Transcript Diapositiva 1 - Idea congress

Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
• Comportamentali
• Endocrine
• Metaboliche
• Respiratorie
Angelo Pietrobelli
Clinica Pediatrica, Università degli Studi di Verona
Nicola Fuiano
Pediatria e Allergologia Pediatrica ASL della Provincia di Foggia
Early-life origins of adult disease: national longitudinal
population-based study of the United States.
Johnson RC, Schoeni RF. Am J Public Health 2011 Dec;101(12):2317-24
Aim:
To examine the relation between
low birth weight (LBW) and
childhood family and neighborhood
socioeconomic disadvantage and
disease onset in adulthood.
Study population:
4378 children followed up to 2007
(when they were aged 39 up to 56
years).
 Conclusions:
 LBW plays an important role
in disease onset.
O.R. by age 50 years
P <.01
P <.01
P <.01
P <.01
Change in prevalence of chronic conditions between childhood
and adolescence among extremely low-birth weight children.
Hack M et al. JAMA 2011 Jul 27: 306(4): 394-401
Aim:
To examine changes in the rates of chronic
conditions between the ages of 8 and 14 years
among extremely low-birth-weight (ELBW) children
compared with normal-birth-weight (NBW) controls.
Chronic conditions
75
74
Study population:
Cohort study conducted from 2004 through 2009:
47
%
37
181 ELBW (weight < 1 kg) and 125 NBW controls of
similar sociodemographic status born from 1992
through 1995 in Cliveland, Ohio.
 Main outcome measures:
Rates of chronic conditions overall (measured with
the revised Questionnaire for identifying Children
With Chronic Conditions) and rates of asthma and
obesity.
ELBW
age 8 years
NBW
age 14 years
Change in prevalence of chronic conditions between childhood
and adolescence among extremely low-birth weight children.
Hack M et al. JAMA 2011 Jul 27: 306(4): 394-401
 Logistic regression
(adjusted for sociodemographic status,
sex, and race):
ELBW children continued to have a
higher rate of chronic conditions
than NBW controls at age 14 years.
Change in prevalence of chronic conditions between childhood
and adolescence among extremely low-birth weight children.
Hack M et al. JAMA 2011 Jul 27: 306(4): 394-401
Asthma requiring medication
Differences in rates of asthma at
age of 14 years
%
%
P = .002
Change in prevalence of chronic conditions between childhood
and adolescence among extremely low-birth weight children.
Hack M et al. JAMA 2011 Jul 27: 306(4): 394-401
Mean z scores for Body Mass Index
in ELBW children
(P < .001)
at age 14 years
0.38 –
0.06 –
at age 8 years
%
0
Change in prevalence of chronic conditions between childhood
and adolescence among extremely low-birth weight children.
Hack M et al. JAMA 2011 Jul 27: 306(4): 394-401
 Results: the scores and rates did not change among NBW controls such
that at the age of 14 years the differences between ELBW and NBW children
in mean z scores for body mass index (0.38 vs 0.56, respectively; adjusted
mean difference -0.2 [95% CI, -0.5 to 0.1]) or rates of obesity (19% vs
20%, respectively; AOR, 1.1 [95% CI, 0.6 to 2.0]) were not significant.
 Conclusions: among ELBW children, rates of overall chronic conditions
and asthma did not change between the ages of 8 and 14 years but the rate
of
obesity
increased.
Compared
with
NBW
controls,
the
rates
of chronic conditions were higher but there were no significant differences
in the rates of asthma or obesity.
1. Preterm infant
2. Small for gestational age
1. Preterm infant
Preterm Infant : born <37 weeks’ gestation
< 37 weeks:
“premature”
“preterm”
Definition
Preterm infants are so different between each other.
Shorter is pregnancy more are risks’ factor for infants.
 “Preterm”:
born between 34 and 36 weeks
of gestational age;
 “Moderate preterm”:
born between, 32 and 33 weeks
of gestational age;
 “Very low birth weight”:
born <32 weeks of gestational age;
 “Extremely very low birth weight”
born <28 weeks of gestational age.
Linee guida della Società Italiana di Neonatologia
Epidemiology
Preterm: Italy situation?
40.000 preterm (6.9%) every year,
1 every 14 born, approximately 110/day;
VLBW: 5.500 year, 1 every 100 born.
 first condition of death during first year of age.
 Italy: 800 death/year
Dati della Società Italiana di Neonatologia
Premature babies – quality of life
- Survival rate directly related to gestational age
- EVLBW (…- 24 - 26weeks) have survival rate close to 85%
-10% VLBW health problems:
- brain,
- ROP,
- growth;
-Preterm infant: high level of SIDS and
high ER access.
2. Small for gestational age
What is small for gestational age (SGA)?
Small for gestational age (SGA) is a term used to describe a baby who is
smaller than the usual amount for the number of weeks of pregnancy.
SGA babies usually have birth weights below the 10th percentile for
babies of the same gestational age.
This means that they are smaller than 90 percent of all other babies of
the same gestational age.
 SGA babies may appear physically and neurologically mature but
are smaller than other babies of the same gestational age;
 SGA babies may be proportionately small (equally small all over) or
they may be of normal length and size but have lower weight and body
mass;
 SGA babies could be premature (born before 37 weeks of pregnancy),
full term (37 to 41 weeks), or post term (after 42 weeks of pregnancy).
Epigenetic regulation and fetal programming
Epigenetic regulation and fetal programming
Gicquel C. et al. Best Pract Clin Endocrinol Metab 2008
Fetal programming encompasses the role of developmental
plasticity in response to environmental and nutritional signals
during early life and its potential adverse consequences (risk
of cardiovascular, metabolic and behavioural diseases) in later
life.
The first studies in this field highlighted an association
between poor fetal growth and chronic adult diseases.
However, environmental signals during early life may lead to
adverse long-term effects independently of obvious effects on
fetal growth.
Adverse long-term effects reflect a mismatch between early
(fetal and neonatal) environmental conditions and the
conditions that the individual will confront later in life.
Epigenetic regulation and fetal programming
Adjusted for gestational age
Large for gestational age
Small for gestational age
• Premature
(before 37 weeks of pregnancy)
• Full term
(37 to 41 weeks of pregnancy)
• Post term
(after 42 weeks of pregnancy)
Epigenetics and food allergy
Hong X et al. Semin Immunopathol (2012) 34:655–669
Food allergy (FA), a major clinical and public health concern
worldwide, is caused by a complex interplay of
• environmental exposures,
• genetic variants,
• gene environment interactions,
• and epigenetic alterations.
Epigenetic alteration has been proposed as one of the
mechanisms to mediate the influence of early life
environmental exposures and gene–environment
interactions on the development of diseases later in life.
Epigenetics and food allergy
Prematurity is proposed to be associated with increased intestinal
permeability and increased food antigen uptake which may lead to an
increased risk of IgE mediated food allergy in premature children.
Robertson DM 1982 - Weaver LT 1984
Very low birth weight (LBW) preterm infants also are considered to have
a wide range of immature digestive and absorptive functions, which
might cause increased macromulecular absorption leading to food allergy.
McNeish AS 1984
Low birth weight (LBW) infants who received cow's milk formula
developed latent systemic sensitization more rapidly than infants born at
term.
Lucas A 1984
Epigenetics and food allergy
An Italian study compared 80 preterm infants with 80 sex-matched- and
age-matched full-term infants at a mean age of 16 months and found no
difference in frequency of positive skin tests to foods between the two
groups.
De Martino M 1989
In the 1995 Manitoba birth cohort composed of 13,980 children:
no association for prematurity and LBW with the risk of food allergy in
childhood.
Liem IJ 2007
In the BBC: prematurity was associated with an increased risk of
recurrent wheezing, but no such associations were found for either food
allergy or eczema.
Kumar R 2008
Epigenetics and food allergy
A Japanese study: the prevalence of food allergy in LBW infants (8.1 %)
was found to be significantly lower than in infants with normal birth
weight at 18 months of age (11.2 %).
Hikino S 2001
Stressful intrauterine milieus (i.e., low birth weight) and genetic
susceptibility to obesity synergistically affect adulthood risk of type 2
diabetes.
Case control study using 2591 type 2 diabetes and 3052 healthy control
subjects.
Li Y et al 2012
2
Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
Comportamentali
Endocrine
Metaboliche
Respiratorie
Depression in young adults with very low birth weight:
the Helsinki study of very low-birth-weight adults.
Räikkönen K et al. Arch Gen Psychiatry 2008; 65(3):290-6
Aim:
- 20.1
- 29.1
to test whether young adults aged 18 to 27 years
with VLBW (<1500 g) differ from term control
subjects in depression symptoms, current use of
antidepressant medication and the rate of
The
VLBWbyparticipants
depression
diagnosed
a physician.
reported 20.1% lower
Study population:
CES-D scores than the
162 VLBW young adults (response rate 65.1%)
(P =.02),
and 172AGA
term controls
control subjects
(response rate
54.8%) and
born 29.1%
between lower
February
22.1978 and
than
November 28.1985 in Helsinki.
the controls (P =.004).
 Main outcome measures:
antidepressant use, history of physiciandiagnosed, Beck Depression inventory score , and
Center for Epidemiologic Studies Depression Scale
Score.
95% CI
-40.8 to - 1.72
95% CI
-53.7 to -8.4
Depression in young adults with very low birth weight:
the Helsinki study of very low-birth-weight adults.
Räikkönen K et al. Arch Gen Psychiatry 2008; 65(3):290-6
Results:
VLBW participants born appropriate for gestational age were 4.8 (95%
CI, 1.3-10.0) times less likely to report a depression diagnosis than
controls (P =.02).
In contrast, 52 VLBW participants born small for gestational age
(birth weight < -2 SDs according to Finnish birth weight charts) reported
36.2% (95% CI, 1.1%-83.5%) higher Beck Depression Inventory scores
(P =.04), were 4.0 (95% CI, 1.1-14.3) times more likely to use
antidepressants (P =.03), and were 2.5 (95% CI, 1.0-6.3) times more
likely to report a depression diagnosis (P =.04) compared with controls.
 Conclusions: this is the first study (to our knowledge) to show that
intrauterine growth pattern may modify associations between VLBW and
depression. Intrauterine growth retardation rather than VLBW per se
may pose a risk of depression in young adulthood.
Disabilities and health of extremely lowbirthweight teenagers:
a population-based study.
Georgsdottir I et al. Acta Paediatr 2012; 101:518-23
Aim:
evaluating of long-term outcome of
extremely low-birthweight (ELBW)
teenagers born in Iceland in 1991-95;
Study population:
30 ELBW and 30 fullterm control;
age range 14-19 years;
assessed for
disabilities,
health problem,
learning difficulties.
Results:
a quarter of the ELBW teenagers had
disabilities.
Birth weight, stress, and symptoms of depression in adolescence:
evidence of fetal programming in a national canadian cohort.
Colman I et al. Can J Psychiatry 2012 Jul;57(7):422-8.
1.50
Aim:
To investigate evidence of fetal programming in
humansThe
by studying
adolescents born
relationwhether
between
at high or low birth weights (LBW) are more
chronic stress
and
likely to experience
symptoms
of depression and
depression
anxietyadolescent
after experiencing
stress.
and
anxiety was more
Study
population:
pronounced in males
3732 members of a prospective Canadian cohort
who were
born SGA
study assessed
for symptoms
of depression and
anxiety(interaction
at age 12 to 15
years
(2006/2007),and
P<
0.05)
had birthweight and gestational age (GA) data
recorded in 1994/1995.
1.31
95% CI
1.08 to 2.08
95% CI
0.99 to 1.72
School-age Outcomes of Extremely Preterm or Extremely Low
Birth Weight Children.
Hutchinson EA et al. Pediatrics 2013; Apr;131(4):e1053-61.
Aim:
To monitor changes in the nature of neurobehavioral deficits in
extremely preterm (EP) or extremely low birth weight (ELBW) survivors.
This study examines cognitive, academic, and behavioral outcomes at
age 8 years for a regional cohort of EP/ELBW children born in 1997.
Setting:
The State of Victoria, Australia;
Methods:
The EP/ELBW cohort comprised all live births with a gestational age <28
weeks (EP) or birth weight <1000 g (ELBW) born in 1997. Of 317 live
births, 201 (63.4%) survived to 2 years of age. A term/normal birth weight
(T/NBW) cohort was recruited comprising 199 infants with birth weights
<2500 g or gestational age <37 weeks. Measures of intellectual ability,
educational achievement, and behavior were administered at age 8.
School-age Outcomes of Extremely Preterm or Extremely Low
Birth Weight Children.
Hutchinson EA et al. Pediatrics 2013; Apr;131(4):e1053-61.
Results:
The EP/ELBW group performed poorer than
the T/NBW Conclusions:
group on measures of IQ,
educational despite
achievement,
certain
ongoing and
behavioral improvements
domains, even after
in theadjustment for
sociodemographic
factors of
and exclusion of
management
children with neurosensory impairment. The
EP/ELBW infants,
rate of any neurobehavioral impairment was
elevated
in rate
the EP/ELBW
group (71% vs 42%),
the
of neurobehavioral
and one-half
of at
subjects
had multiple
impairment
school-age
impairments.
Thetoooutcomes
for those with
remains
high relative
<750 g birth weight or <26 weeks' gestational
to controls.
age were similar to those with a birth weight
of 750 to 999 g or a gestational age of 26 to
27 weeks, respectively.
Retention percentage
94.0
87.0
%
Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
Comportamentali
Endocrine
Metaboliche
Respiratorie
Serum thyroid hormone levels in healthy children from birth to
adulthood and in short children born small for gestational age.
Lem A J et al. J Clin Endocrinol Metab 2012 Sep;97(9):3170-8.
Aim:
to obtain pediatric thyroid hormone reference ranges;
to investigate thyroid hormones in short SGA children before puberty,
during puberty, and during postponement of puberty by GnRH analog;
and to evaluate thyroid hormones during GH treatment.
 Patients and design:
in 512 healthy children (225 females; 0-18 yr), free T(4) (FT(4)), TSH,
total T(4), T(3), rT(3), and T(4)-binding globulin were determined.
Reference ranges were calculated using the linearity, median, and skewness
method. In 125 short SGA children (62 females; mean age 11.3 yr), thyroid
hormones were analyzed before and after 2 yr of GH treatment and
additional GnRH analog.
Serum thyroid hormone levels in healthy children from birth to
adulthood and in short children born small for gestational age.
Lem A J et al. J Clin Endocrinol Metab 2012 Sep;97(9):3170-8.
Results:
Thyroid references showed wide ranges postnatally and age-specific
patterns thereafter, similar in boys and girls.

Untreated short SGA children had similar FT(4) and T(4) levels as the
reference population but significantly higher T(3), rT(3), and T(4)-binding
globulin levels.

During puberty and during GH treatment, FT(4) and rT(3) significantly
decreased, whereas T(3) significantly increased.

Conclusion:
Age-specific thyroid reference ranges are presented. Puberty and GH
treatment both induce changes in peripheral thyroid metabolism, resulting
in more biologically active T(3) at the expense of less inactive rT(3),
possibly mediated by IGF-I. GH treatment induces altered peripheral thyroid
metabolism but does not result in thyroid dysfunction

Neonatal hyperthyrotropinemia is associated with low birth
weight: a twin study.
Zung A et al. Eur J Endocrinol 2013 Jan 17;168(2):263-9
 Background:
Contradictory reports ascribe neonatal hyperthyrotropinemia (HT) to
prematurity or small weight for gestational age.
 Aim:
To evaluate the association between neonatal HT and birth weight (BW),
recovery rate of the disorder, and possible association with perinatal stress.
 Study population:
2595 twin pairs that were screened both for TSH and thyroxine (T(4))
over 3 years were included.
 Methods:
TSH and T(4) levels were evaluated along with BW, birth order, gender,
and 17-hydroxyprogesterone (17OHP) that was considered as a surrogate
marker for stress.
Neonatal hyperthyrotropinemia is associated with low birth
weight: a twin study.
Zung A et al. Eur J Endocrinol 2013 Jan 17;168(2):263-9
 Results:
 Of all the twin pairs, 7.2%
had neonatal HT.
Conclusions:
 Among 156• Elevated
pairs, HTTSH
waslevels
moreare
prevalent
in with
the smaller twins
associated
(64%; P<0.001),
especially
discordant
pairs
P=0.001).
low
BW bothininthe
infants
with HT
and(76%;
in
neonates.
 Seventy-five percent ofnormal
the twins
demonstrated a recovery within
the first few weeks of life.
• A rapid recovery rate is expected
 17OHP levels were similarly
distributed
in most
cases. between twins with and
without HT.
 In a cohort of 1534 twin pairs with normal thyroid function, mean
TSH levels were significantly higher in the smaller than in the larger
twin in the whole group (4.1±3.2 vs 3.8±2.9 mIU/l; P<0.001) and
especially among discordant twins (4.7±3.4 vs 3.8±3.0 mIU/l;
P<0.001).
Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
Comportamentali
Endocrine
Metaboliche
Respiratorie
Maternal and fetal cord blood lipids
in intrauterine growth restriction.
Pecks U et al. J Perinat Med. 2012; 40 (3): 2387-96
Aim: small for gestational age neonates (SGA) could be subdivided into
two groups according to the underlying causes leading to low birth weight.
Intrauterine growth restriction (IURG) is a pathologic condition with
diminished growth velocity and fetal compromised well-being, while nongrowth restricted SGA neonates are costitutionally (genetically determined)
small.
Antenatal sonographic measurements are used to differentiate these two
groups.
Maternal metabolic changes contribute to the pathogenesis of IUGR.
A disturbed lipid metabolism and cholesterol supply might affect the fetus,
with consequences for fetal programming of cardiovascular diseases.
To evaluate fetal serum lipids and hypothesize a more atherogenic
lipoprotein profile in IURG fetuses.
Maternal and fetal cord blood lipids
in intrauterine growth restriction.
Pecks U et al. J Perinat Med. 2012; 40 (3): 2387-96
 Methods:
 umbilical
cord
serum
lipoprotein
(oxLDL)
lipids
and
concentrations
oxidative
were
modified,
measured
enzymatic measurements, or by ELISA.
 Three groups:
IUGR n. 36
SGA n. 22
CN (healthy, adequate for gestational age) n. 97
by
low-density
colorimetric
Maternal and fetal cord blood lipids
in intrauterine growth restriction.
Pecks U et al. J Perinat Med. 2012; 40 (3): 2387-96
Fetal
Results:
•HDL-C
Conclusions:
IUGR
group
Umbilical cord serum lipids
(P < 0.001)
and oxidative
modified,cholesterol supply in IURG
•TC
A disturbed
fetuses;
low-density lipoprotein
(P< 0.01)
Born SGA has been shown to be a risk factor for
(oxLDL) concentrations
SGA group
CN group
measured bydeveloping
colorimetric cardiovascular disease later in life;
enzymatic measurements,
Since HDL-C has anti-inflammatory properties, a
or by ELISA. reduced HDL-C during fetal development,
Atherogenicand
indices
an increase in atherogenic indices, might
 Three groups:
IUGR group
provide a link to this observation
in IUGRratio
oxHDL/LDL-C
IUGR
fetuses. n. 36,
(P < 0.001)
SGA
n. 22,
CN (healthy, AGA) n. 97.
CN group
Low birth weight as cardiometabolic risk
in Japanese high school girls.
Mori M et al. J Am Coll Nutr. 2012 Feb;31(1):39-44.
Objective: to examine the relationships between birth weight and
metabolic syndrome (MS) risk factors in healthy Japanese high school
girls.
Methods: in 2007 and 2008, 243 healthy Japanese high school girls aged
16.4±1.4 years were examined:
anthropometric measurements (including WC),
SBP and DPB,
tryglicerides (TG), high-density lipoprotein cholesterol (HDL), insulin,
blood glucose to calculate insulin resistance after fasting for 3 hours
after lunch.
Low birth weight as cardiometabolic risk
in Japanese high school girls.
Mori M et al. J Am Coll Nutr. 2012 Feb;31(1):39-44.
Results:
prevalence
MS was detected in only 1
girl who had obesity and 2
%
more risk factors (high BP
and high TG)
Low birth weight as cardiometabolic risk
in Japanese high school girls.
Mori M et al. J Am Coll Nutr. 2012 Feb;31(1):39-44.
Results:
180 girls reported their birth weight
Birth weights were significantly inversely related with:
SBP
P = 0.007
DBP
P = 0.033
TG
P = 0.009
Insulin level
P = 0.047
Insulin resistance
P = 0.050
Number of metabolic risk factors
P = 0.022
Low birth weight as cardiometabolic risk
in Japanese high school girls.
Mori M et al. J Am Coll Nutr. 2012 Feb;31(1):39-44.
Results:
Thirteen girls (7,2 %) whose birth weights were lower than 2500 gr. had
significantly higher:
SBP
P = 0.037
DBP
P = 0.032
TG
P = 0.011
Insulin level
P =0.037
Insulin resistance
P = 0.043
than 31 girls (17.2 %) with birth weights equal to or more than 3400 gr.
Low birth weight as cardiometabolic risk
in Japanese high school girls.
Mori M et al. J Am Coll Nutr. 2012 Feb;31(1):39-44.
 Conclusion:
The association of low birth weight could be detected to be significant with
such risks factors of MS as :
SBP,
DBP,
TG,
insulin level,
and insulin resistance even in healthy Japanese school girls,
indicating the importance of follow-up and food educational programme for
children with low birth weight for the prevention of MS in the later life.
Ambulatory blood pressure in young adults with
very low birth weight.
Hovi P et al. J Pediatr 2010 Jan;156(1):54-59.
Objective: we hypothesized that, as compared with a matched control
group at term, young adults with very low birth weight (VLBW < 1.5 kg)
would have higher 24-hour ambulatory blood pressure.
Study design: in the greater Helsinki area: two groups of subjects:
1. 118 18- to 27-year-old subjects born with VLBW,
the mean birth weight was
1.1 kg [± 0.2],
the gestational ages were
29.2 [± 2.3]
 2. 120 term-born subjects, with similar age, sex, and birth hospital,
the mean birth weight was
3.6 kg [± 0.5],
the gestational ages were
40.1
[± 1.0].
Ambulatory blood pressure in young adults with
very low birth weight.
Hovi P et al. J Pediatr 2010 Jan;156(1):54-59.
Methods:
Prevalence of hypertension in the
two groups of subjects
Current education of highereducated parents served as
Conclusion:
an indicator
of childhood
socioeconomic
status.
Higher
rates of hypertension and higher
24-hour
bloodwas
pressure among young
Ambulatory blood
pressure
VLBW may indicate higher risk
measured adults
during with
a 24-hour
for an
adverse
cardiovascular outcomes
period with
oscillometric
device.
Results:
VLBW subjects had, with sex,
age, and body mass index
adjustment,a 2.4 mmHg (95
% confidence interval, 0.2 to
4.6)
• when socioeconomic status was taken
into account, results remained unchanged
The relationship between birth weight and blood pressure in
childhood: a population-based study.
Steinthorsdottir SD et al. Am J Hypertens. 2013 Jan;26(1):76-82.
Objective: to evaluate the association between birth weight and blood
pressure (BP) in healthy 9- to 10-year-old Icelandic children.
Methods: each child underwent 4 seated BP measurements, and the BP
percentile was calculated from the mean of the 4 measurements. Height
and weight were measured and birth weight retrieved from the Icelandic
Birth Registry.
Birth measures and anthropometric data were correlated with BP and BP
percentiles. Multivariable linear regression was employed to examine the
association between BP and birth measures.
The relationship between birth weight and blood pressure in
childhood: a population-based study.
Steinthorsdottir SD et al. Am J Hypertens. 2013 Jan;26(1):76-82.
Results: of 857 children with complete data, 445 were female (51.9%).
The mean BP was 112/64 mm Hg in males and 111/63 mm Hg in females.
The mean birth weight was 3714 ± 620 g.
No correlation was found between birth weight and absolute BP values.
A significant negative correlation between birth weight and both systolic
(r = -0.09, P = 0.005) and diastolic (r = -0.08, P = 0.014) BP percentiles
was observed. Gestational age did not correlate with BP.
Conclusion: in contrast to many previous studies, we found no
association between birth weight and absolute BP in children. However, we
observed a statistically significant negative correlation between birth
weight and BP percentiles. The lack of standardized BP values may partly
explain the conflicting results of previous studies in children, and we
suggest that BP percentiles be examined more thoroughly in association
with birth weight.
Effect of pregnancy for females born small on later life
metabolic disease risk.
Tran M et al. PLoS One 2012;7(9):e45188. Erratum in: PLoS One. 2012;7(11)
Background:
there is a strong inverse relationship between a females own birth
weight and her subsequent risk for gestational diabetes with increased
risk of developing diabetes later in life. We have shown that growth
restricted females develop loss of glucose tolerance during late pregnancy
with normal pancreatic function.
Aim:
to determine whether growth restricted females develop long-term
impairment of metabolic control after an adverse pregnancy adaptation.
Uteroplacental insufficiency was induced by bilateral uterine vessel ligation
(Restricted) or sham surgery (Control) in late pregnancy (E18) in F0
female rats.
Effect of pregnancy for females born small on later life
metabolic disease risk.
Tran M et al. PLoS One 2012;7(9):e45188. Erratum in: PLoS One. 2012;7(11)
Methods:
Uteroplacental insufficiency was induced by bilateral uterine vessel
ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in
F0 female rats.
F1 Control and Restricted female offspring were mated with normal
males and allowed to deliver (termed Ex-Pregnant).
Age-matched Control and Restricted Virgins were also studied and
glucose tolerance and insulin secretion were determined.
Pancreatic morphology and hepatic glycogen and triacylglycerol content
were quantified respectively.
Effect of pregnancy for females born small on later life
metabolic disease risk.
Tran M et al. PLoS One 2012;7(9):e45188. Erratum in: PLoS One. 2012;7(11)
 Results:
Restricted females were born lighter than Control and remained lighter at
Conclusion:
all time points studied (p<0.05).
Glucose tolerance, first phase insulin
secretion and liver glycogen and triacylglycerol content were not different
Our data suggests that pregnancy
across groups, with no changes in β-cell mass. Second phase insulin
the enhanced
peripheral
secretion wasameliorates
reduced in Restricted
Virgins (-34%,
p<0.05) compared to
insulin
sensitivity
in growth
Control Virgins,
suggestive
of enhanced
peripheral insulin sensitivity but
females Growth
and has
deleterious
this was lostrestricted
after pregnancy.
restriction
was associated with
effectshepatic
for hepatic
insulin
sensitivity,which may provide
enhanced basal
insulin
sensitivity,
compensatoryregardless
benefits to
metabolic outcomes often
of prevent
maternaladverse
birth weight.
associated with being born small. A prior pregnancy was associated with
reduced hepatic insulin sensitivity with effects more pronounced in
controls than Restricted.
Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
Comportamentali
Endocrine
Metaboliche
Respiratorie
Occurrence and severity of bronchopulmonary dysplasia and
respiratory distress syndrome after a preterm birth.
Landry JS et al. Paediatr Child Health2011 Aug;16(7):399-403.
Background: bronchopulmonary dysplasia (BPD) remains an important
complication of preterm birth, frequently resulting in prolonged hospital
stay and long-term morbidity.
 Setting: Montreal Children's Hospital (Montreal, Quebec).
 Subjects: a historical cohort study of all preterm infants (gestational
age younger than 37 weeks) admitted between January 1, 1980, and
December 31, 1992.
 Methods: information collected included demographic data, maternal
and perinatal history, and main neonatal outcomes. Independent risk
factors associated with BPD were identified by univariate analysis using
one-way ANOVA, t tests or Mantel-Haenszel χ(2) testing. Severity of
disease was studied using an ordinal multinomial logistic regression
model.
Occurrence and severity of bronchopulmonary dysplasia and
respiratory distress syndrome after a preterm birth.
Landry JS et al. Paediatr Child Health2011 Aug;16(7):399-403.
Results:
Conclusions:
1192 preterm infants were
admitted,
of whom 551factors
developed
respiratory
distress
syndrome
,
associated
with BPD
following
a
and 322 developed BPD.
preterm birth were
For each additional week of prematurity, the risk of developing BPD
the degree of prematurity,
increased by 54% (adjusted OR 1.54/week [95% CI 1.45 to 1.64]).
birth
For each point subtracted
onweight,
the 1 min Apgar score, the risk of
Apgar score
at 1(OR
min,
developing BPD was increased
by 16%
1.16 [95% CI 1.1 to 1.3]).
and the presence of patent ductus arteriosus,
BPD was also associatedpneumothorax
with the presence of patent ductus arteriosus
(OR 3.5 [95% CI 2.1 to 6.0]), pneumothorax in the first 48 h (OR 9.4
or neonatal pneumonia/sepsis
[95% CI 3.6 to 24.8]) or neonatal pneumonia/sepsis in the neonatal
period (OR 1.9 [95% CI 1.1 to 3.2]).
Severity of BPD was associated with gestational age, 1 min Apgar score,
very low birth weight and the presence of neonatal pneumonia/sepsis.
Short term outcomes after extreme preterm birth in England:
comparison of two birth cohorts in 1995 and 2006 (the EPICure
studies). Costeloe KL et al. BMJ 2012 Dec 4;345:e7976
Objective:
To determine survival and neonatal morbidity for babies born between
22 and 26 weeks’ gestation in England during 2006,
and to evaluate changes in outcome since 1995 for babies born
between 22 and 25 weeks’ gestation.
 Setting:
Maternity and neonatal units in England.
 Participants:
3133 births between 22 and 26 weeks’ gestation in 2006;
666 admissions to neonatal units in 1995,
1115 admissions to neonatal units in 2006,
of babies born between 22 and 25 weeks’ gestation.
 Main outcome measures:
Survival to discharge from hospital, pregnancy and delivery
outcomes, infant morbidity unit discharge.
Short term outcomes after extreme preterm birth in England:
comparison of two birth cohorts in 1995 and 2006 (the EPICure
studies). Costeloe KL et al. BMJ 2012 Dec 4;345:e7976
P < 0.001
Results:
Survival
of live born babies
in 2006
%
Short term outcomes after extreme preterm birth in England:
comparison of two birth cohorts in 1995 and 2006 (the EPICure
studies). Costeloe KL et al. BMJ 2012 Dec 4;345:e7976
Results:
in 2006
at discharge
from hospital:
%
Short term outcomes after extreme preterm birth in England:
comparison of two birth cohorts in 1995 and 2006 (the EPICure
studies). Costeloe KL et al. BMJ 2012 Dec 4;345:e7976
Results: for babies born between 22 and 25 weeks’ gestation
from March to December
%
+44.0 %
P < 0.001
Short term outcomes after extreme preterm birth in England:
comparison of two birth cohorts in 1995 and 2006 (the EPICure
studies). Costeloe KL et al. BMJ 2012 Dec 4;345:e7976
Results:
Conclusions:
Survival of
of babies
born between
22 with
and bronchopulmonary
 The proportions
babies surviving
in 2006
25 weeks’ gestation has increased since
1995 but the pattern of major neonatal
circumference < - 2SD were similar to those in 1995, but the proportion
morbidity and the proportion of
treated for retinopathy
prematurity
increased from 13 % to 22 %
survivorsofaffected
are had
unchanged.
dysplasia, major cerebral scan abnormality, or weight and/or head
( P = 0.006 ).
These observations reflect an important
increase in the number of preterm
survivors
at risk
later health
 Predictors
of mortality
andofmorbidity
wereproblems.
similar in both cohorts.
Predictors for asthma at age 7 years for low-income children
enrolled in the Childhood Asthma Prevention Study.
Tamesis GP et al. J Pediatr2013 Mar;162(3):536-542.e2.
Objective:
To identify the predictive factors of early childhood wheezing in children
of low socioeconomic status.
Study design:
The Childhood Asthma Prevention Study
 Participants:
177 low-income children (9-24 months old) with frequent wheezing.
At age 7 years, presence of asthma was assessed through caregiver
reports of physician diagnosis of asthma (CRPDA) and corroborated by
assessment of bronchial hyperresponsiveness (BHR).
Lung function, inflammatory markers, and asthma symptom severity were
compared for children with ±CRPDA, ±BHR, and asthma.
Baseline predictors for CRPDA, BHR, and asthma at 7 years of age were
examined.
Predictors for asthma at age 7 years for low-income children
enrolled in the Childhood Asthma Prevention Study.
Tamesis GP et al. J Pediatr2013 Mar;162(3):536-542.e2.
Results:
Conclusions: this low-income, multi-ethnic
of wheezing
infants differentiated
represents a unique
Maternal group
symptom
report strongly
children with +CRPDA
population ofairflow
childrenmeasurements
with distinct (P < .0001), and
(49%) despite comparable
risks for persistent
asthma.for +BHR (65%)
spirometric characteristics
lung function and
measurements
were different
versus -BHRDetermination
(P < .005). of asthma status at 7 years of
Univariateage
analyses
baseline
predictors
of +CRPDA
requiredrevealed
objectivedifferent
measurement
of BHR
in
and +BHR for childrenaddition
at ageto 7CRPDA.
years. Higher levels of maternal
psychological resources were associated with +CRPDA, but not +BHR.
The association of maternal psychological
resources
+CRPDA
mayofrepresent
Only 39% of
childrenwith
with
a history
frequenta wheezing met the
previously
factor7 inyears,
the with the following
conservative definition
of unrecognized
asthma at age
determination
of low
asthma
among
low- symptom severity,
significant predictors
found:
birthstatus
weight,
baseline
groups
and maternal psychologicalincome
resources.
Conseguenze a lungo termine della prematurità
e del basso peso per l’età gestazionale :
• Comportamentali
• Endocrine
• Metaboliche
• Respiratorie
? Take home message
Pregnancy complications among women born preterm.
Boivin A et al. CMAJ 2012 Nov 6;184(16):1777-84.
Aim:
to
examined
the
relation
between
preterm
birth
and
pregnancy
complications later in life.
Methods:
in the province of Quebec: 7405 women born preterm (554 < 32 weeks,
6851 at 32-36 weeks) and a matched cohort of 16 714 born at term
between 1976 and 1995 who had a live birth or stillbirth between 1987 and
2008. The primary outcome measures were pregnancy complications
(gestational diabetes, gestational hypertension, and preeclampsia or
eclampsia).
Pregnancy complications among women born preterm.
Boivin A et al. CMAJ 2012 Nov 6;184(16):1777-84.
Results
Overall, 19.9% of women born at less than 32 weeks, 13.2% born at 3236 weeks and 11.7% born INTERPRETATION:
at term had at least 1 pregnancy complication at
least once during the study period (p < 0.001).
• Being born preterm,
Women born smallin for
gestational
(both term
addition
to, and age
independent
of, and preterm) had
increased odds of having at least 1 pregnancy complication compared with
being
small for gestational
women born at term and
at appropriate
weight forage,
gestational age.
was associated with a significantly
After adjustment for various
factors,
birth weight for gestational
increased
risk ofincluding
later having
age, the odds of pregnancy complications associated with preterm birth was
pregnancy
complications
elevated by 1.95-fold (95%
confidence
interval [CI] 1.54-2.47) among
women born before 32 weeks' gestation and 1.14-fold (95% CI 1.03-1.25)
among those born at 32-36 weeks' gestation relative to women born at
term.
Low birth weight and health expenditures
from birth to late adolescence.
Hummer M et al. Eur J Health Econ 2013 Apr 2.
Objective:
to analyze the impact of low birth weight (LBW) and very low birth
weight (VLBW) on health care utilization in childhood and early
adolescence.
 Data/methods
using Austrian health insurance administrative panel data linked to the
Austrian birth register, we estimate the effects of LBW and VLBW in
comparison to normal birth weight (NBW) on the number of days spent in
the hospital and on expenditures for medical assistance and medical drugs
among children and young adults between birth and 21 years of age. To
account for the time-invariant heterogeneity of mothers, we control for
sibling fixed effects.
Low birth weight and health expenditures
from birth to late adolescence.
Hummer M et al. Eur J Health Econ 2013 Apr 2.
 Results:
in comparison to their NBW counterparts,
Conclusion:LBW infants spend more days
hospitalized and
is for
spent
on medical
drugs
(particularly
on anti• Wemore
argue
further
counseling
efforts
for
mothers
on the
determinants
and risk
infectives) expectant
for them in
their first
year
of life. Although
the absolute
factors of LBW.
differences in health service utilization between NBW and LBW groups
Moreover,
pre-school
diminish over •time,
LBW newborns
stillscreenings
spend moreespecially
days hospitalized, and
tailored to LBW infants with a particular focus on
their medicalmental
drug and
medical
expenses
arecan
significantly
higher
health
andassistance
behavioral
disorders
be
easily integrated
in the existing
postnatal
motherin early childhood.
During compulsory
schooling,
we observe
a shift toward
child care program in Austria to mitigate the
diseases of the nervous system and mental and behavioral disorders
consequences of negative conditions during
among children born with LBW.pregnancy.
Some of these effects persist until early
adulthood.
Grazie per l’ invito
grazie della cortese attenzione
[email protected]