Sterile Drug Products Used During Delivery and the...

Sterile Drug Products Used During Delivery and the Postpartum PeriodPharMEDium Lunch and Learn Series

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Sterile Drug Products Used During Delivery and the Postpartum Period

LUNCH AND LEARN

p

February 12, 2016

Featured Speaker: Kylie N. Barnes, Pharm.D., BCPS

Clinical Assistant ProfessorUniversity of Missouri ‐ Kansas City School of Pharmacy

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CE Activity Information & Accreditation

ProCE, Inc. (Pharmacist and Tech CE)

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Funding: This activity is self‐funded through

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g y gPharMEDium.

It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Barnes has no relevant commercial and/or financial relationships to disclose.



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Sterile Drug Products Used During Delivery and the Post-partum Period

Kylie N. Barnes, Pharm.D., BCPS

PharMEDium, LLCSpring 2016

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Learning Objectives: Pharmacists1. Evaluate what medications will likely be needed as

supportive care for the patients based on the differentsupportive care for the patients based on the different types of delivery (e.g., natural vaginal delivery, induction, emergency c-section, etc).

2. Evaluate pain management options for pregnant patients during delivery, including PCAs, epidurals, and injectable options.

3 Determine the need for analgesia and/or sedation in a3. Determine the need for analgesia and/or sedation in a pregnant patient in active or scheduled delivery.

4. Design individualized treatment regimens for pregnant patients with pre-eclampsia, eclampsia, hyperemesis, clotting disorder/thrombosis during pregnancy, pre-term labor, or a Group B streptococcus + status pre-delivery. 7

Learning Objectives: Technicians1. List the medications likely needed as supportive care for

the patients based on the different types of delivery (e.g.,the patients based on the different types of delivery (e.g., natural vaginal delivery, induction, emergency c-section, etc).

2. Recognize the pain management options for pregnant patients during delivery, including PCAs, epidurals, and injectable options.

3 Summarize the need for analgesia and/or sedation in a3. Summarize the need for analgesia and/or sedation in a pregnant patient in active or scheduled delivery.

4. Recognize the medications used in pregnant patients with pre-eclampsia, eclampsia, hyperemesis, clotting disorders/thrombosis during pregnancy, pre-term labor, or a Group B streptococcus + status pre-delivery. 8



Plan Varies by Delivery Method

• Term vaginal delivery

• Induced vaginal delivery

• Scheduled cesarean delivery

• Emergency cesarean deliveryEmergency cesarean delivery

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Term Vaginal Delivery

• Routine to give all women an IV during• Routine to give all women an IV during labor– Precautionary to prevent dehydration

– Saves a step later should there be an emergency

• Heparin lock an option p p– Open vein in the event of an emergency

– Not tethered to IV pole

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Induced Vaginal Delivery

• More than 22% of all deliveries involve• More than 22% of all deliveries involve induction– Elective vs. indicated

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Induced Vaginal Delivery: Pitocin

• Most commonly used drug in the US –synthetic form of oxytocin

• Physiology of oxytocin-stimulated labor is similar to spontaneous labor– Stimulates an increase in intracellular calcium

in uterine myometriumin uterine myometrium

– Causes contractions of the uterus. Used to:• Start labor

• Increase the speed of labor

• Stop bleeding following delivery 12




• Individual patients vary in sensitivity and• Individual patients vary in sensitivity and response

• Uterine response occurs 3-5 minutes after infusion

• Steady level of oxytocin in plasma achieved S y y pby 40 minutes

• Typically have better response closer to term

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Induced Vaginal Delivery: PitocinLabor Stimulation with Pitocin

Regimen Starting Dose Incremental Dosage Interval g g(mU) Increase (mU/min)

g(min)

Low-dose 0.5 – 2 1 – 2 15 – 40

High-dose 6 3 – 6 * 15 – 40

*incremental increase is reduced to 3 mU/min in presence ofincremental increase is reduced to 3 mU/min in presence of hyperstimulation and reduced to 1 mU/min with recurrent hyperstimulation

*Adapted from ACOG Practice Bulletin: Induction of Labor August 2009 14




E h h it l t i ll h th i• Each hospital typically has their own titration protocol

• Pitocin generally diluted 10 units in 1000 mL of an isotonic solution – concentration of 10 mU/mL

• Administered by infusion pump that allows precise control of the flow rate

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“Routine” C-Section

• Represents 31 8% of deliveries in the US• Represents 31.8% of deliveries in the US– Most common surgical procedure

• Spinal anesthesia

• Epidural anesthesia

• General anesthesia• General anesthesia

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Emergency C-Section

• Only 0 5 1% of all deliveries• Only 0.5 – 1% of all deliveries

• Usually in response to acute hemorrhage, fetal bradycardia, umbilical cord prolapse, or uterine rupture

• Very quick process – fetal morbidity and V y q p ymortality can be greatly affected by a delay of just a few minutes

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Emergency C-Section

• Coordination of at least six individuals:• Coordination of at least six individuals: surgeon, assistant for the surgeon, anesthesiologist, scrub technologist, circulating nurse and pediatrician

• Currently no standardized protocols exist

• General anesthesia is commonly used

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Additional Concerns

• Drugs used for pain control during labor and deliveryand delivery

• Drugs used for complications– Preterm Labor

– Group B Streptococcus +

– Pre-eclampsia / EclampsiaPre eclampsia / Eclampsia

– Anticoagulation

– Nausea and vomiting/hyperemesis

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PAIN CONTROL DURING LABOR AND DELIVERY

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Pain Control During Labor and Delivery

• Available methods of analgesia• Available methods of analgesia– Parenteral

– Regional• Epidural

• Spinal

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Pain Control: Parenteral• Can be given in intermittent doses by

ti t tpatient request

• Don’t relieve pain, but reduce anxiety and result in sedation

• May be set up via patient-controlled administration (PCA) pain pumps

Agent Usual Dose Frequency Onset

Meperidine 25-50mg IV Q 1-2 hours 5 minutes

Fentanyl 50-100 mcg IV Q 1 hour 1 minute

Butorphanol 1-2mg IV Q 4 hours 1-2 minutes

Morphine 2-5mg IV Q 4 hours 5 minutes

Nalbuphine 10mg IV Q 3 hours 2-3 minutes

*Adapted from ACOG Practice Bulletin: Obstetric analgesia and anesthesia July 200222



Pain Control: Regional

• Partial to complete loss of painp p

sensation below T8 to T10

• Epidural – offers the most effective form of pain relief – Catheter is placed in the epidural space; continuous

infusion of local anesthetic agents or narcotics

– Can be used for c-section delivery or postpartum tubal ligation

– Commonly combine a low-dose local anesthetic (e.g., bupivacaine, or ropivacaine) with an opioid agonist (fentanyl)

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Pain Control: Regional

• Spinal block – single-shot spinal analgesia p g p g– Excellent pain relief for short duration procedures

• C-section delivery

• Second stage of labor

• Rapidly progressing labor

• Postpartum tubal ligation p g

– Long-acting local anesthetic often used, with or without opioid agonist

– Duration approximately 30-250 minutes depending on agent(s) used

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Pain Control: ComplicationsComplication Incidence (%)

Fever > 100.4° FNulliparous women 19%Nulliparous womenMultiparous women

19%1%

Postdural puncture headacheSpinalEpidural

1.5-3%2%

Transient fetal heart decelerations 8%

i h i id dd dPruritus – when opioid addedEpiduralSpinal

1.3-26%41-85%

Inadequate pain relief (epidural) 9-15

*Adapted from ACOG Practice Bulletin: Obstetric analgesia and anesthesia July 2002 25

Pain Control During Labor and Delivery

• In the event the neonate appears depressed• In the event the neonate appears depressed – Naloxone 0.1 mg/kg IV may be indicated to

reverse the effects of the analgesia

• Mother and baby will be on continuous watch

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Pain Control During Labor and Delivery: Breastfeeding

• Intrapartum opioid use may:– Decrease neonatal rooting reflexes and delay

initiation of breastfeeding

– Increase agitation and irritation in infant

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PRE-TERM LABOR

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Pre-Term Labor

• Labor between 20 -37 weeks gestation

• ~12% of all births occur before term

• Leading cause of neonatal mortality

• Most common reason for antenatal hospitalization

• Accounts for:~70% of neonatal deaths

~36% of infant deaths~25-50% of cases of long-term neurologic

impairment in children 29

Pre-Term Labor

• Approximately 30% spontaneously resolves• Approximately 30% spontaneously resolves

• 50% of patients hospitalized with pre-term labor deliver at term

• Delays in delivery are reserved for women where a delay will benefit the newborn y

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Pre-Term Labor: Treatment• Nonpharm

– Bed rest

– Abstention from intercourse/orgasm

– Hydration

• Pharm– Tocolytic drugs – inhibit uterine contractionsTocolytic drugs inhibit uterine contractions

– Antibiotics – treat intrauterine bacterial infections

– Corticosteroids – maturation of fetal lungs

– Magnesium sulfate – fetal neuroprotection

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Pre-Term Labor: Tocolytic Agents

Agent/Class Maternal Side Effects Fetal or Newborn Side Effects

Contraindications

Calcium channel blockers

Dizziness, flushing, hypotension

No known ADRs Hypotension and preload-dependent cardiac lesions, such as aortic insufficiency

NSAIDs Nausea, esophageal reflux, gastritis, and emesis

Oligohydramnios Platelet dysfunction or bleeding disorder, hepatic disorders, GI ulcerative disease, renal dysfunction, asthma

Magnesium sulfate

Flushing, diaphoresis, nausea,loss of deep tendon reflexes, respiratory depression, and cardiac arrest

Neonataldepression

Myasthenia gravis

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Pre-Term Labor: Tocolytic AgentsClass Example Agent and Dose

Calciumchannel

Nifedipine 10-20mg oral loading dose, repeated every 3 to 6 hours until contractions are rare, then followed by long-acting formulations of 30-60mg everychannel

blockerscontractions are rare, then followed by long acting formulations of 30 60mg every 8-12 hours for 48 hours

NSAIDs Indomethacin 50mg oral loading dose, followed by 25 – 50 mg by mouth every 6 hoursTherapy generally limited to 48 hoursUsed before 32 weeks gestation

Magnesiumsulfate

Magnesium sulfate 4-6 g in 10% to 20% solution loading dose given over 30 minutes, followed by maintenance dose of 2g/hourThe IV rate is increased by 1 g/hour until the patient has less than one contractionThe IV rate is increased by 1 g/hour until the patient has less than one contraction per 10 minutes or until the maximal dose of 3 or 4 g/hour is reached IV fluids are restricted to 125 mL/hourDeep tendon reflexes and vital signs, including respiratory rate, should be recorded hourly

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• Effective for up to 48 hours

• Not indicated for use before neonatal viability

• Special circumstances – after an event known to cause pre-term labor (e.g., intra-bd i l )abdominal surgery)

• Women with pre-term contractions, but not cervical change (dilation < 2 cm) in general should not receive tocolytics

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Contraindications to TocolysisContraindications to Tocolysis

Intrauterine fetal demiseLethal fetal anomaly

Nonreassuring fetal statusSevere preeclampsia or eclampsia

Maternal bleeding with hemodynamic instabilityChorioamnionitisChorioamnionitis

Preterm premature rupture of membranesMaternal contraindications to tocolysis (agent specific)

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Pre-Term Labor: Antibiotics

• Given in pre term labor to prevent neonatal• Given in pre-term labor to prevent neonatal Group B streptococcus infection

• Intrapartum prophylaxis with penicillin or ampicillin recommended

(more information later) ( )

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Pre-Term Labor: Corticosteroids

• Direct improvement in neonatal outcomes– Lower severity and frequency of:

• Respiratory distress syndrome

• Intracranial hemorrhage

• Necrotizing enterocolitis

• Death

• Single course recommended for pregnant women between 24 – 34 weeks of gestation– May be given at week 23 in women at risk for

pre-term delivery with 7 days37

Pre-Term Labor: Corticosteroids

• Betamethasone 12mg intramuscularly every 24 hours x 2 doses

• Dexamethasone 6mg intramuscularly every 12 hours x 4 doses

• First dose still given, even if unlikely patient will be able to receive second dose

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Pre-Term Labor: Magnesium Sulfate

• When given with neuroprotection intent• When given with neuroprotection intent– Pre-delivery administration reduces the

occurrence of cerebral palsy

– Does not prolong labor

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GROUP B STREPTOCOCCUS POSITIVE

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Group B Streptococcus + (GBS)

• Asymptomatic, rectovaginal colonization– Approximately 20-30% of pregnant women

• Increases risk for perinatal sepsis and maternal infection

• Prevention– All pregnant women screened at 35-37 weeks

gestation for GBS colonization

– Women who are GBS + receive antibiotic prophylaxis during delivery

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Group B Streptococcus + (GBS): Treatment

First Line Agent Alternative RegimenP i illi G 5 illi it i iti ll A i illi 2 IV i iti ll th 1Penicillin G 5 million units initially; then 2.5 to 3 million units every 4 hours IV until delivery

Ampicillin 2 g IV initially; then 1 g every 4 hours until delivery

Penicillin Allergy: low risk for anaphylaxis

Penicillin Allergy: high risk for anaphylaxisp y p y

(immediate urticarial or bronchospasms)

Cefazolin 2 g IV initially; then 1 g every 8 hours IV until delivery

Clindamycin 900 mg IV every 8 hours (if susceptibility is known)

Vancomycin 1 g IV every 12 hours42



Group B Streptococcus + (GBS)

• Best results when given at least 4 hours before• Best results when given at least 4 hours before delivery

• If GBS status is not known at the time of delivery, give antibiotics if:– Less than 37 weeks gestation

– Rupture of membranes occurred at least 18 hoursRupture of membranes occurred at least 18 hours earlier

– Temperature at or greater than 100.4ºF

• Scheduled C-section delivery, antibiotics are not needed

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Risk Factors:• Previous infant with GBS

disease?• GBS bacteriuria this pregnancy?• Delivery < 37 weeks’ gestation

No

Yes

Collect rectal and vaginal swab for GBS culture at 35-37 weeks’ gestation GBS+

NoGive PCN

(or alternative in case of allergy)

GBS-Not done,

incomplete, or unknown

No prophylaxis needed

Risk factors:Intrapartum fever > 38 C (100.4 F)Membrane rupture > 18 hours

Yes

No44



PRE-ECLAMPSIA / ECLAMPSIA

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Pre-eclampsia

• Disorder in pregnancy characterized by• Disorder in pregnancy characterized by poor perfusion of many vital organs that is completely reversible with the termination of pregnancy

• Occurs in about 4% of pregnancies

• Often asymptomatic, but most related to – Hypertension (> 140/90 mmHg after week 20)

– Proteinuria (> 0.3 g in 24 hour urine collection)

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Pre-eclampsia

Other Signs and Symptoms of Pre-eclampsia and Eclampsia g y p p p

Cerebral FeaturesHeadache DizzinessTinnitus

DrowsinessChange in respiratory rate

Tachycardia

Visual FeaturesDiplopia

ScotomataBlurred Vision

Amaurosis

Fever

Gastrointestinal FeaturesNausea

VomitingEpigastric painHematemesis

Renal FeaturesOliguriaAnuria

HematuriaHemoglobinuria

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Preeclampsia Treatment

• Delivery if pregnancy is at term

• IV magnesium sulfate to prevent seizures– Loading dose of 4-6 g IV over 15 to 30

minutes, followed by 1-2 g/hr as continuous infusion

– Deep tendon reflexes and respiratory statusDeep tendon reflexes and respiratory status checked at least every 2 hours

– If overdosage occurs (e.g., apnea) • Calcium gluconate 10mL of 10% solution IV over 3

minutes is an effective antidote 48



Preeclampsia Treatment

• If a patient is on magnesium and has an eclamptic seizure:– Diazepam 5 to 10 mg IV

– Lorazepam 4 mg IV

– Pentobarbital 125 mg IV

• Most seizures terminate spontaneously• Most seizures terminate spontaneously within 1-2 minutes– Avoidance of injury

– Protection of the airway to prevent aspiration 49

Preeclampsia Treatment• Frequent monitoring of BP, urine protein,

CMP, and platelet counts

• Begin drug therapy for BP if > 140/90mmHg

• Start IV hypertensives if SBP 160-180 or DBP >110 (PO okay if preeclampsia)

Drug Intravenous Dose Interval between Doses

Hydralazine 5-10mg Q 15-20 minutes until desired response

Labetalol 20mg bolus, followed by 40mg

If not effective within 10 minutes, then 80mg every 10 minutes to a maximum total dose of 220mg

Nifedipine 10mg orally 4-8 hours

*Adapted from ACOG Practice Bulletin: Diagnosis and Management of Preeclampsia and Eclampsia January 2002 50



Preeclampsia

• Goals of therapypy– Decrease blood pressure

– Prevent or control seizures

– Deliver a viable infant

• Risk for eclampsia can continue for up to 6 weeks after delivery– Must continue to monitor blood pressure and

urine protein levels 51

ANTICOAGULATION

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Anticoagulation During Pregnancy or Postpartum

• Risk increasesRisk increases fourfold to fivefold during pregnancy due to both physiologic and anatomic changes1-2

• VTE i 1 f• VTE occurs in 1 of every 1000 pregnancies3

• Greatest risk in 3rd

trimester2

*picture from http://bloodjournal.hematologylibrary.org/content/ 114/6/1138/F1.expansion

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Treatment of VTE in Pregnancy

• Guidelines recommend both low molecular• Guidelines recommend both low molecular weight heparin (LMWH) and unfractionated heparin (UFH) use during pregnancy4-5

• Dosing considerations– Pharmacokinetic changesg

– Weight fluctuations

– Increase in renal function

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Treating a Newly Diagnosed VTE in Pregnancy

Hemodynamically Stable Hemodynamically Unstabley y y y

Patient presentationNormal heart rate / blood pressureOxygenating well

Unstable heart rate and/or blood pressureLarge clotsOther maternal comorbidities

TreatmentTherapeutic LMWH – anticipatingdischarge from the hospital

IV UFH: 80 units/kg IV one time followed by 80 units/kg/hour by continuous IV infusion. The dose is adjusted to maintain aPTT atTreatment discharge from the hospital

relatively soonis adjusted to maintain aPTT at 1.5 to 2.5 times control

(or based on hospital protocol)

*Adapted from ACOG Practice Bulletin: Thromboemolism in Pregnancy September 2011 55

Recommended Thromboprophylaxis for Pregnancies

Clinical Scenario Antepartum Management

Postpartum Management

Low-risk thrombophilia w/oprevious VTE

Surveillance orProphylactic LMWH or UFH

Surveillance or postpartum anticoagulation if patient hasprevious VTE Prophylactic LMWH or UFH anticoagulation if patient has risk factors

Low-risk thrombophilia w/ single previous VTE

Surveillance or Prophylactic LMWH or UFH

Postpartum anticoagulation therapy

High-risk thrombophilia w/o previous VTE

Prophylactic LMWH or UFH Postpartum anticoagulation therapy

Thrombophilia or no thrombophilia with > 2

Prophylactic or therapeutic LMWH or UFH

Postpartum anticoagulation therapy

episodes of VTE – not on long-term anticoagulation

Thrombophilia or no thrombophilia with > 2 episodes of VTE – receiving long-term anticoagulation

Therapeutic dose LMWH or UFH

Resumption of long-term anticoagulation therapy

*Adapted from ACOG Practice Bulletin: Thromboembolism in Pregnancy September 2011 56



Current Recommendations

• Most practitioners will use LMWH until week 36

• Switch the heparin in preparation for delivery– Shorter half-life

L i k f id l i l h i h– Lower risk of epidural or spinal hematoma with regional anesthesia

• Typically withhold neuraxial blockade for 10-12 hours after last prophylactic dose of LMWH or 24 hours after last therapeutic dose of LMWH

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Current RecommendationsManagement Type Dosage

Enoxaparin 40mg subQ once dailyProphylactic

Indication for LMWHDalteparin 5,000 units subQ once dailyTinzaparin 4,500 units subQ once daily

Enoxaparin 1mg/kg subQ every 12 hoursTherapeutic

Indication for LMWH

Enoxaparin 1mg/kg subQ every 12 hoursDalteparin 200 units/kg subQ once dailyTinzaparin 175 units/kg subQ once dailyDalteparin 100 units/kg subQ once daily




Current RecommendationsManagement Type Dosage

1st trimesterUFH 5,000 – 7,000 units SC every

12 hours

Prophylactic Indication for UFH

2nd

trimester UFH 7,500 to 10,000 units SC

every 12 hours

3rd trimesterUFH 10,000 units sub-Q every 12 hours unless aPTT is elevated

Therapeutic Indication for UFH

UFH 10,000 units or more sub-Q every 12 hours in doses adjusted to target aPTT in the

therapeutic range 6 hours after injection


Postpartum Anticoagulation

• Start heparin or LMWH no sooner than 4 6

Prophylactic LMWH/UFH for 4-6 weeks

• Start heparin or LMWH no sooner than 4-6 hours after vaginal delivery or 6-12 hour after cesarean delivery

PostpartumAnticoagulation

Vitamin K antagonists for 4-6 weeks with a target INR of 2-3 until initial UFH or

LMWH therapy overlap until the INR is 2 or more for 2 days




Postpartum Anticoagulation

• Some patients will need to continue therapy• Some patients will need to continue therapy for more than 6 weeks after delivery

• Preferred agents

WarfarinLMWH

– Do not accumulate in breastmilk

– Do not induce an anticoagulant effect in the infant

Unfractionated Heparin

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NAUSEA / VOMITING HYPEREMESIS

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Hyperemesis Gravidarum

• Represents the extreme end of the spectrump p– Persistent vomiting not related to other causes

– Clinical diagnosis of exclusion

• Approximately 0.3-3% of pregnancies

• Acute starvation – usually large ketonuria

• Discrete measure weight loss – Typically at least 5% of prepregnancy weight

• Electrolyte, thyroid and liver abnormalities may be present 63


• Most common indication for hospitalization• Most common indication for hospitalization during the first part pregnancy

• Some women experience significant psychosocial morbidity caused by nausea and vomiting of pregnancy, resulting in a decision for pregnancy termination – Poor support from partners reported in 85%

– Common to have subacute disease states (e.g., depression, somatization, hypochondriasis)

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• Effects on fetus• Effects on fetus– Low birth weight

– Small for gestational age infants

– Premature infants

– Pregnancy related hypertension

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Hyperemesis Gravidarum: Treatment

• In severe cases:In severe cases:• Ondansetron 4-8 mg IV Q 8 hours

• Metoclopramide 5-10 mg IV Q 8 hours

• Also available as continuous subcutaneous pumps

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• Ondansetron better at controlling vomitingOndansetron better at controlling vomiting, but had a similar effect to metoclopramide in managing nausea1

• Complications of worsening side effects with pumps have been seen in 25-31% of patients2

1. Kashifard M, Basirat Z, Kashifard M, et al. Ondansetrone or metoclopramide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study. Clin Exp Obstet Gynecol 2013;40:127-30. 2. Reichmann JP, Kirkbride MS. Reviewing the evidence for using continuous subcutaneous metoclopramide and ondansetron to treat nausea and vomiting duringpregnancy. Manag Care 2012;21:44-7. 67


• Methylprednisolone 16mg TID x 3 days followed• Methylprednisolone 16mg TID x 3 days, followed by a 2 week taper with oral promethazine– One RTC found steroids reduce the rates of hospital

readmission within 2 weeks1

– Another found steroids have no effect on need for rehospitalization2

• Risk for oral cleft when used in 1st trimester – use should be “last resort” and avoided before 10 weeks

1. Safari HR, Fassett MJ, Souter IC, et al. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol 1998;179:921-4.

2. Yost NP, McIntire DD, Wians FH, et al. A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy. Obstet Gynecol2003;102:1250-4. 68



Hyperemesis Gravidarum: Hospitalization

• Inpatient management required when:• Inpatient management required when:– Cannot tolerate liquids without vomiting

– Has not responded to outpatient management

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• Intravenous hydration used when not tolerating oral liquidsIntravenous hydration used when not tolerating oral liquids for prolonged periods or signs of dehydration are present

• Prolonged vomiting present add:– Thiamine, dextrose, and vitamins

• Enteral tube feeding (nasogastric or nasoduodenal) should be initiated as first-line when nonresponsive to medicine

d t i t i i htand cannot maintain weight

• Total parenteral nutrition is potentially life-threatening due to associated sepsis and thromboembolic events – Reserved for patients unable to tolerate enteral feedings

ACOG Practice Bulletin: Nausea and Vomiting September 201570



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