Obstetrics & Gynecology: Preterm Labor Mala Arora, Jennifer R Niebyl, Asha Rijhsinghani
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1World Clinics Obstetrics and Gynecology: Preterm Labor2
3World Clinics Obstetrics and Gynecology: Preterm Labor
Editor-in-Chief Mala Arora FRCOG(UK) FICOG FICMCH Guest Editors Jennifer R Niebyl MD Asha Rijhsinghani MD FACOG
June 2012 Volume 2 Number 1
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Cover images: Bicornuate uterus with pregnancy in the left horn. Courtesy: Dr Ashok Khurana (Left) and Dr Asha Rijhsinghani (Right).
WORLD CLINICS Obstetrics and Gynecology: Preterm Labor
June 2012, Volume 2, Number 1
ISSN: 22489517
9789350901755
Printed in India
5Contributors  
 
Editor-in-Chief
 
Guest Editors
 
Contributing Authors
11Preface
Preterm birth is the largest contributor to fetal mortality and long-term morbidity. Its incidence is rising globally, and it is a matter of concern for the health of our future generation. The World Health Organization (WHO) has taken cognizance of this problem. There is a commitment to reduce the incidence of preterm birth globally by a multipronged approach. Basic antenatal care should be provided to all expecting mothers. Healthcare professionals need to have definitive guidelines and protocols of procedures, which are required to prevent, diagnose, and manage preterm labor. Basic neonatal care should be available to all preterm neonates. Community interventions like cessation of smoking at workplace and public utility areas need to be implemented. Medical policy interventions to reduce the number of embryos transferred during assisted conception cycles can help in reducing the incidence of multiple pregnancies. Workplace policies to regulate the working hours of pregnant women have not been formulated in many countries. Reducing the incidence of early induction of labor/cesarean section requires accurate dating of pregnancies and carefully planned management of maternal conditions that predispose to preterm labor. This periodical encompasses the latest guidelines for healthcare professionals for the care of women at high-risk of preterm labor. It is an effort to raise awareness on this issue in the medical fraternity and healthcare policy makers.
Mala Arora frcog (uk) ficog ficmch
Director, Noble IVF Centre, Faridabad 121 007, Haryana, India
Consultant, Fortis La Femme, Greater Kailash, New Delhi 110 048, India
Email: narindermala@gmail.com12
13Editorial
Mala Arora frcog (uk) ficog ficmch Editor-in-Chief
Partus prematurus is delivery prior to 37 weeks of gestation. It is estimated that one in ten babies is born preterm around the globe; of which, 50% die, and many more struggle with lifelong disabilities. The rates of preterm birth are rising globally, including in a developed country like North America, where more than half a million babies are born prematurely. The incidence is quite high in Brazil, India, and Nigeria, whereas much lower in Western Europe, Japan, and Scandinavia. There is an obvious survival gap in preterm infants born in the high-income countries compared to the low-income countries.
Preterm birth is classified as:
Fortunately 85% of preterm births occur between 32 and 37 weeks.
The definition has no lower boundary and generally all live births are counted. The World Health Organization (WHO) defines miscarriage as fetal death less than 24 weeks or less than 500 g. Accurate estimation of gestational age utilizes ultrasound measurement in the first trimester combined with last menstrual period, called the “best obstetric estimate.” In low-resource settings, birth weight is taken as a surrogate marker, although Institute of Medicine considers it a poor surrogate. Most babies are termed preterm, if they weigh less than 1500 grams.
The etiology of preterm birth is varied and may be multifactorial. It is intimately linked to maternal health and factors predisposing to it include:
Empowerment of women, especially adolescents, delaying first pregnancy after teenage, prepregnancy counseling, adequate spacing of pregnancies, appropriate nutrition counseling during pregnancy, and adequate post-delivery family planning services are some of the social strategies that will go a long way in preventing preterm births.
Preterm labor is often unpredictable in a low-risk population (singleton primigravidas). The two available screening modalities are fetal fibronectin (FFN) and cervical assessment. Fibronectin is a protein found between the fetal membranes and uterine lining. Its presence in cervical secretions can predict preterm labor. However, the test is expensive and not widely available. Digital assessment of the cervix and Bishop score of more than 5 at 22–24 weeks has a sensitivity of 11.8% and specificity of 97.6% with a positive predictive value of 18.1%. Thus a soft, central, effacing, and dilating cervix predicts preterm labor in 98% of patients, whereas a long, closed, and firm cervix does not predict absence of preterm labor. However, a cervical scoreBrief of less than 0 by transvaginal ultrasound at 22–24 weeks has a sensitivity of 1.6%; however, the specificity and positive predictive value is 100%. This proves that the earliest changes of impending preterm labor occur at the level of the internal os, which can only be detected by ultrasound. Transabdominal scanning for cervical length is erroneous, as the cervix appears long if the bladder is full.
Transvaginal screening of cervical length with an empty bladder in mid-gestation is currently the gold standard test for predicting preterm labor, and it should be offered to all pregnant women. Cervical length of less than 2.5 cm and/or cervical score of less than 0 in the second trimester is associated with preterm birth at less than 35 weeks of gestation. These women will benefit from progesterone therapy and/or cervical cerclage.
Iatrogenic or provider-initiated preterm births are also on the rise and timely use of corticosteroids should be strictly practiced.
In women with a history of preterm premature rupture of membranes (PPROM), benefit of screening and treatment for bacterial vaginosis (BV) is not clear. In women who are at high risk and known to have BV, treatment with either clindamycin or metronidazole combined with probiotics can be considered. There is no role for routine screening of pregnant women or prophylactic administration of antibiotics.
In women who undergo cervical excision for cervical intraepithelial neoplasia (CIN), the risk of preterm delivery in the subsequent pregnancy is increased.
†Bishop score = Dilation in cm (2) + Effacement in % (2) + Station (2) + Cervical consistency (2) + Position of cervix (2) = 10.
*Cervical score = Cervical length (cm) – Cervical dilation (cm) at the internal os (i.e., a cervix which is 2 cm long but 1 cm dilated at the internal os is a cervical score = 1).
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The risk of preterm delivery increases with increasing depth of cervical excision and shorter procedure to pregnancy interval.
Uterine anomalies like septate uterus, extensive adenomyosis, and submucosal myomas may require hysteroscopic correction prior to pregnancy, and may benefit from progesterone therapy during pregnancy. Pregnancy with intrauterine device (IUD) in situ has a high incidence of preterm labor.
Maternal medical disorders associated with preterm births like anemia, malaria, and HIV are rampant in low-income countries, whereas hypertensive disorders, diabetes, obesity, and substance abuse are more prevelant in high-income countries.
Pregnancies post-assisted reproductive technologies (ART) have an increased incidence of twins and higher order multiple births. These account for a rise in the incidence of preterm births. Even singleton ART pregnancies are at an increased risk of preterm labor. Although prophylactic cervical cerclage and/or progesterone therapy has been used in these patients, there are no randomized controlled trials to prove the benefit of such therapies.
Ideally, all women should be offered transvaginal cervical screening between 19 and 24 weeks. Mid-gestational ultrasound also identifies other risk factors like oligohydramnios, polyhydramnios, amniotic fluid sludge, vasa previa, and congenital fetal anomalies.
Management strategies include:
Administration of antenatal corticosteroids has proven to be beneficial in reducing the incidence of respiratory distress syndrome in preterm infants. The tocolytics of choice are prostaglandin synthetase inhibitors and calcium-channel blockers. Oxytocin receptor agonists are expensive and β-sympathomimetics have unacceptable side effects. Tocolysis delays preterm birth by a few days to a week, thus, providing a window to administer corticosteroids and arrange for an in utero transfer to a center with neonatal intensive care facilities. It does not prolong gestation in preterm labor. Administration of antibiotics in patients with PPROM prolongs latency to onset of labor, thereby, allowing time for corticosteroids to act. Administration of magnesium sulfate for neuroprotection of the premature neonate is being advocated in some countries. However, it should not be combined with calcium-channel blockers due to the possibility of severe maternal hypotension.
Care of the preterm infant at birth requires neonatal resuscitation by providing oxygen or ventilator support. Further care should be targeted at preventing 16hypoglycemia, hypoxia, neonatal sepsis, and hypothermia by kangaroo care. These measures can be instituted in low-resource settings. Neonatal intensive care facilities, ventilator support, and surfactant therapy will further improve outcome in preterm neonates.
Neonatal care of extremely preterm infants poses an ethical and financial dilemma. Many countries like Switzerland and USA offer only palliative care to neonates under 24 completed weeks of gestation. However, this decision needs to be individualized to the needs of the patient.
“Born too soon” is the global action report released in March 2012 that is a joint effort by 50 international and national organizations, including the WHO. It recognizes preterm birth as the second leading cause of death among children less than five years of age. It sets goals to reduce the burden of preterm births globally by 50% between 2010 and 2025. A technical expert group will be convened to realize this goal and a World Prematurity Day will be announced in 2012.
The International Preterm Birth Collaborative (PREBIC) intends to develop clinical interventions to reduce the rates of preterm birth globally. We particularly need to initiate further research in identifying the causal pathways leading to preterm labor and understanding the gestational clock triggering the onset of labor.
Mala Arora frcog (uk) ficog ficmch
Director, Noble IVF Centre, Faridabad 121 007, Haryana, India
Consultant, Fortis La Femme, Greater Kailash, New Delhi 110 048, India
Email: narindermala@gmail.com
17Abbreviations 17 OHPC
17 alpha-hydroxyprogesterone caproate
5-MTHF
5-methyl tetrahydrofolate
AAP
American Academy of Pediatrics
aCL
Anticardiolipin antibody
ACOG
American College of Obstetrics and Gynecology
ACTH
Adrenocorticotropic hormone
AFI
Amniotic fluid index
AHA
American Heart Association
APS
Antiphospholipid syndrome
ART
Assisted reproductive technology
ASD
Autism spectrum disorders
BMI
Body mass index
BPD
Bronchopulmonary dysplasia
BV
Bacterial vaginosis
cAMP
Cyclic adenosine monophosphate
CFAS
Canadian Fertility and Andrology Society
CI
Confidence interval
CIN
Cervical intraepithelial neoplasia
CLD
Chronic lung disease
CNS
Central nervous system
COX
Cyclooxygenase
CP
Cerebral palsy
CPAP
Continuous positive airway pressure
CRH
Corticotropin-releasing hormone
Cx43
Connexin-43
CXCL10
C-X-C-motif-chemokine 10
DES
Diethylstilbestrol
DHEA
Dehydroepiandrosterone
ECM
Extracellular matrix
EPIPAGE
Etude Epidemiologique sur les Petits Ages Gestationnels
ET
Embryo transfer
FDA
Food and Drug Administration
FIRS
Fetal inflammatory response syndrome
FMF
Fetal Medicine Foundation
GAPPS
Global alliance to prevent prematurity and still birth
G-CSF
Granulocyte-colony stimulating factor
GDM
Gestational diabetes mellitus
GIFT
Gamete intrafallopian transfer
HELLP
Hemolysis, elevated liver enzymes, low platelet count
HFEA
Human Fertilization and Embryology Authority
HLA
Human leukocyte antigen
HMGB1
High mobility group box-1
HPV
Human papillomavirus
HSP70
Heat shock protein
ICSI
Intracytoplasmic sperm injection
Ig
Immunoglobulin
IL
Interleukin
IM
Intramuscularly
ISUOG
International Society for Ultrasound in Obstetrics and Gynecology
IUD
Intrauterine device
IUGR
Intrauterine growth retardation
IV
Intravenously
IVF
In vitro fertilization
IVH
Intraventricular hemorrhage
LA
Lupus anticoagulant
LBC
Liquid-based cytology
LEEP
Loop electrical excision procedure
LLETZ
Large loop excision of the transformation zone
MAP
Mitogen activated protein
MFMN
Maternal Fetal Medicine Network
MFMU
Maternal fetal medicine units
MLCK
Myosin light-chain kinase
MRI
Magnetic resonance imaging
MTHFR
Methylene tetrahydrofolate reductase
MV
Mechanical ventilation
NEC
Necrotizing enterocolitis
NETZ
Needle excision of the transformation zone18
NF-κ B
Nuclear factor kappa-B
NHS
National Health Service
NICHD
National Institute of Child Health and Development
NICU
Neonatal intensive care unit
NIH
National Institute of Health
NO
Nitric oxide
NRN
Neonatal research network
NRP
Neonatal Resuscitation Program
NSAID
Nonsteroidal anti-inflammatory drugs
OR
Odds ratio
OXTR
Oxytocin-receptor gene
PCR
Polymerase chain reaction
PDA
Patent ductus arteriosus
PDSA
Plan, Do, Study, Act
PG
Prostaglandin
PROM
Premature rupture of membranes
PRR
Pattern recognition receptors
RAGE
Receptor for advanced glycation end-products
RCT
Randomized control trial
RDS
Respiratory distress syndrome
Rh
Rhesus
ROP
Retinopathy of prematurity
RR
Relative risk
SD
Standard deviation
SGA
Small for gestational age
SLE
Systemic lupus erythematosus
SMFM
Society of maternal fetal medicine
SOGC
Society of Obstetrics and Gynecologists of Canada
SUPPORT
Surfactant positive airway pressure and pulse oximetry trial
SWETZ
Straight wire excision of the transformation zone
TGF
Transforming growth factor
TLR
Toll-like receptors
TNF
Tumor necrosis factor
VON
Vermont Oxford Network
WHO
World Health Organization