The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring.

Method: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics.

Result: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034).

Conclusions: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Keywords: Catch-up growth; Child health; Growth disparities; Intrahepatic cholestasis of pregnancy.

Fig. 1

Selection of women and offspring for assessing the impacts of ICP on metabolism and child growth

Fig. 2

Correlation analysis of baseline characteristics, serological test results and offspring growth indicators between pregnant women with ICP and pregnant healthy controls. A Correlations among baseline characteristics, serological tests and abnormal offspring development. “*” represents P < 0.05. Red indicates a positive correlation, and blue signifies a negative correlation. The intensity of the color directly correlates with the strength of the relationship. Scatter plots depicting the correlation between maximum maternal LDH levels (left) and maximum maternal TBA levels (right) and offspring LAZ or WAZ at different time intervals. LAZ (B) and WAZ (C) values in offspring during the 1- to 6-month age range, LAZ (D) and WAZ (E) values in offspring during the 7- to 12-month age range, and LAZ (F) values in offspring during the 13- to 18-month age range. WAZ values in the 7- to 12-month age range, LAZ values in the 13- to 36-month age range, and WAZ values in the 13- to 36-month age range can be found in Additional file 2: Figure S1. Green represents the control group, and yellow represents the ICP group. Correlation coefficients (R) and p values are provided for each group to indicate the strength and significance of the correlations. Abbreviations: GWG, gestational weight gain; BH, birth height; BW, birth weight; K, child; M, mother; Ab_Dev, abnormal development (LAZ, WAZ, WLZ, BAZ or HCZ < -2); PB, preterm birth; NICU, neonatal intensive care unit; PJON, pathological jaundice of newborn. LAZ, length-for-age score. WAZ, weight-for-age z score. All serum markers are represented by the highest values