G.H.A. Visser

Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins

Background Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years. Methods This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. Findings Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5–38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffiths test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0–1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin. Conclusions There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

Is antenatal steroid treatment effective in preterm IUGR fetuses

There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterine growth restricted (IUGR) fetuses. Fetal lung maturation has been postulated to be enhanced in these fetuses, which may result in little benefit of steroid treatment. Furthermore, corticosteroid treatment may be detrimental, as has been shown in IUGR animal models. The objective of this study was to review the available literature on antenatal steroid treatment of the IUGR fetus. All available reports on antenatal steroid treatment of IUGR and small for gestational age (SGA) fetuses published prior to October 2007 were included in this review. IUGR fetuses are a subgroup of SGA fetuses that are small due to placental insufficiency, which is reflected in abnormal Doppler examination of the umbilical artery. The main outcome measures were respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and neonatal mortality. No difference in neonatal mortality was seen in any of the reviewed studies and RDS, IVH, and NEC incidence did not differ between treated and untreated IUGR fetuses. In SGA fetuses, results on RDS incidence and intracranial outcome were inconclusive. Antenatal steroid treatment does not seem to have an effect on neonatal mortality or morbidity in IUGR fetuses. In SGA fetuses, it remains unclear if antenatal steroid treatment is beneficial due to heterogeneous populations and treatment regimes. A randomized controlled trial should be performed to confirm prior results and answer further questions regarding antenatal steroid treatment of these fetuses.

Predictors of outcome at 2 years of age after early intrauterine growth restriction

To examine the relative importance of antenatal and perinatal variables on short‐ and long‐term outcome of preterm growth restricted fetuses with umbilical artery (UA) Doppler abnormalities.

Maternal Characteristics, Mean Arterial Pressure and Serum Markers in Early Prediction of Preeclampsia

Objectives In a previous study, we have described the predictive value of first-trimester Pregnancy-Associated Plasma Protein-A (PAPP-A), free β-subunit of human Chorionic Gonadotropin (fβ-hCG), Placental Growth Factor (PlGF) and A Disintegrin And Metalloprotease 12 (ADAM12) for early onset preeclampsia (EO-PE; delivery <34 weeks). The objective of the current study was to obtain the predictive value of these serum makers combined with maternal characteristics and first-trimester maternal mean arterial blood pressure (MAP) in a large series of patients, for both EO-PE and late onset PE (LO-PE; delivery ≥ 34 weeks). Methods This was a nested case-control study, using stored first-trimester maternal serum from women who developed EO-PE (n = 68) or LO-PE (n = 99), and 500 uncomplicated singleton pregnancies. Maternal characteristics, MAP, and pregnancy outcome were collected for each individual woman and used to calculate prior risks for PE in a multiple logistic regression model. Models containing prior PE risks, serum markers, and MAP were developed for the prediction of EO-PE and LO-PE. The model-predicted detection rates (DR) for fixed 10% false-positive rates were calculated for EO-PE and LO-PE with or without the presence of a small-for-gestational age infant (SGA, birth weight <10th centile). Results The best prediction model included maternal characteristics, MAP, PAPP-A, ADAM12, and PlGF, with DR of 72% for EO-PE and 49% for LO-PE. Prediction for PE with concomitant SGA was better than for PE alone (92% for EO-PE and 57% for LO-PE). Conclusion First-trimester MAP, PAPP-A, ADAM12, and PlGF combined with maternal characteristics and MAP are promising markers in the risk assessment of PE, especially for EO-PE complicated by SGA.

Severe Umbilical Cord Acidemia and Neurological Outcome in Preterm and Full-Term Neonates

Background: Severe intrauterine hypoxia-ischemia and acidemia may lead to a disturbed neurodevelopment. Objectives: To study the effects of acidemia at birth on neurodevelopment in preterm and full-term neonates. Subjects and Methods: Short- and long-term outcome were studied retrospectively in 44 inborn preterms and 95 full-terms with severe acidemia at birth defined as a pH of the umbilical artery <7.00. Outcome was compared with 67 preterm and 90 full-term non-acidemic neonates (pH > 7.15). Intraventricular hemorrhage (preterms) or seizures (both preterms and full-terms) were considered an adverse short-term outcome. Neonatal death, cerebral palsy or neurodevelopmental delay were considered an adverse long-term outcome. Results: Severe intraventricular hemorrhage (IVH) occurred in 5 of the 44 (11%) acidemic preterms and in none of the 67 (0%) non-acidemic preterms (p < 0.01). Seizures were observed in 9 of the 44 (20%) and 11 of the 95 (12%) acidemic preterms and full-terms, respectively, and in none of the 67 (0%) and 1 of the 90 (1%) non-acidemic preterms and full-terms, respectively (p < 0.001 for preterms, p < 0.01 for full-terms). Nine preterms (6 acidemic, 3 non-acidemic) and 2 full-terms (both acidemic) died in the neonatal period. Adverse long-term outcome occurred in 32% of the acidemic preterms, in 21% of the non-acidemic preterms, in 7% of the acidemic full-terms and in 7% of the non-acidemic full-terms. Conclusions: Acidemia at birth increased the occurrence of severe IVH in preterm neonates and seizures in both preterm and full-term neonates. However, no significant effect of acidemia on long-term outcome could be demonstrated.

Fetal behaviour does not differ between boys and girls.

INTRODUCTION Little is known about sex differences in human fetal heart and behaviour. PATIENTS AND METHODS One hundred twenty-three nulliparous healthy women carrying a male (n=56) or female (n=67) fetus participated in this study. All pregnancies remained uncomplicated and delivery was uneventful. Ultrasound observation of fetal general movements (GM) was performed for 1 h at 15-17 (T1) and 27-28 (T2) weeks of gestation and for 2 h at 37-39 weeks (T3). Fetal heart rate (FHR) monitoring occurred simultaneously with fetal ultrasound observations at T2 and T3. The incidence of GM (percentage of time), FHR and its variability, and the incidences of fetal heart rate patterns (HRP) A-D and behavioural states 1F-4F were compared between boys and girls. RESULTS There were no significant differences between males and females in the distribution of HRP A-D, overall behavioural state distribution, and basal FHR, FHR variability or the presence of GM during quiet and active sleep (or during HRP A and HRP B, respectively). A TimeXSex interaction effect for GM assessed for total record length and a higher %GM in male fetuses at term age were the only significant findings. However, these observations lost statistical significance after adjustment for the effects of fetal wakefulness, which occurred to a higher extent in male than in female fetuses. CONCLUSION Our data do not provide evidence for a difference in fetal functional development or maturation between the two sexes.

Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia

Objective The first aim was to investigate specific signature patterns of metabolites that are significantly altered in first-trimester serum of women who subsequently developed preeclampsia (PE) compared to healthy pregnancies. The second aim of this study was to examine the predictive performance of the selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE]. Methods This was a case-control study of maternal serum samples collected between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies. Metabolomics profiling analysis was performed using two methods. One has been optimized to target eicosanoids/oxylipins, which are known inflammation markers and the other targets compounds containing a primary or secondary biogenic amine group. Logistic regression analyses were performed to predict the development of PE using metabolites alone and in combination with first trimester mean arterial pressure (MAP) measurements. Results Two metabolites were significantly different between EO-PE and controls (taurine and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%. Conclusion Our findings suggest a potential role of taurine in both PE pathophysiology and first trimester screening for EO-PE.

The natural course of monochorionic and dichorionic twin pregnancies: a historical cohort.

Current early diagnosis, surveillance and intervention options make it hard to determine the natural course of twin pregnancies, especially regarding spontaneous preterm delivery and perinatal mortality. We studied the natural course in monochorionic (MC) and dichorionic (DC) twin pregnancies in a historical cohort. Twin pregnancies were studied in a unique database of 651 twin pairs born in the period 1907 to 1938. We examined the effect of chorionicity on gestational age, birthweight, perinatal mortality, intertwin birthweight differences, the incidence of preeclampsia and maternal mortality. Perinatal mortality was 27.7% for MC and 15.8% for DC twins (p < .001). Gestational age and birthweight were stronger predictors of perinatal mortality than chorionicity. Perinatal outcome was poorer for the second twin, especially in DC twins. Delivery before 37 weeks of gestation occurred more often in MC twin pregnancies (48.8% compared to 33.3% in DC twin pregnancies). DC twins were on average 288 g (95% confidence interval 201-376) heavier than MC twins. Severe birthweight discordancy occurred equally in MC and DC twins (18.1%). However, if present, mortality was only increased in MC twins. The birthweight of girls was not affected by the presence of a male co-twin. In this historical cohort MC twin pregnancies had a higher perinatal mortality, caused by a high incidence of low birthweight mainly due to preterm delivery. Mortality did not differ in deliveries after 31 weeks of gestation, which is in contrast to recent data. Apparently, modern obstetrics is more effective in reducing mortality in DC twins.

Bead‐based multiplexed immunoassays to identify new biomarkers in maternal serum to improve first trimester Down syndrome screening

To identify new discriminative biomarkers for Down syndrome (DS) pregnancies using a bead‐based multiplexed immunoassay, and to use the newly identified biomarkers to construct a prediction model for non‐invasive DS screening.

Prenatal maternal stress, HPA axis activity, and postnatal infant development

Abstract Objective : We examined whether psychological and endocrinological measures of stress during pregnancy predicted developmental outcome of human infants in a prospective design. Methods : Self-report data about daily hassles, pregnancy-specific anxiety and perceived stress, salivary cortisol levels and adrenocorticotropic hormone (ACTH) levels were collected in nulliparous women throughout pregnancy. Infant development was measured at 3 and 8 months by means of the Bayley Scales of Infant Development (BSID). Infant temperament was rated by means of observed behavior and maternal report. Results : High levels of pregnancy-specific anxiety in early pregnancy predicted both temperamental and developmental difficulties. High amounts of daily hassles in early pregnancy were associated with lower mental developmental scores. Perceived stress in early pregnancy was related to more difficult behavior and adaptational problems. Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development, whereas higher ACTH levels were related to more adaptational problems. All results were adjusted for a large number of covariates. Conclusion : Increased maternal prenatal stress seems to be one of the determinants of temperamental and developmental variation of infants. The hypothalamic–pituitary–adrenal (HPA) axis may be involved in the harmful effects of prenatal maternal stress on infant development and temperament.