Lisa M. Bodnar

Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

OBJECTIVE Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. METHOD This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. RESULTS Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. CONCLUSIONS For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

Nutrition and Depression: Implications for Improving Mental Health Among Childbearing-Aged Women

Adequate nutrition is needed for countless aspects of brain functioning. Poor diet quality, ubiquitous in the United States, may be a modifiable risk factor for depression. The objective was to review and synthesize the current knowledge of the role of nutrition in depression, and address implications for childbearing-aged women. Poor omega-3 fatty acid status increases the risk of depression. Fish oil and folic acid supplements each have been used to treat depression successfully. Folate deficiency reduces the response to antidepressants. Deficiencies of folate, vitamin B12, iron, zinc, and selenium tend to be more common among depressed than nondepressed persons. Dietary antioxidants have not been studied rigorously in relation to depression. Childbearing-aged women are particularly vulnerable to the adverse effects of poor nutrition on mood because pregnancy and lactation are major nutritional stressors to the body. The depletion of nutrient reserves throughout pregnancy and a lack of recovery postpartum may increase a womans risk of depression. Prospective research studies are needed to clarify the role of nutrition in the pathophysiology of depression among childbearing-aged women. Greater attention to nutritional factors in mental health is warranted given that nutrition interventions can be inexpensive, safe, easy to administer, and generally acceptable to patients.

Maternal Serum 25-Hydroxyvitamin D Concentrations Are Associated with Small-for-Gestational Age Births in White Women

Maternal vitamin D deficiency has been associated with numerous adverse health outcomes, but its association with fetal growth restriction remains uncertain. We sought to elucidate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations in early pregnancy and the risk of small-for-gestational age birth (SGA) and explore the association between maternal single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene and the risk of SGA. We conducted a nested case-control study of nulliparous pregnant women with singleton pregnancies who delivered SGA infants (n = 77 white and n = 34 black) or non-SGA infants (n = 196 white and n = 105 black). Women were followed from <16 wk gestation to delivery. Womens banked sera at <22 wk were newly measured for 25(OH)D and DNA extracted for VDR genotyping. SGA was defined as live-born infants that were <10th percentile of birth weight according to nomograms based on gender and gestational age. After confounder adjustment, there was a U-shaped relation between serum 25(OH)D and risk of SGA among white mothers, with the lowest risk from 60 to 80 nmol/L. Compared with serum 25(OH)D 37.5-75 nmol/L, SGA odds ratios (95% CI) for levels <37.5 and >75 nmol/L were 7.5 (1.8, 31.9) and 2.1 (1.2, 3.8), respectively. There was no relation between 25(OH)D and SGA risk among black mothers. One SNP in the VDR gene among white women and 3 SNP in black women were significantly associated with SGA. Our results suggest that vitamin D has a complex relation with fetal growth that may vary by race.

Severe obesity, gestational weight gain, and adverse birth outcomes

BACKGROUND The 2009 Institute of Medicine (IOM) Committee to Reevaluate Gestational Weight Gain Guidelines concluded that there were too few data to inform weight-gain guidelines by obesity severity. Therefore, the committee recommended a single range, 5-9 kg at term, for all obese women. OBJECTIVE We explored associations between gestational weight gain and small-for-gestational-age (SGA) births, large-for-gestational-age (LGA) births, spontaneous preterm births (sPTBs), and medically indicated preterm births (iPTBs) among obese women who were stratified by severity of obesity. DESIGN We studied a cohort of singleton, live-born infants without congenital anomalies born to obesity class 1 (prepregnancy body mass index [BMI (in kg/m(2))]: 30-34.9; n = 3254), class 2 (BMI: 35-39.9; n = 1451), and class 3 (BMI: > or =40; n = 845) mothers. We defined the adequacy of gestational weight gain as the ratio of observed weight gain to IOM-recommended gestational weight gain. RESULTS The prevalence of excessive gestational weight gain declined, and weight loss increased, as obesity became more severe. Generally, weight loss was associated with an elevated risk of SGA, iPTB, and sPTB, and a high weight gain tended to increase the risk of LGA and iPTB. Weight gains associated with probabilities of SGA and LGA of < or =10% and a minimal risk of iPTB and sPTB were as follows: 9.1-13.5 kg (obesity class 1), 5.0-9 kg (obesity class 2), 2.2 to <5.0 kg (obesity class 3 white women), and <2.2 kg (obesity class 3 black women). CONCLUSION These data suggest that the range of gestational weight gain to balance risks of SGA, LGA, sPTB, and iPTB may vary by severity of obesity.

Maternal Vitamin D Deficiency Is Associated with Bacterial Vaginosis in the First Trimester of Pregnancy

Bacterial vaginosis (BV) is a highly prevalent vaginal infection that is associated with adverse pregnancy outcomes. Vitamin D exerts an influence on the immune system and may play a role in BV. The objective of this study was to examine the association between maternal vitamin D status and the prevalence of BV in early pregnancy. Women (n = 469) enrolled in a pregnancy cohort study at <16 wk underwent a pelvic examination and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D]. BV was diagnosed using Gram-stained vaginal smears interpreted using the method of Nugent. Approximately 41% of women had BV (Nugent score 7-10) and 52% had a serum 25(OH)D concentration <37.5 nmol/L. The mean unadjusted serum 25(OH)D concentration was lower among BV cases (29.5 nmol/L; 95% CI: 27.1, 32.0) compared with women with normal vaginal flora (40.1 nmol/L; 95% CI: 37.0, 43.5; P < 0.001). BV prevalence decreased as vitamin D status improved (P < 0.001). Approximately 57% of the women with a serum 25(OH)D concentration <20 nmol/L had BV compared with 23% of women with a serum 25(OH)D concentration >80 nmol/L. There was a dose-response association between 25(OH)D and the prevalence of BV. The prevalence declined as 25(OH)D increased to 80 nmol/L, then reached a plateau. Compared with a serum 25(OH)D concentration of 75 nmol/L, there were 1.65-fold (95% CI: 1.01, 2.69) and 1.26-fold (1.01, 1.57) increases in the prevalence of BV associated with a serum 25(OH)D concentration of 20 and 50 nmol/L, respectively, after adjustment for race and sexually transmitted diseases. Vitamin D deficiency is associated with BV and may contribute to the strong racial disparity in the prevalence of BV.

Uric Acid Is as Important as Proteinuria in Identifying Fetal Risk in Women With Gestational Hypertension

Gestational hypertension is differentiated into higher and lower risk by the presence or absence of proteinuria. We asked if hyperuricemia, a common finding in pregnancy hypertension, might also be an indicator of increased risk. We examined fetal outcome data from 972 pregnancies collected from 1997 to 2002 in a nested case-control study. Participants were nulliparous with no known medical complications. The frequency of preterm birth, the duration of pregnancy, frequency of small-for-gestational-age infants, and birth weight centile were determined for pregnancies assigned to 8 categories by the presence or absence of combinations of hypertension, hyperuricemia, and proteinuria. In women with gestational hypertension, hyperuricemia was associated with shorter gestations and smaller birth weight centiles and increased risk of preterm birth and small-for-gestational-age infants. Hyperuricemia increased the risk of these outcomes in the presence or absence of proteinuria. Risk was also increased in a small group of women with hyperuricemia and proteinuria without hypertension. Women with only hypertension and hyperuricemia have similar or greater risk as women with only hypertension and proteinuria. Those with hypertension, proteinuria, and hyperuricemia have greater risk than those with hypertension and proteinuria alone. The risk of these outcomes increased with increasing uric acid. Hyperuricemia is at least as effective as proteinuria at identifying gestational hypertensive pregnancies at increased risk. Uric acid should be reexamined for clinical and research utility.

Recommendations for weight gain during pregnancy in the context of the obesity epidemic

The Institute of Medicine and the National Research Council have issued new guidelines for gestational weight gain as well as recommendations for action and research that call for “a radical change in the care provided to women of childbearing age.” For the first time, these guidelines consider the outcomes of both mother and child during and after delivery and the trade-offs between them. The recommendations call for women to begin pregnancy at a healthy weight and to gain within the guidelines, a goal not previously achieved. They also call for individualized preconceptional, prenatal, and postpartum care to help women attain a healthy weight, gain within the guidelines, and return to a healthy weight. Scientific evidence was inadequate to provide specific guidelines by obesity class or to support a public health recommendation to reduce the guidelines below 5-9 kg (11-20 lb) for obese women.

A Diet Quality Index for Pregnancy detects variation in diet and differences by sociodemographic factors.

OBJECTIVE Methods currently used to assess nutritional status during pregnancy have limitations if one wishes to examine the overall quality of the diet. A Diet Quality Index for Pregnancy (DQI-P) was developed to reflect current nutritional recommendations for pregnancy and national dietary guidelines. DESIGN Dietary intake was assessed during the second trimester using a food-frequency questionnaire. The DQI-P includes eight components: % recommended servings of grains, vegetables and fruits, % recommendations for folate, iron and calcium, % energy from fat, and meal/snack patterning score. Scores can range from 0 to 80; each component contributed 10 points. SETTING Two public prenatal clinics in central North Carolina. SUBJECTS N = 2063 pregnant women who participated in the Pregnancy, Infection, and Nutrition (PIN) Study. RESULTS The DQI-P quantitatively differentiated diets. The mean score for the population was 56.0 (standard deviation 12.0). Women who were >30 years old, >350% of poverty, nulliparous and high school graduates had significantly higher overall DQI-P scores. Higher percentages of recommended vegetable servings were consumed by higher-income, older and better-educated women. Greater percentages of recommended intakes of folate and iron were seen among black, low-income and nulliparous women. Higher iron intakes were also seen among women who graduated high school and were less than 30 years old. Other differences were observed for intake of fat and meal/snack pattern. Because this index was based on national recommendations, the DQI-P may be a useful tool for research and public health settings to evaluating overall diet quality of pregnant women.

Nutrient Involvement in Preeclampsia

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed by new-onset increased blood pressure and proteinuria during gestation; for many years these markers were the sole targets for study. More recently, increased attention to the multisystemic nature of the syndrome with involvement of almost all organs, activation of coagulation and increased sensitivity to pressor agents has expanded understanding of the disorder. The epidemiology of preeclampsia, being more common in poor women, long ago suggested that nutrients might be involved in the disorder. Numerous conflicting hypotheses were advanced but the testing of these hypotheses has either been done poorly or not at all. Review of the available data indicates very few studies that provide useful insights. In many studies the syndrome is poorly defined and in most studies nutritional data (questionnaires or biomarkers) are obtained on women with the clinical syndrome. In overtly preeclamptic women it is impossible to decipher cause from effect. Nonetheless, current concepts of the genesis of preeclampsia that include endothelial dysfunction, inflammatory activation, oxidative stress and predisposing maternal factors provide targets for well-designed nutritional investigation. In this review the current concepts of the pathogenesis of preeclampsia are reviewed and available data are assessed in light of these concepts. Targets for nutritional investigation based on the current knowledge of pathophysiology are suggested.

Vitamin D may be a link to black-white disparities in adverse birth outcomes.

In the United States, significant, intractable disparities exist in rates of major pregnancy outcomes between non-Hispanic black and non-Hispanic white women. A previously unexplored candidate influence on the black-white disparity in adverse birth outcomes is maternal vitamin D status. This review summarizes the evidence relating maternal vitamin D to preeclampsia, spontaneous preterm birth, gestational diabetes, and fetal growth restriction, and addresses gaps in our understanding of the contribution of vitamin D to the intractable black-white disparity in these conditions. The literature reviewed highlights strong biologic plausibility of role for vitamin D in the pathophysiology of these poor pregnancy outcomes. Data also suggest that maternal vitamin D deficiency may increase the risk of preeclampsia and fetal growth restriction. Less research has been done in support of relations with spontaneous preterm birth and gestational diabetes, and fetal and infant survival have rarely been studied. Few trials of vitamin D supplementation have been conducted in pregnant women with adequate power to test effects on birth outcomes. Importantly, black pregnant women have rarely been studied in vitamin D—birth outcomes research. Although vitamin D is a promising candidate influence on black-white disparities in preeclampsia, spontaneous preterm birth, fetal growth restriction, and gestational diabetes, these associations require further study in large samples of black US women. Because vitamin D deficiency is widespread and black-white disparities in pregnancy outcomes and infant survival have been resistant to previous interventions, research to test vitamin D as a causal factor is of major public health significance. Target Audience: Obstetricians & Gynecologist, Family Physicians. Learning Objectives: After completion of this educational activity, the reader will be able to appreciate risk factors for inadequate vitamin D status. Understand the basic aspects of vitamin D metabolism. Become aware of recent literature linking inadequate vitamin D status and adverse pregnancy outcomes such as preeclampsia and preterm birth.