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ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 1  |  Page : 1-6

Impact of intrauterine growth restriction and birth weight on infant's early childhood neurodevelopment outcome


1 Department of Pediatrics, Bahrain Defence Force Hospital, Royal Medical Services, Riffa, Bahrain
2 Department of Pediatrics, Division of Neonatology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 Department of Neonatal Intensive Care, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
4 Department of Pediatrics, College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
5 Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia

Date of Web Publication6-Feb-2018

Correspondence Address:
Dr. Fahad Al-Qashar
Department of Pediatrics, Bahrain Defence Force Hospital, Royal Medical Services, Riffa
Bahrain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_16_17

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  Abstract 


Background: Infants with intrauterine growth restriction (IUGR) are at increased risk of perinatal morbidity and mortality in addition to long-term neurodevelopmental impairment due to fetal, placental, or maternal causes. Aim: This study aims to evaluate early childhood neurodevelopmental outcome from 18 to 24 months of age following a pregnancy complicated by IUGR. Study Design: This is an observational cohort study of prospectively collected data from a neonatal follow-up program (NFP) at the King Khalid University Hospital, Riyadh, Saudi Arabia. Results: A total of 65 IUGR infants with a median gestational age (GA) of 36 weeks (28–40 weeks) and a median birth weight of 1595 g (740–2280 g) were enrolled in the NFP. The majority of the mothers were Saudi 63 (97%), with a mean age of 30 years (19–45 years). Sixty-five percent of the infants were born by cesarean section. The prevalence of IUGR was 5.5% with predominance of symmetrical IUGR pattern 52 (80%). The median age of developmental assessment was 15 months (7–33 months). Thirty-two infants (49.2%) had a lower score (moderate 23 (35.4%) and severe 9 (13.4%) by Bayley Infant Neurodevelopmental Screening (BINS). There were no correlations between BINS category and birth weight, GA, gender, or type of IUGR. Catch-up growth was achieved in 44 (66.7%) of the infants at a median age of 9 months. Conclusion: We have demonstrated a higher incidence of poor neurodevelopmental scores at the early ages from 15 to 24 months among infants who were born following a pregnancy complicated by IUGR. BINS scores were not influenced by birth weight, GA, gender, or type of IUGR. IUGR is an independent variable for poor neurodevelopmental outcome. These patients will be followed to preschool ages for further neurocognitive assessment.

Keywords: Bayley Infant Neurodevelopmental Screening, cerebral palsy, fetal growth restriction, intrauterine growth restriction, long-term neurodevelopmental outcome, neonatal follow-up program


How to cite this article:
Al-Qashar F, Sobaih B, Shajira E, Al Saif S, Ahmed IA, Al-Shehri H, Jabari M, Al-Faris A, Al-Sayed M, Loaysobaih, Ali K. Impact of intrauterine growth restriction and birth weight on infant's early childhood neurodevelopment outcome. J Clin Neonatol 2018;7:1-6

How to cite this URL:
Al-Qashar F, Sobaih B, Shajira E, Al Saif S, Ahmed IA, Al-Shehri H, Jabari M, Al-Faris A, Al-Sayed M, Loaysobaih, Ali K. Impact of intrauterine growth restriction and birth weight on infant's early childhood neurodevelopment outcome. J Clin Neonatol [serial online] 2018 [cited 2018 Feb 20];7:1-6. Available from: http://www.jcnonweb.com/text.asp?2018/7/1/1/224807




  Introduction Top


Intrauterine growth restriction (IUGR) refers to infants who do not attain in utero full growth potential due to fetal, placental, or maternal causes.[1],[2],[3],[4] They are at an increased risk of perinatal morbidity and significant long-term morbidity, including neurodevelopmental impairment.[2],[3],[4],[5],[6] There have been inconsistencies in the definition of IUGR across independent studies and more often the term is used interchangeably with small for gestational age (SGA). In addition, several terms have been used to describe infants with low birth weights for their GA-specific weight curve.[5] IUGR commonly refers to a weight <10th percentile for GA on estimated fetal weight curves.[6] SGA is defined as a birth weight <10th percentile for GA on birth weight curves.[7],[8] Not all infants who are SGA were subjected to IUGR.[9] This diagnosis does not necessarily imply pathological growth abnormalities and may simply describe a fetus at the lower-end of the normal range. Studies estimate that true IUGR occurs in about 5% of pregnancies.[1],[2]

Neurodevelopmental problems arising from IUGR may have a significant impact on the quality of life and also constitute a major socioeconomic burden. In a recent systematic review (including 16 studies with individuals ranging in age from 6 months to 3 years), Levine et al. reported higher psychomotor impairment, 10 studies reported motor delays, eight studies showed cognitive delay, and seven studies showed language delays.[2] However, there was a substantial heterogeneity among the studies with respect to the primary outcomes, definitions, sample size, assessment tools, and adjustment for confounding variables. Limited reports have addressed the issues of IUGR and low birth weight in Saudi Arabia.[10],[11] To the best of our knowledge, there are no reported local studies addressing early neurodevelopmental IUGR outcomes in Saudi Arabia. Enrollment of these infants into high-risk programs may facilitate effective early intervention.[1],[12],[13]

Objective of the study

The objective of this study was to evaluate the early neurodevelopmental outcomes at ages from 18 to 24 months among infants born after a pregnancy complicated by IUGR.


  Materials and Methods Top


This is an observational cohort study of prospectively collected data from a neonatal follow-up program at King Khalid University Hospital (KKUH), Riyadh. Data were collected from patients' medical records and the neonatal follow-up database for infants born between January 2010 and December 2014. Infants were screened with Bayley Infant Neurodevelopmental Screening (BINS) at the ages of 18–24 months. Infants at a high risk of neurodevelopmental delay (moderate or severe) were scheduled for further evaluation by more detailed form of neurodevelopmental assessment (Gesell) at 36–48 months of age.[13]

Study measures

BINS is a well-validated screening test designed specifically for high-risk infants from 3 to 24 months. It has been cited as a useful screening instrument by the American Academy of Pediatrics. It offers an alternative to the detailed assessment of infants from ages 3 to 24 months and can be administered by a wide range of healthcare professionals who have limited training and in an acceptable time frame for screening.[13],[14] BINS assesses four conceptual areas of ability: basic neurological functions/intactness (posture, muscle tone, movement, asymmetries, abnormal indicators); expressive functions (gross motor, fine motor, oral motor/verbal); receptive functions (visual, auditory, verbal); and cognitive processes (object permanence, goal-directedness, problem-solving).

Study subjects

Inclusion criteria

Singleton infants diagnosed antenatally as being IUGR and delivered at KKUH with a birth weight <10th percentile.

Exclusion criteria

Multiple births, major congenital malformation, clinical, or confirmed diagnosis of chromosomopathies, congenital infection, or out-born infants.

Data collection

Relevant neonatal data including date of birth, nationality, gender, GA, birth weight, Apgar score, growth parameters, hypoglycemia, polycythemia, and hyperbilirubinemia were collected from the medical records. Information on mother's age, gravidity, parity, living children, abortions, maternal and paternal literacy, mode of delivery, and maternal risk factors were also collected.

Statistical methods

Data were tested for normality using Kolmogorov–Smirnov test and found not to follow a normal distribution. Differences between three GA groups in weeks (28–33, 34–36 and ≥37) and three groups of birth weight in grams (≤1000, 1001–1500, and 1501–2500) were assessed for statistical significance using Kruskal–Wallis test one-way analysis of an independent continuous variables and Pearson's Chi-squared test for categorical variables. Data for maternal and neonatal neurodevelopment were presented in the tables as medians and corresponding ranges. P < 0.05 was considered statistically significant. Data were analyzed using the Statistical Pack-age for Social Science (SPSS, Chicago, IL, USA).

Ethical consideration

Precautions were taken to protect the autonomy and confidentiality of participants and their data. The study was approved by the Research Ethics Committee at KKUH Riyadh.


  Results Top


Between January 1, 2010, and December 31, 2014, there were 65 IUGR infants with a median GA of 36 weeks (28–40 weeks) and a median birth weight of 1595 g (740–2280 g) [Table 1]. The prevalence of IUGR was 5.5%, and symmetrical IUGR was 52 (80%). The majority of the mothers were Saudi (63 [97%]) with a median age of 30 years (19–45 years) who underwent a higher percentage of cesarean sections (42 [65%]). Sixty percent of the infants were females. Seventeen infants (25%) were preterm born before 34 weeks, 24 (37%) were late-preterm at 34–36 weeks, and 24 were full term at ≥37 weeks (37%). Catch-up growth was achieved in 44 (66.7%) of the infants at a median age of 9 months [Table 2].
Table 1: Demographic data of the study population

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Table 2: Counts and percentages (nominal/categorical variables)

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The low scores were classified according to BINS: (1) mild: 33 (50.8%); (2) moderate: 23 (35.4%); and (3) severe: 9 (13.8%) with infant scores of 10 (9, 13), 9 (7, 11), and 6 (1, 9), respectively. Moderate and severe low scores, i.e., 32 (49.2%) had 50% of the predicted value of neurodevelopmental impairment. Full enteral feeds (150ml/kg per day) was achieved at a median age of 7 days (2-88 days) and the median length of NICU stay was 14 days (4-105 days) [Table 3]. The median age of developmental assessment was 15 months (7–33 months) [Table 4]. There was no correlation between GA and BINS category (P = 0.41) or BINS score (P = 0.48) [Table 5]. In addition, as shown in [Table 6], there were no significant correlations between BINS category and birth weight (P = 0.947), GA (P = 0.982), birth weight percentile (P = 0.32), head circumference percentile (P = 0.416), IUGR type (P = 0.347), hypoglycemia (P = 0.377), polycythemia (P = 0.065), Apgar score at 1 min (P = 0.86), Apgar score at 5 min (P = 0.627), maternal and paternal education (P = 0.347 and 0.26, respectively) as shown in [Table 1] and [Table 7]. Catch-up growth was achieved in 44 (66.7%) of the infants at a median age of 9 months [Table 2].
Table 3: Neonatal characteristics of the study population

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Table 4: Infant neurodevelopmental outcome

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Table 5: Gestational age and Bayley Infant Neurodevelopmental Screening category

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Table 6: Birth weight and Bayley Infant Neurodevelopmental Screening category

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Table 7: Bayley Infant Neurodevelopmental Screening category and other variables

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  Discussion Top


Both preterm and term infants born with IUGR are at increased risk of adverse neurodevelopmental outcome during childhood.[1],[2],[3],[4],[5] Our cohort showed that almost 50% of the IUGR infants had lower scores (moderate 35.4% and severe 13.4%) regardless of the GA or birth weight. Studies have estimated that IUGR occurs in approximately 5% to 7% of pregnancies.[1],[2],[3],[4],[5],[6] In our study, the prevalence was 5.5%. Identifying specific causes of the growth restriction is important in assessing risk for poor neurological outcomes.

IUGR is believed to lead to a range of worse neurocognitive impairments including cerebral palsy (CP), intelligence quotients (IQ), poorer academic performance,deficits in short-term memory, attention-deficit/hyperactivity disorders, emotional and behavioral problems, and social disorders than if an infant had appropriate fetal growth.[6],[7],[8]

A Doppler study that identifies absent or reverse end-diastolic umbilical arterial blood flow velocity has a strong predictive value for poor neonatal and long-term outcome.[1] Jarvis et al. showed that IUGR term infants born <10th percentile when compared with children in the 25th to 75th percentiles had 4–6 times the rates of CP.[15] Among a cohort of 334,339 infants who were ≥36 weeks, Wu et al. found IUGR to be an independent variable predictive of CP.[16] The Western Australia study showed an association between IUGR and CP among late preterm (gestation at 34–36 weeks) and term infants with the strongest evidence for late preterm whose birth weights were rd percentile (odds ratio 19.5 and 95% confidence interval [CI] 8.1, 47).[17] In a study by Villar et al., 205 infants with IUGR demonstrated lower cognitive scores.[18] Data from the National Collaborative Perinatal Project (2719 infants) IUGR cohort had significantly lower IQ scores at 7 years of age.[19]

We have demonstrated that approximately 50% of our cohort had lower BINS scores, which are consistent with scores from the above studies. Furthermore, there were no correlations between BINS score and GA (P = 0.48) or birth weight (P = 0.947). This finding suggests that IUGR is an independent variable of neurodevelopmental impairment.

The association between cognitive impairment and IUGR appears stronger than that between CP and IUGR among preterm infants.[7],[8],[12],[17],[20] Dammann et al. followed 324 very low birth weight (VLBW) infants compared by GA at 6 years and found no statistical difference in rates of CP.[20] In a large cohort, McCarton et al. followed 129 preterm infants (<37 weeks GA and <2500 g) and 300 controls to 6 years of age and found a 5-point difference in IQ between the preterm IUGR infants and controls.[7] Kok et al. followed a similar group of 124 preterm infants (<37 weeks GA and/or <2500 g) compared with 410 controls. In that study, IUGR infants had 2.4 times increased risk of cognitive abnormality (95% CI 1.05, 5.55), and significantly more IUGR infants required special education than preterm appropriate-for-gestational-age infants based on a parental questionnaire when the child was 9 years of age.[12] Other small studies found no differences in cognitive and academic abilities when compared with control groups matched by birthweight and GA.[8],[21]

Several lines of evidence showed a strong association between IUGR and adult metabolic and cardiovascular disorders, including coronary heart disease, type 2 diabetes, and insulin resistance.[22],[23],[24],[25],[26] The first putative connection between environmental influence in early life and the risk of cardiovascular disease in adulthood was reported by Barker et al., who followed a cohort of 499 men and women, and found that low birth weight at birth and 1 year of age are associated with an increased risk of death from cardiovascular disease and/or stroke.[23] A recent meta-analysis of fourteen studies involving a total of 132,180 persons that was done to examine this association found low birth weight (<2500 g) as compared with a birth weight of >2500 g to be associated with an increased risk of type 2 diabetes.[24]

Older studies linked slow head growth early in gestation and symmetrical IUGR with worse outcome.[27],[28],[29] Recent data, however, have shown postnatal, rather than antenatal growth and have the strongest influence on neurodevelopment. Symmetry of the restriction at birth may not have as much of an impact on neurodevelopmental outcome as previously believed.[30],[31] Scherjon et al. showed that fetal head growth was not independently associated with developmental score at 3 years of age.[31] Amin et al. found that persistent microcephaly was most associated with adverse neurodevelopmental outcome.[32] Gestational categories may not be as clear-cut as previously believed, which supports our study findings in which IUGR appears to be associated with poor neurodevelopmental outcomes independent from GA or birth weight.

Our cohort showed a catch-up growth rate of 67.7% at the age of 9 months. Most IUGR infants display catch-up growth by 2 years of age, about 10% do not catch up, and this population might benefit from a treatment with growth hormones (GHs), especially former IUGR with persistent short stature and relative GH or insulin-like growth factor-1 resistance. Growing evidence suggests that treatment with GH after 2 years of age may lead to improvement in IQ and developmental outcomes independent of the physical height reached with treatment.[33]

Infants who have both IUGR and extremely low birth weights may be at even greater risk and warrant close follow-up to ensure adequate postnatal growth and developmental progress. Regardless of the cause, enrollment in high-risk infant follow-up programs for early identification of neurological and/or cognitive impairment can facilitate early intervention services, which have been the mainstay of treatment for infants who have developmental delay or CP.


  Conclusion Top


We have demonstrated a higher incidence of almost 50% in poorer neurodevelopmental scores during early childhood ages (from 15 to 24 months) among infants born after a pregnancy complicated by IUGR. Our results showed that the developmental outcome for children with IUGR was not influenced by birth weight, GA, gender, or type of IUGR, suggesting that IUGR is an independent variable for poor neurodevelopmental outcome. These patients are still in the neonatal follow-up program and will be reassessed at preschool age (3–5 years) to explore the effects of postnatal growth on long-term neurodevelopment. We have a few study limitations; in this study, our sample sizes were relatively small and study participants were from a single center. As seen in other retrospective studies, the temporal relationship is frequently difficult to assess. A well-designed multicenter prospective study with strict criteria for the diagnosis of fetal growth restriction is needed to ascertain the association between IUGR and long-term neurodevelopmental impairment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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