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Windham, ME, United States

Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research
Expert Review of Obstetrics and Gynecology | Year: 2013

Despite the lack of consensus among groups issuing recent guidelines, it is possible to identify options that are available for prenatal practitioners. Examples include the following: iodine supplements to protect against hypothyroidism; adjusting l-thyroxine dosage upward in women with previously diagnosed hypothyroidism to account for increased pregnancy needs; and screening for undetected thyroid deficiency via targeted questions and/or thyroid-stimulating hormone testing. Decision-making about thyroid status requires access to reliable, trimester-specific normative data for both thyroid-stimulating hormone and free thyroxine, as well as an understanding of the impact of human chorionic gonadotropin on thyroid function, especially during the first trimester. Continuity of care is enhanced by systematic follow-up postpartum, including attention to postpartum thyroid dysfunction that often occurs among women with raised antibody levels. © 2013 2013 Expert Reviews Ltd. Source

Pinar H.,Brown University | Palomaki G.E.,Brown University | Haddow H.R.M.,Savjani Institute for Health Research | Rowles A.,Brown University | Torabi R.,Brown University
Pediatric and Developmental Pathology | Year: 2014

Identifying growth abnormalities in stillbirths is clinically useful but complicated by maceration. This is an observational study of consecutive postmortem examinations in which femur lengths and gestational age at delivery were collected, along with associated congenital anomalies and extent of fetal maceration. Between 2005 and 2012, 1530 consecutive postmortem examinations were performed and the information recorded. Fragmented fetuses (417), live-born fetuses that survived for more than 24 hours (134), fetuses with any signs of maceration (419), fetuses with known anomalies (98), and records with missing data (249) were excluded. The analyses focused on the remaining 265 nonmacerated stillborn fetuses and infants that survived for less than 24 hours after birth. The relationship between gestational age at delivery and femur length was computed, and a quadratic equation fit the data well between 12 and 40 weeks' gestation (R 5 0.944). Gestational age-specific reference ranges for radiographic femur measurements in stillbirths are equivalent to those for ultrasound-determined measurements in ongoing pregnancies. These reference data may be useful in identifying growth abnormalities in nonmacerated stillborn fetuses. © 2014 Society for Pediatric Pathology. Source

March M.I.,Beth Israel Deaconess Medical Center | Geahchan C.,Beth Israel Deaconess Medical Center | Wenger J.,Harvard University | Raghuraman N.,Beth Israel Deaconess Medical Center | And 12 more authors.
PLoS ONE | Year: 2015

Objective: Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE. Material and Methods: We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions. Results: Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome. Conclusion: PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation. © 2015 March et al. Source

Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research | Craig W.Y.,Foundation for Blood Research | Palomaki G.E.,Brown University | And 8 more authors.
Thyroid | Year: 2013

Background: Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m2) than in the overall study population. We explore this relationship further. Methods: Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4 relationship; (ii) percentages of women in three weight categories at each FT4 decile; (iii) FT4 concentrations in three weight categories at each TSH decile; and (iv) impact of adjusting FT4 for weight-in the reference group and in 190 additional women with elevated TSH measurements. Results: FT4 values decrease steadily as weight increases (p<0.0001 by ANOVA) among women in the reference group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy; the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is lowest in heaviest women regardless of the TSH level. In the reference group, weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment places more light weight women and fewer heavy women below the 5th FT4 centile; the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4 percentage below the 5th FT4 centile is not elevated (3.8% before adjustment, 3.1% after adjustment). Percentage of FT4 values above the 95th centile, however, is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25% of women have FT4 values below the 5th FT4 centile; weight adjustment raises this to 30%; no FT4 values remain above the 95th FT4 centile. Conclusions: During early pregnancy, TSH values are not associated with weight, unlike nonpregnant adults. Lower average FT4 values among heavy women at all TSH deciles partially explain interindividual differences in FT4 reference ranges. The continuous reciprocal relationship between weight and FT4 explains lower FT4 with higher weight. Weight adjustment refines FT4 interpretation. © 2013, Mary Ann Liebert, Inc. Source

Palomaki G.E.,Brown University | Palomaki G.E.,Savjani Institute for Health Research | Kloza E.M.,Savjani Institute for Health Research | Lambert-Messerlian G.M.,Brown University | And 7 more authors.
Prenatal Diagnosis | Year: 2015

Objective: The proportion of circulating cell free DNA derived from the feto-placental unit (fetal fraction or FF) correlates with test success and interpretation reliability. Some fetal disorders are associated with systematically lower FF, sometimes resulting in noninformative results. Methods: We analyzed results from pregnancies tested in a nested case/control study derived from a cohort of 4664 high-risk pregnancies. Low FF was defined before and after adjusting for maternal weight and gestational age. Results: Compared with euploid pregnancies, the median FF was significantly higher in Down syndrome pregnancies (ratio 1.17) and significantly lower in trisomy 18 and triploid pregnancies (ratios 0.71 and 0.19, respectively). Among 2157 pregnancies tested, 13 (0.6%) had FF <3.0% (all noninformative), including three trisomy 18 and three triploidy fetuses. After adjustment, 16 pregnancies (0.7%) had FF <0.3 multiples of the median (six informative), including one trisomy 18 and three triploidy fetuses. Modeled positive predictive values for low and high-risk populations were 7% and 30%, respectively. Conclusion: Among women with noninformative results attributable to low FF, trisomy 18 and/or triploidy risk are sufficiently high to warrant offering additional assessments (e.g. ultrasound). If the testing indication is ultrasound abnormality, amniocentesis and karyotype/microarray should be considered. © 2014 John Wiley & Sons, Ltd. Source

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