Diagnosis of pregnancy and normal physiology

• Pregnancy can be diagnosed clinically only after it is established, and it is confirmed with urine or serum beta-human chorionic gonadotropin (beta-hCG) together with a pelvic ultrasound that shows an intrauterine pregnancy. ^{[3] [4]}
• A urine test is the first test for most women. A serum beta-hCG is more sensitive, can be repeated to check the rate of rise (about a doubling every 48 hours in early normal pregnancy) (Ref 7), and is used when the diagnosis is uncertain.
• On ultrasound, a normal early pregnancy becomes visible once the beta-hCG reaches the discriminatory threshold of roughly 1500 to 2000 mIU per mL on transvaginal scanning (Ref 7).
• Dating is best fixed by a first-trimester ultrasound (crown-rump length), ideally by 13 6/7 weeks; a pregnancy with no ultrasound that confirms or revises the due date before 22 0/7 weeks is "suboptimally dated" (Ref 1).
• Pregnancy is a systemic condition: by the end of the first trimester cardiac output has risen by about 40 to 50 percent (Ref 8), renal blood flow by about 50 to 80 percent (Ref 8) and plasma volume by about 50 percent (Ref 8), driven largely by progesterone and oestrogen.

By the end of this page you should be able to:

1. Explain how pregnancy is diagnosed, the role of urine and serum beta-hCG, and when a pregnancy test can be falsely negative or positive.
2. Describe the ultrasound criteria and the beta-hCG discriminatory zone that separate a normal early pregnancy, a pregnancy of unknown location and an ectopic pregnancy.
3. Date a pregnancy accurately from the last menstrual period and from first-trimester (and later) ultrasound measurements, using current ACOG/NICE/WHO guidance.
4. Outline the normal physiological changes in each major maternal system, with their approximate magnitude, and explain why they occur.
5. Apply the routine pattern of antenatal care and screening recommended by current guidelines, and recognise the red flags that need urgent referral.

Pregnancies are classified in several ways that matter day to day:

• By number: singleton vs multiple pregnancy (twins, triplets).
• By viability: viable vs early pregnancy loss; threatened, inevitable, incomplete or complete miscarriage.
• By position: intrauterine vs ectopic (every pregnancy implanted outside the endometrial cavity; in the UK incidence is about 11 in 1000 pregnancies, roughly 11 000 a year) (Ref 5). ^[5]
• By knowledge of dating: optimally vs suboptimally dated (a pregnancy with no ultrasound that confirms or revises the estimated due date before 22 0/7 weeks is suboptimally dated) (Ref 1).
• By product of conception: a normal pregnancy vs a molar pregnancy or other trophoblastic disease.

Human chorionic gonadotropin (hCG) is the signal of pregnancy. It is a family of four isoforms, each with a distinct biological role and cell of origin: villous syncytiotrophoblasts, multiple primary non-trophoblastic malignancies or tumours, the anterior pituitary gland, and cytotrophoblast cells (Ref 6). The isoform made by the villous syncytiotrophoblast is the one measured in pregnancy tests; its principal jobs are to promote progesterone production by the corpus luteum so that the lining of the uterus is maintained, and to support the growth and differentiation of the trophoblast. Through these actions it allows the coordinated growth of the fetus and uterus, signals to the endometrium that implantation is about to occur, supports growth of the umbilical cord, and promotes fetal growth and organogenesis (Ref 6). ^[6]

Pregnancy affects essentially all women of reproductive age at some point. In countries with good registration, a normal pregnancy lasts about 40 weeks from the LMP (about 280 days) (Ref 1). The factors that most affect how a single pregnancy is managed are not "risk factors for being pregnant" but the context: maternal age, parity, previous pregnancy outcomes, pre-existing medical disease (heart, kidney, respiratory, endocrine, mental health), infections, previous venous thromboembolism, multiple pregnancy, and social deprivation. NICE specifically flags that, compared with white women (8 per 100 000), maternal mortality is 4 times higher in black women (34 per 100 000), 3 times higher in women of mixed ethnicity (25 per 100 000) and 2 times higher in Asian women (15 per 100 000), and that women living in the most deprived areas are more than 2.5 times more likely to die (15 vs 6 per 100 000) (Ref 2). These inequalities are listed because they change how closely a woman should be monitored, not because ethnicity or deprivation is a cause. ^[2]

A normal pregnancy begins with ovulation, fertilisation and implantation, a sequence that is invisible to the patient and to the clinician; the first clinical evidence is the missed period and the positive pregnancy test. The only "risk factors" that raise the chance of an abnormal outcome of the pregnancy are the well-known ones (maternal age, medical disease, multiple pregnancy, previous pregnancy complications) and these are best handled as part of antenatal risk assessment, covered under management below.

Pregnancy starts physiologically when hCG from the syncytiotrophoblast rescues the corpus luteum, so progesterone (and oestrogen) secretion continues instead of the endometrium being shed as a period. hCG is detectable in blood within days of implantation and is the target of pregnancy tests (Ref 6).

From that point on almost every maternal system is remodelled. A useful central idea: many of these changes begin in the luteal phase of every ovulatory cycle and are simply amplified if conception occurs. They appear to be driven largely by progesterone, with oestrogen and other placental hormones layering on top (Ref 8). Teleologically there are two reasons: to provide a suitable environment for the nutrition, growth and development of the fetus, and to protect and prepare the mother for parturition and for feeding the newborn (Ref 8).

The placenta itself is a major endocrine organ: it makes large amounts of oestrogen and progesterone, peptide hormones such as hCG and placental lactogen, corticotrophin-releasing hormone and prostanoids, and it manipulates the maternal immune response so that the fetus is accepted (Ref 8).

Women present for diagnosis for two main reasons: a missed period with symptoms of pregnancy (nausea, breast tenderness, urinary frequency, tiredness), or a positive home test. Common first-trimester symptoms are summarised here, with their mechanisms:

• Nausea and vomiting (often called "morning sickness") are very common in pregnancy; severe vomiting (hyperemesis gravidarum) complicates a smaller fraction. It usually resolves before 16 to 20 weeks (Ref 2). ^[2]
• Breast tenderness and enlargement result from oestrogen and progesterone stimulation of ducts and lobules.
• Urinary frequency in early pregnancy arises from the enlarged uterus pressing on the bladder and, later, from increased renal blood flow and the filtered load of fluid.
• Fatigue reflects the metabolic demand and the hormonal changes.
• Heartburn is common later in pregnancy, related to displacement of the gastro-oesophageal junction through the diaphragm and reduced tone of the lower oesophageal sphincter.
• Constipation results from progesterone-mediated gut hypomotility and increased colonic absorption of water and sodium.
• Symptomatic vaginal discharge is normal in pregnancy (the vaginal epithelium hypertrophies, glycogen increases, and Doderlein's bacilli produce lactic acid, giving a pH of 3.5 to 4.0 (Ref 8); itching, soreness, a bad smell or pain on passing urine suggests infection (Ref 2).

"Presumptive" and "probable" signs of pregnancy (nausea, amenorrhoea, Goodell's sign, Chadwick's sign, Hegar's sign) are clinical clues but are not proof. The diagnosis rests on testing.

Early signs that a doctor can elicit:

• Softening of the cervix (Goodell's sign), softening of the uterine isthmus (Hegar's sign), and bluish discoloration of the cervix/vulva (Chadwick's sign), all from increased vascularity and oedema.
• Enlarged, tender uterus, rising out of the pelvis during the first trimester.
• Palpable fetal parts and audible fetal heart tones come later in pregnancy (by Doppler, later by stethoscope).
• Blood pressure: there is a fall in mean arterial pressure of about 10 mmHg in the first half of pregnancy, with the nadir at 16 to 24 weeks; this is normal and must not be mistaken for improvement or for shock (Ref 8). Blood pressure is lowest on the left side; posture significantly affects the reading, so it should be recorded in the same position each visit (Ref 8).
• Examination also looks for red flags: an adnexal mass or single-sided pelvic pain suggesting ectopic pregnancy, fever suggesting infection, and severe dehydration from hyperemesis.

A woman with a positive pregnancy test is not usually a diagnostic puzzle, but a woman with bleeding, pain or a rising beta-hCG and no visible intrauterine pregnancy is. The possibilities and the features that separate them are set out here.

The diagnosis of pregnancy rests on three things: the clinical story, a biochemical test, and an ultrasound.

Points on interpretation that prevent mistakes:

• False negatives occur with testing too early, very dilute urine, and occasionally with very high "hook effect" levels (rare with modern assays).
• False positives occur with recent pregnancy (miscarriage, abortion, delivery), hCG-secreting tumours (including malignant trophoblastic disease), exogenous hCG (fertility treatment) and, very rarely, pituitary hCG.
• A pregnancy test should not be needed routinely if the story is clear but is essential before diagnosing the cause of pelvic pain or bleeding in a woman of reproductive age.

Dating is part of the diagnosis, because every later decision (screening windows, growth assessment, induction) depends on it.

• By convention gestational age is calculated from the first day of the LMP; the "due date" (EDD) is 280 days (40 weeks) later (Ref 1). ^[1]
• A regular 28-day cycle with ovulation on day 14 is assumed. Only about half of women recall their LMP accurately, and 40 percent of women randomised to first-trimester ultrasound had their EDD changed because the scan disagreed with the LMP by more than 5 days (Ref 1). ^[1]
• First-trimester ultrasound (up to and including 13 6/7 weeks) is the most accurate way to date the pregnancy. The crown-rump length (CRL) has an accuracy of plus or minus 5 to 7 days (Ref 1). The measurement should be the mean of three discrete CRL measurements, taken in a true midsagittal plane with the genital tubercle and fetal spine in view and the maximum straight-line length measured from cranium to rump (Ref 1). ^[1]
• Mean sac diameter is not recommended for estimating the due date, and once the CRL exceeds 84 mm (about 14 0/7 weeks) CRL dating is less accurate, so second-trimester biometry is used (Ref 1). ^[1]
• Redating rules (Ref 1): if ultrasound before 14 0/7 weeks differs from the LMP by more than 7 days, change the EDD; before 9 0/7 weeks a discrepancy of more than 5 days is enough; between 14 0/7 and 15 6/7 weeks a discrepancy of more than 7 days; between 16 0/7 and 21 6/7 weeks more than 10 days; between 22 0/7 and 27 6/7 weeks more than 14 days. In the third trimester dating is least reliable (plus or minus 21 to 30 days) and should only be changed by more than 21 days, with the whole clinical picture taken into account (Ref 1). ^[1]
• If the pregnancy came from assisted reproduction, the ART-derived age is used: for example, a day-5 embryo gives an EDD 261 days after the embryo transfer date, and a day-3 embryo 263 days after transfer (Ref 1). ^[1]
• A pregnancy with no ultrasound that confirms or revises the EDD before 22 0/7 weeks is suboptimally dated, which matters for interpreting later size and tests (Ref 1). ^[1]
• If the woman is unsure of her LMP, date from the earliest ultrasound with a CRL measurement (Ref 1).
• Once a good early scan has been done, do not re-date later in pregnancy (Ref 1).

A normal pregnancy is one in which a gestation sac is seen in the uterus, the dates agree within the rules above, and (after about 6 weeks) (Ref 9) an embryo with cardiac activity is seen appropriate to the size. ^[9]

There is no "treatment" for a normal pregnancy itself; management means confirming it, dating it, anticipating the physiological changes, and providing the routine care and screening recommended by current guidelines.

Approach (Ref 1, Ref 2, Ref 3, Ref 4):

• Confirm and date. A positive home test followed, where appropriate, by a first antenatal ("booking") appointment with a midwife. NICE recommends the booking appointment by 10 plus 0 weeks (Ref 2). Where a woman is unsure of dates or there is any concern, arrange an early ultrasound. ^[2]
• First-trimester ultrasound. NICE recommends an ultrasound between 11 plus 2 and 14 plus 1 weeks to determine gestational age and detect a multiple pregnancy, and (if consented) to screen for trisomies within the NHS fetal anomaly screening programme (Ref 2). ACOG, together with the ultrasound college and the maternal-fetal medicine society, would agree that a first-trimester scan is the most accurate way to date the pregnancy (Ref 1). ^[2]
• Second-trimester ultrasound between 18 plus 0 and 20 plus 6 weeks to screen for anomalies and locate the placenta (Ref 2). ^[2]
• Antenatal screening offered at booking: infectious diseases in pregnancy (HIV, syphilis, hepatitis B), sickle cell and thalassaemia screening, and fetal anomaly screening. Also a full blood count, blood group and rhesus D status; urine testing for protein; an assessment of risk for pre-eclampsia, gestational diabetes and venous thromboembolism; and, for women who smoke, a referral to stop-smoking services (Ref 2).
• Monitoring through pregnancy: blood pressure and proteinuria at every routine face-to-face appointment; symphysis-fundal height after 24 weeks for singleton pregnancies unless regular growth scans are planned; blood tests at 28 weeks (full blood count, blood group and antibodies) and anti-D prophylaxis for rhesus-negative women; reduced-fetal-movement advice after 24 weeks; breech palpation after 36 weeks (Ref 2). ^[2]
• Risk-specific care: at-risk women are advised to take aspirin for pre-eclampsia prophylaxis under the NICE hypertension in pregnancy guidance, and those at risk of gestational diabetes have an oral glucose tolerance test at 24 to 28 weeks (Ref 2). Risk assessment for fetal growth problems is repeated in the second trimester (Ref 2).
• WHO approach: WHO's antenatal care recommendations for a positive pregnancy experience are risk-stratified, emphasise adequate routine contact, and include the maternal and fetal assessment update that recommends ultrasound at least before 24 weeks (Ref 3, Ref 4).
• Common symptoms: mild to moderate nausea and vomiting are common, usually settle before 16 to 20 weeks, and can be managed with a trial of ginger and, where needed, antiemetics chosen from NICE's table of options; symptomatic vaginal discharge gets a swab and treatment of candidiasis with a vaginal imidazole; heartburn with lifestyle advice and, if needed, a trial of antacid or alginate (Ref 2).
• Venous thromboembolism prophylaxis is based on risk assessment at booking and after any admission, using an appropriate body such as RCOG guidance (Ref 2).
• Red flags that need urgent referral: a positive pregnancy test with one-sided pelvic pain and bleeding (exclude ectopic pregnancy), severe vomiting with weight loss or ketosis, heavy bleeding, severe abdominal pain, severe headache or visual disturbance, very high blood pressure, absent or reduced fetal movements after 24 weeks, or suspected fetal growth restriction (Ref 2).
• Early pregnancy information should include modifiable factors: stop smoking, avoid alcohol, take folate supplementation as recommended locally, eat a balanced diet, and be physically active (Ref 2).

NICE organises antenatal care into 10 routine appointments for nulliparous women and 7 for parous women, with more when needed, and recommends that the first booking appointment happen by 10 plus 0 weeks (Ref 2). Starting care can also include occupational and domestic-abuse enquiry, a discussion of mental health, and sharing information with the woman's GP. ^[2]

The diagnosis of pregnancy is not complete when the test is positive but the scan is empty. A pregnancy of unknown location, a falling beta-hCG, or an empty gestation sac each needs serial beta-hCG and repeat imaging, and (where the level is above the discriminatory zone without an intrauterine sac) action to exclude ectopic pregnancy (Ref 5, Ref 7). Methotrexate and surgery are the definitive treatments for ectopic pregnancy and are organised by the early pregnancy team, not by the routine pregnancy pathway, so they are not described here beyond that note.

Pregnancy is the context in which these complications occur; the more a reader wants on each, the further MedGrasp topics on them will go. Briefly:

• Early pregnancy loss is common in the first trimester.
• Ectopic pregnancy (about 11 per 1000 pregnancies in the UK) is the one diagnosis never to miss, because delay is fatal (Ref 5).
• Hyperemesis gravidarum can cause dehydration and weight loss and may need inpatient care.
• Anaemia develops because plasma volume rises more than red-cell mass ("physiological anaemia").
• Infections in pregnancy (and pregnancy-specific infections such as chorioamnionitis, Group B streptococcus carriage) are handled on their own pathways.
• Hypertensive disorders of pregnancy, including pre-eclampsia, and gestational diabetes are the common serious morbidities and are screened for at booking and through pregnancy.
• Venous thromboembolism risk is raised, partly because of the shift in the clotting system.
• Obstetric cholestasis and other liver problems; skin and joint changes (itch, striae, pelvic girdle pain).

For a wanted, uncomplicated pregnancy the usual outcome is a term delivery (about 40 weeks) (Ref 1) of a healthy baby. The main determinants of a poor outcome are the medical and social risk factors in the epidemiology section, and the modifiable ones are where prevention bites hardest: smoking, alcohol and poor nutrition, inadequate folic acid, unsafe medicines, and late or no antenatal care.

There is no "prevention" of pregnancy, but there is prevention of poor outcomes, most of which happens at booking:

• Folic acid and iodine as recommended by local/national guidance before conception and in early pregnancy.
• Vitamin D and iron according to risk and local policy.
• Infectious disease screening (HIV, syphilis, hepatitis B), sickle cell and thalassaemia screening (Ref 2).
• Fetal anomaly screening with the first-trimester combined or second-trimester screening programme (Ref 2).
• Immunisation during pregnancy (influenza, pertussis, RSV and others per national schedule) (Ref 2).
• Modifiable risks: stop smoking, avoid alcohol, take only medicines known to be safe, register early with a midwife.

• Women with medical disease. Heart, kidney, respiratory, endocrine or neurological conditions can make the physiological changes of pregnancy dangerous (for example, the 40 percent (Ref 8) rise in cardiac output is poorly tolerated in heart disease; the massive rise in cardiac output explains why pre-existing heart disease can decompensate). These women need combined medical-obstetric care.
• Very young women (under 20) and women with complex social factors have their own NICE pathway (CG110) (Ref 2).
• Women of higher weight need assessment before and during pregnancy, and bariatric surgery changes timing.
• Women with previous pregnancy loss or subfertility need sensitive, earlier care.
• Men and partners are included in information sharing and decision-making where the woman wants them involved (Ref 2).
• The physiology chapter underlying much of this page is drawn from a women's sample; older adults and children are not normally pregnant, so those groups are outside the scope of this topic.

This section is the heart of the topic: what changes, by how much, and why. Most of the figures come from a single continuous textbook chapter by Broughton Pipkin (Ref 8). In general, many changes are "proactive": they begin in the luteal phase of every ovulatory cycle, so they are already almost complete by 12 to 16 weeks if conception occurs (Ref 8).

• Cardiac output rises by about 40 percent in a first pregnancy and about 50 percent in later pregnancies; twin pregnancies add 15 percent on top (Ref 8). Most of the rise is complete by 14 weeks, from about 4.5 to 6.0 L/min, and cardiac output can rise by a further third (about 2 L/min) during labour (Ref 8). It remains elevated for a short time after delivery before returning toward non-pregnant levels (Ref 8). ^[8]
• Heart rate rises (Ref 8); stroke volume rises from about 64 to 71 mL (Ref 8). ^[8]
• The heart enlarges by about 12 percent (70 to 80 mL) (Ref 8), the apex displaced up and to the left, with a straightened upper left border that can be mistaken for disease on a chest X-ray. ^[8]
• Total peripheral resistance falls from about 1700 dyn/s/cm to about 1200 to 1300 dyn/s/cm, roughly halving by mid-pregnancy, and mean arterial pressure falls by about 10 mmHg early on, reaching its lowest point at 16 to 24 weeks (Ref 8). ^[8]
• Blood pressure measurement must take posture into account; with the woman lying supine, compression of the inferior vena cava (and of the aorta) can cause hypotension.
• The same textbook source tabulates percentage changes in heart rate, stroke volume, cardiac output, systolic and diastolic blood pressure, mean pulmonary artery pressure and total peripheral resistance across the three trimesters; heart rate, stroke volume and cardiac output each rise, while total peripheral resistance falls (Ref 8). ^[8]

• Plasma volume increases markedly in pregnancy, peaking in the third trimester (Ref 8). Total extracellular fluid rises as well (Ref 8). Red cell mass rises during pregnancy, though less than plasma volume, depending on iron intake (Ref 8). Because plasma volume rises more than red cells, haemoglobin concentration and haematocrit fall ("physiological anaemia"). ^[8]
• The white cell count rises (Ref 8), mainly neutrophils, which increase markedly in labour; a neutrophilia in labour is normal. ^[8]
• Fibrinogen rises from 2.5 to 4.0 g/L up to as high as 6.0 g/L (Ref 8); the erythrocyte sedimentation rate rises early (Ref 8); platelet numbers fall modestly and reactivity increases (Ref 8). Factors VII, VIII, VIII:C, IX and X rise; factor XI falls to 60 to 70 percent and factor XIII to 50 percent (Ref 8). Protein S falls, protein C is probably unchanged (Ref 8). ^[8]
• The net effect is a pro-thrombotic state that is protective at delivery but raises the risk of thrombotic disease in pregnancy and the puerperium.

• Tidal volume rises from about 500 mL to about 700 mL (a 40 percent increase) (Ref 8); respiratory rate stays at 14 to 15 breaths per minute (Ref 8), so minute ventilation rises by 40 percent, from about 7.5 to 10.5 L/min (Ref 8). ^[8]
• Progesterone sensitises the medulla to carbon dioxide, driving some over-breathing; arterial PCO2 falls, bicarbonate falls, and arterial pH stays constant. Oxygen consumption rises by about 16 percent by term (Ref 8).
• Residual volume falls by about 300 mL while inspiratory capacity rises by about 300 mL (Ref 8). ^[8]
• Pregnancy is not generally an extra risk for women with respiratory disease, with the exception of severely restrictive disease.

• Renal blood flow increases 50 to 80 percent in the first trimester and falls by about 15 percent thereafter (Ref 8); glomerular filtration rate (creatinine clearance) rises about 25 percent by 4 weeks after the LMP and about 45 percent by 9 weeks (Ref 8). ^[8]
• Plasma osmolality falls by about 10 mOsm/kg and plasma creatinine and urea fall, so "normal" lab ranges are misleading unless pregnancy ranges are used (Ref 8).
• Glycosuria is a feature of normal pregnancy, and up to 200 mg of total protein per 24 hours is accepted in late pregnancy (Ref 8).
• Serum uric acid falls by about 25 percent to mid-pregnancy (normal range 148 to 298 micromol/L, upper limit about 330) (Ref 8). Water is retained (plasma osmotic threshold for thirst falls between weeks 4 and 6), and plasma sodium and potassium concentrations fall slightly despite net gains of about 950 mmol of sodium and 350 mmol of potassium overall (Ref 8). ^[8]
• The ureters and renal pelvis dilate (more on the right), under progesterone and from mechanical effects, raising the risk of urinary stasis and infection.

• Gastric secretion is reduced, motility is low and gastric emptying is delayed; colonic water and sodium absorption rises.
• Heartburn is common (displacement and reduced tone of the lower oesophageal sphincter).
• Hepatic synthesis of albumin, globulin and fibrinogen increases under oestrogen, and bile accumulates (gallbladder larger, empties more slowly).
• Plasma total protein falls by about 1 g/dL in the first trimester (from about 7 to 6 g/dL) (Ref 8), driven mainly by albumin. ^[8]

• Fasting plasma glucose falls by 0.5 to 1.0 mmol/L (Ref 8) by 6 to 12 weeks (Ref 8); insulin rises; later in pregnancy insulin resistance develops (placental hormones), which is why gestational diabetes is tested for at 24 to 28 weeks (Ref 2).
• Lipids rise: triglycerides about threefold and cholesterol about 50 percent (Ref 8); free fatty acids are raised in late pregnancy (Ref 8); fat is deposited mainly in the second trimester (2 to 6 kg) (Ref 8). ^[8]
• Total plasma calcium falls with albumin, but ionised calcium is unchanged (Ref 8); 1,25-dihydroxyvitamin D doubles, doubling gastrointestinal calcium absorption from 24 weeks (Ref 8). ^[8]
• Plasma folate halves by term (greater renal clearance) (Ref 8). ^[8]

• The placenta produces large amounts of oestrogen and progesterone. Oestrogen raises thyroxine-binding globulin and cortisol-binding globulin. Prolactin rises steadily (Ref 8) and the pituitary enlarges by 30 percent in primigravid and 50 percent in multiparous women (Ref 8). ^[8]
• Growth hormone, luteinising hormone and follicle-stimulating hormone are suppressed. Thyroid-stimulating hormone is essentially unchanged, but thyroid tissue may enlarge in up to 70 percent of women (more when iodine intake is low) (Ref 8). ^[8]
• Cortisol (total and free) rises (Ref 8); aldosterone rises progressively (Ref 8); deoxycorticosterone is increased by 8 weeks (Ref 8). ^[8]
• The renin-angiotensin system is activated early, sodium is retained (3 to 5 mmol per day), plasma volume is expanded, but pressor sensitivity to angiotensin II is normally reduced (lost in pre-eclampsia) (Ref 8). ^[8]

• Uterus: from 40 to 100 g to 800 to 1000 g (Ref 8); cavity from 4 mL to about 4000 mL (Ref 8); uterine blood flow from 50 mL/min at 10 weeks to 500 to 600 mL/min at term (Ref 8). Myometrium stays quiescent under progesterone, with Braxton Hicks contractions that do not dilate the cervix. ^[8]
• Breasts: duct growth under oestrogen; alveolar growth under progesterone and prolactin; colostrum from 3 to 4 months; lactation reaches 500 to 1000 mL/day, needing about 500 extra kcal (plus 250 from fat stores) (Ref 8). ^[8]
• Skin: chloasma, linea nigra, striae (from disruption of collagen) (Ref 8); skin blood flow increases, allowing heat loss.
• Joints, posture: relaxin-mediated laxity in pelvic ligaments and the pubic symphysis; lordosis changes.
• Weight: average gain about 12.5 kg in a woman of normal body mass index (about 0.3 kg/week to 18 weeks, 0.5 kg/week from 18 to 28, 0.4 kg/week thereafter). Basal metabolic rate rises by about 5 percent by term. Failure to gain weight is associated with fetal growth restriction; acute excess gain suggests fluid retention (Ref 8). ^[8]
• Immune system: the fetus is an allograft; protection depends on trophoblast HLA-G expression, decidual natural killer cells, a shift toward T-helper 2 (Th2) responses, and the relative suppression of cell-mediated immunity. This makes new and reactivated infections (including malaria) more dangerous; infections contribute to about 40 percent of preterm deliveries (Ref 8). ^[8]

• Conception after IVF: use the ART-derived dates (Ref 1).
• Recent pregnancy: a woman can test positive for weeks after a miscarriage, abortion or delivery.
• Trophoblastic disease: far higher than expected beta-hCG and no normal fetus.
• Pituitary or tumour hCG is rare and causes persistently low hCG without a true pregnancy.
• Women of subfertility: the early beta-hCG curve matters; the discriminatory zone and serial levels are used together.

• Pregnancy is confirmed biochemically (urine or, for more certainty, serum beta-hCG) and confirmed anatomically by an ultrasound showing an intrauterine pregnancy.
• A urine test is the first test; serum beta-hCG is used to track trends and to resolve doubt. A normal early pregnancy roughly doubles its beta-hCG about every 48 hours (Ref 7).
• The transvaginal ultrasound discriminatory zone is roughly 1500 to 2000 mIU/mL: above that level an intrauterine sac should be seen (Ref 7).
• Date the pregnancy with a first-trimester ultrasound (CRL accuracy plus or minus 5 to 7 days) (Ref 1). A pregnancy with no ultrasound before 22 0/7 weeks is suboptimally dated (Ref 1).
• The normal physiological changes are large and start early: cardiac output about 40 to 50 percent higher (almost complete by 14 weeks) (Ref 8), renal blood flow about 50 to 80 percent higher (Ref 8), plasma volume about 50 to 60 percent higher (Ref 8), tidal volume 40 percent higher (Ref 8).
• Pregnancy is a pro-thrombotic state with physiological anaemia, a lower blood pressure in mid-pregnancy, frequent glycosuria, and proteinuria up to 200 mg per 24 hours (Ref 8), all of which are normal.
• Management is largely care, not treatment: confirmation, dating, risk assessment, screening (anomaly, infectious diseases, sickle cell/thalassaemia), and routine antenatal care following NICE/WHO/ACOG/RCOG guidance.
• An ectopic pregnancy (about 11 in 1000 pregnancies in the UK) must be excluded whenever there is pain or bleeding in early pregnancy (Ref 5).