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 Unpublished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


• Altered hormonal milieu


Differential microbiome

Jakobsson et al. Gut. 2014

CSVD

Microbiome and obesity

Turnbaugh et al. Nature. 2006

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

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


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?



following Pre-labour (Elective) Caesarean section compared to

vaginal delivery

Does type of Caesarean section matter?



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

matthew hyde - microbirth - unicef uk · pdf fileassessment of breastfeeding using latch...

Documents