The timing, duration, and severity of nausea and vomiting of pregnancy and adverse birth outcomes among controls without birth defects in the National Birth Defects Prevention Study

Abstract

BackgroundNausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive.ObjectiveTo determine whether NVP and reported medications are associated with adverse birth outcomes.MethodsWe used data from the population‐based, multisite National Birth Defects Prevention Study (1997–2011) to evaluate whether self‐reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy.ResultsAmong 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4–6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7–9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7–9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication.ConclusionMild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long‐lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.

Re-examining the adaptive function of nausea and vomiting in pregnancy

“…Beyond the severity and symptomology of NVP, there is some evidence that the timing and duration of NVP also matters. In a recent analysis of the US National Birth Defects Prevention Study, NVP in the first trimester was associated with a reduced risk of small-for-gestation-age birth, in line with earlier studies which found a general positive association between NVP and better birth outcomes [ 57 ]. However, in the same study, NVP lasting beyond early pregnancy into the second and third trimester was associated with an increased risk of preterm birth [ 57 ].…”

“…In a recent analysis of the US National Birth Defects Prevention Study, NVP in the first trimester was associated with a reduced risk of small-for-gestation-age birth, in line with earlier studies which found a general positive association between NVP and better birth outcomes [ 57 ]. However, in the same study, NVP lasting beyond early pregnancy into the second and third trimester was associated with an increased risk of preterm birth [ 57 ]. Similarly, in an analysis of the Swedish Medical Birth Register, women who experienced in-patient treatment for HG in the first trimester only had a slight increased risk of pre-eclampsia compared to baseline, while women who experienced in-patient treatment for HG in the second trimester experienced significant increased risks of pre-term pre-eclampsia, placental abruption and small-for-gestational-age birth [ 58 ].…”

“…If environmental mismatch exists, the overall implication is that ‘functional’ NVP may be limited to particularly mild forms of NVP. Indeed, as reviewed above, there is some evidence that milder forms of NVP limited to early pregnancy may encourage placental growth and improve birth outcomes [ 16 , 57 ] – and it is possible that mild NVP was positively selected in humans due to this benefit. However, to date, research on NVP from an evolutionary perspective has typically treated NVP (excluding hyperemesis gravidarum ) as a homogenous category without careful consideration of the variations in severity, symptoms, and duration.…”