Premature Birth
Premature birth, also known as preterm birth, is defined as the birth of an infant before 37 completed weeks of gestation. It represents a significant global health challenge, affecting millions of infants annually and contributing substantially to infant mortality and long-term health complications[1]. Understanding the factors that contribute to premature birth is crucial for improving neonatal and long-term health outcomes.
The biological basis of premature birth is complex and multifactorial, involving a combination of genetic, environmental, and maternal factors. Research indicates that both maternal and fetal genetic variations can influence gestational duration and the risk of spontaneous preterm birth[2]. For instance, specific variants in the fetal genome, particularly near pro-inflammatory cytokine genes, have been associated with gestational duration[3], suggesting an involvement of inflammatory pathways in the initiation of labor [4]. Other genetic studies have identified loci associated with early spontaneous preterm delivery [5], and interactions between genes and maternal factors like pre-pregnancy BMI also play a role [6].
Clinically, premature birth is a leading cause of neonatal morbidity and mortality[7]. Infants born prematurely are at an increased risk for a range of health issues, including respiratory distress syndrome, necrotizing enterocolitis, sepsis, and various neurological and developmental disabilities[8]. The degree of prematurity often correlates with the severity of these complications, with extremely premature infants facing particularly challenging outcomes [9].
From a societal perspective, premature birth carries substantial burdens, including emotional distress for families and significant healthcare costs. Its widespread impact on infant health and long-term developmental trajectories makes it a critical area of public health focus, driving extensive research efforts aimed at prevention and improved care[10].
Limitations
Section titled “Limitations”Understanding the genetic architecture of preterm birth is a complex endeavor, and current research, while valuable, operates within several important limitations. These limitations often stem from methodological choices, the inherent complexity of the trait, and the diverse populations studied. Acknowledging these challenges is crucial for interpreting findings and guiding future research directions.
Methodological and Statistical Challenges
Section titled “Methodological and Statistical Challenges”Genetic studies of preterm birth have frequently faced limitations in sample size, which directly impacts the statistical power to detect genetic loci, especially those with smaller effect sizes or less frequent variants. These variants can influence a wide range of biological processes, from fundamental cellular functions to complex developmental pathways and immune responses, all of which are essential for maintaining a healthy pregnancy.
Several variants are found in genes with direct roles in cellular function and early development. For instance, common variants rs201450565 and rs4241495 in the EEFSECgene have been associated with preterm birth[2]. EEFSECis vital for protein synthesis, particularly the incorporation of selenocysteine into selenoproteins, which are critical for antioxidant defense and immune regulation. Disruptions in these processes can contribute to oxidative stress and inflammation, known factors in premature birth. TheWNT4 gene, with variant rs3820282 , encodes a signaling molecule fundamental for embryonic development and placentation, a process that, when compromised, can lead to adverse pregnancy outcomes, including preterm birth[4]. Similarly, the LRP5 gene, featuring variant rs312777 , acts as a co-receptor in the Wnt signaling pathway, suggesting its potential involvement in developmental processes that contribute to normal gestational duration.
Other variants affect genes with regulatory and structural functions important for pregnancy. The KCNAB1 gene, containing variant rs1488425 , encodes a subunit of voltage-gated potassium channels that regulate smooth muscle contraction, a process critical for uterine function during labor. Alterations in uterine contractility due to variants in such genes could influence the timing of birth. TheTGFB1 gene, with variant rs11466328 , produces a powerful cytokine involved in cell proliferation, immune modulation, and tissue repair. Its role in maternal immune tolerance and placental development is paramount, and dysregulation can lead to inflammatory conditions or inadequate tissue remodeling, both risk factors for premature delivery[3]. Additionally, the region encompassing PMP22 and TEKT3, where variant rs7217780 is located, includes genes primarily involved in myelin formation and cilia structure; however, variants in such genomic regions can have broader regulatory impacts on cellular integrity and function relevant to gestation [5].
Finally, variants in non-coding regions and pseudogenes also contribute to the genetic landscape of premature birth. The variantsrs2963463 , rs2946160 , and rs2963457 are located in LINC02227, a long intergenic non-coding RNA. Such lncRNAs are increasingly recognized for their diverse roles in gene regulation, influencing processes like cell growth and differentiation that are crucial for successful pregnancy. Similarly, the variant rs201386833 is situated within the RN7SL712P - AKR1B1P8 region, which contains pseudogenes. While traditionally considered non-functional, pseudogenes can act as regulatory elements, for example, by modulating the expression of functional genes through mechanisms like microRNA sponging. The region of LINC01444 - BNIP3P3, including variant rs148022200 , also involves a lncRNA and a pseudogene, suggesting potential regulatory influences on cellular stress responses and survival pathways. These non-coding variants may subtly alter gene expression patterns, contributing to the complex etiology of premature birth[4].
Core Definition and Gestational Age Measurement
Section titled “Core Definition and Gestational Age Measurement”Premature birth, often referred to as preterm birth (PTB), is precisely defined as a birth occurring before 37 weeks of gestation[6]. This critical threshold signifies the completion of a full-term pregnancy, with births prior to this point being associated with increased morbidity and mortality[3]. Gestational age, the primary metric used to define premature birth, can be determined through various methods, including maternal-reported last menstrual period, first-trimester ultrasound screening, and data extracted from medical birth registries[11]. Accurate assessment of gestational age is paramount for both clinical management and research, as it directly impacts the classification of birth outcomes and subsequent health interventions.
Classification and Subtypes of Preterm Birth
Section titled “Classification and Subtypes of Preterm Birth”Premature birth is further categorized into subtypes based on gestational age at delivery, reflecting varying levels of severity and associated risks. These classifications include “early preterm birth,” typically defined as a birth occurring before 32 weeks of gestation, or more specifically, before gestational week 34+0 (less than 238 days of gestation)[6]. “Late preterm birth” generally encompasses births occurring from 32 weeks up to 36 and 6/7 weeks of gestation[6]. Additionally, premature births are classified by their etiology into “spontaneous preterm birth,” which may involve preterm labor or premature rupture of membranes, and “medically indicated preterm birth,” resulting from medical induction or caesarean section without spontaneous labor or membrane rupture[6]. These distinctions are crucial for understanding underlying causes and tailoring interventions, with researchers often employing stringent exclusion criteria to focus on “natural” gestational duration in studies [3].
Terminology and Diagnostic Criteria in Clinical Practice and Research
Section titled “Terminology and Diagnostic Criteria in Clinical Practice and Research”The terminology surrounding premature birth encompasses key terms like “preterm birth” (PTB), “gestational duration,” and “premature rupture of membranes” (PROM), alongside related concepts such as “intra-uterine infection” (IUI) or “chorioamnionitis”[6]. Clinically, a diagnosis of premature birth involves observing uterine contractions with cervical effacement and dilation, or premature rupture of membranes, all occurring before 37 weeks of gestation[6]. For research purposes, precise operational definitions and diagnostic criteria are essential, often involving the exclusion of pregnancies with specific complications like stillbirths, multiple births, pre-eclampsia, gestational diabetes, or congenital anomalies, to isolate the genetic and environmental factors contributing to spontaneous preterm birth[3]. Such rigorous criteria help to minimize heterogeneity and focus on the underlying biological mechanisms influencing gestational duration [3].
Causes of Premature Birth
Section titled “Causes of Premature Birth”Premature birth, defined as delivery before 37 weeks of gestation, results from a complex interplay of genetic predispositions, environmental factors, and maternal physiological conditions. Research indicates that multiple mechanisms and risk factors often converge, leading to early parturition. The duration of pregnancy is a highly heritable trait, yet it is also significantly influenced by external exposures and the mother’s overall health[3].
Genetic Predisposition
Section titled “Genetic Predisposition”Genetic factors play a substantial role in determining gestational duration and the risk of premature birth, with twin and family studies estimating heritability between 25% and 40%[3]. Both maternal and fetal genomes contribute to this risk, with maternal genetic factors accounting for approximately 20% of the variation in gestational duration and fetal factors around 10% [3]. Specific maternal genetic variants have been identified that are robustly associated with gestational length and preterm birth, including those in genes such asESR1, ADCY5, RAP2C, EBF1, EEFSEC, and AGTR2 [2]. These maternal loci are believed to exert their influence through roles in uterine development, maternal nutrition, and vascular control, highlighting a mechanistic involvement in the timing of birth[2].
Fetal genetic contributions are also crucial, with variants in the fetal genome near pro-inflammatory cytokine genes on chromosome 2q13 showing associations with gestational duration[3]. Additionally, the fetal gene SLIT2has been linked to the risk of spontaneous premature birth and fetal growth[12]. While polygenic risk is evident, the identification of these specific maternal and fetal genetic factors underscores the complex inherited basis of premature birth, with ongoing research continuing to uncover further contributing loci and their interactions.
Environmental and Lifestyle Factors
Section titled “Environmental and Lifestyle Factors”A wide array of non-genetic factors significantly influences the timing of parturition. These environmental and lifestyle elements include maternal stress, smoking, and the presence of urogenital infections[3]. Socioeconomic factors such as educational attainment and general socioeconomic status are also recognized as contributing influences[3]. Furthermore, maternal pre-pregnancy characteristics, including weight (BMI), and lifestyle choices like diet and prenatal multivitamin intake, have been investigated for their impact on premature birth risk[6].
Intrauterine inflammation and microbial colonization or infection of the genital tract are identified as critical mechanisms through which environmental exposures can precipitate premature parturition[5]. These factors can create an environment that triggers early labor, emphasizing the importance of maternal health and hygiene during pregnancy. The interplay of these diverse environmental and lifestyle elements collectively contributes to the multifactorial nature of premature birth.
Gene-Environment Interactions
Section titled “Gene-Environment Interactions”The risk of premature birth is not solely determined by genetic or environmental factors in isolation; rather, it often arises from intricate gene-environment interactions. Genetic predispositions can interact with various environmental triggers, modifying an individual’s susceptibility to premature delivery[6]. For instance, studies have explored specific interactions, such as between genetic variants and maternal pre-pregnancy BMI, demonstrating how a genetic background might confer different levels of risk depending on maternal weight status before pregnancy [6]. This highlights that genetic susceptibilities are not static but can be amplified or mitigated by external environmental influences. Further research is needed to fully explore how other genetic variants interact with lifestyle, dietary exposures, and other environmental factors to influence premature birth risk[6].
Maternal Physiological Factors and Risk Conditions
Section titled “Maternal Physiological Factors and Risk Conditions”Beyond specific genetic variants and external environmental exposures, several maternal physiological factors and pre-existing conditions contribute to the complex etiology of premature birth. The mechanistic roles of maternal genetic variants in processes such as uterine development, maternal nutrition, and vascular control are crucial, as disruptions in these areas can directly affect the pregnancy’s duration[2]. Intrauterine inflammation, whether triggered by infection or other stimuli, is a recognized physiological pathway leading to preterm parturition[5], [3]. Furthermore, the number of previous pregnancies, or parity, is identified as a non-genetic maternal risk factor that influences the timing of birth[3], [6]. These physiological and demographic factors underscore the broad range of maternal health aspects that collectively modulate the risk of premature delivery.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Premature birth, defined as birth before 37 completed weeks of gestation, is a complex trait influenced by a multitude of interacting pathways and mechanisms. These include genetic and metabolic factors, inflammatory signaling, and intricate systems-level integration between maternal and fetal physiological processes. Research highlights the convergence of various risk factors and molecular pathways that ultimately lead to preterm parturition.
Genetic and Epigenetic Regulation of Gestational Duration
Section titled “Genetic and Epigenetic Regulation of Gestational Duration”The timing of birth is under significant genetic and epigenetic control, involving both maternal and fetal genomes. Genomic analyses have linked reproductive aging to hypothalamic signaling, suggesting a role for central regulatory pathways in gestational duration[13]. Maternal genetic variants are robustly associated with gestational length and preterm birth, with roles in uterine development, maternal nutrition, and vascular control[2]. Furthermore, fetal genetic variants, such as those near pro-inflammatory cytokine genes on 2q13 and fetal SLIT2, also associate with gestational duration and spontaneous preterm birth[3]. These genetic influences can operate independently or through gene-environment interactions, such as the interaction between specific genes and maternal pre-pregnancy BMI, highlighting the complex regulatory landscape contributing to birth timing[6].
Inflammatory Signaling and Uterine Dynamics
Section titled “Inflammatory Signaling and Uterine Dynamics”Inflammatory signaling pathways play a critical role in the initiation of preterm labor, with multiple mechanisms converging to produce preterm parturition. Intrauterine inflammation and genital tract microbial colonization or infection are significant contributors, activating intracellular signaling cascades that lead to uterine contractions and cervical changes[5]. Fetal genetic variants near pro-inflammatory cytokine genes on 2q13 further underscore the importance of immune and inflammatory responses in determining gestational duration[3]. These signaling events involve receptor activation and subsequent intracellular cascades, ultimately impacting the uterine environment and its ability to maintain pregnancy.
Metabolic Control of Fetal Growth and Development
Section titled “Metabolic Control of Fetal Growth and Development”Metabolic pathways are crucial for fetal growth and development, with variants in genes like ADCY5 impacting birth weight and fetal growth, potentially through alterations in energy metabolism and flux control[14]. The chromosome 3q25 genomic region is associated with measures of adiposity in newborns, indicating specific metabolic regulatory mechanisms influencing fat deposition and biosynthesis [7]. Maternal nutritional status, including pre-pregnancy BMI, interacts with fetal genetics to influence birth timing and weight, reflecting complex metabolic regulation essential for healthy fetal development[6]. Dysregulation in these metabolic pathways can contribute to deviations in fetal growth and has implications for cardio-metabolic risk factors in adult life [15].
Systems-Level Integration and Disease Pathogenesis
Section titled “Systems-Level Integration and Disease Pathogenesis”Premature birth arises from a complex interplay of genetic, environmental, and physiological factors, demonstrating significant systems-level integration and pathway crosstalk. Maternal and fetal genetic effects on birth weight, for instance, highlight network interactions that are independent yet converge to influence pregnancy outcomes[16]. The integration of genomic information from both mothers and offspring with birth timing data is crucial for understanding these hierarchical regulatory networks and identifying novel risk factors[2]. Dysregulation within these integrated systems, such as inflammation, altered uterine development, or vascular control, can lead to preterm birth, underscoring the need to investigate new preventative and therapeutic measures that target these emergent properties of the maternal-fetal unit[2].
Clinical Relevance
Section titled “Clinical Relevance”Risk Stratification and Prognostic Value
Section titled “Risk Stratification and Prognostic Value”Premature birth, defined as birth before the full term of gestation, significantly increases the risk of both morbidity and mortality in infants[3]. Identifying individuals at high risk for spontaneous preterm birth is crucial for implementing targeted prevention strategies and improving neonatal outcomes. Research indicates that both maternal and fetal genetic factors play a significant role in determining gestational duration and susceptibility to preterm birth. For instance, variants near pro-inflammatory cytokine genes on 2q13 in the fetal genome and fetal SLIT2 have been associated with gestational duration and preterm birth risk, respectively[3].
Furthermore, maternal genetic variants influencing uterine development, nutrition, and vascular control have been robustly linked to gestational length, offering insights into new risk factors and prognostic indicators [2]. The interplay of these genetic predispositions with clinical factors, such as maternal pre-pregnancy BMI, provides a more comprehensive framework for risk assessment, allowing for earlier identification of pregnancies that may benefit from enhanced surveillance or intervention [6]. This integrated approach to risk stratification enables a more precise prediction of outcomes, including the prognosis for neonatal morbidity and mortality.
Clinical Management and Personalized Prevention
Section titled “Clinical Management and Personalized Prevention”The integration of genomic information from both mothers and offspring with detailed birth timing data holds promise for developing novel preventative and therapeutic measures in the management of premature birth[2]. This personalized medicine approach can guide treatment selection and monitoring strategies, moving beyond traditional risk factors to incorporate a deeper understanding of individual genetic susceptibilities. Extensive clinical data collection, including medical, social, and obstetric histories, prior pregnancy details, and current pregnancy complications, is vital for comprehensive risk assessment and informing clinical decisions [5]. Such data, combined with genetic insights, enhances the diagnostic utility of screening tools and the effectiveness of monitoring protocols.
While various mechanisms, including intrauterine inflammation and genital tract infections, converge to cause preterm parturition, understanding the genetic landscape allows for the identification of specific pathways that could be targeted for intervention [5]. Despite potential heterogeneity in study populations regarding exclusion criteria for maternal conditions or pregnancy complications, the overall consistency of genetic findings across cohorts supports their utility for clinical applications [3]. This evidence-based approach facilitates the development of more precise prevention strategies and tailored treatments for pregnant individuals at risk.
Associated Morbidities and Long-Term Outcomes
Section titled “Associated Morbidities and Long-Term Outcomes”Premature birth carries significant short- and long-term implications for the health of the newborn, contributing substantially to infant morbidity and mortality[3]. Low birth weight, a common consequence of prematurity, is directly associated with a heightened risk of severe neonatal morbidities. These include respiratory distress syndrome, necrotizing enterocolitis, and various neurologic and developmental disabilities[7].
These complications extend beyond the immediate neonatal period, impacting long-term developmental trajectories and overall health well into childhood and beyond [7]. Even mild and moderate preterm births contribute to infant mortality, underscoring the broad clinical relevance of preventing and managing prematurity across its spectrum[1]. Therefore, early identification and intervention strategies are critical to mitigate these associated conditions and improve the long-term health outcomes for individuals born prematurely.
Population Studies
Section titled “Population Studies”Epidemiological Trends and Demographic Associations
Section titled “Epidemiological Trends and Demographic Associations”Premature birth, defined as birth occurring before the completion of the full gestational period, is a significant global public health concern, as both early and late gestational durations are linked to elevated rates of infant morbidity and mortality[3]. National vital statistics reports have historically provided foundational data for tracking infant mortality, offering essential context for the broader impact of birth outcomes on population health[17]. Epidemiological investigations consistently reveal that specific demographic factors are associated with the incidence of spontaneous preterm delivery. For example, maternal age, race, and parity are frequently identified as key demographic variables influencing the risk of preterm birth across various populations[5].
Research also highlights notable disparities in preterm birth rates across different racial and ethnic groups. In one genome-wide association study focusing on early spontaneous preterm delivery, African American women comprised a substantial proportion of both cases and controls within the neonatal and maternal validation cohorts, indicating a significant representation of this population in preterm birth research[5]. Such detailed demographic insights are crucial for understanding population-level risk distributions and for developing targeted public health initiatives designed to reduce the burden of premature birth within diverse communities.
Large-scale Genetic Studies and Population Cohorts
Section titled “Large-scale Genetic Studies and Population Cohorts”Extensive population studies, particularly genome-wide association studies (GWAS), have been pivotal in elucidating the genetic underpinnings of premature birth and gestational duration. These studies frequently utilize large-scale cohorts and biobank resources, including those supported by initiatives such as the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research and the March of Dimes Prematurity Research Centers[5]. For instance, a GWAS examining offspring birth weight involved 86,577 women, successfully identifying novel genetic loci and differentiating between maternal and fetal genetic effects that independently influence birth outcomes[18]. Such large sample sizes significantly enhance the statistical power required to detect subtle genetic associations, contributing to a more comprehensive understanding of the genetic architecture underlying these traits.
Longitudinal analyses derived from these substantial cohorts have begun to uncover complex genetic interactions, including gene-environment interactions, such as a newly identified interaction between specific genes and maternal pre-pregnancy BMI on preterm birth risk[6]. Studies have pinpointed fetal genomic variants, including those located near pro-inflammatory cytokine genes on chromosome 2q13, that are associated with gestational duration[3], and the fetal SLIT2gene has been linked to the risk of spontaneous preterm birth and fetal growth[12]. These findings collectively underscore the multifactorial etiology of premature birth, involving distinct contributions from both maternal and fetal genomes, and suggest potential temporal patterns in genetic influences throughout the course of pregnancy.
Methodological Approaches and Cross-Population Insights
Section titled “Methodological Approaches and Cross-Population Insights”Population studies on premature birth employ robust methodologies to ensure the reliability and broader applicability of their findings. Common study designs include case-control studies embedded within larger cohorts, where comprehensive demographic data, detailed medical and obstetric histories, and information on current and prior pregnancies are meticulously gathered through methods like chart reviews and patient interviews[5]. To mitigate potential biases and confounders, statistical analyses are routinely adjusted for variables such as maternal age, race, study site, and parity, often categorized for greater analytical precision [5]. While individual study sample sizes can range from hundreds to tens of thousands of participants, meta-analyses are frequently used to combine data from multiple studies, thereby increasing overall statistical power and the generalizability of the results [3].
Cross-population comparisons are essential for identifying ancestry-specific genetic effects and understanding global geographic variations in the risk of premature birth. Research efforts involve extensive international collaborations among institutions spanning Europe, North America, and Asia, reflecting a concerted global endeavor to unravel the complexities of preterm birth[6]. While some cohorts, such as those investigating spontaneous preterm delivery, exhibit a high representation of specific ethnic groups like African Americans [5], other multi-ethnic genome-wide association studies explore associations, for example, with measures of adiposity in newborns across diverse populations [7]. This broad, inclusive approach is crucial for determining whether identified genetic associations are universal or population-specific, ultimately informing the development of more equitable and effective prevention strategies.
Key Variants
Section titled “Key Variants”Frequently Asked Questions About Premature Birth
Section titled “Frequently Asked Questions About Premature Birth”These questions address the most important and specific aspects of premature birth based on current genetic research.
1. My mom had a premature baby; will I also have one early?
Section titled “1. My mom had a premature baby; will I also have one early?”Yes, a family history of premature birth can increase your personal risk. Genetic variations, which you inherit from either parent, can influence the duration of your pregnancy. While it’s not a certainty, your inherited genetic makeup might make you more susceptible to delivering early compared to someone without that family history.
2. Does my weight before pregnancy affect my baby’s birth time?
Section titled “2. Does my weight before pregnancy affect my baby’s birth time?”Yes, your weight before pregnancy can play a role. Research indicates that interactions between your genes and maternal factors, such as your pre-pregnancy BMI, can influence the risk of spontaneous preterm birth. Maintaining a healthy weight before conception is generally beneficial for pregnancy outcomes.
3. Can a genetic test tell me if I’ll have an early baby?
Section titled “3. Can a genetic test tell me if I’ll have an early baby?”Currently, genetic tests are not routinely used to predict an individual’s risk of preterm birth. While we know specific genetic variations in both you and your baby can influence birth timing, the full genetic picture is highly complex and involves many genes with small effects. More comprehensive research is needed before reliable predictive tests become widely available.
4. Why did my baby come early when I felt healthy?
Section titled “4. Why did my baby come early when I felt healthy?”Premature birth is a complex, multifactorial condition, meaning many factors contribute. Even if you felt perfectly healthy, underlying genetic factors in either you or your baby could have influenced the timing of labor. Sometimes, subtle inflammatory pathways, impacted by genetic variations, can contribute to early labor without obvious symptoms.
5. Does my ethnic background change my risk for an early birth?
Section titled “5. Does my ethnic background change my risk for an early birth?”Yes, your ethnic background can be a factor. Much of the current genetic research on preterm birth has focused on populations of European descent. We know that genetic risk factors can vary across different ancestries, meaning some groups may have unique genetic predispositions or different rates of preterm birth.
6. Can my body’s inflammation affect my baby’s birth timing?
Section titled “6. Can my body’s inflammation affect my baby’s birth timing?”Yes, inflammation is strongly implicated in preterm birth. Specific genetic variants in the fetal genome, particularly near genes involved in pro-inflammatory cytokine pathways, have been associated with gestational duration. These genetic influences can contribute to initiating labor prematurely through inflammatory responses.
7. My sister had full-term babies; why am I worried?
Section titled “7. My sister had full-term babies; why am I worried?”Even with shared family genetics, individual experiences can differ due to a unique combination of genetic and environmental factors. While you share some genetic background with your sister, you each have unique genetic variations and different environmental exposures that can influence your personal risk for an early birth.
8. Can my daily stress actually cause me to deliver early?
Section titled “8. Can my daily stress actually cause me to deliver early?”While maternal stress is recognized as a non-genetic risk factor for preterm birth, its direct interaction with genetic predispositions is still an area of ongoing research. However, chronic stress can influence your body’s physiological responses, which could potentially interact with genetic susceptibilities to affect labor timing.
9. If premature birth runs in my family, can I prevent it with diet?
Section titled “9. If premature birth runs in my family, can I prevent it with diet?”A healthy diet is crucial for a healthy pregnancy, but it’s not a guaranteed prevention for genetically influenced preterm birth. While maintaining a healthy BMI through diet can be beneficial (as BMI interacts with genes), genetic predispositions mean some risk might remain regardless of dietary choices.
10. Why do some babies come early when others stay full term?
Section titled “10. Why do some babies come early when others stay full term?”The precise timing of birth is influenced by a complex interplay of genetic factors from both the mother and the baby, alongside various environmental influences. Differences in these genetic variations, such as those affecting inflammatory pathways or specific genes involved in initiating labor, can explain why some pregnancies end earlier than others.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[2] Zhang, G. “Genetic Associations with Gestational Duration and Spontaneous Preterm Birth.”N Engl J Med, 2017.
[3] Liu, X. “Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.”Nat Commun, vol. 10, 2019, p. 3927.
[4] Bacelis, J. et al. “Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways.” PLoS One, 2016.
[5] Zhang, H. et al. “A genome-wide association study of early spontaneous preterm delivery.” Genet Epidemiol, 2014, PMID: 25599974.
[6] Hong, X. “Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.”Nat Commun, vol. 8, 2017, p. 15729.
[7] Urbanek, M. et al. “The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.” Hum Mol Genet, vol. 22, no. X, 2013, PMID: 23575227.
[8] Jilling, T., et al. “Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight.”Pediatr Res, vol. 84, no. 5, 2018, pp. 663-669.
[9] Hack, M., and A. A. Fanaroff. “Outcomes of extremely immature infants—a perinatal dilemma.” The New England Journal of Medicine, vol. 329, 1993, pp. 1649–1650.
[10] Institute of Medicine, Committee on Understanding Premature Birth and Assuring Healthy Outcomes.Preterm Birth: Causes, Consequences, and Prevention. National Academies Press (US), 2007.
[11] Helgeland, O., et al. “Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth.” Nature Communications, 2019, PMID: 31575865.
[12] Tiensuu, H. et al. “Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2.”PLoS Genet, vol. 15, no. 6, 2019, e1008107.
[13] Brooke, R. J. “A High-risk Haplotype for Premature Menopause in Childhood Cancer Survivors Exposed to Gonadotoxic Therapy.”J Natl Cancer Inst, vol. 110, no. 1, 2018, PMID: 29432556.
[14] Freathy, R. M. “Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight.”Nat Genet, 2010, PMID: 20372150.
[15] Horikoshi, M. et al. “Genome-wide associations for birth weight and correlations with adult disease.”Nature, 2016, PMID: 27680694.
[16] Warrington, N. M. et al. “Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.”Nat Genet, 2019, PMID: 31043758.
[17] Mathews, T. J., et al. “Infant mortality statistics from the 2002 period: linked birth/infant death data set.”National Vital Statistics Reports: From the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System, vol. 53, 2004, pp. 1–29.
[18] Beaumont, R. N. et al. “Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.”Hum Mol Genet, 2018, PMID: 29309628.