Prematurity Labor, Delivery

Prematurity Prematurity Labor, DeliveryLabor, Delivery

Muruvet Elkay, MDMuruvet Elkay, MDPL-IIPL-II

12/16/200512/16/2005

ObjectivesObjectives

Epidemiology Epidemiology Risk factors Risk factors Infection Infection Role of antenatal steroidsRole of antenatal steroids ComplicationsComplications ManagementManagement

Preterm LaborPreterm Labor

Preterm labor (PTL):Preterm labor (PTL): Presence of Presence of contractions which cause progressive contractions which cause progressive effacement and dilatation of the cervix effacement and dilatation of the cervix between 20 and 37 weeks’ gestation. between 20 and 37 weeks’ gestation.

Preterm birth (PB):Preterm birth (PB): Occurs in 6-8% of Occurs in 6-8% of pregnancies. The incidence has remained pregnancies. The incidence has remained stable for more than 25 years.stable for more than 25 years.

Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, MDMD

Terms Related to PrematurityTerms Related to Prematurity

Premature infant: An infant born before 37 Premature infant: An infant born before 37 weeks of estimated GA.weeks of estimated GA.

Low birth weight (LBW): BW<2,500 gLow birth weight (LBW): BW<2,500 g Very low birth weight (VLBW): BW<1,500 gVery low birth weight (VLBW): BW<1,500 g Extremely low birth weight (ELBW): Extremely low birth weight (ELBW):

BW<1,000 gBW<1,000 g Chronologic or birth age: Time since birth.Chronologic or birth age: Time since birth. GA: Estimated time since conception; GA: Estimated time since conception;

postconceptional age.postconceptional age. Corrected age: Age corrected for Corrected age: Age corrected for

prematurity.prematurity.

Ref: David E. Trachtenbarg etal. American Family Physician 1998; 57 (9): 1-11Ref: David E. Trachtenbarg etal. American Family Physician 1998; 57 (9): 1-11

The Epidemiology of Preterm The Epidemiology of Preterm BirthBirth

Racial differences in the rate of pretermRacial differences in the rate of preterm LBWLBW VLBW VLBW

African-American women 13.0% African-American women 13.0% 3.1% 3.1%Asian-Pacific IslandersAsian-Pacific Islanders 7.3 1.0 7.3 1.0Native AmericansNative Americans 6.8 1.2 6.8 1.2 WhitesWhites 6.5 6.5 1.1 1.1HispanicsHispanics 6.4 1.1 6.4 1.1

In a twin, triplet or higher order multiple In a twin, triplet or higher order multiple gestation: 23 % of LBW infants gestation: 23 % of LBW infants

Ref: Jay D. Iams, Clin Perinatol 30 (2003) 651-664.Ref: Jay D. Iams, Clin Perinatol 30 (2003) 651-664.

Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600.

US Incidence of Preterm US Incidence of Preterm Birth 1992-2002Birth 1992-2002

GA, wks Survival RDS IVH Sepsis NEC Intact survival

24 40% 70% 25% 25% 8% 5%25 70% 90% 30% 29% 17% 50%26 75% 93% 30% 30% 11% 60%27 80% 84% 16% 36% 10% 70%28 90% 65% 4% 25% 25% 80%29 92% 53% 3% 25% 14% 85%30 93% 55% 2% 11% 15% 90%31 94% 37% 2% 14% 8% 93%32 95% 28% 1% 3% 6% 95%33 96% 34% 0% 5% 2% 96%34 97% 14% 0% 4% 3% 97%

Neonatal Morbidity and Mortality Neonatal Morbidity and Mortality by Gestational Ageby Gestational Age


Hospital Charges by Gestational Age of Delivery


GA (n)GA (n) Mother ChargesMother Charges Baby ChargesBaby Charges Total ChargesTotal Charges

25-26 weeks (40)25-26 weeks (40) $11,102$11,102 $192,882$192,882 $203,994$203,994

27-28 weeks (58)27-28 weeks (58) $9,765$9,765 $160,234$160,234 $169,999$169,999

29-30 weeks (76)29-30 weeks (76) $10,882$10,882 $70,684$70,684 $81,566$81,566

31-32 weeks (127)31-32 weeks (127) $9,500$9,500 $36,991$36,991 $46,490$46,490

33-34 weeks (208)33-34 weeks (208) $9,016$9,016 $15,450$15,450 $24,447$24,447

35-36 weeks (240)35-36 weeks (240) $6,091$6,091 $8,484$8,484 $14,457$14,457

>36 weeks (204)>36 weeks (204) $4,310$4,310 $2,276$2,276 $6,586$6,586

Etiology of Preterm BirthEtiology of Preterm Birth

Physician-initiated birth (indicated PB):Physician-initiated birth (indicated PB):a. Pre-eclampsia 40%a. Pre-eclampsia 40%b. Fetal distress 30%b. Fetal distress 30%c. IUGR 10%c. IUGR 10%d. Abruption placenta or placenta d. Abruption placenta or placenta previa 10%previa 10%e. Fetal death 5% e. Fetal death 5%

Spontaneous PB:Spontaneous PB: a. Preterm labor (PTL) a. Preterm labor (PTL) b. Preterm premature rupture of b. Preterm premature rupture of membranes (PPROM) membranes (PPROM)

Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600

PTLPTL Previous PBPrevious PB Low body massLow body mass Poor weight gainPoor weight gain Heavy work loadHeavy work load Uterine Uterine

abnormalitiesabnormalities Drug abuse, Drug abuse,

smokingsmoking

PPROMPPROM INFECTIONINFECTION Uterine distensionUterine distension Cervical incompetenceCervical incompetence African-AmericanAfrican-American Low socioeconomic Low socioeconomic

classclass Drug abuse, smokingDrug abuse, smoking

Risk Factors for PTL and PPROM


The Strong Association Between The Strong Association Between Infection and Preterm BirthInfection and Preterm Birth

Incidence of subclinical histologic Incidence of subclinical histologic chorioamnionitis:chorioamnionitis:

50%50% 24 to 28 weeks24 to 28 weeks

10%10% >37 weeks>37 weeks The smaller the fetus, the more likely the The smaller the fetus, the more likely the

chorioamnion cultures are positive:chorioamnion cultures are positive:

80%80% <1000 g<1000 g

30% 30% >2500 g>2500 g


Genome Uteroplacental InsufficiencyBacteria, Virus, Protozoa

Infection:Leukocyte ResponseFetal StressMaternal Stress

↓Progesterone Inhibition ↑TOLL 4 Receptors

Cytokine Cascade:↑TNF, ↑IL6, ↑ IL8, etc

Decidual Activation

Genome

Phospholipase A, prostaglandins, lysolethecin, mettaloproteinases, collagenases, elastases..

Relation of Infection and Preterm Birth

Preterm Labor

PRETERM BIRTH

Rupture of Membrane Cervical Incompetence

Phospholipase A, prostaglandins, lysolethecin, mettaloproteinases, collagenases, elastases..

Ref: Edward R. Newton: Clin Perinatol 32 (2005) 571-600

Risk Factors for Infection-Related Preterm Birth


Historical:Historical:

Idiopatic PL, PROMIdiopatic PL, PROM

History of UTI and STIHistory of UTI and STI Behavioral:Behavioral:

Unintended pregnancyUnintended pregnancy

UnmarriedUnmarried

Multiple partnerMultiple partner Signs and symptoms:Signs and symptoms:

Vaginal dischargeVaginal discharge

Dysuria, dyspareuniaDysuria, dyspareunia

Prophylactic Antibiotics to Prevent Prophylactic Antibiotics to Prevent Preterm BirthPreterm Birth

GBSGBS Incidence of vaginal GBS- 20-25%. Incidence of vaginal GBS- 20-25%. No association between vaginal GBS and No association between vaginal GBS and

PB.PB. Prophylactic antibiotics are not indicated Prophylactic antibiotics are not indicated

for recto-vaginal colonization of GBS.for recto-vaginal colonization of GBS. Antepartum treatment of GBS in urine.Antepartum treatment of GBS in urine.


Therapeutic Antibiotics for Infection-Therapeutic Antibiotics for Infection-Related Preterm BirthRelated Preterm Birth

GBS: GBS: Antepartum treatment of all the womenAntepartum treatment of all the women

with the risk factors: with the risk factors: Maternal colonizationMaternal colonization Previous infant who had GBS sepsis Previous infant who had GBS sepsis Antenatal GBS asymptomatic bacteriuriaAntenatal GBS asymptomatic bacteriuria ROM >12 hrs ROM >12 hrs Intrapartum fever (probable chorioamnionitis) Intrapartum fever (probable chorioamnionitis) GA < 37 wksGA < 37 wks


Antibiotics for Inhibiting PL with Antibiotics for Inhibiting PL with Intact MembranesIntact Membranes

Antibiotics are not recommended.Antibiotics are not recommended.


Antibiotics for PPROM

Risk of chorioamnionitis- 20% between 28 and 34 weeks.

Antibiotics are recommended in nonlaboring women.


ChorioamnionitisChorioamnionitis

Inflammation or infection of the placenta, Inflammation or infection of the placenta, chorion, and amnion.chorion, and amnion.

Histologic, subclinical chorioamnionitis: Histologic, subclinical chorioamnionitis: >50% of preterm deliveries >50% of preterm deliveries <20% of term deliveries<20% of term deliveries

Clinical chorioamnionitis:Clinical chorioamnionitis:5% to 10% of preterm deliveries5% to 10% of preterm deliveries

1% to 2% of term deliveries1% to 2% of term deliveries

Ref: Rodney K Edwards: Obstet Gynecol Clin N Am 32 (2005) 270-296.

Clinical ChorioamnionitisClinical Chorioamnionitis Most frequent identifiable cause of PL.Most frequent identifiable cause of PL.

<30 weeks 50% <30 weeks 50%

PPROM 40% PPROM 40%

PL with intact membranes 30%PL with intact membranes 30%

Maternal fever in the peripartum 10% to 40% Maternal fever in the peripartum 10% to 40% Polymicrobial. Polymicrobial.


Clinical ChorioamnionitisClinical Chorioamnionitis

Diagnostic criteria:Diagnostic criteria:

Maternal fever of greater than 100.4 F and atMaternal fever of greater than 100.4 F and at

least 2 of the following conditions:least 2 of the following conditions: Maternal leukocytosis (>15,000 cells/cubic Maternal leukocytosis (>15,000 cells/cubic

mm)mm) Maternal tachycardia (>100 bpm)Maternal tachycardia (>100 bpm) Fetal tachycardia (>160/bpm)Fetal tachycardia (>160/bpm) Uterine tendernessUterine tenderness Foul odor of the AFFoul odor of the AF


Neonatal Outcomes of Neonatal Outcomes of ChorioamnionitisChorioamnionitis

Intraventricular hemorrhageIntraventricular hemorrhage Periventricular leukomalaciaPeriventricular leukomalacia Cerebral palsyCerebral palsy Increased rates of bacteremiaIncreased rates of bacteremia Clinical sepsisClinical sepsis Increased mortalityIncreased mortality Low Apgar scoresLow Apgar scores HypotensionHypotension The need for resuscitation at the deliveryThe need for resuscitation at the delivery Neonatal seizures Neonatal seizures


Antenatal SteroidsAntenatal Steroids

Indicated in the delivery of a fetus at 24-34 Indicated in the delivery of a fetus at 24-34 weeks’ gestation in the absence of clinical weeks’ gestation in the absence of clinical infection. infection.

Delay of delivery- A minimum of 12 hours.Delay of delivery- A minimum of 12 hours. Duration of benefits-7 days or more? Duration of benefits-7 days or more? Betamethasone or Dexamethasone? Betamethasone or Dexamethasone? Reduces the incidence of IVH and NEC. Reduces the incidence of IVH and NEC. An adverse impact of multiple courses on An adverse impact of multiple courses on

fetal growth and development. fetal growth and development.

Ref: eMedicine Sep 22, 2004: Preterm Labor: Article by Edward R. Newton, MD.

Benefits of Antenatal Steroids Benefits of Antenatal Steroids Last 7 Days or More?Last 7 Days or More?

197 neonates 197 neonates Group I: 98 delivered within 7 daysGroup I: 98 delivered within 7 days

Group II: 99 delivered more than 7 daysGroup II: 99 delivered more than 7 days Group I: Lower incidence of receiving Group I: Lower incidence of receiving

respiratory support more than 24 hrs. respiratory support more than 24 hrs. No significant differences between the groups No significant differences between the groups

in other measures of neonatal morbidity.in other measures of neonatal morbidity.

Ref: Alan M. Peaceman et al. Am J Obstet Gynecol 2005; 193, 1165-9.Ref: Alan M. Peaceman et al. Am J Obstet Gynecol 2005; 193, 1165-9.

Betamethasone or Betamethasone or DexamethasoneDexamethasone

201 preterm singleton infants201 preterm singleton infants GA between 24 and 34 weeksGA between 24 and 34 weeks Neurodevelopmental outcome at 2 years Neurodevelopmental outcome at 2 years

corrected agecorrected age Results: Multiple antenatal courses of Results: Multiple antenatal courses of

DEXAMETHASONE associated with an DEXAMETHASONE associated with an increased risk of leukomalacia and 2-year increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalitiesinfant neurodevelopmental abnormalities..

Ref: Spinillo A et al. Am J Obstet Gynecol 2004;191 (1): 217-24.Ref: Spinillo A et al. Am J Obstet Gynecol 2004;191 (1): 217-24.

Complications of Premature Complications of Premature InfantsInfants

RDSRDS IVHIVH NECNEC ROPROP CLD (BPD)CLD (BPD) InfectionInfection AnemiaAnemia PDAPDA ApneaApnea CryptorchidismCryptorchidism Inguinal herniaInguinal hernia Umbilical herniaUmbilical hernia

SGA and IUGR: Are They SGA and IUGR: Are They Synonymous?Synonymous?

SGA:SGA: Birth weight below the 10 Birth weight below the 10thth percentile percentile for GA or > 2 standart deviations below the for GA or > 2 standart deviations below the mean for GA.mean for GA.

IUGR:IUGR: A process that causes a reduction in A process that causes a reduction in an expected pattern of fetal growth. an expected pattern of fetal growth.

1. Symmetric IUGR 1. Symmetric IUGR

2. Asymmetric IUGR (head-sparing IUGR): 2. Asymmetric IUGR (head-sparing IUGR): All IUGR infants may not be SGA (Ponderal All IUGR infants may not be SGA (Ponderal

index).index).

Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654.

Neonatal Complications of IUGR Neonatal Complications of IUGR or SGAor SGA

Metabolic disorders: Hypoglycemia, Metabolic disorders: Hypoglycemia, hypocalcemiahypocalcemia

HypothermiaHypothermia Hematologic disorders: polycytemiaHematologic disorders: polycytemia Hypoxia: birth asphyxia, meconium Hypoxia: birth asphyxia, meconium

aspiration, persistent fetal circulationaspiration, persistent fetal circulation Congenital malformationCongenital malformation

Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654.

Long-term Complications of IUGR or SGA

Cardiovascular disease Hypertension Type 2 diabetes

Ref: Utpala G et al: Pediatr Clin N Am 2004;51: 639-654

A Premature Infant may be a SGA or IUGR A Premature Infant may be a SGA or IUGR Infant Also- Double Jeopardy!Infant Also- Double Jeopardy!

An adverse outcome resulting from both An adverse outcome resulting from both immaturity and deficient intrauterine immaturity and deficient intrauterine growth.growth.

Increased risk for mortality and major Increased risk for mortality and major neonatal morbidities, including RDS, BPD, neonatal morbidities, including RDS, BPD, ROP, and NEC.ROP, and NEC.

Intensified complications of prematurity Intensified complications of prematurity by the effect of suboptimal fetal growth.by the effect of suboptimal fetal growth.

Ref: Rivka H. Regev et al: Clin Perinatol 2004; 34: 453-473.Ref: Rivka H. Regev et al: Clin Perinatol 2004; 34: 453-473.

Management of Premature InfantsManagement of Premature Infants

Delivery room Delivery room managementmanagement

Temperature and Temperature and humidity controlhumidity control

Fluids and Fluids and electrolyteselectrolytes

Blood glucoseBlood glucose CalciumCalcium NutritionNutrition

Respiratory supportRespiratory support SurfactantSurfactant PDAPDA TransfusionTransfusion Skin careSkin care Other special Other special

considerationsconsiderations

THANK YOUTHANK YOU

Special Thanks to Dr. Manuel V. and Colin Bird MSIIISpecial Thanks to Dr. Manuel V. and Colin Bird MSIII

Prematurity Labor, Delivery

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