Prenatal Conditions Research Articles

A Homozygous AKNA Frameshift Variant Is Associated with Microcephaly in a Pakistani Family.

Primary microcephaly (MCPH) is a prenatal condition of small brain size with a varying degree of intellectual disability. It is a heterogeneous genetic disorder with 28 associated genes reported so far. Most of these genes encode centrosomal proteins. Recently, AKNA was recognized as a novel centrosomal protein that regulates neurogenesis via microtubule organization, making AKNA a likely candidate gene for MCPH. Using linkage analysis and whole-exome sequencing, we found a frameshift variant in exon 12 of AKNA (NM_030767.4: c.2737delG) that cosegregates with microcephaly, mild intellectual disability and speech impairment in a consanguineous family from Pakistan. This variant is predicted to result in a protein with a truncated C-terminus (p.(Glu913Argfs*42)), which has been shown to be indispensable to AKNA’s localization to the centrosome and a normal brain development. Moreover, the amino acid sequence is altered from the beginning of the second of the two PEST domains, which are rich in proline (P), glutamic acid (E), serine (S), and threonine (T) and common to rapidly degraded proteins. An impaired function of the PEST domains may affect the intracellular half-life of the protein. Our genetic findings compellingly substantiate the predicted candidacy, based on its newly ascribed functional features, of the multifaceted protein AKNA for association with MCPH.

Prenatal lung volumes in congenital diaphragmatic hernia and their effect on postnatal outcomes.

Lung volume measurement on fetal MRI is a component of the imaging workup for various prenatal conditions, but its use as a prognosticator has been most heavily studied in congenital diaphragmatic hernia (CDH). Pediatric radiologists who perform and interpret fetal MRI must be familiar with the technical aspects of lung volume measurement to guarantee accurate measurement and reporting. Variability in timing and type of measurement at different fetal centers also requires pediatric radiologists to be up-to-date with the literature and aware of their center's internal data. This paper provides both a how-to guide for measuring fetal lung volumes on MRI and a comprehensive review of the CDH outcome literature to serve as a convenient reference for the pediatric radiologist.

Infant sex and DNA methylation: differentially methylated regions and positions across umbilical cord blood, artery, and placenta samples

BACKGROUND AND AIM: Environmental exposures during embryogenesis may cause epigenetic dysregulation. Fetal sex may act as an effect modifier of the association between prenatal conditions and changes in DNA methylation (DNAm); therefore, it is important to understand sex-specific DNAm patterns. Autosomal cord blood and placental DNAm at several loci has been consistently associated with sex. However, there is limited research regarding differentially methylated regions (DMRs) and comparing sex-specific DNAm across tissues. This study leverages data from the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify sex-associated DNAm profiles in cord blood, placenta, and umbilical artery samples. METHODS: DNAm was measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229). Sex-associated DMRs were identified using DMRcate and differentially methylated positions (DMPs) were identified using limma. Analyses were replicated in an independent cord blood dataset (GEO Accession GSE129841). RESULTS:A total of 183, 257, and 419 DMRs and 2,119, 2,281, and 3,405 DMPs (pBonferroni 0.05) were identified in cord blood, placenta, and artery samples, respectively. Common DMRs were identified across tissues: 39 DMRs overlapped in all three tissues. The majority of DMRs (cord blood: 61%; placenta: 69%; artery: 67%) were annotated to small nucleolar RNAs (snoRNA) genes. In a cord blood replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall, female sex was associated with higher methylation of DMRs and DMPs in cord blood and artery samples, but male sex was associated with higher methylation levels in placenta samples. CONCLUSIONS:Common sex-associated DMRs and DMPs were identified in cord blood, placenta, and artery samples. Further research may provide insights to biological mechanisms that contribute to sex-specific DNAm signatures across fetal tissues, as well as the influence of dimorphism in the epigenome on environmental-induced dysregulation. KEYWORDS: children's environmental health, omics technologies, epigenomics, female, male

Dental Considerations in Pregnancy – A Systematic Review

Background: Good oral health during pregnancy can not only improve the health of the pregnant mother, but also potentially the health of her child. There is inconclusive and contrasting nature of evidence regarding the effect of pregnancy on oral health. So the purpose of this study was to systematically review the dental considerations during Pregnancy for further investigation.
 Methods: For the identification of the studies included in this review, we devised the search strategy for each database. The search strategy used a union of controlled vocabulary and free text terms. The main electronic database used to access the studies were PubMed, PubMed Central, Cochrane Review, Embase and Google Scholar.
 Results: A total of 28 articles fulfilled the criteria and were selected for the review. Some prenatal oral health conditions have adverse effects on the child. Periodontitis is associated with preterm birth, low birth weight infants and high level of cariogenic bacteria in pregnant mother can lead to increased risk of dental caries in the infant. Oral lesions such as gingivitis and pregnancy tumours are benign in nature and require only reassurance and monitoring.
 Conclusion: It has been suggested that some oral conditions may have adverse consequences on their children awareness related to oral health during pregnancy. Oral health care services should be routinely integrated with prenatal care services for all the pregnant women and specific preventive oral health care program should be made an integral part of antenatal care.

Prenatal and Early Postnatal Behavioural Programming in Laying Hens, With Possible Implications for the Development of Injurious Pecking.

Injurious pecking (IP) represents a serious concern for the welfare of laying hens (Gallus gallus domesticus). The risk of IP among hens with intact beaks in cage-free housing prompts a need for solutions based on an understanding of underlying mechanisms. In this review, we explore how behavioural programming via prenatal and early postnatal environmental conditions could influence the development of IP in laying hens. The possible roles of early life adversity and mismatch between early life programming and subsequent environmental conditions are considered. We review the role of maternal stress, egg conditions, incubation settings (temperature, light, sound, odour) and chick brooding conditions on behavioural programming that could be linked to IP. Brain and behavioural development can be programmed by prenatal and postnatal environmental conditions, which if suboptimal could lead to a tendency to develop IP later in life, as we illustrate with a Jenga tower that could fall over if not built solidly. If so, steps taken to optimise the environmental conditions of previous generations and incubation conditions, reduce stress around hatching, and guide the early learning of chicks will aid in prevention of IP in commercial laying hen flocks.

Epigenetic Changes Induced by Maternal Factors during Fetal Life: Implication for Type 1 Diabetes.

Organ-specific autoimmune diseases, such as type 1 diabetes, are believed to result from T-cell-mediated damage of the target tissue. The immune-mediated tissue injury, in turn, is known to depend on complex interactions between genetic and environmental factors. Nevertheless, the mechanisms whereby environmental factors contribute to the pathogenesis of autoimmune diseases remain elusive and represent a major untapped target to develop novel strategies for disease prevention. Given the impact of the early environment on the developing immune system, epigenetic changes induced by maternal factors during fetal life have been linked to a likelihood of developing an autoimmune disease later in life. In humans, DNA methylation is the epigenetic mechanism most extensively investigated. This review provides an overview of the critical role of DNA methylation changes induced by prenatal maternal conditions contributing to the increased risk of immune-mediated diseases on the offspring, with a particular focus on T1D. A deeper understanding of epigenetic alterations induced by environmental stressors during fetal life may be pivotal for developing targeted prevention strategies of type 1 diabetes by modifying the maternal environment.

Genotype by heat stress interactions for production and functional traits in dairy cows from an across-generation perspective

The aim of this study was to analyze time-lagged heat stress (HS) effects during late gestation on genetic co(variance) components in dairy cattle across generations for production, female fertility, and health traits. The data set for production and female fertility traits considered 162,492 Holstein Friesian cows from calving years 2003 to 2012, kept in medium-sized family farms. The health data set included 69,986 cows from calving years 2008 to 2016, kept in participating large-scale co-operator herds. Production traits were milk yield (MKG), fat percentage (fat%), and somatic cell score (SCS) from the first official test-day in first lactation. Female fertility traits were the nonreturn rate after 56 d (NRR56) in heifers and the interval from calving to first insemination (ICFI) in first-parity cows. Health traits included clinical mastitis (MAST), digital dermatitis (DD), and endometritis (EM) in the early lactation period in first-parity cows. Meteorological data included temperature and humidity from public weather stations in closest herd distance. The HS indicator was the temperature-humidity index (THI) during dams' late gestation, also defined as in utero HS. For the genetic analyses of production, female fertility, and health traits in the offspring generation, a sire-maternal grandsire random regression model with Legendre polynomials of order 3 for the production and of order 2 for the fertility and health traits on prenatal THI, was applied. All statistical models additionally considered a random maternal effect. THI from late gestation (i.e., prenatal climate conditions), influenced genetic parameter estimates in the offspring generation. For MKG, heritabilities and additive genetic variances decreased in a wave-like pattern with increasing THI. Especially for THI >58, the decrease was very obvious with a minimal heritability of 0.08. For fat% and SCS, heritabilities increased slightly subjected to prenatal HS conditions at THI >67. The ICFI heritabilities differed marginally across THI [heritability (h2) = 0.02-0.04]. For NRR56, MAST, and DD, curves for heritabilities and genetic variances were U-shaped, with largest estimates at the extreme ends of the THI scale. For EM, heritability increased from THI 25 (h2 = 0.13) to THI 71 (h2 = 0.39). The trait-specific alterations of genetic parameters along the THI gradient indicate pronounced genetic differentiation due to intrauterine HS for NRR56, MAST, DD, and EM, but decreasing genetic variation for MKG and ICFI. Genetic correlations smaller than 0.80 for NRR56, MAST, DD, and EM between THI 65 with corresponding traits at remaining THI indicated genotype by environment interactions. The lowest genetic correlations were identified when considering the most distant THI. For MKG, fat%, SCS, and ICFI, genetic correlations throughout were larger than 0.80, disproving concerns for any genotype by environment interactions. Variations in genetic (co)variance components across prenatal THI may be due to epigenetic modifications in the offspring genome, triggered by in utero HS. Epigenetic modifications have a persistent effect on phenotypic responses, even for traits recorded late in life. However, it is imperative to infer the underlying epigenetic mechanisms in ongoing molecular experiments.

Characteristics of Environmental influences on Child Health Outcomes (ECHO) Cohorts Recruited During Pregnancy.

The objective of this study was to characterize the study designs, recruitment strategies, and other study characteristics among cohorts that initiated during pregnancy as part of the Environmental influences on Child Health Outcomes (ECHO) program. ECHO research programs (cohorts) were reviewed. Only those who had or were currently recruiting during pregnancy were surveyed in 2018 about research recruitment strategies (participant incentives, study burden, community collaboration, and cultural adaptations). Data are presented with cohort characteristics (location, inclusion and exclusion criteria, sociodemographics, medical information, behavioral factors, and biospecimens). Forty-seven of the 84 ECHO pediatric cohorts recruited during pregnancy. Findings demonstrate various recruitment strategies, domains of data collection, and biospecimen collection are all characteristics of successful cohorts. These data that include over 50,000 children from families across the country, many in underserved areas, will be used for research with the potential to lead to profound policy changes. Prenatal conditions such as maternal age, obesity, depression, and drug use can be examined using study data, including biological markers, from pregnancy through childbirth and into childhood and will inform national policies on the role of early life exposures and underlying mechanisms of disease progression.

Integrating behaviour, physiology and survival to explore the outcome of reintroductions: a case study of grey partridge

Personalities, i.e. consistent individual differences in behaviour, have been found in many animal populations. However, the reasons why personalities emerge, how they persist and the consequences they have in a changing environment are poorly understood. Factors influencing personalities include genetic background, prenatal (e.g. hormonal) and postnatal (e.g. environmental) conditions, and the strength of these factors can affect the consistency of personalities over time, and hence their flexibility in a changing environment. In birds, for example, hormones in eggs deposited by mothers can modulate aggressiveness of offspring and environmentally induced nutrition deficits in offspring can reduce neophobia later in life. Hence, investigating the fitness consequences of personalities requires the integration of physiological, behavioural and survival measures. We used the opportunity of a reintroduction project of grey partridge, Perdix perdix , to experimentally explore how multiple pre- and postnatal factors including measures of the hormone corticosterone were related to three behavioural traits. Then, we investigated whether the behaviours were repeatable and related to survival after release into the wild. Grey partridges showed distinct personalities affected by multiple pre- and postnatal factors. Proactive birds had low baseline levels of circulating corticosterone and survived longer after release into the wild compared to reactive and passive personalities. Consequently, the number of survivors after 6 months was substantially higher for proactive than for reactive and passive birds. Integrating data on behaviour, physiology and survival thus allows the investigation of the complex interplay of personality and fitness in a changing environment. • Animals have personalities but what are their fitness consequences in the wild? • We explored factors relating to behaviour of grey partridge bound for release. • Genetic, physiological, individual and social factors affected personalities. • After release, bold birds survived longer than passive and shy individuals. • Integration data on behaviour and physiology can support reintroduction outcome.

Effects of prenatal exposure factors on birth outcomes through mediation of favorable fetal growth conditions using structural equation modeling.

BackgroundBirth weight, birth length, and gestational age are major indicators of newborn health. Several prenatal exposure factors influence the fetal environment. The aim of the study was to investigate the effect of prenatal exposure factors, including socio-demographic, behavioural, dietary, physical activity, clinical and environmental on birth outcomes through the mediation of Favourable Fetal Growth Conditions (FFGC).MethodsData was obtained from six hundred and fifty-six Mother and Child in the Environment birth cohort study in Durban, South Africa from 2013 to 2017. We adopted structural equation models which evaluate the direct and indirect effects by allowing multiple simultaneous equations to incorporate confounding and mediation.ResultsA significant direct and indirect effect of FFGC on newborn weight, length, and gestational age was seen. Gestational weight gain and maternal body mass index in the first trimester exerted a mediation effect between maternal behavioural risk factors and FFGC. Similarly, the level of physical activity during pregnancy was associated with decreased gestational weight gain. The effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC as a latent variable.ConclusionsGestational weight gain and maternal pre-gestational BMI were observed to mediate the association between prenatal behavioural risk factors and favourable fetal growth conditions.Trial registrationRetrospectively registered from 01 March 2013.

Twin-to-Twin Transfusion Syndrome: Diagnostic Imaging and Its Role in Staving Off Malpractice Charges and Litigation.

The study aims to expound upon the imaging-based diagnostic methodologies aimed at identifying twin-to-twin transfusion syndrome (TTTS), a serious, somewhat rare prenatal condition that takes place in pregnancies where identical twins, or other multiples, share a placenta (monochorionic placenta), highlighting how medico-legal outcomes can be affected by provable compliance with consolidated diagnostic guidelines or best practices. It is of utmost importance to produce a prompt identification of TTTS instances; an early diagnosis is in fact critical in order to effectively treat and manage TTTS. By virtue of TTTS being a highly progressive condition, a delay in diagnosis can result in disastrous outcomes; just a few weeks delay in the diagnosis of TTTS can turn out fatal for one or both twins. Hence, most TTTS malpractice claims involve allegations of medical negligence, namely the failure to recognize the condition in a timely fashion, or to proceed with adequate diagnostic and therapeutic pathways. In that regard, case law databases have been pored over (Justia, Lexis, Leagle), and five significant court cases have been examined and discussed in an attempt to identify objective medico-legal standards and bring to the forefront relevant forensic dynamics. In fact, when health professionals are capable of proving adherence to guidelines or best practices, this can shield them from malpractice allegations and ensuing litigation.

Effect of embryonic light exposure on laterality and sociality in quail chicks (Coturnix coturnix japonica)

Lateralization is the ascendency of one side of the body or the brain to control and perform motor or perceptual functions. Light exposure during prenatal life can modulate the expression of visual lateralization (strength and direction) in a variety of species, including birds. Individual lateralization provides cognitive advantages, but the function of lateralization at the population level is less obvious. Recent studies support the hypothesis that intra-specific population-level lateralization may favour coordination between asymmetrical individuals during synergistic (cooperative) social interactions. Since cohesion requires a good coordination, one can therefore imagine that a higher alignment of lateralization within a group, by making coordination between individuals easier, may promote social cohesion. Our study investigated the effect of light on laterality and social behaviour in Japanese quail chicks (Coturnix coturnix japonica). We compared chicks coming from eggs exposed to light during incubation to chicks coming from eggs maintained in complete darkness. We expected light-exposed (LE) chicks to be more aligned than dark-incubated (DI) ones and we wanted to test whether the most aligned chicks were also the most coordinated. We assessed laterality, social motivation, synchronization and spatial cohesion within groups of LE and DI chicks. The prenatal light conditions did not affect either laterality or chicks’ social behaviour, and there was no turning bias at the group level. An absolute laterality index characterizing the alignment of chicks living together showed that the groups with the highest indices were not necessarily the groups with the greatest synchronization and spatial cohesion. This suggests that light does not consistently induce laterality in Japanese quail chicks and that the alignment of the chicks’ turning bias does not influence their social cohesion. Quails are widely used in farm industry and scientific research and better knowledge of the consequences of incubation conditions on their behavioural asymmetries and sociality could help improve their handling and welfare.

Birthweight Differences in Adolescent Monozygotic Twins Influence Androgens, Psychological Morbidity, and Health-Related Quality of Life

Background: Adverse prenatal conditions can exert a long-lasting impact in later life. Patients and Methods: Thirty-eight post-pubertal monozygotic twin pairs (16 female pairs) with divergent birthweight (bw) due to twin-to-twin transfusion syndrome were examined at a median of 15.1 years. Auxological and endocrine parameters were measured. To evaluate effects of intra-twin bw and hormone differences on mental health, adolescents and their parents completed the Strengths and Difficulties Questionnaire (SDQ), identifying psychological problems. Twins answered the questionnaire on health-related quality of life (HrQoL, KIDSCREEN-52). Results: Parents attributed a higher number of psychological challenges to the formerly smaller twins, for example, total difficulties (8.8 vs. 6.5, p = 0.009). Differences in bw were associated with differences in parental evaluation of problems, for example, peer relationship problems (r = −0.57 and p = 0.0001). In contrast, bw differences did not affect subjects’ self-assessment of psychological factors but on physical well-being (r = 0.42, p = 0.017). The formerly smaller discordant twins showed significantly lower HrQoL regarding psychological well-being (24.9 vs. 26.6, T_1,15 = −2.2, and p = 0.043) and moods and emotions (29.8 vs. 32.0, T_1,15 = −2.3, p = 0.039). Higher concentrations of androstenedione were linked to greater psychological well-being (r = 0.39 and p = 0.036) in all twin pairs. Conclusion: Our results show that the prenatal environment leading to bw differences exerts a long-lasting impact on diverging parental evaluation of mental health. Formerly smaller discordant twins showed significantly lower HrQoL regarding psychological well-being and moods and emotions. Higher androstenedione concentrations were linked to greater psychological well-being.

Prenatal disorders and congenital Zika syndrome in squirrel monkeys

During the Zika virus (ZIKV) outbreak in Brazil (2015–2016), the clinical manifestations associated with its infection were complex and included miscarriage and congenital malformations, not previously described. In this study, we evaluated the prenatal conditions of pregnant female squirrel monkeys (Saimiri collinsi) infected during different gestational thirds (GTs) and assessed all clinical aspects, diagnostic imaging, viremia and the immune response. In our study, 75% of the infected animals in the 1st GT group had significant clinical manifestations, such as miscarriage and prolonged viremia associated with a late immune response. Consequently, their neonates showed fetal neuropathology, such as cerebral hemorrhage, lissencephaly or malformations of the brain grooves, ventriculomegaly, and craniofacial malformations. Thus, our study demonstrated the relevance of pregnant squirrel monkeys as a model for the study of ZIKV infection in neonates due to the broad clinical manifestations presented, including the typical congenital Zika syndrome manifestations described in humans.

Do institutional norms affect behavioral preferences: A view from gender bias in the intra-household expenditure allocation in Iran

This paper fills a gap in the literature of gender bias in household expenditure by analyzing how institutional norms affect behavioral preferences in the context of Iran’s household expenditure allocation. Although Iran’s institutional norms and culture show gender bias in various forms, there is no information about gender bias in household expenditure. Using descriptive statistics, Engel Curve method and Tobit method with Household Income and Expenditure Survey data from 1987 to 2007, the paper examines the presence of gender bias in Iran’s household expenditure. Findings show that women and girls suffer bias in food expenditure, an important determinant of female health outcomes such as fertility, prenatal and neonatal conditions. However, other expenditure allocations mostly work favorably for them. These findings are significant for policy prescriptions designed for generating equity in the allocation of household expenditure to foster economic development and creating a template for countries where girls and women face similar constraints.

Relationship between Prenatal Characteristics and Body Condition and Endocrine Profile in Rabbits.

Simple SummaryLitter size is an essential trait in rabbit production, and it depends on ovulation rate and embryonic and foetal survival. The period between 8 and 18 d of gestation is critical for foetal survival, as the placenta controls foetal nutrition during this period. Ovulation rate and foetal survival at 12 d of gestation are affected by body condition and metabolic and hormonal profile. Higher foetal survival is related to a higher number of vessels arriving at the implantation site, and may be due to higher available space for the foetus.This study evaluated the relationship between prenatal characteristics and body condition and endocrine profile. A total of 25 non-lactating multiparous females were used. Body condition, measured as body weight and perirenal fat thickness, non-esterified fatty acids (NEFA), leptin, progesterone and 17β-estradiol were recorded at mating and 12 d of gestation. Ovulation rate, number of foetuses, ovary and foetal weight, length and weight of uterine horn, available space per foetus and maternal and foetal placental morphometry were recorded at 12 d of gestation. Ovulation rate showed a positive linear relationship with number of foetuses, ovary weight and NEFA. A negative linear relationship between ovulation rate and perirenal fat thickness and leptin was obtained. Ovulation rate was maximum when body weight and 17β-estradiol were 4.4 kg and 22.7 pg/mL, respectively. Foetal weight showed a positive relationship with perirenal fat thickness and a negative relationship with leptin. An increase in progesterone and NEFA concentration was related to a positive linear increase in number of foetuses and in uterine horn weight. Space available per foetus was affected both by the number of vessels that reach the implantation site and by position of the foetus in the uterine horn. In conclusion, body condition during mating and early gestation should be maintained within an optimal range to ensure the best prenatal characteristics. While 17β-estradiol, NEFA and leptin affected the ovulation rate, progesterone and NEFA affected foetal development. The number of vessels that reach the implantation site determines early foetal survival.

Immigration and the Short- and Long-Term Impact of Improved Prenatal Conditions

This paper investigates the effects of immigration from a developing country to a developed country during pregnancy on offspring's outcomes. We focus on intermediate and long-term outcomes, using quasi-experimental variation created by the immigration of Ethiopian Jews to Israel in May 1991. Individuals conceived before immigration experienced dramatic changes in their environmental conditions at different stages of prenatal development depending on their gestational age at migration. We find that females whose mothers immigrated at an earlier gestational age have lower grade repetition and dropout rates in high school. They also show better cognitive performance during primary and middle school and in the high school matriculation study program. As adults, they have higher post-secondary schooling, employment rates, and earnings than those whose mothers migrated at a later stage of pregnancy.

A conceptual framework of the impact of maternal early life drought exposure on newborn size in Malawi

The effects of adverse prenatal conditions are not only experienced over the life course but can be passed on intergenerationally. The present study took advantage of a natural experiment from thre...

Exposures influencing the developing central autonomic nervous system.

Autonomic nervous system function is critical for transition from in-utero to ex-utero life and is associated with neurodevelopmental and neuropsychiatric outcomes later in life. Adverse prenatal and neonatal conditions and exposures can impair or alter ANS development and, as a result, may also impact long-term neurodevelopmental outcomes. The objective of this article is to provide a broad overview of the impact of factors that are known to influence autonomic development during the fetal and early neonatal period, including maternal mood and stress during and after pregnancy, fetal growth restriction, congenital heart disease, toxic exposures, and preterm birth. We touch briefly on the typical development of the ANS, then delve into both in-utero and ex-utero maternal and fetal factors that may impact developmental trajectory of the ANS and, thus, have implications in transition and in long-term developmental outcomes. While many types of exposures and conditions have been shown to impact development of the autonomic nervous system, there is still much to be learned about the mechanisms underlying these influences. In the future, more advanced neuromonitoring tools will be required to better understand autonomic development and its influence on long-term neurodevelopmental and neuropsychological function, especially during the fetal period.

Preterm birth, neonatal therapies and the risk of childhood cancer.

Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry-based, case-control design. Combining population-based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age- and sex-matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (<32) and late preterm (32-36) and term (≥37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06-1.57), especially for the early preterm (OR 1.84, 95% CI 1.16-2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25-4.37), retinoblastoma (OR 3.21, 95% CI 1.22-8.41) and germ cell tumors (OR 5.89, 95% CI 2.29-15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.