overview of preterm birth - PowerPoint Presentation

Slide1

overview of preterm birth

Reihaneh

Pirjani

, M.D.

Perinatologist, Assistant Professor

,

Tehran University of Medical Sciences

Slide2

Classification

 — Preterm births are described by gestational age, birth weight, and initiating factor.

●

Gestational age criteria

:

World Health Organization :

•Moderate to late preterm: 32 to <37 weeks

•Very preterm: 28 to <32 weeks

•Extremely preterm: <28 weeks

Centers for Disease Control and Prevention:

•Preterm: <37 weeks

•Late preterm: 34 to 36 weeks

•Early preterm: <34 weeks

Slide3

Classification

 — Preterm births are described by gestational age, birth weight, and initiating factor.

●

Birth weight criteria

 

•Low birth weight (LBW): <2500 grams

•Very low birth weight (VLBW): <1500 grams

•Extremely low birth weight (ELBW): <1000 grams

Slide4

Classification

 — Preterm births are described by gestational age, birth weight, and initiating factor.

●

Initiating factor: spontaneous or

iatrogenic

•Spontaneous: 70 to 80 percent, due to preterm labor (40 to 50 percent) or preterm premature rupture of membranes (20 to 30 percent).

•Provider-initiated: 20 to 30 percent, due maternal or fetal issues (

eg

, preeclampsia, placenta

previa

,

abruptio

placenta, fetal growth restriction, multiple gestation).

Complications of pregnancy can lead to both spontaneous and provider-initiated preterm births.

Slide5

Pathogenesis

The

pathophysiology of preterm labor involves four primary pathogenic processes that result in a final common pathway ending in spontaneous preterm labor and delivery:

●Activation of the maternal or fetal hypothalamic-pituitary-adrenal axis associated with either maternal anxiety and depression or fetal stress

●Infection

●

Decidual

hemorrhage

●Pathological uterine distention

Slide6

Diagnosis

the

diagnosis of preterm labor based upon clinical criteria of regular painful uterine contractions accompanied by cervical change (dilation and/or effacement).

Because

the clinical findings of early labor are poorly predictive of the diagnosis, over-diagnosis is common until labor is well established.

Slide7

Diagnosis

Specific clinical criteria

include

persistent uterine contractions (4 every 20 minutes or 8 every 60 minutes) with documented cervical change or cervical effacement ≥80 percent or cervical dilation >2 cm

.

These criteria were chosen because women who do not meet these criteria are often ultimately diagnosed with false labor and go on to have a late preterm or term delivery

Slide8

A

ppropriate

application of interventions that can improve neonatal outcome

:

antenatal corticosteroid therapy

,

group B streptococcal infection prophylaxis,

magnesium

sulfate for

neuroprotection

,

transfer to a facility with an appropriate level nursery (if necessary).

Slide9

Pregnancies ≥34 weeks of gestation

The 34th week of gestation is the threshold at which perinatal morbidity and mortality are too low to justify the potential maternal and fetal complications and costs associated with inhibition of preterm labor, which only results in short term delay in delivery.

"Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality from preterm delivery"

Slide10

women in preterm labor ≥34 weeks are admitted for delivery.

After

an observation period of four to six hours, women without progressive cervical dilation and effacement are

discharged,

as long as fetal well-being is confirmed (

eg

, reactive

nonstress

test) and obstetrical complications associated with preterm labor, such as

abruptio

placenta,

chorioamnionitis

, and preterm rupture of membranes, have been excluded.

follow-up

in one to two

weeks

Slide11

Pregnancies <34 weeks of gestation

In women <34 weeks with uterine contractions, cervical dilation ≥3 cm supports the diagnosis of preterm labor; further diagnostic evaluation with

sonographic

measurement of cervical length or laboratory assessment of fetal

fibronectin

does not enhance diagnostic accuracy. Treatment of preterm labor is initiated.

Slide12

The diagnosis of preterm labor is less clear in women with contractions, cervical dilation <3 cm, and intact membranes

Measurement of cervical length is useful for supporting or excluding the diagnosis of preterm labor when the diagnosis is unclear.

Slide13

the frequency of preterm birth is low in symptomatic women <34 weeks with cervical length >30 mm

the frequency of preterm birth is increased but still relatively low in symptomatic women with cervical length 20 to 30 mm;

the frequency of preterm birth is high in symptomatic women with cervical length <20 mm

Slide14

Cervical length >30 mm

 — Symptomatic women with cervical length >30 mm are at low risk (<5 percent) of delivery within seven days

the addition of

fFN

testing does not significantly improve the predictive value of cervical length measurement alone

.

Slide15

Cervical length 20 to 30 mm

 — Symptomatic women with cervical dilation <3 cm and cervical length 20 to 30 mm are at increased risk of preterm birth, but most of these women do not deliver preterm.

send a

cervicovaginal

sample for

fFN

testing

If the

fFN

test is positive, we begin interventions to reduce morbidity associated with preterm birth .If the

fFN

test is negative, we discharge the patient after 6 to 12 hours of observation,

Slide16

Cervical length <20 mm

 — Symptomatic women with cervical length <20 mm are at high risk (>25 percent) of delivery within seven days;

Therefore, do not send their

cervicovaginal

samples to the laboratory for

fFN

testing and we begin interventions to reduce morbidity associated with preterm birth

Slide17

Treatment of women <34 weeks with suspected preterm labor

 hospitalize women diagnosed with preterm labor <34 weeks of gestation and initiate the following treatments

A course of 

betamethasone

 to reduce neonatal morbidity and mortality associated with preterm birth.

Tocolytic

drugs for up to 48 hours to delay delivery so that 

betamethasone

 given to the mother can achieve its maximum fetal effect.

Slide18

Treatment of women <34 weeks with suspected preterm labor

 ●Antibiotics for GBS chemoprophylaxis.

●

Magnesium sulfate

 for pregnancies at 24 to 32 weeks of gestation. In

utero

exposure to magnesium sulfate provides

neuroprotection

against cerebral palsy and other types of severe motor dysfunction in offspring born preterm.

Slide19

Antibiotic therapy has no role in the treatment of acute preterm labor in the absence of a documented infection or GBS prophylaxis

Progesterone

 supplementation has no role in the treatment of acute preterm labor.

Slide20

Administration of

tocolytic

drugs

EFFICACY

 — can reduce the strength and frequency of uterine contractions.

these drugs were more effective than placebo/control: 

for delaying delivery for 48 hours (75 to 93 percent versus 53 percent for placebo/control)

  for seven days (61 to 78 percent versus 39 percent for placebo/control), 

but not for delaying delivery to 37 weeks

administration of

tocolytic

drugs

did not

result in statistically significant reductions in important clinical outcomes, such as neonatal respiratory distress and survival

Slide21

Administration of

tocolytic

drugs

PATIENT SELECTION

 — Women in the early phases of acute preterm labor, when cervical dilation is not advanced, are optimum candidates for

tocolytic

therapy

Tocolysis

is indicated when the overall benefits of delaying delivery outweigh the risks.

Because

tocolytic

therapy is generally effective for up to 48 hours, only women with fetuses that would benefit from a 48 hour delay in delivery should receive

tocolytic

treatment

Slide22

Administration of

tocolytic

drugs

PATIENT SELECTION

 

Inhibition of acute preterm labor is less likely to be successful as labor advances to the point that cervical dilation is greater than 3 cm.

Tocolysis

can still be effective in these cases, especially when the goal is to administer antenatal corticosteroids or safely transport the mother to a tertiary care center

Slide23

Lower and upper gestational age limits

The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend not administering

tocolysis

before 24 weeks of gestation,

ACOG and SMFM that 34 weeks of gestation defines the threshold at which

perinatal

morbidity and mortality are too low to justify the potential maternal and fetal complications and costs associated with inhibition of preterm labor and short-term delay of delivery

Slide24

Contraindications

 

 

Tocolysis

is contraindicated when the maternal/fetal risks of prolonging pregnancy or the risks associated with these drugs are greater than the risks associated with preterm birth. Established contraindications to labor inhibition include:

Intrauterine fetal demise

Lethal fetal anomaly

Nonreassuring

fetal status

Preeclampsia with severe features or

eclampsia

Maternal hemorrhage with hemodynamic instability

Intraamniotic

infection

Maternal contraindications to the

tocolytic

drug

Slide25

TREATMENT GOALS

Delay delivery by at least 48 hours when it is safe to do so in order that antenatal corticosteroids (primary or rescue) given to the mother have time to achieve their maximum fetal/neonatal effects.

Slide26

TREATMENT GOALS

Provide time for safe transport of the mother, if indicated, to a facility that has an appropriate level of neonatal care if the patient delivers preterm.

Prolong pregnancy when it is safe to do so and when there are underlying, self-limited conditions that can cause labor, such as

pyelonephritis

or abdominal surgery, and are unlikely to cause recurrent preterm labor.

Slide27

For women at 24 to 32 weeks of gestation

use 

indomethacin

 for first-line therapy.

Data from randomized trials suggest it is superior to placebo

do not use

indomethacin

for more than 72 hours because of concern about premature constriction of the

ductus

arteriosus

and

oligohydramnios

.

Slide28

For women at

32 to 34 weeks

of gestation

use 

nifedipine

 as a first-line agent

Slide29

For women at 24 to 32 weeks of gestation

use 

nifedipine

 as a first-line agent for women who have a contraindication to

indomethacin

therapy :

maternal platelet dysfunction or bleeding disorder,

hepatic dysfunction,

gastrointestinal ulcerative disease,

renal dysfunction,

asthma [in women with hypersensitivity to 

aspirin

].

Slide30

If the first-line drug does not inhibit contractions, discontinue it and begin therapy with another agent.

For second-line therapy, use 

nifedipine

 at 24 to 32 weeks and 

terbutaline

 at 32 to 34 weeks and for patients at 24 to 32 weeks who received

nifedipine

as a first-line agent.

discontinue

tocolytics

48 hours after administration of the first corticosteroid dose.

Slide31

In a 2012 systematic review and network meta-analysis of 95 randomized trials of

tocolytic

therapy for preterm labor, all of the commonly used

tocolytic

agents (

cyclooxygenase

inhibitors, beta-agonists, calcium channel blockers, 

magnesium sulfate

,

oxytocin

receptor antagonists)

were statistically more effective than placebo

/no 

tocolytic

for delaying delivery for 48 hours .

Cyclooxygenase

inhibitors (

eg

, 

indomethacin

) and calcium channel blockers (

eg

, 

nifedipine

) had

the highest probability of being the best therapy for preterm labor

Slide32

A single course of therapy does not delay delivery by weeks or months because

tocolytics

do not remove the underlying stimulus that initiated preterm labor (

eg

, subclinical

intraamniotic

infection, abruption, uterine

overdistension

) or reverse

parturitional

uterine changes (

eg

, cervical dilation and effacement).

Slide33

MOST EFFECTIVE TOCOLYTIC DRUGS

indomethacin

 

Dose

 — The dose of 

indomethacin

 for labor inhibition is 50 to 100 mg loading dose (may be given orally or per rectum), followed by 25 mg orally every four to six hours.

Monitoring

 — If 

indomethacin

 is continued for longer than 48 hours,

sonographic

evaluation for

oligohydramnios

and narrowing of the fetal

ductus

arteriosus

is warranted at least weekly .

Evidence of

oligohydramnios

or

ductal

constriction should prompt discontinuation of this therapy.

Slide34

MOST EFFECTIVE TOCOLYTIC DRUGS

indomethacin

 

Constriction of the

ductus

arteriosus

 — Premature narrowing or closure of the

ductus

arteriosus

can lead to pulmonary hypertension and tricuspid regurgitation in the fetus.

which the duration of 

indomethacin

 exposure exceeded 48 hours

Ductal

constriction appears to depend upon both gestational age and duration of exposure. It has been described at gestations as early as 24 weeks, but is most common after 31 to 32 weeks

Slide35

MOST EFFECTIVE TOCOLYTIC DRUGS

indomethacin

 

Constriction of the

ductus

arteriosus

 —

 

indomethacin

 is 

not

 recommended after 32 weeks of gestation.

Before 32 weeks, fetal

echocardiographic

evaluation is useful for monitoring

ductal

effects if the duration of therapy exceeds 48 hours.

Sonographic

signs of

ductal

narrowing include tricuspid regurgitation, right ventricular dysfunction and

pulsatility

index less than 1.9

Slide36

MOST EFFECTIVE TOCOLYTIC DRUGS

nifedipine

The relative safety, maternal tolerance, ease of administration, and reduction in adverse neonatal outcomes support use of 

nifedipine

 rather than beta-agonists for inhibition of acute preterm labor.

Slide37

MOST EFFECTIVE TOCOLYTIC DRUGS

nifedipine

Contraindications

 — 

known hypersensitivity to the drugs,

hypotension,

preload-dependent cardiac lesions,

should be used with caution in women with left ventricular dysfunction or congestive heart failure.

The concomitant use of a calcium-channel blocker and 

magnesium sulfate

 could act synergistically to suppress muscular contractility, which could result in respiratory depression

Slide38

MOST EFFECTIVE TOCOLYTIC DRUGS

nifedipine

Dose

 —A common approach is to administer an initial loading dose of 20 to 30 mg orally, followed by an additional 10 to 20 mg orally every 3 to 8 hours for up to 48 hours, with a maximum dose of 180 mg/day.

The American College of Obstetricians and Gynecologists suggests a 30 mg loading dose and then 10 to 20 mg every four to six hours.

The half-life of 

nifedipine

 is approximately two to three hours and the duration of action of a single orally administered dose is up to six hours. Plasma concentrations peak in 30 to 60 minutes.

Nifedipine

is almost completely metabolized in the liver and excreted by the kidney.

Slide39

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Beta-agonists

 — 

ritodrine

and 

terbutaline

 have been studied in several randomized, placebo-controlled trials.

Salbutamol

and

hexoprenaline

have also been evaluated, but data are sparse

Although

ritodrine

is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of preterm labor, it is no longer available

Slide40

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Mechanism of action

 — The beta-2 receptor agonists cause

myometrial

relaxation by binding with beta-2 adrenergic receptors and increasing intracellular

adenyl

cyclase

. An increase in intracellular cyclic adenosine

monophosphate

activates protein

kinase

and results in the

phosphorylation

of intracellular proteins. The resultant drop in intracellular free calcium interferes with the activity of myosin light-chain

kinase

. Interference with myosin light-chain

kinase

inhibits the interaction between

actin

and myosin; thus,

myometrial

contractility is diminished. However, target cells eventually become desensitized to the effect of beta-agonists, thereby decreasing efficacy with prolonged use [

62,63

]. The reduction in response over time is known as

tachyphylaxis

Slide41

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Maternal side effects

 — 

related to stimulation of beta-1 adrenergic receptors, which increase maternal heart rate and stroke volume,

stimulation of beta-2 adrenergic receptors, which causes peripheral

vasodilation

, diastolic hypotension, and bronchial relaxation.

The combination of these two cardiovascular

effects leads to tachycardia, palpitations, and lower blood pressure.

tremor ,palpitations ,shortness of breath, and chest

discomfort,Pulmonary

edema

hypokalemia

(39 versus 6 percent with placebo), hyperglycemia (30 versus 10 percent with placebo), and

lipolysis

. Myocardial

ischemia

is a rare complication.

Slide42

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Fetal side effects

 — Beta-agonists cross the placenta.

Fetal effects, such as fetal tachycardia, are analogous to the maternal effects

Neonatal hypoglycemia may result from fetal

hyperinsulinemia

in response to prolonged maternal hyperglycemia.

Slide43

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Contraindications

 — 

women with tachycardia-

sensitive cardiac disease,

poorly controlled hyperthyroidism

poorly controlled diabetes mellitus

Beta-agonists should be used with caution in women at risk for massive hemorrhage (such as women with placenta

previa

or abruption) since the resultant cardiovascular effects (tachycardia, hypotension) may interfere with the mother's ability to respond to ongoing hemorrhage, and may confuse the clinical presentation.

Slide44

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

injectable

 

terbutaline

 should not be used in pregnant women for

prolonged (beyond 48 to 72 hours)

because of the potential for serious maternal heart problems and death.

The FDA also opined that

oral

terbutaline

should not be used for prevention

terbutaline

 injection for an individual patient

in a hospital setting

clearly outweighs the risk.

Slide45

MOST EFFECTIVE TOCOLYTIC DRUGS

Beta-agonists

 

Dose

 — It is often given

subcutaneously

by intermittent injection. The dose is variable: 0.25 mg can be administered subcutaneously every 20 to 30 minutes for up to four doses or until

tocolysis

is achieved. Once labor is inhibited, 0.25 mg can be administered subcutaneously every three to four hours until the uterus is quiescent for 24 hours.

Terbutaline

 can also be administered as a

continuous intravenous

infusion. 2.5 to 5 mcg/min and increasing by 2.5 to 5mcg/min every 20 to 30 minutes to a maximum of 25 mcg/min, or until the contractions have abated. At this point, the infusion is reduced by decrements of 2.5 to 5 mcg/min to the lowest dose that maintains uterine quiescence.

Slide46

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine consider magnesium sulfate an option for short-term prolongation of pregnancy (up to 48 hours) to allow administration of antenatal corticosteroids to pregnant women at risk for preterm delivery within 7 days

Slide47

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Maternal and fetal side effects

 —Diaphoresis and flushing are the most common side effects; magnesium toxicity is related to serum concentration.

Maternal therapy causes a slight decrease in baseline fetal heart rate and fetal heart rate variability, which are not clinically important. Antenatal fetal assessment test results (

eg

, biophysical profile score and

nonstress

test reactivity) are not significantly altered

Slide48

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Maternal and fetal side effects

 —

radiographic bone abnormalities in neonates with in

utero

exposure

to

magnesium

sulfate

 for more than seven days,

a significant difference in the serum values of magnesium, calcium, phosphorus, and

osteocalcin

(a marker of bone formation) at birth between neonates unexposed to magnesium sulfate and those who were exposed

these effects are transient

FDA advised against using magnesium sulfate

infusions for more than five to seven days

to stop preterm labor

The American College of Obstetricians and Gynecologists suggests

limiting magnesium sulfate therapy to 48 hours

in women between 24 and 34 weeks of gestation with preterm labor

Slide49

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

If

tocolysis

is indicated because of persistent preterm labor in a patient receiving 

magnesium sulfate

 for

neuroprotection

, the most effective

tocolytic

with the most favorable side-effect profile should be used

Slide50

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Contraindications

 — 

Magnesium sulfate

 

tocolysis

is contraindicated in women with myasthenia gravis.

Magnesium sulfate

 should also be avoided in women with known myocardial compromise or cardiac conduction defects

Magnesium is eliminated by the kidneys. Thus, in women with impaired renal function doses of administration so the maintenance dose should be reduced or eliminated.

The concomitant use of a calcium channel blocker and 

magnesium sulfate

 could act synergistically to suppress muscular contractility, which could result in respiratory depression

Slide51

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Dose

 — 

Magnesium sulfate

 is usually administered as a 4-6 gram intravenous load over 20 minutes, followed by a continuous infusion of 2 g/hour 

Monitoring

 — In women with normal renal function, signs and symptoms of magnesium toxicity can be assessed by history and physical examinations. Routine magnesium levels are not necessary.

Slide52

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Since 

magnesium sulfate

 is excreted by the kidneys, dosing should be adjusted in women with renal insufficiency (defined as a serum

creatinine

greater than 1.0 mg/

dL

  or an alternative drug should be used.

If magnesium sulfate is given, such women should receive a standard loading dose (since their volume of distribution is not altered), but a reduced maintenance dose (1 gram per hour or no maintenance dose if the serum

creatinine

is greater than 2.5 mg/

dL

 ( 

micromol

/L]) with close monitoring of the serum magnesium concentration every six hours.

Slide53

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

Women with renal insufficiency should receive the maintenance phase of treatment only if a patellar reflex is present (loss of reflexes being the first manifestation of symptomatic

hypermagnesemia

), respirations exceed 12 per minute, and the urine output exceeds 100

mL

per four hours. The urine output and deep tendon reflexes should be closely monitored. Magnesium levels may be useful in monitoring women on maintenance magnesium therapy who have concomitant renal disease.

Slide54

MOST EFFECTIVE TOCOLYTIC DRUGS

Magnesium sulfate

If life-threatening symptoms of magnesium toxicity occur (cardiac or respiratory compromise), 

calcium

gluconate

 (1 gram intravenously over 5 to 10 minutes) is an effective counteractive therapy but should not be used to treat mild symptoms.

Slide55

INEFFECTIVE APPROACHES

Antibiotic therapy

 — Although subclinical genital tract infection clearly contributes to the pathogenesis of preterm birth, there is no evidence-based role for antibiotic therapy in the prevention of prematurity in patients with acute preterm labor

Progesterone supplementation

 — Women in acute preterm labor do not benefit from 

progesterone

 supplementation

Bedrest

, hydration, and sedation

 — There is no convincing evidence that

bedrest

, hydration, or sedation is effective for prevention or treatment of preterm labor .Furthermore, extended and hospitalized

bedrest

increase the risk of

thromboembolic

events

Slide56

Neuroprotective

effects of in

utero exposure to magnesium sulfate

Prematurity is a powerful risk factor for the development of cerebral palsy

In

utero

exposure to 

magnesium sulfate

 before early preterm birth appears to decrease the incidence of cranial ultrasound abnormalities associated with cerebral palsy and, more importantly, the incidence and severity of cerebral palsy in offspring

Slide57

Neuroprotective

effects of in

utero exposure to magnesium sulfate

The mechanism is not well understood, but potential

neuroprotective

actions include

antioxidant effects,

reduction in

proinflammatory

cytokines,

blockage of glutamate activated calcium channels,

stabilization of membranes,

increased cerebral blood flow,

prevention of large blood pressure fluctuations

Slide58

Randomized placebo-controlled trials of maternal administration of magnesium sulfate in women expected to have a preterm delivery within 24 hours have consistently demonstrated a decreased risk of cerebral palsy and severe motor dysfunction in offspring;

however, the possibility of an increased risk of death in a subgroup of fetuses or infants has not conclusively been excluded.

Slide59

Neuroprotective

effects of in

utero exposure to magnesium sulfate

Candidates for treatment

  

Given the current data, administering 

magnesium sulfate

 for

neuroprotection

to women with preterm premature rupture of membranes, preterm labor with

intaact

membranes, or indicated preterm delivery appears to be reasonable

Slide60

The optimal dose of magnesium, gestational age at administration, and reason for preterm birth warrant further study.

Neither the

neuroprotective

mechanism nor the dose response to 

magnesium sulfate

 is well understood.

While it seems likely that the

neuroprotective

We administer 

magnesium sulfate

 to women with preterm premature rupture of membranes or preterm labor who have a high likelihood of

imminent delivery (

ie

, within 24 hours)

, or before an indicated preterm delivery.

If emergency delivery is necessary given maternal or fetal status,

it should not be delayed to administer magnesium sulfate

Slide61

A

4 gram intravenous loading dose followed by a 1 gram/hour infusion.

This therapy is discontinued by 24 hours after initiation if delivery has not occurred.

The upper limit of exposure is also not well defined. We recommend not continuing the magnesium infusion for longer than 24 hours if delivery has not occurred.

Slide62

Neuroprotective

effects of in

utero exposure to magnesium sulfate

Monitoring

 — Urine output and deep tendon reflexes should be closely monitored in all patients.

The maintenance phase of treatment should be continued only if a patellar reflex is present (loss of reflexes being the first manifestation of symptomatic

hypermagnesemia

), respirations exceed 12 per minute, and the urine output exceeds 100

mL

per four hours.

Slide63

Neuroprotective

effects of in

utero exposure to magnesium sulfate

Retreatment

 — Retreatment with 

magnesium sulfate

is not recommended as there are inadequate data regarding any benefit for women who do not deliver after initial magnesium sulfate therapy.

Slide64

Neuroprotective

effects of in

utero exposure to magnesium sulfate

the American College of Obstetricians and Gynecologists (ACOG) encourages physicians electing to use 

magnesium sulfate

 for

neuroprotection

to develop guidelines for its use

Up to date:

we consider women at high risk of imminent (

ie

, within 24 hours) spontaneous or indicated preterm birth between 24 and 32 weeks of gestation candidates for 

magnesium sulfate

 administration for

neuroprotection

.

Slide65

Neuroprotective

effects of in

utero exposure to magnesium sulfate

•If

tocolysis

is indicated, the most effective agent with the most favorable side effect profile should be chosen: 

indomethacin

Slide66

corticosteroid therapy for reduction of neonatal morbidity and mortality

Antenatal corticosteroid therapy leads to improvement in neonatal lung function by enhancing maturational changes in lung architecture and by inducing lung enzymes involved in respiratory function.

Slide67

corticosteroid therapy for reduction of neonatal morbidity and mortality

●Antenatal corticosteroid therapy reduces the incidence of respiratory distress syndrome,

intraventricular

hemorrhage, necrotizing

enterocolitis

, sepsis, and neonatal mortality by approximately 50 percent.

These effects are not limited by gender or race;

efficacy in multiple gestations is unclear, as high-quality data are sparse.

Slide68

corticosteroid therapy for reduction of neonatal morbidity and mortality

GESTATIONAL AGE AT ADMINISTRATION

23 to 34 weeks

 —  recommend administration of antenatal corticosteroids for all pregnant women at 23 to 34 weeks who are at increased risk of preterm delivery within the next seven days.

22 weeks or less

 —At 22 weeks parents should be informed that antenatal corticosteroids may provide a survival benefit while increasing the risk for survival with severe impairment

Slide69

corticosteroid therapy for reduction of neonatal morbidity and mortality

GESTATIONAL AGE AT ADMINISTRATION

After 34 weeks

 — The use of antenatal corticosteroids after 34 weeks of gestation is controversial because of inconsistent data about its efficacy and virtually no data about long-term safety.

Limitations of available data are largely related to the low risk for severe respiratory morbidity after 34 weeks of gestation and lack of information on long-term outcomes after exposure to corticosteroids in late gestation

Slide70

corticosteroid therapy for reduction of neonatal morbidity and mortality

GESTATIONAL AGE AT ADMINISTRATION

37 to 39 weeks of gestation

 — Empiric use of steroids has been recommended prior to cesarean delivery at 37 to 39 weeks of gestation based on two trials

●The Society for Maternal-Fetal Medicine Specialists recommends a two-dose course of antenatal 

betamethasone

 for women at 34

0/7ths

 to 36

6/7ths

weeks of gestation at high risk for preterm birth within seven days

Slide71

corticosteroid therapy for reduction of neonatal morbidity and mortality

Other approaches

●The American College of Obstetricians and Gynecologists states administration of 

betamethasone

 may be considered in women with a singleton pregnancy at 34

0/7ths

 to 36

6/7ths

 weeks of gestation at imminent risk of preterm birth within 7 days, with the following caveats

Antenatal corticosteroid administration should not be administered to women with

chorioamnionitis

.

Medically/obstetrically indicated preterm delivery should not be postponed for steroid administration.

Antenatal corticosteroids should not be administered if the patient has already received a course antenatal corticosteroids.

Newborns should be monitored for hypoglycemia.

Slide72

corticosteroid therapy for reduction of neonatal morbidity and mortality

Other approaches

●The Royal College of Obstetricians and

Gynaecologists

(RCOG) recommends routine administration of antenatal

glucocorticoids

for

(1) all women at risk of preterm birth up to and including 34

6/7ths

 weeks of gestation

(2) all women who must undergo scheduled cesarean delivery before 39

/07ths

weeks of gestation 

Slide73

corticosteroid therapy for reduction of neonatal morbidity and mortality

recommend administration of antenatal corticosteroids to pregnant woman who are at 23 to 34 weeks of gestation and at increased risk of preterm delivery

within the next seven days

.

This approach minimizes the need for salvage (rescue, booster) therapy while allowing most patients to receive a course of antenatal corticosteroids prior to preterm delivery.

Slide74

corticosteroid therapy for reduction of neonatal morbidity and mortality

Some clinicians and patients may choose not to use steroids after 34 weeks of gestation, given uncertainly in the balance between benefits and risks after 34 weeks.

Slide75

corticosteroid therapy for reduction of neonatal morbidity and mortality

A course of antenatal corticosteroids consists of 

betamethasone

 suspension 12 mg intramuscularly every 24 hours for two doses 

or

 four doses of 6 mg 

dexamethasone

 intramuscularly 12 hours apart.

the optimal window of after steroid administration: 24 hours to 7 days after the second dose

Observational data suggest neonatal benefits begin to accrue within a few hours of corticosteroid administration

Slide76

corticosteroid therapy for reduction of neonatal morbidity and mortality

For women at 34

0/7ths

 to 36

6/7ths

 weeks :

who have already received a course of antenatal corticosteroids,

who are expected to deliver vaginally,

whose likelihood of delivery within the next seven days is uncertain,

not administering a course of antenatal corticosteroids .

Slide77

corticosteroid therapy for reduction of neonatal morbidity and mortality

a single course of salvage (rescue, booster) therapy only if:

the patient is clinically estimated to be at high risk of delivery within the next seven days,

more than two weeks have elapsed since the initial course of antenatal corticosteroid therapy,

the gestational age at administration of the initial course was <28 weeks of gestation

Slide78

corticosteroid therapy for reduction of neonatal morbidity and mortality

For salvage (rescue, booster) therapy use

one dose of

12 mg 

betamethasone

 and limit treatment to this one additional dose.

One dose appears to be effective and may minimize complications related to steroid use; however, a two dose course is also reasonable

Slide79

Potential fetal side effects

Fetal heart rate and biophysical parameters

 – Administration of antenatal corticosteroids may be associated with transient fetal heart rate (FHR) and behavioral changes that typically return to baseline by four to seven days after treatment.

The most consistent FHR finding is a decrease in variability on days two and three after administration.

Reduced fetal breathing and body movements can result in a lower BPP score or NR-NST

Slide80

Potential fetal side effects

FHR and behavioral changes may reflect a direct physiologic response of the brain to corticosteroids or they may be an indirect result of a transient increase in fetal vascular resistance and blood pressure

Whether continued close fetal monitoring or delivery is preferable in this setting depends on assessment of the total clinical scenario and clinical judgment.

Slide81

Potential fetal side effects

Doppler flow studies

 –

A

transient improvement

in umbilical artery end-diastolic flow (EDF) after antenatal corticosteroid administration has been described in three studies

The improvement began about eight hours after the first dose of

betamethasone

 and lasted a median of three days (range 1 to 10 days).

other studies have not observed effects on fetal blood flow velocity waveform patterns in the umbilical artery, middle cerebral artery, or

ductus

venosus

However, these observations are based on a small number of events in two studies and need to be confirmed before a change in management of this subgroup of fetuses is considered

Slide82

Potential fetal side effects

However, preterm fetuses with severe early-onset growth restriction and absent or reversed EDF do not have a consistent cardiovascular response to maternal 

betamethasone

 administration.

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Potential adverse effects on infants

 

The safety and effectiveness of steroid administration after 34 weeks is less clear.

In a multifaceted intervention trial (ACT) designed to increase the use of antenatal corticosteroids in low-income and middle-income countries,

increased use of steroids increased neonatal and

perinatal

mortality

in the overall population, which was an unexpected and unexplained finding that may have been related, in part, to increased in

utero

steroid exposure among neonates born at term

Slide84

Multiple gestation

 — We use a standard dosing schedule for both singleton and multiple gestations.

In theory, multiple gestations may require higher doses of antenatal corticosteroids to maximize fetal exposure. However, maternal and cord blood 

betamethasone

 levels were similar in singleton and multiple gestations in a randomized trial.

Slide85

Hypertension

 — 

Betamethasone

 has low

mineralocorticoid

activity compared with other corticosteroids and does not aggravate hypertension.

A

randomized trial supported both the safety and efficacy of antenatal corticosteroid therapy in pregnancies complicated by severe preeclampsia .

Slide86

Diabetes

 — Antenatal corticosteroid therapy should be administered to women with diabetes when indicated; however, hyperglycemia related to corticosteroid administration can be severe in this population if not closely monitored and treated.

The steroid effect on glucose levels begins approximately 12 hours after the first dose and may last for five days.

Women with diabetes generally have been excluded from randomized trials of antenatal corticosteroid therapy because of the adverse effects of steroids on

glycemic

control, thus efficacy in this population is inferred

Slide87

Preterm premature rupture of membranes

 — Antenatal corticosteroid administration improves neonatal outcome in pregnancies complicated by preterm premature rupture of membranes and does not increase the risk of neonatal or maternal infection

Slide88