Fetus
A fetus is the stage of prenatal mammalian development, particularly in humans, commencing approximately nine weeks after fertilization when the major organs have formed and extending until birth.[1] In this period, the organism, genetically a distinct human from conception, exhibits rapid growth, refinement of organ systems, and acquisition of human morphological features such as limbs, facial structure, and skeletal framework.[2][3] During the fetal stage, key milestones include the development of sensory capabilities, including heartbeat detectable by week 6, brain waves by week 8, and viability potential around 24 weeks gestation with medical intervention, though full-term birth at 39-40 weeks optimizes survival and health.[4][5] The fetus maintains a continuum of human development, with empirical evidence from embryology affirming its status as a living member of the species Homo sapiens, characterized by directed growth toward maturity rather than mere tissue.[6][7] Notable controversies surrounding the fetus center on its legal and ethical status, particularly in debates over abortion, where scientific consensus on its biological humanity contrasts with varying philosophical or policy definitions of personhood and rights; for instance, while peer-reviewed biology texts describe it unequivocally as human, institutional sources influenced by ideological biases may equivocate on developmental continuity to support selective termination practices.[2][8] Advances in fetal surgery and imaging have further highlighted its responsiveness to stimuli and capacity for independent survival post-viability, underscoring causal realities of its organismal integrity.[4]Definition and Terminology
Biological Definition
In developmental biology, the fetus is defined as the unborn offspring of a viviparous mammal during the postembryonic phase of prenatal development, following the establishment of the basic body plan in the embryonic stage.[9] This stage is characterized by the presence of all major organ rudiments, with subsequent emphasis on cellular proliferation, tissue differentiation, organ maturation, and physiological refinement rather than initial organogenesis.[10] The term applies across mammalian species, including humans, canines, and bovines, distinguishing the fetus from earlier developmental forms like the zygote, blastocyst, or embryo.[2] In humans, the fetal period begins at the start of the ninth week post-fertilization (equivalent to approximately the end of the eighth week or the conclusion of Carnegie stage 23), when the embryo transitions to a form with recognizable human features such as a large head, limb buds, and early sensory structures.[9] [1] This timing marks the shift from high-risk organ formation—prone to teratogenic disruptions—to a phase dominated by growth, where the organism increases in size from roughly 30 mm crown-rump length to an average of 50 cm at term, while developing coordinated functions like heartbeat (detectable from week 6 but strengthening thereafter) and rudimentary neural activity.[4] [10] The duration extends until parturition, typically 38-40 weeks post-fertilization, during which viability outside the uterus becomes possible after about 24 weeks due to advancements in lung surfactant production and central nervous system integration.[11] Biologically, the fetus remains dependent on placental exchange for nutrients, oxygen, and waste removal, underscoring its status as a distinct developmental entity within the maternal system.[3]Etymology and Historical Usage
The term fetus entered the English language in the late 14th century, borrowed directly from Latin fētus, which denoted "offspring," "bringing forth," or "hatching of young," encompassing both the process of gestation and the developing progeny.[12] This Latin noun traces to the Proto-Indo-European root dhe(i)-, signifying "to suck" or "to nurse," reflecting an association with the nourishment of young in the womb or egg, akin to derivations in Sanskrit dhitih ("nurse, lactation") and dhiyam ("milk").[12] In classical Latin usage, fētus broadly applied to viviparous offspring during pregnancy, sometimes extending figuratively to newborns, without the modern embryological precision distinguishing it from earlier developmental stages.[13] Historically, the word appeared in Middle English texts around 1350–1400, initially referring to the unborn young of viviparous animals, including humans, as an "act of bearing young" or the resultant entity.[14] In Roman medical and legal contexts, such as those preserved in works by authors like Pliny the Elder, fētus described the gestating form in discussions of reproduction and abortion, emphasizing its status as progeny rather than a mere biological process.[13] A variant spelling, foetus, emerged in the late 16th century (first attested 1594) through erroneous Late Latin influence from diphthong patterns in words like foedus, but the original fetus form predominates in etymologically accurate and contemporary medical nomenclature, with foetus now largely obsolete outside certain non-medical British conventions.[15] This evolution underscores the term's shift from a general descriptor of parturition to a specific stage of prenatal development post-organogenesis, formalized in 19th-century embryology.[14]Comparative Embryology and Development
Fetal Stage in Mammals
The fetal stage in placental mammals follows the embryonic period, commencing after gastrulation and the establishment of the basic body plan, including the formation of germ layers and major organ primordia. At this point, the developing organism transitions from primarily organogenesis to phases dominated by cellular proliferation, tissue expansion, and physiological maturation, resulting in an anatomically recognizable form with a distinct head, trunk, limbs, and tail. This stage is marked by the presence of all essential organ systems in rudimentary but functional states, supported by extraembryonic membranes such as the chorion (forming the fetal component of the placenta), amnion (enclosing the fetus in protective fluid), and yolk sac (initially aiding nutrient absorption).[16][17] Key characteristics of the fetal stage include rapid somatic growth, deposition of adipose tissue, ossification of skeletal elements, and development of integumentary features like hair follicles, claws, and pigmentation. Sensory and motor capabilities emerge, such as coordinated movements and responses to stimuli, while internal systems like the cardiovascular, respiratory, and nervous structures refine their connectivity and efficiency. The placenta, derived from trophoblast invasion of the uterine wall, facilitates maternal-fetal exchange of gases, nutrients, and wastes without direct blood mixing, enabling prolonged intrauterine development. In contrast to the embryonic stage's focus on cellular differentiation and vulnerability to teratogens during organ formation, the fetal period emphasizes quantitative growth and adaptive responses to maternal physiology.[16][18] The duration and specific milestones of the fetal stage vary across mammalian species, correlating with adult body size, metabolic rate, and reproductive strategy. In canines, it spans approximately days 35 to 61 of gestation, featuring eyelid fusion, hair growth, and sexual differentiation. Rodent models, such as mice, exhibit a compressed fetal phase post-implantation (around embryonic day 8-12 onward), culminating in birth at 19-21 days, with emphasis on neural circuit formation and thermoregulatory preparation. Larger mammals, like elephants, extend this stage over 18-22 months, prioritizing extensive brain growth and skeletal robustification. Marsupials, with abbreviated uterine phases, exhibit a brief fetal-like period before pouch migration, where fetal membranes play a limited role compared to placental counterparts. These differences underscore evolutionary adaptations in viviparity, where fetal viability hinges on placental efficiency and maternal resource allocation.[18][16]Distinctions from Embryonic Stage
The embryonic stage of human prenatal development encompasses the period from approximately the third week after fertilization (or the end of the second week post-fertilization) through the eighth week of gestation, during which rapid cell differentiation and organogenesis predominate, establishing the foundational body plan including the neural tube, heart, limbs, and major organ systems.[19] In contrast, the fetal stage commences at the ninth week of gestation and extends until birth, shifting emphasis from primary structure formation to substantial increases in size, weight, and functional maturation of pre-formed organs, with the fetus achieving a distinctly human-like appearance by this transition.[3] [20] A primary distinction lies in the developmental priorities: organogenesis, the process of organ formation, is largely completed by the end of the eighth week, rendering the embryo highly susceptible to environmental teratogens that can induce structural malformations, whereas the fetal phase involves refinement and histological specialization of organs alongside exponential growth, reducing the incidence of major congenital anomalies after this point.[19] [21] For instance, during the embryonic stage, exposure to agents like thalidomide primarily affects limb bud development due to ongoing mesenchymal differentiation, while fetal exposures more often result in functional deficits or growth restriction rather than gross structural defects.[22] Morphologically, the embryo exhibits transient features such as pharyngeal arches resembling gill slits, a prominent tail-like caudal eminence, and disproportionate body segments, which regress or transform by the fetal onset; the fetus, by week 9, measures about 3 cm crown-rump length with elongated limbs, a rounded head, and external genitalia beginning to differentiate, marking a departure from the C-shaped embryonic curvature toward proportional human form.[19] Physiologically, embryonic circulation relies on yolk sac and primitive placental support with yolk sac hematopoiesis, evolving into fetal hepatic and bone marrow erythropoiesis by weeks 6-8, after which fetal circulation features advanced shunts like the ductus venosus for hepatic bypass, supporting sustained growth demands.[23] The embryonic period's brevity—roughly one-eighth the duration of the fetal stage—concentrates high-risk cellular migrations and inductions, with over 90% of organ systems initiated, whereas the protracted fetal phase (approximately 30 weeks) prioritizes quantitative expansion, such as brain sulcation and myelinization, and qualitative enhancements like surfactant production in lungs for viability.[20] This temporal and processual divergence underscores the embryonic stage's foundational volatility versus the fetal stage's consolidative stability, as evidenced by viability thresholds remaining near zero before week 9 but emerging post-viability in later fetal development.[24]Human Fetal Development
Transition from Embryonic Period
The embryonic period in human development concludes at the end of the eighth week following fertilization, at which point the developing organism transitions to the fetal stage, characterized by the completion of primary organogenesis and the onset of substantial growth and structural refinement.[25][24] This demarcation aligns with Carnegie stage 23, after which the embryo measures approximately 23-30 mm in crown-rump length, exhibits a distinctly human contour with elongated limbs, separated digits on hands and feet, and nascent external genitalia.[25] The shift reflects a biological continuum rather than an abrupt change, but it is conventionally defined by the relative completion of gross organ formation, reducing teratogenic vulnerability while prioritizing histogenesis and functional maturation.[19] Key morphological milestones at this transition include the formation of the basic facial features, such as fused eyelids, external ear pinnae, and a closed neural tube, alongside the establishment of vital systems like a functional four-chambered heart with detectable ultrasound activity since week 5-6.[19][3] Internally, major organs—including the liver, kidneys, and intestines—have primordia in place, though they remain immature and non-viable outside the uterus; for instance, the gastrointestinal tract rotates into position, and early lung branching (pseudoglandular stage) begins.[19] This period's end also coincides with the disappearance of embryonic tail remnants and the initiation of scalp vascular patterns precursor to hair follicles, signifying a pivot from differentiation to proportional enlargement, with the fetus gaining length at rates exceeding 1 mm per day initially.[19] Physiologically, the transition underscores reduced risk from external disruptors post-organogenesis, as evidenced by epidemiological data showing most congenital malformations arising before week 9 post-fertilization, though functional deficits can still emerge from later insults.[22] Peer-reviewed embryological texts, such as those referencing standardized staging, emphasize this boundary's utility for clinical assessment, enabling prenatal diagnostics like ultrasound to confirm viability and structural integrity from week 9 onward.[26] The designation "fetus" thus denotes not a new entity but an advanced phase where cellular proliferation drives a 45-fold weight increase by term, supported by placental nutrient exchange maturing concurrently.[3]First Trimester Milestones
The fetal stage begins at around 9 weeks gestational age (7 weeks post-fertilization), marking the transition from the embryonic period where primary organogenesis is largely complete, shifting focus to growth, maturation, and structural refinement.[19] [3] By this point, the crown-rump length (CRL) measures approximately 2-3 cm, and the heartbeat is detectable via Doppler ultrasound.[27] [4] In week 9, the upper limbs elongate with elbow formation, toes become visible, and eyelids start developing, while nipples and hair follicles emerge on the skin.[27] [4] The head remains disproportionately large relative to the body, comprising nearly half its size, and essential organs continue expanding in preparation for functional maturation.[4] The CRL reaches about 16-18 mm.[27] By week 10, the head assumes a rounder shape, finger and toe webbing recedes as digits lengthen, and outer ears take form alongside advancing eyelid closure.[27] [4] Intestinal rotation occurs within the abdominal cavity, and facial features sharpen, with nostrils evident.[4] Fetal heart tones become audible via Doppler, indicating circulatory functionality.[4] Week 11 features a broadening face with widely spaced eyes, low-set ears, and fused eyelids that remain sealed until later gestation.[27] Tooth buds for primary dentition appear, the liver initiates red blood cell production, and external genitals differentiate, though not yet distinguishable by ultrasound.[27] [3] The fetus exhibits reflexive movements, including fist clenching, mouth opening, and joint flexion at knees, elbows, and ankles; the CRL approximates 50 mm, with weight around 8 grams.[27] [3] At week 12, the end of the first trimester, fingernails emerge, the facial profile gains definition with a distinct chin, and intestines fully migrate from the umbilical cord into the abdomen.[27] All major organs, limbs, bones, and muscles are present, with the liver producing bile and the fetus capable of swallowing and urinating amniotic fluid, evidencing early digestive and urinary system activity.[3] The CRL measures about 61 mm, and weight reaches approximately 14 grams, reflecting accelerated somatic growth.[27]Second Trimester Milestones
The second trimester of human fetal development, encompassing gestational weeks 13 through 27, is marked by rapid physical growth, refinement of organ systems, and the onset of coordinated movements. By the end of week 13, the fetus measures approximately 7-8 cm in crown-rump length and weighs about 23 grams, with ossification of bones beginning in the limbs and vertebrae.[28] Red blood cells start forming in the spleen and liver during week 14, supporting expanded circulation.[28] Bone development accelerates in weeks 15-16, with the skeleton hardening further and the fetus capable of making sucking motions and grasping. Facial features become more defined, including the formation of eyebrows, eyelashes, and nails; the fetus also begins to produce urine, which contributes to amniotic fluid volume.[28] By weeks 16-18, lanugo hair covers the body for temperature regulation, and vernix caseosa, a protective waxy coating, starts forming on the skin.[29] Maternal perception of fetal movement, known as quickening, typically occurs between weeks 16 and 20, though ultrasound detects movements as early as week 7-8; these include kicks, stretches, and somersaults.[28] [29] Sensory development advances with the maturation of the auditory system; by week 18, the fetus responds to external sounds, and by week 24-26, it can distinguish between loud and soft noises, with the inner ear fully formed.[28] Tooth buds appear under the gums, and the genitals are sufficiently developed for ultrasound visualization around week 18-20, allowing determination of sex in most cases.[30] The lungs begin producing surfactant precursors by week 24, a critical step for potential respiratory function post-birth.[28] Fetal viability emerges as a key milestone toward the end of the second trimester, with survival rates for preterm births increasing significantly after 23 weeks. At 23 weeks, survival is approximately 23-27%, rising to 42-59% at 24 weeks and 67-76% at 25 weeks, though with substantial risks of morbidity due to immature organ systems.[31] [32] By week 27, the fetus weighs about 900 grams, has open eyes capable of blinking, and exhibits rapid eye movements during sleep cycles, indicating neurological maturation.[28]Third Trimester Milestones
During the third trimester (weeks 28–40 of gestation), the human fetus undergoes rapid somatic growth, with weight tripling or quadrupling and length increasing by several inches, alongside critical maturation of organ systems to support independent viability post-birth.[11][33] The brain expands fourfold in volume, driven by gyral folding, axonal proliferation, and initial myelination, shifting metabolic priorities toward neural development.[34] Lungs transition to the alveolar stage, with type II pneumocytes ramping up surfactant synthesis from around 24–34 weeks to reduce surface tension and enable air breathing, though full maturity typically occurs by 36 weeks.[35][3] Key growth metrics include: at 28 weeks, average crown-rump length of 14.9 inches (37.9 cm) and weight of 2.7 pounds (1,210 g); by 36 weeks, 18.6 inches (47.3 cm) and 6.2 pounds (2,813 g); reaching term at approximately 20 inches (51 cm) and 8 pounds (3,619 g).[33] Adipose deposition smooths the skin and insulates against temperature loss, while the skeleton ossifies further, with epiphyseal centers appearing in long bones.[36] Viability improves markedly, with ~94% survival at 28 weeks under neonatal intensive care, rising to near 100% by term, contingent on lung and brain maturity.[33] Sensory and motor developments intensify: eyelids open and close by 28 weeks, allowing response to light; the fetus hears external sounds, exhibiting heart rate accelerations to maternal voice or music.[36] Movements become vigorous but less frequent due to spatial constraints, with the majority assuming cephalic presentation by 36 weeks.[11] The central nervous system regulates breathing efforts and thermoregulation, while bone marrow assumes primary erythropoiesis.[36] Fingernails and toenails reach their tips by 34–38 weeks, and lanugo sheds as vernix caseosa protects the skin.[36] These milestones reflect adaptive preparations for birth, with disruptions like preterm delivery risking respiratory distress from immature surfactant.[35]Fetal Physiology
Organogenesis and Functional Maturation
In the fetal stage, which commences at approximately week 9 post-fertilization, organogenesis transitions from foundational formation—largely completed during the embryonic period—to refinement, hypertrophy, and functional maturation essential for postnatal viability.[19] While basic organ rudiments emerge by week 8, the fetal phase emphasizes cellular proliferation, tissue differentiation, and the onset of physiological activities, such as circulation and excretion, preparing systems for independent function after birth.[19] This maturation is contingent on placental support, with fetal circulation bypassing underdeveloped lungs and partially the liver to prioritize oxygenation via maternal blood.[37] The cardiovascular system achieves structural integrity early in the fetal period, with the four-chambered heart fully partitioned by week 8 and capable of rhythmic contractions detectable as early as week 5-6, transitioning to coordinated fetal circulation by week 9.[38] Functional maturation involves shunting blood through the ductus venosus, foramen ovale, and ductus arteriosus, delivering oxygen-rich blood preferentially to the brain and heart while minimizing flow to the non-ventilating lungs.[37] By the third trimester, cardiac output increases substantially, supporting rapid fetal growth, though full adaptation to pulmonary circulation occurs only at birth with these shunts closing.[39] Respiratory organogenesis progresses through distinct phases during the fetal period: the pseudoglandular stage (weeks 5-16) establishes bronchial branching, followed by the canalicular stage (weeks 16-26) where vascularization and primitive alveoli form, enabling limited gas exchange potential.[40] Functional maturation accelerates in the saccular (weeks 26-36) and alveolar (week 36 to term) stages, with type II pneumocytes producing surfactant from around week 24 to reduce surface tension and prevent alveolar collapse postnatally; viability for extrauterine survival hinges on this surfactant synthesis, often immature before 34 weeks.[41] Lungs remain fluid-filled and non-gas-exchanging in utero, relying on amniotic fluid dynamics for growth.[42] Renal and hepatic systems demonstrate early functionality critical for homeostasis. The metanephric kidneys begin urine production by week 10-12, with glomeruli filtering fetal plasma and contributing to amniotic fluid volume, which expands to 800-1000 mL by term to support lung and musculoskeletal development.[43] The liver, initially dominant in hematopoiesis during the embryonic phase, shifts toward metabolic roles in the fetus, producing bile and glucose from week 12 onward, though it remains semifunctional with much nutrient processing deferred to the placenta.[42] By mid-gestation, the gastrointestinal tract matures to permit swallowing of amniotic fluid around week 12, fostering gut motility and meconium accumulation.[43] Neurological maturation underpins sensory and reflexive capabilities, with the central nervous system exhibiting synaptic formation and myelination progressing from the spinal cord upward, enabling fetal movements detectable by week 8-9 and coordinated responses by the second trimester.[4] Endocrine organs, such as the thyroid and adrenals, activate hormone production—thyroid hormone synthesis begins around week 12 to regulate metabolism, while adrenal maturation in the third trimester prepares for stress responses via cortisol surges that aid lung maturation.[21] Overall, functional immaturity in key systems like the lungs and liver underscores the fetus's dependence on maternal physiology until term, with preterm delivery risking deficits in these processes.[44]Neurological and Sensory Development
The human fetal brain undergoes rapid structural and functional maturation during the fetal period, building on embryonic foundations. Neurogenesis, the production of neurons, peaks at 15-16 weeks gestation and persists until the late second trimester, occurring primarily in the subependymal region of the lateral ventricles with maximal rates at 17-18 weeks.[45] Neuron migration follows, with cells traveling from the subventricular zone to the cortical plate via radial and tangential pathways between 12 and 20 weeks.[45] Synaptogenesis, the formation of neural synapses, initiates around 22 weeks and continues postnatally, enabling the establishment of cortical circuits for processing sensory inputs and coordinating movements.[45] Cortical folding commences at approximately 16 weeks, with pronounced morphological changes in the insular cortex and peri-Sylvian regions from 20 to 26 weeks, regions associated with sensory integration and language precursors; frontal lobe gyri, such as the middle and superior frontal, actively fold between 26 and 28 weeks.[46] Overall brain network efficiency and strength increase progressively from 20 to 40 weeks postmenstrual age, transitioning from posterior-dominant (sensorimotor) to more anterior (associative) connectivity.[47] Myelination, the process insulating neural axons for faster signal transmission, begins in the second trimester but accelerates primarily postnatally, with neuroglial proliferation prominent in the third trimester.[45] Somatosensory development, encompassing touch and proprioception, emerges earliest among the senses, with reflexive responses to perioral stimulation (e.g., mouth region) detectable by 7-8 weeks gestation and extending to facial areas, palms, soles, and limbs by 11-13 weeks, as evidenced by twin interactions and body self-touch.[48] Physiological somatosensory responses are recordable by 14 weeks, supporting hierarchical processing in the somatosensory cortex by 20-26 weeks as layer IV differentiates.[49][50] Auditory capabilities develop with cochlear functionality by 20-22 weeks, enabling sound detection; initial heart rate and movement responses to tones (e.g., 500 Hz) occur around 19 weeks, progressing to discriminatory reactions to maternal voice or specific phonemes like "LA" by 25 weeks, with broader responsiveness from 21-33 weeks.[51][48][52] Visual system maturation includes eye movements starting at 16-18 weeks, eyelid opening at 23-24 weeks, and initial light detection thereafter; pupils constrict and dilate by 31 weeks, permitting directed responses to visual stimuli under adequate illumination, though full acuity refines postnatally.[48][53][54] Gustatory and olfactory senses functionalize in the second trimester, as fetuses swallow amniotic fluid containing flavor compounds from maternal diet, with evidence of chemosensory discrimination by mid-gestation; olfactory processing contributes to responsiveness by 21-33 weeks.[48][55]Evidence of Fetal Pain and Responsiveness
Nociceptors, specialized sensory receptors for detecting potentially harmful stimuli, begin forming in the human fetus as early as 7 weeks gestation, with functional spinal reflex pathways established by 11-12 weeks, enabling withdrawal responses to noxious touch.[56] By 12 weeks, thalamic projections to the subplate zone— a transient structure beneath the developing cortex—emerge, potentially supporting rudimentary sensory processing akin to thalamocortical functions observed in preterm neonates.[57] These developments allow for behavioral responses such as limb flexion or head turning away from invasive stimuli during procedures like amniocentesis, as documented in ultrasound observations.[58] Fetal responsiveness to external stimuli manifests progressively. Auditory responses, including heart rate acceleration and movement cessation, are detectable from 19 weeks, while visual responses to light emerge around 26-28 weeks, coinciding with eyelid opening and retinal maturation.[59] Tactile sensitivity increases with skin innervation; by 14-15 weeks, the fetus exhibits coordinated movements and stress hormone elevations (e.g., cortisol) in reaction to needle insertions during fetal blood sampling, indicating physiological arousal.[60] Electroencephalographic (EEG) patterns resembling adult-like sensory processing appear in preterm infants as young as 22-24 weeks, suggesting capacity for stimulus discrimination beyond mere reflexes.[61] The capacity for conscious pain perception remains contested, hinging on whether subcortical circuits suffice or if thalamocortical connections—maturing between 23-30 weeks—are requisite for the affective dimension of pain.[62] Proponents of earlier sentience cite preterm neonate data, where infants at 21-23 weeks display behavioral, hormonal, and autonomic pain indicators during procedures, implying analogous in utero capability absent cortical maturity barriers.[61] [63] Conversely, reviews emphasizing cortical necessity argue that integrated pain experience requires thalamocortical axons reaching the cortical plate by 24-28 weeks, as subplate activity alone may not confer qualia.[64] [57] Empirical challenges include ethical limits on direct fetal testing, reliance on indirect measures like fetal magnetocardiography showing stress desynchronization by 20 weeks, and observations of fetal opioid administration reducing distress in surgeries.[58]| Gestational Age | Key Development | Evidence Type |
|---|---|---|
| 7-8 weeks | Nociceptor formation and initial sensory nerves | Histological studies[56] |
| 11-12 weeks | Spinal withdrawal reflexes; subplate projections | Ultrasound and neuroanatomical tracing[59] [57] |
| 14-20 weeks | Hormonal stress responses to invasive stimuli; coordinated movements | Blood sampling procedures; cortisol assays[60] |
| 23-28 weeks | Thalamocortical connections; EEG sensory patterns | Neuroimaging in preterms; fetal EEG[61] [62] |