Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT, USA.
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):9913-9921. doi: 10.1080/14767058.2022.2075696. Epub 2022 May 22.
To derive a prescriptive sex-specific fetal growth standard and assess clinical management and outcomes according to sex-specific growth status.
This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational study of 10,038 nulliparas from eight U.S. centers who underwent ultrasounds at 14-20 and 22-29 weeks with outcomes ascertained after delivery. From these, we selected a nested cohort of lower risk participants (excluded those with chronic hypertension, pre-gestational diabetes, suspected aneuploidy, and preterm delivery) to derive a sex-specific equation for expected fetal growth using fetal weights by ultrasound and at birth. We compared the male-female discrepancy in the rate of weight <10th (small for gestational age [SGA]) and >90th (large for gestational age [LGA]) percentiles between the sex-specific and sex-neutral (Hadlock) standards. Using the full unselected cohort, we then assessed outcomes and clinical management according to sex-specific SGA and LGA status.
Overall, 7280 infants in the lower risk nested cohort were used to derive a sex-specific equation with fetal sex included as an equation intercept. The sex-neutral standard diagnosed SGA more often in female newborns (21% vs. 13%, < .001) and LGA more often in male newborns (5% vs. 3%, < .001). The sex-specific standard resolved these disparities (SGA: 9% vs. 10%, = .23; LGA: 13% vs. 13%, = .58). To approximate an unselected population, 1059 participants initially excluded for risk factors for abnormal growth were then included for our secondary objective ( = 8339). In this unselected cohort, 39% (95% CI 37.0-42.0%) of the 1498 newborns classified as SGA by the sex-neutral standard were reclassified as appropriate for gestational age (AGA) by the sex-specific standard. These reclassified newborns were more likely to be delivered for growth restriction despite having lower risk of morbidity (females) or comparable risk of morbidity (males) compared to newborns considered AGA by both methods. Of the 6485 newborns considered AGA by the sex-neutral standard, 737 (11.4%, 95% CI 10.6-12.2%) were reclassified as LGA by the sex-specific standard. These reclassified newborns had higher rates of cesarean for arrest of descent, cesarean for arrest of dilation, and shoulder dystocia than newborns considered AGA by both methods. None were reclassified from LGA to AGA by the sex-specific standard.
The Hadlock sex-neutral standard generates sex disparities in SGA and LGA at birth. Our sex-specific standard resolves these disparities and has the potential to improve accuracy of growth pathology risk stratification.
制定一种具有规定性的胎儿性别特异性生长标准，并根据性别特异性生长状况评估临床管理和结局。
这是 Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) 的二次分析，这是一项前瞻性观察性研究，纳入了来自美国 8 个中心的 10038 名初产妇，她们在 14-20 周和 22-29 周进行了超声检查，分娩后确定了结局。在这些参与者中，我们选择了一个嵌套队列的低风险参与者（排除患有慢性高血压、孕前糖尿病、疑似非整倍体和早产的参与者），以使用超声和出生时的胎儿体重来推导性别特异性的胎儿生长方程。我们比较了性别特异性和性别中性（Hadlock）标准中体重 <10 百分位（小于胎龄儿[SGA]）和>90 百分位（大于胎龄儿[LGA]）的男性与女性之间的差异。然后，我们使用完整的未选择队列，根据性别特异性 SGA 和 LGA 状况评估结局和临床管理。
总体而言，在较低风险的嵌套队列中，有 7280 名婴儿被用于推导包含胎儿性别的性别特异性方程。性别中性标准在女性新生儿中更常诊断为 SGA（21%比 13%，<0.001），在男性新生儿中更常诊断为 LGA（5%比 3%，<0.001）。性别特异性标准解决了这些差异（SGA：9%比 10%，=0.23；LGA：13%比 13%，=0.58）。为了近似于未选择的人群，我们最初排除了 1059 名因生长异常风险因素而被排除在外的参与者，然后将其纳入我们的次要目标（=8339）。在这个未选择的队列中，39%（95%置信区间为 37.0-42.0%）根据性别中性标准被分类为 SGA 的 1498 名新生儿被重新分类为性别特异性标准的适合胎龄（AGA）。与两种方法均被认为是 AGA 的新生儿相比，这些重新分类的新生儿尽管生长受限的风险较低（女性）或具有相似的发病风险（男性），但更有可能因生长受限而分娩。在根据性别中性标准被认为是 AGA 的 6485 名新生儿中，有 737 名（11.4%，95%置信区间为 10.6-12.2%）被性别特异性标准重新分类为 LGA。这些重新分类的新生儿剖宫产因胎头下降阻滞、剖宫产因扩张阻滞和肩难产的发生率高于两种方法均被认为是 AGA 的新生儿。没有新生儿从 LGA 重新分类为 AGA。
Hadlock 性别中性标准在出生时产生 SGA 和 LGA 的性别差异。我们的性别特异性标准解决了这些差异，并有可能提高生长病理风险分层的准确性。
