{
  "id": "pregnancy",
  "title": "Pregnancy",
  "lang": "en",
  "source_lang": "en",
  "summary": "Pregnancy is the period from conception to birth in which an embryo and fetus develop inside the mother's body, typically lasting about 40 weeks in humans.",
  "category": "health",
  "subcategory": "anatomy-physiology",
  "type": "concept",
  "aliases": [
    "gestation",
    "gravidity",
    "prenatal period"
  ],
  "generated_at": "2026-10-15",
  "model": "pro/claude-haiku-5-5",
  "url": "https://aiwiki.page/en/pregnancy/",
  "translations": {
    "zh-Hans": {
      "url": "https://aiwiki.page/zh/pregnancy/",
      "json": "https://aiwiki.page/zh/pregnancy.json"
    }
  },
  "sections": [
    {
      "heading": "",
      "text": "Pregnancy is the condition in which a developing embryo and then a fetus grow inside the uterus of a female mammal. In humans it begins with fertilization of an egg in the fallopian tube and ends with birth, a span usually counted as about 40 weeks from the first day of the last menstrual period. It is one of the central processes of biology and of human reproduction, and it reshapes nearly every organ system of the mother. Its outcome also depends on health systems, social conditions and law, which makes pregnancy a major subject for medicine, public health and the social sciences.\n\nThe entry first defines the terms used to count and classify pregnancies and then follows the biological sequence: conception, implantation, the formation of the placenta, and the embryonic and fetal stages of development. It then covers the changes in the mother's body, the methods used to confirm and monitor a pregnancy, and the influences of nutrition, environment and infection. Complications, labor, delivery and the postpartum period are treated next, followed by global patterns of maternal and infant outcomes, the history of scientific understanding, assisted conception, legal and ethical questions, cultural practices, and open research problems."
    },
    {
      "heading": "Definition and Dating of Pregnancy",
      "text": "In the strict biological sense, pregnancy is the interval from conception, the fertilization of an ovum, to birth. Clinical practice, however, does not start the count there. Gestational age in obstetrics refers to the time since the onset of the last menses, which on average is fertilization age plus two weeks. The two timelines therefore describe the same pregnancy from different starting points, and the gap between them is a convention, not a measurement error.\n\nThe offset exists because the menstrual period is easy to date, while conception usually cannot be observed. Ovulation and conception occur in the middle of the menstrual cycle, so the gestational clock starts approximately two weeks before conception. The arithmetic assumes a regular cycle of about 28 days, and both longer and slightly shorter cycles are considered normal. For this reason, dating based on the last menstrual period (LMP) is adjusted when cycles are irregular. The standard due date is calculated by adding 280 days to the LMP for a 28-day cycle, and adjusted for cycles of other lengths. When other information is lacking, ultrasound measurements of the fetus in the first trimester give the most accurate estimate of gestational age. In the first trimester, crown-rump length, the measurement from the top of the fetal head to the bottom of the torso, is commonly used for estimating gestational age. If an early scan conflicts with the LMP date, it is still the one from the early ultrasound that is used for the rest of the pregnancy.\n\nPregnancies conceived with assisted reproduction can be dated directly. If the pregnancy is conceived by in-vitro fertilization, project gestational age is calculated from the date of embryo transfer and the embryo age at transfer. The embryo's age is then added to that date, which gives a more precise count than the LMP method.\n\nBirth timing is classified by completed weeks. The World Health Organization defines preterm birth as any birth before 37 completed weeks of gestation, or fewer than 259 days since the first day of the woman's last menstrual period. Within this category, the WHO also separates extremely preterm (< 28 weeks) and very preterm (28 to < 32 weeks) births, among other subgroups. Births after the 37th week fall within the term range, but the term range itself has been subdivided. In 2013 the American College of Obstetricians and Gynecologists recommended that the label \"term\" should be replaced with the designations early term (≥37 0/7 and ≤38 6/7 weeks gestation) and full term (≥39 0/7 and ≤40 6/7 weeks gestation). Late-term pregnancy covers 41 0/7 to 41 6/7 weeks' gestation. A birth at or beyond 42 weeks is classified as post-term, defined as live birth after the completion of 42 weeks of pregnancy (≥ 42 0/7 weeks' gestation).\n\nThe division of pregnancy into trimesters, usually three blocks of roughly 13 to 14 weeks, is a counting convention used in clinical care, screening schedules and legal drafting. It is not a biological boundary. Embryonic and fetal development proceed continuously, and changes such as the transition from embryo to fetus or the onset of fetal movement do not coincide neatly with the cut points between trimesters. Clinicians use the trimester labels to organize visits, tests and risk assessment, and the exact boundaries vary somewhat between guidelines."
    },
    {
      "heading": "Conception and Implantation",
      "text": "Fertilization normally occurs in the ampulla, the wide middle section of the fallopian tube, within about a day after ovulation. A single sperm penetrates the secondary oocyte, and the oocyte's block to further sperm entry (the zona reaction) prevents polyspermy. The two haploid nuclei then fuse, restoring the diploid chromosome number. The resulting zygote carries a new combination of maternal and paternal DNA, and its first mitotic divisions begin while it is still moving down the tube. Because the zygote is not growing in mass during these early divisions, the cells become progressively smaller with each cleavage.\n\nAfter several days of cleavage, the embryo forms a solid ball of cells called the morula. The morula enters the uterus after three or four days, and a cavity called the blastocoel forms within it, producing the blastocyst. Cells of the morula begin to differentiate, and the morula changes into the blastocyst by pumping fluid to grow a lumen. The blastocyst stage occurs between 5 and 9 days after conception. Before it can attach to the uterus, the embryo must shed its protective coat: the blastocyst is still enclosed in the egg-coat known as the zona pellucida, and to be able to implant into the uterine wall it must rid itself of this covering.\n\nLineage separation\n\nThe first differentiation event divides the blastocyst into two populations. The blastocyst contains the inner cell mass that will go on to develop into the embryo proper, and an outer cell layer of trophoblasts that will develop into the extraembryonic membranes. The outer layer, the trophectoderm, is controlled by transcription factors such as CDX2, while the inner cell mass depends on OCT4 and NANOG. The formation of the trophectoderm represents the first lineage of the precursor for all trophoblast cells, which segregates the inner cell mass and eventually gives rise to the embryo proper. Later, the inner cell mass splits into the epiblast, which forms the embryo itself and the amnion, and the hypoblast, which contributes to the yolk sac. Trophoblast cells, in contrast, become the source of the placenta, which is treated in the next section.\n\nAttachment and invasion\n\nImplantation proceeds in stages: apposition, attachment and invasion. At 6–7 days after fertilization, the interaction of the polar trophectoderm with the uterine luminal epithelium, which has become decidualized, leads to implantation. Attachment depends on adhesion molecules, including integrins and L-selectins, that bind the trophoblast to the endometrial surface. The uterus is receptive only during a narrow window, which is linked to the secretory phase of the menstrual cycle. Receptivity is shaped by factors such as leukemia inhibitory factor (LIF), which is secreted by the endometrial luminal epithelium. Pinopodes, protrusions on the tips of uterine epithelial cells, appear around 5–7 days after fertilization and are associated with LIF expression.\n\nOnce attached, the syncytiotrophoblast, the invasive layer, digests the endometrium. It synthesizes proteolytic enzymes such as serine proteases, metalloproteinases and collagenases that break down the basement membrane of the endometrial epithelium, allowing the blastocyst to enter fully. The invading trophoblast then reaches the maternal blood supply. The decidualization of the endometrium is finalized as the process concludes. Invasion by the trophoblast allows the embryo to exchange materials with maternal blood, while maternal tissue is remodelled around it.\n\nImplantation failure and early loss\n\nImplantation is inefficient, and many conceptions are lost before a missed menstrual period is noticed. Up to 15% of all clinically recognized pregnancies end in miscarriage, and approximately 50–60% of early pregnancy losses may be attributed to fetal chromosomal abnormalities. Abnormal chromosome number, especially trisomy, is the most common finding. Failure to implant is also a major cause. Repeated implantation failure is generally defined as the failure of pregnancy establishment after three or more failed IVF attempts, or repeated transfer of more than ten morphologically good embryos to a recipient uterus. Among these cases, a high frequency of chromosomal aneuploidy is now well established as a major cause. Endocrine, uterine and immunological factors are also implicated, and the balance among them is still being studied.\n\nHormonal signalling and the embryo-maternal interface\n\nEarly trophoblast differentiation has a direct hormonal consequence. Around the eighth day, some trophoblastic cells differentiate into cells called the syncytiotrophoblast. These cells produce the hormone human chorionic gonadotropin (hCG), which signals the corpus luteum to continue progesterone production and is the basis of pregnancy testing. The first cell types to form from the trophectoderm, the cytotrophoblast and the primitive syncytium, establish the foundation of the placenta. The transition from a structure that merely lies in the uterus to one that communicates with maternal tissue is therefore a process of cell differentiation as much as of physical attachment."
    },
    {
      "heading": "Placenta, Membranes and Umbilical Cord",
      "text": "Origin and structure of the placenta\n\nThe placenta is a mixed organ. Its fetal part develops from the trophoblast, the outer cell layer of the early embryo that gives rise to the extraembryonic tissues. Its maternal part comes from the endometrium, which transforms into the decidua under the influence of progesterone. Decidualization starts in the mid-secretory phase of the menstrual cycle, responds to rising progesterone, and acts mainly through the progesterone receptor. Once the blastocyst implants, the trophoblast differentiates into two principal layers. The outer syncytiotrophoblast is a multinucleated layer formed by cell fusion, and the underlying cytotrophoblast contributes cells to it. The fetal compartment is formed by extraembryonic trophoblast cells that proliferate and differentiate into distinct lineages with specialized roles.\n\nPlacental tissue grows into chorionic villi. Floating villi are bathed in maternal blood, while anchoring villi attach to the decidua through columns of cytotrophoblast cells. During the early phases of placentation the trophoblastic shell gives rise to the second differentiated trophoblast cell type, the invasive extravillous trophoblasts. These cells invade the maternal tissue and remodel the uterine arteries. Spiral artery remodeling begins around the eighth week, and the process is essential for adequate blood supply. Maternal blood volume rises by about 50 percent during pregnancy and uterine blood flow increases 10- to 12-fold, largely because trophoblast cells open the spiral arteries into blood-filled intervillous spaces. Failure of this remodeling is implicated in preeclampsia and intrauterine growth restriction (see Pregnancy complications for details).\n\nMaternal–fetal exchange\n\nThe placenta is hemochorial: maternal blood directly bathes the syncytiotrophoblast, and this surface is the main site of exchange. The syncytiotrophoblast forms the interface between mother and fetus for nutrient transport and gas exchange in floating villi. Oxygen and carbon dioxide diffuse across the thin barrier, while glucose and amino acids are carried by specific transporters, and lipids and cholesterol are moved by receptor-mediated pathways. Waste products move in the opposite direction. Maternal and fetal blood never mix, because fetal blood flows through capillaries inside the villi and is separated from maternal blood by the trophoblast layer. Immunoglobulin G is transported actively across the barrier by the neonatal Fc receptor, which explains the transfer of maternal antibodies that protect the newborn during early life (see Antibody). The barrier is selective rather than absolute, and certain pathogens and drugs can still cross it.\n\nEndocrine function\n\nThe placenta is also an endocrine organ. It releases hormones in pregnancy that are essential for sustaining the pregnancy and facilitating the growth of the fetus. Its first product is human chorionic gonadotropin (hCG), which is secreted by the early trophoblast. hCG keeps the corpus luteum functioning during the first weeks of gestation, so that the ovary keeps producing progesterone. In humans, the placenta takes over progesterone synthesis from about 6 to 8 weeks of gestation until labor. The placenta also secretes estrogens, which promote uterine growth, prepare the mammary glands, and later support uterine contractility. Human placental lactogen (hPL), a polypeptide produced by the syncytiotrophoblast, is detected in maternal circulation after 3–6 weeks of gestation, increases throughout gestation and disappears after placental delivery. hPL promotes glucose availability for the fetus by raising maternal insulin resistance, a function that links placental hormones to metabolic adaptation (see Hormone and Insulin). Hormone levels fall rapidly after delivery of the placenta, which is one of the signals that initiates lactation.\n\nAmniotic sac and amniotic fluid\n\nThe fetus lies within the amniotic sac, a membrane that originates from the epiblast and forms the innermost enclosure of the amniotic cavity. The amnion is avascular, and it is filled with amniotic fluid. The outer membrane, the chorion, contributes to the placental disc. Amniotic fluid cushions the fetus against external mechanical forces and allows free movement, which is necessary for normal musculoskeletal development. It also maintains a stable temperature and helps prevent umbilical cord compression. Fetal swallowing and urination continuously renew the fluid, and fetal lungs take up and expel fluid rhythmically, a process that contributes to pulmonary development. Abnormal fluid volumes, either excessive or insufficient, are clinically significant and are monitored by ultrasonography (see Ultrasonography).\n\nUmbilical cord\n\nThe umbilical cord connects the fetus to the placenta and has a simple but specialized structure. It contains two umbilical arteries, which carry deoxygenated blood from the fetus to the placenta, and one umbilical vein, which returns oxygenated blood. The umbilical cord is made up of amniotic membrane, Wharton's Jelly and blood vessels. The vessels are embedded in Wharton's jelly, a mucoid connective tissue that supports them. This tissue cushions the vessels and protects them from compression, torsion and bending. This mechanical protection is important, because the cord has to remain patent during fetal movement and uterine contractions. Compression of the cord can reduce fetal oxygen supply, which is why cord problems are a recognized cause of fetal distress during labor.\n\nThe cord also forms the connection through which the placenta exchanges materials with the fetal circulation. Its vessels carry the fetal share of nutrients and waste, while the Wharton's jelly and amniotic epithelium serve as a barrier and a structural framework. At birth, the cord is clamped and cut, and the remaining stump dries and falls off within a few weeks."
    },
    {
      "heading": "Embryonic Period: Organogenesis",
      "text": "Timing and scope\n\nThe embryonic period runs from the start of gestational week 4 to the end of week 8. Organogenesis, the formation of all major organs, occurs during this period. Gestational weeks are counted from the last menstrual period, so this window corresponds to roughly weeks 3 to 8 after fertilization, the figure most often cited in the teratology literature. This 3–8 week period is the time of organogenesis when the anlage of each organ system is formed. By the end of the period the embryo has acquired a recognizably human outline. The later fetal period, from about week 8 to birth, mainly involves growth and refinement of structures that already exist.\n\nNeural tube, heart and circulation\n\nThe nervous system is among the first systems to form. Around day 18 of development, the dorsal ectoderm above the notochord thickens into the neural plate. Its edges rise into neural folds, which meet along the midline and fuse, so that the flat plate becomes a hollow tube. The folds meet and fuse along the dorsal midline, zippering shut between roughly days 22 and 28. The cranial end closes first, by about day 25, and the caudal end by day 28. Cranial neuropore closure is completed by day 25, whereas the caudal neuropore closes on day 28. The tube gives rise to the brain and spinal cord. Neural crest cells detach from the closing seam and go on to form much of the peripheral nervous system and most of the face. Closure is one of the most error-prone events of early development: neural tube anomalies are among the most common birth defects worldwide, varying from 0.5 to 10 per 1000 pregnancies. Failure at the cranial end produces anencephaly, and failure at the caudal end produces spina bifida. Because closure is finished before many people know they are pregnant, neural tube defect prevention is best achieved by adequate daily folic acid intake throughout the reproductive years.\n\nThe heart is the first organ to function. A simple heart tube forms from mesoderm, begins to beat in the fourth week, and then folds and partitions into chambers and valves through the following weeks. Early circulation depends on the yolk sac and umbilical vessels, since the definitive placenta is not yet mature. Chorionic villi begin forming by week 3, and the hemochorial placenta—where maternal blood directly bathes trophoblasts—is established by week 8–10. Congenital heart defects are among the most frequent organ-level malformations, and they arise from disruptions to the septation and valve formation that occur in this window.\n\nLimb buds and facial structures\n\nLimbs begin as small outgrowths from the lateral plate mesoderm. Classic fate-mapping experiments in chick embryos showed that cells in this tissue are already positioned to form limbs at a very early stage. Cells in distinct regions of the lateral plate mesoderm are in position to form the limbs as early as the 2-somite stage. Outgrowth of the bud depends on a feedback loop between the underlying mesoderm and the overlying ectoderm. Initial outgrowth of the limb is driven by the Fgf10-Fgf8 feedback loop that operates between the mesoderm and overlying apical ectodermal ridge.\n\nThe face is built around a set of swellings, including the frontonasal prominence and the pharyngeal arches, which are populated largely by neural crest cells. The palate and lip close by fusion of these processes. Clefts of the lip and palate are therefore disorders of fusion within a narrow developmental window. The critical period for most structural defects, including limb malformations and orofacial clefts, is described as the 3rd to 6th week of human embryonic development.\n\nSensitivity to teratogens\n\nThe embryonic period is the most vulnerable stage for structural malformation because organ primordia are forming and dividing rapidly. Almost no defects are predicted to occur prior to the beginning of the 3rd week and a rapidly declining occurrence is observed at the conclusion of the eighth week. Exposure before about week 3 tends to act in an all-or-none manner, killing the embryo or slowing its growth without leaving structural defects. They result in death of the embryo or a generalized slowing of its growth from which it recovers while exhibiting no structural abnormalities.\n\nSensitivity is organ-specific rather than uniform. Each organ has its own window of vulnerability, and some organs such as the brain are sensitive throughout fetal development. Several well-documented examples illustrate this. The sedative thalidomide caused severe limb reduction when taken during the window of limb formation, which is the example that established teratology as a discipline. During the window of susceptibility, teratogens such as thalidomide can severely damage critical milestones of embryonic development. Phenytoin is associated with fetal hydantoin syndrome and facial clefts when taken during organogenesis. Prenatal exposure to alcohol can cause fetal alcohol syndrome, and maternal rubella infection can damage the developing heart, eyes and ears. Valproate is associated with neural tube defects, which is why women taking it are advised to take folic acid before and during pregnancy. Maternal excess glucose has been shown to decrease the expression of Pax3, a gene required for neural tube closure, and to increase the risk of neural tube defects.\n\nA key complication is that the teratogen window and placental protection do not overlap. The placenta's barrier is immature during organogenesis, so the embryo is exposed to substances that a mature placenta would partly filter. The critical period of placental vulnerability in mice aligns with human weeks 2–8, when organogenesis occurs and placental barriers are immature.\n\nAxes, segments and gene regulation\n\nBody plan formation relies on a sequence of signals. Classically, the embryo was thought to become sensitive only after organs began to differentiate, but evidence now shows that the body axes are set earlier. It is generally agreed that the first axes to form are the A-P and D-V axes. The anteroposterior (head-to-tail) and dorsoventral (back-to-belly) axes are specified at the blastocyst stage, around days 4 to 5, and the left-right axis is then assigned using cues from the other two.\n\nOnce the axes exist, the embryo is subdivided into repeated units and organized into signaling centers. The first somites, the paired blocks that will become vertebrae, ribs and muscles, appear at about day 20. Signaling molecules called morphogens create concentration gradients that tell cells their position. In the limb, Sonic hedgehog (Shh) is secreted from a cluster of cells in the distal posterior limb bud mesoderm called the zone of polarizing activity (ZPA) and regulates AP expansion and patterning. At the distal tip, fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal axis. These two centers maintain each other through a reciprocal loop.\n\nPositional information is also encoded by gene expression patterns. The genes of the Hox family provide a positional code along the body's long axis, and the expression of Hox genes is influenced by the distribution of retinoic acid (RA), which is higher in anterior regions of the elongating trunk compared with posterior regions. Much of the detailed molecular evidence comes from mouse, chick and other model animals, and the mechanisms are still being refined."
    },
    {
      "heading": "Fetal Period: Growth and Maturation",
      "text": "From embryo to fetus\n\nThe fetal period begins once the basic body plan is in place. Clinical sources differ on the exact week because some count from fertilization and others from the last menstrual period. Week 9 of gestation is about seven weeks after conception, so the embryonic period ends at roughly 8 weeks after fertilization. The change from embryo to fetus signifies that all the major organs, muscles, and nerves have begun to form. From that point on, the focus shifts to large-scale growth and refinement.\n\nAt the start of the fetal period the body is still small. Crown-to-rump length is about 22 to 23 millimeters, and the weight is only 2 to 7 grams. Body proportions change rapidly. The head remains large relative to the rest of the body, and the features are becoming more recognizable. Over the following months, the limbs lengthen and the head's share of body length falls, while weight accumulates mainly in the second half of pregnancy and especially in the third trimester.\n\nMovement, senses and sex differentiation\n\nMovement begins well before the mother can feel it. The baby makes spontaneous movements and can wiggle the newly formed arms and legs, sometimes bringing the hands toward the face. Maternal perception of movement (quickening) usually occurs around the middle of pregnancy.\n\nSensory structures appear in sequence. The eyes are formed, but the eyelids remain fused and do not open for some time. The mouth, tongue, and the first taste buds are developing. The auditory system matures over the second half of pregnancy, and the fetus responds to sound by the late second and third trimesters.\n\nGenetic sex is fixed at fertilization, through the sex chromosomes, and the gonads then direct differentiation. The external genitalia begin from a common precursor. By 8 to 9 weeks, the genital tubercle forms, and it develops into a penis or clitoris as pregnancy advances. Clear external signs of sex appear by weeks 13 to 14.\n\nBrain and lungs\n\nBrain development accelerates during the fetal period. From week nine, the choroid plexus begins to produce cerebrospinal fluid, which expands the ventricular system of the brain. Neuron production, migration and the folding of the cerebral cortex continue into the third trimester.\n\nLung maturation is the main constraint on survival after early birth. Airways branch during the embryonic and early fetal periods, but the alveoli that exchange gas develop mainly later, and surfactant production rises in the third trimester. For this reason, infants born before about 28 weeks often have respiratory immaturity and chronic lung disease.\n\nViability\n\nViability is better understood as a probability that rises week by week than as a threshold that switches on at a fixed date. Medically, it is a probability that rises week by week, not a switch that flips on a specific date. In industrialized nations, the periviability interval is generally described as roughly 22 to 25 weeks of gestation, during which survival is possible but depends on intensive technology. The World Association of Perinatal Medicine defined viability in terms of maturity to survive the neonatal period with available medical support.\n\nReported survival figures vary with the cohort and the level of care. A British Columbia cohort reported live-birth survival rising from about 6% at 22 weeks to 81% at 25 weeks. Estimates for 23 weeks vary widely, with one review giving survival between 8 and 54 percent at 23 weeks. Antenatal corticosteroids are among the interventions associated with better outcomes in extremely preterm infants, and survival without severe disability remains substantially lower than survival alone. Decisions in this range involve counseling and parental consent, which should be sought prior to any intervention.\n\nAssessment of fetal size and growth\n\nGrowth is assessed mainly by ultrasound biometry. The measurements most commonly used are the biparietal diameter, head circumference, abdominal circumference and femur length. Percentiles have been established for each parameter, and fetal weight can be calculated from them. Accurate dating is a prerequisite for interpretation. An early ultrasound, ideally at 8 to 13 weeks, is more accurate for estimating gestational age than a scan performed later. Ultrasound dating is accurate only to about three weeks when performed at term.\n\nFetal growth restriction (FGR) is commonly defined by an estimated fetal weight below the 10th percentile for gestational age. Severe growth restriction is defined as estimated fetal weight below the third percentile. In 2020 the Society for Maternal-Fetal Medicine added an abdominal circumference below the 10th percentile as a diagnostic criterion, which was quickly adopted by the American College of Obstetricians and Gynecologists in February 2021. Fetal asymmetry does not predict complications and is no longer a recommended criterion. Growth restriction diagnosed before 32 weeks is typically more severe, and it accounts for a substantial share of cases.\n\nSmallness does not always mean pathology. About 70 percent of fetuses with a birth weight below the 10th percentile are constitutionally small, while in the remaining 30 percent the cause is pathologic. Pathological causes include maternal, placental, or fetal factors that prevent the fetus from reaching its expected growth potential. Doppler velocimetry of the umbilical artery is used alongside biometric measurements. Abnormal growth in either direction carries risk: growth restriction significantly increases the risks of intrauterine death, neonatal morbidity and neonatal death. Excessive fetal growth, by contrast, is associated with maternal hyperglycemia, as in gestational diabetes."
    },
    {
      "heading": "Maternal Physiological Adaptation",
      "text": "Blood volume, cardiac output and blood pressure\n\nThe maternal circulation expands more than in most other normal physiological states. Plasma volume rises from early pregnancy and typically increases by about 40 to 50 percent by the third trimester, while red cell mass increases by a smaller proportion, roughly 20 to 30 percent. This disproportion dilutes the hemoglobin concentration, which underlies the so-called physiological anemia of pregnancy and explains why reference values for hemoglobin are lower than in the non-pregnant state. Cardiac output rises by roughly 30 to 50 percent above non-pregnant levels, through a larger stroke volume and a resting heart rate that is commonly 10 to 20 beats per minute higher. Output generally reaches its peak around 20 to 24 weeks and then plateaus.\n\nBlood pressure follows a different course. Systemic vascular resistance falls substantially, which lowers mean arterial pressure during the first half of pregnancy. Diastolic pressure is usually lowest in the second trimester and then returns gradually toward pre-pregnancy values by term. Because this drop is normal, a sustained rise in blood pressure after mid-pregnancy is a clinically significant change, and it is the starting point for evaluating hypertension in pregnancy, as described elsewhere in this entry.\n\nRespiratory and renal changes\n\nOxygen consumption increases by roughly 15 to 20 percent over the course of pregnancy, reflecting the combined needs of the mother, uterus, placenta and fetus. Minute ventilation rises by about 40 to 50 percent, achieved mainly through a larger tidal volume rather than a faster breathing rate. Progesterone is thought to stimulate the respiratory centre, lowering the arterial partial pressure of carbon dioxide to around 30 mmHg. The kidneys compensate by excreting bicarbonate, producing a state of compensated respiratory alkalosis. As the uterus enlarges, the diaphragm is pushed upward and functional residual capacity falls, which can cause breathlessness on exertion even in healthy women.\n\nThe kidney adapts to the expanded plasma volume and to the metabolic demands of pregnancy. Renal plasma flow and glomerular filtration rate both rise substantially, the latter by about 50 percent, and this increase is largely established in the first trimester. As a result, serum creatinine and urea concentrations fall, so that values normal outside pregnancy may indicate reduced filtration during gestation. Because the filtered glucose load increases, mild glycosuria is common and is not by itself diagnostic of diabetes. Progesterone-related dilation of the ureters, together with bladder compression by the uterus, contributes to urinary frequency and to a higher risk of urinary-tract-infection. Sodium and water retention expand the extracellular fluid volume.\n\nMetabolic changes\n\nBasal metabolic rate rises modestly, by roughly 10 to 20 percent in later pregnancy. The total energy cost of gestation is often estimated at around 80,000 kcal, covering fetal tissue, placenta, uterine growth and maternal fat stores. Metabolism changes in phases. In the first half of pregnancy, maternal fat deposition is favoured and insulin sensitivity is relatively preserved. From the second trimester onward, placental hormones, including human placental lactogen, progesterone, cortisol and placental growth hormone, induce insulin resistance in maternal tissues. This shifts circulating glucose toward the fetus, which takes up glucose by facilitated transport that does not depend on insulin. The mother increasingly uses lipolysis, free fatty acids and ketone bodies as fuel, and fasting periods become shorter, which makes ketosis more likely. When pancreatic insulin secretion cannot compensate for this resistance, glucose tolerance falls, which provides the physiological basis of gestational-diabetes and of the broader diabetes-mellitus risk discussed in this entry.\n\nMusculoskeletal and postural changes\n\nHormones, notably relaxin and progesterone, increase the laxity of ligaments and the fibrocartilage of the pubic symphysis, which widens in late pregnancy. The exact role of relaxin in human pregnancy is less fully characterised than in some other mammals. The enlarging uterus moves the centre of gravity forward and upward, prompting a compensatory increase in lumbar lordosis, a wider stance and an altered gait. The abdominal muscles stretch, and separation of the rectus abdominis occurs in many women. Lower back and pelvic girdle pain are common and reflect these changes together with increased spinal load. In the supine position after mid-pregnancy, the uterus can compress the aorta and inferior vena cava, reducing venous return and cardiac output, which is why a left lateral position is commonly advised in later pregnancy."
    },
    {
      "heading": "Hormonal Regulation and Maternal-Fetal Immune Tolerance",
      "text": "Hormones that sustain the pregnancy\n\nEarly pregnancy depends on a hand-off between two hormone sources. The first signal comes from the embryo's outer layer. Human chorionic gonadotropin (hCG), made by the cells that will form the placenta, acts on the corpus luteum, the ovarian structure left behind after ovulation. Without that rescue, the corpus luteum would normally regress within about two weeks, as it does in a non-pregnant cycle. If a pregnancy occurs, then the pregnancy hormone (hCG) keeps the CL alive and its progesterone supports the pregnancy for the next 6–8 weeks until the placenta takes over and the corpus luteum disappears. Blood levels of hCG become measurable roughly two to three weeks after conception and climb to a peak around the eleventh to thirteenth week before declining. In normal pregnancies, detectable levels of hCG begin to appear in the maternal circulation at about 2–3 wks after conception, and reach their peak at ~11–13 wks before declining significantly in the later stages of pregnancy.\n\nThe main hormone of early pregnancy is progesterone. Cells of the syncytiotrophoblast use maternal cholesterol to make it, and the placenta gradually assumes this role. Sources differ on the timing of the handover. One study describes the corpus luteum as the main source until about the sixth week, If conception occurs, the levels of progesterone are maintained at mid-luteal levels by the corpus luteum until about the sixth week. At that time the placenta becomes the main source of progesterone and levels rise from approximately 10-50 ng/mL in the first trimester to 50-280 ng/mL in the third trimester. Another reports that the two sources contribute equally at about the eighth and a half week. Progesterone keeps the myometrium quiescent, and it stabilizes the decidualized endometrium, which nourishes the embryo before the placenta is fully functional. Estrogen rises alongside it. The placenta converts weak androgens from the maternal and fetal adrenal glands into estrogens, and levels climb steadily, increasing 30-fold by childbirth. Estradiol also boosts uteroplacental blood flow, which the growing placenta depends on.\n\nPreparing the uterus, breasts and cervix\n\nThe same hormonal framework that sustains pregnancy gradually shifts the tissues toward delivery and feeding. Progesterone is the principal brake on labor; it promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Near the end of gestation, labor is thought to begin through functional progesterone withdrawal, which raises the estrogen-to-progesterone ratio. Estrogen then increases oxytocin receptors and gap junctions in the myometrium, allowing coordinated contractions. Prostaglandins contribute to both contraction and cervical softening. As a result of these changes, the uterine cervix becomes soft and vulnerable to dilation. Relaxin, another placental hormone, also contributes; in one summary it softens the ligaments in all joints in the body and assists cervical ripening and dilation.\n\nIn the breast, prolactin is the main driver of tissue growth. The level of circulating prolactin begins to increase, eventually rising to approximately 10–20 times the pre-pregnancy concentration. Estrogen and progesterone work alongside it to expand the glandular tissue. Progesterone, however, holds back milk secretion, so lactation does not begin until the placental hormones fall after delivery. Early breastfeeding then stimulates prolactin and oxytocin release further, which is why the timing of hormone withdrawal and suckling matters.\n\nWhy the maternal immune system tolerates the fetus\n\nThe fetus carries paternal antigens and so is partly foreign to the mother. The placenta is an unusual interface. Extravillous trophoblasts, the invasive cells that anchor the placenta in the uterine wall, display an atypical set of human leukocyte antigen (HLA) molecules. Their surface shows HLA-C, HLA-E, HLA-F and HLA-G rather than the full repertoire found on most cells, which limits the signals that maternal T cells and natural killer (NK) cells use to recognize them. HLA-G is central here. It binds inhibitory receptors on decidual NK cells, and EVT-expressed HLA-G can inhibit dNK cytotoxic and killing effects by binding to their inhibitory receptor killer cell Ig-like receptor 2DL4 (KIR2DL4).\n\nDecidual NK cells are the most numerous immune population in the decidua, the transformed endometrium. Other tolerance mechanisms reinforce this. Regulatory T cells migrate to the interface and dampen NK activity through anti-inflammatory cytokines such as TGF-β and IL-10. Decidual stromal cells use indoleamine 2,3-dioxygenase and prostaglandin E2 to restrain NK proliferation and interferon-γ output. Trophoblast cells can also trigger death in activated maternal T cells that carry the Fas receptor. Human chorionic gonadotropin itself has immunomodulatory effects. Newer work describes the interface as an actively regulated site where tolerance and defense coexist, rather than a simple zone of suppression. Decidual NK cells can secrete inflammatory and angiogenic cytokines when stimulated by HLA-G, which supports placental vessel formation and invasion. Immune tolerance is therefore not a passive shield but a balance of restraint and controlled activation within the immune system.\n\nWhen hormonal or immune balance fails\n\nDisruption of these systems is linked to several pregnancy disorders. Reduced HLA-G expression and weakened regulatory signaling between trophoblast and decidual NK cells have been proposed as one mechanism of recurrent miscarriage. Luteal phase deficiency, in which progesterone output is too low, is associated with infertility and spontaneous abortion. In ectopic pregnancy, reduced hCG production appears to impair corpus luteum function, which may be part of why the pregnancy cannot be sustained normally. At the other extreme, high serum hCG in mid to late pregnancy has been associated with preeclampsia, intrauterine growth restriction and Down syndrome. Immune dysfunction at the placenta has likewise been associated with preeclampsia, growth restriction and preterm birth."
    },
    {
      "heading": "Confirmation and Diagnosis",
      "text": "Early symptoms of pregnancy are nonspecific. The most typical are a missed menstrual period, breast tenderness and enlargement, nausea with or without vomiting, fatigue, increased urinary frequency, and altered food preferences. Some women notice light spotting or cramping around the time of implantation. These symptoms overlap with premenstrual syndrome, stress, intercurrent illness, thyroid disorders and ordinary variation in cycle length, so none of them confirms a pregnancy on its own. Confirmation therefore depends on laboratory and imaging methods.\n\nPregnancy tests\n\nPregnancy tests detect human chorionic gonadotropin (hCG), a hormone produced by the trophoblast cells that begin to form the placenta after implantation. In early pregnancy its concentration in blood roughly doubles every one to two days, which is why its level rises quickly and why serial measurements are informative. Urine tests, including common home kits, are designed to detect hCG at a threshold typically around 20 to 25 mIU/mL. Their results are most reliable from about the day of the expected period, which corresponds to roughly four weeks of gestational age. A quantitative hCG blood test is more sensitive and can detect the hormone several days earlier than urine tests. False negatives are most often caused by testing too early or by dilute urine. False positives are uncommon, but they can arise from certain medications, from hCG-secreting tumours, or from residual hCG after a recent pregnancy loss.\n\nUltrasound\n\nUltrasound confirms the pregnancy in a way that hormone tests cannot. Transvaginal scanning, which gives a much closer view of the uterus than abdominal scanning, usually shows a gestational sac within the uterine cavity at about five weeks of gestational age. The yolk sac becomes visible shortly afterward, and a fetal pole with cardiac activity is usually detectable by about six weeks. Ultrasound therefore establishes that the pregnancy is intrauterine, that it contains an embryo, and whether that embryo is alive. Dating relies on the crown-rump length, which is most accurate between about six and fourteen weeks. Measured in this window, it is generally accurate to within about one week, and it is used to correct dates when the last menstrual period is uncertain or when it conflicts with the scan. Diagnostic ultrasound is non-invasive and is widely regarded as safe at the exposure levels used clinically.\n\nMultiple pregnancy\n\nThe first ultrasound also counts the gestational sacs and embryos, which identifies multiple pregnancy. Early scanning is especially valuable for determining chorionicity and amnionicity, meaning how many placentas and amniotic sacs are present. This is best done in the first trimester. A dichorionic pregnancy can often be recognised by a characteristic configuration of the membranes, and a monochorionic pregnancy has a higher risk of complications that require closer surveillance. Twin pregnancies account for a few percent of births in many populations, and their frequency is raised by maternal age, family history, and assisted conception. The risk of higher-order multiples is greater still with fertility treatment. For detailed discussion see twin pregnancy.\n\nAbnormal location\n\nEarly assessment also seeks to identify implantation outside the uterine cavity. The most common form is ectopic pregnancy, in which the vast majority of cases occur in a fallopian tube. Ultrasound may show an empty uterus alongside a mass in the adnexa or free fluid in the pelvis, and rupture can cause severe internal bleeding. Because ectopic pregnancy remains an important cause of maternal death in the first trimester, clinicians combine ultrasound with serial hCG measurements. When neither an intrauterine pregnancy nor an ectopic pregnancy can be seen, the case is classified as a pregnancy of unknown location and followed with repeat testing. Below a certain hCG threshold, a gestational sac may not yet be visible, so a visible sac at a higher level is expected. Rarer variants, such as cervical implantation and heterotopic pregnancy in which both intrauterine and extrauterine pregnancies coexist, are also sought during early examination."
    },
    {
      "heading": "Prenatal Care and Screening",
      "text": "Schedule of visits and routine measurements\n\nPrenatal care is organized as a series of scheduled contacts rather than a single examination. Given evidence that perinatal deaths increase with only four ANC visits and that an increase in the number of ANC contacts, regardless of the country, is associated with an increase in maternal satisfaction, WHO recommends a minimum of eight contacts, placed in the first trimester, the second trimester and the third trimester. The 2016 WHO model places the first contact during the first 12 weeks' gestation, with following contacts taking place at 20, 26, 30, 34, 36, 38 and 40 weeks' gestation. Many health systems still follow older schedules with fewer visits, and national practice varies.\n\nAt each contact, clinicians typically record blood pressure, which is the main means of detecting hypertensive disorders of pregnancy, and body weight, which is tracked against expected gestational weight gain. Urine is tested for protein, glucose and signs of urinary infection. The fetal heart rate is checked by Doppler or handheld device after the early second trimester, and uterine size (fundal height) is measured to estimate growth. Each contact also offers an opportunity to verify vaccination status; at each ANC contact, ANC providers should verify the vaccination status of pregnant women and administer vaccines recommended in the national immunization schedule.\n\nGenetic screening: purpose and limits\n\nGenetic screening estimates the probability that a fetus has a particular condition, most often a chromosomal aneuploidy such as trisomy 21. Cell-free DNA testing analyzes fragments of fetal DNA circulating in the maternal blood. In a large routine population, the positive predictive value for cfDNA testing was 80.9% (95% CI, 66.7 to 90.9), as compared with 3.4% (95% CI, 2.3 to 4.8) for standard screening. The predictive value falls sharply for rarer conditions. A meta-analysis estimated that the pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). For sex chromosome abnormalities, the pooled positive predictive value was 49.4% (95% confidence interval, 45.8–53.1).\n\nThe test also has structural limits. It does not evaluate for anatomical abnormalities like open neural tube defects, and it is not a comprehensive genome-wide analysis. Because of these limits, a positive screening result should be followed with a confirmatory test. Confirmation is made by invasive diagnostic procedures that sample fetal cells directly.\n\nAnomaly ultrasound\n\nThe second-trimester anomaly scan is the main mid-pregnancy structural survey. Traditionally, examination of the fetal anatomy is performed during the second trimester of pregnancy, between 18 and 22 weeks' gestation. Timing is a trade-off: screening for fetal structural anomalies at 18 to 22 weeks' gestation is thought to allow for an optimal balance between maximising detection rates, while leaving sufficient time for counselling, further investigations, and decision‐making prior to 24 weeks' gestation, which is the legal limit for termination in most countries. Before about 18 weeks, the fetal organs may be of insufficient size and development to allow for ultrasound evaluation.\n\nDetection rates vary widely. The fetal anomaly scan boasts a high detection rate for major structural malformations, ranging from 15% to exceeding 90% in some cases. Operator skill and equipment settings also influence results, and the scan cannot detect every health condition.\n\nInformed consent and the distinction between screening and diagnosis\n\nScreening identifies people at higher risk and does not establish whether a condition is present. Diagnostic testing gives a definitive answer, though it may carry a risk of pregnancy loss. Because screening results are probabilistic, the principle of informed consent requires that the pregnant person understand what a test can and cannot show, the likelihood of false positives and negatives, the options available after a result, and her right to decline testing altogether. Counselling is therefore part of the screening pathway itself, not an add-on. The purpose of such screening is to identify certain conditions and thus allow parents to make informed decisions about their pregnancy.\n\nRoutine infection and anemia screening\n\nAt the first visit, standard blood tests usually include blood group and Rh type, hemoglobin or hematocrit to detect anemia, and serological tests for syphilis, HIV and hepatitis B. Rubella immunity is also commonly checked. Screening for syphilis and HIV is performed because both can be transmitted to the fetus and treatment during pregnancy substantially reduces that risk. Hepatitis B status guides whether the newborn receives immunization at birth. Anemia, particularly iron deficiency, is detected early because it is associated with lower maternal reserves for blood loss at delivery and with adverse fetal outcomes. Later in pregnancy, a glucose challenge test is commonly performed at around 24–28 weeks to screen for gestational-diabetes, and a vaginal and rectal swab for group B streptococcus is taken near 36 weeks to guide intrapartum antibiotic prophylaxis."
    },
    {
      "heading": "Nutrition, Environmental Exposures and Lifestyle",
      "text": "Essential Nutrients\n\nFolate has the most precisely quantified protective role in pregnancy. Neural tube closure occurs within the first weeks after conception, often before a missed period prompts a pregnancy test, so protection has to begin before conception. Daily doses of 0.4 to 0.8 mg (400 to 800 µg) of folic acid are the level set for people who could conceive, and the critical window opens at least 1 month before conception and continues through the first 2 to 3 months of pregnancy. Trials and observational studies have shown that 50% or more of NTDs can be prevented with a folic acid–containing supplement taken before and in the early weeks of pregnancy. A 1991 trial among women with a previous affected pregnancy recorded a risk reduction of roughly 72 percent, using a high dose. Uptake remains uneven: in a French national registry covering 2006 to 2016, 14.3% of pregnant women had a prescription for folic acid supplementation during the month preceding conception and for the first 12 weeks of pregnancy.\n\nIron demand rises because maternal red cell mass expands and the fetus and placenta draw on maternal stores. Deficiency increases the risk of maternal anemia, and it is associated with preterm birth and low birth weight. Routine prenatal care therefore usually pairs iron with folic acid, and the WHO recommends daily iron supplementation for pregnant women in settings where anemia is common.\n\nIodine is needed for fetal brain development, and the requirement rises in pregnancy. To maintain normal thyroid function, a mother must increase her production of thyroxine by 40–50%, which requires an additional daily iodine intake of 150–250 μg. Although the thyroid contains a reserve of iodine, this is depleted during pregnancy without supplementation. The WHO target during pregnancy is 250 µg/day once pregnancy is confirmed. Policy differs by country: the WHO advises against universal iodine supplementation in countries with effective salt iodization, while both WHO and Unicef recommend iodine supplementation for pregnant and lactating women in countries where less than 20% of families have access to iodized salt.\n\nProtein supplies amino acids for placental and fetal tissue growth. Severe undernutrition, whether from famine, poverty or chronic illness, is linked to restricted fetal growth and low birth weight, and maternal weight status before conception also influences outcomes.\n\nAlcohol, Tobacco and Drugs\n\nPrenatal alcohol exposure can cause a range of lifelong conditions collectively termed fetal alcohol spectrum disorder (FASD), which includes physical features, growth restriction and neurodevelopmental impairment. Alcohol crosses the placenta freely, and the fetus lacks the capacity to metabolize it efficiently. A meta-analysis of 24 studies estimated the global prevalence of FASD among children and youth in the general population to be 7.7 per 1000 population, while one in every 13 women who consume alcohol during pregnancy would give birth to a child with FASD. Prevalence varies widely by population; the prevalence of alcohol use during pregnancy in the Aboriginal populations of the United States and Canada were found to be approximately three to four times higher, respectively, compared to the general population. Professional guidance is consistent on the central point: there is no safe amount, time, or type of alcohol to drink during pregnancy or when trying to get pregnant.\n\nSmoking exposes the fetus to nicotine and carbon monoxide, which reduces oxygen delivery across the placenta. Associations with restricted fetal growth, low birth weight, placental abruption and sudden infant death are well documented, and cessation support is a standard component of prenatal care. Cannabis and other illicit drugs are associated with growth restriction, preterm birth and neonatal withdrawal, although the size of specific effects is still debated.\n\nMost medicines cross the placenta to some degree, and the principle of teratogenicity, the capacity of an agent to cause structural or functional birth defects, was established after the thalidomide disaster of the late 1950s and early 1960s. Known teratogens include some anticonvulsants, retinoids and certain cytotoxic drugs. Because pregnant people are usually excluded from clinical trials, evidence on most drugs comes from pregnancy registries, cohort studies and exposure-register linkages, which are prone to confounding by the underlying illness. Analgesics such as paracetamol are generally preferred when treatment is needed, and clinicians weigh the risk of untreated maternal disease against any drug-related risk.\n\nInfections That Cross the Placenta or Occur at Birth\n\nSome pathogens reach the fetus through the placenta. Rubella, cytomegalovirus, toxoplasmosis, syphilis, Zika virus and HIV can cause miscarriage, stillbirth, congenital anomalies or developmental problems. Cytomegalovirus is the most common congenital infection. Others are acquired at birth, including group B streptococcus, herpes simplex virus and hepatitis B. Prevention combines pre-conception immunity checks, vaccination, screening and treatment. Rubella vaccination is given before pregnancy, and pertussis vaccination is typically offered in the third trimester, which transfers protective antibodies to the newborn. Syphilis screening is routine, and early treatment with penicillin prevents most cases of congenital syphilis. Antiretroviral therapy substantially reduces mother-to-child HIV transmission. Group B streptococcus is screened for near term, with intrapartum antibiotics given to carriers, and newborns of hepatitis B–positive mothers receive vaccination and immune globulin soon after birth. Advice on food hygiene and avoidance of unpasteurized dairy reduces the risk of listeriosis and toxoplasmosis.\n\nOccupational and Environmental Exposures\n\nHeavy metals are among the best-studied environmental toxicants. Methylmercury, mainly from contaminated fish, crosses the placenta, and the Minamata disease outbreak in Japan and the Faroe Islands birth cohort showed impaired neurodevelopment after prenatal exposure. Lead also crosses the placenta and is associated with reduced cognitive performance in childhood. Radiation is a different case: diagnostic imaging and occupational doses are generally low, and radiation protection bodies consider doses below roughly 50 mGy unlikely to cause malformations, while higher exposures, such as those studied after Hiroshima, Nagasaki and Chernobyl, raised concern for intellectual disability when exposure occurred during specific gestational windows. Air pollution, particularly fine particulate matter (PM2.5), has been associated with preterm birth and low birth weight in large cohort and registry studies, although residual confounding by socioeconomic status is difficult to exclude.\n\nThese exposures are studied through birth cohorts that measure biomarkers in maternal blood, cord blood, placenta or hair; registry linkage combined with satellite-based or modeled exposure estimates; sibling comparisons; and natural experiments such as industrial closures or policy changes. Randomized allocation of pregnant people to harmful exposures is ethically impossible, so causal inference depends on converging evidence from observational designs and animal models. Epidemiological studies also face the challenge that occupational and environmental exposures are often correlated with income, diet and smoking, which complicates attribution of effects to a single agent."
    },
    {
      "heading": "Pregnancy Complications and Disorders",
      "text": "Miscarriage\n\nPregnancy loss before 20 weeks is generally classed as miscarriage, the same event that clinicians call early pregnancy loss. About 80% of pregnancy losses occur in the first trimester, while losses between 12 and 20 weeks make up only 1–5% of cases. Reported rates depend on how losses are counted. Roughly 15–25% of clinically recognized pregnancies end in miscarriage, and including unrecognized early losses raises the figure to 30–60% of all pregnancies. Losses are divided into early clinical pregnancy losses (before gestational week 12) and late clinical pregnancy losses (gestational weeks 12 to 21), and the two groups differ in cause and prognosis.\n\nEmbryonic chromosomal abnormalities are the most common cause. They account for 50-65% of all miscarriages, and trisomies are the single largest group of chromosomal anomalies associated with loss. Maternal age is a major factor, since the risk of aneuploidy rises with age. Other associated factors include older maternal age, obesity, and tobacco use, along with diabetes, autoimmune disease, and drug or alcohol use. Uterine and endocrine conditions and blood-clotting disorders are also implicated in some cases. An estimated 30% of human conceptions are lost before implantation, and a further 30% after implantation but before the missed menstrual period. Most of these losses are never clinically identified.\n\nRecurrent pregnancy loss is defined by ESHRE as three or more consecutive pregnancy losses before 22 weeks of gestation. Among couples who experience additional losses, fewer than 5% have two consecutive miscarriages, and about 1% have three or more. Despite thorough evaluation for these risk factors, the exact cause for recurrent pregnancy loss is unknown in about 50% of cases.\n\nEctopic Pregnancy\n\nAn ectopic pregnancy arises when the blastocyst implants outside the endometrial cavity, and over 95% occur in the fallopian tube. The reported incidence is 1.3–2.4%, and a ruptured ectopic pregnancy is a direct cause of maternal death in the first trimester. Risk is raised by prior tubal surgery, sterilization, prior ectopic pregnancy, and intrauterine contraceptive devices, and by tubal dysfunction or inflammation that impairs the transport of the embryo toward the uterus.\n\nDiagnosis combines transvaginal ultrasound with serial measurement of hCG. Management may be expectant, medical, or surgical. Methotrexate is the usual medical option, and it is generally restricted to patients without fetal heart activity, with β-hCG above 5000 mIU/mL, or with an ectopic mass larger than 4 cm (these are relative contraindications). Single-dose protocols succeed in a large share of selected patients; in one series of 400 women, the overall success rate was 78.5%, and a lower initial hCG predicted success.\n\nPlacental Disorders\n\nIn placenta previa, the placenta attaches inside the uterus in a position that partially or completely covers the cervical opening. The condition is uncommon, and its typical presentation is vaginal bleeding in the second half of pregnancy, which is often bright red and may be painless, sometimes profuse. Ultrasonography can usually confirm the diagnosis. Risk rises with parity and with prior cesarean delivery: the estimated risk increases with the number of cesarean sections, from an estimated 0.9% after one to up to 10% after four or more. Cigarette smoking is also associated with a two- to threefold increase. Management usually involves bed rest for bleeding and delivery by cesarean section, and complications can include placenta accreta, in which the placenta grows too deeply into the uterine wall.\n\nIn placental abruption, the placenta detaches from the uterine wall earlier than it should, reducing oxygen and nutrient supply to the fetus. The most common presentation is vaginal bleeding with cramping during the third trimester of pregnancy, but there could be no visible bleeding because the blood is trapped between the placenta and the uterine wall. Its incidence has been reported at about 0.7% of deliveries in one tertiary center. Risk factors include previous placental abruption, preeclampsia, fetal growth restriction, advanced maternal age, multiparity, smoking and cocaine use, and premature rupture of membranes. Approximately 5% of women with placenta previa develop abruption. Severe cases may require emergency delivery, and maternal complications can include anemia, uterine rupture, and HELLP syndrome.\n\nHypertensive Disorders of Pregnancy\n\nHypertensive disorders are classified as chronic hypertension, gestational hypertension, preeclampsia (including superimposed preeclampsia), and eclampsia. Preeclampsia is defined by new hypertension after 20 weeks of gestation, typically a blood pressure of at least 140/90 mmHg on two occasions at least four hours apart, together with proteinuria or evidence of organ involvement, such as low platelet count, impaired liver or kidney function, pulmonary edema, or neurological symptoms. Eclampsia is the occurrence of seizures in this setting. The underlying process is widely attributed to abnormal placentation, in which inadequate trophoblast invasion of the spiral arteries leads to placental ischemia. For the mother, the risks include stroke, HELLP syndrome, and placental abruption; for the fetus, they include growth restriction, oligohydramnios, and preterm birth. Delivery is the definitive treatment, while magnesium sulfate is used to prevent or treat seizures. Low-dose aspirin started early in pregnancy is recommended for women judged to be at high risk.\n\nGestational Diabetes\n\nGestational diabetes is glucose intolerance first recognized during pregnancy. Screening is usually performed at 24–28 weeks with a glucose challenge or a 75 g oral glucose tolerance test, and women judged to be at high risk may be tested at the first visit. Diagnostic thresholds vary between guidelines; the International Association of Diabetes and Pregnancy Study Groups criteria use fasting, 1-hour, and 2-hour plasma glucose values. Management begins with diet, exercise, and home glucose monitoring, and insulin is added when targets are not met. Oral agents such as metformin are used in some settings. Untreated hyperglycemia increases the risk of fetal macrosomia, shoulder dystocia, neonatal hypoglycemia, and hyperbilirubinemia, and raises the mother's risk of preeclampsia. Women with the condition have a higher long-term risk of type 2 diabetes, and their children have higher rates of obesity.\n\nPreterm Labor and Premature Rupture of Membranes\n\nPreterm labor is defined as regular uterine contractions with cervical change before 37 weeks. Treatment aims to delay delivery long enough to give antenatal corticosteroids, usually for about 48 hours, and to transfer the mother to a center with neonatal intensive care. Tocolytic agents such as nifedipine or atosiban may be used for this purpose, though they do not prevent preterm birth in most cases. Magnesium sulfate is given for fetal neuroprotection when delivery is anticipated before about 32 weeks.\n\nPremature rupture of membranes (PPROM) is rupture of the amniotic sac before 37 weeks without labor. Management of PPROM before viability or in the preterm period balances infection risk against the benefits of prolonging the pregnancy, with antibiotics and corticosteroids commonly used. Maternal risks include chorioamnionitis and placental abruption, while cord prolapse and oligohydramnios can compress the fetus. For the newborn, the principal risks arise from prematurity: respiratory distress syndrome from surfactant deficiency, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, sepsis, and difficulties with thermoregulation and feeding. Survival and long-term outcome depend strongly on gestational age at birth."
    },
    {
      "heading": "Labor and Childbirth",
      "text": "Labor is usually understood as the set of processes by which regular, painful uterine contractions lead to thinning (effacement) and opening (dilation) of the cervix. Its onset depends on a sequence of preparatory changes rather than a single trigger. In the final weeks of pregnancy the cervix begins to ripen, meaning its collagen-rich connective tissue is broken down and it softens. Estrogen, relaxin and prostaglandins all contribute, with prostaglandins playing the most prominent role. Prostaglandins are made by the placenta, the decidua (the modified uterine lining), the myometrium (the uterine muscle) and the fetal membranes, and their production rises in the third trimester as the estrogen-to-progesterone ratio shifts. Clinical management of labor is governed largely by this hormonal balance, with corticotropin-releasing hormone and relaxin also involved in initiating and sustaining it.\n\nPhysiological triggers\n\nOxytocin from the posterior pituitary is the second key driver. Its blood levels rise near term, and the myometrium increases its number of oxytocin receptors, so the uterus becomes more responsive to the hormone. Oxytocin strengthens contractions, and the contractions in turn stimulate the release of prostaglandins from the fetal membranes. This creates a positive feedback loop in which each process reinforces the other. Stretching of the cervix by the descending fetal head also provokes reflex contractions and increases pituitary oxytocin secretion, and the fetal pituitary adds further oxytocin. Prostaglandins act on the myometrium in several ways: they increase contractile force, promote the opening of gap junctions between muscle cells so that contractions spread in coordination, and soften the cervix by remodeling its extracellular matrix. The same hormonal logic underlies the use of synthetic oxytocin and prostaglandin preparations to induce labor when it fails to progress.\n\nStages of labor\n\nClinical practice divides labor into three stages. The first stage runs from the onset of regular contractions to full cervical dilation, about 10 cm. It is conventionally subdivided into an early or latent phase, during which dilation is slow, and an active phase, during which it accelerates. The exact threshold between the two phases varies between guidelines, with some placing it at 4 cm and others at 6 cm. In the active phase, typical dilation rates are often cited as roughly 1 cm per hour in first-time mothers and about 2 cm per hour in women who have given birth before, and prolonged arrest of progress is a recognized sign of possible complications. The second stage begins at full dilation and ends with delivery of the infant. Its duration is highly variable, from less than an hour to several hours, and the fetus descends through the birth canal with or without maternal pushing. During delivery the fetus makes a sequence of rotational and extension movements, from flexion and internal rotation through crowning to the delivery of the shoulders and body. The third stage covers the interval from delivery of the infant to expulsion of the placenta and membranes. Uterine contraction and placental detachment in this stage are supported by oxytocin, and prostaglandins produced in the placenta also contribute to separation and expulsion.\n\nVaginal and operative delivery\n\nMost births proceed vaginally, but operative vaginal delivery (using forceps or vacuum extraction) and cesarean delivery are used when labor cannot safely reach a vaginal birth. Common indications include prolonged or obstructed labor, fetal distress, elevated maternal blood pressure or glucose, multiple pregnancy, and abnormal fetal presentation or position. In a North American case series, the most frequent indications were an elective repeat cesarean, dystocia or failure to progress, malpresentation, and fetal heart rate patterns suggesting distress. The World Health Organization has long discussed population-level targets. Its 1985 consensus statement suggested that no region needed a rate above 10% to 15%, and in 2015 it stated that the priority should be providing cesarean delivery to women who need it rather than reaching a specific rate. Global cesarean rates have risen substantially since the 1990s, and surveys of the rate of unnecessary procedures are a recurring theme in public health debate. Cesarean delivery carries surgical risks for mother and infant, so its use is weighed against those risks in each case.\n\nPain management, attendants and fetal monitoring\n\nPain management in labor ranges from non-drug methods such as movement, positioning, breathing techniques and continuous support to pharmacological options. The most effective pharmacological method is regional analgesia, usually an epidural, which blocks sensation from the lower body. Other options include inhaled nitrous oxide and systemic opioids, each with different benefits and effects on the newborn. Labor care is delivered by midwives, who often manage low-risk births, and by obstetricians, who manage high-risk pregnancies and operative procedures; anesthesiologists are involved when regional analgesia or surgery is needed. Fetal monitoring assesses the baby's heart rate, which may be checked intermittently with a handheld device or continuously with electronic fetal monitoring that records the heart rate alongside uterine contractions. Changes in heart rate patterns can prompt further assessment, including sampling of fetal blood or a change in management. Decisions about these interventions are based on informed consent, and the balance between continuous and intermittent monitoring is an ongoing subject of clinical guidance."
    },
    {
      "heading": "Postpartum Period and Lactation",
      "text": "Immediate care and expulsion of the placenta\n\nImmediate postpartum care concentrates on bleeding and on the completion of the third stage of labor, the interval between the birth of the infant and the expulsion of the placenta. Postpartum hemorrhage is most often defined as a loss of more than 500 mL after delivery, and it is the most common maternal morbidity in developed countries. Some definitions set a higher threshold after cesarean birth, at about 1,000 mL, and the visual estimation of blood loss tends to underestimate the true figure. Routine (\"active\") management of the third stage includes the administration of oxytocin, controlled umbilical cord traction and uterine massage after the placenta is delivered. Oxytocin is the preferred first-line uterotonic and is usually given intramuscularly or intravenously immediately after birth. Hemostasis at the placental bed depends on the myometrium, because the uterine muscle must contract to compress the vessels that supply the site where the placenta was attached.\n\nCauses and management of hemorrhage\n\nSeventy percent of postpartum hemorrhage corresponds to uterine atony, although other estimates place atony at about 80 percent. Atony is the failure of the uterus to contract adequately after delivery, and a soft, \"boggy\" uterus on palpation is its typical sign. Risk is raised by prolonged or rapid labor, oxytocin used for induction or augmentation, magnesium sulfate, and an overdistended uterus caused by multiple pregnancy or excess amniotic fluid. Other causes include retained placental tissue, lacerations of the birth canal, uterine rupture and coagulation disorders, so clinicians are advised not to stop at atony when first-line measures fail. Initial steps include fundal massage and emptying the bladder, followed by uterotonic drugs. If bleeding persists, methylergonovine can be used unless contraindicated by hypertension; carboprost is effective but is avoided in patients with asthma; misoprostol can be given orally or rectally. Uterine tamponade is an additional nonpharmacological option. Massive hemorrhage can lead to hypovolemic shock, disseminated intravascular coagulation, hepatic and renal dysfunction, and acute respiratory distress syndrome. Hemorrhage remains among the top five causes of maternal death across the globe.\n\nInvolution of the uterus\n\nInvolution is the process by which the uterus shrinks back toward its pre-pregnancy size. It usually begins immediately after the delivery of the placenta and continues for several weeks. The main driver is the withdrawal of placental hormones, which triggers autolysis of the enlarged tissue. The uterine muscle fibers are arranged in crossing layers, so their contraction compresses the blood vessels between them and reduces flow. The endometrium regenerates and the lining sheds as lochia, a discharge that normally changes color from bright red to brownish and then yellowish over the first few weeks. Estimates of completion vary: one common account holds that the process is usually completed by six weeks, while another gives a range of 6–8 weeks after delivery. Even when the uterine size has normalized, the endometrial cavity remains larger than in the virgin state. The cervix, pelvic floor and ligaments also return gradually to their earlier state, and hormone levels, including the ovarian cycle, recover at individually variable rates.\n\nLactation physiology\n\nLactation depends on a sequence of hormonal switches. During the second half of pregnancy, prolactin triggers the production of colostrum, but estrogen and progesterone remain high enough to prevent significant lactation. Estrogen and progesterone also inhibit milk secretion by blocking prolactin release. When the placenta is delivered, the sudden fall in these hormones allows copious milk production to begin, a stage often called lactogenesis II. Mature milk is typically secreted about two weeks after delivery. Prolactin, released from the anterior pituitary, is essential for initiating and maintaining production, while oxytocin from the posterior pituitary drives the milk-ejection (let-down) reflex. Suckling stimulates mechanoreceptors in the nipple and areola, and the signal travels to the hypothalamus. Production is governed largely by demand: the more frequent the nipple stimulation and let-down, the more milk is produced. A whey protein known as the feedback inhibitor of lactation accumulates in distended alveoli and slows synthesis when milk is not removed. Dopamine from the hypothalamus tonically suppresses prolactin, and this inhibition is transiently reduced during suckling.\n\nEarly breastfeeding and postpartum complications\n\nEarly breastfeeding matters for both infant nutrition and maternal physiology. Colostrum is rich in immune cells and antibodies and high in protein. Research on early suckling has found that the number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation, and that stress and medical interventions at birth can blunt these responses. Some women experience dysphoric milk ejection reflex, a brief episode of sadness, anxiety or agitation tied to the let-down, and dysregulation of the oxytocin, prolactin and dopamine systems has been proposed as a contributor to such reactions.\n\nBeyond hemorrhage, the principal postpartum complications include infection, such as endometritis, wound infection after cesarean delivery, mastitis and urinary tract infection, which are more likely after prolonged labor, operative birth or retained tissue. Postpartum depression is a common and serious condition that can begin in the weeks after birth and affects a substantial minority of mothers; it is linked to hormonal change, sleep disruption, social isolation and prior mental illness, and it requires screening and treatment within maternal health services."
    },
    {
      "heading": "Global Epidemiology and Maternal Health Outcomes",
      "text": "Scale and trends\n\nThe most recent inter-agency estimates, produced by a group that includes WHO, UNICEF, UNFPA, the World Bank and the UN Population Division, put the number of maternal deaths in 2023 at about 260,000 women. Maternal mortality is usually expressed as a ratio per 100,000 live births, and the global ratio was 197 in 2023, compared with 328 in 2000, a fall of roughly 40 percent. The pace of improvement has slowed markedly since 2016, and the estimates are model-based because many countries lack complete civil registration of deaths.\n\nCauses of maternal death\n\nHaemorrhage is the largest single cause. A WHO systematic analysis covering 2009 to 2020 attributed about 27 percent of maternal deaths to it, and most haemorrhage deaths occur after birth. Hypertensive disorders, including pre-eclampsia and eclampsia, accounted for about 16 percent. Other direct causes in the same analysis included complications of abortion (about 8 percent), embolism (about 7 percent) and pregnancy-related infection (about 7 percent), with sepsis dying out later in the postpartum period. An earlier analysis of 2003 to 2009 data found a similar ranking, with haemorrhage, hypertensive disorders and sepsis together responsible for more than half of deaths. Most of these causes are treatable with timely skilled care, which is why the majority of deaths are regarded as preventable.\n\nNewborn deaths and stillbirths\n\nMaternal and perinatal outcomes are closely linked. UN IGME estimates for 2022 counted about 2.3 million neonatal deaths, roughly one newborn in 58, and the global neonatal mortality rate was about 17 per 1,000 live births in 2024. Stillbirths remained at around 1.9 million in 2023. Neonatal mortality has declined more slowly than mortality among older children, so it now accounts for a growing share of under-five deaths.\n\nDisparities between and within countries\n\nThe burden is sharply unequal. About 94 percent of maternal deaths occur in low and lower-middle-income countries, and sub-Saharan Africa and Southern Asia together account for about 87 percent of the global total, with sub-Saharan Africa alone responsible for roughly 182,000 deaths. The same two regions carry more than 80 percent of neonatal deaths while containing only about 57 percent of live births. Causes also differ by region: in the 2003–2009 analysis, haemorrhage accounted for about 37 percent of maternal deaths in northern Africa but about 16 percent in developed regions, whereas hypertensive disorders were especially prominent in Latin America and the Caribbean. Within individual countries, outcomes vary by income, rurality, ethnicity and the level of local health infrastructure, although the magnitude of these gaps differs widely between settings. Some low-income countries, such as Rwanda and Sri Lanka, have achieved large reductions in maternal mortality, which indicates that progress is feasible across different levels of resources.\n\nHealth and social determinants\n\nAccess to skilled attendance at birth, emergency obstetric care and treatment for complications is the most direct determinant of survival. The longer the delay in reaching such care, the higher the risk of death from haemorrhage or eclampsia. Poverty affects this access through costs, distance and the quality of services, and it also shapes nutrition and the prevalence of anaemia and infection. Adolescent pregnancy is associated with higher risks of obstructed labour and other complications, while women's education is generally linked with earlier and more frequent use of antenatal and delivery services. These factors interact, so interventions that address only clinical care tend to show more limited effects where social disadvantage is severe.\n\nTargets and monitoring\n\nSustainable Development Goal target 3.1 calls for reducing the maternal mortality ratio to below 70 per 100,000 live births by 2030. SDG target 3.2.2 sets a neonatal mortality goal of 12 or fewer deaths per 1,000 live births by 2030. Progress is tracked through the UN Maternal Mortality Estimation Inter-Agency Group, which revises its series as new national data arrive, so that later estimates supersede earlier ones for overlapping years. Projections suggest that current trends will fall short of these targets, and the monitoring reports highlight the need for sustained financing and for strengthening the systems that record deaths."
    },
    {
      "heading": "Historical Understanding of Pregnancy",
      "text": "Ancient medical writing\n\nThe oldest surviving medical texts that address pregnancy come from Egypt. The Kahun Gynaecological Papyrus, found by Flinders Petrie in 1889 at El Lahun, is dated in sources to roughly 1800–1825 BCE. It is the oldest known medical text in Egyptian history, and it addresses gynecological health concerns, pregnancy, fertility, and various treatments. Its diagnostic material is practical rather than theoretical. Among its fertility and pregnancy tests, a woman should moisten barley and emmer with her urine every day, and the sprouting pattern was read as a sign of pregnancy and of the child's likely sex. The papyrus also records treatments for many complaints and at times sees the womb as the source of complaints manifesting themselves in other body parts. Later Egyptian medical papyri, including the Berlin Papyrus, repeat much of the same material.\n\nIn ancient Greece, the central question was how new life was formed. The Hippocratic writings on generation treated the contributions of both parents as seed, while Aristotle's biological works held that menstrual matter supplied the material of the embryo and male semen supplied the form and the moving principle. Aristotle also argued that the heart was the first organ to form. These ideas were built on observation of animals and the body, not on experiment, but they framed generation as a gradual process of formation, a view that later became the basis of the epigenetic position. Chinese medicine developed a parallel and very detailed tradition. The Han-dynasty texts discovered in the Mawangdui tomb at Changsha, including a text on fetal care, describe pregnancy month by month and link the mother's diet, emotions and conduct to fetal health. Later medical canons, such as the Huangdi Neijing and the materia medica tradition, extended these ideas into clinical advice on the management of pregnancy and birth.\n\nEmbryology and anatomy from the Renaissance\n\nRenaissance anatomy, led by Andreas Vesalius's illustrated work on the human body in 1543, provided the structural knowledge needed to study the body in pregnancy. Embryology, however, was shaped by a long dispute between two views. Preformation held that a miniature organism already existed in the egg or the sperm and simply grew. In the late seventeenth century, Antonie van Leeuwenhoek's microscopic observations of sperm encouraged the view that a tiny homunculus lay within the male cell, while ovists placed it in the egg. William Harvey, in his 1651 work on animal generation, argued that all animals came from eggs, but he still considered the embryo to form from an undifferentiated mass. The shift toward modern embryology came in the eighteenth century, when Caspar Friedrich Wolff's 1759 Theoria generationis argued that organs arise progressively from unstructured tissue. This epigenetic view moved the discipline from asking what is pre-existing to studying how structures are formed, and it laid the foundations of the field now known as embryology.\n\nTwentieth-century hormones, imaging and monitoring\n\nThe twentieth century brought the identification of the hormones of pregnancy. In the 1920s and early 1930s, researchers detected a gonadotropin in the urine of pregnant women and developed biological assays that depended on it, which later became the basis of hormone-based pregnancy testing. Estrogen and progesterone were isolated in the early 1930s, and their roles in the ovary and placenta were then mapped. These discoveries are discussed further in the article on human chorionic gonadotropin.\n\nImaging changed obstetrics more than any other technology of the period. In 1958, the Glasgow obstetrician Ian Donald, the engineer Tom Brown and the physician John MacVicar published a paper in The Lancet titled \"Investigation of abdominal masses by pulsed ultrasound.\" Donald had adapted a metal flaw detector and, according to published accounts, the fetus was previously assessed largely by the palpating hands of the obstetrician. After the paper, the use of two-dimensional ultrasound in obstetrics began to flourish, and within a few years it became possible to study fetal growth in vivo from the beginning to the end of human pregnancy. Ultrasound later became a routine tool of prenatal imaging.\n\nFetal monitoring developed in parallel. Electronic recording of the fetal heart rate during labor was introduced in the late 1950s and became widespread in hospitals during the following decades. It was intended to detect fetal distress, and its adoption contributed to the growing reliance on hospital-based, technology-intensive birth.\n\nFrom home to hospital\n\nThe shift of childbirth from home to hospital is one of the most consequential changes in the history of pregnancy. In 1900, only five percent of all births occurred in hospitals. Particularly in urban areas, the shift from home to hospital occurred quickly. By 1935, nearly 75 percent of urban births occurred in hospitals, and nearly all urban births occurred in hospitals by 1950. Rural areas changed more slowly. Before this transition, midwives had been responsible for a large share of deliveries; by the turn of the century they attended approximately half of births, despite having little training in obstetrics. Medical reform documents such as the 1910 Flexner Report recommended hospital delivery and, in effect, the decline of midwifery in the United States, a judgment that later drew criticism.\n\nHospital birth also changed the nature of labor. A 1932 study of 40,143 births found that 24% of hospital births were operative compared to 8% of home births. Maternal mortality did not fall as hospitalization spread. Though hospital births were believed to be safer, there was no decrease in maternal mortality between hospital and home births until the 1940s. Historians have since debated whether the move to hospitals reflected benefits to mothers or the interests of practitioners and institutions, and the introduction of sulfonamide drugs in 1937 is often cited as the point at which medical intervention began to reduce deaths from infection after birth."
    },
    {
      "heading": "Assisted Conception and Multiple Pregnancy",
      "text": "History of in vitro fertilization\n\nLouise Brown, born on 25 July 1978 in England, is recognized as the first human born after conception by in vitro fertilisation (IVF). Her mother had blocked fallopian tubes, and her parents had been trying to conceive for nine years. The procedure was developed by Patrick Steptoe, Robert Edwards, and Jean Purdy. Brown's conception used an unstimulated cycle: she was born as a result of natural cycle IVF, where no stimulation was made. Edwards received the Nobel Prize in Physiology or Medicine in 2010, while his co-workers were not eligible because the prize is not awarded posthumously. By one estimate, more than 12 million children have since been born through IVF worldwide.\n\nSteps of an IVF cycle and embryo transfer\n\nModern IVF begins with ovarian stimulation. Injected gonadotropins are given for roughly 9 to 12 days, during which clinic visits include repeated ultrasounds and blood tests to track follicle growth. A final \"trigger\" injection ripens the eggs, and retrieval typically occurs about 36 hours later. Retrieval is a short procedure: a transvaginal ultrasound guides a thin needle into each follicle to collect the egg, usually under sedation, and takes about 15 to 30 minutes.\n\nIn the laboratory, eggs and sperm are combined either by mixing them in a dish or by injecting a single sperm into each egg, the latter being the intracytoplasmic sperm injection (ICSI) method. Typically, around 65% to 80% of eggs are fertilized. The embryos are then cultured, and transfer usually takes place three to five days after retrieval, with one or two selected for transfer into the uterus. Transfers may be fresh, in the same cycle as retrieval, or frozen, in a later cycle. Because of the hormonal changes needed for implantation, estrogen and progesterone are commonly given to thicken the uterine lining. A pregnancy test follows about two weeks later. One review estimates that approximately 1.9% of all infants are born each year as a result of IVF.\n\nIncidence and mechanisms of multiple pregnancy\n\nMultiple pregnancy is far more frequent after fertility treatment than after spontaneous conception. Among Caucasian women conceiving without treatment, twins occur at about one in eighty pregnancies. In an Israeli population cohort, assisted reproductive technology was involved in 24.1% of twin pregnancies versus 1.7% of singleton pregnancies. Two mechanisms drive this difference. The first is the number of embryos transferred: the risk of multiple pregnancy increases as the number of embryos transferred increases. The second is biological: monozygotic twinning is increased after induced ovulation and in vitro fertilization. Ovarian stimulation can also raise the number of eggs released, so while most of these pregnancies are twins, up to 5% are triplets or greater.\n\nRisks for mothers and infants\n\nFetal and neonatal risks are higher in twins than in singletons, including congenital anomalies, preterm birth, low birthweight, neonatal intensive care admission, perinatal mortality, and stillbirth. Gestational duration falls with each additional fetus: the mean gestational age at delivery is approximately 37 weeks for twins, 33 weeks for triplets, and 28 weeks for quadruplets. Monochorionic twins face additional hazards, including twin-twin transfusion syndrome and a higher incidence of congenital anomalies. Where a multiple pregnancy is high-order, patients are often offered fetal reduction, a procedure that carries a small procedure-related loss rate, approximately 4%. Multiple embryo transfer also affects singletons, since it increases the risk of major congenital anomalies, small for gestational age, low birth weight, and preterm birth in singleton births. Ovarian hyperstimulation syndrome is another recognized risk of IVF.\n\nOutcomes compared with spontaneous pregnancy\n\nAssisted pregnancies are associated with increased risk for adverse perinatal outcomes relative to spontaneous ones. A German retrospective cohort comparing spontaneous conception (N = 14,233) and ART (N = 785) found that every fifth pregnancy after ART was a twin pregnancy, with higher risks for preterm delivery, maternal hospitalization and adverse neonatal outcome. The same authors noted that twin pregnancies can be actively avoided using the single embryo transfer strategy, which is why single embryo transfer has become the default in many guidelines. Within twin pregnancies after IVF, a study found that maternal age significantly influenced prematurity risk, while paternal age, maternal body mass index, and the number of oocytes retrieved or embryos transferred were not associated with gestational duration. Much of the excess risk after assisted conception therefore appears linked to multiplicity and to maternal age, rather than to fertilization in the laboratory itself.\n\nSurrogacy, surplus embryos and legal frameworks\n\nWhen a fertilised egg from egg and sperm donors implants in the uterus of a genetically unrelated surrogate, the resulting child is also genetically unrelated to the surrogate. Surrogacy raises medical concerns, including the physical burden on the carrier and the handling of pregnancies with multiplicity, as well as ethical questions about payment, consent and the welfare of the child. Some countries have banned or otherwise regulated the availability of IVF treatment, giving rise to fertility tourism. Surrogacy law varies accordingly: some jurisdictions prohibit commercial arrangements while permitting altruistic ones, and others set out parentage rules by statute or court order. Surplus embryos are commonly cryopreserved, and their disposition, whether discarding, donating to another couple, or donating to research, is typically governed by consent forms and national rules."
    },
    {
      "heading": "Legal, Social and Ethical Dimensions",
      "text": "Workplace protections\n\nThe main international standard is the ILO Maternity Protection Convention, 2000 (No. 183), which followed earlier conventions adopted in 1919, 1952 and the first ILO conference. It sets a minimum of 14 weeks of maternity leave, with at least six of those weeks after childbirth, and requires that a cash benefit allow the woman to maintain herself and her child. It also bars employers from dismissing a woman during pregnancy or leave, places the burden of proof on the employer to show that a dismissal is unrelated to pregnancy, and extends coverage to all employed women, including those in atypical forms of work. Even so, the ILO estimates that around 830 million women workers are still inadequately protected, nearly 80 per cent of them in Africa and Asia.\n\nImplementation varies widely. Bulgaria provides the longest paid leave of any country in most comparisons, at roughly 58 weeks, while Norway offers 49 weeks at full pay or a longer period at reduced pay. In the United States, there is no federal guarantee of paid maternity leave. The Family and Medical Leave Act instead grants up to 12 weeks of unpaid, job-protected leave to eligible employees, and access depends on employer size, tenure and state programmes. Several small Pacific states also lack a guaranteed paid leave entitlement for mothers. Across countries, the central question is often who pays: where social insurance or public funds cover benefits, employers are less likely to avoid hiring women of childbearing age, a logic built into the ILO standards. Discrimination against women on grounds of maternity remains widespread even where laws exist, and enforcement is a persistent challenge.\n\nLegal recognition of pregnancy and the fetus\n\nMost legal systems do not treat a fetus as a full legal person. Many civil codes make the acquisition of rights conditional on live birth. Argentina's Civil Code, for example, states that rights of the conceived are acquired only if the child is born alive, and that a child not born alive is considered never to have existed. In the United Kingdom, the fetus has traditionally been regarded as part of the pregnant woman without separate rights, while Ireland was the first country to write explicit protection of the fetus's right to life into its constitution, a provision later repealed by referendum in 2018.\n\nIn the United States, the legal status of the fetus has been especially contested. The 1973 decision in Roe v. Wade held that a fetus is not a \"person\" with constitutional rights, and the 2022 decision in Dobbs v. Jackson Women's Health Organization overturned Roe and returned abortion regulation to the states. Since then, several states have adopted personhood-style definitions; a Georgia law from 2022, for example, defines human life to include any stage of development carried in the womb, and Texas defines an unborn child from fertilization. Federal law, through the Unborn Victims of Violence Act of 2004, treats a child in utero as a victim when harmed during certain federal crimes, without granting full constitutional personhood. Legal scholars have also raised questions about how fetal personhood would affect inheritance and property rules, such as the rule against perpetuities. Parental rights, child support and access to health services are typically assigned by separate statutes, so the recognition of pregnancy differs by context.\n\nEthical debates: autonomy, consent and the interests of the fetus\n\nMedical ethics in pregnancy centres on the tension between the autonomy of the pregnant person and the interests of the fetus. Informed consent is generally required for medical treatment, yet in some jurisdictions courts have authorised interventions over a woman's objection, and some state actions, such as detaining a pregnant woman to protect the fetus, have been challenged in court. Legal arguments in such cases often draw on whether the fetus holds constitutional or due-process rights, a question on which national courts and legislatures have reached different conclusions. Human rights frameworks, including the Universal Declaration of Human Rights and the UN Convention on the Elimination of All Forms of Discrimination against Women, are invoked by both sides. Ethical positions therefore tend to reflect the legal culture of each country as much as medical evidence.\n\nSocial determinants of pregnancy experience and outcome\n\nIncome, marital status and the availability of social support are consistently associated with differences in pregnancy experience and outcome. Women with low income are more likely to have limited access to antenatal care, nutrition and safe housing, and they are less able to take unpaid leave. Single mothers may face greater financial and caregiving strain, while stable partnerships and support from family or community networks are linked to better mental health and attendance at prenatal care. These factors interact with the legal protections described above: the value of statutory leave depends on whether a woman is employed in the formal sector and can afford to take it. Public policy responses, such as paid leave, cash benefits and free antenatal services, aim to reduce these disparities, though their effects vary by setting and are measured through social determinants of health research and epidemiological studies."
    },
    {
      "heading": "Cultural Practices and Rituals",
      "text": "Pregnancy and birth are surrounded by customs that differ sharply between societies. Anthropologists treat the rites that accompany biological and social transitions as a shared human pattern. Such ceremonies mark a change in a person's status and usually rest on community tradition, and are found in many societies.\n\nDietary customs and taboos\n\nFood restriction is the most widespread pregnancy custom. A cross-cultural meta-analysis of 32 studies on antenatal dietary restrictions detected a gradient in taboo focus, ranging from no direct physiological interest to fear of varied physiological complications, and a specific concern over increased birth weight and difficult delivery. The same analysis found that agricultural taboos tended to target more cultivated and processed products and showed a stronger association with concerns over increased birth weight. Some restrictions remove important nutrients. In several African countries, pregnant women are usually forbidden from consuming the richest food-sources of iron, carbohydrates, animal proteins and micronutrients. The stated motives include fears about the child's later habits, large babies and prolonged labour, and the beliefs that certain foods stimulate continuous menstruation, leading to infertility in women. Compliance is uneven. In one Ethiopian study, women who did not adhere to these restrictions either secretly ignored certain taboos or compensated with alternative nutritious foods when they could afford to.\n\nMany East Asian and South Asian beliefs classify foods by heat rather than by nutrient content. In China, pregnant women are advised to avoid \"cold\" foods like watermelon and certain seafood to maintain \"yin-yang\" balance. In India, a food is labelled \"hot\" because pregnancy is considered a period of increased heat in the body, women are advised to avoid such 'hot' food items, and the term refers to thermal effect rather than spiciness or temperature.\n\nPostpartum confinement\n\nThe best-documented postnatal custom is the Chinese practice known as zuo yuezi, or \"sitting the month\". The earliest record of the Chinese custom of postpartum confinement dates back over 2,000 years in the Book of Rites, where it was known as yuè nèi. In its classic form, her mother or mother-in-law takes over childcare, cooking, and domestic work while the new mother rests. The woman must avoid certain activities, including taking a bath or shower, participating in social activities, seeing visitors, going out of the house, and washing her hair. A Fujian qualitative study reported that the practice was commonly practiced in urban and rural families to help the mother regain her strength and protect her future health. Its dietary elements include eating more food and avoiding cold food, and the main reasons for adherence were respect for tradition, and following the advice of elders.\n\nThe stated rationale is thermal and humoral. Keeping the body warm is believed to help ensure that your body retains as much heat as possible, and to help you avoid health problems such as rheumatism, arthritis, headaches and body pains later in life. Some elements overlap with biomedical advice. The Fujian study found that several zuo yuezi practices are beneficial, including eating more, eating protein rich food, avoiding housework, and daily vulval and perineal hygiene. Others are contested. Restrictions on bathing and hair washing have been questioned, and in 2015, a new mother in Shanghai following the custom died of heatstroke after wrapping herself in a quilt and turning off the air conditioner, state media reported. The practice also travels. In Vietnam, postpartum confinement practices include a strict rest period of about one month. In Korea, the postpartum period is called \"sanhujori,\" and it lasts for about three weeks. Diaspora communities have adapted the custom, and some people have adapted the tradition to more modern ways.\n\nRites around birth and naming\n\nNaming is among the most formalised birth rituals. In Hinduism, the ceremony is traditionally known as Namakarana or the Namakarana Samskara, and is conducted on the twelfth day after birth. The child is given a name according to their lunar horoscope, and may not be their legal or preferred name; the name from this ceremony is usually reserved for religious activities and horoscopes. Hindu families also hold rites before birth. Some Hindus observe a ritual called Simantonnyana in the seventh month of pregnancy, during which prayers are recited.\n\nIn Judaism, the naming ceremony for Jewish boys is held on the eighth day after birth, usually together with the ritual circumcision. The naming ceremony for girls is called Simchat Bat and can be performed at any time after birth. In Islam, Muslim naming ceremonies, called 'Tasmiyah', start from the moment of birth when the father whispers a prayer in the baby's ear. The later Aqiqah involves the sacrifice of an animal, and the meat is distributed to family, friends, and the needy. This is usually performed on the seventh day after birth. In Japan, a month after birth, the baby is taken to a Shinto shrine.\n\nInteraction with biomedical care\n\nCultural beliefs shape health behaviour in ways that clinicians must account for. Food beliefs persist through generational transmission and social learning, deeply embedded in traditional beliefs and community norms. Knowledge alone does not settle practice: in Cameroon, pregnant women possessed adequate nutritional knowledge but were unable to apply it due to socioeconomic constraints, food taboos, and cultural beliefs. Religious commitments can also conflict with standard obstetric care. If postpartum hemorrhage occurs, blood product transfusion may be declined in some Jehovah's Witness practice.\n\nHealth services have responded by working within cultural frames. A study at a federally qualified health center that serves predominantly Asian immigrants surveyed women in Chinese, Vietnamese and English about \"doing the month\". Without prompting of what DTM was, 58 (37.7%) responded that they had heard of DTM. After an explanatory paragraph, this increased to 117 (76.6%) participants. The result suggests that awareness of such practices is often shallower than assumed, and that culturally framed explanation changes what patients report knowing."
    },
    {
      "heading": "Research Frontiers and Open Questions",
      "text": "Spontaneous preterm birth remains one of the least understood problems in obstetrics. Investigators increasingly treat it as a syndrome with several possible starting points, including infection, reduced blood flow to the placenta, overdistension of the uterus and stress-related immune processes. This complex phenotype is now thought to be a syndrome initiated by multiple mechanisms, including infection/inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress, and other immunologically mediated processes. Upstream signals such as placental senescence and changes in the vaginal microbiome are considered to feed into these pathways. These pathways are influenced by upstream signals from placental senescence and the vaginal microbiome. Many cases appear to be driven by microbes that provoke inflammation harmful to both mother and newborn. Spontaneous preterm birth is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. The sequence linking these triggers to labour before 37 weeks is still not fully mapped, and it is unclear which route dominates in an individual woman.\n\nThe search for predictive biomarkers has so far been disappointing. Reviews of proteomic and multiplex studies have not identified a marker that accurately forecasts the condition, even though many candidates have a plausible mechanistic link to it. According to the existing literature, there are no specific proteomic biomarkers capable of accurately predicting PTB. A meta-analysis of 30 candidate markers judged that none of them was clinically useful for asymptomatic women with singleton pregnancies. None of the 30 novel biomarkers evaluated in this review meets the criteria to be considered a clinically useful test to predict spontaneous preterm birth in women with singleton pregnancies and no symptoms of preterm labour. More recent syntheses are slightly more positive. One review concluded that no single marker is accurate enough on its own, while some panels carry clinically meaningful information, including cervical ultrasonography, urinary metabolite panels and maternal circulating cell-free RNA. No single biomarker can accurately predict sPTB. However, several individual or combined panels of biomolecules, including some commercially available, carry clinically significant predictive information. Critics attribute the stalled progress largely to methodology. Major areas of concern include poor phenotype definition, nonideal study designs and poor rationale for biomarker selection and assays and population stratification issues. Newer efforts use systems biology and machine learning to model pregnancy trajectories, and some groups have profiled maternal blood at mid-pregnancy to look for early molecular signatures. Systems biology, mathematical modeling, and machine learning (artificial intelligence) are being discussed for their potential to map pregnancy trajectories and uncover the patient phenotypes underlying PTB risk.\n\nResearch on the long-term effects of prenatal exposure has grown out of the developmental origins of health and disease (DOHaD) framework. Epidemiological work by David Barker in the 1980s and 1990s linked poor fetal nutrition to later cardiovascular and metabolic disease. David Barker first presented evidence in the 1980s and 1990s which suggested that maternal/fetal undernutrition at various stages of pregnancy could alter the susceptibility of offspring to metabolic and cardiovascular disease in later life. Subsequent studies have strengthened the link between restricted growth or low birth weight and lasting cardiovascular risk. A proposed mechanism for the link with hypertension involves a reduced number of nephrons, the kidney's filtering units, formed during development. It has been proposed that the link between non-optimal prenatal growth and hypertension may be through impaired nephrogenesis. Current work examines diet and pollution as well. Recent studies have provided strong evidence that prenatal exposure to excessive intake of sugar-sweetened beverages, unhealthy dietary patterns, perfluoroalkyl substances, and fine particulate matter may increase risk of adverse health outcomes, such as obesity, cardiometabolic dysfunction, and allergy/asthma. The biological routes behind such effects, particularly transgenerational ones, are still poorly defined. The mechanism(s) for these effects are still unclear. Methodological problems also hamper the field. Paternal, postnatal and social influences have received less attention, which makes it harder to test the hypothesis rather than simply reinforce its assumptions. There has been much less of a focus on other types of exposure, including postnatal factors, paternal factors, and the wider social determinants of health. This makes it difficult to test (rather than merely reinforce) the DOHaD hypothesis. Because the epidemiological designs often compare exposures and outcomes at a single point in time, delayed effects can be missed. This approach to large extent omits the latency times.\n\nThe study of the placental and fetal microbiome illustrates how contested a new research area can be. For more than a century the womb was regarded as sterile, and sequencing studies of placenta, amniotic fluid and meconium later appeared to challenge that view. For more than a century, the prenatal environment was considered sterile. Over the last few years, findings obtained with next-generation sequencing approaches from samples of the placenta, the amniotic fluid, meconium, and even fetal tissues have challenged the dogma of a sterile womb. Subsequent analyses with rigorous negative controls have attributed much of the reported signal to laboratory and environmental contamination, because placental samples contain very little microbial DNA. These contaminants are usually negligible when investigating body sites or environmental niches where bacteria are abundant; however, the issue becomes critical when studying biological material that is inherently low in microbial biomass, such as meconium or placental tissue. Some studies still report a community in first-pass meconium. The authors of one such study proposed either colonization around birth or, less probably, transfer of bacterial vesicles before birth. The first-pass meconium, however, appeared to harbor an actual microbiome, which may be explained by perinatal colonization, or hypothetically, partly by intrauterine colonization through bacterial extracellular vesicles. The question matters because it bears on the origins of the infant gut flora. The existence of microbial communities within the placenta or fetal gut has major implications for the establishment and maturation of the neonatal gut microbiome. Interest in placental function more broadly, including epigenetic regulation and the placenta's responses to maternal conditions, is growing, although the placenta is difficult to study in living humans.\n\nArtificial womb technology aims to support extremely premature infants outside the uterus, a gap that remains between the current limits of neonatal intensive care and the earliest gestational ages that can be supported. Animal experiments, including work on premature lambs in a fluid-filled bag system reported in 2017, have shown that prolonged extra-uterine support is technically possible. Human use remains experimental. Its prospects raise questions about the threshold for intervention, the long-term neurodevelopmental outcome, the consent of parents, and the moral status of a fetus kept in an artificial environment.\n\nClinical trials in pregnant populations face a long-standing tension. Pregnant people were routinely excluded from research for decades, partly because of the thalidomide tragedy, and this left limited evidence on the dosing and safety of many medicines in pregnancy. Efforts to include them have since increased, but pregnancy is still often an exclusion criterion. Ethical constraints are substantial. The fetus cannot give consent, so informed consent must be sought from the pregnant person, and the risks to the fetus must be weighed against any benefit to either party. Placebo-controlled designs are difficult to justify when effective treatment exists, and the physiological changes of pregnancy alter how drugs are absorbed and cleared. For these reasons, observational registries and pregnancy cohort studies are often used alongside, or instead of, randomized controlled trials."
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  "sources": [
    {
      "title": "Gestation",
      "url": "https://en.wikipedia.org/wiki/Gestation"
    },
    {
      "title": "Gestational Age - Pediatrics - MSD Manual Professional Edition",
      "url": "https://www.msdmanuals.com/professional/pediatrics/perinatal-problems/gestational-age"
    },
    {
      "title": "Gestational age determination",
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  ],
  "license": "https://creativecommons.org/licenses/by/4.0/"
}