Robert S. McDuffie

Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study

Aims/hypothesisTo evaluate whether exposure to maternal gestational diabetes (GDM) is associated with adiposity and fat distribution in a multiethnic population of children.MethodsRetrospective cohort study of 82 children exposed to maternal GDM and 379 unexposed youths 6–13xa0years of age with measured BMI, waist circumference, skinfold thickness, and visceral and subcutaneous abdominal fat.ResultsExposure to maternal GDM was associated with higher BMI (pu2009=u20090.02), larger waist circumference (pu2009=u20090.004), more subcutaneous abdominal fat (pu2009=u20090.01) and increased subscapular to triceps skinfold thickness ratio (pu2009=u20090.01) in models adjusted for age, sex, race/ethnicity and Tanner stage. Adjustment for socioeconomic factors, birthweight and gestational age, maternal smoking during pregnancy and current diet and physical activity did not influence associations; however, adjustment for maternal pre-pregnancy BMI attenuated all associations.Conclusions/interpretationExposure to maternal GDM is associated with increased overall and abdominal adiposity, and a more central fat distribution pattern in 6- to 13-year-old youths from a multi-ethnic population, providing further support for the fetal overnutrition hypothesis.

Amniotic fluid tumor necrosis factor-α and interleukin-1 in a rabbit model of bacterially induced preterm pregnancy loss

OBJECTIVEnThe objective of this study was to determine whether the cytokines tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta were produced in the amniotic fluid of the rabbit after intracervical inoculation with Escherichia coli.nnnSTUDY DESIGNnTimed pregnant rabbits on day 21 (70% of gestation) were inoculated with a hysteroscope intracervically with 10(4) to 10(5) colony-forming units Escherichia coli or sterile saline solution. Escherichia coli-inoculated animals (N = 16) were put to death at 4, 8, 12, and 16 hours after inoculation. Control animals (N = 6) were put to death at similar intervals. At death, cultures were taken from endometrium, amniotic fluid, peritoneum, and blood. Amniotic fluid was collected and assayed for tumor necrosis factor bioactivity by a modified fibroblast cytotoxic assay in L929 cells, for interleukin-1 alpha, and interleukin-1 beta with a specific radioimmunoassay, and for prostaglandin E2 and prostaglandin F2 alpha by radioimmunoassay.nnnRESULTSnLevels of amniotic fluid tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta were elevated as early as 4 hours after inoculation in some animals and by 12 to 16 hours after inoculation in all. Levels of all three cytokines correlated significantly with time from intracervical inoculation with Escherichia coli (p < 0.05). Levels of amniotic fluid prostaglandin E2 and prostaglandin F2 alpha correlated significantly with time from intracervical inoculation with Escherichia coli (p < 0.05).nnnCONCLUSIONSnLevels of tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, prostaglandin E2 and prostaglandin F2 alpha are elevated in the amniotic fluid of rabbits after intracervical inoculation with Escherichia coli. Similarity exists between elevations of amniotic fluid cytokines in this model and in cases of intraamniotic infection and preterm labor unresponsive to tocolytics in humans. Modulation of cytokines may offer a strategy for improvement of outcome in this experimental model of infection-induced pregnancy loss.

Adverse perinatal outcome and resistant enterobacteriaceae after antibiotic usage for premature rupture of the membranes and group B streptococcus carriage

Objective: To report a case series of adverse perinatal outcomes associated with resistant Enterobacteriaceae after antibiotic usage for premature rupture of the membranes (PROM) and group B streptococcus. Methods: Maternal and neonatal records were reviewed of four cases in which adverse perinatal outcomes occurred from resistant Enterobacteriaceae after antibiotic usage for either PROM or positive group B streptococcal cultures. Information on clinical setting, antibiotic usage, maternal and neonatal complications, and maternal and neonatal cultures was noted. Results: All four cases were complicated by PROM at 25‐35 weeks gestation. Ampicillin or amoxicillin was used in several clinical settings, including therapeutically for the presence of group B streptococcus, presumptively for PROM, and prophylactically pending the results of group B streptococcal cultures. Clinical chorioamnionitis subsequently developed in all four cases, and in two cases the maternal course was prolonged and complicated by persistent fever and the need for therapy for pelvic vein thrombophlebitis. Two neonates died from fulminant clinical sepsis. A third infant, one of a twin gestation, was stillborn, presumably because of sepsis. In three cases, neonatal and placental cultures revealed Escherichia coli resistant to ampicillin; in the fourth case, Klebsiella pneumoniae was identified, with only intermediate sensitivity to ampicillin. Conclusion: Resistant Enterobacteriaceae associated with adverse perinatal outcomes may result from the use of antibiotics, such as ampicillin or amoxicillin, after PROM. In deciding whether antibiotic therapy for PROM or group B streptococcal prophylaxis is appropriate, the value of purported benefits must be weighed against presumably infrequent but serious outcomes, including neonatal sepsis and death due to selection or overgrowth of resistant organisms. (Obstet Gynecol 1993;82:487‐9)

Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero

OBJECTIVE To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero. RESEARCH DESIGN AND METHODS Retrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured BMI, waist circumference, skinfolds, visceral (VAT) and subcutaneous (SAT) abdominal fat. A measure of breast milk–months was derived from maternal self-report and used to categorize breastfeeding status as low (<6) and adequate (≥6 breast milk–months). Multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status. RESULTS Adequate (vs. low) breastfeeding status was associated with significantly lower BMI, waist circumference, SAT, and VAT at ages 6–13 years. Among youth in the low breastfeeding category, exposure to diabetes in utero was associated with a 1.7 kg/m2 higher BMI (P = 0.03), 5.8 cm higher waist circumference (P = 0.008), 6.1 cm2 higher VAT (P = 0.06), 44.6 cm2 higher SAT (P = 0.03), and 0.11 higher ratio of subscapular-to-triceps skinfold ratio (P = 0.008). Among those with adequate breastfeeding in infancy, the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant. CONCLUSIONS Adequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero. These data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity.

The long-term impact of intrauterine growth restriction in a diverse U.S. cohort of children: the EPOCH study

To explore the long‐term impact of intrauterine growth restriction (IUGR) among a diverse, contemporary cohort of US children.

The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero : the EPOCH Study

Objective:To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study.Subjects:There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (⩾6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years).Results:ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12–26 months (P=0.02), 4–6 years (P=0.03), 6–9 years (P=0.0001) and 9–13 years of age (P<0.0001).Conclusion:Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

OBJECTIVE To estimate the relationship of assisted reproductive technologies and ovulation‐inducing drugs with preeclampsia in multiple gestations. METHODS This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. RESULTS Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty‐nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P < .05 level. CONCLUSION Women who conceive multiple gestations through assisted reproductive technologies have a 2.1‐fold higher risk of preeclampsia than those who conceive spontaneously.

Assisted reproductive interventions and multiple birth.

Objective To investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth. Methods This historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth. Results There was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35, P < .001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth. Conclusion In this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.

Maternal obesity, gestational weight gain, and offspring adiposity: the exploring perinatal outcomes among children study.

OBJECTIVEnTo determine whether adequate vs excessive gestational weight gain (GWG) attenuated the association between maternal obesity and offspring outcomes.nnnSTUDY DESIGNnData from 313 mother-child pairs participating in the Exploring Perinatal Outcomes among Children study were used to test this hypothesis. Maternal prepregnancy body mass index (BMI) and weight measures throughout pregnancy were abstracted from electronic medical records. GWG was categorized according to the 2009 Institute of Medicine criteria as adequate or excessive. Offspring outcomes were obtained at a research visit (average age 10.4 years) and included BMI, waist circumference (WC), subcutaneous adipose tissue (SAT) and visceral adipose tissue, high-density lipoprotein cholesterol, and triglyceride levels.nnnRESULTSnMore overweight/obese mothers exceeded the Institute of Medicine GWG recommendations (68%) compared with normal-weight women (50%) (P < .01). Maternal prepregnancy BMI was associated with worse childhood outcomes, particularly among offspring of mothers with excessive GWG (increased BMI [20.34 vs 17.80 kg/m(2)], WC [69.23 vs 62.83 cm], SAT [149.30 vs 90.47 cm(2)], visceral adipose tissue [24.11 vs 17.55 cm(2)], and homeostatic model assessment [52.52 vs 36.69], all P < .001). The effect of maternal prepregnancy BMI on several childhood outcomes was attenuated for offspring of mothers with adequate vs excessive GWG (P < .05 for the interaction between maternal BMI and GWG status on childhood BMI, WC, SAT, and high-density lipoprotein cholesterol).nnnCONCLUSIONnOur findings lend support for pregnancy interventions aiming at controlling GWG to prevent childhood obesity.

Fetal meconium peritonitis after maternal hepatitis A

Hepatitis A virus has rarely been implicated in congenital infections. After maternal hepatitis A at 13 weeks gestation, ultrasonographic examinations revealed fetal ascites (20 weeks) and meconium peritonitis (33 weeks). After delivery, a perforated distal ileum was resected. Elevated levels of hepatitis A immunoglobulin G persisted in the infant 6 months after delivery.