Definitions Parity & Gravida Parity Gravida is number of deliveries after 20 weeks gestation. Gravida is number of pregnancies a woman has had regardless of outcome. For example, a woman who is currently pregnant & has previously delivered one set of twins & had two spontaneous abortions is described as a gravida 4 para 1 (G4P1). In the UK, gravidity is defined as the number of times that a woman has been pregnant and parity is defined as the number of times that she has given birth to a fetus with a gestational age of 24 weeks or more, regardless of whether the child was born alive or was stillborn. Gravida indicates the number of times a woman is or has been pregnant, regardless of the pregnancy outcome.[3] A current pregnancy, if any, is included in this count. Twin pregnancy is counted as 1. Parity, or "para" indicates the number of pregnancies reaching viable gestational age (including live births and stillbirths). The number of fetuses does not determine the parity.[4] Twin pregnancy carried to viable gestational age is counted as 1.

Trimesters of Pregnancy Average pregnancy is ~280 days or 40 wks when calculated from the first day of LMP. Pregnancy is typically divided into 3 trimesters, ~13-14 wks each. Time between end of 22nd wk of gestation & end of 28th day after birth is considered perinatal period. Developmental or conceptional age is time after fertilization & is about 2 wks < than gestational age. 1st 2 wks after fertilization is pre-embryonic period. Embryonic period is from 2nd wk of conception through 8th wk. Fetal period begins after 8th conceptional week & continues until birth. Organogenesis occurs from 4th through 7th developmental week.

Delivery Abortion (spontaneous or terminal) is delivery before 20 wks' gestation. Term infant is fetus delivered between 37 & 42 wks gestation. Preterm birth is one occurring between 20 & 37 wks' gestation. Post-term (postmaturity) birth occurs after beginning of 43 wks' gestation. Parturition refers to labor, & puerperium is 6 to 8 wks after delivery.

Drug pregnancy categories Category A: Controlled studies in women fail to demonstrate risk to fetus. Category B: Either animal studies have not demonstrated risk & no controlled studies have been done in women, or animal studies have shown risk that has not been confirmed in humans. Category C: Either studies in animals have shown ADE on fetus & no controlled studies have been done in women, or no studies in women or animals are available. Category D: There is evidence of fetal harm, but benefit of medication may outweigh risk. Category X: There is evidence of fetal harm, & no benefit of medication outweighs risk.

Dietary supplementation during pregnancy (American Society for Nutrition, 2009) American Dietetic Association & Institute of Medicine recommend multivitamin & multimineral supplements for: all pregnant women who smoke or abuse alcohol or drugs those with iron deficiency anemia those with poor-quality diets including vegans women carrying ≥2 fetuses.

Iron Requirements Woman needs ~18-21 mg of iron/day during pregnancy; iron absorption from GI tract ↑ by ~15-50%. Average diet does not meet these requirements Some women may already have inadequate body stores of iron before pregnancy → Food & Nutrition Board of the National Research Council recommends daily elemental iron supplementation of 30 mg during 2nd & 3rd trimesters. Prenatal vitamins usually contain 30-60 mg of elemental iron. Women with IDA should be given 60-120 mg of elemental iron daily. IDA during pregnancy generally is associated with Hb & Hct <11% & <33%, respectively, during 1st & 3rd trimesters or Hb & Hct < 10.5% & 32%, respectively, during 2nd trimester.

Folate Requirements NTDs (neural tube defect) can develop within 1st month of pregnancy at a time when many women are unaware of their pregnancy. In 1992, US Public Health Service recommended that all women with child-bearing potential should consume 0.4 mg/day of folic acid to prevent NTDs Foods contain only small amount of this vitamin; overcooking & high fiber diets can ↓ amount. Most prenatal vitamins contain 0.8-1 mg of folic acid. Women who have had NTD-affected pregnancy Should receive genetic counseling because they have 2-3% risk of having another such outcome. Such women should take 4 mg/day of folic acid at least 1 mth before conception & through 1st 3 mths of pregnancy.

Folate Requirements (cont’d) Women who require 4 mg/day of folic acid should be prescribed folic acid tablets rather than just ↑ number of multivitamin tablets (potentially teratogenic dose of vitamin A!). High doses of folic acid do not prevent NTD better than 0.4 mg/day in women without previous history of NTD-affected pregnancies & may complicate diagnosis of B12 deficiency.

Calcium Requirements Calcium is needed during pregnancy for adequate mineralization of fetal skeleton & teeth, especially during 3rd trimester when teeth are formed & skeletal growth is greatest. RDA for calcium during pregnancy is 1,200 mg/day. Large maternal stores can provide calcium if dietary intake is inadequate; however, depleting maternal stores may put pregnant lady at risk for osteoporosis later in life. Foods rich in calcium (e.g., milk, cheese, yogurt, legumes, nuts, dried fruits) or calcium supplements can be used to meet calcium RDA. Supplemental calcium 1–2 g/day decreases the relative risk of hypertension by 30%

Common Complaints of Pregnancy

Nausea & Vomiting during pregnancy (NVP) Occurrs in ~50-80% of pregnancies, during wks 5-12 of gestation. Can have impact on woman's daily activities, work productivity, & QoL. Changes in hormonal levels of estrogen, progesterone, & hCG have been implicated. Mild to moderate NVP has been associated with lower rates of miscarriage, preterm delivery, & stillbirth. Severe NVP can persists in < 1% of pregnancies = hyperemesis gravidarum → detrimental effects on mother & fetus: weight loss of >5% of prepregnancy weight, ketosis & ketonuria, acidosis, hypovolemia & electrolyte abnormalities.

NVP (cont’d) Treatment of hyperemesis gravidarum often requires hospitalization for parental fluid administration, electrolyte replacement, vitamin supplementation, & antiemetic therapy. Reductions in lower esophageal pressure, gastric peristalsis, & gastric emptying may worsen N&V. Patient may be evaluated for other causes of N&V if her symptoms persist (e.g., gastroenteritis, cholecystitis, pancreatitis, hepatitis, PUD, pyelonephritis, & fatty liver of pregnancy).

Nonpharmacologic Management Most mild forms can be managed with psychological support, & lifestyle & dietary changes. Eating smaller frequent meals consisting of low-fat, bland, & dry diet (e.g., bananas, crackers, rice, toast). Avoiding spicy & highly aromatic foods, & eliminating pills with iron. Meals high in protein were more likely to alleviate NVP than carbohydrate or fatty meals. Rest & avoidance of sensory stimuli that contribute to effects of NVP can also be helpful. Vitamin B6, ginger root, acupuncture, acupressure have improved NVP in small number of patients A bland diet is a diet consisting of foods that are generally soft, low in dietary fiber, cooked rather than raw, and not spicy. Fried and fatty foods, strong cheeses, whole grains (rich in fiber), and the medications aspirin and ibuprofen are also avoided while on this diet.

Pharmacologic Management Indicated for treatment of moderate to severe N&V that fails to respond to nonpharmacologic interventions or when N&V threatens mother's metabolic or nutritional status (e.g., hyperemesis gravidarum). Doxylamine with pyridoxine (vitamin B6) can be considered first-line therapy. Prochlorperazine, promethazine & trimethobenzamide: no ↑ in malformations. Metoclopramide can control vomiting & gastric reflux associated with pregnancy. Despite limited safety data, it is antiemetic of choice in many European countries. Ondansetron & droperidol: limited experience. Corticosteroids may improve symptoms, but use during 1st trimester is associated with small but significant risk of fetal oral clefts.

HW: Pharmacological management of N&V of pregnancy (NEJM, 2010)

HW: NEJM, 2010

Constipation Prevalence 25-40%. Light physical exercise & increased intake of dietary fiber & fluid should be instituted first. If additional treatment is needed, supplemental fiber &/or stool softener is appropriate. Osmotic laxatives (polyethylene glycol, lactulose, sorbitol, & magnesium & sodium salts) are acceptable treatments but should be reserved for occasional use only. Polyethylene glycol is considered by some the ideal laxative in pregnancy. Senna & bisacodyl can be used occasionally (caution with near term). Castor oil & mineral oil should be avoided.

Reflux Esophagitis (GERD) Affects ~ 2/3 of pregnant women. Predisposing factors: enlarging uterus ↑ intra-abdominal pressure, & estrogen & progesterone relax esophageal sphincter Lifestyle & dietary modifications: eating smaller meals, avoiding late meals close to bedtime, & elevation of head of bed. Avoidance of salicylates, caffeine, alcohol, & nicotine. If these modifications are not successful, calcium carbonate antacid. Sucralfate (B) is not harmful if normal renal function. H2RAs: evidence supports use of ranitidine & cimetidine. Famotidine (B) & nizatidine (B) are likely safe PPIs should be reserved for complicated or intractable GERD (few data)

Venous Thrombo Embolism Incidence VTE during pregnancy is > than in nonpregnant women. Therapy to prevent or treat VTE during pregnancy must not include warfarin (between wks 6-12 Fetal bleeding, Malformations of nose, Stippled epiphyses, CNS defects

Treatment Recommendations Pregnant women Recommend adjusted dose subcutaneous low molecular weight heparin (LMWH), rather than adjusted dose intravenous unfractionated heparin (IV UFH) (Grade 1B) or vitamin K antagonists (Grade 1A). We recommend against the use of oral direct thrombin inhibitors (eg, dabigatran) or anti-Xa inhibitors (eg, rivaroxaban, apixaban) in pregnant women (Grade 1C). Uptodate 2017

Duration of anticoagulant therapy continue at least six weeks postpartum (Grade 2C). Total duration of anticoagulant therapy at least three to six months for women whose only risk factors for VTE were transient (eg, pregnancy) (Grade 2C). Patients with persistent risk factors for VTE may require longer therapy Thrombolytic therapy should be reserved for pregnant or postpartum patients with life-threatening acute PE (ie, persistent and severe hypotension due to the PE). Uptodate 2017

Prevention Recommendations The risk of venous thromboembolism (VTE) Increased in all trimesters of pregnancy, especially the postpartum period. Antepartum pharmacologic prophylaxis for History of a single idiopathic, pregnancy-associated or estrogen-associated VTE, and in those with a history of multiple VTEs, regardless of the cause (Grade 2C). Known thrombophilia and a history of VTE and for patients with certain "high risk" thrombophilias plus a family history of VTE. Uptodate 2017

Prevention Recommendations Cesarean section and have no additional risk factors for VTE Early ambulation or the use of mechanical devices rather than pharmacologic thromboprophylaxis (Grade 2C). Cesarean section and have additional risk factors for VTE, Use of both pharmacologic and mechanical thromboprophylaxis (Grade 2C). (See 'Cesarean section' above.) Uptodate 2017

Prevention Recommendations Pharmacologic prophylaxis, Heparin-based regimens are safer than oral anticoagulants. Low molecular weight heparin rather than unfractionated heparin provided the patient does not have renal insufficiency (eg, creatinine clearance <30 mL/min) (Grade 2C). Heparin regimens are typically administered during pregnancy at different doses depending upon the risk of thromboembolism and desired degree of anticoagulation (prophylactic, intermediate, therapeutic) Uptodate 2017

Prevention Recommendations Antepartum pharmacologic thromboprophylaxis should be continued until delivery. Postpartum pharmacologic thromboprophylaxis be continued for six weeks to three months. Following cesarean section, thromboprophylaxis is continued until the patient is ambulatory. (See 'Duration' above.) Uptodate 2017

UTI (DiPiro) Asymptomatic bacteriuria: 2-10% & acute cystitis 1-4% of pregnancies. 20-40% of pregnant women with asymptomatic bacteriuria develop pyelonephritis later in pregnancy → importance of early detection. Pyelonephritis complications: premature delivery, low infant birth weight, fetal death, preeclampsia, pregnancy-induced HTN, anemia, thrombocytopenia, & transient renal failure. For screening for UTI in pregnancy, ACOG recommends urine culture both at initial prenatal visit & during 3rd trimester. U.S. Preventive Task Force recommends urine culture between 12 & 16 wks' gestation. In 95% of cases, E. coli is infecting organism. Group B Streptococcus (5%) may correspond to heavy colonization of genitourinary tract, ↑ risk for group B Streptococcus infection in newborn.

UTI (DiPiro) (cont’d) Treatment of asymptomatic bacteriuria is necessary to ↓ risk of pyelonephritis & premature delivery. Cephalexin is safe & effective. Nitrofurantoin should not be used after wk 37 due to concern for hemolytic anemia in newborn. Sulfa-containing drugs should be avoided during last weeks of gestation (Why???). Trimethoprim is relatively contraindicated during 1st trimester Fluoroquinolones & tetracyclines are contraindicated. Duration is commonly 7-10 days (may be 3 days) → repeat culture 10 days after completion of treatment.

UTI (DiPiro) (cont’d) Treatment of acute cystitis is similar to that of asymptomatic bacteriuria; duration is 7-10 days. Acute pyelonephritis complicates 1-2% of pregnancies. Usually hospitalization + parenteral cephalosporins (e.g., cefazolin or ceftriaxone), ampicillin with gentamicin, or ampicillin-sulbactam. Outpatient antibiotic therapy (cephalexin) can be considered if woman has been afebrile for 48 hrs & symptoms have resolved. Total duration of antibiotic therapy for acute pyelonephritis is 10-14 days. Up to 23% of women may experience recurrence → suppression therapy with nitrofurantoin 100 mg nightly is recommended for duration of pregnancy.

HW (DiPiro): Preferred inhaled corticosteroid in pregnancy? The safest two antiepileptic drugs during pregnancy? Need for vitamin K prophylaxis during pregnancy & in neonates? Need for folic acid supplementation in women on AEDs who are planning to conceive & are pregnant?