Intermediary Factors In The Relation Between Stressful Life Events During First Trimester And Neurobehavioral Development Of Toddler

BackgroundPreliminary studies have demonstrated a link between prenatal psychological stress and cognitive, behavioral, and emotional problems in the child. Little is known about the possible underlying mechanisms and there are no direct evidences about the hypothesis that prenatal psychological stress could lead to deleterious programming effects on the fetal HPA axis. It is not clear by now whether there exist other pathways besides fetal programming, through which prenatal stress affect the neurobehavioral development of offspring. Some researches about the effect of prenatal psychological stress on birth outcomes had found that the first trimester is an important window period for exposure while little research involved in the impact of prenatal psychological stress during first trimester on the neurobehavioral development of child.Objectives1. To evaluate the effects of maternal exposure to stressful life events during first trimester on pituitary-adrenocortical axis response to acute stress (delivery).2. To identify whether the stressful life events during first trimester could reduce early breastfeeding.3. To investigate whether the prenatal stress during first trimester was associated independently with neurobehavioral development of offsprings after controlling the family environment and breastfeeding behavior.The final purpose of this paper was to identify the hypothesis that prenatal psychological stress may influence the neurobehavioral development of offsprings through two different paths including deleterious programming effects on the fetal HPA axis and reducing early breastfeeding.MethodsA total 2 522 pregnant women who delivery in the Department of Obstetrics of Hefei Maternal and Child Healthcare Hospital from January to October 2008 participated in the project willingly and were required to complete a questionnaire including Life Events Checklist and Social Support Scale before delivery. Demographic characteristics, pregnancy history and BMI during pregnancy were assessed through the interview/medical charts and delivery outcomes including gestational age at birth, birth weight were obtained from medical charts after delivery. Cord blood were collected immediately after delivery and cortisol (CORT), adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) level were detected by radioimmunity. Two hours after delivery, pregnant women were required to report the perceived impact rating of pain and tension during delivery. Lactation guidance was provided and the onset of lactation data was collected in the hospital during 0-3 days after parturition, and the onset of lactation was defined based on maternal perception of changes in breast fullness. Information about the breastfeeding postpartum was obtained during the telephone interview at 2 month and 4 month postpartum. when infants reach 16-18 months old, the mental development, psychomotor development, and temperament were assessed using Bayley Scales of Infant Development of China Revision (BSID-CR) and Toddler Temperament Scale (TTS).Taken total score of perceived impact to life events during first trimester≥2 as exposure to stressful life events, there were 64 out of 86 pregnant women who were collected cord blood and exposed to stressful life events during first trimester fit the reach requirements and taken as exposed group in section 1 of this study. Among the 64 pregnant women, 31 ones who delivery by spontaneous labour were defined as Exposed group A (EA), and 33 ones who delivery by caesarean section were defined as Exposed group B (EB). Another 64 pregnant women who were collected cord blood and without exposure to stressful life events including 31 ones delivered by spontaneous labour and 33 ones deliverd by caesarean section were defined as Controlled group A (CA) and Controlled group B (CB), respectively. Thirty eight exposed mother-infant pairs and 114 control pairs (matched 1:3 with exposed mother-infant pairs for mother age, education status, delivery mode, infant sex, family economic status, residence ) received follow-up visit when infants was 16-18 months old.ResultsDemographic characteristic and perceived impact rating of pain and tension during delivery had no significant difference between exposed group and control. CORT concentration of EA was 408.80±100.56 ng/ml, which was lower than CA but had no significant difference (Z=1.86, P=0.063). ACTH level in cord blood of EA was significantly higher than CA(8.98±2.86 vs 7.60±2.22; Z=2.38, P=0.018), while DHEAS, ratio of CORT/ACTH and DHEAS/ACTH were significantly lower than CA, (Z=3.23, P=0.001 ; Z=3.29, P=0.001 ; Z=3.92, P<0.001; respectively). Compared with Controlled group B (CB), the level of CORT and ACTH, ratio of CORT/ACTH and DHEAS/ACTH in Exposed group B (EB) had no significant difference but DHEAS level was significantly lower(Z=2.96, P=0.003). CORT level of CA was significantly higher than CB(Z=5.40, P<0.001). Analysis according to neonatal sex showed that CORT level of female neonate in EA was significantly lower than female neonate in CA(382.79±81.74 ng/ml vs 461.04±87.43 ng/ml; Z=2.23, P=0.026) while there was no significant difference between male neonates from EA and CA. Ratios of CORT/ACTH and DHEAS/ACTH in female and male neonate of EA were significantly lower than female and male of CA, respectively(male: Z=2.44, P=0.015;Z=3.20, P=0.001. female: Z=2.29, P=0.022;Z=2.42, P=0.016).The prevalence of delayed onset of lactation (OL) and termination of full breastfeeding were 9.8% and 12.0%, respectively. Multiple logistic regression model after controlling mother age, residence, education status, perceived family economy and social support during pregnancy showed that exposure to stressful life events during first trimester (RR=2.59, 95%CI: 1.52-4.40), gestational BMI gain≥7.61(RR=1.90, 95%CI: 1.27-2.86), cesarean section (RR=2.11, 95%CI: 1.46-3.05), frequency of breastfeeding on day 1 after deliver(RR=2.14, 95%CI: 1.57-2.91) may increase significantly risk of delayed OL. Exposure to stressful life events during third trimester(RR=3.44, 95%CI: 1.67-7.37), pregnant BMI < 18.45(RR=1.88, 95%CI: 1.19-2.97), gestational BMI gain≥7.61(RR=1.56, 95%CI: 1.02-2.39), cesarean section (RR=2.06, 95%CI: 1.42-2.97), frequency of breastfeeding on day 1 after deliver<3 (RR=1.62, 95%CI: 1.18-2.22) and delayed OL(RR=2.24, 95%CI: 1.46-3.44) may increase the risk of early termination of any breastfeeding significantly. Path analysis model showed that delayed OL was an important intermediary role on association among exposure to stressful life events during first trimester, gestational BMI gain, rating of perceived tension to delivery, cesarean section, frequency of breastfeeding on day 1 after deliver and early termination of any breastfeeding. Furthermore, it was identified that maternal stressful life events during first trimester may increase the risk of early termination of any breastfeeding through four pathways.There was no statistic difference of demographic characteristics between control group and exposed group while the infant birth weight of exposed group was significantly lower than control group. Mental Development Index (MDI) of infant in exposed group was significantly lower than that of the control group after controlling gestational age, infant birth weight, duration of full breastfeeding and any breastfeeding(102.43, 95%CI: 99.29-105.57 vs 110.31, 95%CI: 108.55-112.08; F=18.18, P<0.001) while Psychomotor Development Index (PDI) had no significant difference between the two groups. The scores of rhythmicity, emotion and persistency in temperament of exposed infants were significantly higher than control group after controlling covariates, respectively.Conclusions1. Maternal stressful life events during first trimester may change the sensitivity of fetal adrenal cortex to ACTH and down-regulate the response of pituitary-adrenocortical axis to acute stress.2. Exposure to stressful life events during first trimester may reduce early breastfeeding through multiple pathways.3. Prenatal stress during first trimester was associated independently with special impairment of neurobehavioral development in toddler.Evidences from this study support previous hypothesis that prenatal psychological stress may influence neurobehavioral development of offspring through two different pathways including deleterious programming effects on the fetal HPA axis and reducing early breastfeeding.