Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined,Quadruple, Serum Integrated and Integrated Tests

Objective

To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.

Design

Nested case-control study.

Setting

Antenatal screening service.

Population or Sample

532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.

Methods

Stored maternal serum samples (−40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests.

Main Outcome Measures

Median PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).

Results

First trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks’ gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR.

Conclusions

First trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.     

Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down Syndrome screening

Background

As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target.

Methodology/Principal Findings

Placenta and fetal liver at 15.5 days gestation were analyzed by microarray profiling. We confirmed increased expression of genes located at the trisomic chromosomal region. Overall, between the two genotypes more differentially expressed genes were found in fetal liver than in placenta. Furthermore, the fetal liver data are in line with the hematological aberrations found in humans with Down Syndrome as well as Ts1Cje mice. Together, we found 25 targets that are predicted (by Gene Ontology, UniProt, or the Human Plasma Proteome project) to be detectable in human serum.

Conclusions/Significance

Fetal liver might harbor more promising targets for Down Syndrome screening studies. We expect these new targets will help focus further experimental studies on identifying and validating human maternal serum biomarkers for Down Syndrome screening.     

Discovery of Novel Serum Biomarkers for Prenatal Down Syndrome Screening by Integrative Data Mining

Background

To facilitate the experimental search for novel maternal serum biomarkers in prenatal Down Syndrome screening, we aimed to create a set of candidate biomarkers using a data mining approach.

Methodology/Principal Findings

Because current screening markers are derived from either fetal liver or placental trophoblasts, we reasoned that new biomarkers can primarily be found to be derived from these two tissues. By applying a three-stage filtering strategy on publicly available data from different sources, we identified 49 potential blood-detectable protein biomarkers. Our set contains three biomarkers that are currently widely used in either first- or second-trimester screening (AFP, PAPP-A and fβ-hCG), as well as ten other proteins that are or have been examined as prenatal serum markers. This supports the effectiveness of our strategy and indicates the set contains other markers potentially applicable for screening.

Conclusions/Significance

We anticipate the set will help support further experimental studies for the identification of new Down Syndrome screening markers in maternal blood.     

Hospital Admissions in Children with Down Syndrome: Experience of a Population-Based Cohort Followed from Birth

Objective

Children with Down syndrome, the most common genetic cause of intellectual disability, are prone to multiple and varied health-related problems. This study describes patterns of hospitalisations for children and young people with Down syndrome in Western Australia.

Methods

Birth records were linked to the Western Australian population-based Intellectual Disability database to identify all children born with Down syndrome in Western Australia between 1 January, 1983 and 31 December, 1999. These records were linked to the Hospital Morbidity Data System to provide information on all hospitalisations up to 31 December, 2004. Hospitalisation data, coded using ICD-9CM or ICD-10 (v0.5) were grouped into clinically relevant categories using the primary diagnosis. Rates of hospital admission for all and specific diagnoses were expressed in 1000-person-years at-risk and median age at first admission and length of stay were calculated.

Results

Of the 405 children, 395 had one or more hospital admissions, totalling 3786 admissions for all children and an estimated 39.5 person-years in hospital. On average, children were admitted 9.7 times, with an estimated rate of 757.2 admissions per 1000pyr (95% CI: 680, 843). A quarter of all admissions occurred in the first year of life. The average hospital length of stay was 3.8 days (95% CI: 3.7, 4.1). Upper respiratory tract conditions affected the most children (58.5%) and accounted for 12.1% of all admissions. Other disorders which affected a high percentage of children were ear/hearing conditions (50.6%), disorders of the oral cavity (38.0%) and lower respiratory tract conditions (37.5%). Overall, children with Down syndrome were hospitalised at a rate five times (95% CI = 4.3–6.2) that of the general population.

Conclusion

Children with Down syndrome are at increased risk of morbidity for varied causes underlining the importance of comprehensive and targeted primary care for this group.     

Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies

Background

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.

Aim

A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.

Methods

PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.

Results

Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09–1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13–1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10–1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13–1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60–0.94, p = 0.01).

Conclusion

The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.     

Fetal Gender and Several Cytokines Are Associated with the Number of Fetal Cells in Maternal Blood – An Observational Study

Objective

To identify factors influencing the number of fetal cells in maternal blood.

Methods

A total of 57 pregnant women at a gestational age of weeks 11–14 were included. The number of fetal cells in maternal blood was assessed in 30 ml of blood using specific markers for both enrichment and subsequent identification.

Results

Participants carrying male fetuses had a higher median number of fetal cells in maternal blood than those carrying female fetuses (5 vs. 3, p = 0.04). Certain cytokines (RANTES, IL-2 and IL-5) were significantly associated with the number of fetal cells in maternal blood.

Conclusion

The number of fetal cells in maternal blood is associated with certain cytokines and fetal gender.     

Maternal Smoking during Pregnancy and Fetal Organ Growth: A Magnetic Resonance Imaging Study

Objective

To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta.

Design

A case-control study, with operators performing the image analysis blinded.

Setting

Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom.

Participants

A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy.

Methods

Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA).

Main outcome measures

Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes.

Results

Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume.

Conclusion

Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.     

Which Neurodevelopmental Disorders Get Researched and Why?

Aim

There are substantial differences in the amount of research concerned with different disorders. This paper considers why.

Methods

Bibliographic searches were conducted to identify publications (1985–2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.

Results

The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.

Interpretation

Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.     

Informing early intervention: preschool predictors of anxiety disorders in middle childhood

Background

To inform early intervention practice, the present research examines how child anxiety, behavioural inhibition, maternal overinvolvement, maternal negativity, mother-child attachment and maternal anxiety, as assessed at age four, predict anxiety at age nine.

Method

202 children (102 behaviourally inhibited and 100 behaviourally uninhibited) aged 3–4 years were initially recruited and the predictors outlined above were assessed. Diagnostic assessments, using the Anxiety Disorders Interview Schedule, were then conducted five years later.

Results

Behavioural inhibition, maternal anxiety, and maternal overinvolvement were significant predictors of clinical anxiety, even after controlling for baseline anxiety (p<.05). No significant effect of negativity or attachment security was found over and above baseline anxiety (p>.1).

Conclusions

Preschool children who show anxiety, are inhibited, have overinvolved mothers and mothers with anxiety disorders are at increased risk for anxiety in middle childhood. These factors can be used to identify suitable participants for early intervention and can be targeted within intervention programs.     

Triple Test Screening for Down Syndrome: An Egyptian-Tailored Study

Background

The incidence of Down syndrome (DS) in Egypt varies between 1∶555 and 1∶770 and its screening by triple test is becoming increasingly popular nowadays. Results, however, seem inaccurate due to the lack of Egyptian-specific information needed for risk calculation and a clear policy for programme implementation. Our study aimed at calculation and validation of the triple marker medians used in screening Egyptian females as well as to recommend programme conventions to unify screening in this country.

Methods

The study was conducted on 668 Egyptian women, in weeks 15–20 of pregnancy as proven by sonar. Chorionic gonadotropin (CG), α-fetoprotein (AFP) and unconjugated oestriol (uE3) were measured on Siemens Immulite analyzer. Medians of the three parameters were calculated, regressed against gestational age (GA) and weighted by the number of participants/week. Equations were derived to adjust each parameter to the maternal weight and were centered on the median Egyptian weight. Prisca software was fed with the above data, multiples-of-median (MoM) and DS risks were calculated and the screening performance was evaluated at a mid-trimester risk cutoff of 1∶270.

Results

Log-linear [AFP/uE3 = 10^(A+B*^GA)] and exponential equations [CG = A*e ^(B*^GA)] were derived and the regressed medians were found to follow similar patterns to other Asian and Western medians. Oestriol was always lowest (even halved) while CG and AFP were intermediate. A linear reciprocal model best fitted weight distribution among Egyptians and successfully adjusted each parameter to a weight of 78.2 kg. Epidemiological monitoring of these recommendations revealed satisfactory performance in terms of 6.7% initial positive rate and 1.00 grand MoM.

Conclusions

Adoption of the above recommendations is hoped to pave the way to a successful DS screening programme tailored to Egyptian peculiarities.     

Health Conditions and Their Impact among Adolescents and Young Adults with Down Syndrome

Objective

To examine the prevalence of medical conditions and use of health services among young adults with Down syndrome and describe the impact of these conditions upon their lives.

Methods

Using questionnaire data collected in 2011 from parents of young adults with Down syndrome we investigated the medical conditions experienced by their children in the previous 12 months. Univariate, linear and logistic regression analyses were performed.

Results

We found that in addition to the conditions commonly experienced by children with Down syndrome, including eye and vision problems (affecting 73%), ear and hearing problems (affecting 45%), cardiac (affecting 25%) and respiratory problems (affecting 36%), conditions also found to be prevalent within our young adult cohort included musculoskeletal conditions (affecting 61%), body weight (affecting 57%), skin (affecting 56%) and mental health (affecting 32%) conditions and among young women menstrual conditions (affecting 58%). Few parents reported that these conditions had no impact, with common impacts related to restrictions in opportunities to participate in employment and community leisure activities for the young people, as well as safety concerns.

Conclusion

There is the need to monitor, screen and provide appropriate strategies such as through the promotion of healthy lifestyles to prevent the development of comorbidities in young people with Down syndrome and, where present, to reduce their impact.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

Cost Effectiveness of Screening Strategies for Early Identification of HIV and HCV Infection in Injection Drug Users

Objective

To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs) in opioid replacement therapy (ORT).

Design

Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15–59).

Methods

We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).

Results

Adding HIV and HCV viral RNA testing to antibody testing averts 14.8–30.3 HIV and 3.7–7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.

Discussion

Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3–6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.     

The WHO Maternal Near-Miss Approach and the Maternal Severity Index Model (MSI): Tools for Assessing the Management of Severe Maternal Morbidity

Objectives

To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments.

Methods

In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity.

Results

Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56–114.6)). The maternal severity index (MSI) model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909–0.993)).

Conclusion

The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.     

Constructing a population-based research database from routine maternal screening records: a resource for studying alloimmunization in pregnant women

Background

Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues.

Study Design and Methods

Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays.

Results

More than one million (1,191,761) births with valid screening information from 1982–2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time.

Conclusion

This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions, such as the etiological significance of non-anti-D antibodies.     

Socio-Economic and Health Access Determinants of Breast and Cervical Cancer Screening in Low-Income Countries: Analysis of the World Health Survey

Background

Breast and Cervical cancer are the two most common cancers among women in developing countries. Regular screening is the most effective way of ensuring that these cancers are detected at early stages; however few studies have assessed factors that predict cancer screening in developing countries.

Purpose

To assess the influence of household socio-economic status (SES), healthcare access and country level characteristics on breast and cervical cancer screening among women in developing countries.

Methods

Women ages 18–69 years (cervical cancer screening) and 40–69 years (breast cancer screening) from 15 developing countries who participated in the 2003 World Health Survey provided data for this study. Household SES and healthcare access was assessed based on self-reported survey responses. SAS survey procedures (SAS, Version 9.2) were used to assess determinants of breast and cervical cancer screening in separate models.

Results

4.1% of women ages 18–69 years had received cervical cancer screening in the past three years, while only 2.2% of women ages 40–69 years had received breast cancer screening in the past 5 years in developing countries. Cancer screening rates varied by country; cervical cancer screening ranged from 1.1% in Bangladesh to 57.6% in Congo and breast cancer screening ranged from 0% in Mali to 26% in Congo. Significant determinants of cancer screening were household SES, rural residence, country health expenditure (as a percent of GDP) as well as healthcare access.

Discussion

A lot more needs to be done to improve screening rates for breast and cervical cancer in developing countries, such as increasing health expenditure (especially in rural areas), applying the increased funds towards the provision of more, better educated health providers as well as improved infrastructure.     

Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania

Background

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse.

Aims

This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors.

Methods

This population-based survey of mothers of children aged 0–36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was “yes” to 8 or more items on the scale were defined as “at risk of CMD.”

Results

Of the 1,922 mothers (15–48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective.

Conclusions

Taken together, our results indicate the significance of the quality of relations with one’s partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings.     

Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years

Objective

Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child.

Methods

Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12–20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80^th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions.

Results

2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07).

Conclusion

Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.     

Predictors of poor perinatal outcome following maternal perception of reduced fetal movements--a prospective cohort study

Background

Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency.

Objective

To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM).

Design

Prospective cohort study.

Methods

305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression.

Results

22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31–38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01–1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94–0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02–0.99) were independently related to pregnancy outcome. hPL was related to placental mass.

Conclusion

Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.     

A Meta-Analysis of Parental Smoking and the Risk of Childhood Brain Tumors

Objective

Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship.

Methods

A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose–response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels.

Results

A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86–1.07), 1.09 (0.97–1.22), 0.93 (0.85–1.00), and 1.09 (1.00–1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT.

Conclusions

Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.