Preterm birth

Birthweight

 Low birthweight = defines neonates who are born too small

 Births 1500 to 2500 g
Preterm or Premature Births
 neonates who are born too early
 Very low birthweight
• Births 500 to 1500 g
Extremely low birthweight
• Births 500 to 1000 g
 Appropriate for gestational age (AGA)
 Weight is between the 10th and 90th percentiles
 Small for gestational age (SGA) / Fetal- Growth Restriction/ Intrauterine Growth
Restriction
 birthweight is usually < 10th percentile for gestational age
 Large for gestational age (LGA)
 birthweight >90th percentile for gestational age.

PRETERM BIRTH

 Delivery before 37 completed weeks, that is <36 6/7

 Prematurity responsible for incomplete development of various organ
system
 The lungs are particularly affected, leading to respiratory distress syndrome.

Infants born between 34 0/7 weeks and 36 6/7 weeks experience morbidities and mortality
characteristic of premature infants, preterm were subdivided.

Early Preterm
 Births 37 0/7 weeks through 38 6/7 weeks
 Term
 39 weeks to 40 6/7 weeks
 Late preterm births
 Delivery between 34 to 36 weeks' gestation
MORBIDITY and MORTALITY IN INFANTs
 Infants Mortality Rates are used as the outcome of interest, optimal pregnancy
 outcomes vs prematurity at 39 weeks
Respiratory Morbidity is used as the outcome of interest, 38 0/7 through 38

6/7 weeks equivalent 30 weeks.
 After achieving a birthweight of ≥1000 g or a gestational age of 28 weeks
females to 30 weeks males: survival rates reach 95%
 CS delivery was not protective against poor outcomes such as:
 neonatal death
 intraventricular hemorrhage
 Seizures
 respiratory distress and subdural hemorrhage
THRESHOLD OF VIABILITY

 Births before 26 weeks are generally considered at the current threshold of

viability, and these preterm infants pose various complex medical, social,
and ethical considerations.
 Infants now considered to be at the threshold of viability are those born at
22, 23, 24, or 25 Weeks

THRESHOLD VIABILITY AT PARKLAND HOSPITAL

 Decision not to perform caesarean delivery does not necessarily imply that
fetus is “nonviable” or “written off”
 Neonatologists are consulted before delivery and there is
discussion of survival and morbidity
 At 25 Weeks
 All fetal indications for cesarean delivery in more advanced
pregnancies

 At 23 weeks

 Cesarean delivery is not offered for fetal indications

 At 24 weeks

 Cesarean delivery is not offered unless fetal weight is estimated

≥750 g

LATE PRETERM BIRTH

  Infants between 34-36 weeks : approximately 75% of all preterm births

 Associated with increased rates of adverse neurodevelopment

 ACOG: has emphasized that intentional late preterm deliveries should occur only
when an accepted maternal or fetal indication for delivery exists

Four Main Reasons for Preterm Delivery

 Spontaneous unexplained preterm labor with intact membranes

 Idiopathic preterm premature rupture of membranes (PPROM)
 Delivery for Maternal or Fetal Indications
 Twins and higher-order multifetal births

 Risk for Preterm Labor

 multifetal pregnancy
 intrauterine infection
 Bleeding
 placental infarction
 premature cervical dilatation
 cervical insufficiency
 hydramnios
 uterine fundal abnormalities & fetal anomalies.

 Severe maternal illness as a result of infections, autoimmune diseases, and

gestational hypertension also increases preterm labor risks.
 Common End Point of Preterm Labor
 Premature cervical dilation and effacement and premature activation of
uterine contractions

MAJOR CAUSES OF SPONTANEOUS PRETERM LABOR

1. Uterine distension
2. Maternal-fetal stress
3. Premature cervical changes
4. Infection
UTERINE DISTENTION
  Multifetal pregnancy and hydramnios – increased risk of preterm birth
 Acts to initiate expression of contraction associate proteins in the myometrium
 CAP genes- influenced by stretch include those coding for gap-junction proteins
such as
 connexin 43
 thromboxane, etc for oxytocin receptors and prostaglandin synthase.
 Gastrin-releasing peptides (GRP’s)- increase with stretch to promote myometrial
contractility
Stretch induced potassium channel
 upregulated during gestation and downregulated in labor.
 Excessive uterine stretch causes
 premature loss of myometrial quiescence.
 early activation of the placental-fetal endocrine cascade
 Early rise in maternal corticotropin-releasing hormone and estrogen levels
can further enhance the expression of myometrial CAP genes
Prematurely increased stretch and endocrine activity may initiate events that shift the timing of
uterine activation, including premature cervical ripening
MATERNAL – FETAL STRESS

 STRESS is defined as a condition or adverse circumstance that disturbs the

normal physiological or psychological functioning of an individual.
 There is a correlation between maternal psychological stress and the placental–
adrenal endocrine axis that provides a potential mechanism for stress-induced
preterm birth.
 Last trimester- rising maternal serum levels of placental derived corticotropin-
releasing hormone (CRH) works with adrenocorticotropic hormone (ACTH) to
increase adult and fetal adrenal steroid hormone production, including the
initiation of fetal cortisol biosynthesis.
 Rising CRH stimulate fetal adrenal dehydroepiandrosterone sulfate
(DHEA-S) biosynthesis, which acts as substrate to increase maternal plasma
estrogens, particularly estriol.

 Premature rise in cortisol and estrogen early loss of uterine quiascent and
accelerate cervical ripening

 Preterm delivery associated with early activation of the fetal adrenal-placental

o endocrine cascade maternal estrogen levels prematurely elevated
  Preterm birth is associated with a maternal-fetal biological stress response

INFECTION

 Infection as a primary cause of preterm labor in pregnancies with intact

membrane
 Microbial invasion of the reproductive tract is sufficient to induce infection-
mediated preterm
birth- more specifically, there is ongoing
―subcinical infection.
 Women with amnionic fluid bacteria are more likely to develop clinical
chorioamnionitis and preterm ruptured membranes
 The earlier the onset of preterm labor the greater the likelihood of documented
infection
 In preterm pregnancies – bacteria represent an important cause of labor
 In chorioamnionitis with preterm labor, microbes may invaded maternal tissue only
and not amniotic fluid Endotoxins can stimulate amnionic cells to secrete cytokines
that enter amnionic fluid.
PRETERM PREMATURE RUPURE OF MEMBRANES
 Spontaneous rupture of the fetal membrane before 37 completed weeks and
before labor onset
 Intrauterine infection is believed by many to be a major predisposing event

ASSOCIATED RISK FACTORS

 Low socioeconomic status
 Body mass index <19.8
 Nutritional deficiencies
 Cigarette smoking
 Pror PROM

INFECTION

 Infection-induced premature rupture of membrane

 Inflammatory response that leads to membrane weakening
 Intrauterine infections are believed to trigger preterm labor by activation of
 the innate immune system.
 Microorganisms elicit release of inflammatory cytokines such as interleukins
and TNF-α, which in turn stimulate the production of prostaglandin and/or
matrix-degrading enzymes.
Prostaglandins stimulate uterine contractions, whereas degradation of
extracellular matrix in the fetal membranes leads to preterm rupture of
membranes.
CONTRIBUTING FACTORS

 Threatened abortion in early pregnancy is associated with higher rates of later

adverse outcomes
 Birth defects in the fetus may also predispose to preterm birth

LIFESTYLE FACTORS
 Cigarette smoking
 inadequate maternal weight gain and illicit drug use
– low-birthweight neonates
 Overweight and obese mothers
 Young or advanced maternal age
 Poverty,
 Short stature
 Vitamin C deficiency.
 Psychological factors such as
o depression,
o anxiety
o chronic stress.
 Working long hours and hard physical labor are probably associated with
increased risk of preterm birth
GENETIC FACTORS

 Recurrent, familial, and racial nature of preterm birth

 Immunoregulatory genes in potentiating chorioamnionitis in cases of
preterm delivery due to infection
PERIODONTAL DEFECTS

 Gum inflammation is a chronic anaerobic inflammation

 Treatment during pregnancy improved periodontal disease and that it is safe.
However, treatment failed to significantly alter preterm birth rates
 INTERVAL BETWEEN PREGNANCIES

 Short intervals between pregnancies have been known for some time to be
associated with adverse perinatal outcomes.
 Intervals < 18 months and > 59 months were associated with increased risks for
both preterm birth and small for- gestational age newborns.

PRIOR PRETERM BIRTH

 Most important risk factor is prior preterm delivery
o 1st delivery is preterm-3fold risk
o 1st & 2Nd delivery are preterm – 1/3 of women will deliver preterm
o 70% occurred within 2Weeks of the gestational age of the prior preterm
delivery
o Causes of prior preterm delivery also recurred
 Influenced by 3 factors:
1. Frequency of prior preterm deliveries
2. Severity as measured by gestational age
3. Order in which the prior preterm delivery occurred.
BACTERIAL VAGINOSIS

Normal,hydrogen peroxide-producing lactobacillus-predominant vaginal flora

is replaced with anaerobes that include

 Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis

 Bacterial vaginosis has been associated with:
 spontaneous abortion
 preterm labor
 PPROM
 Chorioamnionitis
 amnionic fluid infection
 Environmental factors appear to be important in bacterial vaginosis
development. Exposure to chronic stress, ethnic differences, and frequent or
recent douching have all been associated with increased rates of the
condition
 Gene-environment interaction
 Susceptible TNF-α genotype had a ninefold increased incidence of
preterm birth.
  Using gram staining, relative concentrations of the bacterial morphytes
characteristic of bacterial Vaginosis are determined and graded as the
NUGENT SCORE.
DIAGNOSIS
Symptoms:

 Early differentiation between true and false labor is difficult

 Braxton hicks contraction
o irregular, non rhythmical and either, and either painful or painless
 Pelvic pressure
 menstrual like cramps
 watery vaginal discharge,
 lower back pain

CERVICAL CHANGE
 routine digital examination
 Transvaginal Sonography between 18 and 30 weeks in nulliparas and
multiparas

FETAL FIBRONECTIN
 Glycoprotein is produced in 20 different molecular forms by various cell types,
including hepatocytes, fibroblasts, endothelial cells and fetal amnion cells.
 ACOG does not recommend screening with fetal fibronectin tests.
 fetal fibronectin screening in asymptomatic women have not demonstrated
improved perinatal outcomes.

Preterm Birth prevention

Cervical Cerclage
There are at least three circumstances when cerclage may be used to prevent preterm
birth.

1. The procedure may benefit women who have history of recurrent

midtrimester losses and who are diagnosed with cervical insufficiency
2. Women identified during Sonographic examination to have a short cervix
3. “Rescue” cerclage, done emergently when cervical incompetence is
recognized in women with threatened preterm labor
 Recurrent preterm birth can be prevented in a subset of women who have a history
 of prior preterm births.
ACOG 2016: Women with a singleton pregnancy, prior spontaneous preterm
birth before 34 weeks, cervical length <25mm and gestational age <24 weeks,
cerclage may be considered
PROPHYLAXIS WITH PROGESTIN COMPOUNDS
 Progesterone levels in most mammals fall rapidly before the onset of labor.
 Parturition-triggeringevent – progesterone withdrawal.
 Human parturition involves functional progesterone withdrawal mediated by
decreased progesterone activity of progesterone receptors.
 Administration of progesterone to maintain uterine quiescence may block
preterm labor.

MANAGEMENT OF PPROM
 History of vaginal leakage of fluid, either as continous stream or as a gush.
 Speculum exam to visualize gross vaginal pooling of amniotic fluid, clear fluid
from the cervical canal
 Sonographic exam to assess amniotic fluid volume, to identify the
presenting part, and if not previously determined, to estimate gestational
age.
 Amniotic fluid is slightly alkaline (pH 7.1-7.3) compared with vagina (pH 4.5-
6.0)
CORTICOSTERIODS TO ACCELERATE FETAL LUNG MATURITY
 Single course of antenatal corticosteroids for women with preterm
membrane rupture before 32 Weeks and in whom there was no evidence of
chorioamnionitis.
ACOG (2013)
 Single-dose therapy is recommended from 24 to 32 weeks.
 Gestational age spectrum, wherein the corticosteroid administration in the
late preterm is also under consideration
MANAGEMENT OF PRETERM LABOR WITH INTACT MEMBRANE

 Women with signs and symptoms of preterm labor with intact membranes
are managed much the same as described above for those with preterm
ruptured membranes. If possible, delivery before 34 weeks is delayed.
CORTICOSTEROIDS FOR FETAL LUNG MATURITY
 Effective in lowering the incidence of respiratory distress syndrome and neonatal
 mortality rates if birth was delayed for at least 24 hours after initiation of
betamethasone.
o 12MG Betamethasone every 24 hrs for 2 doses
o 6mg Dexamethasone every 12 hrs for 4 doses.

Rescue Therapy

Administration of second corticosteroid dose when delivery becomes imminent

and more than 7 days have elapsed since the initial dose.
 ACOG (2017)
o Single rescue course of antenatal corticosteroids may be considered in
women before 34 weeks whose prior course was administered at least 7
days previously
.
MAGNESIUM SULFATE FOR NEUROPROTECTION
 Very low birthweight neonates treated with magnesium sulfate for preterm labor
or preeclampsia have reduced incidence of cerebral palsy.

ANTIMICROBIALS

 Given in an attempt to arrest preterm labor.

 ORACLE Collaborative Group study of 6295 women with spontaneous preterm

labor, intact membranes, but without evidence of infection.
o Primary outcomes of neonatal death, chronic lung disease, and major
cerebral abnormality were similar in both groups.
 Not recommended.
 ORACLE II trial
 That fetal exposure to antimicrobials in this clinical setting was associated with an
increased cerebral palsy rate at age 7 years compared with that of children without
fetal exposure.
BED REST

 Most often prescribed interventions during pregnancy, yet one of the least
studied.
 Insufficient evidence to support the use of bed rest and found several studies
showing harm with its use
TOCOLYSIS
 to treat preterm labor
  ACOG(2012) - tocolytic agents do not markedly prolong gestation but may
delay delivery in some women for up to 48 hours.
 Allow transport to a regional obstetrical center
 Permit time for corticosteroid therapy.

 ACOG recommends that women with preterm contractions without cervical change,
especially those with cervical dilation of less than 2 Cm, generally should not be
treated with tocolytics
MAGNESIUM SO4

 Ionic magnesium in a sufficiently high concentration can alter myometrial

contractility
 Calcium antagonist
 May inhibit labor
 Dose:
o 4g IV initially then continous infusion of 2G/hr
 SE:
o pulmonary edema & respiratory depression
PROSTAGLANDIN INHIBITORS
 Act by inhibiting prostaglandin synthesis or by blocking their action on
target organs.
 Group of enzymes collectively termed prostaglandin synthase is responsible
for the conversion of free arachidonic acid to prostaglandins
 Indomethacin
o Non-selective cyclooxygenase inhibitor
o Administered orally, or rectally
SE: oligohydramnios, intraventricular hemorrhage, PDA, sepsis, necrotizing
enterocolitis or neonatal death