Pathophys:(Ann IM 1984;101:683)
20% abort before clinically apparent, another 10% abort later (Nejm 1988;319:189)
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
39-42 wk for maximal perinatal survival in singleton births, 37-38 wk for twins (Jama 1996;275:1432)
Adverse outcomes are not increased by long hours or stress (residents—Nejm 1990;323:1040)
- Asthma management is nearly the same as in the nonpregnant, but be aware that ß agonists like terbutaline inhibit labor (Nejm 1985;312:897), iodides induce fetal goiter (Lancet 1990;1:1241); tetracyclines stain fetal teeth
- Bleeding and/or contractions (pain):
- 1st trimester: Ectopic or threatened abortion, mole, septic abortion
- 2nd trimester: Mole, pyelonephritis, placenta praevia, incompetent cervix, or bicornuate uterus
- 3rd trimester: Premature labor, previa, or abruption, which can be caused by trauma (Nejm 1990;323:1609)
- Venous thromboembolism (Obstet Gynecol 2000;96:1; Ann IM 2007;146:204): #1 cause of maternal mortality in USA; screen if personal or family history of thrombophilia; difficult to distinguish from gestational edema; dx with U/S and spiral CT for pulmonary embolism; warfarin is contraindicated in pregnancy, but LMW heparin is used for prophylaxis and treatment.
- Cardiac disease rx (Nejm 1993;329:250) generally stenotic lesions (AS, MS) a greater problem than insufficiency lesions (MR, AI) because of increased cardiac output during pregnancy (J. Love 12/94); rare (1/10 000) MI (Ann IM 1996;125:751)
- Diabetes: Increased c-section rates because of increased rates of toxemia, macrosomia, and congenital malformations
- GI: (Ann IM 1993;118:366) Esophageal reflux, nausea and vomiting, bloating/constipation from diminished LES pressure and motility; gallstones (2%) and sludge (present by ultrasound in 31% of pregnancies) occur but often revert to normal postpartum (Ann IM 1993;119:116)
- Hyperemesis gravidarum, usually in 1st trimester; for rx see below
- Liver disease, various types including acute fatty liver of pregnancy, intrahepatic cholestasis, et al. (Nejm 1996;335:570)
- Low birth weight (Low Birth Weight)
- Premature rupture of membranes, if before 32 wk gestation, rx for group B strep (Group B Strep Infections) w ampicillin/amoxicillin 250 mg + perhaps erythromycin for chlamydia (Jama 1997;278:989)
- Rheumatologic disorders: safe medications (Bull Rheum Dis 1992;41[2]:1)
- Stroke risk not incr during but is incr for 1st 6 wk postpartum (Nejm 1996;335:768)
- Thyrotoxicosis (Nejm 1985;313:562) more commonly when high HCG levels from gestational trophoblastic disease since HCG structurally close to TSH (Nejm 1998;339:1823); more common postpartum in IDDM pts (10%) (Ann IM 1993;118:419)
- Toxemia of pregnancy (Pregnancy-Induced Hypertension, Gestational Hypertension, Preeclampsia/Eclampsia, Toxemia)
- Urologic: Pyelonephritis from physiologic dilatation or ureters and/or decreased motility and/or compression; proteinuria associated w toxemia; nephrogenic diabetes insipidus in 3rd trimester (Nejm 1984;310:442); chronic renal failure (Nejm 1985;312:836)
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 
2 values too high (Nejm 1986;315:989, 1025)
at 35-37 wk, group B strep culture (Nejm 2000;342:15)
Chem:Serum 
-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 -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)
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 10 000 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.*
| Condition | Drugs of Choice | Alternative Drugs | Comments |
|---|
Acne | Topical: erythromycin, clindamycin, benzoyl peroxide | Systemic erythromycin, topical tretinoin (vitamin A acid) | Isotretinoin is contraindicated |
| Allergic rhinitis | Topical: glucocorticoids, cromolyn, decongestants, xylometazoline, oxymetazoline, naphazoline, phenylephrine, systemic diphenhydramine, dimenhydrinate, tripelennamine, astemizole | | |
| Constipation | Docusate sodium, calcium, glycerin, sorbitol, lactulose, mineral oil, magnesium hydroxide | Bisacodyl, phenolphthalein | |
| Cough | Diphenhydramine, codeine, dextromethorphan | | |
| Depression | Tricyclic antidepressant drugs, fluoxetine | Lithium | When lithium is used in first trimester, fetal echocardiography and ultrasonography are recommended because of small risk of cardiovascular defects |
| Diabetes | Insulin (human) | Insulin (beef or pork) | Hypoglycemic drugs should be avoided |
| Headache |
| Tension | Acetaminophen | Aspirin and nonsteroidal antiinflammatory drugs, benzodiazepines | Aspirin and nonsteroidal antiinflammatory drugs should be avoided in third trimester |
| Migraine | Acetaminophen, codeine, dimenhydrinate | ß-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 |
| Hypertension | Labetalol, methyldopa | ß-adrenergic–receptor antagonists, prazosin, hydralazine | Angiotensin-converting–enzyme inhibitors should be avoided because of risk of severe neonatal renal insufficiency |
| Hyperthyroidism | Propylthiouracil, methimazole | ß-adrenergic–receptor antagonists (for symtoms) | Surgery may be required; radioactive iodine should be avoided |
| Mania (and bipolar affective disorder) | Lithium, chlorpromazine, haloperidol | For depressive episodes tricyclic antidrepressant drugs, fluoxetine, valproic acid | If 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 sickness | Diclectin (doxylamine plus pyridoxine) | Chlorpromazine, metoclopramide (in third trimester), diphenhydramine, dimenhydrinate, meclizine, cyclizine | |
| Peptic ulcer disease | Antacids, magnesium hydroxide, aluminum hydroxide, calcium carbonate, ranitidine | Sucralfate, bismuth subsalicylate | |
| Pruritus | Topical: moisturizing creams or lotions, aluminum acetate, zinc oxide cream or ointment, calamine lotion, glucocorticoids; systemic: hydroxyzine, diphenhydramine, glucocorticoids, astemizole | Topical: local anesthetics | |
| Thrombophlebitis, deep-vein thrombosis | Heparin, antifibrinolytic drugs, streptokinase | | Streptokinase 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
Outline