought to predict neonatal metabolic acidosis at birth using antepartum obstetric characteristics (model 1) and additional characteristics available during labor (model 2). In 5667 laboring women from a multicenter randomized trial that had a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation, we predicted neonatal metabolic acidosis. Based on literature and clinical reasoning, we selected both antepartum characteristics and characteristics that became available during labor. After univariable analyses, the predictors of the multivariable models were identified by backward stepwise selection in a logistic regression analysis. Model performance was assessed by discrimination and calibration. To correct for potential overfitting, we (internally) validated the models with bootstrapping techniques. Of 5667 neonates born alive, 107 (1.9%) had metabolic acidosis. Antepartum predictors of metabolic acidosis were gestational age, nulliparity, previous cesarean delivery, and maternal diabetes. Additional intrapartum predictors were spontaneous onset of labor and meconium-stained amniotic fluid. Calibration and discrimination were acceptable for both models (c-statistic 0.64 and 0.66, respectively). In women with a high-risk singleton term pregnancy in cephalic presentation, we identified antepartum and intrapartum factors that predict neonatal metabolic acidosis at birth.

Home blood pressure monitoring detects unrevealed hypertension in women with a history of preeclampsia: Results of the BP-PRESELF study.

Objectives: The risk of cardiovascular disease more than doubles after hypertensive disorders of pregnancy. As early onset chronic hypertension contributes to cardiovascular risk, implementation of screening strategies, using home blood pressure monitoring (HBPM), may help to improve long-term cardiovascular health.We evaluated whether HBPM among women with a history of preeclampsia/HELLP syndrome is feasible for early detection and management of hypertension. Methods: The BP-PRESELF study is a multicenter randomized controlled trial. Participants were randomized to intervention group with HBPM for the duration of 1 year or the control group with 'usual care'. The primary outcome was feasibility of HBPM during 1 year of follow-up, defined as protocol adherence, protocol persistence and patient acceptance. Secondary outcomes were blood pressure levels and prevalence of hypertension. Results: We recruited 198 women with a mean age of 45 years. Protocol adherence decreased during the first 6 months, after which it stabilized. Protocol persistence remained high throughout follow-up. During the study period, 33 women (34%) in the intervention group were diagnosed with hypertension versus only 10 women (11%) in the control group, P<0.001. At 1-year follow-up, mean systolic blood pressure (SD) was 120.4 (11.6) mmHg in the intervention group versus 126.1 (14.3) mmHg in the control group, P=0.003. Mean diastolic blood pressure (SD) values were 77.1 (8.0) mmHg versus 81.7 (9.4) mmHg, P<0.001, respectively. Adjusted systolic and diastolic differences (95% confidence interval) were -6.81 (-10.17, -3.45) and -4.93 (-7.26, -2.61) mm Hg, with 80% less hypertension at 1-year follow-up in the intervention group. Conclusions: HBPM appears to be feasible for follow-up of blood pressure in women after preeclampsia/HELLP syndrome, while it detected hypertension and blood pressure levels reduced in one-third of women in this group.

Changes in Micronutrient Intake and Status, Diet Quality and Glucose Tolerance from Preconception to the Second Trimester of Pregnancy.

Data on changes in dietary intake and related blood parameters throughout pregnancy are scarce; moreover, few studies have examined their association with glucose homeostasis. Therefore, we monitored intake of folate, vitamin B6, vitamin B12, vitamin D and iron, their status markers, and diet quality from preconception to the second trimester of pregnancy, and we examined whether these dietary factors were associated with glucose homeostasis during pregnancy. We included 105 women aged 18⁻40 years with a desire to get pregnancy or who were already <24 weeks pregnant. Women at increased gestational diabetes (GDM) risk were oversampled. Measurements were scheduled at preconception (n = 67), and 12 (n =53) and 24 weeks of pregnancy (n =66), including a fasting venipuncture, 75-grams oral glucose tolerance test, and completion of a validated food frequency questionnaire. Changes in micronutrient intake and status, and associations between dietary factors and glucose homeostasis, were examined using adjusted repeated measures mixed models. Micronutrient intake of folate, vitamin B6 and vitamin D and related status markers significantly changed throughout pregnancy, which was predominantly due to changes in the intake of supplements. Micronutrient intake or status levels were not associated with glucose homeostasis, except for iron intake (FE µg/day) with fasting glucose (ß = -0.069 mmol/L, p = 0.013) and HbA1c (ß = -0.4843 mmol, p = 0.002). Diet quality was inversely associated with fasting glucose (ß = -0.006 mmol/L for each DHD15-index point, p = 0.017). It was shown that micronutrient intakes and their status markers significantly changed during pregnancy. Only iron intake and diet quality were inversely associated with glucose homeostasis.

[ASalmonellainfection in a pregnant traveller]. / EenSalmonella-infectie bij een zwangere reiziger.

BACKGROUND: Infectious diseases are a common problem in people who travel to countries with poor hygiene standards. Pregnant travellers are subjected to increased risk because of the higher probability of complications in case of certain infectious diseases and the variability of prenatal care quality in these countries. CASE DESCRIPTION: A pregnant patient presented herself at the emergency department with recurring fever and chills, a month after she had been to Indonesia. This was associated with a Salmonella infection; the placenta was the infection reservoir. CONCLUSION: Travelling while pregnant is not without risk. Quick diagnosis and treatment of infections, which may sometimes have an atypical presentation during pregnancy, can be of crucial importance. It is extra important for pregnant people to get travel advice before the trip, so that risks, alarming symptoms and additional hygiene measures can be discussed.

Supplement Use and Dietary Sources of Folate, Vitamin D, and n-3 Fatty Acids during Preconception: The GLIMP2 Study.

An adequate nutritional status during the preconception period is important, particularly for folate, vitamin D, and n-3 fatty acids (i.e., EPA+DHA). We aimed to determine supplement intake and the main dietary sources of folate, vitamin D, and EPA+DHA using the data of 66 Dutch women aged 18⁻40 years who wished to become pregnant. Additionally, associations of these intakes with their blood levels were examined. Dietary intake was assessed with a validated food frequency questionnaire, and supplement use with a structured questionnaire. 25-hydroxyvitamin D levels were determined in serum and folate and phospholipid EPA+DHA levels in plasma. Partial Spearman's correlations, restricted cubic splines and trend analyses over tertiles of nutrient intakes were performed to examine intake-status associations. A large proportion of women did not meet the Dutch recommended intakes of folate (50%), vitamin D (67%), and EPA+DHA (52%). Vegetables were the main contributor to dietary folate intake (25%), oils and fats to dietary vitamin D intake (39%), and fish to dietary EPA+DHA intake (69%). Fourteen percent of the women had an inadequate folate status and 23% an inadequate vitamin D status. Supplemental folate intake, supplemental and dietary vitamin D intake and dietary EPA+DHA intake were significantly associated with their blood levels. In conclusion, even in our highly educated population, a large proportion did not achieve recommended folate, vitamin D and n-3 fatty acid intakes. Promotion of folate and vitamin D supplement use and fish consumption is needed to improve intakes and blood levels of these nutrients in women who wish to become pregnant.

Early neonatal antioxidant capacity after preexisting impaired placental function.

Plasma antioxidant capacity in very preterm infants (n=17), measured as the ferric-reducing ability of plasma (FRAP), increased significantly until day 2 postpartum and decreased thereafter until day 7. Within this period, the FRAP values in matched infants, born after impaired placental function (IPF, n=17), did not change. Their FRAP values were lower and the incidence of oxidative stress-related diseases was significantly higher in these infants.

Comparison of single and repeated antenatal corticosteroid therapy to prevent neonatal death and morbidity in the preterm infant.

INTRODUCTION: In the case of threatened preterm delivery, repeat administration of antenatal corticosteroids is a common practice in women who have not delivered 7-14 days after the first course of corticosteroids. However, the benefits of this policy as compared to single-course administration have not been proven. AIM: Our purpose was to compare neonatal death and morbidity after repeat antenatal courses of corticosteroids with neonatal death and morbidity after a single course. METHODS: We performed a cohort study with matched controls. Neonates treated with repeat antenatal courses of corticosteroids were matched with neonates treated with a single course. Matching criteria were sex, single or multiple gestation, route of delivery, gestational age at delivery and year of birth. Intrauterine growth-restricted infants were matched separately. We excluded neonates with congenital malformation and neonates with an unknown number of antenatal corticosteriod courses. Outcome measures were the incidences of neonatal death, respiratory distress syndrome, intraventricular haemorrhage and necrotizing enterocolitis. RESULTS: From the neonates treated with two or three courses of antenatal corticosteroids, 56 appropriate grown neonates and 24 intrauterine growth-restricted neonates could be matched. The incidences of neonatal death, respiratory distress syndrome, intraventricular haemorrhage and necrotizing enterocolitis did not show statistically significant differences after single and repeat courses of corticosteroids. Appropriate grown and intrauterine growth-restricted neonates showed the same results. CONCLUSION: From our study, it can be concluded that in preterm neonates, repetition of antenatal corticosteroids seems not to improve neonatal outcome.

[Shock in pregnancy: foetal distress may be the first symptom]. / Shock in de zwangerschap: foetale nood kan het eerste teken zijn.

Shock may be difficult to recognize in pregnant women due to the physiological changes that take place in the cardiovascular system. The first symptom of shock may be foetal distress. We present two patients to illustrate this condition. The first patient had an uncomplicated pregnancy until she awoke from a 'pop' in her abdomen followed by an acute feeling of illness. She was hemodynamically stable but because the foetal heart rate pattern was abnormal, an emergency caesarean section was performed. This revealed an intraperitoneal bleeding of the uterine artery in the right broad ligament, caused by ectopic decidualization. The second patient had severe symptomatic renal dilatation in pregnancy which was managed through percutaneous nephrostomy. Following the procedure she became hypotensive, tachycardic and hyperthermic, indications of septic shock. A neonate with signs of asphyxia was born by emergency caesarean section undertaken for acute foetal distress evident from the foetal heart rate pattern.

Women's Attitudes towards the Option to Choose between Karyotyping and Rapid Targeted Testing during Pregnancy.

Objectives. Pregnant women, referred because of an increased risk of fetal Down syndrome, who underwent an invasive prenatal procedure were offered a choice between karyotyping and rapid targeted testing. This study aims to assess women's attitudes and experiences towards what option to choose. Methods. A retrospective multicentre survey (2008-2010) was conducted among 1370 women. General questions were asked about decision making issues, followed by personal questions about their experiences in choice making, test preference, influence of others, and possible regrets. Results. In total, 90.1% of the respondents (N = 825) indicated that pregnant women are able to choose, although 33.1% stated that the choice can best be made by a professional. 18.4% indicated that making a choice places a burden on women. In 96.4%, respondents preferred to have the option to choose again in case of a next pregnancy, whereas 2.7% preferred the choice to be made by a professional. Regret was indicated by 1.2%. Decision making was influenced by others in 64.9%. A slightly higher preference for karyotyping was indicated by 52.7% of the respondents. Conclusions. Positive attitudes and experiences were expressed towards the option to choose. Respondents took decisions freely, although sometimes influenced by a partner or a professional, to follow their individual perspectives.

Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.

Blood plasma of pregnant women contains circulating cell-free fetal DNA (ccffDNA), originating from the placenta. The use of this DNA for non-invasive detection of fetal aneuploidies using massively parallel sequencing (MPS)-by-synthesis has been proven previously. Sequence performance may, however, depend on the MPS platform and therefore we have explored the possibility for multiplex MPS-by-ligation, using the Applied Biosystems SOLiD(™) 4 system. DNA isolated from plasma samples from 52 pregnant women, carrying normal or aneuploid fetuses, was sequenced in multiplex runs of 4, 8 or 16 samples simultaneously. The sequence reads were mapped to the human reference genome and quantified according to their genomic location. In case of a fetal aneuploidy, the number of reads of the aberrant chromosome is expected to be higher or lower than in normal reference samples. To statistically determine this, Z-scores per chromosome were calculated as described previously, with thresholds for aneuploidies set at > +3.0 and < -3.0 for chromosomal over- or underrepresentation, respectively. All samples from fetal aneuploidies yielded Z-scores outside the thresholds for the aberrant chromosomes, with no false negative or positive results. Full-blown fetal aneuploidies can thus be reliably detected in maternal plasma using a multiplex MPS-by-ligation approach. Furthermore, the results obtained with a sample from a pregnancy with 45,X in the cytotrophoblastic cell layer and 46,XX in the mesenchymal core cells show that ccffDNA originates from the cytotrophoblastic cell layer. Discrepancies between the genetic constitution of this cell layer and the fetus itself are well known, and therefore, care should be taken when translating results to the fetus itself.

Effects of antenatal glucocorticoid therapy on hippocampal histology of preterm infants.

OBJECTIVE: To investigate if antenatal glucocorticoid treatment has an effect on hippocampal histology of the human preterm newborn. PATIENTS AND METHODS: Included were consecutive neonates with a gestational age between 24 and 32 weeks, who were born between 1991 to 2009, who had died within 4 days after delivery and underwent brain autopsy. Excluded were neonates with congenital malformations and neonates treated postnatally with glucocorticoids. The brains were routinely fixed, samples of the hippocampus were stained with haematoxylin and eosin and sections were examined for presence or absence of large and small neurons in regions of the hippocampus. Additional staining with GFAP, neurofilament and vimentin was performed to evaluate gliosis and myelination. The proliferation marker Ki67 was used to evaluate neuronal proliferation. Staining with acid fuchsin-thionin was performed to evaluate ischemic damage. RESULTS: The hippocampi of ten neonates who had been treated with antenatal glucocorticoids showed a lower density of large neurons (p = 0.01) and neurons irrespective of size (p = 0.02) as compared to eleven neonates who had not been treated with glucocorticoids. No difference was found in density of small neurons, in myelination, gliosis, proliferation or ischemic damage. CONCLUSION: We found a significantly lower density of neurons in the hippocampus of neonates after antenatal glucocorticoid treatment. Although the pathophysiological and clinical interpretations of these findings are not clear, they are consistent with those from experiments in mice and rhesus monkeys.

Why do parents prefer to know the fetal sex as part of invasive prenatal testing?

Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods. In this prospective study 400 pregnant women undergoing amniocentesis were invited to answer a questionnaire, including information about demographic factors, current pregnancy, and previous children. In two open-ended questions they were asked why they wanted to know the fetal sex after amniocentesis or ultrasound investigation. Scores were given for reasons that could have played a role in the wish whether or not to know the sex of their unborn child. Results. A total of 210 (52.5%) questionnaires were completed. Overall, 69.0% was interested to know the fetal sex as part of the diagnostic test result. The most important reasons were curiosity (77.8%), "just want to know" (68.0%), and "because it is possible" (66.8%). The overall knowledge of sex chromosomal disorders appeared low and did not seem to affect the parent's wish to know the fetal sex. Almost all women (96.6%) planned to have a 20-week ultrasound scan and 96.2% thought the scan to be reliable in detecting the fetal sex. A minority (28%) was willing to learn the fetal sex by ultrasound examination, whereas 65% preferred to learn the fetal sex only after the amniocentesis. Conclusion. Personal values affect the parental desire to know or not to know the fetal sex. This does not appear to be affected by invasive prenatal testing and/or genetic knowledge of sex chromosomal disorders.

Comparison of vaginal and transabdominal collection of amniotic fluid for fetal lung maturity tests.

BACKGROUNDS: The lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) are two tests that can be used to estimate the probability of the occurrence of respiratory distress syndrome (RDS). Our objective was to compare the prognostic capacity of the L/S ratio and the LBC in the prediction of RDS from amniotic fluid that was obtained either transabdominally or vaginally. METHODS: Consecutive women undergoing amniotic fluid sampling for determination of fetal lung maturity were included. In case the membranes were ruptured, amniotic fluid was obtained vaginally. Otherwise, amniotic fluid was obtained by transabdominal amniocentesis. In each specimen, an L/S ratio and a LBC were measured. The predictive capacity of specimens that were obtained vaginally and transabdominally were compared by calculating the area under the receiver-operating-characteristic curve (AUC) analysis. RESULTS: In 260 patients amniotic fluid was collected transabdominally, whereas in the other 67 patients there were ruptured membranes, and fluid was collected vaginally. RDS occurred in 25% of the patients without ruptured membranes, and in 34% of the patients with ruptured membranes. For the L/S ratio, the AUC was 0.56 (SE 0.09) for the vaginally collected specimens, and 0.93 (SE 0.02) in the specimens that were collected abdominally. For the LBC, the AUCs were 0.52 (SE 0.08) and 0.84 (SE 0.03), respectively. CONCLUSIONS: Fetal lung maturity tests that are performed in vaginally obtained specimens in patients with ruptured membranes are of no use in the prediction of RDS.

Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of intrapartum fetal monitoring by cardiotocography plus ST analysis using a strict protocol for performance of fetal blood sampling. METHODS: We performed a multicenter randomized trial among laboring women with a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation. Participants were assigned to monitoring by cardiotocography with ST analysis (index) or cardiotocography only (control). Primary outcome was metabolic acidosis, defined as an umbilical cord artery pH below 7.05 combined with a base deficit calculated in the extracellular fluid compartment above 12 mmol/L. Secondary outcomes were metabolic acidosis in blood, operative deliveries, Apgar scores, neonatal admissions, and hypoxic-ischemic encephalopathy. RESULTS: We randomly assigned 5,681 women to the two groups (2,832 index, 2,849 control). The fetal blood sampling rate was 10.6% in the index compared with 20.4% in the control group (relative risk 0.52; 95% [CI] 0.46-0.59). The primary outcome occurred 0.7% in the index compared with 1.1% in the control group (relative risk 0.70; 95% CI 0.38-1.28; number needed to treat 252). Using metabolic acidosis calculated in blood, these rates were 1.6% and 2.6%, respectively (relative risk 0.63; 95% CI 0.42-0.94; number needed to treat 100). The number of operative deliveries, low Apgar scores, neonatal admissions, and newborns with hypoxic-ischemic encephalopathy was comparable in both groups. CONCLUSION: Intrapartum monitoring by cardiotocography combined with ST analysis does not significantly reduce the incidence of metabolic acidosis calculated in the extracellular fluid compartment. It does reduce the incidence of metabolic acidosis calculated in blood and the need for fetal blood sampling without affecting the Apgar score, neonatal admissions, hypoxic-ischemic encephalopathy, or operative deliveries. LEVEL OF EVIDENCE: I.

Expression in the placenta of neuronal markers for perinatal brain damage.

Determination of S-100 a and b and neuron-specific enolase (NSE) in (cord) blood and amniotic fluid has been used to assess neonatal neuronal damage after compromising conditions. However, these proteins are not only found in nervous tissue, and their expression in placenta and umbilical cord has never been investigated. In this study, S-100 (a and b) and NSE expression in human cord and placental tissue was studied by immunohistochemical analysis. Similar analysis was performed using two other brain-specific markers: glial fibrillary acidic protein and growth-associated protein B-50 (also known as GAP-43 or neuromodulin). Tissue was derived after elective cesarean section in seven women of different gestational ages after uncomplicated or complicated pregnancy. S-100 a and b and NSE immunoreactivity was found in several cell types and structures in the umbilical cord as well as in the placenta of all seven cases. Glial fibrillary acidic protein and B-50 showed no immunoreactivity. These data are of importance for interpreting findings of studies in which S-100 or NSE levels in cord blood or amniotic fluid have been related to neuronal damage in the neonate. The increased levels found may just as well be caused by leakage from placenta or umbilical cord as be caused by brain damage. We conclude that S-100 a and b and NSE are not suitable markers for neonatal brain damage. Brain-restricted proteins such as glial fibrillary acidic protein and B-50 seem more promising.