Cervical pathways for racial disparities in preterm births: the Preterm Prediction Study.

Purpose: Racial disparities in preterm birth have been long recognized, but the social and biological mechanisms for these differences are unclear. Our analysis had three goals: (1) to determine the relation between race and other social risk factors and cervical structure; (2) to determine whether social factors mediate the relation between race and cervical structure; and (3) to determine whether racial disparities in preterm birth (PTB) are mediated through changes in cervical structure observed earlier in pregnancy. Materials and methods: Data from the Maternal Fetal Medicine Unit network Preterm Prediction Study were used to examine the relation between race and other social factors and cervical properties throughout pregnancy in 2920 black and white women. Outcomes included cervical length and dilation; cervical score (cervical length-internal dilation); and whether membranes protruded at 22-24 and 26-29 weeks. Race, education, income, insurance type, and marital status were examined as predictors of the outcomes using linear and logistic regression, adjusting for age, BMI, parity, and smoking. Mediation analysis was used to examine whether (a) any social factors explained racial differences in cervical properties, and (b) whether cervical properties mediated racial differences in risk for preterm birth. Results: Shorter cervical length, especially at a subject's first visit, was associated with black race (adjusted beta -1.56 mm, p < .01) and lower income (adjusted beta -1.48, p =.05). External dilation was not associated with social factors, while internal dilation was associated with black race and lower education. Black race and marital status were associated with lower cervical score. There was no evidence of mediation of the racial effect on cervical properties by any social factor. Shorter cervical length, dilation, and score were all associated with preterm birth (p < .01). Mediation analysis indicated that each of these mediated the effect of race, but explained a small proportion of the total effect (15-25%). Conclusions: Race, and, to a lesser extent, other social factors are correlated with adverse cervical properties. This pathway could explain a proportion of the racial disparity in preterm birth.

How to correct the impact of ethnicity on effectiveness of the second trimester maternal serum screen of fetal Down syndrome?

Objectives: To compare the performance of second trimester maternal serum screen (MSS) for fetal Down syndrome in Thai population between the conventional method using Caucasian reference ranges with ethnic factor correction (CRR-EC) and the method using specific Thai reference ranges (TRRs). Methods: A prospective database of the MSS project was accessed. The concentrations of alpha fetoprotein (AFP), beta-hCG, and uE3 were converted to their multiple of medians (MoMs) by two methods; CRR-EC for Asian women and TRR. The detection rate and false positive rate derived from the two methods were compared. Results: Of 20,229 cases, 35 women had fetal Down syndrome. The detection rates of both methods were comparable, whereas the false-positive rate of TRR was significantly lower (8.8 versus 11.7%; p < .001). The improvement was mainly caused by more accuracy of the MoMs of beta-hCG, not AFP/uE3, based on TRR. Conclusions: The effectiveness of MSS could be improved by using our own reference ranges instead of using ethnic factor correction. With TRR, the false-positive rate or the number of invasive diagnoses could be significantly decreased without compromise of the detection rate. To improve MSS performance, each population should use its own reference ranges.

Vitamin D deficiency and supplementation in pregnancy in a multiethnic population-based cohort.

BACKGROUND: To investigate ethnic differences in vitamin D levels during pregnancy, assess risk factors for vitamin D deficiency and explore the effect of vitamin D supplementation in women with deficiency in early pregnancy. METHODS: This is a population-based, multiethnic cohort study of pregnant women attending Child Health Clinics for antenatal care in Oslo, Norway. Serum-25-hydroxyvitamin D [25(OH)D] was measured in 748 pregnant women (59% ethnic minorities) at gestational weeks (GW) 15 (SD:3.6) and 28 (1.4). Women with 25(OH)D <37 nmol/L at GW 15 were for ethical reasons recommended vitamin D3 supplementation. Main outcome measure was 25(OH)D, and linear regression models were performed. RESULTS: Severe deficiency (25(OH)D <25 nmol/L) was found at GW 15 in 45% of women from South Asia, 40% from the Middle East and 26% from Sub-Saharan Africa, compared to 2.5% in women from East Asia and 1.3% of women from Western Europe. Women from South Asia, the Middle East and Sub-Saharan Africa had mean values that were -28 (95 % CI:-33, -23), -24 (-29, -18) and -20 (-27, -13) nmol/L lower than in Western women, respectively. Ethnicity, education, season and intake of vitamin D were independently associated with 25(OH)D. At GW 28, the mean 25(OH)D had increased from 23 (SD:7.8) to 47 (27) nmol/L (p < 0.01) in women who were recommended vitamin D supplementation, with small or no change in women with sufficient vitamin D levels at baseline. CONCLUSIONS: Vitamin D deficiency was prevalent among South Asian, Middle Eastern and African women. The serum levels of 25(OH)D increased significantly from GW 15 to 28 in vitamin D deficient women who received a recommendation for supplementation. This recommendation of vitamin D supplementation increased vitamin D levels in deficient women.

Epidemiology of Dysglycemia in Pregnant Oklahoma American Indian Women.

CONTEXT: Minority communities are disproportionately affected by diabetes, and minority women are at an increased risk for glucose intolerance (dysglycemia) during pregnancy. OBJECTIVES: In pregnant American Indian women, the objectives of the study were to use current criteria to estimate the prevalence of first-trimester (Tr1) dysglycemia and second-trimester (Tr2) incidence of gestational diabetes mellitus (GDM) and to explore new candidate measures and identify associated clinical factors. DESIGN: This was a prospective cohort study. In Tr1 we performed a 75-g, 2-hour oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) to determine the following: fasting insulin; homeostasis model assessment of insulin resistance; serum 1,5-anhydroglucitol; noninvasive skin autofluorescence (SCOUT). We defined dysglycemia by American Diabetes Association and Endocrine Society criteria and as HbA1c of 5.7% or greater. In Tr2 in an available subset, we performed a repeat OGTT and SCOUT. PARTICIPANTS: Pregnant American Indian women (n = 244 at Tr1; n = 114 at Tr2) participated in the study. OUTCOMES: The prevalence of dysglycemia at Tr1 and incidence of GDM at Tr2 were measured. RESULTS: At Tr1, one woman had overt diabetes; 36 (15%) had impaired glucose tolerance (American Diabetes Association criteria and/or abnormal HbA1c) and 59 (24%) had GDM-Tr1 (Endocrine Society criteria). Overall, 74 (30%) had some form of dysglycemia. Associated factors were body mass index, hypertension, waist/hip circumferences, SCOUT score, fasting insulin, and homeostasis model assessment of insulin resistance. At Tr2, 114 of the Tr1 cohort underwent a repeat OGTT and SCOUT, and 26 (23%) had GDM. GDM-Tr2 was associated with increased SCOUT scores (P = .029) and Tr1 body mass index, waist/hip circumferences, diastolic blood pressure, fasting insulin, and triglyceride levels. Overall, dysglycemia at Tr1 and/or Tr2 affected 38% of the women. CONCLUSIONS: Dysglycemia at some point during pregnancy was common among American Indian women. It was associated with features of insulin resistance and may confer long-term health risks for mother and child.

The fetal frontomaxillary facial angle in normal and trisomy 21 ultrasounds at 11-13(+6) weeks of gestation: findings among the ethnic Chinese compared with Caucasian.

OBJECTIVE: The aim of this research was to compare the fetal frontomaxillary facial (FMF) angle between normal and trisomy 21 fetuses at 11(+0) -13(+6) weeks gestation in a Chinese population. METHODS: A prospective observational study was performed that included 640 euploid and 45 trisomy 21 singleton pregnancies undergoing first trimester ultrasound screening between 11 and 13(+6) weeks of gestation. The FMF angle was measured in the midsagittal plane using the standard technique. RESULTS: The fetal mean FMF angle decreased with the increasing crown-rump length (CRL) from 88.6°at a CRL of 45 mm to 78.5° at a CRL of 84 mm (FMF angle = 100.212 - 0.258 × CRL, R(2) = 0.222, p < 0.001). The overall mean FMF angle in the euploid population was 82.9° ± 4.1° and in trisomy 21 cases, 92.3° ± 5.2°. CONCLUSIONS: Fetal FMF angle is affected by gestational age in a Chinese population, although it remains a significant predictor of fetal trisomy 21.

Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes.

OBJECTIVE: To assess changes in insulin resistance and ß-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 months post partum and relate the findings to gestational diabetes mellitus (GDM). METHOD: Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 months post partum (V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-ß (ß-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide. RESULT: Characteristics were comparable across ethnic groups, except age (South Asians: younger, P<0.001) and prepregnant BMI (East Asians: lower, P=0.040). East and South Asians were more insulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in ß-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their ß-cell function increased significantly less and the percentage increase in ß-cell function did not match the change in insulin resistance. CONCLUSION: Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-ß-cell function than Western Europeans.

Second trimester maternal plasma levels of cytokines IL-1Ra, Il-6 and IL-10 and preterm birth.

OBJECTIVE: To examine the interaction of the cytokines interleukin-1 receptor antagonist (IL)-1Ra, IL-6 and IL-10 to predict preterm birth (PTB) in pregnant Hispanic women (n=470). STUDY DESIGN: In this prospective study, demographic data were obtained prenatally and birth outcome data were obtained from the medical chart. Cytokines were measured from plasma obtained at 22 to 24 weeks gestation. Data analysis utilized logistic regression. RESULT: PTB was predicted by level of IL-1Ra (odds ratio (OR)=2.55; 95% confidence interval (CI)=1.24, 5.24). The interaction between IL-1Ra and IL-6 and between IL-1Ra and IL-10 was significant (Wald=4.01, P=0.04 and Wald=8.84, P<0.003, respectively) and was also predictive of PTB. As IL-1Ra levels increased while IL-10 levels were low, the probability of PTB greatly increased. CONCLUSION: The interactions of select cytokines and cytokine receptor antagonists were associated with PTB. Future research should focus on the changes in cytokines during pregnancy to identify critical periods of change, and examine predictors of the cytokine response.

The value of early second trimester PAPP-A and ADAM12 in screening for pre-eclampsia.

OBJECTIVE: To estimate the pre-eclampsia screening performance of PAPP-A (pregnancy-associated plasma protein-A) and ADAM12 (A Disintegrin And Metalloprotease 12) in the early second trimester of pregnancy. METHODS: Stored frozen serum samples from a previously published nested case-control study comprising 77 women who developed pre-eclampsia and 224 unaffected controls were thawed and assayed for PAPP-A and ADAM12. Levels were converted into multiple of the unaffected median (MoM) values. RESULTS: Neither PAPP-A or ADAM12 were significantly different in women who developed pre-eclamspia compared with unaffected controls (PAPP-A: 0.97 MoM [95% confidence interval 0.73 to 1.25], ADAM12: 1.01 MoM [0.91 to 1.13]). CONCLUSION: Our results do not support the use of PAPP-A or ADAM12 in early second trimester antenatal screening for pre-eclampsia.

Fatty acid composition of mid-trimester amniotic fluid in women of different ethnicities.

OBJECTIVE: To determine whether the fatty acid composition of mid-trimester amniotic fluid differs by ethnicity and pregnancy outcome. METHODS: Fatty acid composition was analyzed by gas chromatography in 198 women undergoing amniocentesis at 15-19 weeks gestation. Cytokine levels were determined by ELISA in a subgroup of 52 subjects. RESULTS: The major fatty acids detected were palmitic acid (31.8%) and stearic acid (31.5%). The n-6 polyunsaturated fatty acids (PUFA), linoleic acid (LA, 18:2) and arachidonic acid (AA, 20:4), were 11.3%, while the n-3 PUFA fatty acids, α linolenic acid (ALA, 18:3) and docosahexaenoic acid (DHA, 22:6), were 3.8% of the total. Palmitic acid was a higher percentage in Asians (40.5%) and Whites (34.5%) than in Blacks (22.2%) and Hispanics (23.7%) (p ≤ 0.0012). Oleic acid (18:1 n-9) was a higher percentage in Blacks (12.2%) and Hispanics (12.1%) than in Whites (9.2%) or Asians (7.5%) (≤0.0002). LA and AA were higher in Blacks (9.0%, 5.4%) and Hispanics (8.6%, 4.1%) than in Whites (6.1%, 3.7%) and Asians (5.5%, 2.9%) (p ≤ 0.0002). DHA did not differ among the ethnic groups or according to pregnancy outcome. A reduced palmitic acid percentage was identified in the six women with preeclampsia (p = 0.0233). Tumor necrosis factor-α levels were inversely proportional to the palmitic acid percentage (p = 0.0275) and positively associated with the percentages of stearic (18:0) (p = 0.0132) and oleic (p = 0.0290) acids. CONCLUSIONS: Amniotic fluid fatty acid composition differed among the ethnic groups and may influence inflammatory mediator production and susceptibility to preeclampsia.

Cumulative stress and maternal prenatal corticotropin-releasing hormone in an urban U.S. cohort.

BACKGROUND: To date, there have been conflicting reports of the association of psychosocial stressors with prenatal corticotropin-releasing hormone (CRH) levels. METHODS: We examined whether racial discrimination, community violence, interpersonal violence (IPV), negative life events, considered independently, and as a composite measure of cumulative stress, were associated with prenatal CRH levels in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a multiethnic pre-birth cohort in urban Boston. Blood was collected between 20 and 37 weeks gestation (Mean=28.1, SD=4.6 weeks gestation). During pregnancy, women were administered the Conflict Tactics Scale survey to assess IPV, the Crisis in Family Systems-Revised survey to assess negative life events, the My Exposure to Violence survey to assess community violence, and the Experiences of Discrimination survey. A cumulative stress measure was derived from these instruments to characterize exposure to high levels of multiple stressors. RESULTS: None of the individual stressors or cumulative stress was associated with CRH in combined analyses including Whites (n=20), Blacks (n=46), and Hispanics (n=110). In separate analyses of Blacks and Hispanics, racial discrimination, community violence, and cumulative stress were associated with CRH in Blacks, but were not associated with CRH in Hispanics. CONCLUSIONS: Though these results require replication, they suggest that the effects of stress on prenatal CRH levels may be mediated by factors that differ between racial/ethnic groups. Further studies in larger samples are warranted to clarify whether associations of chronic stressors and prenatal CRH levels differ by race/ethnicity and to better understand underlying mechanisms.

Normal ranges of fetal nasal bone length during the second trimester in an Iranian population.

OBJECTIVE: To provide a normal reference range for nasal bone length (NBL) during the second trimester of pregnancy in an Iranian population. METHODS: This cross-sectional study was performed on 3201 fetuses at 15 to 28 weeks of gestational age (GA). Both singleton and twin fetuses were evaluated. The relationship between NBL and GA was determined and percentile values for each gestational week were provided. RESULTS: NBL measurement was obtained in 98% of singleton and 96% of twin fetuses. There was a linear relationship between GA and NBL both in singleton (R(2) = 0.62) and in twin (R(2) = 0.74) fetuses. There was no significant difference between twins regarding NBL (p = 0.18). CONCLUSION: We have provided the normal reference range for NBL during the second trimester in an Iranian population. NBL in singleton and twin fetuses is similar and there is no significant difference between twins regarding NBL.

Gestational weight gain and subsequent postpartum weight loss among young, low-income, ethnic minority women.

OBJECTIVE: Document weight change trajectories that lead to gestational weight gain or postpartum weight loss outside clinical recommendations established by the Institute of Medicine. STUDY DESIGN: Women aged 14-25 receiving prenatal care and delivering singleton infants at term (n = 427). Medical record review and 4 structured interviews conducted: second and third trimester, 6- and 12-months postpartum. Longitudinal mixed modeling to evaluate weight change trajectories. RESULTS: Only 22% of participants gained gestational weight within Institute of Medicine guidelines. There were 62% that exceeded maximum recommendations-more common among those overweight/obese (body mass index ≥25.0; P < .0001). 52% retained ≥10 lb 1-year postpartum. Increased weight gain and retention documented among smokers and women with pregnancy-induced hypertension; breastfeeding promoted postpartum weight loss (all P < .02). Body mass index by race interaction suggested healthier outcomes for Latinas (P = .02). CONCLUSION: Excessive pregnancy weight gain and inadequate postpartum weight loss are highly prevalent among young low-income ethnic minority women. Pregnancy and postpartum are critical junctures for weight management interventions.

Effect of Hispanic ethnicity on interpretation of maternal serum screening.

Maternal serum concentrations of alpha-fetoprotein (MSAFP), unconjugated estriol (uE3) and human chorionic gonadotropin (hCG) were measured in the sera of 3,046 Hispanic women and of 15,154 Caucasian women from gestational weeks 14 through 20 between January 1990 and December 1995. Median values for analytes were calculated for each gestational week and the two ethnic groups compared. Our findings indicate that the median values for Hispanics are lower for MSAFP and hCG, but higher for estriol. These differences are not accounted for by differences in median weights of the two ethnic groups. Although these results would suggest that Hispanic women at risk for a fetus with a neural tube defect (NTD) may be missed when cut-offs derived from a Caucasian population are used, in fact, that was not the case in our screening population. However, a disproportionate number of Hispanic women may be identified with an abnormal serum screening test unrelated to a risk for neural tube defects. This does not infer that detection rates are different across different ethnic groups since other factors are involved. Adjustment of medians for Hispanic ethnicity may have a small but significant effect, especially with regard to low values.