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Hyperemesis Gravidarum and the Sex of the Offspring

del Mar Melero-Montes, María; Jick, Hershel

Brief Report

Studies have suggested that offspring of women hospitalized for hyperemesis gravidarum have a different sex ratio than those of women without this diagnosis, but little is known of the potential association between fetal gender and variables such as severity of hyperemesis, gestational trimester, and maternal age. Our findings provide evidence that pregnant women with a diagnosis of hyperemesis gravidarum in the first trimester give birth to a higher proportion of female newborns than do all mothers, regardless of whether they are hospitalized.

From the Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, 11 Muzzey Street, Lexington, MA 02421.

Address correspondence to: Maria del Mar Melero-Montes, M.P.H., Boston Collaborative Drug Surveillance Program, 11 Muzzey Street, Lexington, MA 02421.

The Boston Collaborative Drug Surveillance Program is supported in part by grants from AstraZeneca, Berlex Laboratories, Boots Healthcare International, Bristol-Myers Squibb Pharmaceutical Research Institute, Glaxo Wellcome Inc., Hoffmann-La Roche Ltd., Janssen Pharmaceutica Products, L.P., RW Johnson Pharmaceutical Research Institute, McNeil Consumer Products Company, and Novartis Farmacéutica S.A.

Submitted May 1, 2000; final version accepted July 26, 2000.

Hospitalization for hyperemesis gravidarum (severe nausea and vomiting in pregnancy) has been reported to be associated with a sex ratio of offspring that differs from the general population. 1,2 There is little information on the relation between infant gender and severity of disease, trimester of pregnancy, and maternal age.

We conducted a population-based study to determine the fetal gender distribution of women with hyperemesis gravidarum and compared the distribution with that of all births, based on information present in the General Practice Research Database (GPRD). We also examined the possible association between infant gender and severity of the disease, maternal age, and gestational trimester.

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The GPRD is a large computerized database that encompasses some 3 million actively enrolled people in United Kingdom. 3–5 The information is generated by general practitioners in their daily practices in which they record virtually all patient information on an ongoing basis. The database contains essentially complete anonymous information on demographics, diagnoses, symptoms, referrals, hospitalizations, and drug prescriptions for all patients in the general practices that contribute data. Free text comments relating to diagnoses and therapies are also listed.

We identified all women who delivered a liveborn baby between January 1, 1992 and October 31, 1996, who had a computer-recorded diagnosis of hyperemesis gravidarum (ICD8–638). Cases of hyperemesis gravidarum were derived from computerized patient profiles, which routinely provide information on the date of diagnosis together with the date of delivery, referral status, medication received, and sex of the baby. We excluded women who had spontaneous abortions, termination of pregnancy, or stillbirths. The time from the estimated date of conception to the date of a first recorded diagnosis of hyperemesis was used to determine the trimester of pregnancy.

The computer records of women with the diagnosis of interest were reviewed individually to confirm the diagnosis, the presence of outpatient drug treatment, and the sex of the baby. Women with several diagnoses of hyperemesis gravidarum were counted only once on their first pregnancy with the diagnosis. Admission to the hospital was used as a proxy for severity of disease.

Among pregnant women with hyperemesis gravidarum, we determined the proportion of male fetuses and compared it with that for all births. We also analyzed data for women who developed hyperemesis gravidarum in the first trimester versus second and third trimester and examined maternal age as a possible risk factor. Women admitted to the hospital were compared with women who were not. Finally, we estimated the proportion of women with hyperemesis treated as outpatients with antiemetics.

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We identified 127,647 women in the United Kingdom-based General Practice Research Database who delivered live born babies from January 1, 1992 through October 31, 1996. Among the babies of these women, the proportion of male births was 0.512 (see Table 1). Of the total number of women with live born deliveries, 4126 had a diagnosis of hyperemesis gravidarum; 3249 were diagnosed during the first trimester of pregnancy. The hospitalization frequency in this sub-group was 18.6%. The proportion of male fetuses among mothers with hyperemesis during the first trimester of pregnancy was 0.465. The proportion of male fetuses among women who developed hyperemesis gravidarum during the second and third trimester did not differ much from that of the total study population (see Table 1).

Among women with hyperemesis gravidarum in the first trimester, the proportion of male fetuses was similar for all maternal ages and for different severities of the disease (hospitalized mothers vs. non-hospitalized mothers). Antiemetic medication was prescribed to 30.5% of mothers with a diagnosis of hyperemesis gravidarum during the first trimester.

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We found a decreased proportion of male fetuses among women who developed hyperemesis gravidarum in the first trimester of pregnancy; this decrease was unrelated to age or severity of hyperemesis gravidarum. It has been suggested that maternal serum human chorionic gonadotropin (hCG) levels are influenced by the sex of the fetus, and specifically that hCG concentrations in maternal blood and placenta tissues are higher when the fetus is female. 6 If so, the sex of the fetus would be a cause of hyperemesis gravidarum.

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1. Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A. Sickness in pregnancy and sex of child. Lancet 1999; 354: 2053.
2. Sørensen HT, Thulstrup AM, Mortensen JT, Larsen H, Pedersen L. Hyperemesis gravidarum and sex of child. Lancet 2000; 355: 407.
3. Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 1991; 302: 766–768.
4. Jick H, Terris BZ, Derby LE, Jick SS. Further validation of information recorded on a general practitioner based computerized data resource in the United Kingdom. Pharmacoepidemiol Drug Safety 1992; 1: 347–349.
5. Jick H. A database worth saving. Lancet 1997; 350: 1045.
6. Kauppila A, Huhtanemi I, Ylikorkola O. Raised serum chorionic gonadotropin in hyperemesis gravidarum. BMJ 1979; I: 1670–1671.

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hyperemesis gravidarum,; newborn sex,; first trimester.

© 2001 Lippincott Williams & Wilkins, Inc.