PRETERM LABOR AND PREMATURE RUPTURE OF

MEMBRANES

By; JOYCE F. MWATONOKAMD4

Sept 2016

Preterm infants are those delivered before 37 completed weeks

Early preterm; <33 weeks Late preterm; between 34 and 36

completed weeks. 70% of all preterm births. Early term; 37 wk to 38wk 6days Term; 39 weeks 0 days to 40 weeks 6 days.

Infant mortality is lower than at any other time in human gestation

PRETERM LABOR

Rate of spontaneous preterm births has been decreasing, but there has been a significant rise of induced preterm births

Various morbidities, largely due to organ system immaturity, are significantly increased in infants born before 37 weeks’ gestation compared with those delivered at term

Cont…

(1) Spontaneous unexplained preterm labor with intact membranes

(2) Idiopathic preterm premature rupture of membranes (PPROM)

(3) Delivery for maternal or fetal indications, and

(4) Twins and higher order multifetal births.

Main direct reasons for preterm births

Of all preterm births, 30 to 35 percent are indicated, 40 to 45 percent are due to spontaneous preterm labor, and 30 to 35 percent follow preterm membrane rupture

Cont…

Mechanisms that lead to the onset of preterm labor are complex and multifactorial, but it is likely to occur as a result of the concomitant activation or a cascade of the following events;◦ Functional progesterone withdrawal◦ Increase in corticotrophin-releasing hormone◦ Premature decidual activation◦ Increased prostaglandin production◦ Oxytocin initiation◦ Increased cytokine production

Pathophysiology

Multifetal pregnancy; Uterine stretch increases gap junction proteins, PGs synthesis, receptors for oxytocin and specific contraction associated proteins (CAPS).

Hydramnios Placental infarction, IDIOPATHIC

RISK FACTORS FOR PRETERM BIRTHS

Intrauterine infections; trigger preterm labor by activation of the innate immune system. In this hypothesis, 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.

It is estimated that 25 to 40 percent of preterm births result from intrauterine infection.

Cont…

Fetal anomalies; In a secondary analysis of data from the First- and Second-Trimester Evaluation of Risk (FASTER) Trial, it was found that birth defects were associated with preterm birth and low birthweight (Dolan, 2007

Cont…

Prior Preterm Birth A major risk factor for preterm labor is prior

preterm delivery Increases risk 3 folds

Cont…

Threatened Abortion Vaginal bleeding in early pregnancy is

associated with increased adverse outcomes later

Both light and heavy bleeding were associated with subsequent preterm labor, placental abruption, and subsequent pregnancy loss before 24 weeks

Also anemia

Cont…

Uterine anomalies: Cervical incompetence, malformation of uterus

Cigarette smoking, inadequate maternal weight gain, and illicit drug use have important roles in both the incidence and outcome of low-birthweight neonates (Chap. 12, p. 253).

Overweight and obese mothers have an elevated risk of preterm birth

Maternal factors

Work and physical activities Conflicting results (Goldenberg, 2008). There is some evidence, however, that

working long hours and hard physical labor are probably associated with increased risk of preterm birth (Luke, 1995).

Cont…

As discussed on page 837, psychological factors such as depression, anxiety, and chronic stress have been reported in association with preterm birth

Cont…

Genetic Factors The recurrent, familial, and racial nature of

preterm birth has led to the suggestion that genetics may play a causal role.

As discussed on page 839, several such studies have also implicated immunoregulatory genes in potentiating chorioamnionitis in cases of preterm delivery due to infection

Cont…

Interval between Pregnancies Short intervals between pregnancies have

been known for some time to be associated with adverse perinatal outcomes.

Conde-Agudelo and colleagues (2006) reported that intervals < 18 months and > 59 months were associated with increased risks for both preterm birth and small-for gestational age newborns

Cont…

Severe maternal illness as a result of infections like acute pyelonephritis, diarrhea, acute appendicitis and toxoplasmosis, autoimmune diseases, and gestational hypertension also increases preterm labor risks

These diverse processes culminate in a common end point, which is premature cervical dilatation and effacement and premature activation of uterine contractions.

Cont…

Preterm labor is primarily diagnosed by symptoms and physical examination.

Sonography is used to identify asymptomatic cervical dilation and effacement.

DIAGNOSIS

(1) Regular uterine contractions with or without pain (at least one in every 10 minute);

(2) Dilatation (> 2 cm) and effacement (80%) of the cervix;

(3) Length of the cervix (measured by TVS) < 2.5 cm and funneling of the internal os (see p. 169)

(4) Pelvic pressure, backache and or vaginal discharge or bleeding.

It is better to overdiagnose preterm labor than to ignore the possibility of its presence.

Cont…

Full blood count Urine for routine analysis, culture and

sensitivity Cervicovaginal swab for culture Ultrasonography for fetal well being,

cervical length and placental localization Serum electrolytes and glucose levels when

tocolytic agents are to be used

INVESTIGATIONS

(1) Glucocorticoids to the mother to reduce neonatal RDS, IVH and NEC. Betamethasone (Betnesol) 12 mg IM 24 hours apart for two doses or dexamethasone 6 mg IM every 12 hours for 4 doses is given

(2) Antenatal transfer of the mother with fetus in utero to a center equipped with NICU

(3) Tocolytic drugs (see p. 507) to the mother for a short period unless contraindicated eg; PG synthase inhibitors (indomethacin), MgSO4, Ca channel blockers, Oxytocin receptor antagonists (Atosiban), progesterone

PRINCIPLES OF MANAGEMENT OF WOMEN WITH PRETERM LABOR

(4) Antibiotics to prevent neonatal infection with Group B Streptococcus (GBS)

(5) Careful intrapartum monitoring, minimal trauma and presence of a neonatologist during delivery

(6) Vaginal delivery is preferred, unless otherwise indicated for cesarean birth

If fetus is not compromised, the maternal condition remains good and membranes are intact;

Bed rest; preferably in left lateral position Adequate hydration Prophylactic cervical circlage; for women

with prior preterm birth and short cervix in the present pregnancy

Tocolytic agents

MEASURES TO ARREST PRETERM LABOR

Maternal: Uncontrolled diabetes, thyrotoxicosis, severe hypertension, cardiac disease, hemorrhage in pregnancy, e.g. placenta previa or abruption.

Fetal: Fetal distress, fetal death, congenital malformation, pregnancy beyond 34 weeks.

Others: Rupture of membranes, chorioamnionitis, cervical dilatation more than 4 cm

Contraindications of tocolytics

NB; The American College of Obstetricians and Gynecologists (2012a) has concluded that tocolytic agents do not markedly prolong gestation but may delay delivery in some women for up to 48 hours. This may allow transport to a regional obstetrical center and permit time for corticosteroid therapy.

Cont…

Braxton Hicks contractions; irregular, nonrhythmical, and either painful or painless

Placental abruption Urinary; acute cystitis, pyelonephritis,

nephrolithiasis Gatrointestinal; Constipation

Ddx of Preterm Labor

1. Cervical Cerclage There are at least three circumstances when cerclage

placement may be used to prevent preterm birth. Two are done prophylactically, and a third is done for treatment. The first prophylactic cerclage is used in women who have a history of recurrent midtrimester losses and who are diagnosed with cervical insufficiency. The second prophylactic cerclage is for women identified during sonographic examination to have a short cervix. The third indication is “rescue” cerclage, done emergently when cervical incompetence is recognized in women with threatened preterm labor.

PREVENTION OF PRETERM LABOR

2. Prophylaxis with Progestin Compounds (17-hydroxyprogesterone)

Progesterone levels in most mammals fall rapidly before the onset of labor. This is termed progesterone withdrawal and is considered to be a parturition-triggering event. During human parturition, however, maternal, fetal, and amnionic fluid progesterone levels remain elevated with no decline. It has been proposed that human parturition involves functional progesteronewithdrawal mediated by decreased progesterone activity of progesterone receptors (Ziyan, 2010). It follows conceptually that the administration of progesterone to maintain uterine quiescence may block preterm labor.

Cont…

3. Geographic-Based Public Health-Care Programs

A well-organized prenatal system results in a decreased preterm birth rate in high-risk indigent populations.

Cont…

PROM; Spontaneous rupture of the membranes any time beyond 28th week of pregnancy but before the onset of labor.

When rupture of membranes occur beyond 37th week but before the onset of labor it is called term PROM

and when it occurs before 37 completed weeks, it is called preterm PROM.

PROM

Rupture of membranes for > 24 hours before delivery is called prolonged rupture of membranes.

PROM occurs in approximately 10% of all pregnancies.

Cont…

(1) Increased friability of the membranes; (2) Decreased tensile strength (stretching) of

the membranes; (3) Polyhydramnios; (4) Cervical incompetence; (5) Multiple pregnancy;

PROM; CAUSES

(6) Infection—Chorioamnionitis, urinary tract infection and lower genital tract infection

(7) Cervical length < 2.5 cm (8) Prior preterm labor (9) Low BMI (< 19 kg/m2).

Cont…

A history of vaginal leakage of fluid, either as a continuous stream or as a gush

Often confused with : (a) Hydrorrhea gravidarum—a state where

periodic watery discharge occurs probably due to excessive decidual glandular secretion;

(b) Urine incontinence specially in the later months

(c) Heavy candidiasis

Dx OF PROM

1. Sterile speculum examination to visualize gross vaginal pooling of amniotic fluid, clear fluid from the cervical canal, or both.

2. To examine the collected fluid from the posterior fornix (vaginal pool) for: (a) Detection of pH by litmus or Nitrazine paper. The pH becomes 6–6.2 (Normal vaginal pH during pregnancy is 4.5–5.5 whereas that of liquor amnii is 7–7.5). Nitrazine paper turns from yellow to blue at pH > 6

Confirmation of Dx

Blood, semen, antiseptics, or bacterial vaginosis, however, are all also alkaline and can give false positive results.(b) To note the characteristic ferning pattern when a smeared slide is examined under microscope (fern test); due to crystallization of NaCl on mucus fibers under high estrogen concentration

Cont…

Furning pattern

(c) Centrifuged cells stained with 0.1% Nile blue sulfate showing orange blue coloration of the cells (exfoliated fat containing cells from sebaceous glands of the fetus)

Confirmation of ruptured membranes is usually accompanied by sonographic examination to assess amnionic fluid volume, to identify the presenting part, and if not previously determined, to estimate GA

Cont…

Full blood count Urine for routine analysis and culture High vaginal swab for culture

OTHER INVESTIGATIONS

Vaginal pool/amniosentesis for estimation of Phosphatidyl glycerol and L:S ratio (Lecithin-spingomyelin ratio), for assessment of fetal lung maturity

Ratio is 1 upto 32 wk GA, then Lecithin increases while shingomyelin remains nearly the same

Ratio of 2 or more at 35wk indicates lung maturity, <1.5 ass/c high risk of infant RDS

Centrifuge at 1000 rpm for 3-5min, then TLC (thin layer chromatography)

Fetal lung maturation tests

Shake test or Bubble test (Clement’s) Foam Stability Index (FSI); FSI>47 virtually

excludes the risk of RDS Saturated phosphatidyl choline > 500

ng/mL indicates pulmonary maturity Fluorescence polarization; Presence of

55mg of surfactant per gram of albumin indicates fetal lung maturity

Cont…

Amniotic fluid optical density at 650 mµ greater than 0.15 indicates lung maturity

Lamellar body count > 30,000/µL indicates pulmonary maturity

Orange colored cells cells > 50% suggests pulmonary maturity.

Amniotic fluid turbidity due to vernix caseosa

Cont…

The time from PPROM to delivery is inversely proportional to the gestational age when rupture occurs (Carroll, 1995).

Very few days were gained when membranes ruptured during the third trimester compared with mid-pregnancy

MANAGEMENT OF PROM

Hospitalization Term PROM: If the patient is not in labor and there

is no evidence of infection or fetal distress, she is observed carefully, in the hospital

Generally in 90% of cases spontaneous labor ensue within 24 hours. If it does not, induction of labor with oxytocin is commenced forthwith

Cesarean section is performed with obstetric indications

Expectant Management; increased incidence of fetal neurological damage and clinical chorioamnionitis

Cont…

Preterm PROM: The main concern is to balance the risk of infection in expectant management (while pregnancy is continued) versus the risk of prematurity in active intervention. Ideally the patient should be transferred with the “fetus in utero” to an unit able to manage preterm neonates effectively

Cont…

If the gestational age is 34 weeks or more, perinatal mortality from prematurity is less compared to infection

Labor generally starts spontaneously within 48 hours, otherwise induction with oxytocin is instituted

Presentation other than cephalic merits cesarean section

Cont…

When gestational age is less than 34 weeks, conservative attitude generally followed in absence of any maternal or fetal indications

On rare occasion with bed rest, the leak seals spontaneously and pregnancy continues

Corticosteroids to Accelerate Fetal Lung Maturity

Singledose therapy is recommended from 24 to 32 weeks

There is no consensus regarding treatment between 32 and 34 weeks

Corticosteroid therapy is not recommended before 24 weeks

Use of antibiotics: Prophylactic antibiotics are given to minimize maternal and perinatal risks of infection.

Intravenous ampicillin, amoxicillin or erythromycin for 48 hours followed by oral therapy for 5 days or until delivery is recommended.

Membrane Repair Tissue sealants have been used for various

purposes in medicine and have become important in maintaining surgical hemostasis and stimulating wound healing.

Devlieger and colleagues (2006) have reviewed the efficacy of sealants in the repair of fetal membrane defects such as in preterm ruptured membranes.

Magnesium Sulfate for Fetal Neuroprotection

Preterm labor and prematurity; Chorioamnionitis from ascending infection if

>24hrs Cord prolapse specially when associated with

malpresentation Continuous escape of liquor for long duration

may lead to dry labor Placental abruption Neonatal sepsis, RDS, IVH and NEC in preterm

PROM Perinatal morbidities (cerebral palsy) are high

COMPLICATIONS OF PRETERM LABOR AND PROM

William’s 24th edition Dutta’s text book of obstetrics 7th edition

References;

THANK YOU!