Continuous fetal cerebral blood flow monitoring during labor: A feasibility study.

BACKGROUND: Current methods for fetal surveillance during labor have significant limitations. Since continuous fetal cerebral blood flow velocity (CBFV) monitoring during labor may add valuable information about fetal well-being, we developed a new ultrasound system called VisiBeam. VisiBeam consists of a flat probe (diameter 11 mm) with a cylindric plane wave beam, a vacuum attachment (diameter 40 mm), a scanner, and a display. AIMS: To assess the feasibility of VisiBeam for continuous fetal CBFV monitoring during labor, and to study changes in CBFV during uterine contractions. STUDY DESIGN: Descriptive observational study. SUBJECTS: Twenty-five healthy women in labor with a singleton fetus in cephalic presentation at term. A transducer was placed over a fontanelle and attached to the fetal head with vacuum suction. OUTCOME MEASURES: Achievement of continuous good quality fetal CBFV measures, such as peak systolic velocity, time averaged maximum velocity and end diastolic velocity. Trend plots of velocity measures display changes in CBFV between and during uterine contractions. RESULTS: Good quality recordings during and between contractions were achieved in 16/25 fetuses. In twelve fetuses, CBFV measures were stable during uterine contractions. Four fetuses showed patterns of reduced CBFV velocity measures during contractions. CONCLUSIONS: Continuous fetal CBFV monitoring by VisiBeam was feasible in 64 % of the subjects during labor. The system displayed variations of fetal CBFV not available by today's monitoring techniques and motivates for further studies. However, improvement of the probe attachment is required to ensure good quality signal in a higher proportion of fetuses during labor.

Prelabor rupture of membranes and the association with cerebral palsy in term born children: a national registry-based cohort study.

BACKGROUND: Guidelines regarding management of prelabor rupture of membranes (PROM) at term vary between immediate induction and expectant management. A long interval between PROM and delivery increases the risk for perinatal infections. Severe perinatal infections are associated with excess risk for cerebral palsy (CP) and perinatal death. We investigated if increasing intervals between PROM and delivery were associated with perinatal death or CP. METHODS: Eligible to participate in this population-based cohort-study were term born singletons without congenital malformations born in Norway during 1999-2009. Data was retrieved from the Medical Birth Registry of Norway (MBRN) and the Cerebral Palsy Register of Norway. In line with the registration in the MBRN, intervals between PROM and delivery of more than 24 h was defined as 'prolonged' and intervals between 12 and 24 h as 'intermediate'. Outcomes were stillbirth, death during delivery, neonatal mortality and CP. Logistic regression was used to calculate odds ratio (OR) with 95% confidence intervals (CI) for adverse outcomes in children born after prolonged and intermediate intervals, compared with a reference group comprising all children born less than 12 h after PROM or without PROM. RESULTS: Among 559,972 births, 34,759 children were born after intermediate and 30,332 were born after prolonged intervals. There was no association between increasing intervals and death during delivery or in the neonatal period, while the prevalence of stillbirths decreased with increasing intervals. Among children born after intermediate intervals 38 (0.11%) had CP, while among those born after prolonged intervals 46 (0.15%) had CP. Compared with the reference group, the OR for CP was 1.16 (CI; 0.83 to 1.61) after intermediate and 1.61 (CI; 1.19 to 2.18) after prolonged intervals. Adjusting for antenatal factors did not affect these associations. Among children with CP the proportion with diffuse cortical injury and basal ganglia pathology on cerebral MRI, consistent with hypoxic-ischemic injuries, increased with increasing intervals. CONCLUSION: Intervals between PROM and delivery of more than 24 h were associated with CP, but not with neonatal mortality or death during delivery. The inverse association with stillbirth is probably due to reverse causality.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Congenital anomalies and the severity of impairments for cerebral palsy.

AIM: To study the prevalence of congenital anomalies among children with cerebral palsy (CP) born at term or late preterm, and if CP subtypes and clinical manifestations differ between children with and without congenital anomalies. METHOD: This was a cross-sectional study using data from the Cerebral Palsy Register of Norway and the Medical Birth Registry of Norway. All children with congenital CP born at and later than 34 weeks' gestation in Norway from 1999 to 2009 were included. Anomalies were classified according to the European Surveillance of Congenital Anomalies classification guidelines. Groups were compared using Fisher's exact test, Kruskal-Wallis test, and the Mann-Whitney U test. RESULTS: Among 685 children with CP, 169 (25%) had a congenital anomaly; 125 within the central nervous system. Spastic bilateral CP was more prevalent in children with anomalies (42%) than in children without (34%; p=0.011). Children with anomalies less frequently had low Apgar scores (p<0.001), but more often had severe limitations in gross- and fine-motor function, speech impairments, epilepsy, severe vision, and hearing impairments than children without anomalies (p<0.03). INTERPRETATION: Although children with CP and anomalies had low Apgar scores less frequently, they had more severe limitations in motor function and more associated problems than children with CP without anomalies. WHAT THIS PAPER ADDS: One in four children with cerebral palsy (CP) born at term or late preterm has a congenital anomaly. The added value of neuroimaging to detect central nervous system anomalies in children with CP. Children with anomalies have more severe motor impairments. More severe clinical manifestations are not explained by perinatal complications as indicated by low Apgar scores.

Developmental Coordination Disorder Plus: A Diagnosis by Exclusion?

CASE: Cayden is a 6.3-year-old boy who you have been following in our practice since birth. He was born at 35.5 weeks at 6 pounds 4 ounces following a fraternal twin gestation. Both children were "on target" with their milestones, but Cayden did not seem to progress as quickly as his sister. He did not initiate play with his sister when they were toddlers and Cayden was the "shy" one.

Growth during infancy and early childhood in children with cerebral palsy: a population-based study.

AIM: To describe growth in infancy and early childhood in children with cerebral palsy (CP). METHOD: One hundred and four children with CP born at minimum 36 weeks' gestation in 2002 to 2010 were included. Prospectively collected growth data were requested from public health clinics. We calculated standard deviation (SD) scores (z-scores) for weight and height for 12 set age points for each child from birth to 5 years, and for head circumference from birth to 12 months. RESULTS: Children with CP had normal growth in weight and height if they were born non-small for gestational age (non-SGA) or had mild motor impairments (i.e. Gross Motor Function Classification System [GMFCS] I-II), whereas children born SGA or with severe motor impairments (GMFCS III-V) had reduced growth (p<0.001). Children with feeding difficulties in infancy had reduced growth in weight and height throughout early childhood, while children without feeding difficulties had normal growth. Head circumference growth decreased most severely among children born SGA, who had mean z-scores of -3.0 (95% confidence interval [CI] -3.7 to -2.2) at 1 year. INTERPRETATION: Children with mild CP had normal growth in weight and height until 5 years, and in head circumference during infancy. Feeding difficulties in infancy and being born SGA were strongly associated with reduced growth.

The Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypes.

BACKGROUND: Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia. METHODS: Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study's inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables. RESULTS: A cohort consisting of 496 participants (355 females and 141 males) representing 137 families with increased occurrence of preeclampsia has been established, and blood samples are available for 477 participants. Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria. We also found that about 41% of the index women experienced more than one preeclamptic pregnancy. In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications. CONCLUSION: The data and biological samples collected in this Norwegian Preeclampsia Family Cohort will provide an important basis for future research. Identification of preeclampsia susceptibility genes and new biomarkers may contribute to more efficient strategies to identify mothers "at risk" and contribute to development of novel preventative therapies.

Refined phenotyping identifies links between preeclampsia and related diseases in a Norwegian preeclampsia family cohort.

OBJECTIVE: Preeclampsia is a complex genetic disease of pregnancy with a heterogenous presentation, unknown cause and potential severe outcomes for both mother and child. Preeclamptic women have increased risk for atherothrombotic cardiovascular disease. We aimed to identify heritabilities and phenotypic correlations of preeclampsia and related conditions in the Norwegian Preeclampsia Family Biobank. METHODS: By applying a variance components model, a total of 493 individuals (from 138 families with increased occurrence of preeclampsia) were classified according to 30 disease-related phenotypes. RESULTS: Of parous women, 75.7% (263/338) had experienced preeclampsia and 35.7% of women with and 22.4% without preeclampsia delivered children small for gestational age (SGA). We identified 11 phenotypes as heritable. The increased occurrence of preeclampsia was reflected by the presence [heritability (H2r) = 0.60)] and severity (H2r = 0.15) of preeclampsia and being born in a preeclamptic pregnancy (H2r = 0.25). Other heritable phenotypes identified included SGA (H2r = 0.40), chronic hypertension (H2r = 0.57), severity of atherothrombotic cardiovascular disease (H2r = 0.31), BMI (H2r = 0.60) and pulmonary disease (H2r = 0.91). The heritable phenotype preeclampsia overlapped with SGA (P = 0.03), whereas pulmonary disease was phenotypically correlated with atherothrombotic cardiovascular disease (P < 0.01), SGA (P = 0.02) and BMI (P = 0.02). CONCLUSION: This is the first study identifying the H2r of a range of health-related conditions in preeclamptic families. Our study demonstrates how refinement of phenotypes leads to better H2r estimation and the identification of a biological relationship between preeclampsia and related traits.

Changing patterns of cytomegalovirus seroprevalence among pregnant women in Norway between 1995 and 2009 examined in the Norwegian Mother and Child Cohort Study and two cohorts from Sor-Trondelag County: a cross-sectional study.

OBJECTIVES: To examine cytomegalovirus (CMV) seroprevalence and associated risk factors for CMV seropositivity in pregnant Norwegian women. DESIGN: Cross-sectional study. SETTING: The Norwegian Mother and Child Cohort Study (MoBa) in addition to two random samples of pregnant women from Sør-Trøndelag County in Norway. PARTICIPANTS: Study group 1 were 1000 pregnant women, randomly selected among 46 127 pregnancies in the MoBa (1999-2006) at 17/18 week of gestation. Non-ethnic Norwegian women were excluded. Study groups 2 (n=1013 from 1995) and 3 (n=979 from 2009) were pregnant women at 12 weeks of gestation from Sør-Trøndelag County. OUTCOME MEASURES: CMV seropositivity in blood samples from pregnant Norwegian women. RESULTS: CMV-IgG antibodies were detected in 59.9% and CMV-IgM antibodies in 1.3% of pregnant Norwegian women in study group 1. Women from North Norway demonstrated a higher CMV-IgG seroprevalence (72.1%) than women from South Norway (58.5%) (OR 1.83, 95% CI 1.17 to 2.88). The CMV-IgG seroprevalence was higher among women with low education (70.5%) compared to women with higher education (OR 2.20, 95% CI 1.24 to 3.90). Between 1995 and 2009 the CMV-IgG seroprevalence increased from 63.1% to 71.4% in pregnant women from Sør-Trøndelag County (study groups 2 and 3; p<0.001). The highest CMV-IgG seroprevalence (79.0%) was observed among the youngest pregnant women (<25 years) from Sør-Trøndelag County in 2009 (study group 3). CONCLUSIONS: The CMV-IgG seroprevalence of pregnant Norwegian women varies with geographic location and educational level. Additionally, the CMV-IgG seroprevalence appears to have increased over the last years, particularly among young pregnant women.

Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study.

OBJECTIVE: To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age. DESIGN: Population based cohort study. SETTING: Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway. PARTICIPANTS: All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616,658 control children). MAIN OUTCOME MEASURES: Cerebral palsy and cerebral palsy subtypes. RESULTS: Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥ 37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype. CONCLUSIONS: Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age.

OP006. A preeclampsia genome-wide linkage scan in norwegian families.

INTRODUCTION: Several maternal susceptibility loci for preeclampsia (PE) have been discovered amongst Icelandic, Australian/New Zealand, Dutch and Finnish family cohorts, implicating locus heterogeneity. Through candidate gene studies, allele-specific heterogeneity in different populations is also evident. It is therefore likely that numerous population specific PE susceptibility variants exist, differing in their effect size. Despite on-going efforts to identify susceptibility genes for PE, the causal genetic variants still remain obscure. OBJECTIVES: The aim of this study is to interrogate the genetic architecture of PE susceptibility by performing a genome-wide linkage scan in a novel familial cohort from Norway. METHODS: A total of 480 DNA samples from The Norwegian PE Family Biobank were genotyped at Genomic Core Facility at NTNU. Genome-wide genotyping was performed with the Infinium HumanExome BeadChip (>240,000 markers) (Illumina, USA) that delivers focused coverage of exonic regions of the human genome. RESULTS: A total of 137 families are represented with 222 women with a valid PE diagnosis (SBP⩾140mmHg DBP⩾90mmHg, ⩾2 measurements at least 4h apart with documented proteinuria at ⩾2 occasions occurring after 20weeks of pregnancy), 44 with self-reported PE and 72 women with a healthy pregnancy. The genotyping has just recently been completed with an average call rate of 99.96%. Data and statistical analysis is now underway using MERLIN, R and SOLAR. A description of the Norwegian PE familial cohort plus preliminary results will be presented at the Congress. CONCLUSION: To our knowledge this is the first SNP-based genome-wide linkage study on PE, and the first performed in a novel Norwegian PE family cohort. By using an approach focusing on functionally relevant markers we anticipate the identification of susceptibility loci that are of substantial importance for disease development.

Developmental coordination disorder plus: a diagnosis by exclusion?

CASE: Cayden is a 6.3-year-old boy who you have been following in our practice since birth. He was born at 35.5 weeks at 6 pounds 4 ounces following a fraternal twin gestation. Both children were "on target" with their milestones, but Cayden did not seem to progress as quickly as his sister. He did not initiate play with his sister when they were toddlers and Cayden was the "shy" one.