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Pathophys and Cause

Pathophys:(Ann IM 1984;101:683)

Epidemiology

20% abort before clinically apparent, another 10% abort later (Nejm 1988;319:189)

Signs and Symptoms

Sx: Early: nausea and vomiting (50%); breast engorgement; missed period. Quickening at 20 wk, 1-2 wk earlier in experienced multiparous women

Si:Soft uterine neck, blue cervix by 6 wk. Fetal heart by Doppler at 9-12 wk; by feto- or stethoscope at 18-20 weeks

Course

39-42 wk for maximal perinatal survival in singleton births, 37-38 wk for twins (Jama 1996;275:1432)

Complications

Adverse outcomes are not increased by long hours or stress (residents—Nejm 1990;323:1040)

Lab and Xray

Lab:

Routine initial prenatal package: UA and culture, Hgb/Hct in 1st and 3rd trimesters, ABO and Rh type, VDRL, chlamydia antigen, gc culture, Pap smear; rubella titer (if neg, advise on avoiding exposure during pregnancy and offer postpartum immunization—Nejm 1992;326:663, 702); HIV test in most cases unless “opt out”; sometimes w informed consent but becoming less necessary since thought to be a barrier to diagnosis; AZT rx will decrease fetal transmission from 25% to 8% (Jama 1995;273:977); perhaps toxoplasmosis titer? (Nejm 1994;331:695) and TSH (Nejm 1999;341:549 vs 601)

at 16-20 wk, quadruple markers (AFP, HCG, inhibin, and estriol) for Down's

at 24-28 wk: screen with 50 gm glucose, nonfasting, if 1-h blood sugar is >130-140 mg %, get full GTT; full GTT = 100 gm glucose, FBS <105, 1 h <190, 2 h >165 (but problems even if 120-165), 3 h <145; dx gestational DM by gteq.gif2 values too high (Nejm 1986;315:989, 1025)

at 35-37 wk, group B strep culture (Nejm 2000;342:15)

Chem:Serum beta.gif-subunit tests positive within 2 wk of conception

Hem:Hgb drops by midtrimester from an average of 13.7 gm to 11.5 gm, then usually rises to 12.3 gm in 3rd trimester; if stays up, indicates plasma volume decrease and decreased fetal weight (Ann Obgyn Scand 1984;63:245). Platelets average 322 000 in 1st trimester, 275 000 in 2nd, and 300 000 in 3rd (Jama 1979;242:2696)

Urine:Pregnancy tests now sensitive down to beta.gif-HCG of 50 U and hence 90% positive by 1st day of missed mense, 97% by 7th day (Jama 2001;286:1759)

Xray:Ultrasound at 4-6 wk for gestational sac, at 8-12 wk for crown/rump length, or 14-20 wk for biparietal diameter, if dates unclear; routine ultrasound for congenital anomalies not helpful? (Nejm 1993;329:821 vs 874)

Treatment

Rx:Avoid teratogens, including antibiotics (list—Med Let 1987;29:61); safe meds list (Nejm 1998;338:1135); spina bifida caused by maternal vit A ingestion of gteq.gif10 000 IU qd, esp in 1st trimester (Nejm 1995;333:1369). Bendectin may be ok

TABLE 11.2. SELECTED DRUGS THAT CAN BE USED SAFELY DURING PREGNANCY, ACCORDING TO CONDITION.*

ConditionDrugs of ChoiceAlternative DrugsComments
AcnenavigatorTopical: erythromycin, clindamycin, benzoyl peroxideSystemic erythromycin, topical tretinoin (vitamin A acid)Isotretinoin is contraindicated
Allergic rhinitisnavigatorTopical: glucocorticoids, cromolyn, decongestants, xylometazoline, oxymetazoline, naphazoline, phenylephrine, systemic diphenhydramine, dimenhydrinate, tripelennamine, astemizole
ConstipationnavigatorDocusate sodium, calcium, glycerin, sorbitol, lactulose, mineral oil, magnesium hydroxideBisacodyl, phenolphthalein
CoughnavigatorDiphenhydramine, codeine, dextromethorphan
DepressionnavigatorTricyclic antidepressant drugs, fluoxetineLithiumWhen lithium is used in first trimester, fetal echocardiography and ultrasonography are recommended because of small risk of cardiovascular defects
DiabetesnavigatorInsulin (human)Insulin (beef or pork)Hypoglycemic drugs should be avoided
Headachenavigator
TensionnavigatorAcetaminophenAspirin and nonsteroidal antiinflammatory drugs, benzodiazepinesAspirin and nonsteroidal antiinflammatory drugs should be avoided in third trimester
MigrainenavigatorAcetaminophen, codeine, dimenhydrinateß-adrenergic–receptor antagonists and tricyclic antidepressant drugs (for prophylaxis)Limited experience with ergotamine has not revealed evidence of teratogenicity, but there is concern about potent vasoconstriction and uterine contraction
HypertensionnavigatorLabetalol, methyldopaß-adrenergic–receptor antagonists, prazosin, hydralazineAngiotensin-converting–enzyme inhibitors should be avoided because of risk of severe neonatal renal insufficiency
HyperthyroidismnavigatorPropylthiouracil, methimazoleß-adrenergic–receptor antagonists (for symtoms)Surgery may be required; radioactive iodine should be avoided
Mania (and bipolar affective disorder)navigatorLithium, chlorpromazine, haloperidolFor depressive episodes tricyclic antidrepressant drugs, fluoxetine, valproic acidIf lithium is used in first trimester, fetel echocardiography and ultrasonography are recommended because of small risk of cardiac anomalies; valproic acid may be given after neural-tube dosure is complete
Nausea, vomiting, motion sicknessnavigatorDiclectin (doxylamine plus pyridoxine)Chlorpromazine, metoclopramide (in third trimester), diphenhydramine, dimenhydrinate, meclizine, cyclizine
Peptic ulcer diseasenavigatorAntacids, magnesium hydroxide, aluminum hydroxide, calcium carbonate, ranitidineSucralfate, bismuth subsalicylate
PruritusnavigatorTopical: moisturizing creams or lotions, aluminum acetate, zinc oxide cream or ointment, calamine lotion, glucocorticoids; systemic: hydroxyzine, diphenhydramine, glucocorticoids, astemizoleTopical: local anesthetics
Thrombophlebitis, deep-vein thrombosisnavigatorHeparin, antifibrinolytic drugs, streptokinaseStreptokinase is associated with a risk of bleeding; warfarin should be avoided

*Data are from Smith et al.93

Reproduced with permission from Koren G, et al. Drugs in Pregnancy. New Eng J Med 1998: 228:1135. Copyright 1998 Mass. Medical Society, all rights reserved.

Folic acid 1 mg qd and iron 325 mg qd supplements throughout pregnancy prevents deficiencies; folate periconception at 0.4 mg qd × 1 mo decreases neural tube defect risk by 71% (Peds 1993;493:4), 4 mg po qd if pos family hx

Prenatal visits q 1 mo to 36 wk then q 2 wk if low risk, more if high risk (Jama 1996;275:847) to monitor fetal growth and maternal BP and education

of HYPEREMESIS GRAVIDARUM (Nejm 2010;363:1544): small feedings, stop Fe pills, give vit B6 (pyridoxine) 25 mg po tid × 3 d (Obgyn 1991;78:33); Zofran (ondansetron) first-line; pregnancy category B, so widely used for treatment and prophylaxis; aso antihistamines like diphenhydramine (Benadryl) 25-50 mg po q 4-6 h, or trimethobenzamide (Tigan) 200 mg rectal suppos; or phenothiazines like prochlorperazine (Compazine) 25 mg po or pr qid, or 5 mg im, or promethazine (Phenergan) 25-50 mg po or pr qid, or chlorpromazine (Thorazine) 25-50 mg im q 4 h, or metoclopramide (Reglan) 5-10 mg po/im/iv, safe (Nejm 2009;360:2528); iv fluids and hospitalization for volume depletion and ketosis. Bendectin, contains pyridoxine, safe (Nejm 2009;360:2528) no longer available in US alone but sold as Unisom sleep aid (pyridoxine 1 doxylamine) in US to take po bid and also as diclectin in Canada; probably is safe (Nejm 1998;338:1128)

of seizure disorders in pregnancy: seizure meds incr risk of congenital malformations (Nejm 2001;344:1132); cleft palate and spina bifida increased w all, least w phenobarb, more w valproate (Nejm 2010;363:2185), and most w carbamazepine (Am J Publ Hlth 1996;86:1454) vs only carbamazepine? (Nejm 1991;324:674); phenobarb, esp if given in last trimester, impairs subsequent intelligence (Jama 1995;274:1518) as does valproate (Nejm 2009;360:1597); for phenytoin, one can predict which fetus will be deformed by an enzyme assay of amnion (Nejm 1990;322:1567)

of depression in pregnancy: TCAs ok and, if chronic, 68% relapse if stop (Jama 2006;295:499); SSRIs given after 20th week may incr newborn persistent pulmonary HT (Nejm 2006;354:579) but ok in first trimester (Nejm 2007;356:2675, 2684); Paxil now category D and thought to be the least safe of the SSRIs.

of hypothyroidism: monitor TSH, often need higher thyroid dose in pregnancy

of valvular heart disease in pregnancy (Nejm 2003;349:52)

of gestational diabetes: diet, BS monitoring plus insulin to keep BS <150 clearly decreases newborn size and consequent complications of macrosomia (RCT—Nejm 2005;352:2477)

of asthma in pregnancy (Nejm 2009;360:1862): first choice, inhaled steroids and leukotriene receptor antagonists


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