Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion
Introduction
Neurodevelopmental problems arising from intrauterine insults are a major socioeconomic burden [1]. Small-for-gestational-age (SGA) infants more often display lower intelligence levels, poor academic performance, low social competence, behavioral problems [2], [3], [4], and long-term cognitive impairments [5], [6], [7], [8], [9], [10]. Such deficits are well documented in preterm SGA infants, who are more inclined (vs preterm, normal-sized infants) to show behavioral [11], [12], sensory [13], [14], and cognitive [5], [7], [8], [15] dysfunctions later in life. However, emerging evidence suggests that near-term SGA babies are also at higher risk for adverse neurodevelopmental outcomes [10], [16], [17], [18]. This prospect is of particular concern, given that, according the definition used, between 3 and 10% of newborns are small at birth. A recently published meta-analysis, pooling several studies varying in neurodevelopmental measures, showed that standardized scores in term SGA babies were distinctly below (0.35 standard deviation [SD]) those of normal-sized controls [19].
Near-term SGA babies overall are thought to include both constitutionally small newborns as well as infants with true intrauterine growth restriction (IUGR), whereby in most cases fetal genetic growth potential suffers due to placental insufficiency [20]. The clinical standard to assess placental function is umbilical artery (UA) Doppler study, which is used in preterm babies to reliably distinguish between SGA and IUGR [21], [22], [23]. However, UA Doppler results are less decisive in differentiating near-term SGA and IUGR [24]. Neurobehavioral competencies at birth [25] and neurodevelopment at 2 years of life [18] may subsequently be diminished, even if Doppler studies are normal. This underscores a need to focus on signs of placental dysfunction, which may serve as markers of neurodevelopmental risk in near-term SGA births.
In both preterm [26] and term [27], [28] births, placental insufficiency is attributable to underperfusion. Related histologic manifestations in placentas of preterm babies correspond with observed deficits in mental development at 2 years and rightly should be factored into the neurodevelopmental status of markedly preterm infants [29]. However, there is a dearth of evidence linking histologic signs of PUP to neurodevelopmental outcomes in near-term births.
The objective of this study was to evaluate 2-year neurodevelopmental outcomes in near-term, small-for-gestational-age (SGA) newborns segregated by presence or absence of PUP-related histopathology.
Section snippets
Participants
A cohort of consecutive SGA singleton deliveries (gestational age [GA] ≥ 34 weeks) was recruited between January, 2010 and November, 2012 at a single institution. In each instance, SGA birth was suspected prenatally and confirmed as birth weight <10th percentile by local standards [30]. Pregnancies were dated according to first-trimester crown–rump length [31], while estimated fetal weight (EFW) was calculated using the Hadlock formula [32]. Only those with normal UA pulsatility index at
Results
A total of 104 potential SGA pregnancies were recruited (mean GA [SD], 33.4 [2.0] weeks; range 32–36.3 weeks). Of these, 11 were excluded for various reasons, including abnormal UA Doppler study during follow-up (n = 2), birth weight >10th percentile (n = 6), clinical chorioamnionitis (n = 1), and lack of parental consent for required placental exam (n = 2). Another 10 births were lost during follow-up, having no means of contact for neurocognitive evaluation. Baseline characteristics of births
Discussion
Our study is the first to ascertain that near-term SGA babies lacking prenatal evidence of placental insufficiency but showing PUP-related histopathology have greater risk of abnormal neurodevelopmental outcomes at 2 years of life.
Most of the evidence linking placental pathology and neurologic impairment is derived from cases of medicolegal litigation, where severe fetoplacental circulatory lesions and neurologic impairment or cerebral palsy are frequently coupled [41], [42], [43], [44].
Conclusion
In conclusion, our 2-year follow-up supports the concept that near-term SGA newborns with histologic evidence of PUP have lower neurodevelopmental scores, suggesting compromised neurologic maturation in utero. Such evidence should be considered when evaluating neurodevelopmental outcomes and defining preventive strategies.
Funding source
The study was supported by grants from the Cerebra Foundation (Carmarthen, Wales, UK), and the Thrasher Research Fund (Salt Lake City, USA).
Financial disclosure
The authors have indicated that they have no financial relationships to disclose relevant to this article.
Conflicts of interest
The authors have no conflicts of interest relevant to this article to disclose.
Condensation
This study is the first to ascertain that near-term small-for-gestational-age babies showing placental underperfusion-related histopathology have greater risk of abnormal neurodevelopmental outcomes at 2 years.
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