Should the sex of the fetus be considered when administering antenatal corticosteroids to preterm fetuses?

AIM: We aimed to determine whether the effect of antenatal corticosteroids (ANS) differs in male and female fetuses without anomalies born before 32 weeks in terms of mortality and short-term morbidity. METHODS: This single-center retrospective study included infants born before 32 weeks' gestation and admitted to the neonatal intensive care unit between January 1, 2018, and December 31, 2020. RESULTS: The study included 210 infants with a median gestational age of 28.6 weeks (24-31.6), a birth weight of 1065 g (445-2165), and an ANS use rate of 80%. Compared to female fetuses exposed to ANS, male fetuses exposed to ANS had a lower mortality rate (23% and 11%, respectively, p = 0.038), but there were no differences in intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, respiratory distress syndrome, and APGAR scores of 1st and 5th but an increased rate of bronchopulmonary dysplasia (moderate/severe) (p = 0.008). In addition, the mortality rate was similar in exposed and unexposed female fetuses (p = 0.850). Enzyme activities and steroid levels in the placenta might be different in male and female fetuses, which could explain the results of ANS administration. CONCLUSIONS: In our study, we have shown that ANS has no effect on mortality in female fetuses younger than 32 weeks. Future studies may focus on adjusting the administration of ANS based on fetal sex, altering the dose or taking fetal sex into account when performing ANS.

Dosage escalation of antenatal steroids in preterm twin pregnancies does not improve long-term outcome.

OBJECTIVES: To analyze long-term effects of antenatal betamethasone (≤16 mg, =24 mg and >24 mg) in preterm twins on infant and childhood morbidity. METHODS: Retrospective cohort study among 198 preterm twins. Three follow up time points, including a total of 84 outcomes, were evaluated: first neonatal examination after birth and in the neonatal period up to 10 days after birth using data from the clinic charts; examination from the 21st to the 24th month of life and examination from the 60th to the 64th months, using data from copies of the children's examination booklets sent back by the parents. Dosage-dependent and sex-specific long-term effects of antenatal betamethasone treatment on neonatal, infant and early childhood development and morbidity up to 5.3 years of age were analyzed. RESULTS: Dosage escalation of >24 mg was not associated with improved neonatal, infant or early child hood outcome, independent of twin pair structure. In contrast, higher doses >24 mg were significantly linked to increased rates of congenital infections (OR 5.867, 95% CI 1.895-18.167). Male sex as a factor was obvious for lower rates of apnea-bradycardia-syndrome in neonates, higher rates of no free steps after 15 months in infancy and highest rates of motor clumsiness in early childhood. CONCLUSIONS: Betamethasone dosage escalation >24 mg in twins born between 23+5 and 33+6 weeks of gestation did not improve neonatal, infant or early childhood morbidity. In contrast, higher doses >24 mg total dose resulted in significantly higher rates of congenital infections and are not recommended. For males, 24 mg betamethasone appears to be the preferable dose.

The Effect of Antenatal Steroid Therapy on Early Inflammation Markers and Leukocyte Counts in Premature Infants.

ObjectiveWe investigated the effect of antenatal steroid therapy(AST) on white blood cell (WBC) and neutrophil counts and the inflammatory markers C-reactive protein(CRP), interleukin 6(IL-6), interleukin 10(IL-10), and beta-2 microglobulin(ß2M) in preterm infants.Materials MethodNeonates born at ≤34 weeks of gestation and admitted at hospital between May and November 2018 were included. The neonates were divided into three groups based on AST dose administered: 24 mg betamethasone (full course), 12 mg betamethasone (incomplete course), and no AST. 170 infants were analyzed.ResultsOf these, 45.2% (n = 77) received a full course of AST, 38.8% (n = 66) received an incomplete course of AST, and 15.8% (n = 27) did not receive AST. WBC, CRP, IL-6, IL-10, and ß2M levels were similar between the three groups, whereas neutrophil count was significantly lower in full course AST group.ConclusionConsistent with the literature data, AST was associated with reduced neutrophil count but did not affect the other inflammatory markers studied.

The association of various obstetric and perinatal factors with retinopathy of prematurity.

PURPOSE: To analyze the effects of various obstetric and perinatal factors on the severity of retinopathy of prematurity (ROP). METHODS: Infants born at ≤ 32 weeks of gestation, with less than 1500 g gestational weight and having at least stage 1 ROP, were reviewed. Group1A included treatment-requiring ROP (TR-ROP), and group 2A included the remaining patients not requiring treatment. Group 1B included stage 3 ROP cases, and group 2B included the remaining stage 2 or 1 ROP cases. Group 1C included cases with zone III disease, and group 2C the remaining. The control group (group C) was composed of premature infants without ROP. The multiple comparisons were made among groups 1A, 2A, and C; 1B, 2B, and C; 1C, 2C, and C. RESULTS: A total of 311 infants were included. Group 1A included 34 cases, group 1B 60, group 1C 51, and group C 98. Antenatal steroid administration, gestational diabetes mellitus (GDM), gestational weight (GW), gestational age (GA), sepsis, continuous positive airway pressure (CPAP) time, and invasive mechanical ventilation (MV) time were associated with TR-ROP, stage 3 ROP, and zone I, and II disease (p < 0.05). Pregestational diabetes mellitus (DM) was only associated with stage 3 ROP (p = 0.031). Gestational hypertension was only associated with zone I and II disease (p = 0.034). The use of low-molecular-weight heparin may be protective against stage 3 disease (p = 0.031). CONCLUSION: Antenatal steroid administration, GDM, GW, GA, sepsis, CPAP time, and invasive MV time were risk factors for TR-ROP and stage 3 ROP, while pregestational DM was only associated with stage 3 ROP.

Long term alterations of growth after antenatal steroids in preterm twin pregnancies.

OBJECTIVES: To compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth. METHODS: A retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children's examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years. RESULTS: Overall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%. CONCLUSIONS: ANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease. SYNOPSIS: First-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

Area-based study identifies risk factors associated with missed antenatal corticosteroid prophylaxis in women delivering preterm infants.

AIM: All women delivering a preterm infant should receive antenatal corticosteroid prophylaxis, but many miss this opportunity. We determined the risk factors associated with missed prophylaxis in a geographically defined area of Italy. METHODS: We prospectively studied all mothers who delivered babies between 24 and 31 completed weeks of gestation, from 2009 to 2013, in all maternity units in Tuscany. RESULTS: Of 1232 mothers, 186 (15.1%) did not receive prophylaxis. The risk was higher in migrant mothers, with an adjusted risk ratio (RR) of 1.28 and 95% confidence interval (95% CI) of 1.04-1.56, and in mothers hospitalised for less than 24 hours (RR 4.09, 95% CI: 2.90-5.78). Preterm prelabour rupture of membranes (RR 0.63, 95% CI: 0.41-0.96) and maternal antepartum transfer (RR 0.24, 95% CI: 0.18-0.32) were protective. Hospital level at birth and gestational age did not influence the prophylaxis rate. The population-attributable fractions were 50.4% for late hospital admissions and 10.2% for migrant status. CONCLUSION: In a highly organised network of hospitals, neither level of care nor gestational age influenced prophylaxis. Timely arrival of women in hospital, better recognition of the imminence of delivery and tighter steroids administration guidelines are the most relevant targets to further increase prophylaxis.

Incidence, Risk Factors and Screening Evaluation of Retinopathy of Prematurity in High Birthweight Infants: A Large Cohort Study in Turkey.

PURPOSE: To report and evaluate the incidence and risk factors of retinopathy of prematurity (ROP) and to assess the sensitivity and specificity of Turkish national screening guideline (NSG) in heavier infants with a birth weight (BW) of >1500 g. METHODS: The data of 1784 preterm infants with BW>1500 g, who were screened between 2009 and 2016 in a university hospital in Turkey, were analyzed retrospectively. The rates of any stage and severe (treatment-requiring) ROP incidence were investigated. The possible protective and risk factors were evaluated with univariate analyses and logistic regression analysis. RESULTS: The rate of any stage ROP was 14.1% (n = 251). Severe ROP was observed in 11 infants (0.6%), and 2 of the infants (0.1%) had a gestational age (GA)>32 weeks, which fell outside of the NSG. In logistic regression analysis, BW, GA, O2 therapy duration, and exchange transfusion were determined to be independent risk factors (respectively, p < .001, p < .001, P = .055, and P = .033). Furthermore, antenatal steroid therapy was determined to have a highly significant protective effect on ROP development (p < .001). The sensitivity of Turkish NSG in identifying severe ROP increased from 82% to 100% with the inclusion of risk factors in addition to GA and BW. CONCLUSION: This study shows the presence of severe ROP in mature and heavy infants in Turkey. The positive effect of antenatal steroid use and the negative impact of exchange transfusion have been demonstrated for ROP development in mature infants. Possible risk factors should be evaluated with GA and BW to avoid missing severe ROP.

Maternal adipose tissue, antenatal steroids, and Respiratory Distress syndrome: complex relations.

Çelik HT, Korkmaz A, Özyüncü Ö, Yigit S, Yurdakök M. Maternal adipose tissue, antenatal steroids, and Respiratory Distress syndrome: complex relations. Turk J Pediatr 2019; 61: 859-866. The incidences of maternal obesity and obesity-related maternal, fetal and neonatal complications have increased considerably. Obese people may have lower, normal or increased fat mass independent from their body mass index. We aimed to investigate the relationships between antenatal steroid therapy and maternal body fat ratio for the risk of Respiratory distress syndrome (RDS) in preterm infants. Pregnant women and their newborn infants between 24-34 weeks of gestation, who received a full course of antenatal steroid therapy were included in the study. Mother`s body weight, body mass index (BMI), and body compositions (muscle, fat, water) were calculated using the bioelectrical impedance method 5 days after giving birth. Neonatal characteristics and respiratory outcomes were noted. A total of 42 mothers and their single premature infants were included in the study. Nineteen (45.2%) infants developed RDS (Group 1) while 23 (54.8%) infants did not develop RDS (Group 2). The mean body fat mass (kg), fat ratio (%), truncal fat mass (kg), and truncal fat ratio (%) were statistically significantly higher in Group 1 than in Group 2. The incidence of RDS was significantly higher in the group of mothers with a body fat ratio > 30.0% (n=15/24, 62.5%) when compared with the group of mothers with a body fat ratio ≤ 30% (n=4/18, 22.2%) (p=0.013). Maternal adipose tissue plays an important role and should be taken into consideration especially in obese women, before giving antenatal steroids to achieve positive effects of the therapy in preterm infants.

Do early postnatal body weight changes contribute to neonatal morbidities in the extremely low birth weight infants.

BACKGROUND: The implications of early postnatal body weight changes (Δbw) in the morbidities related to body fluid metabolism in sick preterm infants in not well investigated. The extremely low birth weight infants (ELBW, birth weight <1000 g) have the highest incidence of such morbidities among all neonates. AIM: To determine the relationships between Δbw and neonatal morbidities associated with body fluid metabolism in the ELBW infants. METHODS: In an observational study, the associations between daily weight changes from birth weight (DΔ bw) and oxygen dependence on postnatal day 28 (BPD28), patent ductus arteriosus (PDA), intraventricular-periventricular hemorrhage (IVH), antenatal steroid (ANS) and gestational age (GA) were evaluated. Maximum weight loss (MΔ bw) was correlated with GA, BPD28 and BPD36 (oxygen dependence on postmenstrual 36 weeks). Pearson's correlation co-efficient and multivariate logistic regressions were performed for analysis. RESULTS: DΔ bw correlated inversely with GA on days 1-8 of life (p <  0.01 for all, 0.06 for DOL 2). DΔ bw was associated with a lower risk of BPD28 on days 6 (OR 0.87, 95% CI 0.76-1), 10 (OR 0.86, 95% CI 0.76-0.98) and 11 (OR 0.87, 95% CI 0.77-0.99); with PDA on days 8-11 (OR ranging between 0.89 to 0.92 for the 4 days, 95% CI 0.83 to 0.99) and with IVH on day 5 (OR 0.93, 95% CI 0.86-1) after controlling for GA. DΔ bw was not identified as risk factor for the tested morbidities. ANS decreased DΔ bw on days 4 (OR 0.88, 95% CI 0.78-1) and 10 (OR 0.9, 95% CI 0.84-1). MΔbw correlated directly with BPD28 (r = 0.3, p = 0.004), which declined after controlling for GA (r = 0.2, p = 0.2). CONCLUSIONS: DΔ bw is protective for PDA, BPD28 and IVH, independent of gestational age, whereas, the effects of MΔ bw on BPD are governed by maturation in ELBW infants. ANS decreases DΔbw, which correlates inversely with GA during the first week of life.