Medical Problems in Pregnancy

Medical Disease in Pregnancy=

Erin Snyder, MD

September 26, 2007

Case 1 A 30 y= ear old WF who sees you for Hypertension calls your office to let you know that she= is pregnant.

Question: What complications of pregnancy should she be aware of?

Ø 50% of wome= n with chronic hypertension develop superimposed preeclampsia= . Preeclampsia<= /span> can progress to eclampsia, renal failure, or HE= LLP syndrome. The risks for placental abruption and perinatal mortality inc= rease with preeclampsia and underlying hypertension.<= span style=3D'mso-spacerun:yes'> Development of preeclampsia is more common in those patients with renal insufficiency, history of hypertension during a previous pregnancy, and chronic hypertension for greater than 4 years.

Ø Pregnancy c= auses an increase in blood volume and decreased systemic vascular resistance. The corresponding increase in card= iac output can result in cardiac decompensation in a patient with underlying cardiac disease.&n= bsp; This increases the risk of peripartum cardiomyopathy.

<= /o:p>

Question: She has been on HCTZ with good con= trol of blood pressure for one year. Is this appropriate therapy? Wha= t antihypertensives are regularly utilized in pregnancy, which are contraindicated?

Ø Methyldopa = is a centrally acting agent that is commonly used as first line therapy. Dose is 250mg BID, max 3g/day=

Ø Labetalol is also often used first line. Selective beta blockers (ie, Metoprolol) may incre= ase incidence of small for gestational age infants

Ø Calcium Cha= nnel Blockers such as Nifedipine are generally secon= d or third line

Ø Diuretics s= uch as HCTZ have some role, typically as second agents. They should be avoided in any situ= ation where uteroplacental perfusion is decreased (su= ch as preeclampsia)

Ø ACE-Inhibit= ors/ARBs are contraindicated in 2^nd and 3^=
rd trimesters, but class C drugs for 1^st trimester. The difficulties seem to be associ= ated with development of fetal renal tubular function. The most commonly seen birth defects are: renal dysgenesis, renal failure, <= span class=3DSpellE>oligohydramnios, pulmonary hypop= lasia

Case 2: A 30 = year old WF who sees you for Diabetes calls your office to let you know that she is pregnant.

Question: Wha= t are some of the physiologic changes of pregnancy that may affect her diabetes?<= span style=3D'mso-spacerun:yes'>

Ø Late in the= first trimester, insulin sensitivity is often enhanced. Women who have frequent emesis may= have more hypoglycemia. Late= r in pregnancy, placental hormones are secreted that decrease maternal insulin sensitivity. Caloric requirem= ents are often increased during pregnancy, which may require medication adjustme= nts to prevent hypoglycemia.

Question: She= has been well controlled on metformin 500mg daily f= or the past 3 years. Should you chan= ge her medication regimen?

Ø Complicatio= ns will be minimized in patients who had tight glucose control and minimal complications PRIOR to pregnancy.

Ø Oral hypoglycemics have not been well studied in pregnancy= , and typically patients are changed to an insulin regimen. This allows for variable dosing gi= ven the changing insulin sensitivities during pregnancy. Patients will need to check fastin= g and postprandial blood sugars frequently in order to adjust therapy.=

Ø Glyburide has been studied in pregnant women, and found t= o have efficacy similar to insulin in providing glucose control without maternal or neonatal complications. It do= es not cross the placenta.

Ø Metformin is a category B drug, but has not been well stu= died in humans. It is used in PCOS patients who desire fertility, and no adverse effects have been found in wo= men who get pregnant while on this drug.

Case 3 A 30 y= ear old WF with a BMI of 40, called your office to let you know she is pregnant.

Question: Wha= t are some of the complications seen in obese pregnant women?

Ø Obesity is = an independent risk factor for hypertensive disorders in pregnancy including <= span class=3DSpellE>preeclampsia and eclampsia. Risk of pre-eclampsia doubles with every 5-7 point (kg/m^{2)
increase in BMI. <=
/span>}

Ø There is al= so increased risk of gestational diabetes (OR 2.80 in one large study), and ob= ese women with gestational diabetes have double the risk of developing type 2 diabetes compared to lean women with gestational diabetes.

Ø There is al= so thought to be increased risk of post-term birth, multi= fetal pregnancy, urinary tract infection, and obstructive sleep apnea in obese pregnant women.

Ø During labo= r, there are more delivery complications, such as shoulder dystocia, longer labors, and cesarean sections.

Ø Infants bor= n to obese women are more likely to have congenital abnormalities and macrosomia; and perinatal mortality is increased up to 5 times, even controlling for other risk facto= rs.

Question: Wha= t should you tell your obese patient about pregnancy weight gain?

Ø There is da= ta to recommend increased weight gain during pregnancy for underweight women, as = it has been shown to improve outcomes. Similar data is not present for obese women. However, guidelines have been put = forth by ACOG regarding optimum weight gain for obese women.

o&nb= sp; Normal weig= ht women, with pre-pregnancy BMI 19.9-26, should gain 11-16 kg

o&nb= sp; Overweight = women (BMI 26-29) should plan to gain 7-11.5kg

o&nb= sp; Obese women= (BMI >29) should gain at least 6.8 kg. There is no upper limit given

Drugs with p= roven teratogenic effects in humans*

Drug	Teratogenic effect<= o:p>
Aminopterin, methotrexate	CNS and limb malformations
Angiotensin-coverting-enzyme inhibito= rs	Prolonged renal failure in neonates, decreased skull ossification, renal tubular dysgenesis<= o:p>
Anticholinergic drugs	Neonatal meconium ileus
Antithyroid drugs (<= span class=3DSpellE>propylthiouracil and met= himazole)	Fetal and neonatal goiter and hypothyroidism, aplasia cutis (with meth= imazole)
Carbamazepine	Neural-tube defects
Cyclophosphamide	CNS malformations, secondary cancer<= /p>
Danazol and other androgenic drugs	Masculinization of female fetuses
Diethylstilbestrol	Vaginal carcinoma and other genitourinary defects in f= emale and male offspring
Hypolycemic drugs	Neonatal hypoglycemia
Lithium	Ebstein's anomaly<= o:p>
Misoprostol	Moebius sequence=
Nonsteroidal antiinflammatory drugs	Constriction of the ductus= arteriosus, necrotizing enterocolitis
Paramethadione	Facial and CNS defects
Phenytoin	Growth retardation, CNS deficits
Psychoactive drugs (eg, barbiturates, opioids, and benzodiazepi= nes)	Neonatal withdrawal syndrome when drug is taken in late pregnancy
Systemic retinoids (isotretinoin and etretin= ate)	CNS, craniofacial, cardiovascular, and other defects
Tetracycline	Anomalies of teeth and bone
Thalidominde	Limb-shortening defects, internal-organ defects
Trimethadione	Facial and CNS defects
Valproic acid	Neural-tube defects
Warfarin	Skeletal and CNS defects, Dandy-Walker syndrome

CNS: central nervous system.
* On= ly drugs that are teratogenic when used at clinica= lly recommended doses are listed. The list includes all drugs proven to affect neonatal morphology or brain development and some of the toxic manifestations predicted on the basis of the pharmacologic actions of= the drugs.
3D"[Bullet]" The drug i= s not currently in clinical use.
Sulindac probably = does not have this effect.
Data= from: Koren, G, Pastuszak= , A, Ito, S. Drug Therapy. N Engl J Med 1998; 338:1128. Table 1. p. 1129.