Neurodevelopmental The Neuroscience of Birth & Breastfeeding The DNA The Brain Behaviour Approach to EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY

Dr Nils Bergman ”M.D., D.C.H., M.P.H., Ph.D.” Cape Town, South Africa “needed neural processes” www.skintoskincontact.com

The Neuroscience of Birth & Breastfeeding The Neuroscience of Birth & Breastfeeding The DNA The Brain Behaviour The DNA The Brain Behaviour EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY

ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS

EXPECTED UNEXPECTED BABY MOTHER SEPARATION BIRTH BONDING Sensitization Toxic stress

Insensitive parenting “buffering Disordered “except in the light attachment of mother’s body.” protection of Vulnerability adult support” DISEASE

The Neuroscience of Birth & Breastfeeding The Neuroscience of Birth & Breastfeeding The DNA The Brain Behaviour The DNA The Brain Behaviour EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY

ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS BABY MOTHER SEPARATION BABY MOTHER SEPARATION

BIRTH BONDING Sensitization Toxic stress BIRTH BONDING Sensitization Toxic stress

Insensitive BEYOND BREASTFEEDING Insensitive parenting Feed  Sleep Cycling parenting

Disordered Secure Attuned Disordered ZERO attachment attachment parenting attachment Resilience Vulnerability

SEPARATION HEALTH DISEASE

1 BIRTH Neurodevelopmental Breastfeeding behaviour Approach to S S C Breastfeeding WIRING BREASTFEEDING ON-GOING

BIRTH

Breastfeeding behaviour BONDING Sensitization S S C Breastfeeding WIRING SENSORY BRAIN BREASTFEEDING ON-GOING

SENSORY BRAIN S S C stimulation nutrition S S C stimulation nutrition BREASTFEEDING STATE organization BRAIN Feed  Sleep Cycling Feeding frequency SLEEP cycling WIRING STATE organization BRAIN Feeding frequency

SLEEP cycling WIRING

BIRTH

Breastfeeding behaviour

S S C Breastfeeding WIRING

WIRE BABY There are “needed neural processes” !

... these data indicate ... these data indicate that pups have a unique that pups have a unique learning circuit relying on learning circuit relying on the olfactory bulb for the olfactory bulb for neural plasticity and on neural plasticity and on the hyperfunctioning noradrenergic locus the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. norepinephrine to support the neural changes.

2 Simulated birth (rat) Simulated birth (rat)

The first hours after birth are a CRITICAL PERIOD No compression Nil Those babies In the 14 babies older than 24 h Wrong smell showing the there was greatest no significant increase in difference [Hb O2] were between the between 6 and changes in [Hb 24 h old at O2] during control and colostrum testing Simulated birth (rat) exposure

DOUCET

The secretion of Areolar (Montgomery’s) Glands from The secretion of Areolar Lactating Women Elicits Selective, Unconditional (Montgomery’s) Glands Responses in Neonates

“… breast chemosignals “In early ontogeny the activate oral activity on the sleeping brain may thus nipple that releases a cascade remain sentient of an of behavioral, neural, neuroendocrine organism’s odor and endocrine processes environment.” in the newborn and the mother.” Doucet 2009 17 Doucet 2009 18

3 Fewer AG  delayed grasp

Fewer AG  Slower latch Fewer AG  Weaker suck

Fewer AG  Difference p <0.001 More weight loss day 3 of life Primip high AG 2.3 days Fewer AG  Primip low AG 3.1 days Delayed onset of lactation

In the ‘‘scentless breast’’ (1) ‘‘Breast’’group (fully condition, all infants were uncovered mother’s breast); exposed to the mother’s breast (2) ‘‘Nipple’’group (all remaining fully covered with a perfectly parts covered with plastic film); transparent and airtight plastic (3) ‘‘Areola’’group (remainder of film (polypropylene). the breast and nipple covered); ( the habitual visual scene of (4) ‘‘Milk’’group (milk smeared the breast devoid of An overlooked aspect of the human breast: Areolar glands in relation with on plastic covered breast) breastfeeding pattern, neonatal weight gain, and the dynamics of lactation. corresponding odors ) Doucet 2012

4 Grey bar – odourless … only male newborns opened their eyes longer in plastic film response to odorous breast conditions than to the Black – pooled odors. scentless condition (0.654 vs. 0.425; p<.01).

They displayed significantly longer global oral activity when facing any of the odorous breast with opened eyes, the three other conditions being equivalent ‘‘Breast’’group 0.102 more than odorous breast / opened eyes: 13.27 ‘‘Areola’’group 0.038 odorous breast / closed eyes: 9.92 more than scentless breast / opened eyes: 6.63 ‘‘Milk’’group 0.035 scentless breast / closed eyes: 8.39

Babies more often spontaneously selected a breast treated with a small amount of their own AF applied to the nipple/areola region, than the alternative untreated Related experiments indicate, however, that the breast, during tests beginning several minutes after chemical cues that attract rat pups to the nipples parturition [112]. are not produced in that region. Rather, initial nipple orientation is elicited by the odor of These results are corroborated by a study in which 2- amniotic fluid and saliva that the mother spreads day-old infants were offered a simultaneous choice on her ventrum while grooming herself during between two gauze pads; the length of time oriented parturition [7]. to the odor of their AF was reliably greater than that towards an odorless stimulus pad [92].

Target #1 for 2005: PSN envisions a community that embraces its mothers and babies, and Report that 65% of infants are values the unique placed and remain in opportunity at birth direct skin to skin contact to impact the physical and emotional with their mothers well-being of the newborn. for at least one hour during the first 3 hours after birth.

5 Skin-to-skin and breastfeeding (4)

100 90 80 70 Babies breastfeeding 60 50 40 Mothers intending 30 20 to breastfeed 10 0 3Q05 4Q05 1Q06 2Q06 3Q06 4Q06 1Q07 2Q07 Breastfeeding intention Skin-to-skin one hour Breastfeeding at discharge Breastfeeding by the Neonate

Used with permission: Ruth Stanhiser, MD Registration by skin-to-skin contact

More skin-to-skin  more breastfeeding

Salariya 1978

E Early SSC first hour L Late contact next day 2 2 hourly feeds from birth 4 4 hourly feeds from birth

Group Brf at 12 w Brf duration (days) 2E 64.3% 182 (14 - 392) 4E 55.6% 140 (14 – 322) 2L 55.6% 112 (10 – 294) Thomson 1979 4L 46.2% 77 (11 – 280)

6 DEFENSE NUTRITION REPRODUCTION DEFENSE NUTRITION REPRODUCTION SAFE

HORMONES NERVES MUSCLES HORMONES NERVES MUSCLES = BREASTFEEDING

BIRTH

Breastfeeding behaviour The Neuroscience of Birth & Breastfeeding The DNA The Brain Behaviour S S C Breastfeeding WIRING EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY

ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS BABY MOTHER SEPARATION BIRTH BONDING Sensitization BEYOND BREASTFEEDING Feed  Sleep Cycling

Secure Attuned attachment parenting

WIRE MOTHER OXYTOCIN

7 OXYTOCIN comes from Effects of doula care No doula Doula USA (Kennell et al 1991)

Cervical dilatation Epidural 55% 8% Breastfeeding Caesarean section 18% 8% Forceps delivery 26% 8% OXYTOCIN Skin-to-skin contact Fetal distress 24% 10%

Eye-to-eye contact

“If a Doula was a drug, EARLY CHILDHOOD DEVELOPMENT ECD

it would be unethical “First 1000 days” = not to use it” gestation 270 Dr. John Kennell year one 365 year two 365 total 1000 days

Resilience Vulnerability

1922 -2013 Marshall Klaus & John Kenell HEALTH DISEASE

EARLY CHILDHOOD DEVELOPMENT ECD DOULA- “First 1000 days” = “A WOMAN SERVING WOMEN” BIRTH SUPPORT COMPANION First 1000 sec = 16 minutes = 1st hour First 1000 min = 16,6 hours = 1st day KANGAROO CARE & DOULA = First 1000 hrs = 1st six weeks “KANGAROULA”

Resilience Vulnerability Resilience Vulnerability

HEALTH DISEASE HEALTH DISEASE

8 DOULA and KANGAROULA DOULA and KANGAROULA BIRTH ‘the first 1000 minutes’ ‘previous 1000 minutes’

DOULA KANGAROULA protects protects OXYTOCIN OXYTOCIN BIRTH during after -1000 min +1000 min labour. birth.

DOULA and KANGAROULA DOULA and KANGAROULA

Hunger ”good night’s sleep” thirst Lights SEPARATION

Zero separation Crowds Noise Zero separation Weighing Bathing Lithotomy Perfume SEPARATION Zero separation White coat Caesarean

Breastfeeding Sarcasm OXYTOCIN OXYTOCIN BIRTH BIRTH Separation -1000 min +1000 min 1000 days -1000 min +1000 min 1000 days

CORTISOL  Enemy of oxytocin Stress

Pregnancy Labour Birth Transition Parenting

DOULA

MOTHER NEWBORN SUPPORT SUPPORT Prematurity Breastfeeding Attachment Parenting Counselling Counselling KANGAROULA During the first 24 hours of life newborns ingested 15 g of milk.

9 OXYTOCIN “The newborn may Cingulate Maternal Cingulate Suppressed ferocity appear helpless, but Hypothalamus PROTECTION Pituitary: Hypothalamus Amygdala Pituitary: skin-to-skin contact PROLACTIN  Milk making NUTRITION stimulates prolactin Amygdala: CHOLECYSTOKININ ensures nutrition  Emotion / satiety stimulates oxytocin REGULATION ensures protection OXYTOCIN stimulates cholecystokinin  Gaze increase:  BONDING ensures wellbeing bonding

The first hours after birth are a Critical period concept : CRITICAL PERIOD “Windows of opportunity in early life when a child’s brain is exquisitely primed to receive sensory input in order to develop more advanced neural systems.”

mutual a mother’s brain … psycho-neuro-physiological SENSITIZATION caregivers

BIRTH DOULA and KANGAROULA Breastfeeding behaviour

BIRTH S S C Breastfeeding WIRING ‘the first 1000 minutes’ ‘previous 1000 minutes’ OXYTOCIN DOULA KANGAROULA protects protects OXYTOCIN OXYTOCIN during after labour. birth. WIRE MOTHER

10 BIRTH

Breastfeeding behaviour

S S C Breastfeeding WIRING … infant cues - suckling, vocalisation and tactile BREASTFEEDING ON-GOING stimulation - stimulate OXYTOCIN OXYTOCIN release in the S S C hypothalamus, which may result in the activation of the dopaminergic reward pathway leading to behavioural WIRE TOGETHER reinforcement

key biological systems … that contribute to maternal caregiving behaviour … the oxytocinergic and dopaminergic systems.

… dopamine pathways contribute to the processing of infant-related sensory cues leading to a behavioural response. c

The psychology of human parent-infant relationships Parenting is regulated by key hormones and neurotransmitters Neuroanatomical circuits of parenting Integrative physiology of normal parenting behaviours Brain imaging of human parent-infant relationships HEALTH DISEASE The neurobiology of empathy and parenting Conclusions and critical summary OXYTOCIN CORTISOL (Swain et al, 2007)

11 SOCIAL REWARD CONTROL CONTROL CENTRE CENTRE DOULA and KANGAROULA DOPAMINE OXYTOCIN

CORTISOL EMOTION FEAR CONTROL CONTROL Zero separation CENTRE CENTRE Protect OXYTOCIN … there is considerable overlap in the brain structures Before and after associated with these neural mechanisms … functional

interactions among the circuits. OXYTOCIN BIRTH BIRTH

HEALTH DISEASE -1000 min +1000 min 1000 days RESILIENCE VULNERABILITY WELL-BEING  SUSCEPTIBILITY  MORBIDITY  MORTALITY

BIRTH BIRTH

Breastfeeding behaviour Breastfeeding behaviour

S S C Breastfeeding WIRING S S C Breastfeeding WIRING

BREASTFEEDING BREASTFEEDING ON-GOING ON-GOING Protect OXYTOCIN S S C Before and after S S C BIRTH

WIRE TOGETHER WIRE SUCKLING

Neurodevelopmental Approach to DUAL INGESTION SYSTEMS

BIRTH Alberts: Breastfeeding behaviour BONDING Sensitization S S C Breastfeeding WIRING BREASTFEEDING ON-GOING SENSORY BRAIN SUCKLING versus FEEDING S S C stimulation nutrition

BREASTFEEDING STATE organization BRAIN Feed  Sleep Cycling Feeding frequency SLEEP cycling WIRING

12 Placentals Mammals Mammaliaformes

Cynodonts ANCESTRAL STATE

Synapsids

Amniotes

… into MATURE 300 mya 200 mya 100 mya 50 mya FEEDING300 mya 200 mya 100 mya 50 mya

Placentals Mammals Diphyodontism Mammaliaformes Viviparity = immature ENDOTHERMY Epibubic bone = pouch care WATER Cynodonts Smaller eggs; longer in body e.g. TURTLES ANCESTRAL STATE EGGS MOISTURE The AMNIOTE EGG for eggs extra membranes Hatch with CROCODILES Synapsids TEETH !! DINOSAURS Copes with AIR REPTILES Amniotes

… into … into MATURE MATURE FEEDING300 mya 200 mya 100 mya 50 mya FEEDING300 mya 200 mya 100 mya 50 mya

DUAL INGESTION SYSTEMS Antimicrobials Antimicrobials NUTRIENTS NUTRIENTS Placentals Placentals LACTOSE added Mammals Diphyodontism LACTOSE added Mammals (apocrine glands) (apocrine glands) Mammaliaformes Mammaliaformes ENDOTHERMY LACTATION ENDOTHERMY LACTATION Cynodonts Cynodonts

MOISTURE MOISTURE for eggs for eggs Synapsids Synapsids 100 million years 200 million years 200 million years Amniotes Amniotes FEEDING SUCKLING FEEDING SUCKLING … into … into MATURE MATURE FEEDING300 mya 200 mya 100 mya 50 mya FEEDING300 mya 200 mya 100 mya 50 mya

13 DUAL INGESTION SYSTEMS DUAL INGESTION SYSTEMS

SUCKLING WEANING FEEDING FEEDING SUCKLING

Lactase Digestive Influence of SMELL None Totally dependent enzymes Motor mechanism Chewing – different Suckling – different circuits muscles

INSULIN Increases weight No effect GHRELIN Increases weight No effect LEPTIN Decreases intake No effect CHOLECYSTOKININ Decreases intake No effect AMPHETAMINE Decreases appetite Increases suckling SEROTONIN Agonist improves feeding Antagonist improves suck

SATIETY Infant determined Maternal supply determine

FEEDING SUCKLING

DISRUPTION ROBUST VERY SENSITIVE Must have right conditions Pup-in-a- cup - Pup-in-a- cup - And STIMULI separated and fed by tube separated and fed by tube From day 2 off life  From day 2 off life  Starts to feed normally d21 Starts to feed normally d21 2 days gavage or other, no longer suckles If starved for 24 hours, pup at d3 will feed food from floor. (Can be maintained by smell and other stimuli)

14 Nils’ IDEALIZED VIEW !

PMA 28 40 64 1y 2y

Nils’ IDEALIZED VIEW ! Nils’ QUESTIONS … NICU context?

PMA 28 40 64 1y 2y PMA 28 40 64 1y 2y

Nils’ QUESTIONS … NICU context? Reflections for practice

SUCKLING IS COMPETENT FEEDING IS IMMATURE Suckling and Feeding are NOT THE SAME

PMA 28 40 64 1y 2y

15 BIRTH BIRTH

Breastfeeding behaviour Breastfeeding behaviour

S S C Breastfeeding WIRING S S C Breastfeeding WIRING

BREASTFEEDING BREASTFEEDING ON-GOING ON-GOING

SENSORY BRAIN S S C S S C stimulation nutrition

WIRE SUCKLING WIRE NEURONS

TRIGLYCERIDE Left : glycerol, Right: palmitic acid, oleic acid, alpha-linolenic acid Up to 6 months, In phosphoglycerides, milk is 7.4% fat, glycerol molecule same: two fatty acids esterified

96% of this is TRIGLYCERIDE Phospholipids are a major component of all biological membranes, Sphingomyelin particularly concentrated in BRAIN major part of MYELIN.

TRIGLYCERIDE MYELIN. FATTY ACIDS ARE SPECIES SPECIFIC Up to 6 months, milk is 7.4% fat,

but after 12 months it is 10.7% Dendirification and myelinisation peaks occur at 2 and 6 months is maximal at one year .... At one year: human milk has less protein, but MORE TRIGLYCERIDE !!!

16 “cherry pick”

Breastfeed time years school Income < 1 month 10.9 R$ 1238 > 6 month 12.1 R$ 1915

Group IQ 3.76 points higher from breatsfeeding

BREASTFEEDING AND BREAST MILK

INCREASE IQ

BOTTLE FEEDING & FORMULA

DECREASE IQ

17 Be sure the wet nurse has plenty of milk ... because if she lacks it she may give the baby milk of a goat or sheep or some other animal, because the child ... nourished on animal milk Conceptual change: does not have perfect wits like one fed on Dyad care woman’s milk and always looks stupid and Breast first hour vacant and not right in the head. even Caesarean 14th century Tuscan text Continuous SSC

CHANGE POLICY: Can’t change biology: DISCONTINUE: Giving water Glucose water Infant formula Separation Pacifier (dummy)

BIRTH BIRTH

Breastfeeding behaviour Breastfeeding behaviour

S S C Breastfeeding WIRING S S C Breastfeeding WIRING

BREASTFEEDING BREASTFEEDING ON-GOING ON-GOING

SENSORY BRAIN S S C stimulation nutrition S S C WIRE STATE organization

Feeding frequency TIMING (behavior) WIRE NEURONS SLEEP cycling

18 REM REM REM Not so much duration, or density of any sleep stage, or number of sleep stage episodes, but, NREM NREM cycling between quiet sleep This is a healthy sleep pattern and active sleep This is a very good cycling pattern

is what is important (thanks to Susan Ludington-Hoe)

REM State REM REM REM REM REM

NREM NREM NREM HR

NREM NREM RR 1st hour 2nd hour REM Sleep is supposed to be So in every hour, you would like somewhat active, so to see an EEG pattern that shows this HR increases and RR is irregular

SLEEP CYCLING – SLEEP CYCLING – Separation vs contact Separation vs contact

48 hour baseline chaotic pattern of 48 hour baseline chaotic pattern of Pre-KC SSC activity and quiet HR & RR activity and quiet HR & RR In separation: In SSC: • Dissociated state • Normal cycling • No cycling, chaotic pattern • Non-chaotic pattern

19 SMELL DOUCET The secretion of Areolar (Montgomery’s) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates

modulates state organisation “… breast chemosignals elicits emotional behaviours activate oral activity on the activates pre-feeding actions nipple that releases a cascade anticipatory digestive physiology of behavioral, neural, neuroendocrine regulates pace of ingestive behaviour and endocrine processes in the newborn and the mother.” Schaal 2004 115 Doucet 2009 116

REM

The secretion of Areolar feed FEEDING &HANDLING (Montgomery’s) Glands sleep SLEEPING & CONTAINING “In early ontogeny the sleeping brain may thus NREM remain sentient of an organism’s odor A skin-to-skin contact environment.” session SHOULD NOT be less than one hour HO Doucet 2009 117 or 90 minutes!

BIRTH BIRTH

Breastfeeding behaviour Breastfeeding behaviour

S S C Breastfeeding WIRING S S C Breastfeeding WIRING

BREASTFEEDING BREASTFEEDING ON-GOING ON-GOING S S C WIRE S S C WIRE STATE organization STATE organization STOMACH Feeding frequency TIMING Feeding frequency

SLEEP cycling (behavior) SLEEP cycling

20 CNS: cortical / subcortical (also to PNS)

ANS: emotional / limbic brain How often should CNS (incl SNS) a neonate feed? ANS ANS: myelinated vagus (NA) ENS ANS: unmyelinated vagus (DMC) sub-diaphragmatic STATE organization

BRAIN Internal Feeding frequency ENS: submucous plexus Somatic myenteric plexus environment SLEEP cycling WIRING 122

ENTERIC NERVOUS SYSTEM !! CEPHALIC PHASE GASTRIC PHASE The digestive system is endowed with its INTESTINAL PHASE own, local nervous system referred to as CNS the enteric or intrinsic nervous system. ANS

ENS

Internal The magnitude and complexity of the enteric Somatic environment nervous system is immense - it contains as FEEDBACK LOOPS many neurons as the spinal cord. 123 124

125 126

21 Fetal stomach appears 4 weeks GA. Hydrochloric acid By 11 weeks, wall capable of muscular important for activation of pepsinogen, contraction. inactivation of microorganisms such as bacteria. Pepsinogen activated by acid into active pepsin, “Patterns of antropyloric motility responsible for the stomach's ability to initiate in fed healthy preterm infants” digestion of proteins. ... the neuroregulatory mechanisms Chymosin responsible for the coordination of antro- is an enzyme whose role is to curdle or pyloric motility and gastric emptying are coagulate milk in the stomach, a process of well developed by 30 weeks of PMA. considerable importance in the very young animal. Hassan 2002 127 128

CEPHALIC PHASE milk GASTRIC PHASE INTESTINAL PHASE

Chymosin makes the milk into “cheese” halfway between liquid and solid FEEDBACK LOOPS

stomach empties in 60 minutes 129 130

EVIDENCE FOR FEEDING FREQUENCY ???? Breastfeeding and mother’s milk: Edmond 2006 131 Strong and consistent evidence 132

22 Only case series ... Cup feeding versus bottle feeding: Insufficient evidence Cup feeding higher breastfeeding No mention of greater stability stomach capacity 133 134

4

3.5 Assumption: 3kg baby, requiring 160 ml/kg/day 3 daily requirement = 480ml 2.5 Standard 2 EVIDENCE CARE: 1.5 3 hourly

FOR frequency feeding schedule STOMACH 1 CAPACITY 0.5 0 ???? 0 10 20 30 40 50 60 70 80 volume ingested Edmond 2006 135 136

KEY QUESTION: “Ontogeny of gastric emptying patterns in the human fetus” WHAT IS THE STOMACH VOLUME OF THE NEONATE ??? 137 Sase 2005 138

23 “Growth of the Fetal Stomach in Normal Pregnancies.” Length

Transverse AP diameter

Using +2SD 

Goldstein 1987 139 Goldstein 1987 140

BRADSHAW formula Assumption: 2,5 kg baby 33w GA,

Formula for calculation of stomach capacity (Charles Bradshaw, UCT) requiring 150 ml/kg/day = 375 ml Assumptions: the stomach can be approximated by dividing into three sections, namely a ellipsoidal hemisphere, an ellipsoidal cylinder, and a skewed ellipsoidal cone. Variables: a = anteroposterior radius, t = transverse radius, l = length stomach Relations: the height of the cone and the hemisphere are both the same as ‘a’.

Ellipsoid = 4/3 * Pi* r1*r2*r3 = 4/3 *Pi * a * a * t; therefore volume of hemisphere = 2/3 Pi * a *a * t Cylinder = Area of base * height = (Pi * a * t ) * ( l - 2a ) Skewed cone = 1/3 * base *height = 1/3 * Pi * a * t * a Total volume = 2/3 * Pi *a*a*t + Pi * a * t * (l- 2a) + 1/3 * Pi * a * t * a =Pi a*t*l -Pi * a *a*t = Pi * a * t*(l-a)

Goldstein and Sase data: 45 MIN CYCLES ( 32 cycles/day) 12 ML PER CYCLE = 384 ml Stomach capacity at term 10 - 15141 ml 142

Newborn stomach volume. Only recent study located: “Autopsy” capacity was determined Gastric volumes at birth in Indian post-mortem studies Correlated with gastric pH, “An Autopsy Study of Relationship between gastrin and somatostatin  Perinatal Stomach Capacity and Birth Weight.” 100 autopsies (63 SB, 37 ENND) Tied at cardia and pylorus, filled with “fetus drinks 10 ml portions water, emptied & measured, repeated, of amniotic fluid …” “… obliteration of the gastric curvatures” “due care to minimize stretch artifacts”

Widstrom 1988 143 Naveed 1992 144

24 “An Autopsy Study of Relationship between KERNESSUK 1997 (Russian) Perinatal Stomach Capacity and Birth Weight.” Postmortem: in situ measures Infants above 2500g only: (applied Bradshaw formula) Ave Range Ave Stillborn (n 11) 19.6 ml (10-35) Newborn (n 11) 15 ml Early death (n 9) 17.8 ml (10-25) 2 months (n 11) 35 ml All cases (n 20) 18.8 ml 2-4 m (n 10) 50 ml 4-6 m (n 8) 100 ml

Naveed 1992 145 146

Known references with data: “Observations of the capacity of the stomach in Scammon and Doyle 1920 the first ten days of post natal life.” Anatomic capacity was determined in post-mortem studies “Observations of the capacity of the stomach in Main data set  Alliot 1905 (n 25) the first ten days of post natal life.” Scammon own cases ? (n 13) Zuccarelli’s method: stomach filled at 30 – 35 ml at birth – autopsy to “a pressure of between almost regardless of birth weight 15 and 20 centimeters of water”

Scammon 1920 147 Scammon 1920 148

Zangen S et al Zangen S et al Rapid maturation of gastric relaxation in newborns Rapid maturation of gastric relaxation in newborns

Pressures (mmHg) Pressures (mmHg)

Balloon inflates to Balloon inflates to

15 ml no increase 15 ml no increase 20 ml pressure OK functional capacity physiological

149 capacity …. 150

25 EVIDENCE: (NBn 111009) PROPOSAL: Author Capacity Note: Sase 10-15 ml Live, term fetus The CAPACITY of a Goldstein 10-15 ml Live, term fetus Widstrom 10 mls Live, newborn week old baby’s Zangen 20 mls Live, (pressure) Naveed 20 mls Autopsy (SB) stomach is 20 mls Autopsy (ENND) Kernessuk 15 mls Autopsy (in situ) approx 20 ml. Scammon 30-35 ml Autopsy (water (Alliot) pressure)151 152

4

3.5 Assumption: 3kg baby, requiring 160 ml/kg/day 3 daily requirement = 480ml 2.5 Standard 2 CARE: MOTHER 1.5 3 hourly FUNCTIONAL CAPACITY feeding frequency feeding NATURE: 1 schedule 1 hourly PHYSIOLOGICAL CAPACITY 0.5 schedule 0 RECEPTIVE CAPACITY of stomach 0 10 20 30 40 50 60 70 80 volume ingested 153 INGESTIVE CAPACITY of BABY 154

PROPOSAL: BRAIN CYCLING CEPHALIC PHASE GASTRIC PHASE INTESTINAL PHASE The FEEDING REM NR1 FREQUENCY of the NR2 NR3 NEONATE is NR4 STOMACH FILLING & EMPTYING approx 60 min.

155 156

26 Normal physiology of the Nils’ QUESTIONS … NICU context? Enteric Nervous System

The “niche” (occupation) of a neonate (Alberts) BOND FEED PLAY FEED

SLEEP  SLEEP PMA 28 40 64 1y 2y

“Small and frequent feeds,

according to the sleep cycle”157

FEEDING SUCKLING FEEDING SUCKLING

Influence of SMELL None Totally dependent Influence of SMELL None Current dogma:Totally dependent Motor mechanism Chewing – different Suckling – different circuits Motor mechanism Chewing – different Suckling – different circuits muscles musclesTHE BABY KNOWS WHEN IT HAS INSULIN Increases weight No effect INSULIN Increases weight No effect GHRELIN Increases weight No effect GHRELIN Increases weightHAD ENOUGH!No effect LEPTIN Decreases intake No effect LEPTIN Decreases intake No effect CHOLECYSTOKININ Decreases intake No effect CHOLECYSTOKININ Decreases intake No effect AMPHETAMINE Decreases appetite Increases suckling AMPHETAMINE PROBABLYDecreases appetite Increases NOT suckling !! SEROTONIN Agonist improves feeding Antagonist improves suck SEROTONIN Agonist improves feeding Antagonist improves suck

SATIETY Infant determined Maternal supply determine SATIETY Infant determined Maternal supply determine

WHAT IS THE Assume low resilience STOMACH Assume proportionality  VOLUME OF THE PREMATURE ??

161 162

27 The CAPACITY of a Gastric overfilling syndrome? low birthweight prem from 20ml / 3000g

= 0.007 x BWt (g) 1kg x 0.007 = 7mls

2kg x 0.007 = 14mls 163 164

75 ml per feeding ... ?? ASSUMPTION Zangen S et al Rapid maturation of gastric relaxation in newborns

IMMATURE ???? A balloon in stomach OR can fill to 76 mls OVERWHELMED !!! What does the stomach – without a balloon –

PRESUME: each feed do to 76 mls? .... many aspects of gastrointestinal approximately 75 mls motility are immature in the neonate REFLUX !!!

GER Clues to GER

• Sudden outbursts of crying • Awakens in pain Dr W Sears • Related to feedings • Not easily comforted • “I know baby hurts” • Sour burps, throaty noises • Best when upright

28 Mitchell 2001

Closes AMYLIN pylorus released Pylorus opens

Duodenum Food in empty duodenum

Kerstin Uvnäs-Moberg

HYPOGLYCAEMIA

A babies stomach “Feed intolerance” … empties in … or VOLUME intolerance? 60 minutes. Blood sugar may fall … after 90 minutes ... Options?

29 METABOLIC ADAPTATION SSC Glucose production = Glucose consumption SSC started in the first 20 minutes after birth SNS stress  Glucose consumption INCREASE PSNS dissociation  Separation SSC Cot Glucose production DECREASE Blood glucose (1 hr) 3.17 2.56 HYPOGLYCEMIA

Base excess drop 3.4 1.8 SSC Cot Approximate GLUCOSE Approximate 0h 1h 2h 3h 4h   2 days (Christenson 1992) Blood glucose (1 hr) 3.17 2.56

The Neuroscience of Birth & Breastfeeding Glucose production = Glucose consumption The DNA The Brain Behaviour SSC EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS ENVIRONMENTWHAT IS THE EFFECT OF MATERNAL ABSENCE ON … PSNS dissociation  ENVIRONMENTWHAT IS THE EFFECT OF MATERNAL ABSENCE ON … Separation Glucose production DECREASE TRANSITION NEUROENDOCRINE BEHAVIOURS GENETIC VARIANTS RESILIENCE GENE X ENVIRONMENT BONDING  ATTACHMENT HYPOGLYCEMIA STRESS RESPONES EPIGENETICS MATERNAL NEUROPLASTICITY DOHAD “STABILITY” SSC Cot SLEEP PHYSIOLOGY Approximate GLUCOSE Approximate (MAL) ADAPTATION EEG MRI HRV 0h 1h 2h 3h 4h   2 days MICROBIOTA GUT FUNCTION LONG TERM FOLLOW-UP IMMUNITY HOSPITAL ACQUIRED INFECTION MORTALITY Blood glucose (1 hr) 3.17 2.56 METABOLISM

METABOLISM 1 HOURLY 1 HOURLY 1 HOURLY 1 HOURLY Milk feed Milk feed Milk feed Milk feed

LACTOSE Approximate GLUCOSE Approximate 0h 1h 2h 3h 4h PSNS (vagal)

30 METABOLISM METABOLISM EXPECTED UNEXPECTED HEALTH DISEASE

4 HOURLY 4 HOURLY Milk feed Milk feed

LACTOSE GLYCOGEN FAT LACTOSE GLYCOGEN FAT

4 HOURLY ALLOSTATIC STATE

Approximate GLUCOSE Approximate GLUCOSE Approximate 0h 1h 2h 3h 4h 0h 1h 2h 3h 4h PSNS (vagal) SYMPATHETIC  STRESS PSNS (vagal) SYMPATHETIC  STRESS

The Neuroscience of Birth & Breastfeeding The DNA The Brain Behaviour EPIGENETICS NEURODEVELOPMENT EVOLUTIONARY BIOLOGY

ENVIRONMENT ADAPTATION EXPERIENCE REPRODUCTIVE FITNESS

ENVIRONMENTWHAT IS THE EFFECT OF MATERNAL ABSENCE ON … Weight gain 1st week: TRANSITION NEUROENDOCRINE BEHAVIOURS GENETIC VARIANTS RESILIENCE GENE X ENVIRONMENT BONDING  ATTACHMENT STRESS RESPONES EPIGENETICS MATERNAL NEUROPLASTICITY DOHAD “STABILITY” SLEEP PHYSIOLOGY (MAL) ADAPTATION EEG MRI HRV predicts OBESITY MICROBIOTA GUT FUNCTION LONG TERM FOLLOW-UP IMMUNITY at 30 years HOSPITAL ACQUIRED INFECTION MORTALITY METABOLISM

Large volume feeds Importance  stretched stomach=

doubled absorptive capacity as adult Programming – early life chronic disease

31 ALLOSTASIS ALLOSTASIS elevated activity – sustained over time, ANY STRESS: ANY STRESS: PERCEPTIONS PERCEPTIONS or severe … Psychological Psychological  “NEUROCEPTION” “NEUROCEPTION” changes the “set Neurological Neurological points” for homeostasis Endocrine Endocrine (e.g. increasing blood Immune Immune STRESS RESPONSE STRESS RESPONSE pressure, change in cholesterol level)  RESISTANCE / SENSITIVITY   RESISTANCE / SENSITIVITY  ALLOSTATIC STATE ALLOSTATIC STATE ALLOSTATIC LOAD ALLOSTATIC LOAD ALLOSTATIC OVERLOAD HEALTH DISEASE HEALTH RESILIENCE VULNERABILITY WELL-BEING  SUSCEPTIBILITY  MORBIDITY  MORTALITY

Gastric overfilling syndrome? Nils’ QUESTIONS … NICU context?

SUCKLING IS COMPETENT FEEDING IS IMMATURE

PMA 28 40 64 1y 2y

189

Nils’ QUESTIONS … full term? Nils’ QUESTIONS … full term?

SUCKLING IS SUCKLING IS COMPETENT COMPETENT FEEDING IS FEEDING IS IMMATURE IMMATURE

PMA 28 40 64 1y 2y PMA 28 40 64 1y 2y

32 Nils’ QUESTIONS … full term? Nils’ QUESTIONS … full term?

elevated activity – sustained over time, or severe … SUCKLING IS SUCKLING IS  changes the “set points” for homeostasis COMPETENT COMPETENT (e.g. increasing blood pressure, change in FEEDING IS FEEDING IS cholesterol level) IMMATURE IMMATURE

PMA 28 40 64 1y 2y PMA 28 40 64 1y 2y

Nils’ QUESTIONS … full term?

elevated activity – sustained over time, or severe … SUCKLING IS  changes the “set COMPETENT points” for homeostasis (e.g. increasing blood pressure, change in FEEDING IS cholesterol level) IMMATURE

PMA 28 40 64 1y 2y Only case series ... Insufficient evidence No mention of stomach capacity 196

90

Standardised from 80

20ml capacity 70 for 3kg baby 60 ( x 0.007) 50 LINEAR TERM 40 PREM

Baby weight; freq; req’d size  actual 30

2kg baby: 4hrly 20 ~ 320 ml/6 = 53ml  14ml 10 1,5 baby: 3hrly 0 ~ 240 ml/8 = 30ml  10ml 13w 16w 19w 22w 25w 28w 31w 34w 37w 40w 43w 46w 49w 52w 1,0 baby: 2hrly ~ 160 ml/12 = 13ml  7ml 197 198

33 90 Gastric overfilling syndrome? 80

70

60 Excessive volumes

50 reflux, aspiration, colic LINEAR TERM 40 PREM

30 Excessive time interval

20 hypoglycaemia 10 Clues to GER 0 Adaptations 13w 16w 19w 22w 25w 28w 31w 34w 37w 40w 43w 46w 49w 52w “I know baby hurts” diabetic diathesis, obesity

199 200

Developmental Care of the Gastric overfilling syndrome? Enteric Nervous System

The “niche” (occupation) of a neonate (Alberts)

BOND FEED PLAY FEED

SLEEP  SLEEP

“Small and frequent feeds, according Proposed Management  to the sleep cycle” 201 202

Proposed Management  Proposed Management 

A normal sleep cycle is ONE hour. How often should neonates feed?

REM NR1 NR2

NR3 AS (20 mins) QS (40 mins) SWS Stanley Graven 2006

Babies should be fed All babies should be fed EVERY TIME THEY WAKE !! 203 at least once an hour !! 204

34 Proposed Management  The first Milk Ejection Reflex (MER)

elicited in < 2 minutes works quickly swallowed 1 minute

Feeding time (max) 3 minutes All babies should be fed Repeat every 1 hour at least once an hour !! 205 Prime 2007

The “normal” or usual and common breastfeed 3 minute 20ml feeds x 24/d = 72 minutes takes 15 minutes discomfort after 20 minute 60ml feeds x 8/d = 160 minutes burping time 5 minutes

Feeding time 20 min SMALL AND FREQUENT FEEDS Repeat every 3 hours ARE EFFICIENT !!!! FEWER NURSES NEEDED !!! Prime 2007

The calculated daily requirement for a 3kg baby can be given without increase in pressure ....  MINIMAL RISK

20 mls x 24 feeds PARENTS CAN DO = 480mls / day SAFELY ! All babies should be fed

Zangen 2001 209 at least once an hour !! 210

35 Infant feeding frequency: Proposal based on available evidence and neuroscience

“Small and frequent feeds, adjusted to the sleep cycle” 211

BIRTH

Breastfeeding behaviour S S C Breastfeeding WIRING How often should BREASTFEEDING ON-GOING a neonate feed? SENSORY BRAIN S S C stimulation nutrition a neonate sleep? STATE organization STATE organization BRAIN Feeding frequency Feeding frequency

SLEEP cycling SLEEP cycling WIRING

Infant: Mother-infant synchrony Infant: sleep cycles … at 12 weeks sleep cycles begin to block (circadian) Thomas 2014 begin to block

on diurnal on diurnal SLEEP SLEEP PLAY SLEEP PLAY SLEEP rhythms rhythms  FEED  START at 3 months FEED

STATE organization Can be “adult-like” Feeding frequency at 6 months. Infant sleep cycling and synchronicity with SLEEP cycling maternal sleep ensure development. 216

36 SMELL (& SKIN)

BOND PLAY PLAY   SUCKLE SLEEP    SLEEP SLEEP SLEEP SLEEP SLEEP   FEED FEED modulates state organisation elicits emotional behaviours

activates pre-feeding actions anticipatory digestive physiology Infant sleep cycling and synchronicity with regulates pace of ingestive behaviour

maternal sleep ensure development. 217 Schaal 2004 218

BIRTH SMELL Breastfeeding behaviour (& SKIN) S S C Breastfeeding WIRING BREASTFEEDING ”SLEEP-FEED CYCLING” ON-GOING

modulates state organisation SENSORY BRAIN elicits emotional behaviours S S C stimulation nutrition

activates pre-feeding actions STATE organization anticipatory digestive physiology Feeding frequency WIRE regulates pace of ingestive behaviour SLEEP cycling Schaal 2004 219 BRAIN

BIRTH

Breastfeeding behaviour “Scientific foundation” … a synthesis EVOLUTIONARY NEUROSCIENCE EPIGENETICS S S C Breastfeeding WIRING BIOLOGY Everything else The Brain The DNA BREASTFEEDING ON-GOING

SENSORY BRAIN The Place FITNESS EXPERIENCE ADAPTATION S S C stimulation nutrition ENVIRONMENT

STATE organization BRAIN Feeding frequency ZERO

SLEEP cycling WIRING SEPARATION

37 THE NEUROSCIENCE OF SUMMARY !! SKIN-TO-SKIN CONTACT AND BREASTFEEDING SKIN-TO-SKIN (Regulation) ARE THE SLEEP FEEDING SAME ! (Brain) (Stomach)

www.ninobirth.org LOVE ! www.skintoskincontact.com ( “mind” )

PLAY HOLD FEED

BRAIN WIRING REM NR1 NR2 NR3 NR4 YOUR ACQUISITION CONSOLIDATION MEMORY FORMATION poly-sensory input transfer information P waves short-term memory “SNR” strong signals returns info SLEEP stored cortex amygdala / to neocortex: hippocampus organized Awake and REM NREM stage 4 REM Stanley Graven 2006 PREM

https://www.facebook.com/ninobirth

38 Nelson Mandela

… in describing the measure of a nation, he has argued that:

“There can be no keener revelation of a society’s soul than the way in which it treats its children.”

39