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American Journal of Epidemiology Advance Access originally published online on March 28, 2008
American Journal of Epidemiology 2008 167(11):1305-1311; doi:10.1093/aje/kwn065
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Risk of Oral Clefts in Relation to Prepregnancy Weight Change and Interpregnancy Interval

Eduardo Villamor1, Pär Sparén2 and Sven Cnattingius2

1 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA
2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Correspondence to Dr. Eduardo Villamor, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115 (e-mail: evillamo{at}hsph.harvard.edu).

Received for publication December 19, 2007. Accepted for publication February 26, 2008.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Epidemiologic evidence regarding the influence of maternal obesity on the risk of oral clefts is inconsistent. It is unknown whether increases in maternal weight before pregnancy are related to the risk of these malformations. The authors conducted a population-based cohort study in Sweden among 220,328 women who had their first two pregnancies between 1992 and 2004. The risk of oral clefts during the second pregnancy was estimated in relation to maternal change in body mass index (BMI; weight (kg)/height (m)2) from the beginning of the first pregnancy to the beginning of the second pregnancy. Among women whose second-pregnancy BMI was ≥3 units higher than their first-pregnancy BMI, the adjusted risk of isolated cleft palate was 2.3 times higher (95% confidence interval: 1.4, 4.0) as compared with women whose BMI did not change substantially. BMI change was not related to the risk of cleft lip. Unexpectedly, the birth prevalence of isolated cleft palate per 1,000 livebirths increased linearly with the length of the interpregnancy interval, from 0.3 in women with intervals of <12 months to 0.9 in women with intervals of ≥48 months (adjusted p for trend = 0.002). High prepregnancy maternal weight gain and long interpregnancy intervals appear to be associated with increased risk of cleft palate.

birth intervals; body mass index; cleft lip; cleft palate; obesity; pregnancy

Abbreviations: BMI, body mass index; CI, confidence interval; CL + CLP, cleft lip with or without cleft palate; CP, cleft palate; ICD, International Classification of Diseases; SD, standard deviation


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Oral clefts, including cleft palate and cleft lip with or without cleft palate, are major birth defects that occur in 1–2 livebirths per 1,000 (1). These defects place significant physical and psychological burdens on affected children, who must undergo multiple therapeutic interventions, often including repeated surgeries. Identification of preventable causes of such defects is therefore a research priority (2).

Some maternal nutritional factors, including suboptimal intake of folate (3) and other micronutrients (4), have been identified as potentially preventable causes of oral clefts. Prepregnancy maternal obesity has also emerged as a possible risk factor for oral clefts in some studies (1, 5, 6) but not in others (7–9). Considering the alarming increase in the prevalence of overweight and obesity among women of childbearing age worldwide (10–13), it is important to clarify the potential role of maternal obesity in the etiology of oral clefts. Previous studies have examined the risk of oral clefts in relation to maternal obesity measured around or after conception. However, it is unknown whether weight change before pregnancy could influence the risk of these malformations.

We conducted a nationwide study on successive pregnancies in Sweden to investigate whether changes in maternal body mass index (BMI) from the beginning of the first pregnancy to the beginning of the second pregnancy were associated with risk of oral cleft defects in the second pregnancy.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
We conducted a population-based cohort study among 300,510 women who had their first two consecutive singleton births between 1992 and 2004 as recorded in the Swedish Medical Birth Registry. Seventy-four percent (n = 220,994) of the women had available data on weight and height at the first antenatal care visit of both pregnancies and were included for analyses. In Sweden, weight is measured at the first antenatal care visit, and height is usually self-reported unless the woman is uncertain about it, in which case it is measured. Women with and without anthropometric data did not differ substantially in terms of age, country of origin, educational level, smoking, or interpregnancy interval, which was calculated as the number of complete months between the birth of the first child and the estimated date of conception of the second child. Pregestational diabetes was more frequent in women who lacked anthropometric data (0.54 percent) than in women who were included (0.34 percent) in the analysis. There were no substantial differences in the rates of gestational diabetes, preeclampsia, stillbirth, cleft malformations, or other major malformations between the two groups.

We excluded 79 women with implausible values for weight and 587 women who had a stillbirth during the second pregnancy, since diagnoses (including clefts and other congenital malformations) are not recorded for stillbirths in the Swedish Medical Birth Registry. Thus, the final sample size was 220,328. We calculated prepregnancy BMI as weight (kg)/height (m)2 and estimated interpregnancy change as the difference between BMIs at the first antenatal care visits of the second and first pregnancies. This difference was categorized as less than –1 (BMI decline of >1), –1 to <1, 1 to <2, 2 to <3, or ≥3 units. We retrieved information on smoking, sociodemographic characteristics, and the outcomes of both pregnancies, including the occurrence of major pregnancy and obstetric complications, from the Swedish Birth and Education registries.

The endpoints considered were oral cleft malformations as recorded in the Swedish Medical Birth Registry, following the Swedish versions of the International Classification of Diseases, Ninth and Tenth revisions (ICD-9 and ICD-10, respectively). These included cleft palate (CP) alone (ICD-9 code 749A, ICD-10 code Q35) and cleft lip with or without cleft palate (CL + CLP; ICD-9 codes 749B and 749C, ICD-10 codes Q36 and Q37). CP and CL + CLP are considered two distinct conditions from an etiologic standpoint (14). We also identified infants with other major malformations or chromosome anomalies in the Registry, and we considered each oral cleft outcome to be isolated when it was not associated with other malformations or chromosome anomalies.

We compared the birth prevalences of oral clefts during the second pregnancy according to ordinal categories of interpregnancy BMI change with the Cochran-Armitage test. Next, we estimated adjusted odds ratios and 95 percent confidence intervals using multivariate logistic regression. Odds ratios from these models were adjusted for characteristics that predict interpregnancy BMI change, including maternal country of origin and height; first pregnancy characteristics, including maternal BMI, age, and years of education; obstetric or perinatal complications, including preeclampsia, gestational diabetes, preterm delivery, small- or large-for-gestational-age birth, stillbirth, and infant death; and interpregnancy interval (15). The odds ratios were also adjusted for potential risk factors for cleft malformations, including other major congenital malformations diagnosed at the first pregnancy, paternal age at the first pregnancy (16), year of delivery, smoking (17), and pregestational diabetes (18) at the second pregnancy. Women whose firstborns had oral cleft malformations were excluded from analyses, since they could have had predisposing factors that increased their risk of recurrence. All analyses were conducted with SAS software, version 9 (SAS Institute, Inc., Cary, North Carolina).

The study protocol was approved by the research ethics committee at the Karolinska Institutet.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Mean BMI at first pregnancy was 23.4 (standard deviation (SD), 3.7; median, 22.7). The distribution of BMI at first pregnancy was as follows: <18.5, 3 percent; 18.5–24.9, 71 percent; 25–29.9, 20 percent; and ≥30, 6 percent. BMI increased by a mean of 0.8 units (SD, 2.0; median, 0.7) between the first and second pregnancies, over an average interpregnancy interval of 26 months (SD, 19; median, 21). Mean increases in BMI were 1.2 (SD, 1.8), 0.8 (SD, 1.7), 0.9 (SD, 2.4), and 0.8 (SD, 3.3) for the first-pregnancy categories of <18.5, 18.5–24.9, 25–29.9, and ≥30, respectively.

Prevalences of clefts per 1,000 livebirths in the second pregnancy among women without cleft-affected births in the first pregnancy were as follows: total CP, 0.58; isolated CP, 0.48; total CL + CLP, 0.91; and isolated CL + CLP, 0.87. In univariate analyses, the prevalence of CP was positively related to increasing maternal age (p for trend = 0.01) and paternal age (p for trend = 0.03). CL + CLP was more frequent in Nordic women than in non-Nordic women (table 1).


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  		TABLE 1. Birth prevalence of oral clefts during the second pregnancy according to maternal characteristics of the second pregnancy, Sweden, 1992–2004

 
The adjusted odds for both isolated CP and all CP were 2.3 times higher in women who gained at least 3 BMI units between pregnancies, as compared with women whose BMIs changed between –1 and <1 units (table 2). There was no strong evidence of dose-response associations between weight change and isolated CP or total CP. Change in BMI was not associated with CL + CLP (table 3).


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  		TABLE 2. Odds ratios for cleft palate during a second pregnancy in relation to change in body mass index* from the first pregnancy among women in Sweden, 1992–2004

 

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  		TABLE 3. Odds ratios for cleft lip during a second pregnancy in relation to change in body mass index* from the first pregnancy among women in Sweden, 1992–2004

 
We conducted supplemental analyses to examine whether the association between interpregnancy weight gain and CP could be modified by baseline BMI. There was no evidence of effect modification: For the comparison of BMI change ≥3 with BMI change between –1 and <1, the adjusted odds ratios for isolated CP were 2.41 (95 percent confidence interval (CI): 1.28, 4.54) among women with BMI <25 at the first pregnancy and 2.40 (95 percent CI: 0.83, 6.96) among women with BMI ≥25 at the first pregnancy (adjusted p for interaction = 0.99).

Unexpectedly, we found a positive, significant association between the length of the interpregnancy interval and CP. The prevalence of CP increased with each elapsed year between pregnancies, after adjustment for parental age and other potential confounders (table 4). The adjusted odds ratio for the relation between women with the longest (≥4 years) and shortest (<1 year) interpregnancy intervals was 2.84 (95 percent CI: 1.29, 6.26). Interpregnancy interval was not related to CL + CLP.


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  		TABLE 4. Odds ratios for cleft palate during a second pregnancy in relation to time interval from the first pregnancy among women in Sweden, 1992–2004

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
We found that a large prepregnancy gain in maternal BMI (≥3 units) was associated with significantly increased risk of CP but not CL + CLP. An increase of 3 BMI units would be equivalent to a gain of 8 kg (17.6 pounds) for an average-height (1.65 m or 5 feet, 5 inches) woman who weighed 63 kg (139 pounds) at the first pregnancy.

Previous studies have described associations between prepregnancy maternal obesity and the occurrence of oral cleft malformations. Cedergren and Källén (1) found modest increases in the risks of both CP and CL + CLP associated with prepregnancy BMI >29 in Sweden, while Queisser-Luft et al. (5) reported a threefold increase in the birth prevalence of all orofacial clefts among German women with a prepregnancy BMI of ≥30 as compared with those with a prepregnancy BMI of <30. Similarly, Moore et al. (6) reported a threefold increase in the prevalence of all orofacial clefts at prepregnancy BMIs of ≥28 in the United States. A more recent US study (9) found a marginally significant 27 percent increase in the risk of isolated CP among obese women (BMI ≥30) as compared with women of normal BMI but a lack of association between maternal obesity and CL + CLP. Our results suggest that a positive weight balance between pregnancies, rather than obesity per se, could be associated with increased risk of CP. This association was observed even in women who did not necessarily become obese.

The biologic mechanisms underlying the association between weight gain and CP are not well understood. Undiagnosed type 2 diabetes could be one of them, since insulin resistance and glucose intolerance have been related to congenital malformations in animal and human studies (19). Specific dietary changes that accompany prepregnancy weight gain could also play a role; experiments in mice indicate that increased fat intake appeared to boost the birth prevalence of CP induced by triamcinolone (20). In addition, dietary patterns associated with weight gain leading to obesity are typically poor in folate and other micronutrients (21), marginal intakes of which have been implicated in the etiology of oral clefts.

One limitation of our study is that we lacked information on intake of vitamin supplements, which might have confounded the association between prepregnancy weight gain and CP. However, in other populations, the association between obesity and oral clefts has been independent of maternal intake of vitamin supplements (9). Another potential limitation is that we lacked data on cleft defects in stillbirths. If clefts were more prevalent in stillbirths than in livebirths, exclusion of stillbirths could arguably have biased the association between interpregnancy weight gain and clefts. However, given that interpregnancy weight gain is associated with increased risk of stillbirth (15), the underlying association between weight gain and clefts would actually be stronger than observed. In addition, stillbirths with cleft malformations are likely to represent fetuses that also had other major congenital defects rather than fetuses with isolated cleft defects. In Norway, for example, the proportion of isolated CP among stillbirths (44 percent) was much lower than that among all births (69 percent) (22). While our estimate of non-isolated clefts (1.0/1,000) was lower than that in Norway (2.4/1,000) following our exclusion of stillbirths, the estimate of isolated clefts in our study (4.8/1,000) was very close to the Norwegian estimate (5.3/1,000). Hence, while exclusion of stillbirths could affect estimates of total clefts, it should not considerably bias estimates of isolated clefts.

Our estimate of the birth prevalence of total clefts (1.5/1,000) was also slightly lower than the 1.7/1,000 previously reported in Sweden by Cedergren and Källén (1). One possible explanation is that these authors used the Swedish Birth Registry, the Swedish Registry of Congenital Malformations, and the Hospital Discharge Registry as data sources for clefts, whereas we used only the Swedish Birth Registry, in which a small proportion of malformations is not recorded (23, 24). In consequence, some births of children with clefts may have been misclassified as normal births in our study. This misclassification is unlikely to have biased our estimates of association, since it was not expected to have been differential with respect to interpregnancy weight change.

An additional potential limitation is that we lacked information on week of gestation at the first prenatal care visit, and the estimate of interpregnancy weight change does not account for pregnancy-related weight gain prior to the first prenatal care visit. Nevertheless, 93–95 percent of women in Sweden attend their first prenatal care visit before gestational week 15 (25, 26), and first-trimester weight gain is not substantial. Studies of well-nourished women who were recruited before becoming pregnant have indicated weight gains of approximately 1 kg (2.2 pounds) by gestation week 9 (27) and 2.3 kg (5.1 pounds) by week 13 (28); therefore, major bias due to the estimate of interpregnancy weight change is unlikely.

Finally, we could not differentiate how much of the interpregnancy weight gain corresponded to postpartum weight retention after the first pregnancy as opposed to weight gain between pregnancies. Long-term longitudinal studies suggest that postpartum weight retention during the first year after delivery substantially increases the risk of weight gain after 10–15 years (29, 30). In addition, only 60 percent of normal-weight women return to within 1.5 kg (3.3 pounds) of their prepregnancy weight by 1 year postpartum (31); thus, postpartum weight retention after the first delivery may be a greater component of interpregnancy weight gain than actual weight gain between pregnancies.

It is conceivable that weight gain between pregnancies could be protective against adverse outcomes that are associated with maternal underweight, such as spontaneous preterm birth (32, 33). A potential beneficial effect of weight gain on preterm birth among underweight women would probably outweigh the potential risk of cleft palate. The prevalence of maternal underweight (BMI < 18.5) at first pregnancy in our population was low. Investigators in future studies should examine the potential impact of prepregnancy weight gain on pregnancy outcomes among underweight women in populations with higher prevalences of maternal malnutrition.

We unexpectedly found a strong, linear association between interpregnancy interval and the birth prevalence of CP that was independent of parental age, complications of the first pregnancy, and other variables that have been found to influence time to next pregnancy (34). Unrecognized miscarriages could make the interpregnancy interval appear spuriously long, and the association between interpregnancy interval and birth defects could be biased if these losses are accompanied by malformations. Complex malformations that result in losses, however, would be more likely to affect the birth prevalence of non-isolated clefts than the birth prevalence of isolated clefts; thus, our observed associations between interpregnancy interval and the latter are unlikely to have been compromised by this potential bias. Long interpregnancy intervals may indicate maternal subfertility, which has been previously associated with defects of the urinary tract (35, 36); notwithstanding, a previous study in Sweden did not find an increased birth prevalence of orofacial clefts following infertility treatment (37). Longer interpregnancy intervals could also indicate paternity change, but existing evidence does not support increased risk of recurrent clefts associated with change in paternity (38). Confirmation of our observation in other study populations is required.

In conclusion, in this study, high prepregnancy maternal weight gain and long interpregnancy intervals were associated with increased risk of CP.


   ACKNOWLEDGMENTS
 
The study was supported by grants from the Karolinska Institutet.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Cedergren M, Källén B. Maternal obesity and the risk for orofacial clefts in the offspring. Cleft Palate Craniofac J (2005) 42:367–71.[CrossRef][Web of Science][Medline]
  2. Yazdy MM, Honein MA, Rasmussen SA, et al. Priorities for future public health research in orofacial clefts. Cleft Palate Craniofac J (2007) 44:351–7.[CrossRef][Web of Science][Medline]
  3. Goh YI, Bollano E, Einarson TR, et al. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can (2006) 28:680–9.[Medline]
  4. Krapels IP, van Rooij IA, Ocke MC, et al. Maternal nutritional status and the risk for orofacial cleft offspring in humans. J Nutr (2004) 134:3106–13.[Abstract/Free Full Text]
  5. Queisser-Luft A, Kieninger-Baum D, Menger H, et al. Does maternal obesity increase the risk of fetal abnormalities? Analysis of 20,248 newborn infants of the Mainz Birth Register for detecting congenital abnormalities. Ultraschall Med (1998) 19:40–4.[Web of Science][Medline]
  6. Moore LL, Singer MR, Bradlee ML, et al. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology (2000) 11:689–94.[CrossRef][Web of Science][Medline]
  7. Shaw GM, Todoroff K, Schaffer DM, et al. Maternal height and prepregnancy body mass index as risk factors for selected congenital anomalies. Paediatr Perinat Epidemiol (2000) 14:234–9.[CrossRef][Web of Science][Medline]
  8. Watkins ML, Rasmussen SA, Honein MA, et al. Maternal obesity and risk for birth defects. Pediatrics (2003) 111:1152–8.[Abstract/Free Full Text]
  9. Waller DK, Shaw GM, Rasmussen SA, et al. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med (2007) 161:745–50.[Abstract/Free Full Text]
  10. Surkan PJ, Hsieh CC, Johansson AL, et al. Reasons for increasing trends in large for gestational age births. Obstet Gynecol (2004) 104:720–6.[Web of Science][Medline]
  11. Kanagalingam MG, Forouhi NG, Greer IA, et al. Changes in booking body mass index over a decade: retrospective analysis from a Glasgow maternity hospital. Br J Obstet Gynaecol (2005) 112:1431–3.
  12. Mendez MA, Monteiro CA, Popkin BM. Overweight exceeds underweight among women in most developing countries. Am J Clin Nutr (2005) 81:714–21.[Abstract/Free Full Text]
  13. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999 –2004. JAMA (2006) 295:1549–55.[Abstract/Free Full Text]
  14. Fraser FC. The genetics of cleft lip and cleft palate. Am J Hum Genet (1970) 22:336–52.[Web of Science][Medline]
  15. Villamor E, Cnattingius S. Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study. Lancet (2006) 368:1164–70.[CrossRef][Medline]
  16. Woolf CM. Paternal age effect for cleft lip and palate. Am J Hum Genet (1963) 15:389–93.[Web of Science][Medline]
  17. Meyer KA, Williams P, Hernandez-Diaz S, et al. Smoking and the risk of oral clefts: exploring the impact of study designs. Epidemiology (2004) 15:671–8.[CrossRef][Web of Science][Medline]
  18. Aberg A, Westbom L, Källén B. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. Early Hum Dev (2001) 61:85–95.[CrossRef][Web of Science][Medline]
  19. Eriksson UJ, Cederberg J, Wentzel P. Congenital malformations in offspring of diabetic mothers—animal and human studies. Rev Endocr Metab Disord (2003) 4:79–93.[CrossRef][Web of Science][Medline]
  20. Zhou M, Walker BE. Potentiation of triamcinolone-induced cleft palate in mice by maternal high dietary fat. Teratology (1993) 48:53–7.[CrossRef][Web of Science][Medline]
  21. Vujkovic M, Ocke MC, van der Spek PJ, et al. Maternal Western dietary patterns and the risk of developing a cleft lip with or without a cleft palate. Obstet Gynecol (2007) 110:378–84.[CrossRef][Web of Science][Medline]
  22. Harville EW, Wilcox AJ, Lie RT, et al. Epidemiology of cleft palate alone and cleft palate with accompanying defects. Eur J Epidemiol (2007) 22:389–95.[CrossRef][Web of Science][Medline]
  23. Cnattingius S, Ericson A, Gunnarskog J, et al. A quality study of a medical birth registry. Scand J Soc Med (1990) 18:143–8.[Web of Science][Medline]
  24. Centre for Epidemiology, National Board of Health and Welfare. The Swedish Medical Birth Register—a summary of content and quality. (2003) Stockholm, Sweden: National Board of Health and Welfare. (http://www.sos.se/fulltext/112/2003-112-3/2003-112-3.pdf).
  25. Lindmark G, Cnattingius S. The scientific basis of antenatal care. Report from a state-of-the-art conference. Acta Obstet Gynecol Scand (1991) 70:105–9.[Medline]
  26. Delvaux T, Buekens P, Godin I, et al. Barriers to prenatal care in Europe. Am J Prev Med (2001) 21:52–9.[CrossRef][Web of Science][Medline]
  27. Butte NF, Wong WW, Treuth MS, et al. Energy requirements during pregnancy based on total energy expenditure and energy deposition. Am J Clin Nutr (2004) 79:1078–87.[Abstract/Free Full Text]
  28. Brown JE, Murtaugh MA, Jacobs DR Jr, et al. Variation in newborn size according to pregnancy weight change by trimester. Am J Clin Nutr (2002) 76:205–9.[Abstract/Free Full Text]
  29. Rooney BL, Schauberger CW. Excess pregnancy weight gain and long-term obesity: one decade later. Obstet Gynecol (2002) 100:245–52.[CrossRef][Web of Science][Medline]
  30. Linné Y, Dye L, Barkeling B, et al. Long-term weight development in women: a 15-year follow-up of the effects of pregnancy. Obes Res (2004) 12:1166–78.[Web of Science][Medline]
  31. Linne Y, Dye L, Barkeling B, et al. Weight development over time in parous women—The SPAWN Study—15 years follow-up. Int J Obes Relat Metab Disord (2003) 27:1516–22.[CrossRef][Web of Science][Medline]
  32. Nohr EA, Bech BH, Vaeth M, et al. Obesity, gestational weight gain and preterm birth: a study within the Danish National Birth Cohort. Paediatr Perinat Epidemiol (2007) 21:5–14.[CrossRef][Web of Science][Medline]
  33. Hickey CA, Cliver SP, McNeal SF, et al. Low pregravid body mass index as a risk factor for preterm birth: variation by ethnic group. Obstet Gynecol (1997) 89:206–12.[CrossRef][Web of Science][Medline]
  34. Stephansson O, Dickman PW, Cnattingius S. The influence of interpregnancy interval on the subsequent risk of stillbirth and early neonatal death. Obstet Gynecol (2003) 102:101–8.[CrossRef][Web of Science][Medline]
  35. Li DK. Maternal history of subfertility and the risk of congenital urinary tract anomalies in offspring. Epidemiology (1999) 10:80–2.[CrossRef][Web of Science][Medline]
  36. Honein MA, Moore CA, Watkins ML. Subfertility and prepregnancy overweight/obesity: possible interaction between these risk factors in the etiology of congenital renal anomalies. Birth Defects Res A Clin Mol Teratol (2003) 67:572–7.[CrossRef][Web of Science][Medline]
  37. Wennerholm UB, Bergh C, Hamberger L, et al. Incidence of congenital malformations in children born after ICSI. Hum Reprod (2000) 15:944–8.[Abstract/Free Full Text]
  38. Christensen K, Schmidt MM, Vaeth M, et al. Absence of an environmental effect on the recurrence of facial-cleft defects. N Engl J Med (1995) 333:161–4.[Abstract/Free Full Text]
  39. Marsal K, Persson PH, Larsen T, et al. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr (1996) 85:843–8.[Web of Science][Medline]

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