MINI REVIEW
published: 03 February 2022
doi: 10.3389/fmed.2021.769734
Prematurity and Low Birth Weight in
Neonates as a Risk Factor for
Obesity, Hypertension, and Chronic
Kidney Disease in Pediatric and Adult
Age
Maria Agostina Grillo 1,2 , Gonzalo Mariani 1,3,4 and Jorge R. Ferraris 1,2,5*
1
Pediatric Department Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 2 Pediatric Nephrology Division, Buenos
Aires, Argentina, 3 Neonatology Division, Buenos Aires, Argentina, 4 Instituto Universitario Hospital Italiano de Buenos Aires,
Buenos Aires, Argentina, 5 Pediatric Department, Universidad de Buenos Aires, Buenos Aires, Argentina
Edited by:
Ana Cusumano,
Centro de Educación Médica e
Investigaciones Clínicas Norberto
Quirno (CEMIC), Argentina
Reviewed by:
Brian Duncan Tait,
The University of Melbourne, Australia
Karel Allegaert,
University Hospitals Leuven, Belgium
Jessica Briffa,
The University of Melbourne, Australia
*Correspondence:
Jorge R. Ferraris
jorge.ferraris@hospitalitaliano.org.ar
Specialty section:
This article was submitted to
Nephrology,
a section of the journal
Frontiers in Medicine
Received: 02 September 2021
Accepted: 23 November 2021
Published: 03 February 2022
Citation:
Grillo MA, Mariani G and Ferraris JR
(2022) Prematurity and Low Birth
Weight in Neonates as a Risk Factor
for Obesity, Hypertension, and
Chronic Kidney Disease in Pediatric
and Adult Age. Front. Med. 8:769734.
doi: 10.3389/fmed.2021.769734
Frontiers in Medicine | www.frontiersin.org
Low weight at birth may be due to intrauterine growth restriction or premature birth.
Preterm birth is more common in low- and middle-income countries: 60% of preterm birth
occur in sub-Saharan African or South Asian countries. However, in some higher-income
countries, preterm birth rates appear to be increasing in relation to a reduction in the
lower threshold of fetal viability. The cutoff is at 22–23 weeks, with a birth weight
of approximately 500 g, although in developed countries such as Japan, the viability
cutoff described is 21–22 weeks. There is evidence of the long-term consequences
of prenatal programming of organ function and its relationship among adult diseases,
such as hypertension (HT), central obesity, diabetes, metabolic syndrome, and chronic
kidney disease (CKD). Premature delivery before the completion of nephrogenesis and
intrauterine growth restriction leads to a reduction in the number of nephrons that are
larger due to compensatory hyperfiltration and hypertrophy, which predisposes to the
development of CKD in adulthood. In these patients, the long-term strategies are early
evaluation and therapeutic interventions to decrease the described complications, by
screening for HT, microalbuminuria and proteinuria, ultrasound monitoring, and renal
function, with the emphasis on preventive measures. This review describes the effects of
fetal programming on renal development and the risk of obesity, HT, and CKD in the future
in patients with low birth weight (LBW), and the follow-up and therapeutic interventions
to reduce these complications.
Keywords: preterm neonates, low birth weight, chronic kidney disease, arterial hypertension, fetal programming,
extrauterine growth restriction, intrauterine growth restriction, small gestational age
INTRODUCTION
Preterm birth affects ∼11% of births worldwide. The availability of new therapeutics and
the increasing complexity of neonatal intensive care units have allowed the survival of
infants born at 22 or 23 weeks with birth weights close to 500 g (1–3). The annual
prevalence of prematurity in Argentina is between 8 and 9% (4). In this article, we
define preterm newborns (PTNs) as those born before 37 week gestational age (GA); small
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adaptive response becomes harmful. The increased glomerular
surface area leads to sodium retention and systemic HT
and glomerular hyperfiltration disrupts renal autoregulatory
mechanisms generating intraglomerular HT (19). These
processes render the nephrons sclerotic and this leads to a
further decrease in the number of nephrons that reduces the
filtration surface, and the remaining nephrons must hypertrophy,
manifesting with microalbuminuria and then proteinuria as
surrogates of hyperfiltration (12). As a consequence, arterial
and glomerular HT is produced, generating glomerulosclerosis,
further reducing the number of nephrons (Figure 2). In the
terminal phases of CKD, widespread deposition of extracellular
matrix in the renal interstitium is recognized as a final common
pathway for nephron destruction, resulting from the maladaptive
repair of damaged nephrons (20).
Whereas growth restriction increases disease risk in
all individuals, often a second hit is required to unmask
“programmed” impairments. Programmed disease outcomes
are demonstrated more commonly in male offspring compared
with females, with these sex-specific outcomes partly attributed
to different placenta-regulated growth strategies of the male
and female fetus. An extremely common and severe “second
hit” for women, known to unmask a variety of conditions in
adult life, is pregnancy; it is the greatest physiological “stress
test” that a woman can experience in her life. Females who were
born small are at an increased risk of pregnancy complications
(preeclampsia, gestational diabetes, HT, thyroid, and liver and
kidney diseases). The fetus that developed in the womb may
also have been exposed to suboptimal conditions and may be
programmed to develop the disease in later life, consequences
of being born small due to uteroplacental insufficiency. Male
fetuses grow at a faster rate than do females and this accelerated
growth trajectory makes male fetuses more vulnerable during
disturbed pregnancies, with less favorable outcomes occurring
throughout the life course of the individual. These sexually
dimorphic adaptations are regulated by the placenta. In animal
models (e.g., rats), uteroplacental insufficiency results in LBW
and programs sex-specific offspring dysfunction and deficits that
affect males more than females: development of increased SBP in
adult life. This is despite both sexes having decreased nephron
number, earlier glomerular hypertrophy, and impaired glucose
tolerance, and reduced insulin secretion. Although women are
generally less susceptible to programmed disease development,
under the physiological demands of pregnancy, various disease
states are often unmasked (21).
for gestational age (SGA) as neonates with a birth weight less than
the 10th percentile for their GA; low birth weight (LBW) and very
low birth weight (VLBW) as those with birth weight <2,500 and
1,500 g, respectively, and extremely low birth weight (ELBW) as
those with birth weight <1.0 kg.
Preterm newborns and SGA are particularly vulnerable to
the development of hypertension (HT) and chronic kidney
disease (CKD). In the former, there is premature exposure to
the conditions of extrauterine life, in organs that are not yet
prepared for it, where the premature arrest of the development
of the vascular tree results in stiffer and narrower arteries, which
predisposes to glomerular and endothelial damage, structural
alterations due to glomerular hyperfiltration, and increased
systolic blood pressure (SBP) in children and adults (5, 6).
Preterm infants may also have either an appropriate birth weight
for GA or maybe SGA if they experienced superimposed growth
restriction. Such growth restriction per se is also associated
with programming effects in the kidney (7). In SGA infants
who have had intrauterine growth restriction (percentile drop
throughout pregnancy as a consequence of an alteration in
placental circulation), exposure to intrauterine stress generates an
altered “fetal programming,” inducing changes at the molecular
level and in the functioning of systems, with alterations in renal
growth and a decrease in the number of nephrons, which would
increase the incidence of HT, CKD, and the risk of metabolic
alterations, such as insulin resistance. Pregnancies affected by
maternal HT have greater short-term fetal complications, such as
fetal death and SGA, as a consequence of placental insufficiency
due to preeclampsia (8, 9). The association between preeclampsia
and SGA is based on abnormal placental development and
decreased placental perfusion, secondary to alteration of the
maternal spiral arteries, with spontaneous vasoconstriction of
the arteries and placental ischemia, reperfusion-type injury, and
oxidative stress (10, 11) (Figure 1).
PATHOPHYSIOLOGY
Nephrogenesis ends at 36 weeks and the reduction in the
number of nephrons has consequences for renal health. The
number of glomeruli in the normal human embryo increases
from week 10, reaches its largest increase between 18 and 32
weeks and is completed between 32 and 36 weeks (12). Each
normal kidney has an average of 600–800 thousand glomeruli.
Birth weight correlates with the number of glomeruli, estimating
an additional 2,32,217 nephrons in each kidney for each 1 kg
of birth weight (13, 14). The number of nephrons is reduced
by factors that restrict intrauterine growth: micronutrient
deficiencies, infections, hypoxia, drugs (nephrotoxic or not,
such as beta-lactams), maternal hyperglycemia, glucocorticoids,
smoking, or alcohol consumption during pregnancy. The
nephron endowment reached at birth will be the one with which
the individual will spend the rest of his or her life (13–16).
According to Brenner’s hyperfiltration theory (17, 18),
humans with a decreased nephron endowment can maintain
a normal GFR as individual nephron hypertrophy to increase
the total surface area available for renal work. Over time, this
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EFFECTS OF PREMATURITY ON
NEPHROGENESIS
The number of glomeruli is significantly lower in all groups
of preterm infants (22). As 60% of nephrons are formed
during the third trimester, children born preterm have a
significantly lower number of nephrons at birth, which does
not catch up adequately postnatally (7). The progression of
postnatal nephrogenesis, evaluated in autopsies in preterm
infants, evidenced the persistence of glomerulogenesis after
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Small Neonates and CKD
FIGURE 1 | Pathophysiology of fetal “programming” in SGA infants in relation to the decrease in the number of nephrons and postnatal HT. HIF-1, hypoxia-induced
factor-1; SGA, small for gestational age; VEGF, vascular endothelial growth factor; EPC, neonatal endothelial progenitor cells. Modified from Stritzke et al. (9) and
Crump et al. (11).
terminal epithelial differentiation fate, others (Notch, Brn-1,
IRX, KLF4, and Foxi1) regulate the differentiation of specific
nephron segments and cellular types (25). Moreover, epigenetic
changes, characterized by alterations in chromatin structure, lead
to stable and potentially hereditable changes in gene expression.
In particular, DNA methylation has been strongly implicated in
fetal renal development and disease (25).
Studies in clinically stable PTN demonstrate that plasma
creatinine correlates with GA. Plasma creatinine at birth reflects
tubular reabsorption of creatinine. Creatinine increases in the
first 36–92 h of life and then gradually decreases. In PTN with
GA <32 weeks, the increase in plasma creatinine is greater and
the decrease more gradual (being greater in those born with
<28 weeks), probably due to a slow progression of glomerular
function and tubular creatinine reabsorption (26). Tubular
creatinine reabsorption may be a physiological phenomenon in
birth but altered and with a gradual decrease as postnatal
age progressed. Neonates more than 40 days old with acute
kidney injury (AKI) showed lower glomerular counts, unlike
those with longer survival and without renal failure, but had
glomerulomegaly as a compensatory mechanism (23). However,
the development of animal models (surgical renal ablation, renal
fibrosis, or others) would be important for the study of the effects
of prematurity on nephrogenesis (24).
The causes underlying a reduced number of nephrons in
an individual are both genetic and environmental. Ongoing
interaction between genes and the environment from prenatal
to adult life will contribute toward defining the renal potential
of an individual. Signaling molecules and transcription factors
have been implicated in determining segmental nephron identity
and functional differentiation. Whereas some of these genes
(p53 gene family, hepatocyte nuclear factor-1) promote the
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FIGURE 2 | Pathophysiological consequences of altered nephrogenesis in preterm newborns (PTN) and SGA infants.
with children with adequate prenatal and postnatal growth (22).
Both intra- and extrauterine growth restrictions were associated
with reduced GFR. However, rapid “catchup” growth (i.e., an
upward crossing of weight centiles) or increase in BMI leads
to the development of higher blood pressure, insulin resistance,
and cardiovascular risk already in childhood. These findings are
most marked in those who were born small and became relatively
larger (28).
Along the same lines, in children aged 1–7 years with a history
of PTN and SGA, decreased GFR (78 ± 26.8 ml/min/1.73 m2 ),
microalbuminuria (85 ± 187 mg/gr), increased SBP in 21%, and
diastolic blood pressure (DBP) in 37% of patients were observed,
with mean SBP and DBP between 10 and 15 mmHg above
the mean of healthy term newborns. Renal volume increased
until 2.5 years of age and then decreased, implying glomerular
hypertrophy in the first stage and then possibly glomerular
sclerosis (29).
the “immature” kidney due to slow urinary flow and increased
creatinine leakage along the immature tubular structures (19).
Preterm newborns may present with AKI events (8–24%)
secondary to renal hypoperfusion, asphyxia, respiratory distress
syndrome, nephrotoxic drugs exposure (prenatal or postnatal),
and infections. In addition, PTNs who are SGA are more
vulnerable to renal injury, as SGA has greater nephron depletion
and renal dysfunction (22). Decreased glomerular filtration rate
(GFR) and increased microalbuminuria have been observed in
children and adults who were PTN and SGA, compared with
adult PTN but with adequate weight for GA (22).
Epidemiologic studies have shown that incomplete recovery
from episodes of AKI constitutes a risk factor for progressive
CKD, and CKD, in turn, increases susceptibility to AKI: the
proximal tubule, therefore, becomes a primary target of injury
and progression of CKD (20). Preterm and critically ill newborns
are predisposed to developing AKI because of renal function
immaturity and incomplete nephrogenesis in the early postnatal
period, which can be irreversibly impaired by drug exposure, and
cellular injury to glomeruli or tubules, which may impair repair
capacity and increase susceptibility to renal disease later in life
(7). In the US, 40% of ICU neonates experienced AKI, it was
found that AKI was only recorded in the discharge summary
in 13.5% of infants, and none were referred for nephrology
follow-up (27). This study illustrated the lack of awareness of the
potential long-term impact of neonatal AKI.
On the other hand, PTNs are at risk of extrauterine
growth restriction (EUGR), defined as growth below the 10th
percentile of growth expectancy, generating consequently greater
alterations in nephrogenesis and renal function in adulthood.
A lower GFR was evidenced in children examined at 7 years
of age (preterm <30 weeks whether SGA or EUGR) compared
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LONG-TERM CONSEQUENCES IN THE
KIDNEY OF THE PRETERM AND SGA
NEONATE
Early renal complications are related to immaturity in tubular
function (tubulopathy of prematurity), presenting inadequate
free water management, electrolyte and acid-base imbalance, and
mineral and protein losses (30). The increase in GFR that occurs
from birth is accompanied by a “parallel” increase in tubular
functions to avoid water and solute losses through urine. The
activity of the Na+ -K+ -ATPase pump is proportional to GA,
which explains the lower reabsorption capacity in PTN <32
weeks (31). Insensible water losses increase in inverse relation
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weight adequate for GA. Whereas there were no differences in
blood urea or creatinine values, preterm-born adolescents had
a significantly lower GFR compared with term neonates (126.2
vs. 134.3 mL/min/1.73 m2 ). Microalbuminuria was found in 7%
of PTN patients, especially in women or in those with a high
BMI (40). A meta-analysis, which included more than 2 million
individuals, found that a history of SGA was associated with an
80% increased likelihood of microalbuminuria. Another study
described a 6.3% increase in the urine albumin–creatinine ratio
for every 100 g reduction in birth weight (41, 43).
In adults, the incidence of CKD under 43 years of age, who
were born PTN, was evaluated in a large cohort study in Sweden.
Of the 4,305 participants, 0.1% had a diagnosis of CKD with the
overall incidence rate being 4.95 per 100,000 person-years at all
ages examined. The incidences per GA at birth were 9.24 for
PTN, 5.90 for early term neonates (37–38 weeks), and 4.47 for
full-term neonates (39–41 weeks); PTN and early term neonates
had two times the risk of CKD compared with full-term neonates.
Moreover, GA was inversely related to CKD risk, with the risk
being higher in PTNs and SGA; this association was stronger for
the development of CKD in childhood and was maintained in
adulthood (44). We can hypothesize that the possibility of CKD
will be higher in the extremely preterm neonate (<28 weeks)
and very preterm (28–32 weeks) compared with moderate to
late preterm (32–37 weeks) since they are born in the period
of exponential nephrogenesis and exposed to several risk factors
that can compromise its correct development.
A Norwegian birth registry study showed that birth weight
less than the 10th percentile for the population was associated
with a relative risk of 1.7 for end-stage kidney disease (ESKD)
during the first 38 years of life, where LBW was associated
with an increased risk of ESKD due to any cause (congenital
malformations, hereditary diseases, and glomerular diseases) (45,
46). An investigation in a subgroup aged 18–42 years, excluding
subjects with congenital renal disease, found that LBW per se
was not significantly associated with developing ESKD, but being
SGA was. In this Norwegian study among those 18–42 years
old, being SGA (birth weight less than 10th percentile for GA)
was significantly associated with the risk of ESKD, and the
effect was much stronger in those born preterm with SGA than
those born at term with SGA (RRs of ESKD of 4.02 and 1.41,
respectively). These population level data suggest that both SGA
and prematurity are important risk factors and likely potentiate
each other’s effects, with preterm SGA infants being at the highest
risk. (45, 47) On the other hand, renal risk in children born
preterm was similar between appropriate GA and SGA and also
between VLBW and LBW (25).
to GA. The kidney is in frank natriuresis, inversely proportional
to GA, and in PTN <35 weeks, the tubule is unable to conserve
sodium. Early onset neonatal hyponatremia in PTNs is secondary
to excess water intake associated with increased antidiuretic
hormone secretion (30, 31). Serum bicarbonate is lower in PTN
(with renal threshold 18 mEq/L) or weight <1,300 g (renal
threshold 14 mEq/L); the mechanisms that regulate bicarbonate
absorption and secretion have progressive maturation (31).
Late complications with increased risk of CKD, HT, and
hypercalciuria in adulthood, are more evident in those PTNs
who were born SGA as a consequence of intrauterine growth
restriction secondary to placental insufficiency.
ARTERIAL HT
There is an inverse relationship between birth weight and systolic
HT in adolescence (32, 33). A study by Mhanna et al. evaluated
blood pressure, obesity, and weight gain as risk factors for HT in
204 patients over 3 years of age, who had been born weighing
<1,000 g, with GA of 26 weeks (34). In this population, they
found a prevalence of HT of 7.3%, associated with an increase
in the body mass index (BMI) and with higher weight gain
from birth.
Along the same lines, in another study, over 6,269 PTNs,
528 were SGA and had a higher risk of HT, with the incidence
being higher with smaller fetal size. When compared to PTN with
adequate birth weight for GA, the SGA had an increased risk of
HT of 54% (35).
The risk of presenting HT is also maintained in adulthood. A
meta-analysis including preterm-born adults concluded that the
mean difference between preterm-born adults and controls was
4.2 mmHg for SBP and 2.6 mmHg for DBP. In another metaanalysis of 1,571 adults born with VLBW (< 1,500 g) vs. 777
full-term controls, mean blood pressure averages were higher for
subjects <1,500 g; they had 3.4 mmHg higher SBP and 2.1 mmHg
higher DBP than controls. The only perinatal event associated
with higher blood pressure was maternal preeclampsia (36).
These differences are considerable given that, at the population
level, it is estimated that a 2 mmHg reduction in SBP results in a
7 to 14% reduction in mortality from ischemic heart disease and
a 9 to 19% reduction in mortality from stroke (35–37).
In PTN and SGA patients, a history of breastfeeding was a
protective factor for the development of arterial HT; subjects with
a birth weight under 2,500 g who were breastfed had a lower
prevalence of HT (38). Both breastfeeding during the first months
of life and avoiding rapid weight gain in childhood have been
shown to prevent the later risk of obesity and dyslipidemia and
reduce glucose tolerance (7).
CHRONIC KIDNEY DISEASE
EVALUATION, DIAGNOSIS, AND
PREVENTION
Reduced nephron endowment and neonatal AKI contribute to
the development, HT, and kidney disease (39–42).
Renal function was compared in adolescents born with a
history of SGA and mean GA of 27.8 weeks and mean weight of
1,048 g, with adolescents of the same age born at term and birth
There are currently no guidelines to identify infants at increased
risk of developing CKD due to a low number of nephrons, either
congenital or acquired.
However, children and adults who were PTN or SGA need
long-term follow-up and early preventive actions to help preserve
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FIGURE 3 | Follow-up proposal for PTN and/or SGA infants in three stages: avoid, reduce, and treat. Cr, creatinine; Cis C, cistatine C; Up/Ucr, urine protein or urine
creatinine; UMicroalb/Ucr, urine microalbuminuria or urine creatinine; Ucal/Ucr, urine calcium or urine creatinine; BP, blood pressure; ACEi, angiotensin-converting
enzyme inhibitors; ARBs, angiotensin II receptor blockers.
renal function and CKD. Clinical follow-up should be structured
according to greater or lesser risk of developing CKD in the
future with the participation of pediatricians and pediatric
nephrologists with varying degrees of intervention (48). On
the other hand, obstetricians should monitor fetal development,
avoiding all risk factors for prematurity and SGA, in close contact
with neonatologists (Figure 1).
These interventions should include counseling the parents
and then the older patient on how to avoid potentially
nephrotoxic drugs exposures (antiinflammatory, antibiotics) (49,
50), other aggravating factors (such as dehydration and urinary
tract infection), and control of risk factors for CKD progression
(obesity, HT, diabetes, dyslipidemia, anemia, and smoking). HT
is an important risk factor for the development of CKD, and
effective blood pressure control has been shown to delay the
progression of CKD (49). Another risk factor is AKI during the
perinatal period with a prevalence between 12.5 and 39.8% in
PTN <1,500 g (51), and with progression to subsequent CKD
between 10 and 50% (52).
Early detection of potential indicators of hyperfiltration,
such as impaired renal reserve, blunted solute clearance, and
microalbuminuria, may provide subtle clues to the presence of
reduced nephron number (25).
One follow-up option proposed is as follows in all visits for BP
controls, assess growth parameters including BMI, and perform
family education on the potential risk of CKD, and continue
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this follow-up until after adolescence and adulthood (49). BP
control should begin before 1 year of age (48) and in children over
5 years of age, control with annual ambulatory blood pressure
monitoring should be performed (5, 48).
At 6 months after discharge from the neonatal intensive care
unit, it is suggested that laboratory tests with serum creatinine
and/or cystatin C, and microalbuminuria be performed, and then
the periodicity of these tests should be adjusted according to these
results or the appearance of comorbidities: history of AKI in the
neonatal period or during infancy, HT, obesity, and ultrasound
abnormalities. In these cases, blood and urine laboratory controls
should be performed annually (48, 49) (Figure 3).
The development of nephrocalcinosis in PTNs confers an
additional risk for CKD. Nephrocalcinosis in PTN <32 weeks
and birth weight <1,500 g has a reported prevalence of 7–64%
(53), with a resolution of up to 75% within the first year of life
(48, 53).
Although some studies describe alterations in renal
size on ultrasound monitoring (small kidneys in preterm
patients), there is no evidence to indicate systematic
ultrasound monitoring. However, baseline ultrasound is
recommended to detect small kidneys, renal asymmetries, or
structural alterations.
From the age of 18 years, BP, BMI, serum creatinine, and
microalbuminuria should be monitored two times a year until
the age of 40 years and then annually (7, 48, 49).
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Regarding nutritional recovery, rapid growth (catchup)
should be avoided to prevent exacerbation of the renal and
cardiovascular risk associated with obesity (44, 45). From
childhood onward, an adequate “nephroprotective” dietary
pattern should be followed, consisting of a reduction in
sodium, carbohydrates, saturated fats, and avoidance of excess
protein, combined with increased physical activity and restraint
of smoking.
Postnatal catchup growth is encouraged in PTNs and SGA
in developing countries with the aim of improving resistance to
infections, reducing stunting, malnutrition, and reaching normal
neurodevelopment. However, this rapid growth can be linear,
or present with unbalanced growth in weight and height, with
risk of obesity and HT in adulthood (54, 55). Thus, the rapid
and continuous upward crossover of weight percentiles during
early childhood, with increasing BMI, has been associated with
an increased risk of obesity, HT in adulthood, and progression
to CKD in PTN, being more accelerated in those who develop
obesity (50). HT should be treated aggressively, and in case of
microalbuminuria and/or proteinuria, inhibitors of the reninangiotensin axis should be indicated.
The importance of this very close follow-up will be to
implement treatment in the early stages of CKD (1 o 2, cl > 60
ml/min/1.73 m2 ).
The role of strategies played in the clinical management
of neonatal intensive therapies in the development of CKD is
largely unexplored. Patients are often exposed to medications
or situations that compromise nephrogenesis and frequently
experience AKI. In recent years, results from the Assessment
of Worldwide Acute Kidney Epidemiology in Neonates
(AWAKEN) cohort studies have shown the importance of
prevention and early detection of AKI given its association with
long-term problems (56). If these are independent risk factors
for CKD, avoiding nephrotoxins and decreasing the incidence of
AKI could lead to better long-term outcomes.
Finally, we must remember that PT and LBW are
important risk factors for mortality in childhood and young
adulthood (57, 58).
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CONCLUSION
Hypertension and CKD have a significant impact on overall
morbidity and mortality. It is difficult to quantify the impact
of fetal programming on these diseases, but both PTN and
SGA have been associated with an alteration in nephrogenesis
with the consequent decrease in nephrons, so they have a
higher risk of CKD in adulthood, with a higher risk at
the lower birth weight (up to 70%). We consider that we
are facing a “silent epidemic” of CKD in these patients, so
preventive strategies should be implemented early to avoid the
progression of CKD. This requires not only a multidisciplinary
team (obstetricians, neonatologists, pediatricians, nephrologists,
neurologists, cardiologists, and nutritionists), but also public and
state measures aimed at awareness, information, and prevention.
There are gaps that require collaborative, prospective, and
randomized research studies in the area, which will help to
optimize cost-effective strategies.
AUTHOR CONTRIBUTIONS
MG and JF: concept and design and drafting of the manuscript.
MG, JF, and GM: acquisitions, analysis, and interpretation
of data. GM: critical revision of the manuscript. All authors
contributed to the article and approved the submitted version.
SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fmed.
2021.769734/full#supplementary-material
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Small Neonates and CKD
Conflict of Interest: The authors declare that the research was conducted in the
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