Hyperemesis gravidarum or NVP in relation to fetal abnormality




1.   Studies into 60,000 births in Leipzig Clinic found deformed children after hyperemesis exceeded the mean (Noack, 1963). He noted that these observations were made during a period when drugs now suspected of causing deformities had not yet come on the market. From Ref (10)

2.   98 cases of hyperemesis gravidarum, 6.1% deformity. In the same clinic the overall incidence of deformity 0.65%, 1949-56. Mey R. Ref from (10).

3.   165 patients with hyper emesis, 8.3% incidence of deformity. Total births in the same clinic, 0.98% incidence of deformity. 1949-59. Holbein, 1961. Ref from(10).

4.   Doring and Hossfeld reported that 4% of infants of 649 women with hyperemesis were malformed, while the control group without hyperemesis (8,422 women) showed only 1.5% malformation rate. 1964. Ref from (29).

5.   Fairweather points out that the definition of what constitutes a deformity clouds observations of the incidence of fetal deformity in hyperemesis. 1968. (10)




1.   Congenital Dislocation of the Hip (CDH). 6,376 pregnancies in study population, 894 women used anti-emetics. 37 women had babies with CDH and 13 of these took anti-emetic drugs compared to the expected four. (16)

2.   Hip Dysplasia. 3,068 hyperemetic women in study population. 60 infants with CDH compared to the expected 47. (29)

3.   Undescended Testicles. 2,068 hyperemetic women, 21 infants had undescended testicles. This figure was roughly twice the expected one, but this diagnosis in the newborn period is uncertain. (28)

4.   No significant increase in congenital hernia or undescended testicles in the vomiting n=9,255 compared to the non-vomiting group n=7,143. (20)

5.   Down’s Syndrome. 3,068 hyperemetic women, nine women had a baby with Down’s Syndrome. Three times the expected number. (29)

6.   Cleft Palate deformity. Peer and Stream reported on 228 cases of cleft palate which showed that in 10% of cases the mother had suffered from hyperemesis in pregnancy. Ref from (10)

7.   Cleft Palate. 3,068 hyperemetic women, no association between hyperemesis gravidarum and cleft lip or palate was found. (29)

8.   An increase in central nervous system abnormalities was observed in the offspring of hyperemetic women. Hyperemesis 6/413; no vomiting 3/833. Abnormalities in hyperemetic offspring: two anencephalics, one microcephaly, one craniosynostosis, one separation of cranial sutures and one cranial suture separation with hydrocephaly. (22)

9.   Most women who reported vomiting were mothers of longitudinal limb defects (98 cases) (e.g. absence of radius and thumb where longitudinal bands of limb tissue were missing). These were infants born alive with these defects within New South Wales and the Australian capital territory between 1970 and 1981 inclusive.
The estimate of risk association with vomiting in the first trimester for women of the longitudinal group and their controls were significant. RR = 2.3 (CL 1.3, 4.0). (97)




1.   Cardiac defects. 3,068 hyperemetic women. There were 24 cardiac defects, close to the expected number of 22. (29)

2.   6,376 pregnancies. 894 took anti-emetic drugs. Only two of 35 women who had infants with congenital heart disease took anti-emetic drugs. (16)

3.   The most severe nausea during pregnancy was associated with a lower risk for congenital heart defect (CHD) in the child compared to no nausea (or 0.81, 95% confidence interval (CI) 0.67-0.99). The lower risk tended to disappear with less severe levels of nausea and the trend was statistically significant.

         998 cases mothers. 3,029 control mothers. (67)
A possible reason for the lower risk of CHD among children with mothers who took anti-nauseant medication may be that they had more severe nausea of pregnancy which could not be measured by our scale. Alternatively, maternal use of high doses of Vit B6 (contained in Bendectin) may have had a protective effect on the embryonic heart development. (67)




  1. 246 hyperemesis patients, only 2% incidence of deformity - no greater than average incidence for the population as a whole. 1968. (10)
  2. In a study of maternal states in relation to congenital malformations, in a survey of 14,813 pregnancies, found no relationship between hyperemesis gravidarum and congenital malformation. 1950. 15 patients with hyperemesis gravidarum. (84)
  3. 30 patients with hyperemesis gravidarum showed no fetal deformity. 1990. (36)
  4. There was no statistical difference in congenital abnormalities in babies born to women who had hyperemesis gravidarum. Hyperemesis gravidarum 1/164, controls 2/209 1%. 1995. (64)
  5. The foetuses of gravidas admitted with hyperemesis gravidarum are not at increased risk of congenital abnormalities. 138 patients with hyperemesis gravidarum. 1996. (62)
  6. The pregnancy outcome between hyperemesis gravidarum (193 patients) and the general population (13,053 pregnant women in the study) was similar for the incidence of fetal abnormalities. 1996. (61)
  7. Major malformations, 3 (1.9%) in 162 patients treated for HG over three years. This number is comparable to our normal population. (82)
  8. 20 patients with hyper emesis gravidarum, none showed any signs of congenital abnormalities. (125)
  9. No congenital malformations have occurred in 130 pregnancies complicated by hyperemesis gravidarum. (150)
  10. In a review of over 33,000 pregnancies complicated by nausea and vomiting there was no evidence that vomiting or a diagnosis of hyperemesis gravidarum was associated with an increased or decreased incidence of malformations. (147)


Pooled population 936 pregnancies with HG in 9 references.


(Five References)


  1. Vomiting during pregnancy does not increase the risk of having a malformed infant. 9,255 women vomited, 7,143 did not vomit. 1986. (20)
  2. No statistically significant association observed between nausea and vomiting of pregnancy and fetal abnormality, 873 women in study population. 1989. (44)
  3. Our observations indicate that nausea and vomiting of pregnancy does not imply an excess risk of malformations. 309 singleton pregnancies in study. (13)
  4. There was no general increase in the risk for a congenital malformation but sooner the opposite an apparently protective effect. 16,536 women used meclozine in the first 12 weeks of pregnancy mainly for NVP. Compared to 540,660 births whose mothers did not use meclozine. 2003. (133)
  5. In a review of over 33,000 pregnancies complicated by nausea and vomiting there was no evidence that vomiting or a diagnosis of hyperemesis gravidarum was associated with an increased or decreased incidence of malformations. (147)



Pooled population of 67,115 pregnancies in 5 references.




1.   No significant association for freedom of nausea with fetal abnormality. 7,767 pregnancies, 2,253 no nausea. (51)

2.   Here were no major malformations among the offspring of 130 women not experiencing nausea and vomiting. There were two major malformations among 246 women experiencing vomiting (0.81%). (123)


Summary of results in Review item 35


a.   Fetal abnormality associated with hyperemesis gravidarum. (No specific abnormalities named in these references)

        (10) (plus 3 references from 10) (29)                                   Five References

b.   Specific fetal abnormality associated with hyperemesis gravidarum.

         Congenital dislocation of the hip 1 positive reference (16)   One Reference

         Hip Dysplasia   1 positive reference (29)                              One Reference

         Undescended testicles 1 positive, 1 negative reference

         each (28) (20)                                                                      Two References

         Down’s Syndrome 1 positive reference (29)                         One Reference

         Cleft palate 1 positive, 1 negative reference (10) (29)          Two References

         Central nervous system 1 positive reference (22)                One Reference

         Skeletal malformations 1 positive reference (97)                 One Reference

                                                                                                      Total:   Nine References

c.   Specific fetal abnormalities less likely to occur with hyperemesis gravidarum. (apply to seven different abnormalities)

         Congenital hernia   1 reference (20)                                     One Reference

         Cardiac defects   3 references (29) (16) (67)                        Three References

                                                                                                        Total:   Four References

d.   No increased fetal abnormality associated with hyperemesis gravidarum.  (968 women with HG 2805 controls)

       (10) (36) (61) (62) (64) (82) (84) (125)                                  Ten References

e.   No increased risk of fetal abnormality associated with pregnancy nausea and vomiting.

(13) (20) (44) (133) (147)                                                                Five References

f.   No significant association with freedom from nausea and fetal abnormality.

         (51) (123)                                                                                Two References


The spread of evidence in these papers suggest there is no positive correlation between NVP or HG and congenital abnormalities.



Major malformations defined as the presence of any congenital anomaly that has an adverse effect on either the function or social acceptability of the individual. (135)


1.   Major congenital defects occur in 1-3% of the general population at birth. Careful follow up increases the number detected to up to 5% later in life. (130)

2.   In summary it is probably not far wrong to say that 2 to 3 percent of all live born infants show one or more significant congenital malformations and that at the end of one year this figure is doubled by the discovery of malformations not manifest at birth. (131)

3.   In the cohort of women (n=187) exposed to ginger during pregnancy all of whom used it during the first trimester the results do not suggest that there is a higher risk of major malformations above the base-line rate of 1-3%. (135)

4.   In all pregnancies there is a base-line risk of 1-3% of having a baby with a major congenital abnormality. (136)

5.   Percentage of all congenital malformations to total births in Northern Ireland.

         1966      3.3%

         1976      3.2%                        (137)

6.   The rate of congenital disorders diagnosed at birth among infants exposed to Bendectin (14 of 1000) is identical to that among infants who were not exposed (14 of 1000). (138)

7.   The 2-3% risk that any pregnancy has just by chance for serious malformation. (139)

8.   Of 291 women in study a total of 9 babies (3%) were born with a major or minor congenital abnormality. In the year 2000 there were 770 (4.3%) birth defects in South Australia, this included minor and major malformations. (140)




In all pregnancies there is a base-line risk of 1-3% of the baby having a major congenital abnormality at birth.                                                                                    Eight References


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Evidence is mounting from biological research that GDF15, the key driver of cancer cachexia, is linked to severe NVP

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