Matthew Hyde - Microbirth - UNICEF UK · PDF fileAssessment of breastfeeding using LATCH...
Transcript of Matthew Hyde - Microbirth - UNICEF UK · PDF fileAssessment of breastfeeding using LATCH...
Microbirth:the science behind a film
Matthew J Hyde PhD
Neonatal Medicine, Imperial College London, Chelsea and Westminster Campus.
What attracted film makers to focus on
Caesarean section?
Effects of Caesarean section: Short-term
• Neonatal morbidity and mortality (Villar, 2007)
• Delayed lung maturation (Faxelius, 1983)
• Altered hormonal profile (Hagnevik, 1984)
• Poor thermogenesis (Christensson, 1993)
• Altered metabolism:
We have known this for a long time!
Effects of Caesarean section: Long-term
Effects of Caesarean section: Long-term
Long term
• Asthma (Thavagnanam, 2008)
• Type 1 Diabetes Mellitus (Cardwell, 2008)
• Coeliac Disease (Marild, 2012)
• Atopy (Bager, 2008)
All immune related conditions …
… What about obesity?
Mode of delivery and BMI in adulthood
Unadjusted mean BMI difference between adults born by Caesarean
section (all types) and vaginal delivery
Darmasseelane et al. PLoS One 2014
Meta Analysis (n > 35,000)
Conclusion: Caesarean Delivery associated with increased BMI in adulthood
(0.44 units [95%CI 0.17-0.72])
Mode of delivery and obesity in adulthood
Unadjusted odds ratio for incidence of obesity between adults born by
Caesarean section (all types) and vaginal delivery
Darmasseelane et al. PLoS One 2014
Meta Analysis (n > 35,000)
Conclusion: Caesarean Delivery associated with increased odds for obesity in
adulthood (OR 1.22 [95%CI 1.05-1.42])
Mode of delivery and BMI in childhood
Darmasseelane et al. Unpublished
Unadjusted mean difference in BMI z-score
Participant level meta analysis (n > 500,000 children)
Conclusion: Caesarean Delivery associated with increased BMI z-score in
childhood (Mean difference in BMI z-score = 0.12 [95%CI 0.09-0.16])
When adjusted for maternal BMI and birth weight:
Mean difference in BMI Z-score 0.07 (95%CI 0.04, 0.10)
Why the link?
N.B. not a proven causal link; no Randomised controlled trial data
But there are plausible biological mechanisms:
• Differential microbiome
• Altered hormonal milieu at birth
• Breastfeeding success
Focus on later life obesity
Plausible biological mechanisms
• Differential microbiome
• Altered hormonal milieu
• Breastfeeding success
Differential microbiome
Jakobsson et al. Gut. 2014
CSVD
Microbiome and obesity
Turnbaugh et al. Nature. 2006
Plausible biological mechanisms
• Differential microbiome
• Altered hormonal milieu
• Breastfeeding success
Parameter Study
Plasma Concentration
P-value
CS
neonates
VD
neonates
Noradrenaline (nmol∙l-1) (Otamiri, 1991) 9.9 33.5 < 0.05
(Faxelius, 1984) 13.9 21.4 NS
(Faxelius, 1983) 3.4 14.1 < 0.01
(Hagnevik, 1984) 5.8 31.0 < 0.01
(Jones and Greiss, 1982) 12.8 22.7 < 0.01
(Zanardo, 2006) 2.7 5.8 < 0.01
(Agata, 1995) 30.4 69.93 < 0.05
Adrenaline (nmol∙l-1) (Otamiri, 1991) 3.6 4.7 NS
(Faxelius, 1984) 1.3 4.3 < 0.05
(Faxelius, 1983) 0.6 2.6 NS
(Hagnevik, 1984) 1.1 4.2 < 0.05
(Jones and Greiss, 1982) 4.2 10.8 < 0.01
(Agata, 1995) 3.2 6.5 < 0.05
Cortisol (nmol∙l-1) (Faxelius, 1983) 196 663 < 0.01
(Bird, 1996) 271 512 < 0.05
(Dobric, 1998) 435 629 < 0.05
(Zanardo, 2006) 125 393 < 0.001
Altered hormonal milieu
Metabolic processes at birth
At birth, neonatal blood glucose is maintained by initiation of
• Breakdown of liver glycogen stores
• Release of fatty acids from adipose tissue
• Gluconeogenesis
• Onset of enteral feeding
This is driven by increased secretion of
• Catecholamines (adrenaline/noradrenaline)
• Glucagon : insulin
• Thyroid hormones
Mode of delivery and metabolism
(Values are least square means; error bars show SEM;
PLCS n=6, VD n=6)
p < 0.001
0
0.5
1
1.5
2
2.5
3
3.5
4
PLCS VD
Mode of Delivery
Liv
er
lip
id c
on
ten
t
(g∙1
00
g o
f li
ve
r ti
ssu
e-1
)
-100
-50
0
50
100
-150 -100 -50 0 50 100 150
t[2]
t[1]
PCA_6.M4 (PLS-DA), CS vs VD
t[Comp. 1]/t[Comp. 2]
Colored according to classes in M4
R2X[1] = 0.128653 R2X[2] = 0.0681346 Ellipse: Hotelling T2 (0.95)
2
1
SIMCA-P+ 12.0.1 - 2012-04-30 15:31:03 (UTC+0) PLS-DA scores plot from 1H NMR spectra of urine
collected within a week of birth from term infants
(born 38-42 weeks GA) by either CS (●; n = 15) vs.
VD (▲; n = 15)
Data previously presented at the Neonatal Society: Hyde et al. Summer Meeting 2009 & 2012
Piglets: Human Infants:
Transcriptomics – Cluster Plot
CS-FTPN6
CS-FTPN3
CS-FTPN8
CS-FTPN12
VD-FTPN9
VD-FTPN11
VD-FTPN2
VD-FTPN4
Plausible biological mechanisms
• Differential microbiome
• Altered hormonal milieu
• Breastfeeding success
Breastfeeding success
Is breastfeeding linked to obesity?
Effect of Caesarean on breastfeeding initiation
Effect of Caesarean on breastfeeding duration
Does type of Caesarean matter?
Does breastfeeding reduce obesity?
Yan et al. BMC Public Health. 2014
Most recent meta analysis comparing ever vs never breastfed
Conclusion: Babies who were ever breastfed had an reduced odds of obesity
(OR 0.78 [95% CI 0.74-0.81]) compared to those who were never breastfed
Meta analysis: ever vs never breastfed and later obesity
Randomised controlled trial data: Probit
Martin et al. JAMA 2013
13,879 children, cluster randomised to receive intervention designed to
increase breast feeding. All mothers initiated breastfeeding.
Conclusion: At 11.5 years there was no difference in mean BMI between the
groups (mean difference 0.16 [95% CI -0.02 – 0.35]).
Instead were more likely to have a BMI ≥ 85th Centile in
the intervention group (OR 1.17 [95% CI 1.01 – 1.39])
Caesarean section and breastfeeding initiation
Prior et al. AmJClinNutr. 2012
Adjusted (maternal BMI) odds ratio initiation of breastfeeding
following Caesarean section (all types) compared to vaginal delivery
Unadjusted odds ratio
Caesarean section and breastfeeding duration
Prior et al. AmJClinNutr. 2012
Unadjusted odds ratio for reports of continuation of breastfeeding at
6 months following Caesarean section (all types) compared to
vaginal delivery
Does type of Caesarean section matter?
Prior et al. AmJClinNutr. 2012
Adjusted (maternal BMI) odds ratio initiation of breastfeeding
following Pre-labour (Elective) Caesarean section compared to
vaginal delivery
Does type of Caesarean section matter?
Prior et al. AmJClinNutr. 2012
Adjusted (maternal BMI) odds ratio initiation of breastfeeding
following In-labour Caesarean section compared to vaginal delivery
Conclusion: Pre-labour Caesarean, but NOT In-labour Caesarean, is
associated with reduced breastfeeding initiation
Can we do anything to change this?: More support?
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
VD ILCS PLCS
Breast
Milk
Mixed Formula
VD (%) 54.8 27.4 17.9
ILCS (%) 36.9 41.7 21.2
PLCS (%) 41.4 27.6 31.0
Chi-Square test, p=0.03
Exclusive Formula Feeding
Exclusive Breast Feeding
Mixed Feeding
Can we do anything to change this?
Perhaps we should start by understanding why
it is occurring?
• Maternal attitudes
• Effect of the disruption of Caesarean
surgery and recovery
• Physiological differences
Physiological mechanisms
• Effects of anaesthesia in both mother and baby
• Absence of the compression of the baby in CS
delivery
• Differences in maternal hormones during lactation
• Differences in initial bonding
• Differential appetite control between CS and VD
babies
Breastfeeding and anaesthesia
Baumgarder, et al. J Am Board Fam Pract. (2003)
Absence of foetal compression during birth
Abel et al. Dev Psychobiol. (1998)
Hormonal control of lactation
Nissen E, et al. Early Human Dev. (1996)
CS VD
Hormonal control of lactation
CS = (n=17)
VD = (n=20)
Nissen E, et al. Early Human Dev. (1996)
Differences in initial bonding
Appetite regulation following Caesarean section
Appetite is regulated by a complex neuro-endocrine
system
Feed back between digestive organs and satiety
centre via a number of peptides
Some evidence the balance of these peptides may
differ between CS and VD babies
This may help explain differences in delay in breast
feeding uptake
Appetite regulation following Caesarean section
Ghrelin :
- Increased in CS babies (p < 0.01) suggesting increased
appetite Chiesa C, et al. Clin Chem. (2008)
Leptin:
- Cord leptin is higher following VD than CS (p < 0.01)
suggesting increased appetite in CS babiesYoshimitsu N, et al. Obstet Gynecol. (2000)
- Cord leptin is positively correlated to cord cortisolPapageorgiou P, et al. J Mat-Fetal Neonatal Med. (2004)
Caesarean section and breastfeeding
Plausible physiological factors driving reduced
breastfeeding after Caesarean section
But NO proven cause
Urgent need to identify causal factors so we can tailor
support accordingly
In the mean time, babies born by Caesarean section
deserve the highest levels of support possible
What about preterm babies?
Preterm infants at disadvantage for healthy microbiome
- Immaturity
- PROM
- Antibiotic use
- Higher CS rate
- H2 blockers for reflux
- Periods of fasting
- Parentral nutrition
- Less human milk exposure
- Sterile environments
Preterm vs term microbiome
Arboleya, et al. FEMS. (2012)
Preterm vs term microbiome
Long term outcomes unknown
Supporting women to provide breastmilk for their infants
Further studies to understand impact of donor milk
Longitudinal follow-up studies of preterm infants
Take home messages
Babies born by Caesarean section have unique needs
Considering mode of delivery is relevant in clinical decision making
The long term effects of Caesarean section are only beginning to
become apparent – this is a space which needs watching very
carefully
Pregnant women have a right to be properly informed about long
term effects associated with Caesarean section
Preterm babies have a particular disadvantage when it comes to
developing a healthy microbiome
Acknowledgements
Professor Neena Modi
All my colleagues in the Neonatal Medicine Research Section
Collaborators:
Professor Elaine Holmes, Dr Julian Marchesi, Dr Robert Boyle, at Imperial
College London
Professor Dame Tina Lavender, University of Manchester
CS and breastfeeding LATCH score
Assessment of breastfeeding using LATCH
scoring:
L = How well infant latches to the breast
A = Amount of audible swallowing
T = Mother’s nipple type
C = Mother’s level of comfort during feeding
H = Support the mother requires to help her hold the infant to feed
Cakmak H, et al. Int J Nursing Studies. (2007)
CS and breastfeeding LATCH score
Breastfeeding point averages
Groups
First
breastfeeding
Second
breastfeeding
Third
breastfeeding p
X ± SD X ± SD X ± SD
Vaginal delivery
(n=82)7.46 ± 0.97 8.70 ± 0.82 9.75 ± 0.45 p<0.001
Caesarean delivery
(n=118)6.27 ± 1.51 7.80 ± 0.91 8.81 ± 0.80 p<0.001
Cakmak H, et al. Int J Nursing Studies. (2007)
CS and delayed initiation of breastfeeding
500 infants born at Port Harcourt General Hospital in Nigeria 1992-93
Mean time of breastfeeding initiation was
VD: 3.35 -/+ 2.6 hours
CS with GA: 6.50 +/- 3.4 hours
CS with spinal 5.9 +/- 1.9 hoursAwi DD, et al. Niger J Clin Pract. (1995)
2064 women who gave birth in Taiwan June-Oct 2003
Breastfeeding initiation within 30 minutes of birth
CS = 7.6 % vs. VD = 19.0 % p<0.001
Exclusive breastfeeding on discharge
CS = 14.2 % vs. VD = 20.2 % p<0.001
More babies of CS mothers received some breast milk during lactation,
but the % of exclusively breastfed babies was lowest in CS babiesChein L, et al. Birth. (2007)
Why is the timing of the first breastfeed important?
Nakao, Y et al. Int Breastfeed J. (2008)
The physiological importance of early enteral feeding
Effect of type of feed on body composition over the 1st year
Gale et al. Am J Clin Nutr 2012
Meta analysis of almost 1000 infants
Conclusion: Breast feeding is associated with significantly increased fat mass
deposition during the first six months post-birth, but by one year there is a
trend towards higher fat mass in formula fed infants
Rate of weight gain and odds of overweight in infancy
Jones-Smith et al. J Am Dietetic Soc 2007
Prospective study, Mexico, 1997-2005, 163 children
Conclusion: Growth in the first year predicts overweight at age 4-6