“Essential insights”

What obstetricians should

know about preterm neonates
Dr.Nazira Sadique DGO/DNB(OG).,
Dr.Vignesh Kumar S MD.,DM(Neo).,
Consultants Metamorphosis 2024
Cloudnine Hospital,T.Nagar.
Dr S.Vignesh kumar MBBS.,MD Paeds., DM (Neo).,

He is a Neonatologist (DM Neonatology) from our prestigious Madras medical College

(Institute of Child Health and Hospital for children).

He has got 12 years of experience in field of Paediatrics & Neonatology.

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His special area of interest is in Intact survival of Extreme preterm neonates and intensive
neonatal care.
Please

His area of research is functional Echocardiography in neonates & prevention of infections in

children’s.

No of publications in reputed journals:4

Awards: Metamorphosis 2024
1st place in IAP paediatric quiz in district level-2012.

1st place in IAP paediatric quiz in state level-2012.

3rd place in IAP paediatric quiz in national level 2013.

 Synopsis

❑ Introduction
❑ Clinical case scenario
❑ Take home points
Interplay of causes of Preterm Labour syndrome
man not necessarily valid.
Clinical scenario 1
 Clinical scenario 1

❖ Mrs.A,G2P1L1,Booked case,Previous LSCS,Previous child:1.5 yrs

❖ GA:26 wks ,Minimal Draining Per vaginum
❖ Not a known case of Hypertension or DM

❑ Clinical Examination:
❖ Uterus relaxed,FH:good,Liquor adequate
❖ OS open
❖ Minimal clear liquor.

❖ High vaginal swab taken.

❖ Blood investigation:CBC/CRP
❖ USG: Liquor adequate,single deep pocket 3.8cm, EFW:850gms.
CL:2.4cm.
 Case 1 cont…

❑ Patient admitted
❑ IV antibiotics started.
❑ Patient is having frequent painful contractions.

Dr Vignesh

Are we justified in giving steroids to this patient?

 Candidates for a first antenatal corticosteroids course

Gestational Age UpToDate

23+0 to 33+6 weeks Yes
Indications: Induction/cesarean for obstetric or medical
indications
Preterm prelabor rupture of membranes

Tocolysis for active preterm labor

WHO recommendations(2022)
 A single course of corticosteroids is recommended for pregnant
women between 24 0/7 weeks and 33 6/7 weeks of gestation who are
at risk of preterm delivery within 7 days, including for those with
ruptured membranes and multiple gestations
Candidates for a first antenatal corticosteroids course

Not considered
<22+0 weeks candidates for
ACS

Moore KL, Persaud TVN. The respiratory system. In: The Developing Human, 5th ed, WB Saunders, Philadelphia 1993. p.226.
Candidates for a first antenatal corticosteroids course

22+0 to
22+6 wks Counselling
Aggressive
neonatal
resuscitation
 Case 1 cont….
Dr.Nazira

What are the predictors that this patient might

progress to preterm birth?
 Predictors of Preterm labour

❑Cervical length (CL) measured by transvaginal

ultrasound (TVUE)
❑It identifies women at risk to benefit from
corticosteroids or in utero transfer.

Best Pract Res Clin Obstet Gynaecol. 2018 Oct:52:23-32.doi: 10.1016/j.bpobgyn.2018.05.002. Epub
2018 Jul 7.Predictors of preterm birth Yves Ville 1, Patrick Rozenberg 2
 Predictors of Preterm labour

❑ Asymptomatic women at risk, should be screened from 16-18

weeks, every 2 weeks up to 24 weeks.

❑ 15% of unjustified hospitalizations and treatment could be

avoided.

Best Pract Res Clin Obstet Gynaecol. 2018

oct:52:2332.doi:10.1016/j.bpobgyn.2018.05.002. Epub 2018 Jul 7.
Predictors of preterm birth Yves Ville 1, Patrick Rozenberg 2
 Biochemical markers for the prediction of PTD

❑ Markers of intrauterine infection/inflammation:

⮚ Bacterial vaginosis
⮚ CRP
⮚ Cervical IL-1, IL-2, IL-8

❑ Markers of extracellular matrix degradation:

⮚ Cervical fibronectin (fFN)
⮚ Placental alphamicroglobulin (PAMG-1).
Clinical scenario 2
 Clinical scenario 2

❑ Mrs B G2P1L1,GA:28 wks, MCDA twins,previous child:4 yrs

❑ C/O Draining P/V &Lower abdominal pain
❑ Not Hypertensive or diabetic.
❑ Mother had received a complete course of antenatal steroids at
25 weeks in view of impending preterm labour.
❑ Painful&regular contractions.
❑ OS:open,leaking P/V
❑ Lab: CBC,CRP-sent,high vaginal swab taken.
❑ USG scans:
Fetus A:900 gm,Fetus B:750 gm.
No evidence of abruption.,FH:good.CL:1.5cm.
 Dr.Vignesh

Are we justified in giving repeat dose of AN steroids in this case?

 USE OF RESCUE (SALVAGE, BOOSTER) ACS

American College of • A single repeat dose of betamethasone 12

Obstetricians and
mg rather than the standard two doses of
Gynecologists (ACOG)
12 mg 24hours apart is reasonable.
recommends:
 USE OF RESCUE (SALVAGE, BOOSTER) ACS

Rescue ACS can be provided

<34+0 weeks as early as seven days from
the prior dose

Walters A, McKinlay C, Middleton P, et al. Repeat doses of prenatal corticosteroids forwomen at risk of preterm birth for improving
neonatal health outcomes. CochraneDatabase Syst Rev 2022; 4:CD003935
 USE OF RESCUE (SALVAGE, BOOSTER) ACS

Recommendation should only be applied to women between 24 and 34 weeks

of gestation at time of the repeat course

Administration to women with a pregnancy >34 weeks’ gestation should be

avoided.

WHO recommendations on antenatal corticosteroids for improving preterm birth

outcomes. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.
 REPEATED OR RESCUE COURSES
clinics in perinatology-Alan Jobe

Repeat courses of antenatal corticosteroids may improve neonatal pulmonary status

Repetitive retreatment may be harmful.

US NICHD trial undelivered pregnancies were retreated weekly until 34weeks gestation

64% of infants had 4 or more repeat courses.

Significant reduction in birth weight

Increase in small for gestational age infants

 Case scenario 2
Dr.Vignesh

What are the long term implications in this fetus exposed

to antenatal steroids ?
 Dr.Vignesh
Betamethasone or Dexamethasone?
 Betamethasone VS Dexamethasone

Betamethasone VS Dexamethasone
Betamethasone VS Dexamethasone

Betamethasone phosphate Dexamethasone

phosphate
Dose 2 doses 4 doses
12 mg(3 ml) 6 mg(1.5ml)
24 hrs apart 12 hrs apart
Onset of action Rapid Rapid
Duration of action Longer Shorter
Half life(t1/2) 2 times more less

Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and

Dexamethasone in Reproductive Age Women in India Clin Transl Sci (2020) 13, 391–399;
doi:10.1111/cts.12724
 Betamethasone phosphate VS Dexamethasone
phosphate
Betamethasone Dexamethasone
IVH Less
Cost Less Less
Widespread availability Yes Yes
WHO essential medicine No Yes
list
Fetal biophysical profile More effect Less effect
Injections 2 4
PVL Less More
Long term More studies Ongoing studies
neurodevelopment
 Clinical case scenario 2

Dr.Vignesh

Any other antenatal intervention which can improve

neurodevelopmental outcomes in this infant?
 Magnesium Sulphate

Neuroprotection
Less than 32 weeks’ gestation

Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008;359(9):895–905.
Brookfield KF, Vinson A. Magnesium sulfate use for fetal neuroprotection. Curr Opin Obstet Gynecol 2019;31(2):110–5.
 MOA of MgSO4

❑Calcium channel antagonist

❑Prevent excessive activation of NMDA receptors

Inhibit the proinflammatory pathway

Tang J, He A, Li N, et al. Magnesium Sulfate-Mediated Vascular Relaxation and Calcium Channel Activity in Placental
Vessels Different From Nonplacental Vessels.
J Am Heart Assoc 2018;7(14)https://doi.org/10.1161/JAHA.118.009896.
 BEAM trial
❑ 6 g IV loading dose administered over 20 to30 minutes
followed by an IV maintenance infusion of 2 g/h.

❑ Rate of moderate or severe cerebral palsy was reduced in

the magnesium group compared with the placebo group
(1.9% vs 3.5%; P 5.03).

Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral
palsy. N Engl J Med 2008;359(9):895–905.
 (ACTOMgSO4)

❑ Less than 30 weeks’ gestation

❑ 4 g IV loading dose administered during 20 minutes

followed by 1 g/h IV maintenance dose (ACTOMgSO4).

❑ Reduced rates of motor dysfunction

Crowther CA, Hiller JE, Doyle LW, et al. Australasian Collaborative Trial of Magnesium Sulphate
Collaborative G. Effect of magnesium sulfate given for neuroprotection before preterm birth: a
randomized controlled trial. JAMA 2003;290(20): 2669–76.
 (PREMAG) trial

❑ 4 g IV bolus dose over 30 minutes without a

maintenance dose.

❑ Reduced rates of white matter injury and mortality in

the magnesium group but not statistically significant.

Marret S, Marpeau L, Zupan-Simunek V, et al. Magnesium sulphate given before very-preterm birth to protect
infant brain: the randomised controlled PREMAG trial. BJOG 2007;114(3):310–8.
 META-ANALYSIS
MgSO4
❑ Reduced risk of cerebral palsy in children exposed in
utero to magnesium sulfate
[relative risk(95% CI) 0.7 (0.55–0.89)]

Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34
weeks’ gestation: a systematic review and meta-analysis. Am J Obstet Gynecol 2009; 200:595–609.
Clinical scenario 3
 Clinical scenario 3

❑ Mrs C Unbooked case,GA: 27 wks came to OPD with signs of

imminent eclampsia.decision to stabilize her &take her for
hysterotomy.EFW:800 gms.
❑ One dose of steroids given,
❑ Inj MgSO4 4gm loading given followed by 1 gm/hr
maintenance started.
❑ Delivered by LSCS.
❑ Cried immediately after birth.
 Dr.vignesh

Do you like to recommend any other antenatal

interventions to improve outcome of this
neonate at this point of care?
 Delayed Cord Clamping
ILCOR GUIDELINES
❑Deferring clamping of the umbilical cord for at
least 60 seconds.
(Strong recommendation, high-certainty
evidence).

❑Number needed to treat for benefit (NNTB) 40

Take home points
 Risk factors associated with preterm birth
Risk Factor Comment
Maternal Ethnicity Africans & Africo-
Characteristics caribbeans are at
higher risk
Socio-demographic factors Maternal age
Poverty
Education
Access to health
care services

Nutritional status Low BMI

Overweight
Obese women
Life style Behavioural Depression
Stress
Anxiety

Smoking
Drugs, alcohol
 Risk factors associated
Risk factors
with preterm birth
Comment
Cervical history Cervical Surgery Cone Biopsy
Large excision
transformation zone
Cervical insufficiency Cervical length<25 mm
Pregnancy history Short interpregnancy <6 months
interval
Previous preterm birth or 20% risk of recurrence
mid trimester loss
Current gestation Multiple gestation
IVF Implantation of multiple
embryos
Advanced maternal age
Vaginal bleeding Abruption
Placenta previa
Bacterial vaginosis Overgrowth of Atypical
microorganisms
Asymptomatic
bacteriuria
QUiPP App
Perinatal optimization
 “Essential insights”
What obstetricians should know about preterm
neonates

Dr.Nazira Sadique
Dr.Vignesh kumar S
 Dexamethasone phosphate is preferred to
Betamethasone phosphate:
• Less IVH
• Less injection site reactions
• Reduced need for C section (ASTEROID trial)
• Reduced duration of NICU stay
• Less effect on Fetal Bio-physical profile
• More widely available
• Included in WHO essential medical list