2 r o f g n i t a E " Antenatal care 8 \200 The aims of antenatal care are to: \200 Detect any disease in the mother \200 Ameliorat e the discomforts of pregnancy \200 Monitor and promote fetal well- being \200 Prepare mothers for birth \200 Monitor trends to prevent or detect any early complications of pre gnancy: BP is the most important variable (eclampsia, p48). \200 Is thromboprophylaxis (p 16) or aspirin (p3 and p31) needed? Who should give antenatal care? Midwives may manage car e, calling in doc- tors if risks (p4) or speci \201 c needs arise. Book by 12 weeks: see w ithin 2 weeks if already \211 12 weeks pregnant. Women with BMI \211 35 need consultant c are. The 1st antenatal visit is very comprehensive. \200\207Find a language interpreter if she needs one. Avoid using relatives (con \201 dentiality issues). History: \200 Usual cycle length; LMP (a normal period?); see Naegele \200\231s rule (p1). \200 Contraception ; drugs; past history, eg surgery to abdomen or pelvis. \200 Any fertility problems; outc ome and complications of past pregnancies. \200 Is there family history of diabetes, BP \200\200, fetal abnormality, or twins? \200 Does she have concurrent illness (p20 \200 \22335)? Has she been \200\230cut \200\231 (p247). If past or family history of DVT or embolism, screen for thrombophilia. Is gestational diabetes (GDM) a risk? Screen (75g glucose tolerance test) at 18 28wks) i f previous (GDM); at 24wks if BMI >30, previous baby >4.5kg, 1st degree relative diabetic, family origin (FO) from area of high risk of diabetes. \200 Past mental illness? If serio us (schizophrenia, bipolar disorder) or past post- natal problems, get antenatal assessment ; put management plan in notes. s c i r t e t s b O Is she poor (eg gas/electricity supply cut off )? Unmarried? Unsupported? Subject to domest ic violence? (p514) A substance abuser? (p362). \200\230Healthy Start Vitamins for Women \200\231 \200\224folic acid + vitamins C & D (10 g/d) are free to some during pregnancy an d for 1 year after birth (Healthy Start Scheme UK). \200 Avoid p t s & blue/soft cheese (eg Brie, Camembert, to avoid listeria, p35); Toxoplasmosis advice: p34. Avoid liver (p2). Advise UK mothers to have vita- min D (above) if family of origin is African, or as listed below,1 or housebound, covered when outdoors, have BMI >30, or are diet vit. D depleted.2 Examination: Check heart, lungs, BP, weight (record BMI), and abdomen. Is a cervical smear needed? Varicose veins? Sensitively ask if genitally \200\230cut \200\231 (p246). Tests: B lood: Hb, group (antibodies if Rh \200\223ve, p116), syphilis & rubella ( chick- en-pox) s erology, HBsAg (p36 & p26) HIV test; sickle test if black, Hb electro- phoresis (p22) and 2 5-hydroxyvitamin D if relevant. 28 Take an MSU (protein; bacteria). Arrange tests to exclud e Down \200\231s (p12). If she is foreign, a TB contact, or a hospital worker, consider CXR after 14 weeks. Off er early ultrasound to establish dates, exclude multiple pregnancy and aid with Down \200\231s tests and an 18 \200\22320-week anomaly scan. Suggest: Parentcraft /relaxation classes; dental visit. Enquire about problems and anxieties. Consider need for iron and folate (p85 and p22). Advise on: Smoking, alcohol, diet, correct use of seat belts (above or below the bump, not over it) and adequate rest. Ensure knowledge of social secu- rity bene \201 ts. Usual exercise and travel are OK (avoid malarious areas) up to 36 week s (singleton): 29 check with airline. Intercourse OK if no vaginal bleeding. Later visits C heck urine for albumin, BP, fundal height. Check lie and presen- tation at 36 weeks. Do Hb and Rh antibodies at 28 & 34 weeks and give anti-D then if needed (p9). Visits are at <12 w eeks then at 16, 25, 28, 31, 34, 36, 38, 40, and 41 weeks (primip). Weigh only if clinicall y indicated. The head is usually engaged (p40) by 37 weeks in Caucasian primips (if not, consider: large (or malpositioned) head, small pelvis or obstruction, placenta praevia, or wrong estimatio n of dates). 1 FO=family of origin from India, Pakistan, Bangladesh, Saudi Arabia, United Arab Emirates, Iraq, Jor- dan, Syria, Oman, Qatar, Kuwait, Lebanon, Egypt, or if black Caribbean. 2 Vitam in D containing foods include oily \201 sh, meat, eggs, forti \201 ed margarine, and bre akfast cereal. 9 9 Using anti-D immunoglobulin Dose: 250U for gestations <20 weeks, 500U if >20 weeks, (1500U if no Klei- hauer). Give in deltoid (buttock absorption too slow); IV \200\22530 or SC if bleeding disorder; as soon as possible after incident, by 72h (some protection if by 10d). From 20+0 weeks do Kleihauer test (FBC bottle of maternal blood; fetal RBCs therein are les s susceptible to lysis, so can be counted to measure the bleed \200\231s volume). Don \200 \231t give anti-D if already sensitized ie antibodies to anti-D are present. Postnatal use: 500U is the normal dose after 20+0 weeks \200\231 gestation. 37% of Rh \200\223 ve women g ive birth to Rh \200\223ve babies and these women do not need anti-D. \200 Anti-D should be given to all Rh \200\223ve women where the baby \200\231s group cannot be determined (eg macerated stillbirths), or if the baby \200\231s group is unknown 72h post delivery. s c i r t e t s b O Do a Kleihauer test on all eligible for anti-D. 500U anti-D can suppress im- munization by up to 4mL of fetal red cells (8mL of fetal blood), but 1% of women have transplacental hemo rrhage (TPH) of >4mL, especially after manual removal of placenta, and with cesarean sectio n. A Kleihauer test is especially important in stillbirth, as massive spontaneous transplac ental hemorrhage can be the cause of fetal death. Where >4mL TPH is suggested by the Kleiha uer screen, a formal estimation of the TPH volume is required and 500U anti-D given for eve ry 4mL fetal cells transfused (maximum 5000U anti-D at 2 IM sites/24h). Note: Kleihauer tes ts can be negative where there is ABO incompatibility as fetal cells are rapidly cleared fr om the maternal circulation. Liaise with the transfusion service. Check maternal blood ever y 48h to determine clearance of cells and need for continuing anti-D. Any mother receiving anti-D prenatally (see below), should also receive it postnatally unless she delivers an Rh-negative baby. Use of anti-D in miscarriage in Rh \200\223ve mothers 1 Anti-D should be given to all havin g surgical or medical terminations of pregnancy or evacuation of hytadiform mole (p264), un less they are al- ready known to have anti-D antibodies. Give 250U if <20 weeks; 500U (and Kleihauer) if >20+0 weeks \200\231 gestation. 2 Anti-D should always be given where spontaneous miscarriage is followed by medical or surgical evacuation. 3 Anti-D should be given where spontaneous complete miscarriage occurs after 12+0 weeks \200\231 gestation. 4 Threatened miscarriage \211 12+0 weeks give anti-D; if bleeding continues in- termittently give anti-D 6-weekly until delivery. 5 Routine anti-D is not recommended with threatened miscarriage before 12 weeks \200\231 ge station (but consider if viable fetus, heavy or repeated bleed- ing, and abdominal pain). Use of anti-D in pregnancy in Rh \200\223ve mothers 1 Give anti-D 500U at 28 and 34 weeks t o rhesus negative women (primip an- tenatal sensitization falls from 0.95% to 0.35%). Anti- D may still be detect- able in maternal blood at delivery. Still give postnatal anti-D, if indicated (as above). Take 28-week blood sample for antibodies before 28-week anti-D. 2 When signi \201 cant TPH may occur: with chorionic villus sampling; external cephalic ve rsion; APH; uterine procedures (eg amniocentesis, fetal blood sampling); abdominal trauma; intrauterine death. Use 250U before 20 weeks \200\231 gestation, 500U (and do Kleihauer) af ter 20 weeks. 3 Anti-D should be given in cases of ectopic pregnancy. 4 For threatened miscarriage, see a bove. Prenatal diagnosis 10 \200 \200\230The \201 rst half of pregnancy can become a time of constant \200\234exams \200 \235 to see if the baby can be allowed to graduate to the second half of pregnancy \200\231 . Those at high and, increasingly, those at low risk of having an abnormal baby are off ere d prenatal diagnosis to allow better treatment of the expected defect, or (more often) if t hey would wish to terminate any abnormal fetus. Cell-free fetal DNA circulating in maternal blood may be useful in the future. High-risk pregnancies \200 Maternal age >35 (chromoso me defects). \200 Previous abnormal baby or family history of inherited condition. Proble ms \200\207Anxiety while false +ve results are sorted out is a big problem. \200 Termina ting normal fetuses, eg \200 fetus of carriers of X-linked conditions. \200 Most abnorm alities are in low-risk groups ( \200\230 missable by selective screening). \200 Service s available, their quality, and populations made eligible vary widely. \200 Termination o f female fetuses in cultures valuing males more highly. \200 Devaluation of positive view of handicapped or \200\230special needs \200\231 children. Ultrasound at 11+0 \200\22313+ 6 weeks dates pregnancy, screens for nuchal translucen- cy (see BOX) and chorionicity (p68) . Further anomaly scan is at 18 weeks. Skilled operators detect many structural anomalies. See BOX opposite and p46. Ultra- sound best detects externally impinging structural abnorm ality, eg anenceph- aly/spina bi \201 da. Internal structural abnormality detection rate, eg for heart disease and diaphragmatic hernia, remains <50%. Fetuses with false +ve sug- ge stion of abnormality are mostly associated with \200\230soft signs \200\231 on ultrasound, eg nuchal thickening (eg trisomy 21), choroid plexus cysts (trisomies 18 and 21), and echo genic bowel (trisomy 21 and cystic \201 brosis). Use of \200\230soft signs \200\231 may increase false +ves 12-fold. \200 -Fetoprotein (AFP) AFP is a glycoprotein synthesized by the fetal liver and GI tract. Fetal levels fall after 13 weeks, but maternal (transplacenta l) serum AFP continues to rise to 30 weeks. Maternal AFP is measured at 17 weeks. In 10% wi th a high AFP there is a fetal malformation, eg an open neural tube defect (but closed defe cts are missed), exomphalos, posterior urethral valves, nephrosis, GI obstruction, teratoma s, Turner \200\231s syndrome (or normal twins). In 30% of those with no malformation, ther e is an adverse outcome, eg pla- cental abruption and third trimester deaths. \200\207Moni tor closely. 1 in 40 with a low AFP have a chromosomal abnormality (eg Down \200\231s). AFP is lower in diabetic mothers. NB: as this test is non-speci \201 c on its own, it is of u se for prelimi- nary screening; those with abnormal values may be off ered further tests (s ee below, and p12 for the \200\230quadruple test \200\231). Amniocentesis Use continuous u ltrasound. Fetal loss rate is 1% at 16 weeks \200\231 gestation, but 5% for early amnioc entesis at 10 \200\22313 weeks (not recom- mended as \200\200 talipes and respiratory prob lems). Amniotic \202 uid AFP is measured (a more accurate screen for neural tube defects than maternal serum), and cells in the \202 uid are cultured for karyotyping (+enzyme and gene probe analy- sis). Cell culture takes 3wks, so an abnormal pregnancy must be terminat ed at a late stage. Is anti-D needed (p9)? Chorionic villus biopsy At 10+ weeks, placenta i s sampled by transcervical or transabdominal approach under continuous ultrasound control. Karyotyping takes 2 days, enzyme and gene probe analysis 3 weeks, so termination for ab- no rmality is earlier, safer, and less distressing than after amniocentesis. Fetal loss rate i s 4%. Use up to 20 weeks (cordocentesis preferable thereafter). It does not detect neural tube defects, may cause fetal malformation, and is not recommended in dichorionic multiple pregnancy. \200\22531 Is anti-D needed (p9)? Fetoscopy is carried out at 18wks with ultras ound guidance to \201 nd external malformations, do fetal blood samples, or biopsy. Fetal loss rate is 4%. s c i r t e t s b O 11 High-resolution ultrasound and fetal nuchal translucency (FNT) \200 Early scans (at 11 \200\22314 weeks) may detect 59% of those with structural ab- normality and 78% of those wi th chromosome abnormality. It is best at detecting CNS defects, neck abnormalities, GI, and renal defects: less good for spina bi \201 da, heart and limb defects. With a combination of early and later scans up to 81% of malformations may be diagnosed. 32 \200 Fluid accu mulation in the neck at 10 \200\22314 weeks \200\231 gestation (increased fetal nuchal tran slucency, FNT) may re \202 ect fetal heart failure, 33 and be seen in se- rious anomaly of the heart and great arteries. 34 Meta-analysis shows that taking the 99th percentile as a cut off for cardiac screening enables 33% of heart abnormalities to be detected antenatally . 35 Referring 99th percen- tile fetuses for echocardiography may show 106 cardiac abnormal ities per 1000 fetuses examined. 36 \200 There is a strong association between chromosoma l abnormality and FNT. In one study, 84% of karyotypically proven trisomy 21 fetuses had a nuchal translucency >3mm at 10 \200\22313 weeks \200\231 gestation (as did 4.5% of chromoso m- ally normal fetuses). s c i r t e t s b O The greater the extent of FNT, the greater the risk of abnormality. \200 Nuchal transluce ncy screening may be used to see who may bene \201 t from more invasive chorionic villus s ampling (or amniocentesis p10, which may delineate the precise chromosomal abnormality, eg trisomies). Note: posi- tive predictive value of screening is 4% so 96% of women with a \200\230positive \200\231 test undergo an \200\230unnecessary \200\231 invasive procedure (chorionic villus sampling in the \201 rst trimester or amniocentesis in the second trime ster). If nuchal screening was used as the only screening test 2 or 3 normal pregnancies wo uld be lost after chorionic villus sampling, and 1 after amniocentesis, for every 4 pregnan cies correctly detected with trisomy 21. It is useful for screening twins as early detection is best, for if selective fetocide is t o be used risk of miscarriage is 3-fold higher if done after 16 weeks. Monochorionic twins have a higher false +ve rate for nuchal trans- lucency thickness than dichorionic twins or singletons. In the 25% of monochorionic twins with FNT discordance of >20 %, more than 30% had early fetal death or severe twin \200\223twin transfusion syndrome (10% if less discord ance). 37 \200 Note that the degree of neck \202 exion during the ultrasound examinatio n may in \202 uence nuchal measurements. Other \200\230soft markers \200\231 for Down \200\231s syndrome are fetal nasal bone appea rance, the Doppler velocity wave form in the ductus venosus and tricuspid regur- gitation. 38 \200 Systematic review shows that of all chromosomally normal fetuses (eu- ploid) with signi \201 cant nuchal thickening, 70 \200\22390% have normal outcome, 2.2 \200\22310.6% miscarry, 0.5 \200\22312.7% have neurodevelopmental problems, and 2.1 \200\2237.6% of malfo rmations were undiagnosed before birth. 39 Tests to detect Down \200\231s syndrome 12 \200 The 1st antenatal diagnosis of Down \200\231s syndrome was in 1968. Initially there was amn iocentesis for older mothers (Penrose noted an association with mater- nal age in 1933; see table). Then screening by blood test was introduced, then nuchal screening (p11). Maternal age & Down \200\231s1 Fetuses with Down \200\231s at 16 weeks1 \200\224 \200\224 \200\224 \200\224 \200\224 1 : 420 1 : 325 1 : 250 1 : 200 1 : 150 1 : 120 1 : 100 1 : 75 1 : 60 1 : 45 1 : 35 1 : 30 1 : 20 Live births with Down \200\231s 1 : 1250 1 : 1400 1 : 1100 1 : 900 1 : 750 1 : 625 1 : 500 1 : 350 1 : 275 1 : 225 1 : 175 1 : 140 1 : 100 1 : 85 1 : 65 1 : 50 1 : 40 1 : 25 Age of mother (yrs) 40 From 2007, the UK NHS has aimed for screening tests giving detection rates of 75% with a fa lse +ve rate of <3%. Tests estimate risk of Down \200\231s taking into account results from nuchal scanning, blood tests, and the woman \200\231s age. Where risk of Down \200\231s is >1 : 250 ( 5% of pregnancies) she will be off ered tests such as chorionic villus sampling (p10) and amniocentesis (p10). Early ultrasound is vital for dating pregnancies for these tests. The combined test combines nuchal translucency (NT) + free \200 -human chorionic go nadotrophin ( \200 HCG) + pregnancy associated plasma protein (PrAP-A or PAPP-A) + the woma n \200\231s age. Used between 10 weeks 3 days and 13 weeks 6 days. It achieves detection ra tes of 95% of all aneuploides, 86% trisomy-21, and 100% of trisomy-18 and trisomy-13. PrAP- A levels are 19.6% lower in smokers. 41 In multiple pregnancy risk is calculated per pregn ancy if monochorionic; per fetus when dichorionic or trichorionic. 42 The integrated test T his is better than the combined test if there are good facilities for NT measurements avail able and the woman is prepared to wait for 2nd trimester results. It involves NT + PrAP-A i n the 1st trimester + the quad- ruple test in the 2nd trimester. Do not use 2nd trimester t ests for triplets. \200 42 The quadruple test combines maternal \200 -fetoprotein (AFP) + unconjugated estriol + free \200 HCG or total \200 HCG + inhibin-A + the woman \200\231s age in the 2nd trimes- ter. Use between 15 weeks + 0 days and 20 weeks + 0 days so useful for women presenting in the 2nd trimester. The emotional cost to the mother is impossible t o calculate: 43 56 out of every 57 women under 37yrs old who had a +ve test proved, after a mniocentesis, not to have an aff ected fetus. Amniocentesis causes fetal loss ( 0.86% 44), and these losses will sometimes be of normal babies. New screening regimens in the 1st trim ester go some way to mitigating distress and anxiety. 15 \200\22319 20 \200\22324 25 \200\22329 30 \200\22331 32 33 34 351 36 34 38 39 40 41 42 4 3 44 \211 45 s c i r t e t s b O We have no idea of the best way of counseling parents before the test. If we just hand out a lea \202 et, few will read it, and then when it comes to amniocente- sis and termination , many will refuse \200\224and the screening test wastes money, as well as laying health au thorities open to litigation: \200\234I never understood that I might lose a normal baby \200 \200\235 The alternative is to provide full details at the time of the initial blood test. The irony is that gaining informed consent is then the most expensive part of the tes t, and one which itself could cause much dis- tress. \201\201Imagine an overjoyed expectan t mother arriving in the clinic serene- ly happy in ful \201 lling her reproductive potent ial: the quintessence of health. She leaves only after being handed ethical conundrums of q uite staggering proportions, involving death, disease, and human sacri \201 ces, and a tim etable for their resolution that would leave even the most fast-moving philosopher breathle ss and disorientated, and which may leave her forever bereft of one of Nature \200\231s mos t generous gifts: the fundamental belief in one \200\231s own wholeness. 1 Sources vary: if we look just at births to mothers aged 35, the proportion with Down \200 \231s in 4 studies was 1 : 265; 1 : 270; 1 : 35040,45 and 1 : 400 (ACOG 1999)46 Why the dif f erence between 16wks and time of birth? Because of spontaneous miscarriages of fetuses wi th Down \200\231s syndrome between 16wks and birth. 13 Preimplantation genetic diagnosis Preimplantation genetic diagnosis (PGD) is an early form of prenatal diagno- sis in which embryos created in vitro are analyzed for well-de \201 ne d genetic defects. Defect-free embryos are then used for implantation. It is used in those with high risk of genetic disease, eg carriers of monogenic disease or chromosome structural abnormalities (eg translocations) who have repeatedly terminated preg nancies due to prenatal tests showing abnor- mality, who have concurrent infertility, who h ave had recurrent miscarriage (as occurs with translocation carriers), and for those with m oral or religious objections to termination. It has also been used to screen for aneuploidy (PGD-AS) in those undergoing in vitro fertil ization hoping to enhance chance of ongoing pregnancy (eg in the case for women >37 \200 \22340 years old \200\224but see below). s c i r t e t s b O Pioneered in the early 1990s, PGD has resulted in >1200 pregnancies (preg- nancy rate 24%), of which 5% of babies had some kind of abnormality. PGD selection of embryos by HLA type s o that a child born after using this technol- ogy can be used as a stem cell donor to save a sibling from certain conditions (eg with Fanconi anemia, \200 thalassaemia, or leukemia ) is controversial, but possible. Some clinics select sex of implanted embryo eg for \200 \230family balancing \200\231. Genetic analysis at the single cell level occurs using 1st polar body of an egg, or 2nd pol ar body (extruded after fertilization and completion of second meiotic division), or using blastomeres from cleavage-stage embryos. The blastocyst is the latest stage from which cell s can be used but is little used as it leaves little time for analysis as embryos must be t ransferred before day 5 or 6. Biopsied surplus embryos can be cryopreserved but implantatio n rate for these is only 12%. Fluorescence in situ hybridization (FISH) is used for analysis of chromosomes and polymeras e chain reaction (PCR) for analysis of genes in monogenic dis- eases. PGD can currently be applied for detecting 33 monogenic diseases. Gene analysis for X-linked conditions has the advantage that healthy male embryos and non-carrier female embryos can be transferred. Sexi ng embryos for X- linked conditions remains useful for conditions where the single gene is not known (eg non-fragile-X X-linked mental retardation), has been judged too dif- \201 c ult a search, and for women eg over 37 who do not wish to wait for speci \201 c tests to b e developed. Pregnancy rates are 17% after testing for structural chromosome abnor- mality (including tr anslocations), 16% after sexing, 21% after testing for monogenic diseases. This is lower th an the expected rate of 20 \200\22325% expect- ed for regular IVF. For PGD-AS 25% pregnancy rates are achieved overall for women of previously poor prognosis due to advanced maternal age (a lower proportion than those where preimplantation genetic screening is not used), 4 7 repeated IVF failure (but only 8% do get pregnant), and recurrent miscarriage (28% pregna ncy rate achieved). The placenta 14 \200 The placenta is the organ of respiration, nutrition, and excretion for the fetus. It produc es hormones for maternal wellbeing. It immunologically protects the fetus from rejection an d allows the passage of maternal IgG antibodies. Development At term the placenta weighs 1/ 7th the weight of the baby. It has a blood \202 ow of 600mL/min. The placenta changes thr oughout pregnancy as calcium is deposited in the villi and \201 brin on them. Excess \201 brin may be deposited in diabetes and rhesus disease, so \200\201 fetal nutrition. Pl acental types Velamentous insertion (1%): umbilical vessels go within the membranes before placental insertion. Placenta succenturia: (5%) There is a separate (succenturiate) lobe aw ay from the main placenta which may fail to separate normally and cause a PPH or puerperal sepsis. Vasa praevia: Fetal vessels from velamentous insertion or between lobes (succenturi a, or bilobe placenta) risk damage at membrane rupture causing fetal hemorrhage. Cesarean d elivery is needed (urgent if fetal compromise at membrane rup- ture, elective if detected a ntenatally by ultrasound). Placenta membranacea (1/3000) a thin placenta surrounds the baby . Some is in the lower segment so predisposes to APH. It may fail to separate in the 3rd st age. Placenta accreta: There is abnormal (morbid) adherence of all or part of the placenta to the uterus, termed placenta increta myometrium in \202 itrated, placenta percreta if pe netration reaches the serosa. These 3 types predispose to PPH and need hysterectomy. Incide nce \200\200 with the number of previous cesarean sections. Diagnose prenatally (color dop pler US/MRI p78). Placenta praevia The placenta lies in the lower uterine segment. It is fo und in 0.5% of pregnancies. Risks are of signi \201 cant hemorrhage by mother and fetus. Avoid PV examinations, advise against penetrative intercourse. 10 Associations: Cesarean se ction; sharp curette TOP; multiparity; multiple pregnancy; mother >40 years; assisted conce ption; de \201 cient endometrium-manual removal of placenta, D&C, \201 broids, endometri tis . Ultrasound (US) at <24 weeks \200\231 gestation shows a low-lying placenta in 28% but with lower segment development only 3% lie low at term. Transvaginal ultrasound is superio r to transabdominal for localizing placentas accurately, and, if combined with 3D power Dop pler/MRI, diagnoses vasa praevia and placenta accreta. It has not been shown to in- crease bleeding. Repeat US at 32wks if major praevia, 36wks if minor. s c i r t e t s b O Major placenta praevia (placenta covers the internal os) requires cesarean section for deli very. Minor placenta praevia (placenta in lower segment but does not cross the internal os) : aim for normal delivery unless the placenta en- croaches within 2cm of the internal os (e specially if posterior or thick). Presen- tation may be as APH (separation of the placenta as the lower segment stretches causes bleeding) or as failure for the head to engage ie a h igh presenting part. Problems are with bleeding and with mode of delivery as the placenta o bstructs the os and may shear off during labor, or may be accreta (5%), especially af- ter a previous caesar (>24%). Poor lower segment contractility predisposes to postpartum hemorr hage. Cesarean section should be consultant-performed or supervised with consultant anesthe tic attendance at 38wks, (36 \200\2237wks with steroid cover, crossmatched blood + hematolo gist available, 48 if accreta suspected), at a hospital with blood bank and level 2 critica l care beds. 49 Ad- mitting those with major placenta praevia at \211 35 weeks \200\231 ge station so that im- mediate help is available, is controversial, and not practiced by many UK units but admit at 34wks if major praevia and there has been bleeding. After delivery Ex amine the placenta for abnormalities (clots, infarcts, am- nion nodosum, vasa praevia, sing le umbilical artery). Weigh the placenta (weight >25% of the baby suggests congenital nephr otic syndrome). Blood may be taken from the cord for Hb, Coombs \200\231 test, LFTs, and bl ood group (eg for rhesus disease), or for infection screens, if needed. 15 Fig 1. Seven spiral arteries are here seen to have been successfully invaded by trophoblast and they are now \202 ooding the vast intervillous spaces with hot ma- ternal blood \200 \224producing the slow whooshing crescendos heard by the ultrasound probe as the backdrop t o the faster fetal heart beat. To get to the fetus proper, nutrients have a 6-part journey: maternal blood space \200\203 syncytiotrophoblast \200\203 trophoblast basement membrane \200\203 capillary basement membrane \200\203 capillary endothelium \200\203 fetal bloo d. 50 In pre-eclampsia, trophoblast invasion is too shallow: there is no progress beyond th e super \201 cial portions of the uterine spiral arterioles. So these spiral arterioles re tain their endothelial linings and remain narrow-bore, high-resistance vessels, resulting i n poor maternal blood \202 ow. The mother may raise her blood pressure to compensate for this \200\224but the price may be eclampsia (p49). 51 s c i r t e t s b O Plasma chemistry in pregnancy Non-pregnant 97.5 2.5 146 138 Trimester 1 2.5 135 Trismester 2 97.5 2.5 140 132 Trimester 3 2.5 133 Centile Na+ mmol/L Ca2+ mmol/L 97.5 141 97.5 141 2 2.6 2.3 2.5 2.2 2.2 2.2 2.5 corrected 2.3 2.6 2.25 2.57 2.3 2.5 2.3 2.59 Albumin g/L 44 50 39 49 36 44 33 41 AST IU/L 7 40 10 28 11 29 11 30 ALT IU/L 0 40 6 32 6 32 6 32 0 4 0 1.6 1 1.8 7 7.3 TSH Calcium corrected for plasma albumin (OHCM p670) Other plasma reference intervals (not analyzed by trimester) Non-pregnant Pregnant \211 450 (can be \200\200 \200\200 in normal pregnancies) Alk phos IU/L 3 \200\223300 Bicarbonate mmol/L 24 \200\22330 Creatine mol/L 70 \200\223150 Urea mmol/L 2.5 \200\2236. 7 Urate mol/L 150 \200\223390 \200 C-reactive protein does not change much in pregnancy . \200 Platelets \211 150 \211\210 109/L (beware if 120 \211\210 109/L see p48). \200 TSH may be low <20 weeks in normal pregnancy (suppressed by HCG); see above & p25. \200 Protein S falls in pregnancy, so protein S de \201 ciency is diffi cult to diagnose. \200 Activated protein C (APC) resistance is found in 40% of pregnancies so special tests are needed when looking for this. Genotyping for factor V Leiden and prothrombin G20210A ar e unaff ected by pregnancy. 20 \200\22325 24 \200\22368 2 \200\2234.2 116 \200\223276 (24wks), 110 \200\223322 (32wks), 120 \200\223344 (36wks) Thromboprophylaxis52 \200\207Pregnancy is a hypercoagulable state: consider need for throm boprophylaxis pre-pregnancy, at booking, if admitted to hospital, throughout the antenatal period, at start of labor and once delivered. If needed refer to Trust-nomi- nated expert i n thrombosis in pregnancy. Screen women with non-estrogen provoked thromboembolism for thro mbophilia before the next pregnancy. \200\207In all pregnant women avoid immobility and de hydration. \200\207For women with 3 or more persisting risk factors (MINIBOX), consider an tena- tal and postnatal low molecular weight heparin (LMWH) prophylaxis, starting as early in pregnancy as possible as risk is throughout (risk \200\201 by \211 60 \200\22370%). Con tinue normal dose prophylaxis when admitted in labor. Treat for 6 weeks postpartum, and sup ply graduated compression stockings postpartum. \200\207If BMI >40, or cesarean in labor, give LMWH for 7 days postpartum. Thromboprophylaxis after vaginal delivery: Risk factors: ( Thrombophilia/past thromboem- bolism considered separately.) If BMI >40 off er treatment. O ff er to all women with two of the risk factors opposite (see MINIBOX). Treatment: Treat wi th low molecular weight heparin (LMWH) eg enoxaparin starting as soon as possible after del ivery (as long as no postpar- tum hemorrhage and \211 4h after epidural cathe- ter siting or removal \200\2246h if that was traumatic). Continue for 7 days including at home. Dose o f enoxaparin: if the early pregnancy weight (EPW) is 50 \200\22390kg, give 40mg/24h SC; if EPW <50kg, give 20mg/24h sc; if EPW 91 \200\223130kg give 60mg/24h SC, if EPW 131 \200\2231 70kg give 80mg/24h SC, if EPW >170kg give 0.6mg/kg/24h SC. If heparin is contraindi- cated, use TED compression stockings (TED= transverse elastic graduated). If 3 or more risk facto rs give stockings and LMWH. Women with past venous thromboembolism (VTE ) thrombophilia: Action depends on risk: VH = very high; HR = high risk; IR = intermediate risk. \200 (VH ) If recurrent VTE (+antiphospholipid syn- drome or antithrombin de \201 ciency) or alread y on long-term warfarin, use high-dose pro- phylactic LMWH, eg enoxaparin 40mg/12h SC if 50 \200\22390kg EPW (or 75% of weight adjusted therapeutic dose (WATD)). WATD=1mg/kg/12h (kg is the EPW), prenatally and 1.5mg/kg/24h postnatally. This is given prenatally. Withhold at onset of labor (halve to /24h the day before and the day of induction). Give for 6wks post partum or revert to warfarin day 5 \200\2237 postnatally. 16 \200 Risk factors \200 Age >35 years old \200 Early pregnancy BMI >30 \200 Smoker \200 P arity \211 3 \200 Multiple pregnancy \200 Assisted reproduction \200 Gross varicose veins \200 Paraplegia \200 Sickle cell disease/SLE \200 Nephrotic syndrome \200 Som e cardiac causes \200 Past thromboembolism1 \200 Thrombophilia \200 Myeloproliferativ e dis. \200 In \202 ammatory bowel dis. \200 Hyperemesis/dehydration \200 Pre-eclamp sia \200 Immobility for \211 3 days eg symphysis pubis dysfunc- tion s c i r t e t s b O Ovarian hyperstimulation \200 Major infection (eg pyelo- nephritis, wound infection) so hospital admission Labor lasting >24h \200 Mid-cavity forceps \200 Elective cesarean \200 Blood loss >1L /transfused \200 Surgery in puerperium eg evacuation of retained products of conception \200 Postpartum sterilization \200 Lon g travel time ( \211 4h) (HR) Previous VTE unprovoked/idiopathic or estrogen (or pregnancy)-relat- ed; or VTE + (1st degree relative with VTE or thrombophilia); or VTE + docu- mented thrombophilia: give LMWH antenatally and 6 weeks postpartum. (IR) If a single previous VTE provoked by major risk factor no longer present and no other risk factors give LMWH for 6wks postpartum (PP). Women with asymptomatic thrombophilia: See p33. 1 Non-estrogen related provoked thromboembolism eg previous major surgery is not a risk fac tor. 17 Minor symptoms of pregnancy \200\207Before prescribing any drug, think \200\224Is it neces sary? Is it safe? Consult Data-sheets a national teratology information service (tel 019 1 232 1525uk). Symptoms and signs in the \201 rst 10 weeks: Early symptoms are amenor- rh oea, nausea, vomiting, and bladder irritability. Breasts engorge, nipples enlarge (darken a t 12 weeks), Montgomery \200\231s tubercles (sebaceous glands on nipples) become prominent. Vulval vascularity increases and the cervix sof- tens and looks bluish (4 weeks). At 6 \200\22310 weeks the uterine body is more globu- lar. Temperature rises (<37.8 C). Headach es, palpitations, and fainting are all commoner in pregnancy. Dilated peripheral circulatio n \200\200sweating and feeling hot. Management: In- crease \202 uid intake: take showers . If feels faint from postural hypotension, stand slowly. Urinary frequency is due to press ure of the fetal head on the bladder in later pregnancy. Exclude UTI. Abdominal pain: See p 38. Breathlessness is common. See p6. Constipation tends to occur as gut motility decreases . Adequate oral \202 uids and a high- \201 bre diet help combat it. Avoid stimulant laxa tives \200\224they increase uterine activity in some women. Increased venous distensibility and pelvic congestion predispose to hemorrhoids (if they prolapse, rest the mother head do wn, apply ice packs and replace them) and varicose veins. Resting with feet up and properly worn elastic stockings help. Re \202 ux oesophagitis and heartburn occur as pyloric sphin cter relaxation al- lows irritant bile to re \202 ux into the stomach. Cigarettes and spic es should be avoided, small meals taken, and antacids may be used. Use more pillows, and a semi-recumbent position. Third trimester backache: Due to pelvic ligament and muscle relaxa tion, pain tends to be worse at night. A \201 rm mattress, \202 at shoes, standing with back straight, and pelvic support from physiotherapy all help. Carpal tunnel syndrome (p71 4) in pregnancy is due to \202 uid retention. Advise wrist splints until delivery cures t he problem. Itch/itchy rashes are common (up to 25%) and may be due to the usual caus- es ( OHCM p64, check LFT \200\224see p26) or to pruritic eruption of pregnancy (PEP = prurigo of pregnancy) \200\224an intensely itchy papular/plaque rash on the abdo- men and limbs. PEP is most common in \201 rst pregnancies beyond 35 weeks \200\231 gestation. Emollients and weak topical steroids ease it. Delivery cures it. If vesicles are present, think of pemphi goid gestationis (PG): a rare (1 : 50,000) condition which may cause fatal heat loss and ca rdiac failure; the baby may be brie \202 y aff ected; refer early (prednisolone may be nee ded). PG may recur in later pregnancies. Ankle oedema: This is a very common, almost normal , manifestation of preg- nancy. Measure BP and check urine for protein (pre-eclampsia, p48) . Check legs for DVT. It often responds to rest and leg elevation. Reassure that it is harm less (unless pre-eclampsia). Leg cramps 33% get cramp, the latter half of pregnancy, severe in 5%, often worse at night. Raising the foot of the bed by 20cm will help. Chloasma: This is a patch of darker pigmentation, eg on the face: p586. Nausea aff ects 80%. Vomiting oc curs in 50%. It may start by 4 weeks and decline over the following weeks. At 20 weeks 20% may still vomit. Most re- spond to frequent small meals, reassurance, and a stress-free en vironment. It is associated with good outcome (fewer fetal losses). Hyperemesis: p18. s c i r t e t s b O Hyperemesis gravidarum 18 \200 This is de \201 ned as persisting vomiting in pregnancy which causes weight loss (>5% of p re-pregnancy weight) and ketosis. It aff ects 1% of pregnant women. Risk is increased in yo uth, non-smokers, primips, working outside home, pre- existing diabetes, hyperthyroidism, p sychiatric illness, family history, those with previous eating disorders and multiple or mo lar pregnancy (hence the idea that excessively high HCG levels may be the cause \200\224whe reas steeply rising oestrogens may cause the very common feature of morning sickness). Rare ly, hyperemesis has been fatal. Recurrence rate 15% (10% if changed paternity). 53 Presenta tion Inability to keep food or \202 uids down; weight \200\201 (2 \200\2235kg) nutri- tional de \201 ciency, dehydration, hypovolaemia, tachycardia, postural hypoten- sion, el ectrolyte disturbance with hypokalaemia and hyponatraemic shock, polyneuritis (B vitamins \200\201), behavior disorders, liver and renal failure. There may be ptyalism (inability to swallow saliva) and spitting. Tests Do PCV and U&E to help guide IV \202 uid regimen. 50 % have abnormal LFTs (usually raised aminotransferase and bilirubin). TFTs are abnormal in 60% of those with hyperemesis. This is biochemical hyperthyroidism with raised free thyroxi ne and suppressed TSH. In women with hyperemesis thyroxine is con- verted to reverse tri-io dothyronine in the tissues which is physiologically in- active so stimulating metabolic rat e less and conserving energy stores. The severity of hyperemesis correlates with the degree of biochemical hyperthy- roidism, and those with abnormal TFTs require longer hospitalizat ion to pre- vent readmission. The biochemical hyperthyroidism settles as vomiting settles s o does not require treatment in its own right. Chart losses, weigh, record pulse and standi ng and lying blood pressure. Exclude UTI. Do ultrasound scan to exclude twins or hydatidifo rm mole. Treatment Admit to hospital. Give thromboprophylaxis (eg enoxaparin 40mg/24h SC) a nd anti-embolic stockings. Spend time optimizing psychological wellbeing. Is she worried ab out how her other children are being cared for? s c i r t e t s b O