**Background:** Nausea and vomiting in pregnancy (NVP) affects 50–80% of pregnant women and is correlated with human chorionic gonadotropin (hCG) levels. Hyperemesis gravidarum (HG) is a severe condition with an incidence of 0.2–1.5%, characterized by consistent nausea, vomiting, weight loss, and dehydration. Previous research has suggested that HG may increase the risk of placenta-associated complications, while NVP may be protective against miscarriage. This systematic review aimed to investigate correlations between NVP or HG and adverse pregnancy outcomes and hCG levels.
**Methods:** A systematic search was conducted in PubMed, Embase, and CINAHL Complete on 28 September 2021. Studies on pregnant women with nausea in the first or second trimester reporting pregnancy outcomes or hCG levels were included. Primary outcomes were preterm delivery (PTD), preeclampsia, miscarriage, and fetal growth restriction (FGR). Secondary outcomes included small for gestational age (SGA), low birth weight (LBW), intrauterine fetal death (IUFD), placental abruption, fetal sex, and hCG levels. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated using GRADE. The protocol was registered with PROSPERO (CRD42021281218).
**Key Results:** The search yielded 2023 potentially relevant studies; 23 were included (20 case-control, 3 cohort studies). Fourteen studies included women with HG. For women with HG, meta-analyses showed: increased risk for preeclampsia (OR 1.18, 95% CI 1.03 to 1.35), PTD (OR 1.35, 95% CI 1.13 to 1.61), SGA (OR 1.24, 95% CI 1.13 to 1.35), and LBW (OR 1.35, 95% CI 1.26 to 1.44). A higher fetal female/male ratio was observed (OR 1.36, 95% CI 1.15 to 1.60). For women with NVP, meta-analyses could not be performed due to high heterogeneity, but most studies indicated lower risk for PTD and LBW and higher risk for SGA. Miscarriage was reported in three studies but could not be pooled due to heterogeneity. FGR was reported in only one study. Five studies reported hCG levels, showing higher levels in women with HG, but results could not be pooled due to different measurement methods and units. The GRADE assessment rated the certainty of evidence as very low for all assessed outcomes (preeclampsia, PTD, miscarriage, FGR, SGA, LBW) due to risk of bias, inconsistency, and imprecision.
**Clinical Implications:** The findings suggest that women with HG may have an increased risk for adverse placenta-associated outcomes, while women with milder NVP may have a reduced risk. This potential dose-response relationship between nausea severity and pregnancy outcomes could inform clinical counseling and monitoring. The higher female/male fetal ratio in both NVP and HG suggests an interesting sexual dimorphism that warrants further investigation. However, the very low certainty of evidence means clinicians should interpret these findings cautiously. The review highlights the need for future studies with lower risk of bias, better control for confounders, and stratification of HG by severity to improve the evidence base for managing these common pregnancy conditions.