Purpose: To investigate the relationship between preterm delivery and developmental outcomes in children born at 34 - 36 weeks of gestation (late preterm period). Methods: This study reviewed the cases of singleton late preterm children and full-term (38 - 40 weeks of gestation) children born at Showa University Hospital. The developmental outcomes at 3 years of age were assessed based on the results of questionnaires sent to the families by mail. In addition, the incidence of developmental delays was compared between the late preterm and full-term children. In the full-term control group, perinatal characteristics (neonatal gender, Apgar score, Cesarean delivery, birth weight < 10th percentile, birth weight < 3rd percentile) were matched with those of the late preterm cases. We compared categorical variables using Fisher’s exact test. For variables with a non-normal distribution, Welch’s t -test was applied. A p-value of <0.05 was considered to be statistically significant. Results: The rate of return of the questionnaires was 25.9% (121) among the cases and 25.8% (163) among the controls. The frequency of developmental delays was 6.6% among the cases, compared with 4.3% among the controls. Conclusions: Matching the perinatal characteristics of the subjects, the frequency of developmental delays was similar between the two groups.
In recent years, remarkable improvements have been observed in the field of neonatology, thus resulting in better short-term prognoses among late preterm infants in most cases. In addition, the need to terminate the pregnancy is often assessed during the late preterm period in order to avoid sudden aggravation of maternal complications, such as preeclampsia, and fetal complications, such as a non-reassuring fetal status or intrauterine fetal death. On the other hand, evidence suggests that, although the frequency of an abnormal state during the neonatal period has decreased, late preterm children are at risk of developmental delays over the long term [
However, it is possible that more late preterm infants exhibit perinatal characteristics that adversely affect developmental outcomes compared to full-term infants. It is also unclear whether the poor long-term developmental outcomes of late preterm children are caused by the timing of delivery in the late preterm period itself or rather the incidence of perinatal complications during the period of delivery. We hypothesized that a lack of differences in the perinatal characteristics between late preterm and full-term children would result in a lack of differences in developmental outcomes between these groups. Therefore, the aim of the present study was to clarify the effects of late preterm birth on the developmental outcomes observed at 3 years of age, regardless of perinatal complications. We suppose the study significant for obstetricians to determine the timing of delivery at late preterm period.
We sent letters to the all parents of singleton children born at 34 - 36 weeks of gestation (late preterm period) at Showa University Hospital, Tokyo between January 2003 and October 2010, requesting the participation in this study. Only cases who consent to the participation were enrolled (cases). After obtaining the perinatal characteristics from the patients’ medical reports, a case-control study with matched pairs was conducted. We chose randomly the same number of singleton children born at 38 - 40 weeks of gestation (full-term) at our hospital during the same study period with matching perinatal characteristics (gender, Apgar score, Cesarean delivery, birth weight < 10th percentile, birth weight < 3rd percentile).We sent letters to the parents of full term children in the same way, and only cases who consent to the participation were enrolled (controls). Infants with congenital anomalies, hearing loss or chromosomal defects were excluded from the study.
Questionnaires were then sent with a stamped return envelope to the parents of the subjects inquiring about the developmental outcomes observed at 3 years of age. Only patients whose development was assessed by a pediatrician at 3 years of age were enrolled.
The incidence of developmental delays at 3 years of age was subsequently compared between the cases and controls. A developmental delay was defined as a diagnosis of a developmental delay at 3 years of age requiring therapy with special supportive programs. In contrast, normal development was diagnosed when the family reported normal developmental checkup findings at 3 years of age and indicated no developmental problems on the questionnaire.
The statistical analysis was performed using the JMP® Version 10 software program. We compared categorical variables between two groups using Fisher’s exact test. For variables with a non-normal distribution, Welch’s t-test was applied. A p-value of <0.05 was considered to be statistically significant. The study protocol was approved by the ethics board of Showa University. Informed consent was obtained from each patient’s parent or legal guardian.
Among 8276 children born during the study period, 469 (5.7%) were born during the late preterm period. The rate of response to the questionnaires was 29.2% (136) among the cases and 29.0% (184) among the controls.
We excluded subjects for whom answers were indistinct or records of the developmental checkup at 3 years of age were missing. Ultimately, 121 cases and 163 controls were enrolled in the present study.
The maternal and neonatal demographics of the cases and controls are shown in
The incidence of developmental delays in the cases and controls is demonstrated in
The perinatal characteristics of the cases with developmental delays at 3 years of age are demonstrated in
In the present study, the incidence of developmental delays at 3 years of age was 6.6% in the late preterm children and 4.3% in the full-term children matched for perinatal characteristics. Matching the perinatal characteristics of the subjects, the incidence of developmental delays was similar between the two groups; however, the number of candidates was too small to clarify the differences. Further research is thus needed to investigate the incidence of developmental delays in late preterm children. At the neonatal demographics, Gestational weeks at delivery and Birth weight were significantly different between two groups. The reason is that cases were born at late preterm period, and controls were born at full term.
Late preterm children have been shown to have more neuro developmental problems, such as developmental
Controls n = 163 | Cases n = 121 | p-value | |
---|---|---|---|
Maternal | 34.7 ± 4.7 | 33.1 ± 4.2 | 0.214 |
Age at delivery (y.o) | 1 (0 - 6) | 1 (0 - 6) | 0.886 |
Gravitas | 0 (0 - 3) | 0 (0 - 3) | 0.472 |
Parity | |||
Neonatal | |||
Gestational weeks at delivery | 38.9 ± 0.8 | 35.2 ± 0.8 | <0.001* |
Cesarean section | 47.2% (77) | 48.8% (59) | 0.811 |
Birth weight (g) | 2900 ± 429 | 2289 ± 469 | <0.001* |
Birth weight < 10th percentile | 24.5% (40) | 24.8% (30) | 0.811 |
Birth weight < 3th percentile 12.3% (20) | 12.3% (20) | 13.2% (16) | 0.858 |
Male | 52.7% (86) | 51.2% (62) | 0.811 |
Apgar score 1 min | 8 (1 - 10) | 8 (1 - 10) | 0.781 |
Apgar score 5 min | 9 (1 - 10) | 9 (1 - 10) | 0.713 |
Umbilical artery pH | 7.29 ± 0.08 | 7.31 ± 0.09 | 0.075 |
Umbilical artery pH < 7.2 | 11.5% (18) | 7.4% (9) | 0.414 |
The data are presented as the mean ± standard deviation, median (range) or frequency. *p < 0.05.
Controls n = 163 | Cases n = 121 | p-value | |
---|---|---|---|
Developmental delay at 3 years old | 4.3% (7) | 6.6% (8) | 0.429 |
Developmental characteristics | |||
Pervasive developmental disorder | 0.6% (1) | 1.7% (2) | 0.577 |
Attention deficit hyperactivity disorder | 0% (0) | 0.8% (1) | 0.426 |
Language difficulty | 2.5% (4) | 0.8% (1) | 0.398 |
Motor difficulty | 0% (0) | 1.7% (2) | 0.181 |
Intellectual disability | 1.2% (2) | 1.7% (2) | 0.763 |
Gestational weeks at delivery | |||
34 (n = 31) | 9.7% (3) | ||
35 (n = 31) | 3.2% (1) | ||
36 (n = 59) | 6.8% (4) | ||
38 (n = 68) | 2.9% (2) | ||
39 (n = 46) | 8.7% (4) | ||
40 (n = 49) | 2.0% (1) |
Cases | |||||||
---|---|---|---|---|---|---|---|
Case | Age | Gestational weeks at delivery | Birth weight (g) | Gender 1/5 min | Apgar score | UmA pH | Mode of delivery |
1 | 32 | 36 | 2293 | male | 7/9 | 7.36 | C/S |
2 | 38 | 34 | 1511‡ | male | 8/9 | 7.27 | C/S |
3 | 25 | 34 | 1695† | female | 8/9 | 7.23 | C/S |
4 | 27 | 36 | 2390 | male | 8/9 | 7.34 | TV |
5 | 35 | 35 | 2431 | male | 8/9 | 7.35 | TV |
6 | 36 | 36 | 2912 | male | 8/10 | 7.24 | TV |
7 | 24 | 36 | 3651 | male | 8/9 | 7.40 | TV |
8 | 33 | 34 | 2340 | male | 9/9 | 7.40 | TV |
Controls | |||||||
Case | Age | Gestational weeks at delivery | Birth weight (g) | Gender 1/5 min | Apgar score | UmA pH | Mode of delivery |
1 | 33 | 39 | 3385 | male | 1/1 | 6.95 | C/S |
2 | 40 | 40 | 3102 | male | 7/8 | 7.16 | TV |
3 | 35 | 39 | 2234‡ | female | 8/9 | 7.27 | TV |
4 | 31 | 39 | 2269‡ | male | 8/9 | 7.34 | TV |
5 | 41 | 38 | 3105 | male | 8/9 | 7.35 | C/S |
6 | 41 | 38 | 2887 | male | 8/9 | 7.30 | C/S |
7 | 33 | 39 | 3328 | male | 8/9 | 7.43 | TV |
‡Birth weight < 3rd percentile, †Birth weight < 10th percentile, UmA: Umbilical artery, Mode of delivery: Method of childbirth (Cesarean section or transvaginal delivery). C/S: Cesarean section, TV: Transvaginal delivery.
*Corresponding author.
This study is associated with several limitations. Although all perinatal treatment was administered at a single hospital and the perinatal characteristics were accurately and appropriately matched between the two study groups, the presence of a development delay was assessed solely based on the results of the questionnaires sent to the families by mail, with a low response rate. However, to date, this study is the first to compare long-term developmental outcomes between late preterm children and full-term children with respect to perinatal complications in Japan. We believe that our findings provide new insight into the management of pregnant females in the preterm period as a pilot study.
It is well known that there is an association between developmental delays and both fetal growth restriction [
We declare that all authors have no conflicts of interest relevant to this article.
This study was supported by Department of Obstetrics and Gynecology, Showa University, School of Medicine.