TY - JOUR
T1 - Long-term health outcomes of children born to mothers with hyperemesis gravidarum
T2 - a systematic review and meta-analysis
AU - Nijsten, Kelly
AU - Jansen, Larissa A. W.
AU - Limpens, Jacqueline
AU - Finken, Martijn J. J.
AU - Koot, Marjette H.
AU - Grooten, Iris J.
AU - Roseboom, Tessa J.
AU - Painter, Rebecca C.
N1 - Funding Information: This systematic review was funded by the Amsterdam Reproduction & Development (AR&D) research institute (grant number 23346 ) and the Dutch Heart Foundation (grant number 2013T085 ). Publisher Copyright: © 2022 The Author(s)
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Objective: Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health. Data Sources: MEDLINE and Embase were searched from inception to September 6, 2021. Study Eligibility Criteria: Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included. Methods: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I2>75%), we did not provide a pooled odds ratio. Results: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04–2.91; I2, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25–6.93; I2, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07–2.39; I2, 0%; 95% prediction interval, 0.83–3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings. Conclusion: Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.
AB - Objective: Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health. Data Sources: MEDLINE and Embase were searched from inception to September 6, 2021. Study Eligibility Criteria: Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included. Methods: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I2>75%), we did not provide a pooled odds ratio. Results: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04–2.91; I2, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25–6.93; I2, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07–2.39; I2, 0%; 95% prediction interval, 0.83–3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings. Conclusion: Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.
KW - autism spectrum disorder
KW - cardiometabolic risk factors
KW - dyssomnias
KW - hyperemesis gravidarum
KW - long-term effects
KW - meta-analysis
KW - neurodevelopmental disorders
KW - systematic review
KW - testicular neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85130069785&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ajog.2022.03.052
DO - https://doi.org/10.1016/j.ajog.2022.03.052
M3 - Review article
C2 - 35367190
SN - 0002-9378
VL - 227
SP - 414-429.e17
JO - American journal of obstetrics and gynecology
JF - American journal of obstetrics and gynecology
IS - 3
ER -