Discussion
Prematurity remains the leading cause of neonatal morbidity and
mortality. Intrauterine growth restriction is another first-line cause
of the adverse neonatal prognosis, both as a single pathology or in
association with prematurity. According to studies, there is a
concordant relationship between preterm birth and intrauterine growth
restriction.5 Intrauterine growth restriction shows
chronic fetal distress based on placental dysfunction, with placental
abnormal vascularization leading to hypoperfusion, ischemia, and release
of reactive oxygen species in the context of oxidative stress.
Both prematurity and intrauterine growth restriction have an increased
incidence among pregnancies complicated with
preeclampsia6, results that are consistent with the
data in the literature. In this context, we decided to highlight the
unfavorable short-term prognosis of prematurity, as well as intrauterine
growth restriction, in both preterm and term infants with low birth
weight.
According to the results obtained, the frequency of premature births in
the Emergency University Hospital of Bucharest, a multidisciplinary
hospital in which multiple complex cases are addressed, was
approximately 13%. The cases of complicated preterm infants with
intrauterine growth restriction accounted for 6.5% of all premature
births recorded in the clinic during the 3 years of study and about 1%
of all births. The cases of newborns with low birth weight for the
gestational age accounted for about 2% of all births recorded during
the study period. Thus, the data obtained are consistent with reports in
the literature; the proportion of intrauterine growth restriction among
preterm births is higher than that among term births.5
Another parameter that was consistent with the published reports is the
predominance of female fetal sex in cases of intrauterine growth
restriction 7,8 and the predominance of male sex among
premature births. However, the difference was not significant;
therefore, according to the results, we can consider the following
conclusions of the study by Quinones et al,9 focusing
mainly on the influence of fetal sex on the perinatal prognosis of cases
of intrauterine growth restriction: fetal sex is not associated with
unfavorable perinatal prognosis in cases of intrauterine growth
restriction.
The purpose of the analysis of the values of the Apgar index as a marker
of the immediate neonatal adaptation was to objectively highlight the
difference of adaptation, especially in the case of premature infants
with low weight for gestational age and those infants with weight
corresponding to their gestational age. The values obtained were not
different from expectations, more specifically, the adaptation of
preterm infants with low weight for the gestational age was the most
deficient, with a median value of 7. Figure 1 shows that there were no
values that deviated significantly from the value of the median, with
the distribution being proportional. However, the degree of adaptation
was higher in the group of premature infants with weight corresponding
to the gestational age, as expected. In figure 2, it appears that the
values of the Apgar index were higher in this group. However, in the
single cases of small Apgar index, the median assigned to group 2 was 8.
The most favorable adaptation was noted in the newborns in group 3. In
groups 2 and 3, maximum values of the Apgar score were noted.
Birth by caesarean section predominated in all study groups, with a
statistically significant difference noted among the 3 groups. This is
justified by the fact that birth by cesarean section of premature
infants is associated with lower neonatal mortality10,
which is explained by the possibility of early and promising neonatal
intensive care.11 Additionally, in this context, it is
worth mentioning that the birth weight is inversely proportional to the
rate of neonatal complications, in which the impact of the vaginal birth
decreases with increasing fetal weight.12 Even though
premature birth is not an absolute indication of cesarean delivery, this
mode of birth provides a better prognosis for preterm infants by
avoiding prolonged labor and allowing for a less traumatic
birth.12
Regarding obstetric factors, it is not surprising that we obtained a
higher incidence of pelvic presentation among preterm infants; however,
the incidence of pelvic presentation among low-weight newborns for
gestational age was slightly higher than that in the general population.
The data at the general population level show an incidence of caesarean
section of 4%-40% among term births an 25%-60% among premature
births, which is inversely proportional to the gestational age. As can
be seen in Figure 3, the incidence of pregnancy-induced hypertension
predominates in cases of growth restriction, both in premature newborns
and particularly in newborns with term growth restriction. This
situation is also characteristic of preeclampsia, except that it
prevails in preterm infants with intrauterine growth restriction and low
weight for gestational age. These results confirm the results of other
studies, namely that placental functional disorders belong to the group
of progressive multifactorial pathologies that present deteriorating
signs and symptoms over time.
Fetal malformations predominated in the group of premature newborns with
growth restriction, which is consistent with published reports on the
association of fetal malformations with intrauterine growth
restriction13,14and prematurity.15The umbilical cord pathology, mainly the true cord knot, did not have a
significant association with intrauterine growth restriction, which is
consistent with the data in the literature; however, this association
has not been fully established and is still being studied16,17,18. Regarding the multiple nuchal cord, a
statistically significant association has not yet been evidenced between
these condition and adverse neonatal prognosis.19According to the results obtained in our study, the incidence of
multiple nuchal cord was higher in the groups with growth restriction.
Essentially, the purpose of our study is to show that intrauterine
growth restriction, a condition closely related to placental
dysfunction, is a common diagnosis that is associated with an increased
risk of perinatal mortality and morbidity. The fetal response consists
in circulatory adaptations, respectively brain-sparing reflected by the
value of cerebroplacental ratio, which has a better predictability index
of adverse outcomes especially in fetuses with intrauterine growth
restriction 20. The meta-analysis published in 2016,
which had the aim to evaluate the perinatal predictability value of
cerebroplacental ratio concluded that abnormal cerebroplacental ratio is
associated with increased rates of unfavorable perinatal outcome, having
a moderate-high specificity and sensitivity21. An
abnormal cerebroplacental ratio was associated with higher rates of need
of neonatal intensive care and neonatal complications and suggest a
poorer perinatal outcome of fetuses with intrauterine growth
restriction21. Regarding the normalization of the
cerebroplacental ratio, the results of a recent sub-analysis which
started from the hypothesis that normalization of this ratio associates
a poorer perinatal outcome due to the loss of the compensatory mechanism
of brain sparing, showed that there is no additional worsening of the
perinatal prognosis given by this normalization22.
Recent studies have analyzed the impact of the abnormal cerebroplacental
ratio on neurodevelopmental outcome in fetuses with intrauterine growth
restriction. Meher et al in his review suggested that the brain sparing
phenomenon has not only a protective benefit but is associated with a
poorer psychomotor development at one and two years caused by implied
cerebral hypoxia23.
In the context of the results obtained, as well as of the discussions
regarding the advantages of the expectant management for both short and
long-term outcome, the decision regarding choosing the most appropriate
time for termination of the pregnancy becomes even more difficult. Thus,
each case should be treated individually with a therapeutic behavior
guided by the main pathology but also the associated one in order to
reduce the rate of iatrogenic prematurity among the fetuses with
intrauterine growth restriction but also to offer them the best
prognosis.
Further, with reference to Table 4, which contains the frequency and
comparative analysis of all the neonatal complications studied for the 3
groups, one can observe the objective impact of intrauterine growth
restriction during the immediate neonatal period.
Thus, as discussed in the results chapter, the highest frequency of
neonatal complications occurred in study group 1. Statistical
significance was obtained for the following complications:
cardio-vascular arrest (P <0.001), acute respiratory failure
(P <0.001), ulcer-necrotic enterocolitis(P <0.001),
hypoxia present in 58% of premature cases with growth restriction and
in 23% of cases of gestational age weight (P <0.001),
respiratory distress (P <0.001), cerebral edema (P = 0.004),
intraventricular hemorrhage (P <0.001), cerebral hemorrhage (P
= 0.003), pulmonary hemorrhage (P <0.001), neonatal infection
(P <0.001), hypoglycemia(P <0.001), retinopathy (P
<0.001), anemia (P <0.001), hemorrhagic disease (P =
0.002), disseminated intravascular coagulation (P <0.001),
disease of hyaline membranes (P <0.001), neonatal sepsis (P =
0.002), need for intensive neonatal therapy (P <0.001), and
death (P <0.001).
Intrauterine growth restriction is associated with an increased risk of
both antenatal and neonatal complications. There is an increased
negative impact on prognosis when fetuses with intrauterine growth
restriction are born premature. In our study, newborns with low weight
for gestational age had an increased incidence in complications in
comparison to newborns with adequate weight, specifically:
cardio-vascular arrest, 0.1% in the general population and 1% in the
present study; acute respiratory failure, 0.45% in the general
population and 2% in the present study12; however,
respiratory distress, cerebral edema, ulcer-necrotic enterocolitis,
pulmonary hemorrhage, persistence of the arterial canal, cerebral
hemorrhage, seizures, retinopathy, hemorrhagic disease, disseminated
intravascular disease, and hyaline membrane disease were absent in term
infants with low birth weight for gestational age, indicating that these
newborns have a good neonatal adaptation by leaving an environment
already unfit for their well-being, i.e. intrauterine.