Perinatal outcomes of infants born to mothers with hyperemesis gravidarum: A systematic review and meta-analysis

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Background: Hyperemesis gravidarum is the severe form of nausea and vomiting during pregnancy and can lead to undernutrition and low maternal weight gain. Previous epidemiologic and animal studies have shown that undernutrition and low maternal weight gain in pregnancy can increase the risk of unfavorable perinatal outcomes, like shorter gestational age, small for gestational age and lower weight at birth. Objective: To evaluate the effect of hyperemesis gravidarum on perinatal outcomes. Search strategy: OVID Medline and Embase were searched from inception to February 9th, 2022. Study eligibility: Studies reporting on perinatal outcomes of infants born to mothers with hyperemesis gravidarum or severe nausea and vomiting in pregnancy were included. Case reports, case series, animal studies, reviews, editorials and conference abstracts were excluded. Data collection and analysis: Two reviewers independently selected and extracted data. Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale. We conducted meta-analyses where possible. Results: Our search yielded 1387 unique papers, of which 61 studies (n = 20,532,671 participants) were included in our systematic review. Meta-analyses showed that hyperemesis gravidarum was associated with preterm birth < 34 weeks (2 studies n = 2,882: OR 2.81, 95 %CI: 1.69–4.67), birth weight < 1500 g (2 studies, n = 489,141: OR 1.43, 95 %CI: 1.02–1.99), neonatal resuscitation (2 studies, n = 4,289,344: OR 1.07, 95 %CI: 1.05–1.10), neonatal intensive care unit admission (7 studies, n = 6,509,702: OR 1.20, 95 %CI: 1.14–1.26) and placental abruption (6 studies, n = 9,368,360: OR 1.15, 95 %CI: 1.05–1.25). Hyperemesis gravidarum was associated with reductions in birthweight > 4000 g (2 studies, n = 5,503,120: OR 0.74, 95 %CI: 0.72–0.76) and stillbirth (9 studies, n = 3,973,154: OR 0.92, 95 %CI: 0.85–0.99). Meta-analyses revealed no association between hyperemesis gravidarum and Apgar scores < 7 at 1 and 5 min; fetal loss, perinatal deaths and neonatal deaths. Conclusion: Hyperemesis gravidarum is associated with several adverse perinatal outcomes including low birth weight and preterm birth. We also found that pregnancies complicated by hyperemesis gravidarum less frequently were complicated by macrosomia and stillbirth. We were unable to investigate underlying mechanisms.

Original languageEnglish
Pages (from-to)30-51
Number of pages22
JournalEuropean Journal of Obstetrics and Gynecology and Reproductive Biology
Publication statusPublished - 1 May 2023


  • Birth outcomes
  • Hyperemesis gravidarum
  • Meta-analysis
  • Perinatal outcomes
  • Systematic review

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