the origins of health and disease: the influence of maternal diseases and lifestyle during...

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The origins of health and disease: the influence of maternal dlifestyle during gestation

Italian Journal of Pediatrics 2013, 39 :7 doi:10.1186/1

Lucetta Capra ( [email protected] )Giovanna Tezza ( [email protected]

Federica Mazzei ( [email protected] L Boner ([email protected] )

Italian Journal of Pediatrics
mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]


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The origins of health and disease: the influenmaternal diseases and lifestyle during gestati

Lucetta Capra 1* * Corresponding authorEmail: [email protected]

Giovanna Tezza 2

Email: [email protected]

Federica Mazzei 2 Email: [email protected]

Attilio L Boner 2


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Introduction

Several epidemiological studies have revealed that exposure to an unfavoin early life is associated with a significantly increased risk of later disetermed early life programming . Factors that adversely affect thepostnatal environment such as maternal diseases and their treatmentsnutrition and activity as well as exposure to pollutants can alter fetapersistent effects on health.

Major maternal causal diseases include psychiatric-neurologic disordersleep related breathing disorders, and anemia. Furthermore, an increahighlights the weight of a mothers nutrition and of micro-nutrients, and exposure to pollutants, from preconception through lactation, in programorgan systems and homeostatic pathways of her offspring.


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protective feature against the development of obesity; and a risk factor forbehaviours like overeating and little exercise, that are behaviours inevitabchild.

Moreover, children of mothers with high levels of anxiety-depressive disoof gestation, have almost twice the risk (RR = 1.68) of developing astand a half years [6]. Nevertheless, exposure to maternal depression and the first year of life, has only a limited association with successive asthma

Another aspect that must be considered is the influence of maternal psycthe development and morphology of the fetal brain. Children whose manxiety-depressive syndrome have less developed areas of the brcontrolling cognitive functions, particularly the prefrontal cortex, the struthe schedule of action, reasoning, working memory, attention and some [1]. Consequently the baby is exposed to an increased risk of a tendenc


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birth the concentrations of long half-life antidepressants, like paroxetine, Furthermore, the potent inhibition of serotonin re-uptake and affinity for mmay be responsible for the withdrawal syndrome and excessive muscarini

Epilepsy and antiepileptic drugs in pregnancy

Epilepsy is a frequent neurological disorder affecting 0.4-0.8% of pregnawith epilepsy have a higher risk of preeclampsia, gestational hypertpregnancy and excessive bleeding postpartum. They also have higher inci

anomalies and delayed cognitive development in their children. It has bincreased risk of complications is due to the epilepsy per se, the use of anthe combination of both factors [21]. Recent studies powerfully point to amedications and the dose used in pregnancy. The use of anti-epileptic drughas been associated with the development of anticonvulsant embryopathydevelopment of major malformations growth retardation and hypoplasia


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of as a vicious cycle. The woman with diabetes, diagnosed before or durinhigh-risk pregnancy with potential complications extend well beyond tThe infant of the woman with diabetes is at high risk of becoming obeseType 2 diabetes at a young age. The young woman whose mother hpregnancy is at risk of perpetuating the cycle by becoming obese and before or during her childbearing years [29]. Moreover, metabolic condare associated with a higher likelihood of autism spectrum disordedevelopmental delays (OR = 2.35) [30]. In fact, in a diabetic anpregnancy, poorly regulated maternal glucose can result in adverse

Prolonged fetal exposure to elevated glucose levels results in chronic fetawith a consequent trigger to increased oxygen consumption and metchronic intrauterine tissue hypoxia [31]. This can profoundly affect including alterations in myelination and cortical connectivity and aberratineurons [32].


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together with cigarette smoking confer a risk of COPD which is highe[40].

Breathing disorders during sleep or sleep deprivation during pregn

There is a number of breathing disorders during sleep, ranging from simpforms of obstructive sleep apnea syndrome and obesity-hypertensiontrimester, when gestational sleep disorder breathing (SDB) is most prevalence of habitual snoring has been evaluated to be present in betwee

pregnant women [41]. About 7% of women with respiratory disorders durbaby small for gestational age, with a more than threefold increased ribaby with low Apgar scores and a higher risk of mortality [42]. SDB gestational diabetes with a risk 2 to 7 times higher than the controlmechanisms depicted in Figure 2 [43,44]. The onset of hypertension is with maternal morbidity but also with increased fetal mortality or


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cortisol. As a result, longitudinal growth of the fetus could be impaircortisol. Another possible explanation is that iron deficiency causes ox

erythrocytes and the feto-placental unit. Iron deficiency can also increase infections, which can stimulate the production of CRH and are a major risdelivery [55]. Moreover, offspring of mother with anemia had double(OR = 2.42) and more than triple the risk of current asthma at the age of s[56]. On the basis of such evidences, the fact that low to moderate dose irin early pregnancy benefits fetal growth in women with iron deficiency isrecommended daily dietary allowance for iron in pregnancy is 27 mg insadult non pregnant population. Lactation requires a daily dietary allowancThe positive effect on fetal growth could be explained by a preferential trplacenta and fetus [58]. Even the lack of other micro-nutrients such as seD and C, zinc and folic acid is responsible for the onset of disorders affecsystem in the offspring [46].


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stress and immune function in human adults has been documentemononuclear cells from healthy young women whose mothers experien

life events during their pregnancy (Prenatal Stress, PS group), and from agroup, were stimulated with phytohemagglutinin (PHA), and subsequent was measured. A bias for T-helper 2 (Th2) cytokine production due to anIL-4 relative to IFN-gamma after PHA stimulation was observed in PS sIL-6 and IL-10 were also significantly elevated suggesting a direct prenatal stress exposure and alterations in immune parameters in adult wchildren whose mothers experienced interpersonal violence and traumhave twice the risk of developing asthma during their childhood [70].

Exposure to maternal stress also affects the childs cognitive performanccomprehension and reasoning, all of them principally realized in the prebrain region is known to develop later in term of myelination and synapof its protracted development and the expression of glucocorticoid rece


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continues into adult life. This is associated with transient wheezing illnchildhood and increases the risk of chronic obstructive pulmonary disease

Also passive exposure of pregnant women to ETS may lead to asthmpassive exposure to ETS, mainly during the third trimester of pregnancassociated with asthma- and allergy-related symptoms after adjusting for in a multivariate analysis (current wheeze: OR = 1.42, pruritic rasconsequence public health policies should be oriented not only towards but also reinforce elimination of ETS exposure of pregnant women [79]. Ipassive smoking increases the incidence of wheeze and asthma in childrenby at least 20%. Preventing parental smoking is crucially important tasthma. Nicotine, in fact, causes higher placental vascular resistance, decrthe uterus, and increases the concentration of carboxyhaemoglobin, all facchronic hypoxia and reduced fetal development [80]. In addition, cmothers have a higher risk (RR = 1.5) of being overweight or obese [8withdrawal promotes overeating and weight gain, and on the other,


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view that tightly woven encasements surrounding feather pillows act as a [91].

In addition, chemicals used for cleaning are responsible for increasing dommore than doubling the risk of wheeze (RR = 2.3), [92] and they cand FEF 25-75 [93]. This derives from both a detrimental effect on the devin the prenatal period (epigenetic effect?) but also from the effects in the pparticular, this association was noted for the use of cleaning sprays [85]ingredients such as alcohol, ammonia, chlorine, glycol and glycohydroxide (caustic soda), acrylic polymers and terpenes [94]. When spraycleaned, these compounds enter easily into the airways, irritating them [86

The role of environmental pollution

In New York City it has been shown that prenatal exposure to pollutants


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It has been reported that women who consumed high amounts of fish durilower incidence of postpartum depression during the first six months af

vs. 11.19% of women with low intake), while not all authors agree on ththe development of the brain and cognitive functions [92,102]. Fish is an polyunsaturated fatty acids (docosahexaenoic acid DHA-EPA-and acidand essential nutrients that are not produced by the human body, and whirole in the development of the neurological, immune and cardiovasculaessential for the development of the brain and retina, tissues that have thof these substances during the second half of pregnancy and early in childall types of fish can be consumed during pregnancy, because in some kindof mercury is higher. Salmon, shrimp and hake are recommended becausefatty acids and low in mercury, whereas large deep-water fish like tAtlantic shark should be avoided [103,104]. Small-sized fish, like sardinebecause of their high content of selenium, an element capable of redumercury [105].


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preterm delivery in the period 20-28th week of gestation by 70% and by 32nd week period; but has no influence on the labor thereafter. In fact, lo

folic acid can alter the function of lymphocytes and neutrophils, incbacteriuria in pregnancy, which in turn can increase the risk of preterm del

Conclusions

Studies in both animal and human models have shown that exposure during the critical stages of pregnancy can alter the expression of gene

leads to changes that may persist throughout life causing increased susceAdverse events that lead to embryonic, fetal or neonatal epigenetic chanfor altering the mechanisms of growth and metabolism observed laterhealth of the child and issues that will determine its appetite and metabolitemperament in life depend on the type and amount of nutrients that the b

b ll i d d i f i hi h i i d b f d f


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Intr a-uterine insults:MalnutritionPlacental dysfunctionHypoxiaDecreased blood flow

Catch upgrowth

HypernutrObesityPhysical inAgeing

PRENATAL POSTNATAL

Change in


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Sleep disordersand intermittent

hypoxemia

Shorter sleepdurationP

REGNANCY

Sleepdisorder

breathing

Loss of

sleep

Change inadipokines

Inflammation

SympatheticTone

OxidativeStress

AlteratedHPA axis

Figure 2

the origins of health and disease: the influence of maternal diseases and lifestyle during...

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