Female fertility treatment and adverse birth outcomes: a multistate analysis of pregnancy risk assessment monitoring system data.

OBJECTIVE: The popularity of fertility treatments has continued to rise, however, the potential health risks of these treatments for both mother and infant are not fully known. Our objective was to determine the association between fertility treatments and adverse birth outcomes of intended pregnancies using the Pregnancy Risk Assessment Monitoring System (PRAMS) data. METHODS: Data from 27,018 intended pregnancies, collected from 2009 to 2018 in the United States, were included in our analysis. PRAMS data consisted of questionnaire and birth certificate data. SAS 9.4 was used for analyses accounting for complex survey weights. All analyses were conducted separately for singleton and twin births. Weighted percentages with 95% confidence intervals (CIs) were estimated for maternal characteristics and birth outcomes. Multivariable logistic regression was used to determine adjusted odds ratios (OR) and 95% CIs for associations of fertility treatment use and adverse birth outcomes. RESULTS: Close to 12% of women reported the use of any fertility treatment. Among those using fertility treatments, the most common type was assisted reproductive technology (ART) for both twin (68.7%, 95% CI: 62.3, 75.2) and singleton births (45.1%, 95% CI: 42.0, 48.1). Use of any type of fertility treatment for singleton births was associated with increased odds of a cesarean delivery (OR: 1.31, 95% CI: 1.16, 1.47), preterm birth (OR: 1.42, 95% CI: 1.20, 1.67), a small-for-gestational age infant (OR: 1.20, 95% CI: 1.00, 1.44), and an infant hospital stay >5 days (OR: 1.34, 95% CI: 1.11, 1.62). Use of fertility treatment for twin births was associated with cesarean delivery only. In analyses examining associations for specific types of treatment (medication alone, ART, insemination) with birth outcomes, results varied by treatment type. CONCLUSIONS: In this large population-based sample of women who intended to become pregnant and had a live birth, fertility treatment was associated with adverse birth outcomes. Patients seeking fertility treatment should be appropriately counseled on the risks of adverse maternal and infant birth outcomes overall and by treatment type. Maternal support and resources to prevent adverse birth outcomes among women using fertility treatments are warranted.

The complex aetiology of cerebral palsy.

Cerebral palsy (CP) is the most prevalent, severe and costly motor disability of childhood. Consequently, CP is a public health priority for prevention, but its aetiology has proved complex. In this Review, we summarize the evidence for a decline in the birth prevalence of CP in some high-income nations, describe the epidemiological evidence for risk factors, such as preterm delivery and fetal growth restriction, genetics, pregnancy infection and other exposures, and discuss the success achieved so far in prevention through the use of magnesium sulfate in preterm labour and therapeutic hypothermia for birth-asphyxiated infants. We also consider the complexities of disentangling prenatal and perinatal influences, and of establishing subtypes of the disorder, with a view to accelerating the translation of evidence into the development of strategies for the prevention of CP.

Acquiring genome-wide gene expression profiles in Guthrie card blood spots using microarrays.

Standard Guthrie cards have been widely used to collect blood samples from essentially all USA and Japanese neonates for newborn screening programs. Thus, archival blood spot samples are a unique and comprehensive resource for molecular pathology studies. However, the challenge in using these samples is the presumed low quantity and degraded quality of nucleic acids that can be isolated from these samples, particularly the RNA. Here, we report a new assay using Agilent 4x44K microarrays for acquiring genome-wide gene expression profiles from blood spots on Guthrie cards. Due to the small amount of RNA obtained from each sample, major modifications, such as concentrating and amplifying the RNA and using a different labeling procedure, were performed. Approximately 9000 expressed genes can be detected after normalization of data, an increment of 260% in detection power compared with previously reported cDNA microarrays made in-house with standard procedures. The correlation coefficients in technical and biological replicates were 0.92 and 0.85, respectively, confirming the reproducibility of this study. This new and comprehensive assay will add value to the utility of archival Guthrie cards (e.g. neonatal blood spot cards) and open new opportunities to molecular epidemiology, pathology, genomic, and diagnostic studies of perinatal diseases.

Cerebral palsy and aging.

Cerebral palsy (CP), the most common major disabling motor disorder of childhood, is frequently thought of as a condition that affects only children. Deaths in children with CP, never common, have in recent years become very rare, unless the child is very severely and multiply disabled. Thus, virtually all children assigned the diagnosis of CP will survive into adulthood. Attention to the adult with CP has been sparse, and the evolution of the motor disorder as the individual moves through adolescence, young adulthood, middle age, and old age is not well understood. Nor do we know what happens to other functional domains, such as communication and eating behavior, in adults with CP. Although the brain injury that initially causes CP by definition does not progressively worsen through the lifetime, the effects of CP manifest differently throughout the lifespan. The aging process must inevitably interact with the motor disorder, but we lack systematic, large-scale follow-up studies of children with CP into adulthood and through adulthood with thorough assessments performed over time. In this paper we summarize what is known of the epidemiology of CP throughout the lifespan, beginning with mortality and life expectancy, then survey what is known of functioning, ability, and quality of life of adults with CP. We conclude by describing a framework for future research on CP and aging that is built around the World Health Organization's International Classification of Functioning, Disability, and Health (ICF) and suggest specific tools and approaches for conducting that research in a sound manner.

Archived unfrozen neonatal blood spots are amenable to quantitative gene expression analysis.

BACKGROUND: State laws in the USA mandate that blood be drawn from all newborn infants to screen for health-threatening conditions. These screening assays consume only a small portion of the blood samples, which are collected on filter paper ('Guthrie') cards. Many states archive unused blood spots, often in unrefrigerated storage. OBJECTIVES: While individual RNA transcripts have been identified from archived neonatal blood spots, no study to date has performed quantitative analysis of archived blood spot RNA. METHODS: We demonstrate that RNA can be isolated and amplified from newborn blood spots stored unfrozen for as long as 9 years, and can be analyzed by microarray and qPCR. RESULTS: Microarray assays of archived neonatal blood spots consistently detected 3,000-4,000 expressed genes with correlations of 0.90 between replicates. Blood spot mRNA is amenable to qPCR and we detected biologically relevant expression levels of housekeeping and immune-mediating genes. CONCLUSIONS: These experiments demonstrate the feasibility of using blood spots as a source of RNA which can be analyzed using quantitative microarray and qPCR assays. The application of these methods to the analysis of widely collected biological specimens may be a valuable resource for the study of perinatal determinants of disease development.