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Hyperemesis Gravidarum and Adverse Perinatal Outcomes
Abstract & Commentary
By John C. Hobbins, MD, Professor of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado, is Associate Editor for OB/GYN Clinical Alert.
Dr. Hobbins reports no financial relationships relevant to this field of study.
Synopsis: A recent meta-analysis has suggested that there is a modestly increased risk for preterm birth, SGA, and low birth weight in patients suffering from hyperemesis gravidarum.
Source: Veenendaal MV, et al. Consequences of hyperemesis gravidarum for offspring: A systematic review and meta-analysis. BJOG 2011;118:1302-1313.
How often are we asked whether a patient who has had severe nausea and vomiting in early pregnancy has a greater chance of adverse outcome in her pregnancy? Intuitively, one would think that there might be some effect on the fetus and/or placenta, but since there have been few red flags in the literature to the contrary, I have been inclined to be (and I guess I will continue to be) reassuring.
A meta-analysis recently published in the British Journal of Obstetrics and Gynaecology does show some elevation of risk in the 0.3-2% of patients with the most severe form of the spectrum, hyperemeis gravidarum (HG).1 The authors reviewed 205 studies. After applying rigorous exclusionary criteria, 24 papers remained that dealt with the short- and long-term effects of HG. These studies were either cohort (n = 10), case-control (n = 13), or cross-sectional (n = 1) in design. Four studies were prospective.
Those who were admitted with, or simply diagnosed to have, HG had an increased chance of having a female infant (odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.21-1.34). Low birth weight occurred in 6.4% in infants with HG vs 5% in controls (OR = 1.42; 95% CI, 1.27-1.58), and small-for-gestational age (SGA) occurred in 17.9% of those with HG, compared with 12.7% in controls (OR = 1.28; 95% CI, 1.02-1.68). There also was a significant increase in preterm delivery (OR = 1.32; 95% CI, 1.04-1.68).
The categories in which HG had no significant impact were in perinatal deaths, Apgar scores, and congenital anomalies. Only one long-term study was conducted involving HG and showed no differences in neurological outcomes at 1 year of age between groups. Interestingly, one study did show an increase in testicular cancer in men younger than 40 years of age whose mothers had HG.
I have been waffling when asked questions by pregnant patients about the possible ill effects of persistent nausea and vomiting because single reports in the literature have had conflicting results. Actually, I am surprised that a meta-analysis has not been put together before now. Now, we can say that there may be only a modest increase in low birth weight, SGA, and preterm birth, but not in perinatal death, anomalies, or long-term neurological outcomes. Nevertheless, it should be cautioned that these outcome data only apply to the most severe forms of nausea and vomiting in pregnancy, and, in fact, may not be due to the nausea and vomiting, per se, but rather to a separate predisposition for the outcomes in patients who are prone to this condition. This could not be addressed in the meta-analysis.
Since even less is known on how to best treat patients with HG, given the paucity of trials using various methods, one simply relies on anecdotal experience. First-line management should be trying to maintain adequate fluid and electrolyte balance, as well as avoiding vitamin deficiencies (especially thiamin). Some medications can help, most of which have not been studied adequately. These include various antihistamines and antiemetics. We definitely have had good success with the serotonin antagonist, ondansetron (Zofran), in many patients with intractable nausea and vomiting. Even some over-the-counter medications, such as Unisom (a nighttime medication), can work in milder forms of nausea. Acupuncture has been reported to be successful in some individuals.
Treating the fallout of HG is very important. If oral fluid replacement and small feedings do not work, home-based parenteral alimentation of IV fluid replacement is effective in keeping patients from needing repeated hospitalizations. Fortunately, the huge majority of miserable patients can count on their discomfort being short-lived. And yes, those grandmothers asserting that this first trimester nausea and vomiting means that their granddaughters' fetuses are girls are right more often than wrong.