Definition of Preterm Birth Preterm birth, Postterm pregnancy, Fetal growth restriction

Chen-Hsiang Yu Department of Obstetrics and Gynecology, National Cheng Kung University Medical College and Hospital

Infants delivered prior to the completion of 37 weeks ( American College of Obstetrics and Gynecology ) Low birth weight: Newborn birthweight less than 2500 gm Very low birthweight: Newborn birthweight less than 1500 gm Extreme low birthweight: Newborn birthweight less than 1000 gm

Impact of preterm birth

Chances of survival Quality of life ( intellectual and physical ) Lower limit of survival ( 24 wk, 26 wk ) Upper limit of significant prematurity( 1600 gm, 1900 gm) Long-term outcomes

Survival rates by birthweight

Birthweight(gm) 500 750 751 1000 1001- 1250 1051 1750 1751 2000 2001 2500 2501 3000 3001 3500 3501 4000 > 4000 Total Live births 34 52 54 82 138 667 2488 5695 4071 1400 14733 Neonatal death Survival 20 6 6 3 3 11 3 3 1 2 61 41 85 89 96 98 98 99.9 99.9 100 100 99.6

Factors affecting Neonatal Mortality and Morbidity following Preterm Birth

Gestational age Birth weight Congenital abnormality ? Premature rupture of membrane ? Underlying complications

Risk factors of Preterm Births

Epidemiologic factors: Prior preterm birth, black race, teenage or older mothers, low education, low socioeconomic status, cigarette smoking, unmarried or not living with a partner, heavy/stressful occupation, low maternal pre-pregnancy body mass index, poor or excessive weight gain

Causes of preterm birth

Obstetric
1. Antepartum hemorrhage: previa or abruption 2. Preeclampsia 3. Multiple gestations Fetus 1. Polyhydramnios 2. Fetal anomaly

Identification of Women at risk for Preterm Birth

Risk-scorning system: Useless ! Prior preterm birth Cervical dilation and cervical length Vaginosis (anaerobes, Gardnerella vaginalis, Mobiluncus species, Mycoplasma hominis ) Signs and symptoms (show, pain, pressure, watery discharge ) Fetal fibronectin( > 50 ng/ml ) Ambulatory uterine contraction testing

Maternal 1. Cervical incompetence 2. Fibroid of uterus 3. Severe infection: Chorioamnionitis 3. Uterine anomaly 4. Autoimmune disease 5. Trauma Idiopathic

Recurrent spontaneous preterm births according to prior outcomes

First birth Second birth Next birth preterm (%)

Diagnosis of Preterm Labor (ACOG)

Contractions occurring at a frequency of 4 in 20 minutes or 8 in 60 minutes plus progressive change in the cervix Cervical dilatation greater than 1 cm Cervical effacement of 80 percent or greater

Term Preterm Term Preterm

--------Preterm Preterm

5 15 24 32

Preterm Prematurely Rupture of Membrane (PPROM)

Risk factors: Preceding preterm birth, Occult chorioamnionitis, multiple fetuses, abruptio placenta Treatment of PPROM 1. Nonintervention or expectant management, in which spontaneous labor is simply awaited 2. Intervention that may include corticosteroids, given with or without tocolytic agents to arrest preterm labor in order that the corticosteroids have sufficient time to induce fetal maturation

Quality of evidence to support use of corticosteroids to promote fetal maturation

Evidence Neonatal mortality Respiratory distress syndrome Intraventricular hemorrhage Preterm ruptured membrane Delivery at 24 28 weeks Delivery at 29 34 weeks Delivery > 34 weeks Treatment-to-delivery interval < 24 hours 24 hr 7 days > 7 days good good good fair good good Inadequate for or against fair good Inadequate for or against !

Methods used to inhibit Preterm Labor

Bed rest: Not effective ! Hydration and sedation: Not effective Beta-adrenergic receptor agonists: Ritodrine or Terbutaline Magnesium sulfate Prostaglandin inhibitors: Indomethacin Calcium-channel-blockers: Nifedipine Oxytocin analogue ( Atosiban ) Nitric oxide donor drugs: Nitroglycerin Progestin: 17-hydroxypreogesterone caproate 250mg qw Antibiotics: not effective and not recommended

Potential complications of Tocolytic agents

Magnesium sulfate: Beta-adrenergic Respiratory agonists depression Pulmonary edema Weakness diplopia Hyperglycemia Muscular paralysis Hypokalemia Cardiac arrest Hypotension Indomethacin: Arrhythmia Hepatitis Myocardial ischemia Renal failure Nifedipine: Premature closure of Ductus arterisus Transient hypotension Oligohydramnios

Recommended Management of Preterm Labor

Confirmation of preterm labor For GA < 34 weeks and no indication of delivery 1. Fetal and maternal well-being monitoring 2. Tocolysis 3. Glucocorticoid 4. GBS prophylaxis For GA > 34 weeks or Tocolysis is contraindicated: 1. Monitoring labor progression and fetal wellbeing 2. GBS prophylaxis

Post-term pregnancy
Postterm, prolonged, postdate, postmature pregnancy 42 completed weeks ( 294 days ) or more from the first day of the last menstrual period (ACOG)

Perinatal mortality
Gestational age Fetal death mortality (wk) Odds ratio 40 41 42 >43 1.0 1.48 1.77 2.90 Neonatal Odd ratio 1.0 1.24 1.44 1.89

Outcomes in Postterm Pregnancies compared with pregnancies delivered at 40 weeks

Non-stress test ( NST )

Outcome Meconium Oxytocin induction Shoulder dystocia Cesarean section Macrosomia( >4500gm)

40 weeks 19 % 3% 8% 0.7% 0.8 %

Postterm 27 % 14 % 18 % 1.3% 2.8%

Meconium aspiration

0.6%

1.6%

Post-maturity syndrome
Wrinkled, patchy peeling skin Long ,thin body suggesting wasting Advanced maturity ( open-eyed, unusually alert, old, worried looking )

Recommendations by ACOG for evaluation and management of prolonged pregnancies

Antenatal surveillance of postterm pregnancies should be initiated by 42 weeks despite a lack of evidence that monitoring improves outcomes There is insufficient evidence that initiating antenatal surveillance between 40 and 42 complete weeks improves outcome No single antenatal surveillance protocol for monitoring fetal wellbeing in a postterm pregnancy appears superior to another . It is unknown whether induction or expectant management (antenatal surveillance) is preferable in the postterm patients with a favorable cervix There is good evidence that either induction or expectant management will result in good outcomes in postterm patients with unfavorable cervices Prostaglandin gel can be used safely in postterm pregnancies to promote cervical changes and induce labor

Evaluation and Management of Post-term Pregnancy

Women with postterm pregnancy who have an unfavorable cervix can either undergo labor induction or be managed expectantly Prostaglandin can be used for cervix ripening and labor induction Delivery should be effected if there is evidence of fetal compromise or oligohydramnios It is reasonable to initiate antenatal surveillance between 41 and 42 weeks despite lack of evidence that monitoring improves outcomes An nonstress test (NST) and amniotic fluid volume (AFI) assessment should be adequate, although no single method has been shown to be superior Many recommended prompt delivery in a woman with a postterm pregnancy, a favorable cervix, and no other complications

42 completed weeks Certain Stated LMP

Plus Yes Auscultated FHR 17 20 WK or Fundal height between 18 30 WK + 2 cm to LMP WK or Ultrasound before 26 weeks No No Yes

Fetal Growth Restriction

Decreased fetal Movement ?

Uncertain
Oligohydramnios ?

Weekly visits

Induction of labor

Small-for-gestational-age: Body weight below the 10th percentile for their gestational age Fetal growth restriction Metabolic abnormalities: UV PO2, PCO2, pH, lactate, glucose , NRBC, Hb Mortality and morbidity: fetal demise, birth asphyxia, meconium aspiration, neonatal hypoglycemia, hypothermia, abnormal neurologic development Accelerated maturation?

Induction of labor

Fetal growth restriction

Symmetric fetal growth restriction (HC / AC < 95th percentile ) Asymmetric fetal growth restriction Outcome ?

Risk factors for fetal growth restriction

Constitutionally small mothers Poor maternal weight gain and nutrition Social deprivation Fetal infection (TORCH ) Congenital malformations Chromosomal abnormality Primary disorders of cartilage and bone Chemical teratogens Vascular disease Chronic renal disease Chronic hypoxia Maternal anemia Placental and cord abnormalities Multiple fetuses Antiphospholipid antibody syndrome Extrauterine pregnancy

Fetal vascular and biophysical responses in placental insufficiency

Increase umbilical arterial blood flow resistance: S/D Blood flow centralization: low central-to-peripheral (CPR) vascular impedance ration (Brain sparing effect) Chronic placental dysfunction Abnormal brainstem maturation and reflexes Decline in cardiac function, with an increase in venous Doppler indices Normalization of cerebral Doppler indices Decline in global fetal movement, fetal breathing movement, body movement and tone loss Worsening cardiac function reflexes the worsening hypoxemia: abnormal fetal heart rate pattern

Normal umbilical artery waveform

Absent end-diastolic velocity waveformReverse end-diastolic velocity waveform

Fetal vascular and biophysical responses in placental insufficiency

Early circulatory abnormalities: abnormal umbilical artery flow, CPR and brain sparing effect Late circulatory abnormalities: oligohydramnios, loss of fetal tone or movement, abnormal venous flow, overt heart rate deceleration

Biophysical Profile ( BPP )

Fetal body movement Fetal breathing movement Fetal tone Amniotic fluid index Non-stress test ( NST )

Why combine Doppler and BPP(1)

Fetal deterioration may be manifested through abnormal behavior, central deregulation of cardiorespiratory function, alterations in vascular tone in oxygen-sensitive vessels and cardiovascular dysfunction. The initial alterations in Doppler velocities occur long before there are detectable abnormalities of growth and acid-base balance. (Pre-disease period ) Neither CTG nor BPP alone provide the pre-disease information in the absence of overt signs of compromise The application of Doppler and BPS information in tandem allows an assessment of the immediate fetal condition and the institution of appropriate longitudinal management.

Why combine Doppler and BPP(2)

Delaying delivery by up to 2 weeks can achieve an average weight gain of 200 gm in fetus without affecting overall perinatal mortality Each day, between 25 and 29 weeks, in utero may reduce neonatal mortality by 1- 2 % The combination of the BPP with multivessel arterial and venous Doppler is better in the prediction of critical outcomes than either modality alone (perinatal mortality, acidemia at birth, major neonatal morbidity)

Management of Growth-restricted fetuses

Growth restriction near term : prompt delivery Growth restriction remote from term: (<34 wk) Normal amniotic fluid volume Oligohydramnios Fetal testing ( cardiotocography, Doppler study, and Biophysical profile )