50 Years Ago in The Journal of Pediatrics Turner's Syndrome in the Male.
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ABSTRACT: To determine the incidence, risk factors and need for surgery for retinopathy of prematurity (ROP) among very-low-birth-weight (VLBW) infants. This was a retrospective study of all VLBW infants managed by the department over 14 years, from 1988 to 2001. Preterm infants were examined according to the Royal College of Ophthalmologists' guidelines, and retinopathy was graded following the International Classification of ROP. All VLBW infants examined for ROP were included and data were retrieved retrospectively and analysed for maternal, medical, obstetric and neonatal risk factors using logistic regression. Of the 564 VLBW infants who fit the screening criteria, ROP was detected in 165 (29.2%) of VLBW infants; of whom 49% of infants had stage 1 disease, 24% were at stage 2, and 27% were at stage 3 or more. Among 45 infants with stage 3 disease or more, treatment was needed in 62.2% (28/45). No ROP was detected in infants greater than 33 weeks of gestation. Only 0.6 % (1/164) of infants greater than 30 weeks of gestational age (GA) needed surgery for ROP. Using birth weight (BW) criteria, stage 3 ROP was noted only in 1% (6/564) of infants with BW >1000 g. Of all ROP requiring surgery, 89% (25/28) of infants were <1000 g as compared to 11% (3/28) who were >1000 g infants. The median age of onset of ROP was 35 weeks (range, 31 to 41) corrected age. By univariate analysis for threshold ROP, preeclampsia, prenatal betamethasone exposure, gestational age, birth weight, 1-minute Apgar score, hyaline membrane disease (HMD), surfactant usage, hypotension, septicaemia, intraventricular haemorrhage duration of supplemental oxygen, ventilation and chronic lung disease were associated with ROP requiring surgery (i.e., threshold ROP, P <0.05). However, using multiple logistic regression analyses for ROP, maternal preeclampsia [odds ratio (OR), 2.52; confidence interval (CI), 1.32 to 4.7], birth weight (OR, 0.99; CI, 0.996 to 0.999), pulmonary haemorrhage (OR, 4.61; CI, 1.04 to 20.4), duration of ventilation (OR, 1.06; CI, 1.04 to 1.08) and duration of continuous positive airway pressure (CPAP) (OR, 1.02; CI, 1.01 to 1.04) were factors predictive of development of threshold ROP. The incidence of ROP among VLBW infants was 29.2%. ROP was strongly associated with smaller, more immature and sicker infants. The median age of onset of ROP was 35 weeks (range, 31 to 40 weeks) postmenstrual age. Infants <30 weeks of GA and/or infant with BW <1000 g are at considerable risk for threshold ROP. The main risk factors for development of threshold ROP by regression analysis are maternal preeclampsia, birth weight, and presence of pulmonary haemorrhage, duration of ventilation and continuous positive pressure ventilation. We suggest that both immaturity and compromised pulmonary function are both important aetiological factors in the development of ROP. Prevention of prematurity, control of preeclampsia, judicious use of ventilation and oxygen therapy are the only promising factors that may reduce the incidence and severity of ROP in this high-risk infant.Annals of the Academy of Medicine, Singapore 03/2005; 34(2):169-78. · 1.36 Impact Factor
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ABSTRACT: The predominant etiologic theory of preeclampsia is that reduced uteroplacental perfusion is the unique pathogenic process in the development of preeclampsia. Decreased uteroplacental blood flow would result in lower birth weights. To date, no study has assessed the effect of preeclampsia on birth weight by gestational age. Thus, the authors conducted a retrospective cohort study based on 97,270 pregnancies that resulted in delivery between 1991 and 1996 at 35 hospitals in northern and central Alberta, Canada. Differences in mean birth weight between women with preeclampsia and normotensive women ranged from -547.5 g to 239.5 g for gestational age categories ranging from < or = 32 weeks to > or = 2 weeks. The birth weights were statistically significantly lower among mothers with preeclampsia who delivered at < or = 37 weeks, with an average difference of -352.5 g. However, the birth weights were not lower among preeclamptic mothers who delivered after 37 weeks (average difference of 49.0 g). In Alberta, 61.2% of preeclamptic patients gave birth after 37 weeks of gestation. The authors conclude that babies born to mothers with preeclampsia at term have fetal growth similar to that of babies born to normotensive mothers. This finding does not endorse the currently held theory that reduced uteroplacental perfusion is the unique pathophysiologic process in preeclampsia.American Journal of Epidemiology 02/2002; 155(3):203-9. · 4.78 Impact Factor
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ABSTRACT: Retinopathy of prematurity (ROP) is a major cause of blindness in children in developed countries. ROP is a two-phase disease, beginning with delayed retinal vascular growth after premature birth (Phase I). Phase II follows when Phase I-induced hypoxia releases factors to stimulate new blood vessel growth. Both oxygen-regulated and non-oxygen-regulated factors contribute to normal vascular development and retinal neovascularization. Vascular endothelial growth factor (VEGF) is an important oxygen-regulated factor. A critical non-oxygen-regulated growth factor is insulin-like growth factor-I (IGF-I). In knockout mice, lack of IGF-I prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF-I levels prevent VEGF-induced activation of Akt, a kinase critical for vascular endothelial cell survival. We found that premature infants who develop ROP have low levels of serum IGF-I compared to age-matched infants without disease. IGF-I is critical to normal vascular development. Low IGF-I predicts ROP in premature infants, and restoration of IGF-I to normal levels might prevent ROP.Growth Hormone & IGF Research 07/2004; 14 Suppl A:S140-4. · 2.26 Impact Factor
25. Holmstrom G, Thomassen P, Broberger U. Maternal risk factors for ret-
26. Shah VA, Yeo CL, Ling YL, Ho LY. Incidence, risk factors of retinopathy
of prematurity among very low birth weight infants in Singapore. Ann
Acad Med Singapore 2005;34:169-78.
Study Group. Eur J Pediatr 1997;156:939-43.
29. Xiong X, Demianczuk NN, Saunders LD, Wang FL, Fraser WD. Impact
of preeclampsia and gestational hypertension on birth weight by gesta-
tional age. Am J Epidemiol 2002;155:203-9.
30. Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol
31. Hellstrom A, Perruzzi C, Ju M, Engstrom E, Hard AL, Liu JL, et al. Low
IGF-I suppresses VEGF-survival signaling in retinal endothelial cells:
direct correlation with clinical retinopathy of prematurity. Proc Natl
Acad Sci U S A 2001;98:5804-8.
32. Hellstrom A, Carlsson B, Niklasson A, Segnestam K, Boguszewski M,
de LL, et al. IGF-I is critical for normal vascularization of the human ret-
ina. J Clin Endocrinol Metab 2002;87:3413-6.
33. Hellstrom A, Engstrom E, Hard AL, bertsson-Wikland K, Carlsson B,
is associatedwith retinopathy ofprematurityandother complicationsof
premature birth. Pediatrics 2003;112:1016-20.
34. Ferrazzi E, Bellotti M, Galan H, Pennati G, Bozzo M, Rigano S, et al.
Doppler investigation in intrauterine growth restriction–from qualita-
tive indices to flow measurements: a review of the experience of a collab-
orative group. Ann N Y Acad Sci 2001;943:316-25.
35. Soares CR, Silveira RC, Procianoy RS. Ophthalmic artery blood flow in
very-low-birth-weight preterm infants. Invest Ophthalmol Vis Sci 2010;
50 Years Ago in THE JOURNAL OF PEDIATRICS
Turner’s Syndrome in the Male
Steiker DD, Mellman MJ, Bongionvanni AM, Eberlein WR, Leboeuf G. J Pediatr 1961;58:321-9
drome (TS) were ‘‘chromatin negative’’ emerged only 7 years before this report. Using the ‘‘nuclear sexing’’ sys-
tem, the interpretation of the absence of Barr bodies (sex chromatin), based on the 1947 Jost experiments in rabbits,
was that individuals with TS were genetic males who had undergone prenatal castration resulting in female genitalia
with an abnormal genotype rather than a ‘‘chromosomal male’’ or case of ‘‘sex reversal’’ appeared only 2 years before
Steiker et al reported their five cases of apparent TS in males. Thus, it is easy to understand their confusion regarding
the relationship between these boys and the classic triad of sexual infantilism, congenital webbed neck, and cubitus
valgus that comprisedthe initial description of girls with TS. Not only is a female phenotypenow part of its definition,
but the manifestations of TS are believed to be primarily caused by haploinsufficiency of one or more of the multitude
of genes on the X chromosome, such as SHOX.
A likely candidate forwhat was presumed male Turnersyndrome is Noonan syndrome,which is caused by PTPN11
deletions in ?50% of cases. Although one or more of the five boys probably had Noonan syndrome, it is unlikely that
they all did, given the disparate phenotypes. Distinguishing among children with overlapping features such as short
stature, abnormal auricles, high arched palate, low posterior hairline, and short or webbed neck was surely a challenge
50 years ago, and, despite advances in molecular and clinical genetics, sometimes remains one to this day. The authors
are to be commended for attempting to reconcile a bewildering set of observations, causing them to go so far as to
suggest that the features of TS were unrelated to the emblematic chromosomal pattern. This insinuation might
seem preposterous to us today, but we should remember the importance of an open mind and consider every conceiv-
able explanation for our findings until the inexorable process of scientific discovery allows the ‘‘truth’’ to become
lthough described clinically more than two decades earlier, the recognition that most patients with Turner syn-
Erica A. Eugster, MD
Alan D. Rogol, MD, PhD
Riley Hospital for Children
THE JOURNAL OF PEDIATRICS
Vol. 158, No. 3
Fortes Filho et al