Increasing nausea and vomiting of pregnancy is associated with sex-dependent differences in early childhood growth: the GUSTO mother-offspring cohort study

Abstract

Background: Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes.

Methods: In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex.

Results: 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0-36+ 6 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted β = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years.

Conclusions: Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health.

Trial registration: Clinicaltrials.gov identifier NCT01174875 .

Keywords: Child anthropometry; Child growth; Hyperemesis gravidarum; Premature birth.

Conflict of interest statement

KMG, CYS and SYC are part of an academic consortium that has received research funding from Nestle. KMG, YSL and CYS have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. The other authors have no financial or personal conflict of interest to declare.

© 2021. The Author(s).

Figures

Fig. 1

Association between severity of nausea and vomiting of pregnancy (NVP) and offspring anthropometry from birth to 72 months (m) in boys (1a-1c) and girls (1d-1f). The regression co-efficient in z-score for offspring length/height (1a and 1d), weight (1b and 1e) and body mass index (1c and 1f) with 95% confidence intervals (CI) for each NVP group (mild-moderate: inverted black triangle; severe: green triangle; severe with hospitalisation: red dot) at each time point, relative to the reference group (no NVP, represented by the horizontal black line at 0 on the y-axis) is shown. Adjustment was made for maternal age, ethnicity, pre-pregnancy BMI, maternal education, parity, gestational age and smoking during pregnancy. Number of children contributing data at each time point is shown in the table. Statistically significant differences are highlighted by a light grey background with p values indicated as follows: No NVP vs mild-moderate: + p < 0.05, ++ p < 0.01; no NVP vs severe: * p < 0.05, ** p < 0.01; no NVP vs severe with hospitalization: # p < 0.05, ## p < 0.01

Fig. 2

Association between the severity of nausea and vomiting of pregnancy (NVP) and change in offspring conditional length/height (2a and 2c) or weight (2b and 2d) gain in boys (blue) and girls (red), at 3-monthly intervals from birth to 12 months (2a and 2b) and at annual intervals from birth to 72 months (2c and 2d). The regression co-efficient in z-score with 95% confidence intervals (CI) for each NVP group [mild-moderate (mNVP): inverted triangle; severe (sNVP): triangle; severe with hospitalization (shNVP): dot] at each time point, relative to the reference group (no NVP, represented by the horizontal dotted line at 0 on the y-axis) is shown. Adjustment was made for maternal age, ethnicity, pre-pregnancy BMI, maternal education, parity and smoking during pregnancy. Statistically significant differences compared with the no NVP group occur where the 95%CI does not cross 0. Statistically significant interaction-p for sex differences are highlighted in brackets: *p < 0.05 and trend #p = 0.101