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Background Adverse life events and chronic psychological distress before and during pregnancy have frequently been associated with preterm birth (PTB) but the biological underpinnings remain unclear. We investigated the association between corticosteroid levels in pre-pregnancy and first-trimester hair and the risk of PTB. Methods We followed 1,808 pregnant women from a prospective pre-birth cohort study in Lima, Perú. Hair samples were taken at the end of the first pregnancy trimester. The two most proximal 3cm segments to the scalp (representing pre-pregnancy and first-trimester) were analyzed to obtain hair cortisol and cortisone concentrations (HCC and HCNC). PTB was defined as birth < 37 completed gestational weeks. We constructed four generalized propensity scores for pre-pregnancy and first-trimester HCC and HCNC to create corresponding inverse probability weights before fitting marginal structural models for estimating the effect of HCC and HCNC on PTB risk. Results Pre-pregnancy Log HCC was not independently associated with PTB risk (RR = 0.97; 95%CI: 0.79, 1.19). In contrast, one SD increase from the mean first-trimester Log HCC was independently associated with a 37% (95%CI: 1.11, 1.69) increased risk of PTB. Although imprecise, pre-pregnancy Log HCNC was negatively associated with PTB risk (RR = 0.84; 95%CI: 0.58, 1.20), whereas the association between first-trimester Log HCNC and PTB risk was positive (RR = 1.20; 95%CI: 0.87, 1.65). Conclusions Our findings show that chronic corticosteroid levels in early pregnancy are causally linked to PTB risk in pregnant Peruvian women. This finding contributes to understanding the biological underpinnings of PTB better to enhance PTB prevention.
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Preterm birth (PTB) is an adverse pregnancy outcome affecting ~15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. PTB cases delivered ≥ 20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥ 37 weeks but < 42 weeks). After imputation (TOPMED) and quality control, we assessed the association of ~6 million SNPs with PTB and GA using multivariable regression models adjusted for maternal age and the first two genetic principal components. In silico functional analysis (FUMA-GWAS) was conducted among top signals detected with an arbitrary P < 1.0×10-5 in each GWAS. We sought to replicate genetic associations with PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. Mean GA was 30 ± 4 weeks in PTB cases (N=933) and 39 ± 1 in the controls (N=1,279). PTB cases were slightly older and had higher C-sections and vaginal bleeding than controls. No association was identified at genome-wide level. Top suggestive (P < 1.0×10-5) signals were seen at rs13151645 (LINC01182) for PTB, and at rs72824565 (CTNNA2) for GA. Top PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Top GA variants were enriched in intronic regions and cancer pathways, and these genes were upregulated in the brain and subcutaneous adipose tissue. In combination with non-genetic risk factors, top SNPs explained 14% and 15% of the phenotypic variance of PTB and GA in our sample, but these results need to be interpreted with caution. Variants in WNT4 associated with GA in Europeans were replicated in our study. The genetic risk score based in European markers, was associated with a 2-day longer GA (R2=0.003, P=0.002) per standard deviation increase in the score in our sample. This genetic association study identified various signals suggestively associated with PTB and GA in a non-European population; they were linked to relevant biological pathways related to the metabolism of progesterone, prostanoid, and steroid hormones, and genes associated with GA were significantly upregulated in relevant tissues for the pathophysiology of PTB based on the in-silico functional analysis. None of these top variants overlapped with signals previously identified for PTB or GA in Europeans.
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Introducción. El embarazo adolescente es un problema de salud pública con consecuencias médicas y sociales. Objetivo. Determinar las características clínicas y epidemiológicas de las adolescentes multíparas atendidas en el Instituto Nacional Materno Perinatal entre 2014 y 2016. Material y métodos. Estudio descriptivo de serie de casos. La población estuvo constituida por todas las adolescentes puérperas multíparas atendidas en el Instituto Nacional Materno Perinatal entre 2014 y 2016 cuyos datos fueron incluidos en el Sistema Informático Perinatal. Resultados. Se incluyó un total de 567 adolescentes, el 96,3% de las pacientes pertenecían a la adolescencia tardía, eran convivientes (80,8%), con secundaria incompleta (51,3%), amas de casa (88,7%), con mediano riesgo social (54,7%) e IMC pre gestacional normal en el 57,7%. La mayoría (70.7%) fueron gestantes no controladas, con inicio tardío de controles prenatales (75{5%), predominancia de partos a término (86{2%) y eligieron a los inyectables (45{9%) como anticoncepción al egreso. La mayoría tuvo dos embarazos (85,7%), dos partos (95,9%), ningún aborto (89,2%) y hubo predominio de partos vaginales (67,5%). Conclusión. Las características clínicas y epidemiológicas de las multíparas adolescentes son similares a estudios previos realizados en Perú, con excepción del predominio de partos a término. Palabras Claves: embarazo; adolescencia; paridad; cesárea
Introduction. Adolescent pregnancy is a public health problem with medical andsocial consequences. Objective.Determine the clinical and epidemiological characteristics of multiparous puerperal adolescents attendedat the Instituto Nacional Materno Perinatal between 2014 and 2016. Material and methods.A descriptive case series study. The population was made up of all the multiparous adolescent postpartum women attended at the Instituto Nacional Materno Perinatal between 2014 and 2016 whose data were included in the Perinatal Computer System. Results.A total of 567 adolescents were included,96.3% of the patients belonged to late adolescence, were living in common law union (80.8%), with incomplete secondary education (51.3%), housewives (88.7%), with medium social risk (54.7%) and normal pregestational BMI in 57.7%; the majority (70.7%) were uncontrolled pregnant women, with late onset of prenatal controls (75.5%), predominance of term deliveries (86.2%) and they chose injectables (45.9%) as contraception at discharge. The majority had two pregnancies (85.7%), two deliveries (95.9%), no abortion (89.2%) and predominance of vaginal deliveries (67.5%). Conclusions.The clinical and epidemiological characteristics of adolescent multiparous are similar to previous studies carried out in Peru, with the exception of predominance of term deliveries. Key words:pregnancy; adolescence; parity; cesareansection