Assessment of gestational age in newborns by neurosonography

Early Human Elseiier EHD Development, Scientific 25 (1991) Piblishers Ireland 209 209-220 Ltd 01146 Assessment of gestational age in newborns bY neurosonography Chao-Ching Department of Pediatrics. (Received 1I National October Huang and Tsu-Fuh Cheng Kung University 1990; revision received Hospitul. I February Yeh Tainan. Taiwan (Republic 1991; accepted I April of China) 1991) Summary Current methods for estimating gestational age using clinical parameters can be inaccurate in prematurity. A simplified ultrasonographic system, based on cerebral sulcal development, for clinically determining fetal maturation in newborns was developed and studied in 148 newborns (92 appropriate-for-gestational-age, 54 small-for-gestational-age and 2 large-for-gestational age). This ultrasonographic sulcal method correlates better with the gestational age by dates than by the Dubowitz scoring system in the neonates less than 30 weeks’ gestation. There are significant correlations between gestational age assessed by dates and by sonographic sulcal age in both appropriate-for-gestational-age (R = 0.91, P < 0.001) and small-for-gestational-age newborns (R = 0.92, P < 0.001). Maternal hypertension during pregnancy is a significant risk factor associated with accelerated fetal cerebral maturation in 12 neonates. Although overestimate of gestational age may occur in neonates born to mothers with hypertension, cranial ultrasonography is an accurate and convenient method of estimating gestational age in neonates. gestational age; sulcal age; sonography. Introduction There is a need for an easy and accurate clinical method to assess the gestational age in newborns. A rapid and simple method of maturational assessment that can be accurate, less disturbing and applicable to all newborn infants at cribside, Correspondence to: Chao-Ching Kung University Hospital, 0378-3782/91/S3.50 0 Huang, Tainan I38 Shen-Li 70428 Taiwan, Road, Republic Department of China. 1991 Elsevier Scientific Publishers Ireland Published and Printed in Ireland Ltd. of Pediatrics, National Cheng 210 regardless of their well-being, is necessary [ 1,2]. The small-for-gestational-age (SGA) infant can present with many serious problems during labor and after delivery, such as hypoxia and acidosis, hypoglycemia, hypocalcemia, congenital infections and congenital anomalies [1,3]. Subsequent growth and neurodevelopment of the SGA neonates who survive the neonatal period is of prognostic importance as compared with the appropriate-for-gestational-age (AGA) newborns [3]. The ultrasonographic biometry in the third trimester is unable to assess the gestational age of a fetus with growth retardation. Conventional clinical methods rely on selected physical and neurologic findings at birth, which can be easily altered in conditions such as maternal diabetes, maternal toxemia and birth asphyxia [4,5]. The postnatal age at the time of examination can also significantly alter the neurologic findings, leading to inaccurate gestational age assessment [2]. Furthermore, conventional methods are inaccurate for preterm infants less than 32 weeks’ gestation [6]. Sequential gyral and sulcal developments of human cerebrum throughout pregnancy have been used by neuropathologists to verify the clinical estimates of gestational age particularly between 22 and 34 weeks gestation [7,8]. Real-time ultrasonography provides an easy assessment and non-invasive method of visualizing anatomic structures of the brain in newborn infants [9]. By studying the sulcal development at birth, we report an ultrasonographic method to assess the gestational age and compare with other gestational parameters in AGA and SGA newborn infants. Materials and Methods Cranial ultrasonography examinations were performed prospectively on 148 newborns whose gestational ages were judged from definite maternal last normal menstrual period as 38 weeks or less. Only infants whose mothers had regular menstrual cycles and appropriate uterine size at initial prenatal examinations were included for study. The infants were admitted to the neonatal special care unit and cranial ultrasounds were performed during the first 2 postnatal days when informed consents for study were obtained. All the scans were done by one of the authors (C.C.H.). The clinical information was not disclosed to the ultrasonic examiner until the scans were completed, and ultrasonographic gestational age determined and recorded. Assessment of gestational age by Dubowitz score was performed immediately after admission, usually before 12 h of age. The clinical informations available included: complications of pregnancy, mode of delivery, birthdate, scan date, estimated date of confinement (EDC) based on mother’s last menstrual period, gestational age by Dubowitz score, birth weight, head circumference, body length, chest circumference and epicanthal distance. Infants with congenital brain malformations or severe intraventricular hemorrhage were excluded from the study. Ultrasonographic examinations were performed through anterior fontanelle using Aloka SSD 630 sector scanner with 5.0 and 7.5 mHZ transducers. Images were taken in coronal, midsagittal, parasagittal and tangential planes and were photographed. The following structures were identified: parieto-occipital fissure (5.0 mHZ, midsagittal plane), calcarine fissure (5.0 mHZ, midsagittal plane), cingulate sulcus (7.5 mHZ, midsagittal plane), postrolandic sulcus (5.0 mHZ, tangential plane), lateral Fig. I. 7.5 mHZ Transducer. (A) Midsagittal plane: anterior part of cingulate sulcus (arrow head) appears at 26 weeks. (B) Midsagittal plane: the cingulate sulcus develops and extends posteriorly by 29 weeks. (C) Parasagittal plane: the cingulate sulcus becomes curved and secondary sulci (arrow) begin to develop from it at 31 weeks. a. anterior. Fig. 2. 7.5 mHZ Transducer. (A) Midsagittal plane: secondary sulci developed from cingulate sulcus at 33 weeks. (B) Parasagittal plane: tertiary sulci developed at 36 weeks. (C) Parasagittal plane: more branching and anastomosis of tertiary sulci forming cobblestone-like cortical sulci at 38 weeks. a. anterior. Fig. 3. 5.0 mHZ Transducer and midsagittal planes. (A) Parieto-occipital fissure (arrow head) is well developed by 24 weeks. (B) Calcarine fissure (arrow) begins to develop from parieto-occipital fissure at 25 weeks. (C) more development of the calcarine fissure by 28 weeks. a, anterior. Fig. 4. 5.0 mHZ Transducer. (A) Tangential plane: postrolandic sulcus (arrow) appears Tangential plane: inferior temporal sulcus is well developed by 33 weeks (arrowhead). plane: insular sulci (arrows) are mature and fan-shaped at 36 weeks. a, anterior. by 28 weeks. (B) (C) Parasagittal 213 sulcus (5.0 mHZ, coronal plane), inferior temporal sulcus (5.0 mHZ, tangential plane), insular sulci (5.0 mHZ, parasagittal plane), secondary and tertiary sulci from cingulate sulcus (7.5 mHZ, midsagittal and parasagittal planes) (Figs. 14). The gestational age assessed by sonographic sulcal development was determined according to the developments of the above sulci based on previous anatomical and ultrasonographic studies [7,8, 10-121, and the age of the presence of most mature sulci was taken as sulcal gestational age (Table I). SGA newborn was defined as one whose birth weight was less than the tenth percentile of the weight for the corresponding gestational age [13]. Simple linear regression analysis was performed between the gestational age judged by EDC and gestational age by Dubowitz score, sonographic sulcal age and other gestational variables including birth weight, head TABLE I Selected gestational age-dependent 24-25 weeks Prominent parieto-occipital Early branching 26-27 weeks More maturation Appearance based on cerebral fissure of calcarine fissure cingulate weeks 28-29 Development of whole cingulate Appearance of postrolandic Closing of lateral sulcus 30-31 patterns fissure of calcarine of anterior sulcal-gyral sulcus sulcus sulcus weeks Covering of insula Bending and curvature of cingulate sulcus Appearance of inferior temporal sulcus Occasional secondary sulci budding from cingulate 32-33 weeks Branching of secondary sulci from cingulate Appearance of partial insular sulci sulcus sulcus 34-35 weeks Further development of insular sulci More maturation of secondary sulci Occasional tertiary sulci 36 weeks Development of tertiary sulci Maturation of insular sulci 38 weeks Cobblestone pattern of tertiary sulci from cingulate sulcus sonographic examinations. 214 circumference, body length, chest circumference and epicanthal distance. Gestational age estimated by dates and by sonographic sulcal pattern was correlated. If the latter was advanced by more than 2 weeks, cerebral maturation was considered to be accelerated. The significance of the correlation coefficient was tested by F-test. Results The mean gestational age by EDC was 33 weeks (range: 23-38). The mean birth weight was 2000 g (range: 48O”OOO g). To study the correlation of gestational age by EDC with sonographic sulcal age and gestational age assessed by Dubowitz score in different degree of prematurities, the 148 newborn infants were divided into groups based on the gestational age assessed by EDC. Significant correlations of the gestational age as assessed by EDC with the gestational age assessed by Dubowitz score and by sonographic sulcal age are found in all the three different groups of newborns (Table II). For extremely premature infants < 30 weeks’ gestation, sulcal ultrasonographic assessment of gestational age correlates better with gestational age assessment by dates than that by Dubowitz assessment. Of the 148 newborns, there were 92 AGA, 54 SGA and 2 large-for-gestational-age (LGA). The maternal complications during pregnancy included 4 cases of diabetes mellitus, 11 cases of hypertension (2 cases of chronic hypertension, and 9 cases of pregnancy-induced hypertension: 4 hypertension, 4 preeclampsia, 1 eclampsia), 5 cases of placenta previa, 4 cases of maternal infection and 2 cases of abruptio placenta. Table III demonstrates the population of each number of infants in various gestational age of the AGA and SGA newborns. The 2 LGA newborns were not included in this analysis. In order to understand the correlation between sonographic sulcal age with gestational age by dates in AGA and SGA newborns, regression lines between gestational age by EDC and sonographic sulcal age with 95% confidence intervals in the AGA and SGA infants are shown in Figs. 5, 6. Regression lines are also calculated on gestational age by EDC for each gestational variable (Tables IV, V). There are good correlations between gestational age assessed by EDC and gesta- TABLE II Correlation of gestational age as assessed by dates from last normal menstrual period with gestational age as assessed by Dubowitz score and by sonographic sulcal age in the three different groups of newborns. R, correlation coefficient. R P < 30 weeks n = 27 30-34 weeks n = 43 Gestational Sulcal Gestational age by Dubowitz score age age by Dubowitz score 0.63 <O.OOl 0.76 <O.OOl 0.50 0.001 35-38 weeks n = 78 Sulcal age Gestational age by Dubowitz score Sulcal 0.50 0.009 0.52 <O.OOl 0.61 <O.OOl age 215 TABLE III The population and birth weight categories of AGA and SGA neonates gestational age; BW, birth weight; n, case numbers. GA (weeks) AGA ” at various gestational ages. GA, SGA ” BW (kg) BW (kg) 23 24 I 3 0.70 0.72-0.90 I 0 0.45 - 25 26 27 28 I 4 3 2 0.72 0.9&1.10 0.92-1.15 1.02-1.20 0 0 0 2 0.7U.82 29 30 31 32 7 3 4 9 1.25-1.72 1.35-1.68 I.%-I.88 1.58-2.18 3 0 4 I 0.85-1.05 33 34 35 36 6 12 9 6 I .9%2.43 2.14-2.55 2.62.75 1.60 1.49-1.78 1.761.94 I .68-2.09 31 38 I5 I 2.662.90 2.73-3.05 I 3 7 IO IO I2 1.89-2.40 y E 4.5352 r.0.91 al=92 + 1.12-1.34 I .45 I .9&2.40 I .89-2.5 I O.S5384(SA) 1 30 Sonogrrphic 40 Svlcal Age (Weeks) Fig. 5. Regression line of gestational age assessment sonographic sulcal age with 95% confidence interval by dates from last normal in AGA newborn infants. menstrual period and 216 30 Sonsgraphic Sulcsl Age (Weeks) Fig. 6. Regression line of gestational age assessment sonographic sulcal age with 95% confidence interval by dates from last normal in SGA newborn infants. menstrual period and tional age by sonographic sulcal age in AGA and SGA newborns. The sonographic sulcal age correlates best with gestational age by EDC as compared with other gestational variables in either AGA or SGA newborns. There were 12 neonates who demonstrated accelerated sonographic sulcal age more than 2 weeks in advance than their gestational age assessed by dates, as evidenced by earlier appearance of sulcal pattern. History of hypertension among the mothers of the 12 neonates with accelerated cerebral maturation was 67% (8) and in neonates without accelerated cerebral maturation was 2% (3). There is a significant association between accelerated fetal cerebral maturation and maternal TABLE IV Correlation of gestational age by EDC with gestational variables in AGA neonates, age by EDC; X, each gestational variable; R, correlation coefticient. Gestational age by Dubowitz Sulcal age Birth weight Head circumference Body length Epicanthal distance Chest circumference All P values <O.OOl. score R Regression 0.90 0.91 0.89 0.86 0.84 0.76 0.84 Y Y Y Y Y Y Y = = = = = = = -1.193 4.535 21.744 -1.198 9.794 10.715 7.169 line + + + + + + + 1.033 0.856 5.699 1.148 0.530 3.514 0.937 x X X X x x X n = 92. Y, gestational 217 TABLE V Correlation of gestational age by EDC with gestational variables in SGA neonates, age by EDC; X, each gestational variable; R, correlation coefficient. n = 54. Y. gestational R Regression 0.90 0.92 Y = -0.498 + 1.0008 X Y = 0.493 + 0.978 x Birth weight Head circumference Body length Epicanthal distance 0.79 0.82 0.74 0.75 Chest circumference 0.78 Y Y Y Y Y Gestational Sulcal age All P values age by Dubowitz score line = 25.024 + 5.206 X = 4.119 + 1.029 X = 14.908 + 0.446 X = 14.945 + 3.206 X = 13.968 + 0.753 X <O.OOl. hypertension (Table VI). Five tion were SGA, while 49 of the were SGA. SGA and the use with accelerated fetal cerebral of the 12 neonates with accelerated cerebral matura136 neonates without accelerated cerebral maturation of steroids are not significant risk factors associated maturation. Conventional clinical methods of gestational age assessment have demonstrated useful degrees of accuracy. However, applying these criteria with complex scoring systems to a sick newborn may be disturbing, or misleading when the muscle tone [ 1,2,4,5]. is altered by birth asphyxia, paralysis, or other metabolic disturbances These methods have limitations, particularly for the very low birthweight infants TABLE VI Association between accelerated cerebral maturation, maternal NB, newborn; GA, gestational age; NS, not significant. No. of NB GA by EDC With maternal Without maternal (weeks) hypertension hypertension I2 23-35 8 136 23-38 3 hypertension, With SGA SGA and use of steroids. Without SGA Use of steroid No steroid NB with accelerated cerebral maturation NB without accelerated cerebral maturation x= = 66.6 P e 0.05 ~~,,,ss,~, = 3.84146 (chi-square). 4 5 7 3 133 49 87 32 x= = 0.15 P > 0.05 9 I04 x= = 0.013 P > 0.05 218 [3,4,6,12]. Although obstetrical serial longitudinal sonographic measurements and dates calculated from the last normal menstrual period are the most reliable methods to estimate fetal development [ 131, this information is not always available in every high-risk newborn. Developmental maturation is a much more reliable guide to gestational age and no organ lends itself better to this than the brain [8]. Gestational development of the brain by sequential appearance of particular sulci had been documented by neuropathologists and the average time of development of cerebra] fissure, sulci and gyri can give an accurate estimate of maturity [7,X,14]. Based on the gestational sulcal developments defined by neuropathologists, cerebral ultrasonography can be used to demonstrate the sulcal maturations and assess the gestational age in newborn infants. Like the electroencephalographic assessment of gestational age which relies on the distinctive regional and hemispheric electrical patterns at various gestational ages [14], there are consistent and sequential sulcal developments determined by ultrasound [9,10,12] at each gestational age. There are few sulci and only prominent parieto-occipital fissure and wide-opened lateral sulcus are found at 24-25 weeks. More sulci and gyri, such as calcarine, cingulate, postrolandic and inferior temporal sulci develop in sequence by 30-31 weeks [7,8]. Thereafter, the sulci become more complicated and secondary sulci begin to branch from cingulate sulcus at 31-32 weeks, and tertiary sulci are formed after 35-36 weeks. Fan-shaped three- to fourinsular sulci can also be demonstrated by 34-35 weeks [7,8]. These sulcal developments can be easily demonstrated by ultrasound at the bedside, and used as a landmark for gestational age assessment. Identification of the maturation of a single sulcus may not be very reliable for gestational age assessment [10,15]. Examination of the presence and maturation of several distinctive sulci, which develop in sequence, may be more accurate than identification of the maturation of a single sulcus [12]. Instead of using a complicated scoring system as described by Murphy et al. [12], the gestational age can be directly estimated from specific sonographic findings at that gestational period. Because of the complexity of tertiary sulci, Murphy et al. suggested that it was difficult to assess gestational age after 34 weeks of gestation. With the demonstration of fan-shaped mature insular sulci and cobblestone-like tertiary sulci, as described in this study, the fetal maturation in late gestation can be assessed. The estimation of gestational age by sulcal maturation correlates better than the Dubowitz scoring method with gestational age by date in the newborns with gestational age less than 30 weeks and 35-38 weeks. These findings substantiate the general impression that Dubowitz scoring is less reliable in the very low birth weight premature neonates or neonates with perinatal insults, and gestational age by sonographic sulcal assessment can be more helpful in these newborns. Although the examiner who performed the Dubowitz score might not be totally blind to the obstetric assessment of gestational age. The Dubowitz score examination was performed immediately after the neonates were admitted to the special care unit and objectively followed each item of the scoring system. The gestational age by Dubowitz score was no better than the sonographic sulcal age in correlation with the gestational age by date. The bias, that might enter into Dubowitz assessment of gestational age, could be minimal. 219 The sonographic sulcal age correlates best with the gestational age by EDC in both AGA and SGA groups. The gestational age assessment by sulcal maturation is not only reliable in AGA neonates but also in the SGA group. According to autopsy study by Hadi [16], chronic maternal hypertension and fetal intrauterine growth retardation were significantly associated with accelerated intrauterine cerebral maturation. Accelerated fetal brain maturation occurred in all the cases with maternal pre-existing chronic hypertensive disease, and in all the growthretarded fetuses. In our 12 neonates who were more than 2 weeks in advance of sonographic sulcal age as compared with the gestational age by dates, maternal hypertension played a significant role in acceleration of fetal cerebral maturation. SGA, in contrast to the study by Hadi [ 161, is not a significant risk factor associated with accelerated cerebral maturation. Although sonographic sulcal age assessment may overestimate the gestational age in some chronically stressed neonates, especially those whose mothers have hypertension, it is still an useful means in assessing gestational age of AGA and SGA neonates. Further study is needed to evaluate any difference in the postnatal sulcal development between full-term and premature neonates with the same postconceptual age. Ultrasonographic sulcal examination provides a non-invasive and convenient method to assess the cerebral maturation in newborn infants. It is also a good clinical morphologic indicator of gestational age. Except in cases of congenital brain malformation, severe intracerebral hemorrhage or neonates with maternal hypertension, the estimation of gestational age is not affected by conditions such as intrauterine growth retardation, very low birthweight or any metabolic alternation. The ultrasonographic examination can be performed either immediately after birth or in the first few days of life. We believe that this method can be used accurately to assess the gestational age in newborn infants. References I 2 3 4 5 6 7 8 9 IO Narayanan, I., Dua, K., Gujral, V.V., Mehta, D.K., Mathew. M. and Prabhaker, A.K. (1982): A simple method of assessment gestational age in newborn infants. Pediatrics, 69, 27-32. Ballard, J.L., Novak, K.K. and Driver, M. (1979): A simplified score for assessment of fetal maturation of newly born infants. J Pediatr., 95, 769-774. Spellacy, W.N. (1990): Intrauterine growth retardation. 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