Changes in pre-pregnancy weight and weight gain during pregnancy: retrospective comparison between 1986 and 2004

QUESTIONS UNDER STUDY: To compare the incidence of pre-pregnancy overweight, obesity, and difference in weight gain during pregnancy in the years 1986 and 2004, in women delivered at the maternity unit of our hospital. METHODS: Retrospective study. Maternity records of patients delivered in the years 1986 and 2004 were compared. Data extraction included booking weight, height, weight gain, birth weight as well as information on mode of delivery and gestational age at delivery. RESULTS: During the year 1986 and 2004 a total of 690 and 668 patients respectively were included in the analysis. The pre-pregnancy BMI > or =25 doubled over the 18-year period (from 15.9 to 30.1%). In 1986 only 2.6% of all pregnant women gained more than 20 kg, while in 2004 14.2% (p <0.0001) did so. The caesarean section rate was significantly higher in 2004 than 18 years earlier (28.3 and 9.3%, p <0.0001). CONCLUSIONS: We found a significant increase in all parameters between these two groups. Pregnant women are today heavier at the booking visit, are more overweight, and gain more weight during pregnancy. A similar trend is seen in the newborn babies, who have a higher birth weight than those born 18 years ago.

Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene

CONTEXT: Thyroid transcription factor 1 (TITF1/NKX2.1) is expressed in the thyroid, lung, ventral forebrain, and pituitary. In the lung, TITF1/NKX2.1 activates the expression of genes critical for lung development and function. Titf/Nkx2.1(-/-) mice have pituitary and thyroid aplasia but also impairment of pulmonary branching. Humans with heterozygous TITF1/NKX2.1 mutations present with various combinations of primary hypothyroidism, respiratory distress, and neurological disorders. OBJECTIVE: The objective of the study was to report clinical and molecular studies of the first patient with lethal neonatal respiratory distress from a novel heterozygous TITF1/NKX2.1 mutation. Participant: This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3,460 g and Apgar scores were normal. Soon after birth, she developed acute respiratory failure with pulmonary hypertension. At neonatal screening on the second day of life, TSH was 31 mU/liter (N <15) and total T(4) 245 nmol/liter (N = 120-350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day. RESULTS: Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient's lymphocyte DNA revealed a novel heterozygous TITF1/NKX2.1 mutation (I207F). This mutation was not found in either parent. In vitro, the mutant TITF-1 had reduced DNA binding and transactivation capacity. CONCLUSION: This is the first reported case of a heterozygous TITF1/NKX2.1 mutation leading to neonatal death from respiratory failure. The association of severe unexplained respiratory distress in a term neonate with mild primary hypothyroidism is the clue that led to the diagnosis.

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.

Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy.

We identified a new point mutation in the CYP19 gene responsible for aromatase (P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated protein that is inactive due to the absence of the functional regions of the enzyme. Aromatase deficiency was suspected prenatally because of the severe virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum estrogens, but had a normal level of serum free testosterone; in comparison with the high serum concentration of androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard GnRH stimulation tests were normal. This finding suggests that the contribution of estrogen to the hypothalamic-pituitary gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum estradiol concentrations strongly correlate with circulating inhibin levels, and thus, low inhibin levels may contribute to the striking elevation of FSH in young girls with aromatase deficiency. In contrast, estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum inhibin levels remain elevated even though levels of FSH, LH, and testosterone are decreased.

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER NCT02164604 ; Date of registration: 13.06.2014.

Outcome in neonates with necrotizing enterocolitis and patent ductus arteriosus.

BACKGROUND There is no agreement of the influence of patent ductus arteriosus (PDA) on outcomes in patients with necrotizing enterocolitis (NEC). In this study, we assessed the influence of PDA on NEC outcomes. METHODS A retrospective study of 131 infants with established NEC was performed. Outcomes (death, disease severity, need for surgery, hospitalization duration), as well as multiple clinical parameters were compared between NEC patients with no congenital heart disease (n=102) and those with isolated PDA (n=29). Univariate, multivariate and stepwise logistic regression analyses were performed. RESULTS Birth weight and gestational age were significantly lower in patients with PDA [median (95% CI): 1120 g (1009-1562 g), 28.4 wk (27.8-30.5 wk)] than in those without PDA [median (95% CI): 1580 g (1593-1905 g), 32.4 wk (31.8-33.5 wk); P<0.05]. The risk of NEC-attributable fatality was higher in NEC patients with PDA (35%) than in NEC patients without PDA (14%)[univariate odds ratio (OR)=3.3, 95% CI: 1.8-8.6, P<0.05; multivariate OR=2.4, 95% CI: 0.82-2.39, P=0.111]. Significant independent predictors for nonsurvival within the entire cohort were advanced disease severity stage III (OR=27.9, 95% CI: 7.4-105, P<0.001) and birth weight below 1100 g (OR=5.7, 95% CI: 1.7-19.4, P<0.01). CONCLUSIONS In patients with NEC, the presence of PDA is associated with an increased risk of death. However, when important differences between the two study groups are controlled, only birth weight and disease severity may independently predict mortality.

Incidence of preeclampsia in pregnant Swiss women.

QUESTION UNDER STUDY The epidemiology of preeclampsia in Switzerland is known only from a retrospective registry study. This analysis aimed to prospectively determine the incidence of preeclampsia in a cohort of pregnant women in Switzerland. METHODS Pregnant women presenting at gestational week 11-14 at their obstetrician's office were consecutively included and prospectively followed-up until the end of pregnancy. Ultrasound characteristics, blood pressure measurements, body mass index, and personal history were recorded. Duration of pregnancy, occurrence of preeclampsia, birth weight and Apgar scores were recorded as outcomes. RESULTS There were 1,300 pregnancies with follow-up available for analysis. Median age was 30 years (interquartile range [IQR] 27-33), median body mass index (BMI) 23.3 kg/m² (IQR 21.2-26.1), median systolic blood pressure 117 mm Hg (IQR 109-126) and median diastolic blood pressure 70 mm Hg (IQR 64-77). A total of 30 women developed preeclampsia, corresponding to an incidence of 2.31% (95% confidence interval [CI] 1.62%-3.28%). Of the women with preeclampsia, 6.66% (95% CI 2.04%-21.42%) had early-onset preeclampsia, 13.33% (95% CI 5.45%-29.83%) progressed to eclampsia, whereas 10% (95% CI 3.63%-28.75%) developed HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count). Nulliparity and prior history of preeclampsia were more frequently seen in pregnancies with preeclampsia than in pregnancies without preeclampsia. BMI, as well as systolic and diastolic blood pressure were higher in pregnancies subsequently developing preeclampsia. CONCLUSION The incidence of preeclampsia in Switzerland is in line with frequencies observed elsewhere in the world. Extrapolation to a national level indicates that about 1,911 (range 1,340-2,713) preeclampsia cases per year can be expected to occur in Switzerland.

A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents.