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Bucharest, ROMANIA
Preterm birth
Manuela Russu, MD, PhD
Habilitated Professor
Head of “Dr. I. Cantacuzino”
Discipline of Obstetrics & Gynecology
MCR, 2018
Definitions
1935: American Academy of Pediatrics: prematurity as a live-born infant
weighting ≤ 2500 g. These criteria were used widely until it became apparent that
there were discrepancies between GA and birthweight because of IUFGR
1961: WHO: added gestational age as a criterion for premature infants, defined as
those born at ≤ 37 wks . A distinction was made between low birthweight (≤
2500 g) & prematurity ( ≤ 37 wks )
1995: American College of Obstetricians & Gynecologists:
suggested: “preterm birth be defined as those infants
delivered prior to the completion of 37wks”
With continued improved care of the preterm infant, other definitions have been
developed: for example, the Collaborative Group on Antenatal Steroid Therapy
(1981) reported that:
the great preponderance of mortality and serious morbidity from preterm birth is
prior to 34 weeks
Moreover, low birthweight, defined as less than 2500 g, has been modified now to
describe very-low birthweight, infants weighting ≤ 1500 g; and
extremely-low birthweight, those who weight ≤ 1000 g
Fetal development
With respect to GA: fetus/ infant: preterm, term, or postterm
With respect to size: fetus/ infant: normally grown or
appropriate-for-gestational age, small in size or small-
for-gestational age, overgrown or large-for-gestational
age
• In recent years, the term small for gestational age has been
widely used to categorize an infant whose birthweight is usually
below the 10th percentile for its GA
• Other often-used terms have included fetal growth retardation or
intrauterine growth retardation
• Within the past 10 years: term “restriction” has largely replaced
the term “retardation”, because the latter may erroneously convey
mental delay rather than only the intended suboptimal fetal
growth
Fetal development
The infant whose birthweight is above the
90th percentile has been categorized as large-
for-gestational age, and the infant whose weight
is between the 10th and 90th percentiles is
designated appropriate-for-gestational age
Thus, an infant born before term can be small or large
for GA and still be premature according to chronological
GA
Moreover, some premature infants have also suffered
growth restriction in utero. It is important to recognize that
prematurity may not only encompass those births occurring
before term, but also frequently includes infants who have
suffered subnormal in utero growth
WHITE PAPER OF PRETERM BIRTH, 2012
Romanian Demographic Data
Thorsen et al, 1996: a prospective study of 3600 Danish women: BV diagnosed before 24 wks
was not related to ruptured membranes before 37 wks or to low birthweight
Neonatal Complications of Preterm Birth
Neonatal Morbidity (compozite) & mortality are strongly influenced by GA,
specially in pregnancies before 28 wks
- RDS; - Bronchopulmony Dysplasia
- intraventricular Hemorrhage;→ leukomalacia, hydrocephalus
- Necroziting Enterocolitis; Neonatal Sepsis
- Death: Prematurity is the second cause of mortality in the first 5 yrs of
life, worldwide - Chang HH, et al, 2011
The premature survivors have serious future health problems:
- visual (post-hyperoxygenation retinopathy), hear, neurological
development : neonatal encephalopathy, cerebral palsy,
- mood and/or learning problems during childhood, and adolescence
Trudinger BJ, Cook CM, Thompson RS, et al (1988)- Low-dose aspirin therapy
improves fetal weight in umbilical placental insufficiency. Am J Obstet Gynecol. 159(3):681-
5.
- in utero transfer
* Many studies of the last 10-15 yrs did not revealed notable
benefits when propfilactic antibiotics were used, special when
intact membranes -Hutzal CE, et al, 2008, or from the
prognosis of preterm neonates -Cochrane Database Syst Rev,
2013
* Preterm Labor with Intact Fetal
Membranes
The cornerstone of treatment of women with signs & symptoms of
preterm labor and intact membranes is to avoid delivery prior to 37
wks if possible
Antimicrobials, for the purpose of delaying delivery in
women with preterm labor, have been studied specifically in
women with intact membranes
• Results with a variety of antimicrobial agents have been
disappointing
Romero, 1993; Gordon, 1995; Klebanoff, 1995; Cox, 1996
• It is likely that administration of antimicrobials after
preterm labor has begun is too late to interfere with
propagation of the cytokine cascade that modulates uterine
activity
Management (6)
Medication: b) Antibiotics
Cases with sexually transmited diseases, vaginitis, UTI, severe
respiratory infections must be adequate treated
In USA ( last 30 yrs): eritromycine, ampiciclyne, clindamycine
Kenyon S, et al, 2010; McGregor JA, et al,1986;
Miller JM, et al,2000
Cases with intact membranes, with vaginal positive cultures
with groupe B streptococus: were treated long time with
intravenous Peniciline, for prevention of vertical perinatal
prevention, even it was proved that it does not substantially
reduce the rate of PB
Cases with premature ruptured membranes will benefit from
antibiotics during the duration of waiting corticoids’ effects and
the moment of birth with the lowest risks of morbidity /mortality
of the preterm baby Kenyon S, et al, 2010
Preterm Labor with Intact Membranes
3. Glucocorticoid Therapy
Liggins, Howie, 1974: randomized study to evaluate the effects
of maternally administered betamethasone (12 mg i.m. in 2
doses 24 hs apart) to prevent respiratory distress in subsequently
delivered preterm infant. Infants born before 34 wks had a significantly
lowered incidence of respiratory distress & neonatal mortality from
hyaline membrane disease if birth was delayed for at least 24 h after
completion of 24 h of betamethasone given to the mother and for up to
7 days after completion of steroid therapy (best efficacy = in 3 to 7
days, after completed regimen)
The mechanism by which betamethasone or other corticosteroids are
currently thought to reduce the frequency of respiratory distress involves
induction of proteins that regulate biochemical systems within type II
cells in the fetal lung that produce surfactant (Ballard PL, Ballard
RA, 1995). The physiological effects of glucocorticoids on
the developing lungs include increased alveolar surfactant,
compliance, & maximal lung volume
Management of Preterm Labor
c) Glucocorticoid Therapy
Meta-analysis for randomized trial of cortico-steroids for
fetal maturation:
reduces respiratory distress by 50%
reduces neonatal mortality by 50%
NIH Consensus Development Panel,1995:
data are insufficient to assess effectiveness of
corticosteroids in pregnancies complicated by:
• hypertension
• diabetes mellitus
• multiple gestation
• fetal growth restriction
• fetal hydrops
On debates:
- the use of corticoids in multiple pregnancy
Batista L, et al, 2008; Choi SJ, et al, 2009
- extra extreme prematurity (< 24 wks)
Hayes EJ, et al, 2008; Mori R, et al, 2011
- intrauterine fetal growth restriction
Torrance HL, et al, 2009; Vidaeff AC, et al, 2011.
Indomethacin
Hepatitis Nifedipine
Renal failure Transient hypotension
Gastrointestinal bleeding
Intrapartum Management of preterm birth
Whether labor is induced or spontaneous, continuous electronic
monitoring for abnormalities of fetal heart & uterine contractions
Fetal tachycardia, specially in the presence of ruptured membranes,
is suggestive of sepsis
Intrapartum acidemia (umbilical artery blood pH < than 7.0) may
intensify some neonatal complications usually attributed solely to
prematurity
Prevention of infection with streptoccocus group B: ampicillin 2
g i.v. every 6 hs until delivery for women in labor prior to 37 wks
Magnesium sulfate: reduces incidence of cerebral palsy
when surviving infants with birthweights < 1500 g. Magnesium
given to fetus via the mother perhaps playes a role in regulation of
vasculature supplying the germinal matrix of fetal brain that is
especially vulnerable to hemorrhage in preterm infant (Nelson &
Grether, 1995)
a liberal episiotomy once the fetal head reaches the perineum
Management for active preterm birth
Many debates regarding the route of delivery in preterm birth
Cesarean Section– increased up to 35%
< 32 weeks – cesarean section
32-34 weeks – discussed
Reddy UM, Zhang J, Sun L, et al. Neonatal mortality by attempted route of delivery
in early preterm birth. Am J Obstet Gynecol 2012
Fetal outcome is directly influenced by the degree of
prematuriry and not by the route of delivery
Rules imposed to be respected for all deliveries with preterm babies:
- conduction of labort under CTG monitoring
- integrity of membranes up to expulsion,