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Community and International Nutrition

Weight Loss During Pregnancy Is Associated with Adverse Pregnancy Outcomes among HIV-1 Infected Women¹

Eduardo Villamor^*,2, Michele L. Dreyfuss^**, Ana Baylín^*, Gernard Msamanga and Wafaie W. Fawzi^*,

^* Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA; ^** Department of Population and Family Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD; and Department of Community Health, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania

²To whom correspondence should be addressed. E-mail: evillamo{at}hsph.harvard.edu.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
In a prospective study of 1002 pregnant, HIV-1 infected Tanzanian women, we examined the incidence of fetal death, preterm delivery, low birth weight (LBW), and small for gestational age (SGA) births in relation to maternal anthropometry at the first prenatal visit, weight loss, and low weight gain during pregnancy. Anthropometric measurements were obtained monthly during the 2nd and 3rd trimesters. Low maternal height and weight at the first visit were significantly related to lower mean birth weight and increased risk of SGA, but not to preterm delivery. Maternal stature < 150 cm was significantly related to fetal death. Weight loss during pregnancy, defined as a negative slope of the regression of weight measurements on the week of gestation, occurred in 10% of the women. It was related to increased relative risk (RR) of fetal death (RR = 1.83, 95% CI = 0.93, 3.57), preterm delivery (RR = 1.85, 95% CI = 1.40, 2.44), and LBW (RR = 2.85, 95% CI = 1.69, 4.79) after adjusting for multivitamin supplementation, height, primiparity, baseline weight, malaria, CD4 cell count, HIV disease stage, and intestinal parasitoses. The significant association with fetal death was stronger for weight loss during the 2nd trimester, whereas increased risks of preterm delivery and LBW were higher for weight loss during the 3rd. Similar but weaker associations were found with low weight gain during pregnancy (slope < 25th percentile). We conclude that poor anthropometric status at the first prenatal visit and weight loss during pregnancy among HIV-1 infected women are strong risk factors for adverse pregnancy outcomes.

KEY WORDS: • HIV • weight gain during pregnancy • fetal loss • birth weight • preterm delivery

Among presumably HIV-uninfected populations, maternal anthropometry is one of the strongest predictors of the outcome of pregnancy. Short maternal stature, low prepregnant weight, and low weight gain during pregnancy are independently related to increased risks of intrauterine growth retardation (IUGR)³ (1,2), preterm delivery (3–5), and possibly fetal death (6–8).

HIV infection is often accompanied by wasting, a progressive loss of body mass manifested in weight loss (9). Wasting is a cause of stillbirth, preterm delivery, and IUGR (10–13), yet it is virtually unknown whether maternal anthropometry plays a role in the pathogenesis of these adverse outcomes among HIV-infected women. Weight loss during pregnancy is likely to occur at the expense of maternal rather than fetal tissues, and may therefore constitute an indicator of maternal wasting in the course of HIV disease. If maternal weight loss during pregnancy is an important predictor of poor gestational outcomes among HIV-infected women, specific interventions to prevent weight loss could also prevent such adverse outcomes.

We showed previously that among HIV-1 infected women, multivitamin supplementation during pregnancy is related to large and significant reductions in the risks of fetal death, preterm delivery, small for gestational age (SGA) births, and low birth weight (LBW) (14). We also found that multivitamins increased weight gain during the last trimester of pregnancy, and significantly decreased the risk of maternal weight loss (15), a manifestation of wasting among HIV-infected persons. If weight gain during pregnancy is associated with pregnancy outcomes in this population, it is possible that the beneficial effect of multivitamins on these outcomes may have been mediated in part through their effect on maternal weight gain.

We carried out a longitudinal study among HIV-1 infected Tanzanian women to examine the following: 1) whether maternal height, weight, BMI, and/or mid-upper arm circumference (MUAC) at the first prenatal visit are associated with fetal death, preterm birth, LBW, and SGA birth; and 2) whether weight loss during pregnancy, low rate of weight gain, and/or reductions in MUAC increase the risk of these adverse pregnancy outcomes.

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Study design and population. We conducted a prospective study among HIV-1 positive, pregnant women who participated in a vitamin supplementation trial in Dar es Salaam, Tanzania. Details of the study were published previously (14). Briefly, 1069 HIV-1 positive women who were between 12 and 27 wk of gestation according to the last menstrual period date were randomly assigned to receive a daily oral dose of 1 of 4 regimens: 1) multivitamins (B, C, and E) and vitamin A; 2) multivitamins alone; 3) vitamin A alone; or 4) placebo. At the first visit, a trained nurse collected information on the woman’s age, education, socioeconomic and marital status, and obstetric history. A complete physical examination was carried out and blood, urine, stool, and vaginal specimens were collected. At every scheduled monthly follow-up visit after randomization, trained and supervised staff from the study clinic obtained anthropometric measurements using calibrated instruments according to the study protocol. Height was measured to the nearest 0.1 cm, weight was measured to the nearest 100 g, and MUAC was obtained at the midpoint between the olecranon and the acromion process with a nonstretchable tape to the nearest 0.1 cm. At delivery, a research midwife weighed infants to the nearest 10 g on a standard beam balance immediately after birth. Birth length was obtained on an infant length board. All women received 120 mg ferrous iron and 5 mg folic acid supplements daily, and weekly malaria prophylaxis according to the standard of prenatal care. Antiretroviral medications were not available in Tanzania at the time of the study.

Specimens collected at baseline were used to examine CD3, CD4, and CD8 T-lymphocyte subsets (FACS count system, Becton-Dickinson), hemoglobin and blood cells count (CBC5 Coulter Counter, Coulter Corporation), serum retinol and vitamin E concentrations using HPLC (Shimadzu Scientific Instruments), and selenium concentration by a graphite-furnace atomic absorption spectrophotometric method (PerkinElmer). Malaria infection was diagnosed from thick- and thin-smear blood films; virtually all malaria parasitemia was due to P. falciparum. The presence of intestinal protozoa and helminthes was assessed through macroscopic examination of stool for worms and microscopic observation of eggs, larvae, trophozoites, and cysts using saline and iodine wet mount, and the formalin-ether concentration technique.

    Definition of exposures: maternal anthropometry at the first visit. Of 1069 women randomized, 1002 had a baseline measurement of weight, had singleton pregnancies, and had a known date of pregnancy outcome; these constituted the study base. Sociodemographic characteristics of this group did not differ from those in the initial 1069. Anthropometric variables at first visit for these analyses included maternal height, weight, BMI, and MUAC. Because weight, BMI, and MUAC vary greatly by week of gestation at the first visit (range: 12 to 27 wk), they were grouped by week of gestation and then categorized in quartiles. Height was categorized in quartiles.

    Weight loss and low rate of weight gain during pregnancy. Analyses of weight loss during pregnancy were restricted to women with at least 2 weight measurements between recruitment and delivery, singleton pregnancies, and a known date of pregnancy outcome (n = 957). We fitted a simple linear regression model for each woman’s set of weight measurements during pregnancy (outcome) with week of gestation as predictor. A regression slope 0 was used to define "weight loss," whereas a regression slope below the 25th percentile of the distribution of slopes was used to define "low rate of weight gain" (15). We also estimated trimester-specific slopes of weight gain by regressing weight on week of gestation among women who had at least 2 measurements between wk 12 and 26 (2nd trimester) and then among women with at least 2 measurements between wk 27 and delivery (3rd trimester). Trimester-specific weight loss and low rate of weight gain were defined as trimester-specific regression slopes 0 and < 25th percentile of their distributions, respectively. The estimation of the weekly rate of weight gain from a linear regression model assumes a linear pattern overall and within trimesters of pregnancy. Both linear and quadratic models were found to be appropriate to model weight gain during pregnancy (16).

    MUAC change during pregnancy. We fitted a simple linear regression of MUAC measurements over time. Change in MUAC was defined by categorizing the slopes in quartiles of their distribution. Because MUAC change did not vary by trimesters, only overall change was estimated.

    Definition of outcomes. Gestational age was based on the recall of the last menstrual period date at recruitment. Fetal death was defined as either an abortion (delivery before 28 wk of gestation) or a stillbirth (delivery at or after 28 wk); preterm delivery as birth before 37 wk, and low birth weight as <2500 g. Birth weight and length were also considered as continuous variables. Small for gestational age newborns were those with birth weight below the 10th percentile for gestational age according to the reference by Brenner and colleagues (17).

    Statistical data analyses. In univariate analyses, we compared the incidence of binary outcomes by categories of exposures using the ² test. For continuous outcomes (birth weight and birth length), the distributions by categories of predictors were compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. Values in the text are means ± SD, unless otherwise stated.

Adjusted relative risks (RR) and 95% CI were estimated for binary outcomes using multivariate binomial regression models (18). Adjusting variables in these multivariate models were previously reported predictors of both pregnancy outcomes (14,19) and weight gain during pregnancy (20) in this population, including multivitamin supplementation, height, literacy, primiparity, malaria, CD4 cell count, stage of HIV disease according to the WHO’s classification, selenium concentration, and intestinal parasitoses. The models examining associations between weight loss or low weight gain during the 3rd trimester and pregnancy outcomes were also adjusted for weight loss or low weight gain during the 2nd trimester, respectively.

For continuous outcomes such as birth weight and length, we estimated differences in the mean between exposure categories using multivariate linear regression models that adjusted for the potential confounding variables mentioned above. The CIs around these differences were built using empirical variances (21).

    Ethical clearance. The study protocol was approved by the Research and Publications Committee of Muhimbili University College of Health Sciences, the Ethical Committee of the National AIDS Control Program of the Tanzanian Ministry of Health, and the Institutional Review Board of the Harvard School of Public Health.

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Characteristics of the study population. On average, the 1002 women who constituted the study base for these analyses were 24.6 ± 4.8 y old (range: 15–45 y) and attended the first prenatal care visit at gestation week 20.5 ± 3.3. Among the women, 13% did not have formal education, and most had not completed secondary schooling (89%). One-third (33%) were nulliparous. The majority cohabited with a partner (88%) and did not contribute to the household income (75%). At baseline, symptomatic HIV disease (above stage 1 of the WHO classification) was present in 24% of the women, and 12% had CD4 cell counts < 200/mm³. The prevalence of anemia (hemoglobin < 110 g/L) at first visit was 82%; 19% of the women had malaria parasites in capillary blood, and 20% had intestinal parasites, most frequently hookworm (11%) and Ascaris lumbricoides (6%). Height was 156.6 ± 5.9 cm, whereas baseline weight and MUAC were dependent on the week of gestation at first visit (Table 1). The differences in median weight and MUAC between women attending prenatal care after wk 24 and before wk 15 were 3.5 kg and 1.5 cm, respectively.

There were 77 fetal deaths among the 1002 women (8%) including 28 abortions and 49 stillbirths. Of the 925 live births, 228 were preterm (25%). The birth weight was known in 822 of the live births (3017 ± 507 g); the proportions of LBW and SGA births were both 11%. Baseline characteristics did not differ between the group of 822 women with known birth weight and the 925 women who had live births.

    Anthropometric indicators at first prenatal visit and pregnancy outcomes. Maternal weight, BMI, and MUAC at the first visit were not associated with fetal death or preterm delivery; however, women with short stature (<150 cm) had a higher incidence of fetal death (14/106, 13%) than women with height 150 cm (63/896, 7%) (RR = 1.88, 95% CI = 1.09, 3.23, P = 0.02). After adjustment for maternal education, the RR was slightly attenuated but remained significant (RR = 1.79, 95% CI = 1.04, 3.08, P = 0.04). With additional adjustment for covariates including primiparity, multivitamin supplementation, and characteristics at the first prenatal visit (CD4 cell counts, stage of HIV disease, malaria, or intestinal parasites), the RR was further attenuated (RR = 1.57, 95% CI = 0.91, 2.72, P = 0.11). There was no evidence of a linear association between height and fetal death. Height was not related to preterm birth.

Maternal anthropometric indicators at baseline were strongly related to the newborn’s anthropometry (Table 2). Maternal height was associated with a significant positive trend in birth weight, and with a negative trend in the risk of SGA, but not with birth length or with the risk of LBW. Higher maternal weight and BMI at baseline were both related to significantly increased birth weight and length; children born to mothers in the highest quartile of weight were 231 g heavier (P < 0.0001) and 0.8 cm longer (P = 0.01), on average, than those whose mothers were in the lowest weight quartile. Baseline weight and BMI were also related to lower risk of SGA, but not to LBW, after adjustment. Compared with the lowest quartile, MUAC above the 75th percentile of the week of gestation distribution was related to 104 g higher birth weight (P = 0.03) and 0.5 cm greater length (P = 0.07), but not to higher risk of LBW or SGA.

Weight loss during pregnancy was a strong predictor of the newborn’s anthropometric characteristics (Table 4). After adjusting for confounding, children born to women who lost weight during pregnancy were, on average, 406 g lighter (P < 0.0001) and 1.2 cm shorter (P = 0.0005) than children whose mothers did not lose weight. The effect on birth weight was greater when the weight loss occurred during the 3rd trimester (207 g, P < 0.0001) than during the 2nd (121 g, P = 0.07). Consistent with the findings on birth weight as a continuous variable, there was also a significant increase in the risk of LBW associated with maternal weight loss. There were no significant associations between weight loss and SGA.

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
In this prospective study of HIV-infected women, low maternal height, weight, and BMI at the first prenatal visit were related to lower birth weight and increased risk of SGA birth, but not to preterm birth. Short stature appeared to be associated with increased risk of fetal loss. Weight loss or low weight gain during pregnancy were related to elevated risks of fetal death, preterm birth, and LBW, as well as lower mean birth weight and length. Large decreases in MUAC were associated with fetal death and lower mean birth weight and length. Maternal weight loss and MUAC change during pregnancy were not related to SGA birth.

The direction and magnitude of the associations between anthropometry at the first visit and pregnancy outcomes are consistent with reports from HIV-uninfected populations. In a study of women from urban settings in 6 West African countries, a 2.2-fold increased risk of stillbirth was reported for maternal stature < 150 cm (22), which is comparable to the crude relative risk of 1.9 in our group of HIV-infected women for the same cutoff point. Increased risk of late fetal death related to short maternal stature may be attributed in part to a higher occurrence of cephalopelvic disproportion and obstructed labor (23); on the other hand, short stature could be an indicator of lower socioeconomic status with material deprivation that may lead to psychosocial stress during pregnancy and spontaneous abortion (24,25). Adjustment for indicators of an advanced stage of HIV disease and parasitic infections resulted in an attenuation of the risk estimate; this may indicate that these adjusting covariates could be in the causal pathway between short stature and fetal loss.

In our study, height was also associated with increased risk of SGA births, a measure of IUGR, but not with preterm delivery, in agreement with Kramer’s meta-analyses on the determinants of low birth weight among HIV-negative women (26). Our RR estimate for IUGR was higher (2.2 for height 152.1 vs. > 160.1 cm) than that reported in the meta-analyses (1.27 for height < 158 cm), probably due to the higher cutoff point used in the latter; it was, however, comparable to the summary odds ratio estimate from the WHO Collaborative Study on Maternal Anthropometry and Pregnancy Outcomes, 1.9 for cutoff points ranging between 146 and 157 cm (2).

We found that weight, BMI, and MUAC at the first prenatal visit were positively related to decreased risk of IUGR (as measured through SGA births), but not to lowered incidence of preterm birth. First visit measurements may not accurately represent the prepregnant status because the week of gestation at recruitment varied between 12 and 27, and it is likely that some weight gain had taken place before attending prenatal care. However, single anthropometric measurements at one point during the 2nd or 3rd trimesters can be useful predictors of intrauterine growth (27). Our crude RR estimate of 2.8 for the association between low weight at wk 12–27 (cutoff range 47.6–52.0 kg) and IUGR among HIV-infected women is similar to the summary odds ratio estimate for weight at wk 20 reported from the multicenter WHO Collaborative Study among HIV-negative women (cutoff range 40–53 kg), 2.77 (2). The magnitude of the association between low BMI and IUGR among HIV-infected women in our study (RR = 2.5 for cutoff range 19.6–21.5 kg/m²) was also comparable to that reported in the WHO study for BMI at week 20 (OR = 2.1 for cutoff range 17.9–21.3 kg/m²). It was stronger, however, than the association reported for prepregnant BMI in a recent study of Chinese women: 1.8 for BMI < 18.5 kg/m² (28). Also comparable with studies among HIV-negative women was our RR estimate for the relationship between low baseline MUAC (range 23–23.5 cm) and IUGR; although we found a crude 1.7 increased risk, the WHO Collaborative Study reported an OR of 1.6 for MUAC < 21–23 cm at any time point during gestation. In our study, the association became attenuated and was not significant after adjustment. Neither low weight nor low BMI at wk 20 or 28 was related to increased risk of preterm birth in the WHO study, as they were not in our study of HIV-infected women.

The mean rates of weight gain for the 2nd and 3rd trimesters of pregnancy in this population, 0.32 and 0.25 kg/wk, respectively, were lower than those reported from several studies conducted among well-nourished, presumably HIV-uninfected adult women from the United States and Europe, values that ranged from 0.40 to 0.56 kg/wk during the 2nd trimester and 0.30 to 0.54 kg/wk during the 3rd (1,29–31). It is expected that wasting during pregnancy is more common among HIV-infected than -uninfected women living under the same conditions, as suggested by a study of women in Dar es Salaam, Tanzania, in which HIV-infection was significantly associated with a higher prevalence of MUAC < 22 cm at the first prenatal visit (32). In spite of this, we did not find further evidence in the literature that suggested differences in the pattern of weight gain by HIV status. In a study from Rwanda, the slope of the gestational weight gain curve among HIV-infected women was not significantly different from that of HIV-negative women (33), and the rates of weight gain we found in the present study were similar to or higher than those of presumably HIV-uninfected women from poor settings: 0.35 and 0.27 kg/wk for 2nd and 3rd trimesters, respectively, in a group of Filipino mothers (34), 0.22 and 0.20 kg/wk in rural Kenyan women (35), 0.20 kg/wk between wk 14 and 40 in women from rural Tanzania (36), and 0.13 kg/wk between wk 24 and 33 among rural Malawian women (37).

In our study, weight loss or low weight gain (<0.15 kg/wk) during the 2nd trimester of pregnancy was associated with 2.8- and 2.0-fold increases in the risk of fetal death during the 2nd or the 3rd trimesters, respectively. Although weight loss during pregnancy was not reported as a sole risk factor for fetal death among HIV-uninfected women, some studies showed that low gestational weight gain is associated with higher risk of antepartum death (6,8,38,39). Among presumably HIV-negative women from Mozambique, total weight gain < 1 kg between <21 wk gestation and delivery was related to a 5 times higher risk of intrauterine fetal death in univariate analyses (39). In Sweden, weight gain 0.24 kg/wk between gestation wk 14 and 25 (2nd trimester) was related to a crude 1.7-fold increase in the risk of term or preterm antepartum deaths (6). In our study, exposure to weight loss during the 3rd trimester did not have a significant effect on fetal death; this may be due in part to a lack of statistical power because abortions were necessarily excluded in the analyses of 3rd trimester weight loss since they occurred before the beginning of the exposure period (wk 27). Also, women who had a negative pattern of weight change earlier in pregnancy were exposed for a longer period to potential biological mechanisms that mediate the relationship between weight loss and fetal death.

In this group of HIV-infected women, weight loss or low weight gain had a significant impact on the risk of preterm delivery, in agreement with a study among women of undetermined HIV status from Canada in which a 74% excess risk was related to weight gain < 0.27 kg/wk (5), and with the U.S. National Maternal and Infant Health Survey in which weight gain < 0.23 kg/wk was related to a 3.6-times increased risk of preterm birth among women of normal weight (3). Weight loss during the 3rd trimester was more strongly related to preterm birth than weight loss during the 2nd trimester in our population, consistent with a study of low-income women in the United States (40).

We also found that weight loss or low weight gain during pregnancy was related to lower mean birth weight and length and to higher risk of LBW (<2500 g). The strength of the association between low weight gain and LBW in our population of HIV-infected women (RR = 1.6, for weight gain < 0.12 kg/wk) is comparable to that reported in the WHO Collaborative Study (OR = 1.7, for cutoff range 0.08–0.21 kg/wk) (2). It was of similar magnitude also for the 3rd trimester (RR = 1.2), but weaker for the 2nd trimester in the Tanzanian mothers than in the WHO meta-analysis. Weight loss during the 3rd trimester was also more strongly related to birth weight than weight loss during the 2nd trimester, suggesting that among HIV-infected women, the effect of maternal wasting may be similar to the experience of populations under extreme nutritional stress during late pregnancy (41). The rate of weight gain in our study population was not significantly associated with the risk of SGA births, which indicates that in this group of HIV-infected mothers, the possible effect on mean birth weight and length may have been mediated preferentially through the observed reduction in the risk of preterm delivery.

Precise mechanisms to explain adverse pregnancy outcomes as a consequence of weight loss among HIV-infected women are yet to be determined. They may include severe protein-energy deficiency, specific micronutrient deficiencies, the incidence of infections, and hormonal alterations in the course of HIV-related wasting. Weight loss during the 3rd trimester was documented when daily energy intake decreased to between 2092 and 4144 kJ (500 and 1000 kcal) during the Dutch famine; this resulted in elevated rates of fetal death (42) and IUGR (43). In some controlled trials, protein-energy supplementation during pregnancy was related to both increased maternal weight gain and decreased risk of stillbirth as well as improved fetal growth (44,45). Indicators of specific micronutrient deficiencies including calcium, vitamin B-6, and folic acid were related to fetal death in a few observational studies among women of undetermined HIV status (46,47). In our population of HIV-infected women, supplementation with high doses of vitamins B, C, and E greatly reduced the incidence of fetal loss, low birth weight, SGA births, and preterm delivery (14) as well as lowered the risk of maternal weight loss and low weight gain during the 3rd trimester (15). It seems unlikely, however, that the positive effect of multivitamin supplements on pregnancy outcomes is mediated only by their effect on maternal weight gain, because the strongest association between weight loss and fetal death was observed during the 2nd trimester, whereas the effect of vitamins on weight gain appeared to be evident only during the 3rd trimester (15). In addition, the RR estimates for the effects of multivitamins on fetal loss, birth weight, or preterm delivery remained unchanged after controlling for maternal weight loss, a hypothesized intermediate variable, compared with the unadjusted estimate reported previously (14). Last, we did not observe associations between weight loss and SGA births.

Infections are important causes of stillbirth, preterm delivery, and LBW in developing countries, especially those by ascending genitourinary bacteria, syphilis, and malaria (12,19,48,49). On the other hand, among HIV-infected persons, secondary infections are also significant predictors of low gestational weight gain (20) and HIV-related loss of body mass (50,51), possibly through secretion of proinflammatory cytokines. Loss of fat mass due to infection during pregnancy might represent a decrease in available substrate for fetal growth. In addition, weight loss could be a risk factor for chorioamnionitis through an impairment in specific immune responses (52), which increases the risk of stillbirth and preterm delivery.

Our study has some limitations. First, late entrance into prenatal care, although common in developing settings, prevented us from examining the relations between maternal anthropometry during the first trimester and pregnancy outcomes. Second, the comparison of the associations between anthropometric indicators and the outcomes by trimesters may be limited by the fact that not all women contributed measurements to both trimesters considered; nevertheless, the subsets of women who had measurements taken during the 2nd or 3rd trimesters were not different from each other in terms of baseline characteristics.

In summary, we found that among HIV-1 infected women, poor maternal anthropometric status at the first prenatal visit is associated with lower birth weight and IUGR (defined as SGA births) but not with preterm delivery. The direction and magnitude of these associations are comparable to those reported among HIV-uninfected women living in poor settings. Also, weight loss and low weight gain during pregnancy are related to increased risks of fetal death, LBW, and preterm delivery, but not significantly to IUGR. Although this lack of association with IUGR appears to be in contrast with the literature among HIV-uninfected women, it is not possible to generalize from a single study that among HIV-positive women, weight loss is related to LBW only through increased risk of preterm delivery. Examination of potential risk factors for weight loss among HIV-infected women should provide clues to identify public health interventions that may prevent a significant proportion of adverse pregnancy outcomes in populations with limited access to antiretroviral treatment.

	ACKNOWLEDGMENTS

 
We thank the women who participated in this project, the study investigators, coordinator, physicians, and research assistants as well as laboratory technicians, nurses, midwives, and administrative staff who made the study possible.

	FOOTNOTES

 
¹ Supported by the National Institute of Child Health and Human Development (NICHD R01 32257), and the Fogarty International Center (National Institutes of Health D43 TW00004).

³ Abbreviations used: IUGR, intrauterine growth retardation; LBW, low birth weight; MUAC, mid-upper arm circumference; RR, relative risk; SGA, small for gestational age.

Manuscript received 25 January 2004. Initial review completed 13 February 2004. Revision accepted 16 March 2004.

	LITERATURE CITED

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

1. Strauss, R. S. & Dietz, W. H. (1999) Low maternal weight gain in the second or third trimester increases the risk for intrauterine growth retardation. J. Nutr. 129:988-993.[Abstract/Free Full Text]

2. World Health Organization (1995) Maternal anthropometry and pregnancy outcomes: a WHO collaborative study. Bull. WHO 73(suppl.):1-68.

3. Schieve, L. A., Cogswell, M. E., Scanlon, K. S., Perry, G., Ferre, C., Blackmore-Prince, C., Yu, S. M. & Rosenberg, D. (2000) Prepregnancy body mass index and pregnancy weight gain: associations with preterm delivery. The NMIHS Collaborative Study Group. Obstet. Gynecol. 96:194-200.[Abstract/Free Full Text]

4. Chang, S. C., O’Brien, K. O., Nathanson, M. S., Mancini, J. & Witter, F. R. (2003) Characteristics and risk factors for adverse birth outcomes in pregnant black adolescents. J. Pediatr. 143:250-257.[Medline]

5. Kramer, M. S., Coates, A. L., Michoud, M. C., Dagenais, S., Hamilton, E. F. & Papageorgiou, A. (1995) Maternal anthropometry and idiopathic preterm labor. Obstet. Gynecol. 86:744-748.[Abstract]

6. Stephansson, O., Dickman, P. W., Johansson, A. & Cnattingius, S. (2001) Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth. Am. J. Obstet. Gynecol. 184:463-469.[Medline]

7. Stephansson, O., Dickman, P. W., Johansson, A. L. & Cnattingius, S. (2001) The influence of socioeconomic status on stillbirth risk in Sweden. Int. J. Epidemiol. 30:1296-1301.[Abstract/Free Full Text]

8. Tavris, D. R. & Read, J. A. (1982) Effect of maternal weight gain on fetal, infant, and childhood death and on cognitive development. Obstet. Gynecol. 60:689-694.[Abstract/Free Full Text]

9. Wanke, C. A., Silva, M., Ganda, A., Fauntleroy, J., Spiegelman, D., Knox, T. A. & Gorbach, S. L. (2003) Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting. Clin. Infect. Dis. 37(suppl. 2):S81-S84.

10. Ticconi, C., Mapfumo, M., Dorrucci, M., Naha, N., Tarira, E., Pietropolli, A. & Rezza, G. (2003) Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe. J. Acquir. Immune Defic. Syndr. 34:289-294.

11. Ellis, J., Williams, H., Graves, W. & Lindsay, M. K. (2002) Human immunodeficiency virus infection is a risk factor for adverse perinatal outcome. Am. J. Obstet. Gynecol. 186:903-906.[Medline]

12. Ayisi, J. G., van Eijk, A. M., ter Kuile, F. O., Kolczak, M. S., Otieno, J. A., Misore, A. O., Kager, P. A., Steketee, R. W. & Nahlen, B. L. (2003) The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya. AIDS 17:585-594.[Medline]

13. Brocklehurst, P. & French, R. (1998) The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis. Br. J. Obstet. Gynaecol. 105:836-848.[Medline]

14. Fawzi, W. W., Msamanga, G. I., Spiegelman, D., Urassa, E.J.N., McGrath, N., Mwakagile, M., Antelman, G., Mbise, R., Herrera, G., Kapiga, S., Willett, W. & Hunter, D. J. (1998) Randomized trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 351:1477-1482.[Medline]

15. Villamor, E., Msamanga, G., Spiegelman, D., Antelman, G., Hunter, D. J., Peterson, K. E. & Fawzi, W. W. (2002) Effect of multivitamin and vitamin A supplements on weight gain during pregnancy among HIV-1 infected women. Am. J. Clin. Nutr. 76:1082-1090.[Abstract/Free Full Text]

16. Villamor, E., Gofin, R. & Adler, B. (1998) Maternal anthropometry and pregnancy outcome among Jerusalem women. Ann. Hum. Biol. 25:331-343.[Medline]

17. Brenner, W. E., Edelman, D. A. & Hendricks, C. H. (1976) A standard of fetal growth for the United States of America. Am. J. Obstet. Gynecol. 126:555-564.[Medline]

18. Wacholder, S. (1986) Binomial regression in GLIM: estimating risk ratios and risk differences. Am. J. Epidemiol. 123:174-184.[Abstract/Free Full Text]

19. Dreyfuss, M. L., Msamanga, G., Spiegelman, D., Hunter, D. J., Urassa, E.J.N., Hertzmark, E. & Fawzi, W. W. (2001) Determinants of low birth weight among HIV-infected pregnant women in Tanzania. Am. J. Clin. Nutr. 74:814-826.[Abstract/Free Full Text]

20. Villamor, E., Msamanga, G., Spiegelman, D., Peterson, K. E., Antelman, G. & Fawzi, W. W. (2003) Pattern and predictors of weight gain during pregnancy among HIV-1 infected women from Tanzania. J. Acquir. Immune Defic. Syndr. 32:560-569.

21. White, H. (1980) A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity. Econometrica 48:817-830.

22. Chalumeau, M., Bouvier-Colle, M. H. & Breart, G. (2002) Can clinical risk factors for late stillbirth in West Africa be detected during antenatal care or only during labour?. Int. J. Epidemiol. 31:661-668.[Abstract/Free Full Text]

23. Liselele, H. B., Boulvain, M., Tshibangu, K. C. & Meuris, S. (2000) Maternal height and external pelvimetry to predict cephalopelvic disproportion in nulliparous African women: a cohort study. Br. J. Obstet. Gynaecol. 107:947-952.

24. Brandt, L. P. & Nielsen, C. V. (1992) Job stress and adverse outcome of pregnancy: a causal link or recall bias?. Am. J. Epidemiol. 135:302-311.[Abstract/Free Full Text]

25. Fenster, L., Schaefer, C., Mathur, A., Hiatt, R. A., Pieper, C., Hubbard, A. E., Von Behren, J. & Swan, S. H. (1995) Psychologic stress in the workplace and spontaneous abortion. Am. J. Epidemiol. 142:1176-1183.[Abstract/Free Full Text]

26. Kramer, M. S. (1987) Determinants of low birth weight: methodological assessment and meta-analysis. Bull. WHO 65:663-737.[Medline]

27. World Health Organization (1995) Physical Status: The Use and Interpretation of Anthropometry 1995 WHO Geneva, Switzerland.

28. Ronnenberg, A. G., Wang, X., Xing, H., Chen, C., Chen, D., Guang, W., Guang, A., Wang, L., Ryan, L. & Xu, X. (2003) Low preconception body mass index is associated with birth outcome in a prospective cohort of Chinese women. J. Nutr. 133:3449-3455.[Abstract/Free Full Text]

29. Institute of Medicine (1990) Nutrition During Pregnancy: Part I: Weight Gain 1990 National Academy Press Washington, DC.

30. Abrams, B., Carmichael, S. & Selvin, S. (1995) Factors associated with the pattern of maternal weight gain during pregnancy. Obstet. Gynecol. 86:170-176.[Abstract]

31. Siega-Riz, A. M., Adair, L. S. & Hobel, C. J. (1994) Institute of Medicine maternal weight gain recommendations and pregnancy outcome in a predominantly Hispanic population. Obstet. Gynecol. 84:565-573.[Medline]

32. Villamor, E., Msamanga, G., Spiegelman, D., Coley, J., Hunter, D. J., Peterson, K. E. & Fawzi, W. W. (2002) HIV status and sociodemographic correlates of maternal body size and wasting during pregnancy. Eur. J. Clin. Nutr. 56:415-424.[Medline]

33. Ladner, J., Castetbon, K., Leroy, V., Nyiraziraje, M., Chauliac, M., Karita, E., De Clercq, A., Van de Perre, P. & Dabis, F. (1998) Pregnancy, body weight and human immunodeficiency virus infection in African women: a prospective cohort study in Kigali (Rwanda), 1992–1994. Int. J. Epidemiol. 27:1072-1077.[Abstract/Free Full Text]

34. Siega-Riz, A. M. & Adair, L. S. (1993) Biological determinants of pregnancy weight gain in a Filipino population. Ann. N.Y. Acad. Sci. 678:364-365.[Medline]

35. Jansen, A.A.J., Kusin, J. A., Thiuri, B., Lakhani, S. A. & ’tMannetje, W. (1984) Machakos project studies No. XXIV. Anthropometric changes during pregnancy in rural African women. Trop. Geograph. Med. 36:91-97.

36. Moller, B. O., Gebre-Medhin, M. & Lindmark, G. (1989) Maternal weight, weight gain and birthweight at term in the rural Tanzanian village of Ilula. Br. J. Obstet. Gynaecol. 96:158-166.[Medline]

37. Huddle, J. M., Gibson, R. S. & Cullinan, T. R. (1998) Is zinc a limiting nutrient in the diets of rural pregnant Malwian women?. Br. J. Nutr. 79:257-265.[Medline]

38. Naeye, R. L. (1979) Weight gain and the outcome of pregnancy. Am. J. Obstet. Gynecol. 135:3-9.[Medline]

39. Osman, N. B., Challis, K., Cotiro, M., Nordahl, G. & Bergstrom, S. (2001) Perinatal outcome in an obstetric cohort of Mozambican women. J. Trop. Pediatr. 47:30-38.[Abstract/Free Full Text]

40. Hickey, C. A., Cliver, S. P., McNeal, S. F., Hoffman, H. J. & Goldenberg, R. L. (1995) Prenatal weight gain patterns and spontaneous preterm birth among nonobese black and white women. Obstet. Gynecol. 85:909-914.[Abstract]

41. Neufeld, L., Pelletier, D. L. & Haas, J. D. (1999) The timing hypothesis and body proportionality of the intra-uterine growth retarded infant. Am. J. Hum. Biol. 11:638-646.

42. Smith, C. (1947) Effects of maternal undernutrition upon the newborn infant in Holland (1944–1945). J. Pediatr. 30:229-243.

43. Stein, A. D., Ravelli, A.C.J. & Lumey, L. H. (1995) Famine, third-trimester pregnancy weight gain and intrauterine growth: the Dutch famine birth cohort study. Hum. Biol. 67:135-150.[Medline]

44. Ceesay, S. M., Prentice, A. M., Cole, T. J., Foord, F., Weaver, L. T., Poskitt, E.M.E. & Whitehead, R. G. (1997) Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial. Br. Med. J. 315:786-790.[Abstract/Free Full Text]

45. Mora, J. O., Clement, J., Christiansen, N., Suescun, J., Wagner, M. & Herrera, M. G. (1978) Nutritional supplementation and the outcome of pregnancy. III Perinatal and neonatal mortality. Nutr. Rep. Int. 18:167-175.

46. Ronnenberg, A. G., Goldman, M. B., Chen, D., Aitken, I. W., Willett, W. C., Selhub, J. & Xu, X. (2002) Preconception folate and vitamin B(6) status and clinical spontaneous abortion in Chinese women. Obstet. Gynecol. 100:107-113.[Abstract/Free Full Text]

47. Ebbs, J. H., Tisdall, F. F. & Scott, W. A. (1941) The influence of prenatal diet on the mother and child. J. Nutr. 22:515-521.

48. Goldenberg, R. L. & Thompson, C. (2003) The infectious origins of stillbirth. Am. J. Obstet. Gynecol. 189:861-873.[Medline]

49. Andrews, W. W., Hauth, J. C. & Goldenberg, R. L. (2000) Infection and preterm birth. Am. J. Perinatol. 17:357-365.[Medline]

50. Macallan, D. C., Noble, C., Baldwin, C., Foskett, M., McManus, T. & Griffin, G. E. (1993) Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection. Am. J. Clin. Nutr. 58:417-424.[Abstract/Free Full Text]

51. Paton, N.I.J., Macallan, D. C., Jebb, S. A., Noble, C., Baldwin, C., Pazianas, M. & Griffin, G. E. (1997) Longitudinal changes in body composition measured with a variety of methods in patients with AIDS. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 14:119-127.[Medline]

52. Fields, S. J., Livshits, G., Merlob, P. & Sirotta, L. (1997) On the relationship between pregnancy weight gain and chorioamnionitis. Am. J. Hum. Biol. 9:545-553.

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