Gestational weight gain during the second and third trimesters and adverse pregnancy outcomes, results from a prospective pregnancy cohort in urban Tanzania.

BACKGROUND: Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort. METHODS: We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women's gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated. RESULTS: According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36-0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95-1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03-3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03-2.44). CONCLUSIONS: A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings. TRIAL REGISTRATION: This trial was registered as "Prenatal Iron Supplements: Safety and Efficacy in Tanzania" (NCT01119612; http://clinicaltrials.gov/show/NCT01119612 ).

Pregnancy is a critical lifetime event for both mother and the offspring, with implications in short-term and long-term health consequences. Gestational weight gain (GWG) is an important modifiable factor for pregnancy outcomes related to infant body size and weight and prematurity. Countries in sub-Saharan Africa (SSA) have long had poor rates of insufficient GWG and pregnancy complications associated with insufficient GWG. Nevertheless, some SSA countries are experiencing economic transitions accompanied with changes in lifestyle and nutrition, which might impact pregnancy experiences, including GWG and pregnancy outcomes. This study aimed to characterize recent GWG patterns and the associations of both inadequate and excessive GWG with adverse pregnancy outcomes, using an urban pregnancy cohort in Tanzania. This study found that 42.0%. 22.0%, and 36.0% of women had insufficient, adequate, and excessive GWG, respectively. Insufficient GWG was associated with higher risks of small infant size and low infant body weight, and excessive GWG was associated with higher risk of preterm birth, particularly among women with body mass index 18.5­25.0 kg/m². Results from the present study highlight that both insufficient and excessive GWG are of potential public health concerns in urban centers of SSA, concerning upward trends in obesity and possibly obesity-related pregnancy consequences. Local public health practitioners should continue to advocate longitudinal GWG monitoring and care among African pregnant women, and optimal GWG with feasible and effective clinical guidelines should be developed to prevent both over- and under-gaining of maternal weight during pregnancy.

Pre-pregnancy fat intake in relation to hypertensive disorders of pregnancy.

BACKGROUND: Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant. OBJECTIVES: We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN). METHODS: We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders. RESULTS: During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05-1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07-2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87-1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00-2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75-1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%-51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33-0.92). CONCLUSIONS: Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply.

Associations between predicted vitamin D status, vitamin D intake, and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity.

BACKGROUND: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent. OBJECTIVE: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status. RESULTS: Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P-trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04). CONCLUSIONS: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously.

Pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion.

PURPOSE: To investigate the relation between pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion (SAB). METHODS: Our prospective cohort study included 15,590 pregnancies from 11,072 women with no history of SAB in the Nurses' Health Study II (1991-2009). Beverage intake was assessed every 4 years using a validated questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously at <20 weeks gestation. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the relative risks (RRs) and 95 % confidence intervals (CIs). RESULTS: There was a positive linear trend across categories of pre-pregnancy caffeine intake and risk of SAB such that women consuming >400 mg/day had 1.11 (95 % CI 0.98, 1.25) times the risk of SAB compared to women consuming <50 mg/day (p trend = 0.05). Total coffee intake had a positive, linear association with SAB. Compared to women with no pre-pregnancy coffee intake, women consuming ≥4 servings/day had a 20 % (6, 36 %) increased risk of SAB (p trend = 0.01). There was no difference in the association between caffeinated and decaffeinated coffee and risk of SAB. Pre-pregnancy intake of caffeinated tea, caffeinated soda, and decaffeinated soda had no association with SAB. CONCLUSIONS: Pre-pregnancy coffee consumption at levels ≥4 servings/day is associated with increased risk of SAB, particularly at weeks 8-19.

Vitamin D supplementation and growth in urban Mongol school children: Results from two randomized clinical trials.

BACKGROUND: Symptomatic vitamin D deficiency is associated with slowed growth in children. It is unknown whether vitamin D repletion in children with asymptomatic serum vitamin D deficiency can restore normal growth. OBJECTIVE: We tested the impact of vitamin D-supplementation on serum concentrations of 25-hydroxyvitamin D [25(OH)D] and short-term growth in Mongol children, with very low serum vitamin D levels in winter. DESIGN: We conducted two randomized, double-blind, placebo-controlled trials in urban school age children without clinical signs of rickets. The Supplementation Study was a 6-month intervention with an 800 IU vitamin D3 supplement daily, compared with placebo, in 113 children aged 12-15 years. A second study, the Fortification Study, was a 7-week intervention with 710 ml of whole milk fortified with 300 IU vitamin D3 daily, compared with unfortified milk, in 235 children aged 9-11 years. RESULTS: At winter baseline, children had low vitamin D levels, with a mean (±SD) serum 25-hydroxyvitamin D [25(OH)D] concentration of 7.3 (±3.9) ng/ml in the Supplementation Study and 7.5 (±3.8) ng/ml in the Fortification Study. The serum levels increased in both vitamin D groups-by 19.8 (±5.1) ng/ml in the Supplementation Study, and 19.7 (±6.1) ng/ml in the Fortification Study. Multivariable analysis showed a 0.9 (±0.3 SE) cm greater increase in height in the vitamin-D treated children, compared to placebo treated children, in the 6-month Supplementation Study (p = 0.003). Although the children in the 7-week Fortification Study intervention arm grew 0.2 (±0.1) cm more, on average, than placebo children this difference was not statistically significant (p = 0.2). There were no significant effects of vitamin D supplements on differences in changes in weight or body mass index in either trial. For the Fortification Study, girls gained more weight than boys while taking vitamin D 3 (p-value for interaction = 0.03), but sex was not an effect modifier of the relationship between vitamin D3 and change in either height or BMI in either trial. CONCLUSIONS: Correcting vitamin D deficiency in children with very low serum vitamin D levels using 800 IU of vitamin D3 daily for six months increased growth, at least in the short-term, whereas, in a shorter trial of 300 IU of D fortified milk daily for 7 weeks did not.

Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia.

Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20-58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10-20/20-30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (-2.3 ng/mL; 95% CI: -4.1, -5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar.

Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth.

OBJECTIVE: To evaluate prospectively the relationship between prepregnancy folate intake and risk of spontaneous abortion and stillbirth. METHODS: Women in the Nurses' Health Study II who self-reported a pregnancy between 1992 and 2009 were included in this analysis. Dietary folate and supplement use was assessed every 4 years, starting in 1991, by a food frequency questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously (spontaneous abortion less than 20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Among the 11,072 women, 15,950 pregnancies were reported of which 2,756 (17.3%) ended in spontaneous abortion and 120 (0.8%) ended in stillbirth. Compared with women in the lowest quintile of prepregnancy folate intake (less than 285 micrograms/d), those in the highest quintile (greater than 851 micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95% confidence interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This association was primarily attributable to intake of folate from supplements. Compared with women without supplemental folate intake (0 micrograms/d), those in the highest category (greater than 730 micrograms/d) had a relative risk of spontaneous abortion of 0.80 (95% CI 0.71-0.90) after multivariable adjustment (P trend <.001). The association of prepregnancy supplemental folate with risk of spontaneous abortion was consistent across gestational period of loss. A similar inverse trend was observed with the risk of stillbirth, which fell short of conventional significance (P trend=.06). CONCLUSIONS: Higher intake of folate from supplements was associated with reduced risk of spontaneous abortion. Women at risk of pregnancy should use supplemental folate for neural tube defect prevention and because it may decrease the risk of spontaneous abortion. LEVEL OF EVIDENCE: : II.

Vitamin D status and hypertensive disorders in pregnancy.

PURPOSE: Several studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear. METHODS: Among women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4-36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%). RESULTS: We did not detect an association between plasma 25(OH)D concentration (mean 58, standard deviation 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval, 0.77-1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval, 1.01-1.72) per each 25 nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest that this association was not because of reverse causation. Although the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension. CONCLUSIONS: These data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy.

Vitamin D deficiency in reproductive age Mongolian women: a cross sectional study.

Vitamin D production is critical not only for rickets prevention but for its role in several chronic diseases of adulthood. Maternal vitamin D status also has consequences for the developing fetus. This study assessed the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D]<20ng/ml) and insufficiency [25(OH)D=20-29ng/ml] in spring, among reproductive age Mongolian women. Blood was drawn in March and April, 2009 from 420 Mongolian women, 18-44 years of age. Serum 25(OH)D concentrations were measured, anthropometric measurements were performed and information was collected by interview on lifestyle, dietary and reproductive factors. Logarithm-transformed 25(OH)D levels were compared across risk factor categories by analysis of variance. Linear regression analysis was used to assess the independent associations of factors with vitamin D status. Cutaneous vitamin D3 synthesis was assessed between December and July using a standard 7-dehydrocholesterol ampoule model. The vast majority of women 415 (98.8%) had serum 25(OH)D<20ng/ml (50nmol/l) with an additional 4 women (<1%) in the insufficient range (20-29ng/ml); only one women (0.2%) had sufficient levels (>30ng/ml or 75nmol/l). 25(OH)D concentrations were positively and independently associated with educational status and use of vitamin D supplements, but not with other demographic, lifestyle, reproductive, or anthropometric factors. 25(OH)D levels were not associated with dietary factors in this population, as there is little access to foods containing vitamin D in Mongolia. No production of previtamin D3 was observed until March and was maximally effective in April and was sustained through July. These data suggest that the prevalence of vitamin D deficiency in spring among reproductive age women in Mongolia is high. Given the lack of naturally vitamin D-rich food in the diet and limited use of vitamin D supplements, food fortification and/or supplementation with vitamin D should be considered among these women.

Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia.

OBJECTIVE: Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs. METHODS: By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January-March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D(3) (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months. RESULTS: At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5-10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P < .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31-0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28-0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; P(interaction) = .27). CONCLUSIONS: Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency.

Randomized trial of fortified milk and supplements to raise 25-hydroxyvitamin D concentrations in schoolchildren in Mongolia.

BACKGROUND: The optimal public health strategy for maintaining 25-hydroxyvitamin D [25(OH)D] concentrations in schoolchildren in Mongolia is unknown. OBJECTIVE: The objective was to compare the effectiveness of different supplement and fortified milk regimens to increase 25(OH)D concentrations in Mongolian schoolchildren. DESIGN: Twenty-one classrooms of 579 children aged 9-11 y were randomized to interventions with an equivalent content of vitamin D(3): 1) a one-time seasonal supplement of 13,700 IU, 2) 300 IU/d from supplements, 3) 300 IU/d from fortified ultra-high-temperature pasteurized milk from the United States, 4) 300 IU/d from fortified pasteurized Mongolian milk, or 5) unfortified pasteurized Mongolian milk (control). RESULTS: In January, the mean (±SD) serum 25(OH)D concentration was 8 ± 4 ng/mL (20 ± 10 nmol/L), and 98% of the children had a concentration <20 ng/mL (50 nmol/L). In March, concentrations were 8 ± 4 ng/mL after unfortified milk, 20 ± 6 ng/mL after fortified Mongolian milk, 29 ± 10 ng/mL after fortified US milk, 21 ± 6 ng/mL after daily supplements, and 12 ± 4 ng/mL after seasonal supplements (each greater than unfortified milk, P < 0.01). Seasonal supplementation was less effective than was daily supplementation (P < 0.0001). Despite consuming daily supplements or fortified milk, 41% of the children still had concentrations <20 ng/mL (50 nmol/L). Children with lower baseline 25(OH)D concentrations experienced slightly larger 25(OH)D responses to intervention than did children with higher concentrations (P = 0.002). CONCLUSIONS: In this population with extremely low vitamin D concentrations, delivery of 300 IU vitamin D/d via supplements or in fortified milk improved 25(OH)D concentrations but failed to raise concentrations uniformly to >20 ng/mL (50 nmol/L). The daily low-dose intervention was superior to the seasonal larger-dose intervention. Higher doses may be needed to prevent deficiency in schoolchildren in Mongolia and at other northern latitudes. This trial is registered at clinicaltrials.gov as NCT00886379.

Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility.

OBJECTIVE: To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility. DESIGN: A prospective cohort study. SETTING: The Nurses' Health Study II. PATIENT(S): Eighteen thousand five hundred fifty-five married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. INTERVENTION(S): None, observational study. MAIN OUTCOME MEASURE(S): Incident reports of infertility caused by anovulation. RESULT(S): During 8 years of follow-up, 438 women reported infertility caused by ovulatory disorder. There was an inverse association between frequency of multivitamin use and ovulatory infertility. The multivariate-adjusted relative risk (95% confidence interval) of ovulatory infertility was 0.88 (0.60, 1.28) for women consuming two tablets per week or less, 0.69 (0.51, 0.95) for women consuming three to five tablets per week, and 0.59 (0.46, 0.75) for women consuming six or more tablets per week, when compared with women who did not use these supplements (P, trend <.001). Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility. CONCLUSION(S): Regular use of multivitamin supplements may decrease the risk of ovulatory infertility.

Diet and lifestyle in the prevention of ovulatory disorder infertility.

OBJECTIVE: To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility. METHODS: We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility. RESULTS: Increasing adherence to a "fertility diet" pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the "fertility diet" pattern score was 0.34 (95% confidence interval 0.23-0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women's age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29-86%). CONCLUSION: Following a "fertility diet" pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle. LEVEL OF EVIDENCE: II.

Diet during pregnancy and risk of preeclampsia or gestational hypertension.

PURPOSE: We sought to examine associations of first-trimester intake of calcium, n-3 and n-6 fatty acids, trans fatty acids, magnesium, folate, and vitamins C, D, and E with preeclampsia (PE) and gestational hypertension (GH). METHODS: We studied associations of diet with PE or GH among 1718 women in the prospective cohort study Project Viva, using logistic regression and adjusting for maternal age, prepregnancy body mass index, first trimester systolic blood pressure, race/ethnicity, education, and parity. We assessed first-trimester diet using a validated semiquantitative food frequency questionnaire. RESULTS: A total of 59 (3%) women developed PE, and 119 developed (7%) GH. We found a somewhat-lower risk of PE associated with higher intake of the elongated n-3 fatty acids docosahexaenoic and eicosapentaenoic acids (odds ratio [OR] 0.84, 95% confidence interval [95% CI]: 0.69-1.03 per 100 mg/day), fish (OR 0.91, 95% CI 0.75-1.09 per serving/day), and the ratio of docosahexaenoic + eicosapentaenoic to arachadonic acid (OR 0.82, 95% CI 0.66-1.01). We did not observe a lower risk of GH or PE with a greater intake of calcium; vitamin C, D, or E; milk; magnesium; folate; or with lower intake of n-6 or trans fatty acids. CONCLUSIONS: Our results support a potential benefit for elongated n-3 fatty acids in preventing preeclampsia.

Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age.

BACKGROUND: Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown. OBJECTIVE: We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age. DESIGN: The participants were 1194 mother-child pairs in Project Viva-a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (>or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma). RESULTS: The mean (+/-SD) total vitamin D intake during pregnancy was 548 +/- 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend < 0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results. CONCLUSION: In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood.

Iron intake and risk of ovulatory infertility.

OBJECTIVE: To evaluate whether iron supplement use or greater intake of total, heme and nonheme iron is associated with lower risk of ovulatory infertility. METHODS: We conducted a prospective cohort study among 18,555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999 (mean baseline age+/-standard deviation 32.6+/-3.6). Diet was assessed twice during follow-up and prospectively related to the incidence of infertility due to ovulatory disorder. RESULTS: During the 8 years of follow-up, 438 women reported infertility due to ovulatory disorder. Women who consumed iron supplements had a significantly lower risk of ovulatory infertility than women who did not use iron supplements (relative risk 0.60, 95% confidence interval 0.39-0.92), after adjusting for potential confounders. Total nonheme iron intake, primarily consumed as multivitamins and iron supplements, was inversely associated with the risk of infertility (relative risk Quintile 1 compared with 5, 95% confidence interval 0.39-0.92; P, trend .005.) Heme iron intake was unrelated to ovulatory infertility in multivariable adjusted analyses. CONCLUSION: Consumption of iron supplements and nonheme iron from other sources may decrease the risk of ovulatory infertility. LEVEL OF EVIDENCE: II-2.

Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age.

BACKGROUND: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. OBJECTIVE: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. DESIGN: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated, and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. RESULTS: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03] and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). CONCLUSION: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.

Changes in dietary intake from the first to the second trimester of pregnancy.

Maternal diet may influence outcomes of pregnancy and childhood. Diet in the first trimester may be more important to development and differentiation of various organs, whereas diet later in pregnancy may be important for overall fetal growth as well as for brain development. To our knowledge, no studies have examined individual-level changes in food and nutrient intake from the 1st to 2nd trimester of pregnancy. The objective of this study was to examine changes in dietary intake from the 1st to 2nd trimester of pregnancy. As part of the ongoing US prospective cohort study, Project Viva, we studied 1543 women who completed food-frequency questionnaires that assessed dietary intakes during the 1st and 2nd trimester of pregnancy. For both foods and energy-adjusted nutrients, we examined changes in dietary intake from 1st to 2nd trimester. Reported mean energy intake was similar for the 1st (2046 kcal) and 2nd (2137 kcal) trimesters. Foods and energy-adjusted nutrients from foods whose overall mean intakes increased more than 5% from 1st to 2nd trimester were skim or 1% dairy foods (22%), whole-fat dairy foods (15%), red and processed meat (11%), saturated fat (6%) and vitamin D (7%). Intake of caffeinated beverages (-30%) and alcoholic beverages (-88%) decreased more than 5%. Because mean multivitamin intake increased by 35% from the 1st to 2nd trimester, total micronutrient intake increased appreciably more than micronutrient intake from foods only. Correlations across trimesters ranged from 0.32 for vitamin B12 to 0.68 for fruit and vegetables. In conclusion, for many outcomes of pregnancy and childhood, the incremental information obtained from assessing complete diet in both early and late pregnancy may not outweigh the burden to participants and investigators. However, investigators should assess caffeine, alcohol, and vitamin and supplement use in both the 1st and 2nd trimester, and consider doing so for foods and nutrients for which trimester-specific hypotheses are well substantiated.

Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort.

Previous studies, mainly among populations with high consumption of seafood, have suggested that increased marine n-3 polyunsaturated fatty acid (PUFA) intake during pregnancy promotes longer gestation and higher birth weight. Few studies have isolated the contribution of fetal growth to birth weight. Using data from 2,109 pregnant women in Massachusetts enrolled in Project Viva from 1999 to 2002, the authors examined associations of marine n-3 PUFA and seafood intake with birth weight and birth-weight-for-gestational-age z value (fetal growth) using linear regression; length of gestation using median regression; and low birth weight, preterm delivery, and being small for gestational age using logistic regression. After adjustment for maternal and child factors, birth weight was 94 (95% confidence interval: 23, 166) g lower and fetal growth z value 0.19 (95% confidence interval: 0.08, 0.31) units lower in the highest compared with the lowest quartile of first-trimester n-3 PUFA intake. Results for the second and third trimesters were similar, and findings for seafood paralleled those for n-3 PUFA. Elongated n-3 PUFA intake and seafood intake were not associated with length of gestation or risk of preterm birth. Results from this US cohort support the conclusion that seafood intake during pregnancy is associated with reduced fetal growth.

Maternal calcium intake and offspring blood pressure.

BACKGROUND: Few data exist on the intergenerational influence of calcium intake during pregnancy on offspring blood pressure. METHODS AND RESULTS: As part of the ongoing US prospective cohort study Project Viva, we analyzed 4091 Dinamap blood pressure measurements from 936 six-month-old infants whose mothers had completed food frequency questionnaires during the second trimester of pregnancy. We used mixed models to estimate effects of maternal calcium intake on offspring systolic blood pressure. Mean+/-SD daily total maternal calcium intake was 1494+/-523 mg, consisting of 1230+/-486 mg from foods and 264+/-191 mg from supplements. Mean+/-SD 6-month blood pressure was 89.9+/-12.9 mm Hg. From bottom to top quartile of dietary calcium from foods adjusted for energy intake and measurement conditions, mean infant systolic blood pressures were 91.0, 90.2, 90.9, and 90.2 mm Hg (trend P=0.62). From calcium supplements only, the values were 91.5, 90.2, 90.4, and 88.4 mm Hg (trend P=0.006). After further adjustment for demographic, anthropometric, dietary, social, and economic variables, the decrease in 6-month systolic blood pressure was -3.0 mm Hg (95% CI, -4.9 to -1.1) for each 500-mg increment of maternal supplemental calcium intake during pregnancy. We did not find evidence of effect modification by maternal vitamin D or potassium intake or by infant body mass index. First-trimester calcium intake was not associated with offspring blood pressure. CONCLUSIONS: These observational data suggest that supplementing maternal midgestational calcium intake may lower offspring blood pressure, thus helping to prevent hypertension in the next generation.