Hyperemesis gravidarum: epidemiologic features, complications and outcome

European Journal of Obstetrics & Gynecology and Reproductive Biology 63 (1995) 135 138

ELSEVIER

GYNECOLOGY

Hyperemesis gravidarum: epidemiologic features, complications and outcome Asher Bashiri *~, Lily Neumann b, Eli Maymon ~, Miriam Katz ~' "Dt7)artment (~/ Obstetrics and GynecoloL~v, Soroka Medical Center and the Faculo" ~)['Health Sciences, Ben-Gurion Unirersio~ ~/ the Negev, Beer-Shera, Israel ]'EpidemioloL~v l~')tit, Soroka Medical Center and the Faeul O" ~[' Health Sciences, Ben-Gurion lJTuversity ~/' the Negev, Beer-Sheca, Israel Received 6 March 1995: revision received 26 June 1995: accepted 22 August 1995

Abstract

During the period of 4 years between 1985 and 1988, 190 patients suffering from hyperemesis gravidarum (HG) were hospitalized at the Soroka Medical Center, From the 190 patients, 164 were followed up throughout their pregnancies and delivered at our Medical Center. The epidemiology of HG as well as the incidence of maternal complications and pregnancy outcome were analyzed and compared with 209 controls. The incidence of HG in our patient population was 6.3/1000 live births. The patients in the study group had fewer pregnancies and deliveries and more spontaneous abortions in the past than in the control population. Premature contractions and vaginal bleeding during the first trimester were more common among women with HG. Other complications of pregnancy were no more common than among controls. Women with HG in their current pregnancy had a lower incidence of spontaneous abortions (3.1%) as compared with previously reported rates in the general population (15%). Perinatal outcome was no different in women with HG than in the controls. Women with severe HG did not have statistically significant differences in the incidence of pregnancy complications and their pregnancy outcome was the same as in those without severe HG.

Keywords: Hyperemesis gravidarum: Epidemiology; Pregnancy outcome 1. Introduction H y p e r e m e s i s g r a v i d a r u m ( H G ) is a s y n d r o m e t h a t occurs in the first h a l f o f p r e g n a n c y and is m a n i f e s t e d by v o m i t i n g often so severely that patients require h o s p i t a l i z a t i o n . H G is not a s s o c i a t e d with either a p p e n dicitis o r pyelitis. T h e v o m i t i n g can cause weight loss, d e h y d r a t i o n , k e t o n u r i a , ketosis, a n d electrolyte i m b a l ances [1,2]. W h i l e nausea a n d v o m i t i n g are c o m m o n d u r i n g p r e g n a n c y a n d are present in over 50% o f p r e g n a n t w o m e n . H G is relatively rare a n d occurs in only a b o u t 0.5% o f p r e g n a n c i e s [1,3]. Since n a u s e a and v o m i t i n g in p r e g n a n c y are m o s t c o m m o n d u r i n g the first trimester o f p r e g n a n c y , when H C G a n d estradiol are at p e a k levels, these s y m p t o m s can be a t t r i b u t e d , at least in part. to h o r m o n a l influences [4]. Several studies have e v a l u a t e d the o u t c o m e o f p r e g n a n c i e s ' c o m p l i c a t e d ' by nausea a n d vomiting. These studies d e m o n s t r a t e d that p r e g n a n c i e s c h a r a c t e r * Corresponding author, Tel.: + 972 7 434233. 0301-211595/$09.50 :t~ 1995

SSD10301-2115(95)02238-3

ized by n a u s e a a n d v o m i t i n g have better o u t c o m e , e.g. fewer a b o r t i o n s [5,6], a lower rate o f stillborn fetuses, a n d a r e d u c e d risk o f p r e m a t u r e delivery (before the 37th week o f p r e g n a n c y ) [7]. T h e e t i o l o g y o f H G r e m a i n s unclear. It is believed to involve e n d o c r i n o l o g i c a l , allergenic, a n d p s y c h o n e u rotic factors [1,2,4]. In all likelihood, H G represents an extreme degree o f the c o m m o n - p l a c e nausea a n d v o m i t ing o f p r e g n a n c y , a n d these entities share, at least in part, a c o m m o n etiological basis. In a d d i t i o n , little has been p u b l i s h e d a n d little is k n o w n o f the course a n d o u t c o m e o f pregnancies c o m p l i c a t e d with H G . O n e study d e m o n s t r a t e d that w o m e n with H G h a d a reduced risk o f fetal loss, b u t the n e o n a t e s h a d a higher risk for congenital a n o m a l i e s o f the central nervous system [8]. O t h e r studies have shown that infants b o r n to h y p e r e m e t i c m o t h e r s have a lower birth weight t h a n c o n t r o l g r o u p s [3,9,10]. In one study the investigators f o u n d that H G was m o r e c o m m o n in w o m e n w h o s u b s e q u e n t l y gave birth to female infants [10]. T h e p u r p o s e o f the present study was to evaluate the association between the clinical course, obstetric corn-

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A. Bashiri el al. , European Journal o~ Ob,~tetric.~ & @'necolo~,U' amt R~7~roduclive Biology 63 (1995) 135 138

Table 1 Sociodemographic characteristics o1" the study groups Parameter

HG patients n - 190

Control patients n - 209

P

Ethnic origin Jewish Bedouin

91.5% (174) 8.5% (16)

61.7% (129) 38.3% (80)

<0.001

Average age (years) Average number of pregnancies Average number of deliveries Prior spontaneous abortion

26.6 2.8 2.1 27.4% (52 190)

27.7 3.6 3.3 17.2% (36,209

< 0.05 <0.01 < 0.00 I <0.05

Table 2 Obstetric complications in HG patients Complication

HG patients n - 164

Control patients n - 209

P

Eclampsia Vaginal bleeding during the first trimester Premature contractions Premature rupture of membranes IUGR Gestational diabetes

1.8% 5.5% 7.3% 4.2% 4.2% 7.9%

6.2% (13/209)

NS <0.01 < 0.001 NS NS NS

(3:164) (9:164) 12/164) (7,'164) (7,164) (13,164)

plications and birth outcome in pregnant women with HG, and to determine the epidemiological characteristics of these women. In particular, we aimed to assess whether the presence of HG had any detrimental impact on the outcome of pregnancy. 2. Materials and methods

The study was conducted in the Soroka Medical Center in Beer-Sheva, Israel during a period of 4 years (1985-1988) and included all women diagnosed with hyperemesis gravidarum (HG) according to the diagnostic criteria defined by Fairweather [1]. The retrospective study employed a checklist which included (1) demographic items such as age, ethnic origin, number of the present pregnancy and birth, and previous spontaneous abortions, (2) items relating to complications of pregnancy and childbirth, such as eclampsia, vaginal bleeding, premature contractions, premature rupture of membranes, intrauterine growth retardation (IUGR), and gestational diabetes, and (3) items relating to birth outcome such as type of delivery, birthweight, gender, placental pathology, spontaneous abortion, perinatal mortality, congenital malformations, the number of fetuses, and the presence of meconium. Data was collected from all women diagnosed with H G during the study years, and was compared with a control group chosen at random from the women who gave birth during the same time span in the Soroka Medical Center and who did not suffer from HG. Since

1.4% (3/209) 8.1'>, (17/209) 8. I%, (17209)

26 women were not in follow-up nor did they deliver at Soroka Medical Center, the study group according to pregnancy complication and outcome was 164 women. Statistical analyses were conducted using the t- or Z2-statistic as appropriate. In the second part of the study we analyzed a subset of women with the most severe cases of HG using pre-determined criteria, and compared pregnancy complications and birth outcome between this group of women and controls. HG was defined as severe if one or more of the following were present at the time of hospitalization: (1) hematocrit > 43%: (2) women with creatinine levels between 0.8 1.5 mg/dl and/or blood urea levels above 20 mg/dl: and (3) ketonuria + 3 by ketostix. 3. Results

Sociodemographic features of the study and control populations are presented in Table 1. Table 2 details obstetric complications throughout pregnancy in the two study groups. Vaginal bleeding during the first trimester was more common in HG patients. It was diagnosed by a speculum examination and no other source of bleeding was observed except that from the cervical canal. Preterm contractions were also more common among HG patients. The diagnosis was based on the presence of regular uterine contractions registered by external tocometer in patients complaining of lower abdominal pain. Pregnancy outcome is presented in Table 3. In the study group the risk of

A. Bashiri et al. / European Journal of Obstetrics & Gynecoh)gy and Reproductire Biology 63 (1995) 135 138

137

Table 3 Pregnancy outcome HG patients n = 164

Control group n - 209

Gestational age at delivery (weeks) Vaginal delivery Spontaneous abortion

38.8 82.3% (135/164) 3.1% (5/164)

39.1 90.4% (189/209) 15.1% (general population)

Gender of offspring Male Female Average weight at birth (g) Pregnancy with single fetus Perinatal mortality Meconium Congenital anomalies Placental pathology

49.4% (81 ) 50.6% (83) 3122 91.4% (150/164) 1.9% (3/164) 9.7% (16/164) 0.6% (1 / 164) 3.2% (5/1641

49.7% (104) 50.2% (105) 3145 95.7% (200/209) 1.9% (4/209) 12.9% (27/209) 1.0% (2/209) 0.5% ( 1/209)

spontaneous abortion was 3.1%, compared to a prevalence of 15% in previously reported populations (P < 0.001). There were no statistically significant differences in any of the other parameters tested between the study and control groups. According to the criteria mentioned in Materials and methods, 113 women were diagnosed as suffering from severe HG. No statistically significant differences were found between women diagnosed as suffering from severe H G and the controls in terms of I U G R , placental pathology, spontaneous abortions, perinatal mortality, congenital anomalies, birth weight, and gestational age at delivery. 4. Discussion

We studied all women with H G in the Soroka Medical Center during the years 1985 1988. The incidence of H G in our study group (0.6%) was consistent with that reported in the literature [1,3]. Most women with H G were Jewish. Bedouin women represented over 40% of pregnancies in the Soroka Medical Center during the study years, but only 8.5% of the cases of HG. This difference was highly significant. We propose two possible explanations for this difference. The first possibility is that Bedouin women are less aware of the potentially serious consequences of this situation and do not refer themselves to medical attention. Alternatively it is possible that the actual incidence a m o n g Bedouin women is lower. Similarly low rates have been reported among African and Eskimo women [4]. We also found that H G is more prevalent among younger women, and a m o n g women with fewer previous pregnancies and deliveries. These findings are consistent with previous reports [8,10]. It is possible that this stems from psychological components of HG. Younger women with less prior obstetric experience (and a particular personality make-up) may be less prepared for pregnancy, and thus develop HG.

It is noteworthy that 27.4% of women with H G reported a spontaneous abortion in a previous pregnancy compared to 17.3% in the control group, a statistically significant difference. This finding is consistent with reports in the literature which showed that H G is more prevalent in women who reported unsuccessful or complicated pregnancies in the past Ill]. The explanation for this phenomenon may be related to the same psychological factors previously addressed, i.e. a fear or reticence from pregnancy due to the past failures. Evidence for such a factor could be elicited using a questionnaire that would evaluate these emotions. It would be of interest to conduct a prospective study of women with complicated pregnancies and undesirable pregnancy outcomes such as stillbirths, and to monitor the rate of H G in future pregnancies. We proposed to examine the hypothesis that the hormonal causes of H G might also alter intrauterine conditions in a manner that would negatively affect the course of pregnancy and its outcome. Our results confirmed this theory only in regard to premature contractions and vaginal bleeding in the first trimester which were both significantly more common among women with H G compared to controls. This finding has not been reported previously in the literature and justifies further investigation. In addition, the above may show a biased opinion due to the fact that none of the women in the control group were with vaginal bleeding or premature contractions. Previous studies have reported lower birth weights, higher rates of female infants, and fewer multiple fetuses among women with H G than controls [3,10]. We found only one statistically significant difference between the study and control groups relating to pregnancy outcome. This was in the incidence of spontaneous abortions during the present pregnancy. A m o n g women in the H G group the percentage of spontaneous abortions was 3.1% compared to approxi-

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A. Bashiri et al. ,' European Journal ~[' Obstetrics & Gynecology and R~7)roductiec Bioh)gy 63 (1995) 135 138

mately 15% in the general population. Thus, HG would appear to be a protective factor for spontaneous abortion. This is consistent with previous reports concerning nausea and vomiting in pregnancy [6,10,12,13]. Another study found a similar percentage of spontaneous abortions (3.3%) among w o m e n with HG, but did not find a difference compared to w o m e n with morning sickness but who were diagnosed as HG [4]. Therefore the same protective factor, namely nausea and vomiting, would appear to be in effect without regard to degree of severity of vomiting which, at the extreme, is manifested as HG. We found no association between parameters of pregnancy outcome and degrees of severity of HG (as assessed by predetermined criteria). Other criteria for determining the degree of severity of HG should be set. The extent of maternal weight loss due to HG might be one possible criterion, In one study which used this latter criterion, w o m e n with H G had infants of lower birth weight than controls [9]. Since w o m e n do not usually remember their pre-pregnancy weight, we would recommend conducting a cohort study of maternal weight. References [I] Fairweather DVI. Nausea and vomiting in pregnancy. Am J Obstet Gynecol 1968: 102:135 175.

[2] Fairweather DVI. Nausea and vomiting during pregnancy. Obstet Gynecol Annu 1978: 7:91 105. [3] Chin RKH, Lo TT. Low birth weight and hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1988: 28:179 183. [4] Jarnfelt-Samsioe A. Nausea and vomiting in pregnancy: a review. Obstet Gynecol Survey 1987: 41:422 427. [5] Medalie Jtl. Relationship between nausea and:or vomiting in early pregnancy and abortion. Lancet 1957: ii: 117 119. [6] Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome. A meta-analytical review. Br J Obstet Gynecol 1989; 96:1312 1318. [7] Klebanoff MA, Koslowe PA, Kaslow R, Rhoads GG. Epidemiology of vomiting in early pregnancy. Obstet Gynecol 1985; 66: 612 616. [8] Depue RH, Bernstein L, Ross RK, Judd HL, Henderson BE. Hyperemesis gravidarum ill relation to estradiol levels, pregnancy outcome and other maternal factors: A sero-epidemiologic study. Am J Obstet Gynecol 1987: 156:1137 1141. [9] Gross S, Librach C, Cecutti A. Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome. Am J Obstet Gynecol 1989: 160:906 909. [10] Kallen B. Hyperemesis during pregnancy and delivery outcome: a registry study. Eur J Obstet Gynecol Reprod Biol 1987: 26: 291 302. [11] Chin RKH. Antenatal complications and perinatal outcome in patients with nausea and vomiting-complicated pregnancy. Eur J Obstet Gynecol Reprod Biol 1989: 33:215 219. [12] Weigel MM, Weigel RM. Nausea and vomiting of early pregnancy outcome. An epidemiological study. Br J Obstet Gynecol 1989: 96:1304 1311. [13] Petitti DB. Nausea and pregnancy outcome. Birth 1986; 13: 223 226.